Tumours Of The Head and Neck

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					CHAPTER 15 - Tumors of the Head and Neck
 John J. Coleman III
 Mark R. Sultan

CONGENITAL LESIONS
Thyroglossal Duct Cysts
The thyroid gland originates from the pharyngeal floor at the foramen cecum during
the fourth week of gestation. It enlarges, becomes bilobed, and descends ventrally in
the midline of the neck in close approximation to the developing hyoid bone. During
this descent the patent diverticulum is called the thyroglossal duct. The duct normally
resorbs by the tenth week of gestation. When all or a portion of this duct persists,
thyroglossal duct cysts or sinuses are formed.

Classically these cysts present as midline masses in childhood, although they have
been reported to be as much as 2 cm from the midline and may present for the first
time in adults. Eighty percent occur at or just below the hyoid bone. A maneuver to
differentiate them from Delphian lymph nodes or other central masses is to have the
patient protrude the tongue. The level of the cyst is elevated by protrusion,
demonstrating its embryologic origin from the base of the tongue. Unlike branchial
cleft remnants, thyroglossal duct cysts generally do not have external sinuses. A
significant proportion do become infected, however, usually during the course of an
upper respiratory tract infection. Approximately 5 percent of the cysts contain
functional thyroid tissue, and rare cases of thyroglossal duct carcinoma have been
reported.

The differential diagnosis for midline neck masses about the hyoid bone includes
lingual thyroid tissue. In rare cases this is the patient's only active thyroid gland.
Therefore, the presence of thyroid tissue in its normal anatomic location must be
confirmed either clinically or by radioactive scan before any midline neck mass is
excised, and careful postoperative observation for hypothyroidism is imperative.

Sistrunk is credited with the development of a technique for excising thyroglossal
duct cysts and sinuses that minimizes the risk of recurrence. He described resection of
the cyst with the central portion of the hyoid bone, following the sinus superiorly to
its presumed site of origin, the foramen cecum, and excising it in its entirety.

Branchial Cleft Anomalies
Branchial cleft cysts, sinuses, and cartilaginous remnants result from the incomplete
fusion of the branchial clefts. The branchial clefts, appearing in week 4 of embryonic
life and normally involuting fully by week 7, contribute to the formation of various
head and neck structures in the developing embryo. When a portion of a cleft persists,
epithelium-lined cysts or sinuses, with or without cutaneous openings and
cartilaginous rests, may result. These anomalies usually present in the first decade of
life but may go undetected until adulthood. The majority of branchial cleft cysts and
sinuses are lined by squamous epithelium, although ciliated columnar epithelium has
been reported as well. Branchial cleft carcinoma occurs rarely when there is a history
of a branchial cleft cyst, the subsequent development of epidermoid cancer at that site,
and no other primary lesion. Branchial cleft cysts also contain lymphoid tissue and
may enlarge in response to upper respiratory tract infections.
The most common types of branchial cleft anomalies are those of the second cleft and
are found at the middle and lower thirds of the sternocleidomastoid muscle.
Cartilaginous rests from the first branchial cleft typically are subcutaneous, usually
appear medial to the tragus, and may be managed by simple excision. Cysts and
sinuses often extend more deeply into the neck. The fistulous tract courses superiorly
along the carotid sheath and then medially over the hypoglossal nerve between the
internal and external carotid arteries to end at the pharynx adjacent to the tonsillar
fossa. A stairstep incision is sometimes needed to follow this circuitous route. First
branchial cleft cysts and sinuses are located above the level of the hyoid bone just
below the body of the mandible and extend superolaterally through the parotid gland
to end within the membranous external auditory canal. Excision of these cysts and
sinuses is recommended to avoid the complications associated with recurrent
infection. Dissection must be meticulous to avoid injury to the facial, hypoglossal,
vagus, and lingual nerves and to the carotid vessels. Anomalies of the third branchial
cleft are rare. Like second cleft anomalies, they arise anterior to the middle and lower
thirds of the sternocleidomastoid muscle. However, they course behind the carotid
artery to end at the pyriform sinus.

Hemangiomas and Vascular Malformations
Congenital vascular lesions must be clearly classified as hemangiomas or vascular
malformations in order to assess their prognosis and establish appropriate
management plans. The distinctions between the two have been clarified on the basis
of cellular and clinical characteristics. Hemangiomas have an increased mitotic
activity and as such may be considered true neoplasms. They are typically absent at
birth or may be present as a faint vascular blush. During the first several months of
life they may undergo a rapid proliferative phase, during which they sometimes grow
to large size. Although the majority of hemangiomas undergo spontaneous involution
by the age of seven, complications such as ulceration and bleeding, obstruction of the
eye with subsequent amblyopia, nasal airway obstruction, and rarely
thrombocytopenia (Kasabach-Merritt syndrome) may mandate early surgical
resection. Systemic dexamethasone therapy, or the intravenous administration of
interferon-a, for a short course has been found to arrest the growth of large lesions
during their proliferative phase. The use of intralesional steroid injections or
sclerosing agents may be successful in achieving temporary control of smaller
hemangiomas in certain locations such as the lip or eyelid. Photodynamic laser
therapy may be helpful in preventing the onset of the proliferative phase of
hemangiomas.

Vascular malformations, unlike hemangiomas, have a normal rate of endothelial cell
turnover. They result from congenital errors in vascular morphogenesis and are
classified by their vessel of involvement—capillary, venous, arterial, lymphatic, or
combined. High-flow lesions result from gross abnormalities connecting the arterial
and venous systems and may cause catastrophic problems of massive hemorrhage,
high-output congestive heart failure, and hemolytic anemia. Chronic increased blood
flow may be associated with skeletal abnormalities such as bone hypertrophy and
distortion. Capillary, venous, and arterial malformations may occur anywhere in the
head and neck. Lymphatic malformations (cystic hygromas) classically occur in the
neck or the floor of the mouth. All malformations are present at birth, although they
may not be clinically evident until the ectatic vessels suddenly dilate under hormonal
or other physiologic influences. They normally grow proportionally with the child and
do not regress spontaneously, unlike hemangiomas. Therefore, the management of
malformations often is surgical. Indications for early surgical resection include
recurrent infections, obstructive symptoms (e.g., respiratory distress), hemorrhage,
and significant aesthetic deformities.

Because vascular malformations of the head and neck often are highly infiltrative, a
complete preoperative evaluation of the extent of the lesion and its vascularity must
be obtained. Angiography usually is necessary, sometimes for diagnosis, but usually
to determine the contributory vessels. When technically possible, complete extirpation
of the malformation should be performed while preserving normal anatomic
structures. Preoperative embolization by arteriographic technique may decrease blood
flow temporarily, making surgical resection safer and more practical.

Vascular birthmarks, in the past descriptively named “strawberry” or “capillary”
hemangioma, “port-wine stains,” “cavernous hemangiomas,” and “cystic hygromas,”
are now classified by their major vessel of involvement—capillary, venous, or
lymphatic malformation. Accurate description is crucial, since the prognosis and
management of vascular birthmarks depend directly on their correct classification as
hemangiomas or malformations.

In deep-seated subcutaneous vascular malformations such as those sometimes
occurring in the cheek or pharynx, physical examination may be inadequate for
accurate delineation. Further evaluation often is necessary and may include computed
tomography (CT) or magnetic resonance imaging (MRI), angiography, or technetium-
labeled red blood cell scintigraphy. Definitive diagnosis in any patient with a vascular
mass may require open biopsy to rule out a malignancy, which may occasionally have
similar radiographic characteristics.

BENIGN LESIONS
Lip
The lower lip may be subject to chronic irritants such as pipe smoking or lip biting
and, more important, to the damaging effects of chronic actinic exposure. In affected
individuals the epidermis of the vermilion becomes atrophic and the dermis reveals
elastosis. The basal layer of the epidermis then develops dysplasia, creating
thickening of the superficial mucosal layer, the stratum corneum. This thickening or
hyperkeratosis is clinically visible and palpable. With progression, the dysplasia
extends upward into the epithelium, producing parakeratosis, the accumulation of
nucleated cells, near the epithelial surface. This is manifested clinically by scaling of
the lip. A proliferation and abnormal orientation of epithelial cells, dyskeratosis, may
then follow, ultimately leading to carcinoma in situ. With penetration of the basement
membrane, an invasive squamous cell carcinoma develops. When dyskeratosis or
carcinoma in situ is present over a large extent of the surface of the lower lip, excision
of the entire vermilion (“lip shave”) should be considered. The lip is then resurfaced
by advancing the labial and buccal mucosa to the mucocutaneous junction.

Oral Cavity
A variety of benign lesions arise in the oral cavity. They may be grouped by location
into those affecting the buccal mucosa, gingiva, or tongue or by their causation, such
as inflammatory or ulcerative. For many, their significance lies in their possible
premalignant potential or in their mimicking of true malignancies.
The oral lining contains countless mucous glands, the minor salivary glands. A
submucosal accumulation of mucus results in a mucous retention cyst. Since the
majority of these cysts have no epithelial lining, it is believed that they are most often
caused by rupture of the duct system, with extravasation of mucus, and not by ductal
obstruction, as was previously thought. The most common location for a mucous cyst
or mucocele is the labial mucosa of the lower lip (Fig. 15-1). These lesions are
typically less than 1 cm in diameter, smooth, rounded, and have a bluish hue. The
treatment of choice is excision. Marsupialization alone is reserved for extensive
lesions. A ranula is a type of mucous retention cyst that arises from major salivary
glands, most commonly the sublingual glands. This too is managed by excision, but
given its location in the floor of the mouth and, in some cases, its large size, it may
require a meticulous dissection to avoid nerve injury and postoperative hemorrhage. It
is frequently necessary to resect the affected sublingual gland in-continuity to prevent
recurrence.

An epulis is a granulomatous lesion of the gingiva; as elsewhere in the body, it
represents an exaggerated inflammatory response to minor injury. Two subtypes exist:
congenital epulis is typically found in the anterior maxilla of newborns; epulis
gravidarum occurs in approximately 1 percent of pregnant women and normally
resolves spontaneously when the pregnancy is concluded. Only symptomatic epulides
need be excised.

Peripheral giant cell reparative granulomas also occur most commonly on the gingiva.
The “giant” cell of origin resembles an osteoclast. These granulomas are polypoid,
submucosal, and fibrous. They can create ulceration and hemorrhage of the overlying
mucosa. Radiographs may reveal erosion of the underlying bone. Excision must be
complete to prevent recurrence. The term “peripheral” refers to the soft-tissue origin
of these tumors as opposed to the central giant cell reparative granulomas, which,
although similar histologically, arise within bone. The peripheral giant cell reparative
granulomas are four times more common than the central type. The latter are
expansile endosteal lesions that typically present in the mandible of young adults.
They also have been reported in the paranasal sinuses, orbit, cranial vault, and
temporal bone. They must be distinguished from true giant cell tumors of bone (which
have malignant potential), brown tumors of hyperparathyroidism, traumatic bone
cysts, and fibrous dysplasia. Thorough curettage is generally curative.

The tongue and the larynx are common locations for the development of papillomas.
They are caused by the human papillomavirus, which induces squamous epithelial
proliferation into soft, irregular, pedunculated lesions that may recur and cause
obstruction of the airway. Eradication may be accomplished by excision or
cauterization using a carbon dioxide laser. Other common benign masses of the
tongue include fibromas, neurofibromas, and lingual thyroid nodules. The latter may
lie dormant through childhood and then rapidly enlarge during puberty.

In 1926 Abrikossoff described rare benign tumors involving the tongue, which he
named granular cell myoblastoma because of their presumed embryonal muscle cell
of origin. They are now believed to derive from Schwann cells and have been found
to arise throughout the aerodigestive tract, particularly in the larynx. In the tongue
they typically occur as firm, submucosal swellings in the middle one-third and may
therefore mimic squamous cell carcinoma. Wedge excision is curative.

The oral lining is subject to a number of ulcerative conditions. The idiopathic
aphthous ulcer is the most common type. The cycle of painful ulceration and
spontaneous healing may occur several times a year and persist for many years. Other
similar ulcers have identifiable causative factors, including viral infection with herpes
simplex, nutritional deficiencies including vitamin B, folate, or iron, and emotional
stress. These ulcers often respond to topical steroids. Multiple painful oral ulcerations
may be a manifestation of pemphigus vulgaris. This may be accompanied by severe,
generalized toxicity. The disease typically occurs in the fifth to seventh decade of life
in patients of Mediterranean descent. The ulcers begin as intraepithelial bullae that
subsequently rupture and ulcerate. The overlying epithelium may be rubbed off easily
(Nikolsky's sign). In erythema multiforme, persistent or recurrent painful oral
ulcerations arise within a background of diffuse oral erythema. Biopsy examination
reveals a perivascular lymphocytic cellular infiltrate. Separate skin involvement may
or may not be present. A variety of causes have been proposed. Management with
systemic steroids and antimetabolites is often necessary.

Discrete, painful ulcers are also present in necrotizing sialometaplasia. This is a
benign inflammatory disease of minor salivary glands that usually occurs on the hard
palate. It is believed that local trauma leads to progressive local ischemia and
ulceration. The histologic differentiation from squamous cell cancer or
mucoepidermoid carcinoma can be extremely difficult by incisional biopsy.
Therefore, although these ulcers will ordinarily heal spontaneously in 6 to 10 weeks
without specific treatment, in cases where the correct diagnosis remains unclear after
incisional biopsy, complete excision of the ulcer is prudent.

The description and significance of leukoplakia and erythroplasia will be reviewed
later in this chapter. Other white plaquelike lesions of the oral cavity include white
sponge nevus, lichen planus, and oral hairy leukoplakia. Histologically, all reveal
parakeratosis. White sponge nevus is a rare familial ectodermal disease that diffusely
involves the oral cavity in a benign, self-limited manner. Lichen planus is a
degenerative mucocutaneous disease with a probable autoimmune basis. Oral lesions
may appear with or without cutaneous manifestations and may at times become
erosive. Oral squamous cell carcinoma has been found in association with lichen
planus with an incidence varying between 0.09 and 10 percent in different series.
Therefore, as in oral leukoplakia, systemic and topical retinoids are being evaluated in
the treatment of oral lichen planus to reverse the condition itself and, more important,
to suppress the presumed heightened potential of the oral mucosa toward degeneration
into invasive carcinomas in these conditions. Oral hairy leukoplakia is a form of
parakeratosis recently described in patients with AIDS or other forms of
immunosuppression such as in patients with renal transplants or leukemia. Thick,
shaggy plaques typically appear on the lateral surface of the tongue and become
symptomatic when superinfected with Candida. Management includes antifungal
medication, antiviral agents, or surgical excision.

Nose
Polyps arise commonly within the nasal cavity and paranasal sinuses. They occur with
equal frequency in males and females and in all age groups after adolescence. Ten
percent of children with cystic fibrosis may also develop nasal polyps. The polyps are
often multiple, involving both sides of the nasal cavity and the paranasal sinuses.
They may present with nasal obstruction, mucoid nasal discharge, or anosmia. Those
that arise in the region of the turbinates and ethmoids are mainly allergic in origin,
while those of the posterior nasal cavity are most often infectious. Medical
management should include an evaluation for allergies. Aspirin should be stopped or
avoided, since an association exists between aspirin use and the formation of nasal
polyps. If the allergic evaluation is negative, an empiric trial of antimicrobials is
begun. Steroid nasal sprays may be helpful. When medical management fails, surgical
intervention may be necessary. Simple polypectomy carries a high rate of recurrence,
and more extensive endoscopic or open excision may be necessary.

Papillomatous growths may occur on the nasal skin or within the nasal cavity. The
squamous papilloma is an exophytic verrucous lesion caused by the papillomavirus
and is present on the skin of the nasal sills, columella, or alae. It is managed as are
other cutaneous warts. The inverted papilloma (also called schneiderian papilloma,
squamous papilloma, or papillomatosis) is a polypoid mass occurring on the lateral
nasal wall, typically in middle-aged men. The name is derived from its histologic
appearance of an “inverted” proliferative growth pattern. The significance of this
lesion lies in its presentation with symptoms of nasal obstruction, its recurrence rate
of 50 percent with polypectomy alone, and its association with concurrent (8 percent)
and subsequent (4 percent) invasive squamous cell carcinoma. More extensive
resection and close follow-up are therefore indicated and can lower the recurrence rate
to 6 percent.

Juvenile nasopharyngeal angiofibromas are benign but highly expansible and
destructive fibrovascular neoplasms that typically arise in adolescent males between
10 and 20 years of age. Originating in the superior nasal cavity, they can erode widely
into the paranasal sinuses, orbit, pterygomaxillary fossa, and middle cranial fossa.
Early symptoms include nasal obstruction and epistaxis, and more advanced lesions
can produce anosmia, proptosis, or cranial nerve dysfunction. Management commonly
requires preliminary angiographic embolization followed by surgical extirpation.
Approximately 10 percent require a combined intracranial/extracranial approach.
Radiation therapy is generally reserved for residual or recurrent disease, although its
successful use as a primary modality has also been reported.

Paranasal Sinuses
Although the terms are often used interchangeably, mucous retention cysts and
mucoceles of the paranasal sinuses are different entities with distinct pathogeneses,
natural histories, and connotations. Mucous retention cysts arise as a result of
blockage of secretion from microscopic secretory ducts of mucous glands within the
lining of the paranasal sinus cavity, possibly as a sequela of sinusitis. The fluid mass
that results remains separate from the bony wall of the sinus and so continues to be
surrounded by air within the sinus, except at its base. Rarely, they can enlarge to
occupy the entire sinus, at which point it would be difficult to distinguish them from
the more virulent mucoceles. Radiographically they appear as discrete masses that are
profiled by sinus air. The most common location for mucous retention cysts of the
paranasal sinuses is in the maxillary sinus, where they usually present as an
asymptomatic incidental finding on x-ray. Ten percent of routine sinus radiographs
reveal evidence of these cysts in the maxillary sinus. They are considered the most
common benign lesions of the maxilla. Treatment is rarely necessary.

As opposed to the indolent mucous cyst, mucoceles of the paranasal sinuses, although
benign, can be expansile, highly destructive lesions. These result from macroscopic
blockage of a sinus ostium by epithelial or osseous neoplasms or inflammatory
processes, or as a result of trauma (e.g., facial bone fractures). Mucinous secretions
then accumulate within the entire sinus. With persistent secretion a pressure effect on
the entire sinus wall is produced, displacing both the epithelial lining and the bony
wall. This ultimately can result in thinning and destruction of the wall such that the
mucocele can “invade” adjacent vital structures. CT or MRI scanning is needed to
delineate the complete extent of the process, but clinical distinction from a carcinoma
can be difficult. Mucoceles most commonly arise within the frontal sinuses, followed,
in order of frequency, by the ethmoidal, maxillary, and sphenoidal sinuses. In the
frontal sinus location they most often present with frontal headaches. Sixty percent of
frontal sinus mucoceles erode through the floor of the sinus (the orbital roof) causing
proptosis and frontal swelling. Left untreated, diplopia and even blindness can result.
Symptoms resulting from mucoceles of the other sinuses depend on their direction of
spread. Fortunately, intracranial extension is rare. Mucoceles that become infected are
called pyoceles and present with the additional signs and symptoms of sinusitis. The
most definitive treatment of a mucocele includes the evacuation of the contents of the
sinus through an open approach. The entire mucosal lining of the sinus must then be
removed and the sinus duct occluded with muscle or bone. The question remains
controversial as to whether or not the remaining sinus itself should then be obliterated,
and if so, with what material (e.g., muscle, fat, cancellous bone).

Larynx
The most common benign neoplasm of the larynx is the papilloma, accounting for
more than 90 percent of laryngeal tumors. Papillomas, probably caused by the human
papillomavirus, usually arise on the vocal cords and usually present with hoarseness.
They may be found at any site in the larynx as well as on the hypopharyngeal or
pharyngeal walls and present as pedunculated exophytic masses. Laryngeal
papillomas may be grouped into juvenile or adult types, depending on the age at
onset. In the juvenile group there is a 2:1 female predominance, and ratio is reversed
in the adult group. The typical course of each type is also distinctly different. In adults
the masses are most often solitary and rarely recur after excision. In the juvenile
group the lesions tend to be multiple and may recur and spread rapidly after excision.
The reason for these differences is not known. Laryngeal papillomas are usually
treated with laser obliteration.

Other, less common benign tumors of the larynx include oncocytic tumors and
granular cell myoblastomas. The former present as a smooth submucosal mass, and
the latter as a sessile mucosal mass. The most common location for both is the vocal
cords, and so they too typically present with hoarseness. Chondromas of the larynx
are rare benign cartilaginous neoplasms most commonly occurring on the cricoid
cartilage. They can cause hoarseness, respiratory obstruction, or dysphagia. All of
these benign neoplasms are managed by conservative excision.

A laryngocele is a herniation of the laryngeal ventricle. Three forms exist, categorized
by their site of presentation. An internal laryngocele remains confined to the larynx
and presents as an enlargement of the false cord. An external laryngocele protrudes
through the thyrohyoid membrane, causing swelling in the anterior neck.
Combinations of these two types, called mixed laryngoceles, occur as well. The
pathogenesis is believed to be associated with chronic increases in intralaryngeal
pressure. Corroborative evidence for this theory includes the fact that singers and
musicians have a propensity for their development. Symptoms depend on the site of
presentation, with the internal variety often causing hoarseness and the external most
commonly remaining asymptomatic. Treatment includes ligation of the stalk of the
laryngocele and repair of the ventricular weakness.

Odontogenic and Bone Tumors
Odontogenic Tumors
A variety of cysts and tumors of the mandible and maxilla may arise from the
progenitor cells of tooth development. The majority of these odontogenic lesions are
benign and may be treated conservatively. Ameloblastomas (adamantinomas) arise
from dental lamina and often are associated with impacted teeth in young patients.
Their usual presentation is that of a painless mass of the jaw with a multilocular,
radiolucent appearance on x-ray. They occur four times more frequently in the
mandible than in the maxilla. Although slow-growing, they may grow to large size
and erode adjacent bone (Fig. 15-2). Treatment consists of resection of the entire
lesion with a margin of bone to prevent local recurrence. Myxomas and Pindborg
tumors (calcifying epithelial odontogenic tumors) are similar in their presentation and
management, and they too require an en bloc resection for cure.

A second group of odontogenic tumors, including calcifying odontogenic cysts
(Gorlin's cysts), ameloblastic fibromas, cementomas, and keratocysts, are generally
less aggressive than those discussed above and are treated effectively by enucleation
and excision of the entire lining of the lesion.

Nonodontogenic Tumors
The tumors in this group arise from bone that is not involved in tooth development.
Torus is a benign, slow-growing projection from the surface of bone. The torus
palatinus occurs in the midline of the hard palate, and the torus mandibularis usually
develops on the lingual surface of the mandible opposite the premolars, often
bilaterally. They are both common lesions. In the United States 20 percent of the
population have a torus palatinus and 8 percent a torus mandibularis. There is
evidence that they are genetically inherited by autosomal dominant genes with
incomplete penetrance. Tori often begin around puberty and are slow-growing. They
can induce ulceration of the overlying mucosa, thus mimicking a mucosal neoplasm.
No therapy is needed unless they interfere with speech, mastication, or the use of
dentures, at which time simple excision is performed.

Exostoses are similar to tori and also commonly occur in the jaws. There are localized
overgrowths of bone that may be nodular, pedunculated, or flat and are often multiple.
They most often present in the maxilla at the canine fossa as a hard, discrete,
submucosal mass. Only symptomatic masses require excision.

Osteomas are slow-growing tumors of mature bone that arise within (intraosseous) or
at the periphery of the involved bone. The peripheral lesions often are attached to the
cortical bone by a dense pedicle. Involvement of the bones outside of the face and
skull is rare. They most commonly arise on the mandible on the lingual aspect of the
ramus or on the lower border of the angle of the mandible. Osteomas also may occur
in the paranasal sinuses, where they may grow to a large size. Excision is advised
when continued growth encroaches upon vital structures or becomes cosmetically
unacceptable. Multiple osteomas are one of the manifestations of Gardner's syndrome,
the others being multiple inclusion cysts of the skin, supernumerary teeth, and familial
polyposis.

Fibrous dysplasia is a benign bone disorder of unknown cause in which cortical bone
is replaced by immature fibrous tissue. The fibrous tissue often proliferates and
extends beyond normal boundaries, distorting and compressing vital structures.
Seventy percent of patients have involvement of a single bone—monostotic—and 30
percent have the polyostotic form. In the head and neck, the mandible or maxilla is
most often involved. Albright's syndrome includes polyostotic fibrous dysplasia,
precocious puberty, café- au-lait spots, and several endocrine abnormalities. The
management of the patient with fibrous dysplasia is dictated by the aggressiveness of
the disease and ranges from observation only to extensive local resection and
reconstruction. Malignant degeneration occurs in 1 percent of the patients and may be
related to prior radiation therapy. Malignant degeneration should be suspected in any
lesion that undergoes rapid growth or produces significant pain.

CARCINOMAS
General Considerations
Malignant neoplasms that arise in the head and neck area or upper aerodigestive tract
share the general behavior of most solid tumors: local growth, locoregional spread,
and distant metastasis. Their effect, however, before therapy and as a consequence of
therapy, depends much more than most other neoplasms' on local disruption of
function. The two main vegetative functions of the human being—alimentation and
respiration—are effected by the intricate synergy of the bone, nerve, muscle, and
mucosa- lined cavities that make up the head and neck. Invasive carcinoma disrupts
this fine balance, resulting not only in the proliferation of abnormal cells but also in
the derangement of feeding, breathing, and speaking, which may present as
malnutrition, upper airway obstruction, and recurrent aspiration pneumonia. Thus
unlike the case of adenocarcinoma of the breast, colon, and stomach, malignant
melanoma, squamous cell carcinoma of the lung, and most other solid tumors, in
which the fatal event is almost always disseminated malignancy, as many as 60
percent of patients with a fatal head and neck malignancy die without clinical
evidence of metastasis beyond the local/regional disease. Central nervous system
invasion, rupture of the great vessels, airway obstruction, and invasive local infection
are common causes of death in these patients (Fig. 15-3). Because of the predominant
local and locoregional natural history of this disease, significant attention must be
paid to local diagnosis and therapy.

Most malignant tumors that develop above the clavicles are squamous cell carcinomas
(epidermoid carcinomas) originating from the respiratory and stratified squamous
epithelium of the upper aerodigestive tract. Although there are some differences in the
natural history of tumors arising at the various sites of the upper aerodigestive tract,
probably dependent on characteristics of blood supply, lymphatic drainage, or
histologic variation specific to that area, most squamous cell carcinomas of the head
and neck behave similarly. Their unique clinical expression then depends on the
interruption of normal activity inherent in their epicenter and those areas to which
they spread (Fig. 15-4). So nasopharyngeal carcinoma may present with nasal
stuffiness and progress to cranial nerve dysfunction and central nervous system
invasion as well as neck metastasis; and carcinoma of the floor of the mouth may
present with pain, tethering of the tongue, and dysphagia, resulting in malnutrition
and, sometimes, aspiration.

Moreover, the therapeutic approach to the malignancy may interfere with normal
function. Laryngectomy and glossectomy obviously impair speech and swallowing
tremendously. Radiotherapy, used alone or in combination with surgery, may result in
deficiencies of olfaction, salivation, and infection control in the upper aerodigestive
tract. Hence the survival of the patient with head and neck cancer requires
consideration of both tumor growth and residual local function in formulating the
therapeutic plan. The appropriate selection of radiotherapy, extirpative surgery,
chemotherapy, and reconstructive surgery is crucial in the physician's attempt to
prolong life and restore reasonable function and appearance. A multidisciplinary
approach to this group of tumors is essential.

In both children and adults neoplasms other than squamous cell carcinoma, benign
and malignant, and other clinically important masses arise in the head and neck area
(Fig. 15-5). Although some of these are more likely to progress to early metastatic
disease, most have significant local effect in both their clinical expression and
therapy. In adults salivary neoplasms are the next most important group of lesions in
the head and neck.

Epidemiology
Squamous cell carcinoma of the head and neck is not a major public health problem in
the United States. Combined upper aerodigestive tract sites account for approximately
23 new cases per 100,000 males and 8 per 100,000 females, or roughly 6 percent of
new cancers in males and 2 percent in females. There are 30,000 to 40,000 new
cancers of the head and neck and 10,000 to 15,000 deaths per year. Approximately
one-third of patients who develop a squamous cell carcinoma of the upper
aerodigestive tract will die from it. Incidence and mortality rates in the United States
have remained relatively stable over the past 40 years in white males but have
increased dramatically for most sites in nonwhite males and in females of both groups
(Fig. 15-6). Like many solid tumors, the incidence of disease increases with age in
both sexes, being very rare below age thirty except in immunocompromised patients.
In the United States there seems to be a clear-cut relationship between squamous cell
carcinoma of the upper aerodigestive tract and the chronic use of tobacco and alcohol
together. Although the use of either tobacco or alcohol alone increases the likelihood
of squamous cell carcinoma of the upper aerodigestive tract, the cumulative abuse
greatly increases the risk (Fig. 15-7). Previously noted increases in the incidence of
squamous cell carcinoma in females were probably a result of the more widespread
acceptance of cigarette smoking among women over the past 30 years. In the Western
world the combination of tobacco and alcohol of various forms seems to be the
predominant cause of this disease; and though there is some slight variation, the
mortality rate is similar from country to country. Cigarette, cigar, and pipe smoking,
chewing tobacco, and snuff have all been implicated, as have distilled beverages,
beer, wine, and even mouthwash, which in many forms has a high content of alcohol.
The previously demonstrated relationship of asbestos and tobacco in the
carcinogenesis of lung cancer is probably operant in squamous cell carcinoma of the
upper aerodigestive tract as well.

Squamous cell carcinoma of the head and neck is endemic in other parts of the world,
with incidences reaching as high as 50 percent of new cancers in Bombay, India,
where chewing of pan, a combination of tobacco, betel nut, and lime (CaOH2), causes
buccal carcinoma. Throughout southeast Asia the use of betel nut and tobacco
combinations similarly results in a high frequency of oral cancers. In cultures such as
those of South Asia and Southeast Asia, where alcohol is not commonly used, the
prevalence of vitamin deficiency and local submucosal fibrosis of the oral mucosa
may play an important adjuvant role. Reverse smoking (smoking of cigarettes and
cigars with the lighted end inside the mouth) similarly contributes to the high
incidence of palate and oral cancers seen in India and some parts of Central and South
America. In South Africa unusually high rates of nasal and paranasal cancers have
been discovered, where nickel contaminates the tobacco inhaled as snuff, and where it
and other substances are industrial contaminants among workers in the nickel,
furniture, and shoe industries.

In southern China and the Pacific Rim countries, carcinoma of the nasopharynx is
extremely common in both men and women, up to twenty times more common than
in the United States. The causative factors are unclear, although inhaled fumes,
cooking smoke, chemical pollutants, or others have been proposed, as has the
ingestion of salted fish. The role of the Epstein-Barr virus (EBV) in the causation and
natural history of nasopharyngeal carcinoma is unclear. Infection with EBV is
prevalent in this group, and there seems to be a close relationship between elevated
serum EBV titers and risk. Despite the differences in proposed causative agents
throughout the world, it appears clear that an important factor in the origin of
squamous cell carcinoma is a chemical carcinogen and that a linear dose- time risk
ratio is likely. Prevention should be possible.

Carcinogenesis
The simplest explanation of the causation of squamous cell carcinoma falls within the
accepted principles of chemical carcinogenesis, more specifically cocarcinogenesis,
where an initiating agent (perhaps some contaminant or metabolite of tobacco)
induces an irreversible change in the DNA of the affected cell. A promoting agent
(perhaps alcohol, vitamin deficiency, local inflammation secondary to trauma, poor
hygiene, or submucosal fibrosis) allows that irreversible change to manifest itself as a
histologically and clinically identifiable malignancy. Initiation involves alteration of
the DNA by addition through covalent bonding, replacement, deletion, or other
mechanism. Promotion theoretically involves facilitation of expression of the
abnormal DNA via activation of cell surface and cytoplasmic protein receptors or
other reactions with the epithelial cell. This theory is consistent with many of the
epidemiologic and clinical characteristics of squamous cell carcinoma of the upper
aerodigestive tract. The indictment of chronic use implies that initiation alone is not
sufficient for malignancy. In addition to the sites in the nasopharynx and larynx where
inhaled and exhaled tobacco smoke contact, high-dose exposure is possible to the
mouth, tongue, and buccal mucosa as metabolites of tobacco are secreted into saliva
and sit pooled in the lingual and buccal sulci. The chronic inflammation attendant to
frequent alcohol use may stimulate local proliferation of epithelial cells and react with
reproducing cells to allow expression of the previously altered DNA.
The role of viral carcinogenesis via initiation or promotion is unclear but certainly
suspicious. Patients with papillomatosis caused by human papillomavirus of the nasal
cavity and larynx have been noted to be at higher risk for development of invasive
squamous cell carcinoma. Recent studies of DNA from squamous cell carcinoma of
the nasal cavity and paranasal sinuses using the polymerase chain reaction have
identified human papillomavirus (HPV) types 16 and 18, whereas they were not
identified in tumors of other histologic type (adenocarcinoma, adenoid cystic, etc.).
HPV 16 genomes also have been found in squamous cell carcinoma of the larynx,
buccal mucosa, tongue, and cervical lymph node metastases. Elevated antibody to
Epstein-Barr virus is associated with the presence of nasopharyngeal carcinoma but is
not specific enough to be of clinical use, since viral infection is common. That the
virus plays either an initiating or a promoting role in carcinogenesis is suggested by
the presence of the Epstein-Barr viral genome in cervical metastases as well as in the
primary tumor arising in the nasopharynx but its absence in lymph nodes of Epstein-
Barr-antibody-seropositive patients that did not contain tumor and its absence in
metastatic tumors of other histology.

Although malignancy of the head and neck is not commonly associated with familial
syndromes, benign tumors such as exostoses, sebaceous cysts, and sebaceous
adenomas may be seen in the genetic alteration that causes Gardner's syndrome and
Muir-Torre's syndrome. Of the identified oncogenes, several have been discovered in
squamous cell carcinoma. The int-2 oncogene related to fibroblast growth factor and
the C-myc gene that codes for a DNA-binding protein concerned with regulation of
cell growth have been demonstrated in 11 of 21 and 2 of 21 squamous cell carcinoma
tumors studied. Improved methods of DNA characterization will clarify the role of
viral transformation, heredity, and increased susceptibility in the pathogenesis of
squamous cell carcinoma.

Current molecular biologic and genetic investigations of squamous cell carcinoma of
the head and neck have not yet produced useful mechanisms of therapy.
Overexpression of oncogenes and increased levels of oncoproteins, such as the a6b4
integrins (cell surface adhesion molecules and receptors for extracellular matrix
proteins), and the HER2/neu oncoproteins have been associated with rapid
locoregional spread and metastasis. Inactivation of tumor suppressor genes by
deletion or other mutations seems to be a common mechanism of tumor initiation and
subsequent progression. It has been theorized and partially demonstrated that the
formation of a head and neck tumor requires many genetic events. In vitro analysis of
several lines of squamous cell carcinoma have demonstrated common allelotypes with
deletions at the 9p21, ep, and 17p chromosome sites. The level of p53 mutations may
predict the responsiveness of tumor to radiotherapy and chemotherapy. Another
potential therapeutic mechanism being investigated is the elaboration of humorally
and cellularly mediated antibodies to these overexpressed tumor cell proteins. The
further delineation of the genetic identity of squamous cell carcinoma and the
manipulation of protein synthesis will have a major role in future treatment.

The protean manifestations of AIDS include a number of abnormalities in the head
and neck. Proliferative lymphocyte deposits in the nasopharynx have been noted to
cause eustachian tube dysfunction and may be precursors of the commonly seen
extranodal lymphomas. Squamous cell carcinomas of the upper aerodigestive tract
appear to be disproportionately common and unusually aggressive in patients with
AIDS, as in other immunodeficient states such as chronic lymphocytic leukemia. Oral
and pharyngeal presentations of Kaposi's sarcoma are common in HIV-positive
patients and occasionally require surgical or radiotherapeutic intervention (Fig. 15-8).
Cystic degeneration of lymph nodes in the parotid and submandibular glands also
occurs, and in one series this was the presenting symptom of newly diagnosed HIV
infection.

Natural History
Malignancy in the head and neck follows a relatively predictable course along the
continuum of histologic changes from early evidence of hyperplasia with atypia to
poorly differentiated invasive malignancy. The sequential presentation of these
abnormalities fits well with a theory of chronic exposure to one or several chemical
carcinogens. The normal oral and oropharyngeal cavities are lined with stratified
squamous epithelium similar to the skin but without the characteristic keratinization.
Another difference between the skin and oral mucosa is the lack of distinct rete ridges
in the mouth in normal states. Immediately subjacent is the basement membrane,
beneath which lies the submucosa, containing lymphoid aggregates and lymphatic
channels, blood vessels, and mucous and serous glands. In most areas of the oral
cavity and oropharynx, mucosa and submucosa cover muscle. Within the epithelial
layer are terminations of the nerves mediating the special senses of olfaction and taste
as well as other nerve fibers. The larynx, nasal cavity, and paranasal sinuses are lined
by pseudostratified columnar ciliated epithelium, which overlies a similar
arrangement of minor salivary glands, nerves, and blood vessels.

Viral infection, chronic irritation by ill-fitting dentures, trauma, or infection from poor
dental hygiene may elicit a response from the epithelium known as hyperplasia or
papillomatosis, in which cells with normal DNA configuration and organelle structure
proliferate, resulting in more prominent intraluminal projection as well as extension of
the mucosa deeper into the submucosa. Despite these changes there are none of the
cellular manifestations of malignancy (mitoses, pyknotic nuclei, prominent nucleoli,
etc.), and the basement membrane beneath the mucosa remains intact.

Most of the clinical changes that reflect these histologic alterations, including
hyperplasia, hyperkeratosis, and pseudoepitheliomatous hyperplasia (the aggressive
end of this spectrum, which may be confused clinically with malignancy), have been
grouped under the term leukoplakia (white patch). Histologic analysis shows
hyperkeratosis and parakeratosis or orthokeratosis (appearance of nuclei in the most
superficial layers of the mucosa with or without inflammatory cell infiltrate and
acanthosis). Earlier approaches required the removal of all leukoplakia, which was
believed to be a precursor of invasive malignancy. More recent thinking, however,
suggests that this change is not in itself premalignant but simply evidence of chronic
irritation.

Cellular manifestations of malignancy result in the diagnosis of epithelial dysplasia.
Lack of a normal cellular progression to maturation characterizes dysplastic
epithelium. Nuclei are larger, are hyperchromatic, and show mitotic activity. Cells
may be pleomorphic with basophilic cytoplasm. Cell layers become disorganized,
with loss of the gradual ascent to the epithelial surface and the presence of immature
cells at the basement membrane as well as the epithelial surface. The extent of the
individual cellular changes and loss of normal polarity determines whether the entity
is termed dysplasia, severe dysplasia, or carcinoma in situ. All of these changes,
however, overlie an intact basement membrane. The change from hyperplasia to
dysplasia is thought to be irreversible and the initial step in carcinogenesis. The
clinical manifestation of these histologic changes has been termed erythroplasia or
erythroplakia, or red patch. These lesions appear reddish, are frequently exudative,
and may have associated leukoplakia. Biopsy or excision is mandatory, because they
are premalignant and may also indicate the presence of another adjacent malignancy.

The cellular changes of carcinoma in situ with loss of the integrity of the basement
membrane become invasive squamous cell carcinoma. Deranged cellular function
results in intracellular keratinization or keratin pearl formation (Fig. 15-9). Growth
into the oral cavity may be manifested grossly as an exophytic carcinoma, whereas
invasion into the adjacent muscle or bone produces ulcerative lesions.

In addition to the continuum of changes from hyperkeratosis to invasive carcinoma,
patients with squamous cell carcinoma frequently demonstrate another phenomenon
consistent with the theory of chemical carcinogenesis. Field cancerization or the
condemned mucosa phenomenon is the finding of epithelial abnormalities throughout
the entire upper aerodigestive tract in a patient with squamous cell carcinoma at one
site (Fig. 15-10). Erythroplakia in the oral cavity increases the risk of invasive
carcinoma in the pharynx, larynx, esophagus, and lung. The incidence of synchronous
malignancies in the upper aerodigestive tract has been reported to range from 4.4 to
more than 10 percent, with lung, esophagus, and other head and neck sites being most
common.

Other anatomic abnormalities and functional disorders are also more frequent in
patients with upper aerodigestive tract malignancy. Barrett's esophagus and
esophagitis have been reported to occur in 33 percent of patients undergoing
laryngoesophagectomy for advanced laryngeal carcinoma. An overall incidence of
esophageal disease of 54 percent was found, with synchronous esophageal cancer in
25 percent of these patients. Metachronous or subsequent malignancies also appear at
a higher frequencies in patients with squamous cell carcinoma of the upper
aerodigestive tract than in the general public. Lung, esophagus, and other head and
neck sites are more common, with a risk of up to 27 percent. Cessation of smoking
and alcohol intake may or may not be protective.

The phenomenon of field cancerization and the high frequency of synchronous and
metachronous malignancies in patients with squamous cell carcinoma of the head and
neck fit nicely with the current theories of oncogenesis. Within the condemned
mucosa there may be multiple subpopulations of neoplastic cells, each the clonal
expression of a common initial abnormality. Different environmental conditions,
subsequent mutations caused by the chronic insult of chemical carcinogens, and
amplification of genetic abnormalities at one site more than another may explain the
simultaneous appearance of erythroplasia, well-differentiated local carcinoma, and
poorly differentiated lymph node metastasis as the disease progresses clinically and
histologically. The application of the theory of tumor heterogeneity to the entire
mucosal surface explains many of the characteristics of individual tumors such as
resistance to chemotherapy and radiotherapy as well as the patient's systemic response
to disease.
Although theories of malignancy that espouse a stepwise progression from local to
locoregional to metastatic disease have been shown to be inaccurate for breast and
gastrointestinal solid tumors, squamous cell carcinoma of the head and neck does
seem to spend a considerable portion of its natural history in the local or locoregional
stages. After passage through the basement membrane, malignancy invades the
surrounding mesenchymal tissue, be it muscle, cartilage, or bone. Proteases and
collagenolytic and osteoclastic enzymes facilitate the destruction of the adjacent
tissues. Invasion of subjacent nerves opens the perineural spaces, and tumor emboli
may pass in the perineural lymphatics. The usual spread of tumor is from the primary
site via the subjacent lymphatics (Fig. 15-11) to the neck or by continued local
invasion through nerve and bone to the base of the skull. The virulence of the primary
tumor and its likelihood of metastasis or ability to cause the death of the host have
been estimated by a number of methods. The size of the primary tumor is the main
parameter determining its clinical stage in the TNM (tumor-node- metastasis) staging
system adopted by the American Joint Committee on Cancer (AJCC) and other
worldwide organizations (Fig. 15-12). Although it is a crude method, it is fairly
reliable in suggesting the prognosis of the patient and the appropriate form of therapy.

Histologic characteristics such as degree of differentiation (primarily a function of
nuclear morphology), pattern of invasion (blunt pushing borders vs. noncohesive
jagged borders), microvascular invasion, perineural invasion, and tumor thickness
have been used to predict the likelihood of lymph node metastasis and overall
prognosis. The amount of tumor angiogenesis within the cancer as measured by the
intensity of staining of the endothelium is a cogent predictor of aggressiveness.
Advances in biochemical and molecular investigation have allowed more careful
consideration of the primary tumors. Flow cytometric analysis of tumor suspensions
shows that aneuploidy is common in primary tumors (68 percent) and in cervical
metastases (82 percent). Aneuploid tumors are more likely to metastasize than are
diploid tumors. Correlation also has been found between thymidine labeling index and
the T stage of squamous cell carcinomas, with T3 lesions having significantly more
activity than T1. Further subcellular analysis of squamous cell carcinoma has
attempted to correlate abnormalities and thus predict behavior.

Expression of histocompatibility antigens HLA-1 and HLA-2 on squamous cell
carcinoma demonstrates marked tumor heterogeneity, particularly in poorly
differentiated tumors. The relationship of growth factors to primary tumor
development and progression is unclear, but, as in other tumors, such as breast and
brain, growth factor receptors have been identified on squamous cell carcinoma of the
head and neck. Higher absolute levels of epithelial growth factor receptor and
demonstration of amplification of the gene for epithelial growth factor receptor in
squamous cell carcinoma of the upper aerodigestive tract may indicate that epithelial
growth factor plays an important role in local tumor behavior. The histologic,
biochemical, and genetic characteristics of head and neck tumors also have been used
in an attempt to predict response to radiotherapy and chemotherapy.

As with most solid tumors, the most cogent prognosticator of head and neck cancer is
the presence or absence of lymph node metastases. In the unoperated patient, passage
of tumor emboli through the lymphatics follows an orderly pattern, with the anatomic
triangles of the neck reflecting the site of primary disease. In the patient who has
undergone previous surgical therapy or radiotherapy or who has extensive tumor that
blocks normal lymphatic flow, metastasis from a primary tumor may not follow the
usual pathways, and a neck mass may not predict accurately the site of recurrence or
new primary disease (see Fig. 15-3 B). Clinical and ultimately pathologic staging of
the neck according to the AJCC system depends on number of lymph nodes, size of
lymph nodes, fixation to the skin or subjacent neck muscles, and laterality with
respect to the primary tumor (ipsilateral, contralateral, and bilateral). Although there
are many determinants of primary tumor behavior, size and differentiation are useful
predictors of the risk of metastasis. Increasing T stage is generally reflected by
increasing N stage. Distant metastasis, however, is more closely related to N stage
than to T stage. In a study of 160 patients with extensive disease in the neck, N3a,
only 63 completed combined therapy with surgery and radiation and, of these, only 13
showed no evidence of disease at 2 years. Disseminated disease was the most
common cause of death, followed by failure at the primary site and in the neck.

Lymph node metastases appear to behave in some ways similarly to primary disease
in that micrometastases are not as poor a prognostic indicator as clinically palpable
metastatic disease. Spread of the tumor outside the capsule of the lymph node may
occur in clinically negative and positive lymph nodes and is a poor prognostic sign,
indicating a more aggressive tumor. In a study of stage III carcinoma of the oral
cavity, the 2-year survival rate of patients with no lymph node metastases was 87
percent; with intracapsular lymph node metastases, 75 percent; and with cervical
metastases with extracapsular spread, only 39 percent. The incidence of extracapsular
spread of cervical disease increases with the size of the lymph node. Proportional to
increase in extracapsular spread is the likelihood of recurrent disease, and thus of
death.

Uncontrolled growth of squamous cell carcinoma in the neck results in carotid artery
hemorrhage, invasion of the sympathetic ganglia resulting in Horner's syndrome,
erosion of the cervical vertebrae, invasion of cranial nerves IX, X, and XI (jugular
foramen syndrome) and of cranial nerve XII at the base of the skull, airway
obstruction, and brachial plexus palsy. The site of the primary tumor dictates not only
the site of cervical metastasis but the frequency as well. Although the size of the
primary lesion at presentation is important, it seems that independent of size,
squamous cell carcinomas of the tonsil and the base of the tongue have high rates of
metastasis to the neck, and lesions of the buccal mucosa and palate have low rates.

Distant metastases from squamous cell carcinoma have been reported to range from
31 percent of patients with no evidence of cervical metastases to 59 percent of those
with extensive neck disease. Despite this relatively high incidence, they are not
uniformly the cause of death. Although any site is possible, lung, bone, skin, and liver
are the most common metastases. Systemic effects of both local and systemic
disseminated tumors include hypercalcemia from bone metastasis and elaboration of
parathormonelike peptides as well as syndrome of inappropriate antidiuretic hormone
secretion (SIADH) from vasopressinlike substances. There is some evidence that the
widespread use of chemotherapy has changed the natural history of metastatic
squamous cell carcinoma, increasing the frequency of patients dying with
disseminated disease.

Diagnosis and Evaluation
History and physical examination are the most important considerations in the
diagnosis of carcinoma of the upper aerodigestive tract. A history of chronic tobacco
and alcohol abuse places the patient in the high-risk category. Males over forty with
such a history comprise 70 to 80 percent of most series of patients with head and neck
cancer. A previous occurrence of lung cancer, esophageal cancer, or other head and
neck malignancy, diseases causing immunodeficiency such as renal failure with its
therapy by transplantation, malnutrition, and AIDS are also significant.

Symptoms referable to the tumor itself usually are mild and not commensurate with
the size of the tumor, often because of the patient's generally stoic personality and
denial. Late-stage presentation is common in these patients. Barkley noted that 36
percent of patients presenting with oropharyngeal lesions had local disease alone and
that the remaining 64 percent already had cervical or disseminated metastases. Pain at
the site of the tumor is not a frequent complaint. Because otitis media and externa are
relatively rare problems in adults, pain in the ear in a patient over forty may be a
manifestation of tumor in the oral cavity, oropharynx, or larynx via referred pain
pathways, including the lingual to auriculotemporal nerves, glossopharyngeal to
tympanic nerve, or vagus to auricular nerve. Prograde neural symptoms such as
formication (the feeling of ants crawling along the lip or cheek) may represent mental
or infraorbital nerve invasion by buccal, labial, or alveolar carcinoma. Family
members or the patient may note changes in speech caused by tethering of the tongue
(Fig. 15-13). Constant or variable hoarseness is the sign of vocal cord impairment by
local growth of laryngeal or hypopharyngeal cancer or by paralysis in the neck of the
recurrent laryngeal nerve. The sensation of scratchiness or tickling in the throat,
gagging on food, or nocturnal choking secondary to aspiration may all represent
interference with the synergistic mechanisms of swallowing and breathing. Airway
compromise is usually a late symptom but occasionally may be the first presentation
in an emergency setting. The typical American patient, then, is male, over forty, with
a long history of tobacco and alcohol abuse, frequently with underlying psychologic
or behavioral disorder such as depression or antisocial personality with withdrawal.

Visualization of the entire upper aerodigestive tract, using a systematic approach that
includes inspection of the facial and cervical surface anatomy and contour, intraoral
examination, and indirect (mirror) laryngoscopy with nasopharyngoscopy, is essential
for diagnosis and staging (Fig. 15-14). In addition to size, shape, and projection into
the cavity (exophytic or degree of ulceration), it is important to note the mobility of
the tongue and its position relative to the midline (hypoglossal nerve function), any
fixation of the tongue to the adjacent mandible, and any direct invasion of the
mandible. Mirror examination of the oropharynx and hypopharynx and larynx should
note the patency of the vallecula, the distensibility of the pyriform sinuses, and the
normal adduction to the midline of the vocal cords. Interference with vocal cord
function may result as hypopharyngeal lesions invade the medial wall of the pyriform
sinus or by paralysis of the recurrent laryngeal nerve. By retracting the soft palate
forward with a transnasal catheter, visualization of the nasopharynx is possible with
the mirror. The vault of the nasopharynx, the choanae, and the eustachian tube should
be examined. The condition of the teeth and gums should be evaluated and the
presence of torus palatinus or torus mandibularis noted. Limited motion of the
mandible may come from direct tumor invasion or, more frequently, from invasion of
tumor through the retromolar trigone area or tonsillar fossa to the pterygoid muscles.
Infiltration or inflammation of the internal and external pterygoids limits jaw motion
and causes the uncomfortable symptom of trismus, an ominous clinical sign.
Compilation of the appropriate information about the primary tumor allows clinical
staging. The distinct anatomic site, size, pattern of growth, and invasion of adjacent
structures are all necessary to assign the appropriate T stage.

Examination of the neck will reveal the presence or absence of lymph node
metastases. The site of the primary tumor should predict the most likely site of
metastatic disease (see Fig. 15-11). Enlargement or inflammation of the
submandibular gland may interfere with evaluation of the neck. Careful palpation,
preferably performed with the examiner standing behind the seated patient, allows
systematic and sequential evaluation of the submental, submandibular,
jugulodigastric, midjugular, juguloomohyoid, posterior triangle, and supraclavicular
lymph node stations. The number of lymph nodes, lymph node size, and any fixation
to the skin or subjacent muscle allows the examiner to assign an N stage. Tumors with
no evident primary site are manifested as lymph node metastases in 3 to 4 percent of
malignancies. Cervical metastases of squamous cell carcinoma comprise two- thirds
of these cases. Furthermore, the initial manifestation of the subsequently discovered
disease is a neck mass in 25 percent of the patients with carcinoma of the oral cavity,
oropharynx, and thyroid, and in 50 percent of patients with carcinoma of the
nasopharynx. Because of variable extension into the neck, parotid gland masses may
present as a cervical lymph node. The characterization of masses in the neck can be
guided largely by age. In children congenital and inflammatory masses predominate;
in young adults, inflammation or proliferative disorders of the lymphatic system; and
in adults, metastatic disease from the upper aerodigestive tract and skin.

Careful physical examination, including neurologic examination of the remainder of
the head and neck area, may reveal evidence of more extensive disease such as
cavernous sinus invasion, as documented by extraocular movement disorders, or
invasion of the cervical sympathetics, as indicated by Horner's syndrome.

Distant metastases are evaluated by history, physical examination, laboratory
procedures, and radiology. Pleuritic pain or shortness of breath may indicate lung
involvement, and distinct pain at a specific site may indicate spread to distant bone.

Before treatment planning, definitive histologic confirmation of disease is necessary.
If a primary site is visible, a wedge biopsy specimen should be taken at the edge of
the tumor to include some adjacent normal tissue, fixed in formalin, and examined
histologically. Touch preparations and other cytologic methods are occasionally
helpful but suffer from lack of specificity and sensitivity. Although the extent of the
tumor usually can be assessed by direct visualization, the use of vital dyes such as
toluidine blue may help to delineate the extent of the disease, staining only the
malignant and dysplastic epithelium and washing off the surrounding inflamed tissue.
Hematoporphyrin dyes share this characteristic of differential uptake by tumor and
normal cells and have occasionally been of use in demarcating index tumors and
identifying and sometimes treating multicentric disease. Because of the significant
incidence of synchronous primary tumors, evaluation of the rest of the upper
aerodigestive tract may be useful. The value of triple endoscopy—bronchoscopy,
esophagoscopy, and direct laryngoscopy—has been debated, but it is advisable for the
ideal work-up of an advanced head and neck cancer in a patient with a long history of
tobacco and alcohol use.
Since treatment planning depends a great deal on the clinical stage of disease, and
since therapies vary greatly in morbidity to the patient, precise and accurate staging is
essential. Extent of resection and volume of radiotherapy depend on a reliable
assessment of the degree of invasion of the primary tumor. The use of adjuvant
chemotherapy or radiotherapy or the inclusion of neck dissection in the surgical plan
usually is determined after careful analysis of the neck. Various radiologic studies
may help to define the extent of the disease.

Radiologic evaluation of intraoral disease usually involves assessment of the
mandible. If tumor abuts the mandible in the lingual or buccal sulcus and is not easily
mobile, it may penetrate the cortex. In edentulous patients, tumor descends through
the cortical defects left by the previous teeth along the occlusal ridge. Once the
medullary canal has been invaded, spread may occur locally or by way of the inferior
alveolar nerve. In dentulous patients, direct invasion of the lingual plate occurs, and
spread usually does not extend within the bone beyond the extent of the soft- tissue
tumor. Dental films taken directly at the site of tumor contact show cortical invasion
or widening of the periodontal membrane. Panoramic films and mandibular series
show the extent of disease within the mandible by cortical disruption and widening of
the inferior alveolar canal or mental foramen. Simple plain-film radiographic analysis
of the mandible, however, may be inaccurate, with one series of 111 patients
revealing a false-negative rate of 44 percent and a false-positive rate of 9 percent.
Technetium-99m radionuclide bone scans have been advocated for diagnosis of
mandibular invasion. Although their sensitivity is greater in general than plain films,
their specificity is not great, with false-positive rates of 53 percent and false-negative
rates of 12 percent. In large tumors bone scans are even more likely to be false-
positive because of surrounding inflammation. CT is a highly sensitive method of
diagnosing cortical invasion, but the presence of metal tooth fillings interferes with its
accuracy (Fig. 15-15). MRI is probably the most accurate and useful method of
evaluating the mandible in suspicious but not definitive cases, because it can
accumulate and reformat data in any plane without repositioning the patient, it offers
superior separation of cortical and marrow images, and it is unaffected by dental
fillings.

Analysis of the extent of intraoral and paranasal sinus tumors in difficult- to-examine
areas such as the parapharyngeal space, larynx, and nasopharynx is assisted by both
CT and MRI. Correlation between extent of disease determined at operation and
preoperative CT scanning was found in 78 percent of 26 patients evaluated by high-
resolution CT, and 94 percent when MRI with contrast enhancement with gadolinium
DTPA was used. Particular advantage is obtained in evaluation of muscle and bone
invasion, but mucosal detail is difficult to assess with both CT and MRI (Fig. 15-16).

The administration of agents such as gadolinium with MRI provides better soft-tissue
contrast and can suggest the differences between tumor and surrounding
inflammation. By reformatting images in several planes, a three-dimensional
characterization of the tumor is possible that can better demonstrate tumor
relationships to nearby normal structures and can aid in more accurate staging. MRI-
directed stereotactic surgical techniques have been used in neurosurgery and in the
administration of radiotherapy and may have a role in surgical extirpation of
carcinoma of the head and neck.
Since survival seems to depend on eradication of regional as well as local disease,
evaluation of the neck for the risk of metastatic disease is crucial to the overall
treatment plan. Surgery or radiotherapy may be used to remove regional disease in the
lymph nodes if there is disease that is clinically apparent (palpable N+) or if there is
high risk of disease in a clinically negative neck (N0). As has been discussed, the size
of the primary tumor (T stage), its histologic parameters, and its site all may suggest
an increased likelihood of subclinical disease in the neck. Unfortunately, physical
examination of the neck may be faulty, with false-negative rates ranging from 16 to
60 percent. Although of some importance, the rates of false positivity are generally
lower and usually not as clinically relevant. Lymphangiography has been unrewarding
in the evaluation of the neck. CT has recently been evaluated and found in most
studies to be slightly more sensitive than physical examination: 82 percent sensitivity
versus 75 percent, 93 percent versus 70 percent, and 90 percent versus 82 percent in
three studies. Implicit in this advantage is the ability of CT to upstage disease from
N0 to N+ and suggest the need for neck dissection. Gadolinium-enhanced MRI
appears even more sensitive—92 percent sensitivity versus 82 percent for CT
scanning and 75 percent for physical examination—and is also useful in upstaging
disease. Although these technologies are not necessary in every case of clinical
staging, they are of significant value in decision-making when physical examination
of the neck is difficult because of obesity, anatomic variation, or previous surgical or
radiation therapy. Micrometastases of less than 3 mm, however, are still undetectable
by any available technology, although position emission tomography using fluorine
18–labeled 2-deoxyglucose (PET-FDG) has demonstrated exquisite sensitivity in
early studies of squamous cell carcinoma and melanoma metastatic lymphadenopathy.

Therapy
Decision-making on therapy is based almost completely on the clinical stage (TNM)
of the tumor at the time of presentation. Although histologic characteristics may to a
slight degree influence the treatment, the size of the local tumor and the extent of
invasion of adjacent structures (T stage); the presence or absence, the number, and the
laterality of cervical metastases (N stage); and the presence or absence of distant
metastatic disease (M stage) dictate therapy. Definitive or curative treatment methods
all are oriented toward total extirpation of local and locoregional disease, with the
expected subsequent decrease in disseminated disease. Palliative procedures, which
may produce relief of pain, relief of airway obstruction, or improvement in local
function and hygiene, similarly require complete macroscopic tumor removal at the
primary site and in the neck and may occasionally be justifiable in the presence of
distant metastases. Subtotal resection of local or locoregional disease is unlikely to be
of any benefit in any situation.

Definitive therapy may consist of surgery alone, radiotherapy alone, surgery with
radiotherapy as a preoperative or postoperative adjuvant, or chemotherapy delivered
either systemically by intravenous route or locally by intraarterial infusion before
either or both modalities as neoadjuvant therapy. For small tumors (less than 2 cm,
T1), surgery or radiotherapy, well planned and appropriately executed, in most cases
will have equivalent local control and survival rates (Fig. 15-17). The choice of the
method, then, depends on patient compliance, volition, associated disease, expense,
interference with normal function, and available facilities. As the size of the tumor
increases to T2 stage or greater, the likelihood of local control and ultimate cure with
radiotherapy alone decreases, so surgery or surgery with adjuvant radiotherapy
becomes preferable (Fig. 15-18). In the larynx, where staging is more a function of
invasion of adjacent structures than of tumor size, and where function is completely
dependent on preservation of structure, radiotherapy is usually the first choice for T1
and T2 lesions and is occasionally used as definitive therapy for T3 lesions. Advanced
disease has a poor prognosis even with combined treatments of surgery and
radiotherapy.

Unfortunately, postoperative adjuvant chemotherapy has been unsuccessful in
prolonging life in controlled randomized trials. Despite high response rates to
preoperative administration of cisplatin and 5-fluorouracil there has not been the
survival advantage that had been demonstrated with chemotherapy for breast disease.
One possible role for chemotherapy, however, is as a predictor of successful therapy
and thus an indicator of which patients may be treated with radiotherapy instead of
surgery with better preservation of function. In several prospective studies patients
with T3 or T4 laryngeal tumors were treated with cisplatin, 100 mg/m2 body surface
area, and 5-fluorouracil, 100 mg/m2/day × 4 for three courses. Patients with complete
response (disappearance of all tumor) were then treated by either radiotherapy alone
or the more conventional approach of surgery (laryngectomy) with postoperative
adjuvant radiotherapy. Patients with less than complete responses were treated with
surgery plus radiotherapy. Results show no difference in survival between patients
who respond completely to chemotherapy whether they had been treated primarily
with surgery, radiation therapy, or not. Patients with incomplete response to
chemotherapy had much poorer survival than either group of complete responders.
These findings may indicate that the natural history of tumors that respond completely
was more benign and that they can be treated less aggressively, preserving function.
Approximately 30 to 40 percent of patients treated with chemotherapy and
radiotherapy can survive with a preserved larynx. Nonresponders probably
demonstrate greater tumor heterogeneity or clonal resistance to therapy and thus are
unlikely to have their tumor controlled by any therapy. The results of these trials on
carcinoma of the larynx have stimulated investigators to study other head and neck
sites for the possibility of organ preservation. Given a 40 to 50 percent complete
response to chemotherapy, improved techniques in patient selection (genetic analysis
of tumors), and radiotherapy, there is speculation that higher cure rates with
preservation of function are possible. Salvage surgery in these previously irradiated
patients, however, is difficult, with major complication rates approaching 40 to 50
percent.

The basic principle of solid tumor therapy is en bloc treatment, either resection or
radiotherapy of the primary tumor and the regional disease in the neck. The decision
of whether to treat the neck or not depends on the presence of clinically discernible
metastatic disease or the risk of micrometastases to the neck. As primary tumor size
increases, risk of neck disease increases at a greater rate for some primary sites than
others (Fig. 15-19). When palpable lymph nodes are present in the neck, confirmation
of metastatic disease may be obtained with fine-needle aspiration and cytologic
examination, or the decision to proceed with therapy may be made on purely clinical
grounds. Palpable or radiologically positive lymph node metastases require surgical
therapy in the form of some type of neck dissection, usually performed in continuity
with the resection of the primary tumor. Subclinical disease or micrometastases may
be treated by a modification of neck dissection or radiotherapy, depending on the
modality chosen for treatment of the primary site.

The lymph nodes draining the head and neck are contained in a fascial envelope,
between the superficial and deep layers of the investing fascia of the neck. Within the
layers of the investing fascia lie the sternocleidomastoid muscle and the spinal
accessory nerve (CN XI). The cervical lymph nodes lie between the investing fascia
and the deep cervical fascia (Fig. 15-20) or prevertebral fascia and can be removed in
toto with the jugular vein, the sternocleidomastoid muscle, and the accessory nerve, as
in the classical radical neck dissection described by Crile in 1906 (Fig. 15- 21). The
lymphatic connections between the tumor and the cervical metastases should remain
intact with en bloc resection, and all the lymph- node-bearing tissue of the exposed
side of the neck, including the anterior and posterior triangle, is removed.

The major morbidity of neck dissection is secondary to paralysis of the trapezius
muscle by resection of the accessory nerve. Because of this, Bocca in 1967 suggested
preservation of the nerve. Other surgeons have demonstrated techniques in which the
jugular vein and the sternocleidomastoid muscle also can be left intact. These
methods are particularly useful in prophylactic (elective) neck dissections when there
is no clinical evidence of metastatic disease to the neck. Although there is some
debate about the quality of function after modified neck dissection, it seems likely that
long-term function is improved when the spinal accessory nerve is preserved, and the
likelihood of survival is not significantly impaired by the lesser procedure.

Since the site of potential neck metastasis can be fairly accurately predicted by the
location of the primary squamous cell carcinoma, and since the lymph-node-
containing areas of the neck have been described as discrete anatomic areas
demarcated by muscles, fascial condensations, and the triangles of the neck, it has
been suggested that in addition to leaving the accessory nerve and the
sternocleidomastoid muscle intact, only those lymph nodes at risk should be resected.
The concept of selective neck dissection, customized to the site of primary disease,
has gained support. Thus for carcinoma of the lip, anterior tongue, floor of the mouth,
and buccal mucosa, supraomohyoid neck dissection might be used, removing the
submental, submandibular, upper and midjugular lymph nodes (Levels I, II, and III).
If a nasopharyngeal lesion or posterior scalp melanoma was the primary site, the
suboccipital, retroauricular, upper and midjugular, and posterior triangle lymph nodes
(Levels II, III, IV, and V) would be removed via a posterolateral neck dissection. In
primary sites of the pharynx or larynx, a lateral neck dissection including upper,
middle, and lower jugular nodes (Levels II, III and IV) might be appropriate. In
thyroid disease, removal of the paratracheal, perithyroidal, and precricoid nodes in an
anterior compartment neck dissection might be appropriate (Fig. 15-22). Although it
seems obvious that control of disease in the neck by its surgical removal with some
form of neck dissection should improve survival, there is no well-designed
prospective study to prove the equivalency or superiority of neck dissection or
radiotherapy for the clinically negative (N0) neck or to suggest which operation of the
several described should be used.

Approximately 70 percent of patients in the United States who present with squamous
cell carcinoma of the upper aerodigestive tract have advanced disease, stage III or
stage IV. Even with aggressive therapy late- stage disease has a high recurrence rate.
Recurrent disease may occur at the primary site in the previously treated neck and in
the contralateral neck. Just as with primary disease, the therapy of recurrent disease is
based on wide local resection and clearance of the involved or at-risk regional lymph
nodes. The extent of resection depends on involvement by tumor and the proximity to
the great vessels and the central nervous system. If tissue tolerance to ionizing
radiation allows, postoperative adjuvant radiotherapy may be useful, even as a second
course. For unresectable recurrent disease, combinations of chemotherapy and
radiotherapy or chemotherapy alone as well as laser or other noninvasive surgical
methods of tumor reduction may provide some palliation in reducing bulk, alleviating
pain and airway compression, but long-term survival does not appear to be improved.

The therapy of distant metastases of squamous cell carcinoma of the upper
aerodigestive tract has been unsuccessful. The lung is a common site of metastasis for
head and neck cancer, but it must be realized that a solitary lesion in the lung of a
patient with a previous squamous cell carcinoma of the head and neck is more likely
to be a primary lung cancer than a metastatic deposit. The patient should be
aggressively evaluated and treated for that primary cancer. Resection of metastatic
disease to the lung, however, has not proved salutary in most cases. Second primary
tumors or metachronous tumors are a significant problem in head and neck cancer.
Prevention of recurrent disease and of new primary disease and reversion of possible
premalignant entities may be possible with chemoprevention. Isotretinoin, a vitamin
A analogue, and beta carotene have reduced concomitant premalignant changes, and
have possibly reduced the incidence of second primary malignancies in patients with
epidermoid carcinoma of the upper aerodigestive tract.

Immunotherapy
Because of prolonged alcohol abuse and coincident malnutrition, many patients with
squamous cell carcinoma of the head and neck present with various manifestations of
immunodeficiency. There is evidence that anergy and deficient cellular immunity
result in poorer survival rates for squamous cell carcinoma of the head and neck as
well as for other malignancies.

Cell-mediated immunity has been demonstrated to be depressed in head and neck
cancer patients. The cause of this depression is uncertain, however, and surgery,
radiotherapy, the malignancy itself, and suppression of natural killer cell function by
circulating immune complexes all have been implicated. Natural killer cells have been
shown to function as a recognition and defense mechanism against metastatic disease
from primary squamous cell carcinoma. The effects of humoral or B-cell-mediated
immunity on the progression of head and neck carcinoma are not as clear. Unlike
some malignant cells, the squamous cell carcinoma tumor cultures have not been
particularly immunogenic, and cell-specific immune manipulation has not yet been
achieved.

Nonspecific cellular immunostimulation with various agents, such as levamisole,
thymosin, and interferon, however, has shown some promise both as an adjuvant and
as palliative method. Natural killer cells from patients with head and neck cancer
treated in vitro with interleukin-2 (IL-2) show increased activity after therapy,
suggesting that IL-2 negates some of the suppressive agents in the serum. The use of
IL-2 has been extended to the clinical arena, with infusion of this agent with
intramuscular interferon-a reversing in vivo depressed natural killer cell activity.
Perilesional injection of IL-2 in recurrent inoperable head and neck carcinoma
resulted in temporary but dramatic response in 65 percent of 20 patients treated.
Systemic recombinant interferon-a given intramuscularly resulted in one complete
response, one partial response, and two stabilizations of disease in 14 patients treated
with a second cycle, with salutary effect being attributed to a rise in natural killer cell
activity.

Although the benefit is as yet uncertain, it appears likely that more specific
characterization of the antigenic identity of squamous cell carcinoma and more
precise manipulation of effector cells through natural or synthetic lymphokines will
ultimately help in the adjuvant therapy of head and neck cancer.

Reconstruction
In the treatment of head and neck cancer, as in any other disease, there is a hierarchy
of priorities. Survival obviously is of first concern and depends a great deal on
adequate surgical or radiotherapeutic ablation and possibly adjuvant chemotherapy or
immunotherapy. Freedom from pain fortunately is accomplished in most cases of
successful ablative therapy. Preservation or restoration of function as well as
appearance is the next consideration and relies largely on the ability of the surgeon to
repair the created defect with local, regional, or distant tissues. Finally, but perhaps
most practically important to the patient, is the efficiency of the treatment regimen.
Efficiency dictates that the therapy be delivered in a time period commensurate with
the natural history of the disease.

Advanced squamous cell carcinoma has a high recurrence rate. Eighty-nine percent of
patients whose local or regional disease recurs have their recurrence within 2 years of
therapy. Thus restoration of function and appearance in this group of patients with a
high failure rate and short disease-free intervals should be performed as quickly as
possible. A multiple-stage method of reconstruction carried out over several months
may prolong recovery. The most efficient methods are single-stage reconstructions
performed at the time of the ablative surgery.

In the past there was considerable reluctance to perform immediate reconstruction
after resection of malignancy. Fear of cloaking persistent or recurrent disease, coupled
with realistic assessment of the poor results from multiple procedures, led to
recommendations that the patient be observed for 1 to 5 years after surgery. The
functional disability inherent in major oral or oropharyngeal resection usually
mandated permanent gastrostomy for feeding and tracheostomy for safe maintenance
of the airway. The attendant loss of taste, speech, swallowing, and other corollary
functions made the postoperative state of the patient with head and neck cancer
miserable.

Improved methods of reconstruction, better pathologic analysis at surgery, and a more
comprehensive understanding of the natural history of the disease have made single-
stage reconstruction at the time of the initial surgical resection the current standard of
care in most instances. Resection of the primary disease and regional metastatic
disease, confirmation of disease clearance by frozen-section examination of the
margin of resection, and immediate reconstruction are usually possible for squamous
cell carcinoma of the upper aerodigestive tract. In malignancies for which frozen-
section analysis may be inaccurate, when bone is involved, in recurrent disease with
previous radiotherapy, or when there is uncertainty about other aspects of the
resection, secondary reconstruction may be more appropriate.

The upper aerodigestive tract is a complex mixture of cutaneous cover, epithelial
lining, bone, and cartilaginous framework all joined in a complex arrangement by
muscle and driven in intricate synergy to facilitate the main vegetative functions of
the organism, alimentation and respiration. This complex mobile structure and the
heavy colonization of the mucosal surfaces by bacteria as well as the deleterious
effects of adjuvant radiotherapy (acute inflammation in the early stages and fibrosis
and vasculitis in later stages) all make reconstruction extremely difficult.

The basic needs presented by surgical resection are restoration of continuity of the
alimentary tube with epithelial lining, provision of reliable external coverage for
protection of the great vessels and bony structures, and separation of the central
nervous system and upper aerodigestive tract. Restoration of oral continence,
facilitation of the coordinated motions of the tongue and larynx, and maintenance of
an open passage for swallowing while separating the oral, oropharyngeal, and nasal
cavities are refinements on the basic demand that are necessary for a reasonable
quality of life. Accurate analysis of the wound created by the surgical resection is the
first element required for successful reconstruction. Size, exposure of the central
nervous system, mobility of the removed parts, presence of bacterial colonization or
invasive infection, type of tissue removed (mucosa, bone, cartilage), history of
previous surgery or radiotherapy, likelihood of subsequent surgery or radiotherapy,
exposure of the carotid or jugular vessels, and effect of external appearance all are
important wound characteristics that affect the choice of reconstructive techniques.
Whether to attempt to satisfy only the basic reconstructive needs or to restore as many
missing elements as possible is a difficult decision involving patient desires and
compliance, surgical skill, consideration of disease stage, and many other factors.

The past 15 years have brought enormous advances in reconstructive techniques that
have affected mainly the efficiency of therapy in restoring the patient to reasonable
function and appearance rapidly. Indirectly, however, improved reconstructive
techniques have an impact on survival, since more aggressive resections, salvage of
radical radiotherapy, and decrease in postoperative complications with attendant
infection and malnutrition are accomplished with relative safety. The fundamental
improvement has been the ability to transfer large volumes of well- vascularized
tissue to the area.

Although flap reconstruction of the external surface of the nose was taught by the
early Hindu surgeon Sushruta, and the Renaissance saw a number of reconstructive
attempts at nasal and other external defects (by distant flaps attached to the defect and
divided after parasitizing their blood supply from local tissues), major reconstructions
have been a relatively recent phenomenon. Throughout the development of surgical
technique that followed the introduction of general anesthesia in 1846, the principle of
random flaps of skin being attached and divided remained the mainstay of the
reconstructive effort. Large segments of tissue from the chest and back were moved in
multiple stages to the oral cavity, face, and pharynx.

In 1965 Bakamjian described the deltopectoral flap, which possessed an axial or
direct arterial blood supply from the perforating vessels of the internal mammary
artery and vein to the skin of the chest and shoulder. This provided a relatively
reliable large segment of tissue that was particularly useful in the reconstruction of the
pharynx. The forehead flap, another axial pattern flap, based on the superficial
temporal vessels, was described in 1963 and, despite its disfigurement of the donor
site, became a useful method of reconstruction of the oral cavity. With the realization
in the 1970s that the blood supply to the skin came not only from the randomly
oriented subdermal plexus vessels and axial cutaneous vessels but also from
perforating vessels from the subjacent muscles, the musculocutaneous concept
transformed reconstruction, particularly that of head and neck defects. Large flat
muscles of the thorax could be rotated on their long vascular pedicles to supply a
large volume of well-vascularized tissue in a single operation on the oral cavity,
pharynx, or soft tissues of the face. Moreover, if recurrence of disease mandated a
subsequent resection, another thoracic musculocutaneous flap was available to repair
the defect. The pectoralis major, latissimus dorsi, trapezius, sternocleidomastoid, and
platysma muscles all are useful, either alone or with their overlying skin. Now much
larger and more complex wounds could be addressed at a single operation, returning
the patient to reasonable function and appearance promptly.

Some of the problems with the thoracic musculocutaneous flaps are the effect of
gravity on bulky flaps, additive morbidity to the shoulder girdle when neck dissection
is performed, and variable blood supply to the skin, particularly in the pectoralis
major musculocutaneous flap, depending on where the skin portion of the flap is
located. Furthermore, there is no reliable method of transporting vascularized bone
with a regional musculocutaneous flap.

Despite these disadvantages, the musculocutaneous concept has made immediate
reconstruction of the head and neck resection the accepted procedure in most cases.

An offshoot of the success of reconstructive efforts with musculocutaneous flaps has
been the increased interest in vascular anatomy (Fig. 15-23). Subsequent research and
improvements in microscope and instrument technology have resulted in the ability to
transfer tissue of many different types from various sites of the body by separating
arterial supply and venous drainage of the tissue and reattaching it to blood vessels in
the head and neck. Bone, muscle, skin, fascia, and combinations of these are available
for various sites, as are intraabdominal viscera. Microvascular reconstruction or free
tissue transfer has made it possible for the surgeon to close virtually any defect in the
head and neck, no matter how large or complex. Even more important, however, is
that the large number of methods available allows the reconstructive surgeon to
choose the method or methods most suitable to a specific site and analyze the results
(Table 15-1). Just as each wound has its own characteristics, so does each flap.
Vascular pedicle length, bulk, type of epithelium, presence and durability of bone, and
thickness of soft tissue all can be evaluated to select the most appropriate replacement
for the individual problem (Fig. 15-24).

Complications
The therapy of squamous cell carcinoma of the head and neck usually requires two
potent modalities—surgery and radiotherapy—directed at an area that is heavily
contaminated with saprophytic and pathogenic organisms in a patient who is
frequently malnourished and immunodeficient, and may be noncompliant. Since
many patients present with advanced disease, the failure rate even for combined
therapy is high as a result of disseminated disease as well as local or locoregional
failure. It is therefore imperative to deliver the therapy in a form that is efficient and
results in the patient's rapid return to function, reasonable appearance, and whatever
social situation the patient may be able to recover. Recognition of the inevitable
sequelae of therapy—complications—and rapid resolution or, preferably, prevention
are thus of great importance.

Complications specific to head and neck cancer therapy can be categorized as
anatomic, injury to nerves or blood vessels within the field of surgery; physiologic,
the results of interference with blood or lymphatic supply to the area secondary to
surgery or radiotherapy; technical, surgical rearrangements that result in secondary
problems; and functional derangements of normal behavior secondary to therapy. All
of these can then be grouped into catastrophic or noncatastrophic complications,
which will in large part dictate the surgeon's approach to them, whether preventive or
therapeutic.

The most appropriate approach to complications is prevention. Restoration of positive
nitrogen balance, preoperative pulmonary hygiene, control of diabetes mellitus, and
weaning from alcohol and tobacco are important nonspecific measures. Preoperative
antibiotics decrease the likelihood of wound infection and its sequelae. Numerous
studies have shown that previously administered radiotherapy, particularly if given in
definitive therapeutic doses, increases the risk of complication. Dental hygiene or
rehabilitation before definitive surgery is important in patients whose mandible has
been previously irradiated to prevent subsequent osteoradionecrosis. Patient education
is crucial to ensure cooperation in what may be a difficult postoperative rehabilitation.

Other than injury to the thoracic duct, which may result in significant fat and protein
loss through a chylous fistula, most anatomic complications are nerve injuries, either
purposeful or otherwise secondary to primary tumor resection or radical neck
dissection. The accessory, marginal mandibular, mylohyoid, and cervical plexus
sensory branches are frequently sacrificed in neck dissection. Injuries caused by
traction, electrocautery, or other technical misadventure may occur to any structure
but are most likely to affect hypoglossal, lingual, mandibular, vagus, phrenic, facial,
recurrent laryngeal, motor branches to the cervical plexus and cervical sympathetic
chain. Careful technique during surgery, adequate hemostasis to allow good
visualization, and knowledge of normal and pathologic anatomy will decrease the
likelihood of anatomic complications.

Previous surgery, the planned surgery, and radiotherapy all may interfere with blood
supply to the head and neck, resulting in local and systemic problems. Irradiation
alone or combined with surgery result in a 22 to 30 percent incidence of clinical
hypothyroidism, particularly in laryngeal surgery. Hypoparathyroidism, transient or
permanent, may result in up to 10 percent of cases of thyroidectomy and must be
considered after laryngopharyngectomy. Obstruction of one or both jugular veins,
particularly when combined with lymphadenectomy, results in lymphedema of the
face and may result in intracerebral edema, particularly if excessive fluid is
administered during surgery. Head elevation, diuretics, and judicious fluid
management, however, usually allow collateral flow through the vertebral veins to
resolve these problems.
Surgical misadventure, poor planning or execution, or the presence of infection will
result in technical complications. Respiratory problems can result from pneumothorax
precipitated while operating in the mediastinum or supraclavicular fossa. Hematoma
may cause acute upper airway obstruction. Tracheostomy may cause subcutaneous
emphysema, tracheoinnominate fistula, or subglottic stenosis. The combination of
infection and local ischemia of skin or mucosa may result in wound infection, suture
line breakdown, flap necrosis, osteomyelitis, and osteoradionecrosis. Exposure of a
previously irradiated carotid artery usually results in a bacterial infection and rupture
and must be treated as a surgical emergency. Careful planning, meticulous attention to
watertight closure of the pharynx and oral cavity, and provision of adequate
independently well-vascularized tissue for reconstruction will minimize the likelihood
of technical complications.

Restoration of function is one of the main goals of head and neck cancer therapy.
Although some dysfunction is inherent in all therapy, proper selection of
reconstructive methods, attention to intrinsic function of the structures resected and
those remaining, and careful and patient postoperative rehabilitation will decrease the
severity of the common functional complications: chronic airway obstruction,
aspiration pneumonia, dysphagia, dysphonia, and mental depression.

The potential for catastrophe is great in head and neck cancer surgery. Recognition of
a complication and realization of the likelihood of rapid deterioration are important to
prevent catastrophic complications. Tetany from hypoparathyroidism, acute airway
obstruction from hematoma or a dislodged tracheostomy tube, tracheoinnominate
fistula, and carotid hemorrhage all can lead to rapid death. Any complication that
occurs in a patient who has been previously irradiated must be aggressively resolved.
Carotid artery exposure, oropharyngocutaneous fistula, or skin flap necrosis in the
irradiated neck could result in subsequent invasive infection of the great vessels and
death (Fig. 15-25). Oropharyngocutaneous fistula is relatively common, ranging from
6 to 38 percent of head and neck cancer cases, and can be treated expectantly if
salivary flow can be diverted and the carotid arteries protected by well-vascularized
tissue. The pectoralis major musculocutaneous flap is a useful method of closing
major fistulas and covering the great vessels at the same time. Pharyngocutaneous
fistulas of moderate size may be treated by the sternocleidomastoid musculocutaneous
flap (Fig. 15-26).

Oral Cavity
Anatomy and Physiology
The anatomic borders of the oral cavity are the mucosal surfaces of the lip externally
and the anterior tonsillar pillar posteriorly. The oral cavity usually is considered as a
number of distinct entities: the lips, the buccal mucosa, the gums (mandibular and
maxillary, including the retromolar trigone), the floor of the mouth, the mobile
tongue, and the hard palate. Thus the oral cavity is the aditus of the long
seromuscular-mucosal tubular conduit of food and liquid that allows the organism to
obtain nourishment. As such it is modified in several ways to facilitate the initiation
of alimentation. The lips are a sphincter that allows the oral cavity to be sealed after
intake of food and liquid. The buccal surfaces and the buccinator muscles help to
collapse and expand the oral cavity to facilitate passage of food back to the pharynx.
The hard palate provides a stable platform against which the mobile tongue can push
and separates the oral and nasal cavities. The floor of the mouth and the gums are
structural components of the reservoir and aid in the preparation functions of the oral
cavity in the process of eating; the mobile tongue is the main propulsive agent in the
oral cavity. Each site also has a distinct contribution to the modulation of air expelled
from the lungs that results in speech.

Therapy
Carcinogenesis in the oral cavity and the natural history of subsequent disease are
generally similar independent of anatomic area, although TNM staging has not been a
perfect prognosticator for all sites, and histology and site play an important role in
outcome. The consequences to the patient of therapy, particularly surgical therapy,
however, are very different and depend very much on the function of the area
involved and the success with which it can be reconstructed.

Lip Etiology
In the United States and Canada, carcinoma of the lip is common, with a marked male
predominance of 20:1. The lower lip is by far the most common site, being involved
in approximately 95 percent of cases, and has squamous cell carcinoma as the most
common histology. Basal cell carcinoma predominates in the upper lip. The habit of
pipe smoking, with chronic thermal injury, was for many years believed to be the
carcinogenic stimulus. Recently, however, it has become clear that the protuberant
lower lip is exposed to higher doses of ultraviolet radiation, resulting in malignancy
that behaves similarly to UV-induced skin cancer. Farmers and other outdoor workers
in their sixth to ninth decades, of Celtic and northern European origin, who live in
areas of high sunlight exposure are at highest risk. Chronic exposure to sun results in
loss of the anatomic vermilion border, the junction between the skin and mucosa of
the lip, followed by leukoplakia or carcinoma in situ and by invasive malignancy (Fig.
15-27).

Pathology
Well-differentiated stage I lesions comprise the majority, 60 to 80 percent, of most
clinical series. Local recurrence after surgery or irradiation occurs in 10 to 20 percent
of cases, but salvage therapy (subsequent surgery with or without radiation or
chemotherapy) may be successful. Nodal metastases, usually to the submental or
submandibular nodes, are present in 10 to 15 percent of cases and occur in tumors of
all histologic differentiation. Treatment by local excision or radiation results in cure
rates of approximately 90 percent for stage I disease and 55 to 80 percent in stage II
locoregional disease. Aggressive carcinoma of the lip seems to follow a pattern of
perineural invasion, down the mental nerve to involve the mandible and pterygoid
space, and ultimately via the trigeminal nerve to the base of the skull.

Therapy
Surgical therapy requires resection of the disease with a clear margin of normal tissue
around it. If lymph nodes are involved, ipsilateral or bilateral neck dissection is
indicated. Elective or prophylactic node dissection for the patient with the N0 neck
usually is not recommended in epidermoid carcinoma of the lip. The functional goal
in lip reconstruction is restoration of oral continence and reasonable appearance.
Because the lower lip is longer and more protuberant than the upper lip, primary
closure of defects of approximately 25 percent of the upper lip and 35 percent of the
lower lip will result in satisfactory appearance and function. The lip opposite the
resection is an important donor site for larger defects. Cross-lip flaps from either the
upper or lower lip of the Abbé or Estlander type and advancement of lateral labial and
buccal elements are useful, depending on the size and site of the defect. Preservation
of sensory and motor function of the remaining orbicularis oris muscle also is
possible, to maintain the most efficient sphincter mechanism, using the Karapandzic
principle. When the entire lower lip is resected, the damming function can be restored
by a radial forearm free flap including palmaris longus tendon, which is inset to the
adjacent oral musculature to serve as a dynamic sling. Since the tissue at risk is oral
mucosa on the protuberant area of the lip, preneoplastic changes of leukoplakia or
dysplasia should be treated by mucosal resection, vermilionectomy (lip shave), and
advancement of the labial mucosa to the sun-exposed margin of the skin (mucosal
advancement).

Buccal Mucosa Anatomy and Physiology
The buccal mucosa extends from the commissures of the lips to the
pterygomandibular raphe and from the maxillary (upper) to the mandibular (lower)
alveoli on both sides. The subjacent structures include the buccal fat pad and
buccinator muscle, and the surface of the buccal mucosa permits entry to the oral
cavity of Stensen's duct from the parotid gland. This area modulates speech and oral
capacitance.

Pathology
Buccal mucosa cancer comprises about 5 percent of all oral cancers, and, as with
other sites, there is a significant male predominance (3:1). There is a high incidence of
advanced disease on presentation, with 18 percent stage I, 36 percent stage II, and 44
percent stage III, with a 56 percent incidence of nodal metastasis. Large cancers of the
buccal mucosa are less likely than tumors of other oral sites to have subclinical
metastases to the neck. A subset of lesions arising in the buccal mucosa is verrucous
carcinoma, which presents as an exophytic mass that has the cellular histology
characteristic of malignancy but lacks the invasive aspects. Verrucous carcinoma is
more common in females than in males and may be related to human papillomavirus.
The buccal mucosa is the most common site of this variant of squamous cell
carcinoma, which shows warty dense keratinization, sharply circumscribed deep
margins, pushing borders, and inflammatory infiltrate. There is a high incidence of
multicentricity of malignancy in patients with verrucous carcinoma, with up to 40
percent having other sites of invasive carcinoma, so it probably represents a part of
the spectrum of field cancerization (see Fig. 15-10 E). There is some concern that
radiation of this lesion may result in dedifferentiation or change to a more malignant
histology, but this observation may be a manifestation of tumor cell heterogeneity and
clonal resistance to radiotherapy rather than actual malignant degeneration.
Carcinoma of the buccal mucosa, both verrucous and infiltrative, occurs commonly in
chronic tobacco chewers and snuff dippers in the United States and in people who use
pan in India and Southeast Asia.

Therapy
Surgical resection with or without adjuvant radiotherapy results in survival rates of 50
to 60 percent, with 60 to 75 percent for localized disease and 25 to 45 percent for
locoregional disease. The route of invasion of epidermoid carcinoma of the buccal
mucosa is through the buccinator muscle and buccal fat pad dorsally toward the
pterygoid musculature or lateral to the skin. In either case significant limitation of oral
motion and discomfort on chewing (trismus) occurs.
Surgical resection frequently creates a full-thickness defect of mucosa, muscle, and
skin with or without adjacent mandible or maxillary tuberosity. For extensive lesions,
restoration of function requires replacement of internal lining as well as external skin
coverage. Although the forehead flap based on the superficial temporal vessels and
the deltopectoral flap from the shoulder were the standard in the 1960s and 1970s,
recent methods have included the combined use of pectoralis major musculocutaneous
flap for lining and deltopectoral skin flap for skin coverage or the latissimus dorsi
musculocutaneous flap folded on itself to provide both internal and external surfaces
(Fig. 15-28). Fasciocutaneous flaps such as the scapula and radial forearm can provide
ample tissue for both defects and vascularized bone as well when transferred as a
microvascular free flap. For smaller defects, intraoral flaps of mucosa and muscle
such as tongue flaps, palate mucoperiosteal flaps, or advancement flaps have been
useful. Split- thickness skin grafts, though successful in the short term, ultimately
result in fibrosis and difficulty with chewing. For superficial lesions that extend over
the mandibular alveolus and require supple coverage, the platysma musculocutaneous
flap is an excellent choice (Fig. 15-29).

Hard Palate Pathology
The roof of the mouth, bounded by the soft palate posteriorly and the teeth anteriorly
and laterally, is not a common site of intraoral squamous cell carcinoma. More
common in this area are tumors, both benign and malignant, of the minor salivary
glands (Fig. 15-30). Squamous cell carcinoma in the United States usually is a disease
of elderly male smokers and remains superficial for prolonged periods before
extending through periosteum and bone and spreading either cephalad into the nasal
cavity or maxillary antrum or dorsally through the pterygopalatine fossa. Epidermoid
carcinoma of the hard palate is more common in India and Venezuela, where reverse
smoking (with the lighted end of the cigarette inside the mouth) is practiced.

Therapy
Treatment is surgical resection with or without adjuvant radiotherapy. Because of the
underlying bone, definitive radiotherapy is rarely useful. Cervical metastases are
relatively rare in disease of the hard palate, with only 10 to 25 percent of patients
presenting with disease at either the prevascular facial nodes or the jugulodigastric
nodes. Occult metastases are rare, so elective neck dissection is not part of the
therapeutic regimen. Five-year survival rates range from 33 to 75 percent, depending
on stage, with an average of 55 to 60 percent for all patients.

Small to moderate-sized defects of the hard palate are best treated with a dental
prosthesis in both the dentate and edentulous patient; massive defects may require
temporalis muscle flap or local flaps and skin grafting or free tissue transfer, since
support for the prosthesis may not be available. The inflammatory process of the
minor salivary glands of the hard palate, necrotizing sialometaplasia, which produces
an ulcerative lesion with erythematous borders similar to squamous cell carcinoma,
may be confused with malignancy. Biopsy examination, however, will show no
evidence of malignancy, and the disease is self-limited, usually requiring no therapy.

Floor of Mouth Anatomy and Physiology
The floor of the mouth is the horseshoe-shaped area between the mobile tongue and
the lingual surface of the mandible. The papillae that allow Wharton's ducts to empty
into the oral cavity lie at the anterior border of this area; posteriorly, the floor of the
mouth blends into the glossopalatine fold and the retromolar trigone. In this natural
reservoir there may be prolonged contact of the floor of mouth mucosa with
carcinogenic agents dissolved in the saliva after oral ingestion or inhalation. This area
provides capacity, allowing the tongue to sit low in the mouth, thus increasing the
volume of the oral cavity and preventing obstruction of the direct route between the
lips and the pharynx.

Pathology
Approximately 13 to 17 percent of oral lesions arise in this area, the third most
common site after the lip and mobile tongue. Because of the proximity of the mucosa
to the hyoglossus and mylohyoid muscles of the submandibular triangle, and because
of the rich lymphatic supply, direct extension of tumor into the neck and bilateral
cervical metastases are frequent, especially in anteriorly located lesions. Medial
growth at the primary site also invades the ventral surface of the tongue, and lateral
growth invades the mandible. Advanced-stage disease is common, with 46 to 52
percent of patients presenting with stage III or stage IV disease. Subclinical disease in
the neck or micrometastases in the clinically negative neck are common, with overall
neck involvement increasing with primary tumor size and ranging from 15 percent for
tumors less than 2 cm (T1) to 50 percent for tumors greater than 4 cm (T3).

Therapy
Because the tumor may abut or actively invade the mandible, resection with an
adequate margin of normal tissue in this area frequently requires removal of the
mandibular periosteum or actual resection of a segment of mandible. Uncertainty
about invasion of the mandible or proximity may require removal of the medial cortex
(marginal mandibulectomy) or a segment of the mandible. Because of the proximity
of the mandible, therapeutic doses of radiation may result in ischemic necrosis of the
bone, osteoradionecrosis. Combined therapy, surgical resection of the primary tumor
with neck dissection en bloc or pull-through resection followed by adjuvant
radiotherapy, is appropriate for advanced disease. Survival rates are strongly
dependent on stage, ranging from 68 to 91 percent for stage I to 35 to 46 percent for
stage III disease. Recurrence at the primary site frequently involves the mandible or
the suprahyoid complex of muscles and may require laryngectomy because of
invasion of the preepiglottic space.

Reconstruction of the floor of the mouth presents a number of challenges. The
watertight seal of the oral cavity, the continuity of the mandibular arch, and the
mobility of the tongue all depend on this area. For superficial lesions with normal
well-vascularized muscle beneath them, split-thickness skin grafts have been
advocated. Although they may be successful initially in covering the area, the
contracture inherent in this method may result in tethering of the mobile tongue to the
subjacent muscle or to the mandibular periosteum. If the neck is not involved by
tumor, a musculocutaneous island flap of platysma muscle based on the facial artery
provides supple skin coverage. Bulky thoracic musculocutaneous flaps, such as
pectoralis major, provide skin for lining but may be compressed by the intact
mandible, resulting in ischemic necrosis, or may push the tongue back in the oral
cavity, limiting movement and obstructing the pharynx and airway. The thin pliable
skin of the volar forearm, based on the radial artery and its venae comitantes as the
radial forearm free flap, provides an excellent lining for this area that can drape over
the mandible and allows free movement of the tongue while providing a watertight
seal. Vascularized segments of bone and skin of varying size also are available as free
tissue transfers from the fibula, scapula, dorsum of the foot, and other sites with high
success rates if the mandible must be resected (Fig. 15-31).

Gums, Gingivae, Alveolar Ridge Pathology
Squamous cell carcinoma arising on the gums constitutes 10 to 17 percent of oral
cavity malignancies. Eighty percent of lesions arise on the mandibular alveolus.
Although the male predominance persists at this site, there seems to be a less direct
relationship with tobacco and alcohol, and the causation may be related in some cases
to chronic trauma from poorly fashioned dentures or jagged teeth. The thin layer of
mucosa allows invasion of the underlying mandibular or maxillary bone in 35 to 50
percent of cases. Direct invasion through the periosteum is most common in patients
with teeth, but spread through the empty sockets along the occlusal ridge and
subsequent perineural invasion are common in edentulous patients. Cervical
metastases occur in 30 to 45 percent of the cases, depending largely on the size of the
primary.

Therapy
Surgical resection requires removal of the subjacent bone by partial or total
maxillectomy or total mandibulectomy. Maxillary defects of moderate size can be
treated with dental prostheses, and mandibular defects reconstructed with various
combinations of skin and bone as previously described.

Oral Tongue Anatomy and Physiology
The tongue is a complex muscular structure covered with mucosa and receiving motor
innervation from the hypoglossal nerve. The bulk of the tongue is made up of the
superior and inferior longitudinal muscles joined by the vertical and transverse
intrinsic muscles. Inferoposteriorly and laterally the tongue is connected to the hyoid
bone by the hyoglossus muscle, and superiorly and anteriorly to the mandible by the
genioglossus muscles. The styloglossus and palatoglossus muscles attach the tongue
superiorly to the base of the skull. These junctions allow the tongue great mobility,
promoting synergy with the larynx and the pharyngeal and palatine muscles. Beneath
the smooth ventral surface of the tongue, along the floor of the mouth, are the
numerous openings of the sublingual ducts. On the dorsal surface are papillae, with
specialized sensory organs for taste at the base. Also opening onto the tongue are the
ducts of the minor salivary glands. Sensation is provided to the tongue by the lingual
nerve carrying fibers of cranial nerve V, and taste by the glossopharyngeal and chorda
tympani of VII. Differentiation of sweet, sour, salt, and bitter taste relies a great deal
on intact function of the tongue. As a mucosa-covered muscle, the tongue is the major
propulsive force in the oral cavity. It initiates and continues movement of the food
bolus to the pharynx, generating pressure of up to 120 mmHg. Numerous
investigators have demonstrated that dysfunction after surgery for oral cancer depends
almost exclusively on the amount of tongue resected.

Pathology
In most series of oral cancers, the oral or mobile tongue is second only to the lip as
the most common primary site. Tobacco and alcohol are the most common associated
factors, but chronic irritation from jagged teeth or dental appliances also may be
involved. Although the sixth and seventh decades are the peak periods, sporadic
occurrence of squamous cell carcinoma in the tongue has been described in patients
under thirty and in renal transplant and other immunosuppressed patients and may not
be linked to the usual carcinogenic stimuli. In India, submucosal fibrosis seems to be
a predisposing influence, and in Scandinavia, Plummer-Vinson syndrome, glossitis,
iron-deficiency anemia, and achlorhydria may be related.

Malignancy of the mobile tongue occurs most frequently at the midportion of the
lateral tongue and is frequently asymptomatic (Fig. 15-32). Radial spread through the
tongue may extend submucosally to the base of the tongue and across the midline or
laterally to the floor of the mouth. Because of the rich lymphatic supply, ipsilateral
metastases are common to the submandibular and submental nodes. Clinical evidence
of cervical metastasis is present in 40 to 61 percent of patients, and subclinical disease
in the N0 neck is found in 25 to 31 percent. As in other sites, the presence of lymph
node metastases seems to be the most important prognosticator, with survival rates of
73 to 92 percent for localized disease (T1, T2, N0) and only 31 to 45 percent with
regional metastasis.

Therapy
Definitive therapy for carcinoma of the oral tongue can be attempted with either
external beam radiotherapy or interstitial radiotherapy. External radiation in doses to
65Gy may be useful, but with the implantation of afterloading devices (tubes into
which iridium-192 or radium needles can be placed) doses in the range of 100Gy to
150Gy can be delivered over a small area with greater effect.

The surgical therapy of carcinoma of the tongue consists of resection of the tumor
with a margin of normal tissue and en bloc removal of the regional lymph nodes.
Unfortunately, evaluation of the extent of local disease is difficult in tongue cancer.
Although several authors have demonstrated respectable 5-year survival rates (48 to
62 percent) with partial glossectomy with or without en bloc or discontinuous neck
dissection, a generally accepted uneasiness about the ability to obtain clear margins
has led to the common use of adjuvant radiotherapy. Hemiglossectomy, or resection
to the median raphe, has been advocated by some for lesions involving any part of the
lateral tongue.

Extensive lesions of the tongue may extend posteriorly to involve the larynx. Even in
those patients who do not demonstrate invasion of the larynx, widespread
involvement of the tongue or resection of the base of the tongue may predispose the
patient to aspiration and ultimate respiratory failure. Despite skepticism on the part of
some surgeons, total glossectomy with or without laryngectomy has been shown to be
a valuable procedure for both cure and palliation. A 3-year survival of 53 percent has
been achieved in one series, with 80 percent of patients demonstrating intelligible
speech if the larynx is preserved and 93 percent regaining the ability to maintain their
nutritional status by oral alimentation.

Although attempts have been made to innervate muscle of various types transplanted
to replace the tongue, there is no satisfactory way to reconstruct the tongue.
Denervation of the tongue by resection of, or injury to, both hypoglossal nerves
usually renders the patient incapable of swallowing or of effective speech. After
surgical resection of a portion of the tongue, the reconstructive goal is to allow free
mobility of the remaining tongue while providing a watertight seal to the oral cavity.
If the floor of the mouth is not involved in the resection, simply skin grafting of the
raw surface may suffice. Suturing the edge of the resected tongue to alveolar or
buccal mucosa usually tethers the tongue, impeding its mobility. Advancing the
posterior mobile tongue or setting back the excess anterior tongue may provide the
optimal solution. Although the pectoralis major flap has been advocated for intraoral
reconstruction, its bulk tends to push the tongue back or pull it down into the neck,
interfering with its motion and the subsequent elevation of the larynx necessary for
effective swallowing and speech. Furthermore, its thickness and weight effectively fix
the tongue to the adjacent mandible, further interfering with its motion. The lateral
arm or radial forearm free flap provides lightweight supple tissue more appropriate for
restoring tongue, floor of mouth, and mandibular alveolar epithelial lining.

The defect of total glossectomy consists of the tongue, floor of the mouth, and
sometimes pharyngeal and laryngeal mucosa. Restoration of oral continence usually
requires significant amounts of soft tissue. The pectoralis major flap serves well to
replace the entire floor of the mouth, as does the jejunal free flap, which also can
replace the pharynx and cervical esophagus. If the larynx is preserved in total
glossectomy, the radial forearm free flap serves as an excellent diaphragm to pull the
hyoid bone anteriorly toward the mandible and assist in swallowing.

When a portion of mandible must be resected for carcinoma of the oral tongue, the
urgency of reconstruction depends on what part of the mandible has been resected.
Although any mandibulectomy results in some dysfunction, partial mandibulectomy
lateral to the mental foramen usually is well tolerated, the main morbidity being
weakness of chewing and malocclusion of the remaining teeth. Resection of the
symphysis or anterior segment of the mandible, however, is a much more devastating
problem and requires immediate reconstruction. Vascularized bone from scapula,
fibula, iliac crest, radius, or metatarsal is excellent for reconstruction. If appropriate
soft tissue is not available, two free tissue transfers can be performed to satisfy the
individual needs of the wound.

Pharynx
Anatomy and Physiology
The pharynx is the continuation of the muscular tube that constitutes the alimentary
tract. It is anatomically divided into three sections, each with a slightly different
function: the nasopharynx, the oropharynx, and the hypopharynx (see Fig. 15-4). An
important role of the pharynx is separating the respiratory and the alimentary tracts,
and its specialized structures reflect this function. The nasopharynx is unique in the
pharynx in that it is a rigid cavity bounded on three sides by bone—superiorly by the
base of the skull and posterior sphenoid sinus, anteriorly by the posterior rim of the
ethmoid plate and the choanae, passages from the nasal cavity into the nasopharynx,
and posteriorly by the pharyngeal tubercle of the occipital bone and the atlas and axis,
with their prevertebral fascial and muscular coverings. The inferior surface is the
nasal side of the soft palate. The lateral sides of the nasopharynx give entry to the
eustachian tubes (to decompress the middle ear), and the roof is the site of a collection
of lymphoid tissue, the pharyngeal tonsil.

The oropharynx is the muscular tube that serves as transit area from the propulsive
oral cavity and the recipient nasal cavity to the alimentary and respiratory tracts. This
mucosa-lined muscular tube contains the base of the tongue (from the circumvallate
papillae back), the tonsils, the oral soft palate, the lateral pharyngeal walls, and the
posterior pharyngeal wall. The dominant muscular entity that receives the propulsive
energy of the tongue is the superior constrictor muscle, attached on both sides to the
pterygomandibular raphe and wrapping 270 degrees to constitute the posterior and
lateral walls. Contraction of this muscle closes the palatopharyngeal sphincter, or
Passavant's ridge, elevating the palate. This action closes the nasopharynx and pushes
the bolus of food into the hypopharynx. Up-and-down motion of the palate is
regulated by the tensor veli palatini and levator veli palatini muscles (attached to the
base of the skull) and the palatopharyngeus muscle (attached to the lateral pharyngeal
wall). Lack of synergy in these muscles is seen in patients with cerebrovascular
accidents and hypoxia neonatorum and markedly interferes with speech and
swallowing.

The anatomic boundaries of the hypopharynx are reflections of the anatomy of the
larynx. The posterior pharyngeal wall runs from the tip of the epiglottis to the inferior
border of the cricoid cartilage. The anterior border is the postcricoid mucosa, and the
lateral surfaces are the mucosal cavities on both sides of the larynx known as the
pyriform sinuses. The middle pharyngeal constrictor muscle, with its attachments to
the hyoid bone and prevertebral fascia, and the inferior pharyngeal constrictor, with
its distal condensation of the cricopharyngeus muscle attached to the lateral surfaces
of the thyroid and cricoid cartilages, serve as the pharyngeal sphincters. When they
contract they close off the entrance of the cervical esophagus to air and direct it
through the larynx. When they relax they allow food through the pharynx and into the
cervical esophagus. The inferior constrictor and cricopharyngeus muscles serve as the
upper esophageal sphincter and may become hypertonic, a condition known as
cricopharyngeus spasm. Zenker's diverticulum, a lateral outpouching of the
pharyngeal wall that may collect undigested food and result in chronic aspiration, is
the consequence of chronic hypertension of the upper esophageal sphincter (Fig. 15-
33). Resolution of this upper esophageal sphincter hypertension has been obtained
temporarily by injection of botulinum toxin, but permanent treatment requires
transection of the muscle (cricopharyngeus myotomy) with or without resection and
closure of the mucosal diverticulum.

Base of Tongue Pathology
Carcinoma arising behind the circumvallate papillae in the base of the tongue
frequently remains asymptomatic and undiagnosed until late-stage disease has
developed. Even when patients complain of pain, either local or referred, as with
otalgia, difficulty in examination or reluctance of primary care physicians to perform
indirect laryngoscopy and palpation of the base of the tongue results in misdiagnosis
and prolonged therapy for pharyngitis, tonsillitis, and other less serious problems. The
central location gives rise to cervical lymphatic metastases in up to 70 percent of
patients, and there are bilateral metastases in 17 to 25 percent of cases.

Histology and gross morphology in this region predict to some degree the behavior of
the lesion and the appropriate therapy. In addition to epidermoid carcinoma, minor
salivary gland lesions are also seen. Exophytic lesions, with cells resembling
lymphocytes and absence of keratin pearls, arise in the tissues of Waldeyer's ring, the
tonsils (lingual and palatine), and the base of the tongue. These lymphoepitheliomas
behave like nasopharyngeal carcinoma and have been characterized as
undifferentiated carcinomas with lymphocytic infiltration. Such lesions are more
radiosensitive, both at the primary site and as cervical metastases, than most other
infiltrative keratin-producing squamous cell carcinomas, with 2-year local control
rates of 75 percent for T1 lesions and 67 percent for T2 lesions.

Carcinoma arising in the base of the tongue spreads anteriorly into the oral tongue,
superiorly up to the tonsillar pillar, and inferiorly into the lateral pharyngeal wall and
into the vallecula, preepiglottic space, and larynx. Because of the proximity and
functional relationship of the base of the tongue to the larynx, interference with
laryngeal elevation and closure of the epiglottis, with the attendant aspiration
pneumonitis, is a hallmark of carcinoma of the base of the tongue.

Therapy
Advanced disease at the primary site or disease with cervical metastases requires
surgical therapy. If the lesion is lateral enough, partial glossectomy may be adequate.
Since resection of the base of the tongue usually removes the hypoglossal nerve to the
tongue in that area, subtotal or posterior glossectomy is unlikely to leave functional
tongue. Radical resection may require total glossectomy with or without
laryngectomy (Fig. 15-34). In most patients, if the oncologic requirements of the
resection do not dictate removal of the larynx, reconstruction with the larynx in situ is
appropriate. Surgical therapy or surgery combined with postoperative adjuvant
radiotherapy results in 5-year survival rates of 50 to 60 percent for stage III disease
and 20 to 25 percent for stage IV disease. Advanced primary disease or disease in the
neck is unlikely to be successfully controlled locally with radiotherapy alone, and
surgical salvage after radiotherapy has been dismal, with a high incidence of
osteoradionecrosis of the mandible.

Reconstruction of defects arising from resection of the base of the tongue should
effectively close the pharynx and oral cavity with tissue that will heal primarily and
withstand subsequent irradiation and still not interfere with the function of tissues left
intact by the curative resection. Elevation of the larynx, the normal motion that occurs
during the early pharyngeal phase of swallowing to close the epiglottis, cannot occur
if the tongue is tethered to the side of the pharynx or oral cavity or if bulky tissue such
as the pectoralis major flap is interposed into the area of the resection. The provision
of sensate tissue into the area surrounding the larynx, to prevent aspiration, is also an
important consideration. Occasionally local tissue can be mobilized for closure
without tension to avoid fistula formation and to provide sensate mucosa. More
commonly, however, mucosa or skin to line the tongue, mandible, and pharyngeal
wall is necessary. Buccal and palatal flaps have been described for small and
moderate-sized defects, but free tissue transfer of skin from radial forearm or lateral
arm or lateral thigh flaps are more appropriate for the more common extensive
defects. Neurotized free tissue transfer reconstructions of the pharynx and oral cavity
have shown two-point discrimination and other measures of sensitivity that are
characteristic of the recipient site (upper aerodigestive tract) rather than the donor site
(arm, back), suggesting that cerebral cortical integration of the reconstruction favors
the recipient site.

Tonsil Pathology
Squamous cell carcinoma of the tonsil may arise in the tonsil, the tonsillar bed, or the
tonsillar pillars (Fig. 15-35). As one of the Waldeyer's ring structures, the tonsil
shows a higher incidence of lymphoepithelioma than other sites. Whatever the
histology, it is second only to the larynx in frequency as a site of upper aerodigestive
tract primary malignancy, with 12,000 new cases per year in the United States. Like
most upper aerodigestive tract tumors, tonsillar carcinoma presents with
predominately late-stage disease, with 28 to 32 percent of patients presenting with
stage I or stage II disease, 35 to 40 percent stage III, and 40 to 45 percent stage IV.
Cervical metastases at the time of presentation are seen in up to 67 percent of patients,
and subclinical disease in the N0 neck in 10 percent of patients. Determination of the
extent of local disease in advanced tumors is of considerable importance in decision-
making and execution of therapy. Growth of the tumor upward into the soft palate
occurs in 60 percent of patients, downward to the base of the tongue in 56 percent,
into the nasopharynx in 9 percent, and down the lateral pharyngeal wall to the
epiglottis in 27 percent of cases. The site of local extension is particularly important,
because in treating patients with radiotherapy, geographical misses as a result of
underestimating the local extent of disease were a common reason for failure.

Therapy
Carcinoma of the tonsil appears to be more radiosensitive than other primary-site
squamous cell carcinomas. The usual approach to disease originating at this site is to
treat for curative intent with radiotherapy ranging from 55Gy to 70Gy to the primary
site and bilateral cervical lymph node drainage areas (Fig. 15-36). If there is bulky
neck disease or extension of the primary tumor into adjacent bone or pterygoid
muscles, surgical resection, reconstruction, and postoperative adjuvant radiotherapy
are safer and more effective. Risk of local recurrence is directly related to size of the
primary tumor, and recurrence is even more likely when the predominant spread of
tumor was into the base of the tongue.

The challenge of reconstruction in tonsillar disease is a function of the dimensions of
local growth of the lesion and the history of previous radiation. The soft-tissue defect
in the lateral wall of the pharynx created by a superficial lesion can easily be
resurfaced with a skin graft, a deltopectoral flap, or a fasciocutaneous free flap. Radial
spread up to the soft palate or down into the pharynx demands that the surface of the
flap be contoured in several planes without obstructing the pharynx, usually requiring
a free tissue transfer of relatively pliable skin, such as the radial forearm, lateral arm,
or lateral thigh. Invasion of the ascending ramus of the mandible can be treated by
addressing the soft-tissue defect alone by transposing a pectoralis major
musculocutaneous flap into the lateral pharynx, using the skin for internal lining and
the muscle for coverage of the carotid vessels in the neck. In the patient with teeth,
soft-tissue reconstruction alone will lead to malocclusion of the dental arches and
other problems. Skin and bone together are available with a number of methods. The
scapula and the deep circumflex iliac artery free flaps are particularly suited to the
lateral defect created by radical resection of the tonsil and mandible.

Soft Palate Anatomy and Physiology
The soft palate is the mucosa-lined fusion of the inferiorly based palatopharyngeus
and palatoglossus muscles and the superiorly based levator and tensor veli palatini
muscles. Extending backward from the posterior margin of the palatine bone, directly
opposite the superior constrictor muscle and its bulge, which creates Passavant's
ridge, its main function is to open and close the passageway between the nasal cavity
and nasopharynx and the oral cavity and oropharynx. This obturating and modulating
effect has obvious importance in speech and in swallowing.
Pathology
Isolated carcinoma of the soft palate is rare, the disease usually occurring in
combination with other frank malignancies or premalignant entities such as
leukoplakia or erythroplakia and not showing the usual male predominance.

The oral side of the soft palate is by far the most common site for malignancy, which
usually extends down the tonsillar pillars to the base of the tongue. Superior and
posterolateral spread to the nasopharynx and posterior pharyngeal wall is less
common. Ipsilateral cervical lymph node metastases to the jugulodigastric nodes
occur in 40 to 50 percent of cases, and, because tumors often pass over the midline,
bilateral metastases are seen in 15 percent of cases.

Therapy
Treatment of soft palate carcinoma follows the usual principle that small primary
lesions are effectively eradicated by radiotherapy in the range of 65Gy and that
combined therapy, surgery with adjuvant radiotherapy, is necessary for best results in
larger tumors. The importance of radiotherapy as a treatment was particularly
emphasized in the past because of the inability to reconstruct the soft palate and the
devastating functional result. Nonrandomized studies of surgery and radiotherapy
have shown 5- year survival rates of 31 to 44 percent, with the size of the primary
lesion, the absence of a synchronous primary upper aerodigestive tract tumor, the
absence of cervical metastases, and moderately to well differentiated histology being
favorable prognostic features.

Resection or dysfunction of the soft palate results in escape of air and oral contents
into the nasal cavity and ultimately out the nares. Advances in prosthetic technology
have made the use of a dental prosthesis a possible solution in some cases. For defects
that do not include the lateral and posterior pharyngeal wall, a superiorly based flap of
pharyngeal mucosa and muscle sutured into the margin of the palatal resection will
obturate the opening between the nasopharynx and oropharynx. More extensive
defects require the introduction of epithelium-lined soft tissue; the lateral arm, lateral
thigh, and radial forearm free flaps are ideal when soft tissue alone is needed, and the
scapula free flap when both skin and bone are necessary (Fig. 15-37).

Posterior Pharyngeal Wall Anatomy
The posterior and lateral pharyngeal walls extend from the oropharynx down into the
hypopharynx, where the lateral pharyngeal walls end as the lateral walls of the
pyriform sinus and the posterior wall extends to the cervical esophagus. The
lymphatic drainage of the posterior pharyngeal walls is to the jugulodigastric,
midjugular, and juguloomohyoid nodes but also directly to the retropharyngeal group
of lymph nodes.

Pathology
Because of its location and the nonspecific symptoms of mild dysphagia and
odynophagia, squamous cell carcinoma of the posterior pharynx usually is detected at
a late stage, with 39 to 55 percent of patients presenting with palpable cervical
metastases. Local spread of disease is cephalad toward the nasopharynx and lateral to
the lateral pharyngeal walls and larynx.
Therapy
Using combinations of surgery and radiotherapy, 3- to 5-year survival rates of 25 to
32 percent overall have been reported.

The location of the posterior pharyngeal wall as the farthest border of the
aerodigestive tract and its proximity to the larynx have presented some problems both
of access for surgical resection and of potential for appropriate reconstruction.
Accurate resection of local disease requires visual access. Midline division of the lip,
mandible, and tongue, the median labiomandibular glossotomy, allows visualization
of the posterior pharynx. If disease is limited to the posterior wall, the surface can be
relined with a split-thickness skin graft or allowed to epithelialize. Circumferential
disease requires more complete pharyngeal resection and sometimes
pharyngolaryngectomy. Reconstruction of the complete or partial circumferential
defect may be accomplished with a free autograft of jejunum or a radial forearm free
flap. If the larynx can be preserved, aspiration will be less likely if free mobility of the
larynx is maintained and sensate epithelium is restored, either by sensory-innervated
free tissue transfer or by skin grafting.

Hypopharynx Pathology
In addition to the posterior pharynx, the hypopharynx contains the pyriform sinuses
and the postcricoid area. Tumor growth in this area, the lateral and posterior mucosal
border of the larynx, is intimately related to the function of the larynx, a facet
recognized in the staging systems used in assessing the extent of hypopharyngeal
disease (Fig. 15-38). Thus the T stage of the pyriform sinus lesion increases not with
tumor size but with extent into the medial wall or with fixation of the vocal cord
caused by direct extension of disease. Another consideration in hypopharyngeal
carcinoma, as in disease of the cervical esophagus, is the problem of submucosal
extension of tumor. Spread of disease into the cervical esophagus discovered at
surgery may simply represent clinical understaging of disease, but it also could be
multifocal disease or field cancerization. Local spread of disease is cephalad toward
the nasopharynx or distal into the cervical esophagus, as well as medial and lateral
toward the larynx. Advanced-stage local disease is common, with only 10 to 15
percent of cases confined to only one site in the hypopharynx.

The lymphatic drainage of the area is copious, with primary nodal stations in the
midjugular, juguloomohyoid, and retropharyngeal lymph node chains. Even with
small lesions there is a likelihood of lymph node metastasis, with 55 to 64 percent of
patients presenting with palpable lymphadenopathy, and 41 percent of patients with
clinically negative N0 necks demonstrating metastatic disease after elective neck
dissection. Even with small primary lesions (T1) localized to one part of the
hypopharynx, the risk of cervical micrometastases in the clinically negative neck is
high (40 percent). Distant metastases at presentation and with treatment of disease
appear to be more common than at other primary sites, occurring in up to 47 percent
of the cases.

Therapy
Since it is unusual for hypopharyngeal lesions to present at an early stage, the
treatment usually is combined, consisting of surgery followed by adjuvant
radiotherapy. The extent of the operation depends on the proximity to the larynx, and
the laryngopharyngectomy with bilateral modified neck dissection is the procedure
that is most frequently necessary. With such an approach, survival rates of 20 to 40
percent have been achieved.

When the larynx can be saved, primary closure of the surgical defect is the most
effective method. Preservation of the superior laryngeal nerves, the sensory
innervation to the area, is an important consideration to allow swallowing to proceed
without aspiration. When the larynx is removed with the hypopharyngeal lesion,
however, the goals of reconstructive surgery are rather simple restoration of
alimentary continuity with the least likelihood of fistula formation or other
devastating problems and with the ability to restore esophageal speech. Primary
closure of the pharyngeal mucosa after partial laryngopharyngectomy for pyriform
sinus lesions results in a high likelihood of fistula formation (43 percent) and stenosis
(48 to 73 percent), both of which interfere with swallowing and esophageal speech
(Fig. 15-39).

Although use of local tissue, including the anterior wall of the larynx and the base of
the tongue, and skin of the neck has been described, the extent of surgery, the history
of previous radiotherapy, or the likelihood of subsequent adjuvant radiotherapy
usually require the importation of distant tissue. The deltopectoral flap from the chest
was the mainstay of pharyngeal reconstruction after laryngectomy but is at least a
two-stage procedure with a fairly high risk of failure or persistent fistula. The
pectoralis major musculocutaneous flap has been advocated for both circumferential
and partial defects of the pharynx. The effect of gravity, the inhomogeneous blood
supply, and the bulk of the flap result in a high rate of fistula formation and
dysphagia, making a free autograft of bowel or skin a preferable method. When a
circumferential defect is present, the problem of bulk and gravity can be circumvented
somewhat by skin grafting the prevertebral fascia as the posterior wall of the
neopharynx (new pharynx) and using the pectoralis major muscle and its overlying
skin as a 270- degree reconstruction to complete the pharyngeal conduit.

When total esophagectomy is part of the treatment for carcinoma of the hypopharynx,
transposition of the stomach or colon through the thorax can reconstitute the
alimentary canal. Gastric pull-up—in which the stomach, based on the right gastric
and gastroepiploic vessels, is brought through the chest, and the fundus or cardia
sutured to the base of the tongue or pharyngeal remnant—is a fairly reliable technique
but has a mortality rate of 10 to 20 percent in most series. Right or left colon
interposition usually is reserved for caustic strictures but occasionally is useful in
hypopharyngeal or cervical esophageal lesions.

Reconstruction of the circumferential defect resulting from pharyngolaryngectomy by
transfer of a free autograft of bowel and revascularization of microvascular
anastomosis was first performed in the early 1960s. Although colon, stomach, and
jejunum have all been used, the greatest experience has been with jejunal free
autograft. Successful reconstruction using the jejunum, either in a tube reconstruction
for circumferential defects or as a patch for partial defects, has been achieved in 92
percent of patients treated with this method, allowing 83 percent of the total group to
achieve total oral alimentation. Mortality with this method has been less than 5
percent, with few abdominal or thoracic problems. Complications in the neck, though
frequent, usually resolved without further surgery, and the segment of bowel was able
to withstand radiotherapy without major problems (Fig. 15-40). Although segments of
jejunum may be used in the unusual situation in which the larynx has been left in situ,
the secretory nature of the mucosa sometimes makes aspiration a problem, and
another method may be preferable. In addition to segments of bowel, fasciocutaneous
free flaps from the radial forearm, lateral arm, lateral thigh and posterior thigh have
been used as either a tube or a patch for hypopharyngeal reconstruction.

Squamous cell carcinoma of the cervical esophagus presents the same reconstructive
demands as that of the hypopharynx; when disease is localized, the resected portion
esophagus may be replaced with a patch of skin as either a vascularized transposition
flap or a free tissue transfer. The mode of spread of the local disease, however, may
involve submucosal skip areas and thus require total esophagectomy. The lymphatic
drainage of the cervical esophagus is oriented more toward the mediastinum and
parapharyngeal nodes than laterally into the neck, and hence a different approach is
required for lymphadenectomy.

Nasopharynx Etiology
Carcinoma of the nasopharynx is seen intermittently in the Western world, comprising
about 0.25 percent of new cancers in the United States. It is endemic in southeastern
Asia, however, particularly in southern Chinese populations such as those originating
from Kwantung province and constitutes 21 percent of cancers in Taiwan, 18 percent
in Hong Kong, and 14 percent in Indonesia. The incidence is much lower in Asians
who have immigrated to North America but still seven times higher than in the white
population, suggesting genetic susceptibility to an environmental carcinogen. The
sporadic and genetically linked cases of nasopharyngeal carcinoma behave in the
same manner. There is a high association of the Epstein-Barr virus with this
malignancy.

Pathology
The nasopharynx is a small, mucosa-lined, boxlike cavity at the base of the skull
containing the pharyngeal tonsil and the openings of the eustachian tubes and the
sphenoid sinus. Tumors arising in this area present local symptoms that vary with
their pattern of growth and spread. Lesions that are exophytic and grow out into the
cavity may obstruct the eustachian orifices or the choanae, leading to hearing loss (15
percent), nasal stuffiness or obstruction (30 percent), and epistaxis (22 percent).
Infiltration and bony erosion of the base of the skull into the cavernous sinus results in
cranial nerve palsies in 16 to 25 percent of cases, the most commonly involved being
the abducens nerve, followed by the trigeminal nerve and the oculomotor nerve,
resulting in paresthesias and diplopia. The most common presenting sign of
nasopharyngeal carcinomas is a mass in the neck secondary to cervical metastasis (60
percent). The site of cervical metastasis may be the jugulodigastric nodes or the
posterior triangle. Mirror examination of the nasopharynx is an important part of any
evaluation of suspicious cervical adenopathy.

Staging of nasopharyngeal carcinoma in the past has been relatively inaccurate
because of difficulty with examination. CT has helped to delineate invasion of both
the paranasopharyngeal fascial planes and the bony skull in the absence of cranial
nerve palsy. Recent staging systems have included histology, multiple symptoms,
time from onset of symptoms, location of cervical adenopathy (supraclavicular), and
local extent of disease. Variance of histology also has been related to survival and
thus is important in prognosis. Keratinizing squamous cell carcinoma has the worst 5-
year survival rate at 21 percent; the rate for spindle cell is 41 percent, round cell 51
percent, and mixed nonkeratinizing 54 percent. These histologic predictors of
therapeutic response are consistent with the subset of tumors arising as variants from
Waldeyer's ring, the lymphoepitheliomas.

Therapy
Despite the frequent presence of cervical lymph node metastases, nasopharyngeal
carcinoma is a curable disease. Radiotherapy in doses varying from 50Gy to 84Gy to
the primary site with 50Gy to 70Gy to both sides of the neck results in 5-year survival
rates varying from 100 percent for stage I disease to 34 percent for stage IV, with
overall survival rates ranging from 29 to 49 percent. The total dose of radiotherapy
has an effect on survival, with patients receiving lower total doses having poorer
survival. Even the presence of skull-base invasion and cranial nerve dysfunction is not
a sign of incurable disease. Sixty-two percent of cranial nerve defects can be reversed
by radiotherapy, with an overall 31 percent survival rate in this subset of patients.
Residual disease at the primary site occasionally may be resected by craniofacial
technique, and residual neck disease may be eradicated by radical neck dissection.
Distant metastatic disease in nasopharyngeal carcinoma is common, particularly in
patients who have bulky cervical metastases. At present, however, adjuvant
chemotherapy has not been particularly successful in improving survival.

Nasal Cavity and Paranasal Sinuses
Etiology
The nasal cavity and paranasal sinuses (maxillary, ethmoid, frontal, and sphenoid) are
the aditus to the respiratory tract and function to filter impurities from the inspired air,
regulate its temperature, and humidify it. As such they are exposed to the many
carcinogens in the air, and yet malignancies in these sites are rare. In the Western
world they constitute 0.3 percent of all malignancies, with a slightly higher incidence
in men than in women. In the Orient this is a more common primary site, comprising
1 percent of new cancers and 23 percent of head and neck cancers in Japan. Endemic
areas are found in South Africa, where inspired snuff has a high concentration of
nickel. There also may be an increased risk of adenocarcinoma of the paranasal
sinuses in woodworkers secondary to inspired wood dust. The disease presents most
frequently in the fifth to seventh decades.

Pathology
Squamous cell carcinoma is the most common histology (60 to 80 percent), although
minor salivary gland lesions, adenocarcinoma, adenoid cystic carcinoma, and
mucoepidermoid carcinoma make up about 20 percent of the tumors. Other
malignancies, such as teratocarcinoma, lymphoma, osteogenic sarcoma, schwannoma,
fibrous dysplasia, carcinosarcoma, and melanoma, occasionally are encountered.
Lymph node metastases are uncommon, with only 15 percent of cases presenting in
the neck, since the retropharyngeal lymph nodes are the first station of drainage.
There is a questionable relationship between nasal and sinonasal malignancy and the
inverting papilloma of the nasal cavity.

Late-stage disease is common, since symptoms usually are rather diffuse, including
nasal obstruction (35 percent), local pain (16 percent), epistaxis (12 percent), and
cheek swelling (29 percent). Loosening of maxillary teeth or paresthesias also may
occur. Diagnosis is made by intranasal biopsy through a speculum or by antrostomy
through the lateral nasal wall or labial buccal sulcus (Caldwell-Luc procedure). The
maxillary sinus is by far the most common site of origin of the disease (62 percent),
followed by the nasal cavity (26 percent), ethmoid sinus (10 percent), and sphenoid
sinus (2 percent).

Therapy
Treatment of paranasal sinus tumors is by a combination of radiotherapy and surgery.
Radiotherapy alone provides poor palliation and unacceptably low survival rates.
Preoperative radiotherapy to 60Gy combined with radical surgery has been the usual
approach, resulting in 3-year survival rates ranging from 13 to 32 percent for all sites,
35 to 40 percent for nasal cavity, and 38 to 53 percent for maxillary sinus. Failure of
therapy is most commonly manifested by local recurrence (70 percent) and only rarely
disease in the neck (5 percent).

Surgical resection involves en bloc removal of the affected sinus and the surrounding
involved structures. Total maxillectomy with or without orbital exenteration may be
required for adequate clearance. The introduction in 1963 of the intracranial-
extracranial approach to tumors, the craniofacial technique, has improved the ability
to safely remove tumors of the ethmoid and other paranasal sinuses and has increased
5-year survival rates from the range of 30 percent to 58 percent.

Reconstruction of the postoperative defect that has been previously irradiated is a
difficult problem. Unnatural passageways among the paranasal sinuses, oral cavity,
nasal cavity, and external environment interfere with the normal flow of air, drying
the mucosa and causing discomfort and bleeding as well as interfering with
alimentation and speech. Small defects can be obturated with nasal or dental
prostheses. Larger defects, however, require three-dimensional reconstruction with
free tissue transfer with the intention of restoring pathways of air and ingested
substances to as normal a state as possible to improve function and appearance (Fig.
15-41).

Larynx
Anatomy and Physiology
The larynx is a complex, mucosa-lined, bony and cartilaginous box whose function
depends on motion coordinated with the adjacent tongue and pharynx. The larynx is
divided into three anatomic areas: the supraglottic larynx, from the epiglottis to the
ventricle, including the preepiglottic space, hyoid bone, arytenoid processes, and false
vocal cords; the glottic larynx, including the true vocal cords and the anterior
commissures; and the subglottic area, surrounded by the cricoid cartilage. The
different clinical behavior of supraglottic lesions comes in part from their separate
embryologic origin. The supraglottis is a derivative of the pharyngobuccal anlage, and
malignancy arising in this area behaves similarly to pharyngeal carcinoma, with early
metastatic disease to the neck. The glottis arises from the tracheobronchial anlage, and
malignancy is more likely to be indolent, with lower incidence of cervical metastases.

The predominant function of the larynx is the modulation of air inspired through the
nose and nasopharynx and expired from the lungs. Coordination of respiration with
swallowing is a complex function that prevents food from entering the respiratory tree
and air from entering the digestive tract. As air enters the pharynx it is shunted to the
larynx, which sits in its neutral position with the epiglottis open. Air is then drawn
through the larynx by negative pressure from the thorax and prevented from entering
the esophagus by the sphincter action of the middle and inferior constrictor muscles.
Saliva and other oral contents are prevented from entering the larynx by sensitive
reflexes mediated by the sensory component of the superior and recurrent laryngeal
nerves and the intrinsic and extrinsic muscles of the larynx. In the act of swallowing,
the food bolus is prevented from entering the larynx by the simultaneous relaxation of
the middle constrictor muscle and the elevation of the larynx toward the relatively
fixed epiglottis, which seals the aditus. This elevation is initiated as the food passes
through the faucial arch by the intrinsic and extrinsic muscles of the tongue pulling
through the hyoid bone. Speech is produced by air expired from the lungs through the
larynx, mouth, and nose. The thickness and degree of abduction or adduction of the
cords produce tone and volume, and the actions of the tongue, palate, lips, and buccal
mucosa modify the expelled air into an articulated pattern, speech. Although the
respiratory tract can be short-circuited and separated from the digestive tract by
tracheostomy, either with or without laryngectomy, the maintenance of normal speech
and swallowing depends on adequate synergy in the pharyngolarynx and oral cavity
of tongue, larynx, and pharyngeal musculature and normal central nervous system
afferent and efferent signals. Perhaps more than at any other body site, therapeutic
decision-making in laryngeal carcinoma by both patient and physician has been
influenced by the desire to preserve the voice.

Etiology
Carcinoma of the larynx is the most common malignancy of the upper aerodigestive
tract in the United States, with about 10,000 new cases presenting each year. As with
most other head and neck cancers the risk for development for laryngeal cancer is
directly proportional to the amount of exposure to tobacco, with a lesser relationship
to alcohol intake. Changing mores have decreased the male-to-female ratio for
incidence of laryngeal carcinoma from 11:1 in 1960 to 4.5:1 in 1990. Furthermore,
women with carcinoma of the larynx are more likely to have supraglottic than glottic
laryngeal cancers. Increasing age also is a risk factor, although disease in young
patients has been reported and likewise is related to tobacco use. Black patients in the
United States have an increased risk of developing laryngeal carcinoma at a younger
age and a slightly lower male- to-female ratio (3.5:1) than the general population.
Other risk factors suggested have been metal dust (particularly nickel), asbestos, hair
dyes, and wood dust, but these are likely cofactors to the insult created by tobacco
smoke. The relationship of papillomas of juvenile or adult onset in the causation of
the larynx is unclear.

Diagnosis
Because of the obvious symptoms of hoarseness, other voice changes, tickling in the
throat, and coughing, carcinoma of the glottic larynx is more likely than many upper
aerodigestive tract malignancies to present with early-stage disease. Evaluation of the
patient includes indirect (mirror) laryngoscopy as well as physical examination of the
neck (Fig. 15-42). The geographic site and extent of the lesion, whether confined to
the larynx or spreading beyond, are of importance, but the mobility of the vocal cords
also is crucial, since it predicts invasion of the tumor into the deep structures of the
larynx. CT and MRI are useful in determining whether there is invasion of the thyroid
cartilage in the staging process (Fig. 15- 43). Definitive staging and diagnosis to
clearly define extent usually require direct laryngoscopy and biopsy, which can be
performed with a rigid laryngoscope with the patient anesthetized or with a flexible
fiberoptic scope with the patient awake and able to inspire and vocalize.

Pathology
The biologic behavior of malignancy in the various areas of the larynx is somewhat
different and plays a major role in the choice of therapy. Supraglottic laryngeal
carcinoma or extrinsic laryngeal carcinoma is more likely than glottic cancer to
present with advanced-stage disease. There is an abundant lymphatic supply that
extends anteriorly through the preepiglottic space as well as laterally to the midjugular
and paratracheal lymph nodes. Involvement of the preepiglottic space occurs in 29
percent of clinically unremarkable supraglottic tumors. Micrometastases in the
clinically negative neck also are common, with 26 to 33 percent of necks showing
metastases and 25 percent bilateral metastases. In patients with inadequate primary
therapy for supraglottic carcinoma recurrence in the neck and distant metastases is
more likely than local recurrence alone.

The vocal cords (glottis) or intrinsic larynx is a small area that is in constant use and
thus regularly exposed to carcinogenic stimuli. When tumors are confined to the small
cartilaginous box with its paucity of lymphatics, they usually behave indolently.
When tumors extend outside the glottis—transglottic lesions—a more aggressive
pattern is noted. Unlike supraglottic cancer, early changes are noticeable and appear
to have a long natural history, making them amenable to less radical therapy.
Keratosis or thickening of the keratin layer of the squamous mucosa results in
transformation to carcinoma in situ in 14 percent of cases and microinvasive cancer in
28 percent of cases over a period of 2 to 24 months. Keratosis with atypia progresses
to carcinoma in situ in 18 percent and invasive carcinoma in 25 percent in 1 to 24
months, and carcinoma in situ progresses to invasive carcinoma in 38 percent of cases
in 8 to 48 months. Recognition and treatment of these early changes in laryngeal
mucosa is crucial to prevention of disease and prolonged survival.

Therapy
This rather indolent behavior and the low likelihood of clinically evident or
micrometastatic cervical disease (1 to 7 percent in T1 and T2 lesions, 13 percent with
T3 lesions) make glottic cancer more suitable for less radical therapies, with a high
probability of salvage after failure of primary therapy. Because of the propensity for
submucosal extension, however, advanced- stage disease with cartilage invasion
requires initial radical therapy.

Subglottic carcinomas are rare, comprising only 1 to 2 percent of all laryngeal
carcinomas, and tend to spread by submucosal extension down the trachea and
through the cricoid cartilage and cricothyroid membrane into the soft tissues of the
neck. Because of their rarity, they frequently present with advanced-stage local
disease, although cervical metastasis is not as common as in supraglottic disease.
Radical combined therapy, surgery and radiotherapy, is necessary.

Despite the peculiarities of growth of squamous cell carcinoma of the glottic larynx,
prognosis for carcinoma at all sites is related to similar variables predicting other
sites. Unifactorial and multifactorial analyses have identified the presence of lymph
node metastases, advanced local disease, vocal cord fixation, histologic grade,
ulceration, site within the larynx, male gender, and 3H-thymidine labeling index as
significant factors in survival after therapy with both surgery and radiotherapy.

Because of the importance of preserving the voice and because of the low incidence
of subclinical cervical metastases in glottic cancer, radiotherapy has become the
accepted treatment for most early squamous cell carcinomas of the larynx.
Conventional radiotherapeutic techniques that deliver doses of 60Gy over 30 fractions
over 6 weeks result in cure rates of 80 to 90 percent for T1,N0 carcinoma of the
glottis and 70 to 90 percent for T2,N0. Furthermore, salvage of radiotherapy failures
with voice preservation by subtotal laryngectomy is possible in 75 percent and overall
surgical salvage in 92 percent of T1 patients and 82 percent of T2 patients. More
advanced T3 lesions also have been approached with standard radiotherapy and
hyperfractionation (more than one course per day) in doses of 65Gy to 76.8Gy
through ports that include the cervical lymphatics, resulting in local control rates of 36
to 67 percent over 2 to 4 years and surgical salvage of 67 to 83 percent. Such high-
dose radiotherapy does, however, result in significant complication rates, such as
persistent laryngeal edema and chondronecrosis.

Radiotherapy as treatment for supraglottic carcinoma is somewhat more controversial
because of the late-stage presentation and the tendency for bilateral cervical
metastases to occur. Although control rates of 74 percent for T1 and T2 supraglottic
lesions have been obtained, and 40 percent for T3 and T4 lesions with radiation and
surgery held as a salvage method, the possibility of preserving the voice with
supraglottic laryngectomy and treatment with preoperative or postoperative adjuvant
radiotherapy has made this combined approach more popular for late-stage disease or
disease with ominous histologic features.

The surgical approach to the larynx is varied, with the unifying principle that local
and locoregional disease may be eradicated with preservation or restoration of
whatever function is possible. Early lesions of the glottis, such as keratosis with
atypia, carcinoma in situ, or minimally invasive carcinoma, that involve the mobile
cord and do not extend to the anterior or posterior commissures may be treated with
reasonable success by removal of the mucosa over the cord by vocal cord stripping.
Performed transorally, by either laser diathermy or sharp dissection, this technique
has minimal morbidity, leaving good voice quality. T1 lesions of more bulk but
confined to one cord may be removed by cordectomy, occasionally performed
transorally but usually by opening the larynx through laryngofissure. Although this
interferes with voice quality, most patients are cured, and surgical salvage by total
laryngectomy is a successful backup procedure.

The conventional therapy for cancers that cross the anatomic boundaries of the
supraglottis and glottis or the glottis and subglottis, and the so- called transglottic
lesions, is total laryngectomy. Glottic lesions that cross the anterior or posterior
commissure and are not felt to be amenable to radiotherapy similarly require total
laryngectomy. Depending on the presence of palpable lymph nodes or suspicion of
metastatic disease because of the site of primary disease, radical or modified radical
neck dissection may be indicated. Removal of all disease is the aim of total
laryngectomy, although whole-organ pathologic examinations have shown presence
of microscopic disease at the margins in up to 30 percent of cases, with anterolateral
(19 percent), posterolateral (11 percent), postcricoid (7 percent), and superior margins
being most commonly involved. Free margin status is the most reliable predictor of
local control, with 48 percent of patients with positive margins developing local
recurrence. When total laryngectomy is used as definitive therapy for advanced-stage
disease, 3- to 5-year survival rates of 65 to 69 percent for T3,N0 and T3,N1 lesions
and 45 to 54 percent for T4,N0 lesions have been reported.

The goal of voice preservation when surgical extirpation is a necessary part of therapy
is met in two ways: by conservation surgery, removing only part of the larynx, or by
reconstruction of a voice-producing mechanism after total laryngectomy.

In conservation surgery lesions confined to one part of the larynx are removed with
the goal of preserving enough larynx to allow speech that is superior to esophageal or
mechanical speech. Standard supraglottic laryngectomy or horizontal
hemilaryngectomy is appropriate in patients where lesions are smaller than 3 cm, the
vocal cords are mobile, a margin of 5 mm is possible at the anterior commissure, there
is no cartilage or preepiglottic space invasion, the pyriform sinus apex and postcricoid
and interarytenoid areas are clear, and tongue mobility is normal. The approach to the
larynx is through the thyroid cartilage, removing the epiglottis, false cords, and
ventricular mucosa en bloc with the hyoid bone. If posterior extension involves the
arytenoid cartilage on one side, this may be included with the specimen. Although
postoperative aspiration for a limited period of time is frequently seen, good voice
quality is usually obtained and the temporary tracheostomy can almost always be
removed. Total laryngectomy as a salvage procedure for intractable aspiration, fistula,
or recurrent disease is successful in 33 to 50 percent of cases. Five-year survival rates
in the range of 70 to 85 percent for supraglottic carcinoma make it superior to
radiotherapy, although no prospective randomized studies have tested this thesis.

Vertical hemilaryngectomy is the standard conservation procedure carried out for
invasive carcinoma of one vocal cord or a vocal cord and the anterior commissure that
does not invade the thyroid cartilage. Total resection of the cord and its subjacent
muscle and adjacent cartilage is necessary. Access to the larynx is obtained posterior
to the cord by cutting through the thyroid cartilage, leaving the external
perichondrium sutured to the sternothyroid muscle. The cord with or without the
ipsilateral arytenoid cartilage is resected, and if the commissure is involved, the keel
of the thyroid cartilage is resected as well. The strap muscles and perichondrium or a
cartilage graft provides a buttress against which the normal cord can be apposed.
Five-year survival rates of 75 to 87 percent for stages I to III disease treated in this
fashion have been reported, again superior to radiotherapy alone. As with supraglottic
laryngectomy, removal of the temporary tracheostomy and resumption of oral
nutrition without aspiration usually is possible, with voice preservation. Extended
hemilaryngectomy has been described for T3 lesions, where a small segment of
vocalis muscle with its overlying cartilage, with sensory and motor innervation left
intact, is used with the adjacent hypopharyngeal mucosa to create a phonatory shunt
through which air from the lungs can be forced to provide speech. Although
permanent tracheostomy is necessary, voice quality has been described as superior to
esophageal speech and obtainable in a high percentage of cases.

Voice restoration after total laryngectomy is a difficult problem. Despite widespread
availability of speech therapy and extensive preoperative teaching and aggressive
postoperative rehabilitation, only 24 to 45 percent of alaryngeal patients acquire
esophageal speech. Inability to expel air from the stomach, cricopharyngeus spasm,
and other physiologic reasons have been cited, but depression and social and
emotional withdrawal play an important part as well. Mechanical devices inserted into
the airway have been remarkably unsuccessful, although external vibrators do allow
intelligible speech of low volume. Various attempts have been described to create a
neolarynx or neoglottis, a mucosal or epithelial diaphragm which fits over the
transected end of the cricoid or trachea and serves as a pathway for air inspired
through the tracheostomy to exit through the oral cavity as speech. With these various
methods, good speech quality may be obtained in 50 to 75 percent of cases, but there
is a significant risk of aspiration, requiring takedown of the reconstruction. A simple
tracheoesophageal puncture described by Singer, maintained patent by a small tube,
allows pulmonary air to enter the esophagus and thus the pharynx, to be modulated by
the tongue, lips, and buccal mucosa. This method has allowed fluent speech
restoration in 71 to 88 percent of patients with little risk of aspiration or other serious
complication. This procedure may be performed either at a second stage after healing
of the wound or at the time of laryngectomy, whether closed by primary
approximation or reconstructed with a pectoralis major flap, gastric pull-up, or free
tissue transfer. Transplantation of the larynx has as yet been unsuccessful, but
research is continuing with this method.

Extensive surgery on the larynx is associated with complications. Pharyngocutaneous
fistula occurs in up to 38 percent of laryngectomies and has been associated with
previous radiotherapy, malnutrition, and cell- mediated immunodeficiency.
Prophylactic metronidazole has been suggested as a method to prevent fistula, but
prompt recognition and closure with well-vascularized tissue will prevent prolonged
drainage and rupture of the adjacent irradiated carotid vessels. Problems specific to
the method of reconstruction also occur, such as regurgitation of acid and food after
pharyngogastrostomy after gastric pull-up or hypersecretion of mucus after jejunal
autograft. The problem of stenosis after laryngectomy, particularly in the patient who
receives adjuvant radiotherapy, is similar to that after pharyngolaryngectomy.
Combined with the alterations in cricopharyngeus function (upper esophageal
sphincter mechanism), stenosis greatly impedes the acquisition of esophageal speech.
Interposition of well-vascularized soft tissue, such as the radial forearm or lateral arm
free flap, can decrease the likelihood of postlaryngectomy speech and swallowing
problems (Fig. 15-44).

Nonepidermoid malignancies of the larynx are uncommon. Adenosquamous
carcinoma is a poorly differentiated aggressive lesion that behaves in a manner similar
to advanced squamous cell carcinoma. Rhabdomyosarcoma, chondrosarcoma,
schwannoma, and other mesenchymal malignancies have been reported in both
children and adults. Carcinoid or moderately differentiated neuroendocrine carcinoma
behaves in a fashion similar to malignancy in other sites and may be treated by partial
or total laryngectomy, depending on its stage. Adjuvant radiotherapy and
chemotherapy do not seem to contribute to the cure of the patient. Anaplastic small
cell carcinoma (oat cell) also occurs in the larynx rarely and, like its counterpart in the
lung, is associated with smoking and increased age. Prognosis is also similar to lung
disease, with average survival of 10 months after diagnosis. Multimodal therapy with
chemotherapy as the basis is the most appropriate approach.
One of the most difficult problems associated with laryngectomy is recurrence of
disease at the stoma. Occurring in approximately 5 percent of patients, it may be the
result of submucosal subglottic extension or unresected pretracheal or paratracheal
lymph node metastasis. Resection of disease is possible in some patients by
mediastinal dissection, repositioning the stoma lower and removing the soft tissues of
the superior mediastinum to the innominate vessels. Esophageal reconstruction may
be performed by gastric pull-up or jejunal free autograft, and interposition of
vascularized pectoralis major muscle usually is necessary to separate the great vessels
from the stoma. With this aggressive surgical approach, 17 to 28 percent of the
patients can be treated successfully.

Benign lesions of the larynx may present a diagnostic problem but usually are seen in
different age groups and rarely affect mobility of the vocal cords. Tuberculosis of the
larynx, though rare, may mimic malignancy. Papillomatosis may present in children,
possibly secondary to contamination of the fetus at delivery by the human
papillomavirus, a DNA virus. This persistent problem may require tracheostomy,
since repeated excisions by laser or other means may result in laryngeal or subglottic
stenosis. Adult-onset papillomatosis of the larynx may come with immunosuppression
of various types as recurrent disease or as an opportunistic infection. Immunotherapy
with the bacille Calmette-Guérin (BCG) has been suggested as an adjuvant of surgery.
Vocal nodules or singer's nodules and polyps and sebaceous cysts also may occur in
the mobile cords and may be treated by simple excision.

CONNECTIVE TISSUE NEOPLASMS
Soft-Tissue Sarcomas
General Considerations
Soft-tissue sarcomas arise within tissues that develop embryologically from the
mesoderm, such as skeletal and smooth muscle, adipose and fibrous tissue, and
endothelial cells. They are uncommon tumors overall, with fewer than 5,000 new
cases diagnosed each year in the United States. Less than 10 percent of all sarcomas
arise in the head and neck; they represent less than 1 percent of all head and neck
malignancies. This low incidence, with the attendant difficulty in developing a
comprehensive management plan, may partially account for the poor survival rates in
adults with soft-tissue sarcomas. Unlike epidermoid carcinoma, the most important
determinant of the biologic behavior of sarcomas is histologic grade. Low-grade
tumors tend to recur locally, while high-grade lesions often metastasize early to
distant sites, including lung, liver, and bone. Other prognostic indicators include the
histologic type, the location, the size and the degree of local invasion of primary
lesions, and the presence of locoregional or distant metastatic disease.

Typically soft-tissue sarcoma of the head and neck presents as a painless mass. The
more advanced or more deeply invasive lesions may cause pain, obstructive
symptoms, or cranial nerve deficits. Evaluation of local extent of disease in soft-tissue
sarcomas is similar to that of squamous cell carcinoma and includes indirect
laryngoscopy, palpation endoscopy, and CT or MRI. Depending on histology and
stage of disease, a metastatic work-up should be performed. Pleomorphic sarcomas of
the head and neck, like those arising in other areas, frequently demonstrate cellular
changes consistent with indolent disease in one part of the tumor and characteristic of
very aggressive disease in another part. A generous incisional biopsy often is
necessary to confirm the diagnosis. The mainstay of treatment for the majority of
these lesions in adults remains extensive local resection with clearly negative margins
(tumor no less than 1 mm from the surgical margin). Regional node dissections
usually are performed only if nodal disease is clinically evident. In adults, adjuvant
radiation therapy and chemotherapy may be of some worth, whereas in children their
therapeutic value has been clearly established.

Fibrosarcoma
This is the most common type of soft-tissue sarcoma in adults. There is a bimodal age
distribution, with the first peak in infants under 2 years of age and the second in adults
40 to 60 years of age. Fibrosarcoma often presents as a painless mass of the face or
neck. Histologically, many fibrosarcomas are low grade. The rate of metastasis to
regional nodes is 5 percent, but 50 percent metastasize to lungs, liver, or bone. With
aggressive local resection, 5-year survival rates around 45 percent have been reported.

Malignant Fibrous Histiocytoma
The reported incidence of these tumors in the head and neck has grown in recent years
because of the reclassification of other high-grade sarcomas as malignant fibrous
histiocytomas. Two histologic variants exist, myxoid and inflammatory, with the
latter carrying a poorer prognosis. Whereas local recurrence remains the most
common manifestation of treatment failure, the incidence of nodal metastasis may
approach 50 percent. Therefore, in addition to aggressive local resection, prophylactic
neck dissection is advocated in some centers, depending on stage of disease. The 5-
year survival rate is approximately 50 percent.

Angiosarcoma
These rare cutaneous malignancies most often present as an ulcerated painless mass of
the scalp or face in middle-aged men. They are highly aggressive tumors, with
perivascular extension most often cited as the cause of local failure as well as of
distant metastasis. Radiation therapy and chemotherapy have both been used as
adjuvants to local resection, but 5- year disease-free survival is rare.

Rhabdomyosarcoma
This is the most common type of soft-tissue sarcoma in children, and after lymphoma
is the second most common malignancy of the head and neck in children. Two
important histologic subtypes have been identified. The embryonal variant occurs in
young children (average age four) and carries the better prognosis. Seventy-nine
percent of orbital rhabdomyosarcomas are of the embryonal type. Most of these
neoplasms are now treated successfully with a combination of radiation therapy and
chemotherapy (vincristine, doxorubicin, and cyclophosphamide), yielding survival
rates of 77 to 90 percent. Alveolar rhabdomyosarcoma occurs in older children
(average age ten) and in the cervical soft tissues. While the initial response rate to
radiation therapy and chemotherapy is comparable to that of embryonal
rhabdomyosarcoma, the rate of local recurrences and of distant metastasis is
significantly higher, decreasing survival rates to approximately 50 percent at 5 years.
The Intergroup Rhabdomyosarcoma Study has established specific multimodal
treatment protocols for each type and stage of disease. To date the improvements in
management of rhabdomyosarcoma in children have not yet been realized in adults.

Neural Tumors
Esthesioneuroblastoma (Olfactory Neuroblastoma)
This rare tumor arises from the supporting cells of the olfactory neuroepithelium at
the apex of the nasal cavity. In its earlier stages it may present as a fleshy upper nasal
mass causing epistaxis, unilateral nasal obstruction, or rhinorrhea. In its more
advanced stages the tumor may extend throughout the cribriform plate into the
anterior cranial fossa, invading the frontal lobe and leading to anosmia, rhinorrhea,
headaches, or even personality changes. While this tumor may arise in all age groups,
it has higher incidence in the third and fourth decades of life and a slight male
predominance. When esthesioneuroblastoma is suspected on the basis of the history or
CT scans showing bony erosion, a biopsy procedure of the nasal mass should be
performed in the operating room because its highly vascular nature. Metastasis occurs
in 20 percent of cases, most commonly to the cervical lymph nodes (often bilateral),
lungs, and bone, but the majority of patients succumb to aggressive intracranial
extension. Therefore, surgical treatment is directed at complete local control. Early
lesions may be resected through a lateral rhinotomy and complete ethmoidectomy.
More extensive tumors require a combined neurosurgical- craniofacial effort, with
exposure and complete resection of the cribriform plate and ethmoid sinuses from
both a superior and inferior approach. Adjuvant radiation therapy may improve local
control and survival, and inoperable tumors often are treated with radiation therapy
alone.

Paraganglioma
Paragangliomas or chemodectomas are neoplasms that arise from neural crest cells
and histologically resemble their adrenal gland counterpart, the pheochromocytoma.
They are classified by their location: carotid body, jugular (arising from the glomus
jugulare), vagal body, orbital, and laryngeal. Although these extraadrenal
paraganglionic cells do contain small amounts of catecholamines, it is rare for them to
produce a clinically significant excess of catecholamines. The most common of the
paragangliomas, the carotid body tumor, usually presents as an asymptomatic neck
mass. Chemodectomas at other sites often produce compressive symptoms resulting
in hearing loss, tinnitus, or facial nerve paralysis. Only 6 percent of these tumors are
malignant, and only 4 percent metastasize. Malignancy is determined by clinical
behavior rather than histology. They are highly vascular and have a characteristic
appearance on angiography, with carotid body tumors separating the internal and
external carotid vessels by a mass effect. When technically feasible, treatment should
include complete resection, which in the carotid body tumor requires subadventitial
dissection. The poor-risk patient with an asymptomatic mass may be managed more
conservatively.

Osteogenic Sarcoma
Ten percent of osteogenic sarcomas occur in the head and neck. Most arise in the
mandible or maxilla in the third or fourth decade of life. Risk factors include prior
radiation therapy, fibrous dysplasia, and retinoblastoma. These malignancies present
most frequently as a hard mass with radiographic changes of cortical destruction as
well as new bone formation. These tumors are highly infiltrative not only of bone but
also of secondary mucosa and muscle and must be resected with a wide zone of
adjacent soft tissue. Nodal metastasis is uncommon; however, distant metastasis to
lung occurs in some patients if local control is not achieved. There has nonetheless
been some enthusiasm for chemotherapy administered after surgical resection.
Radiation therapy is generally reserved for curative situations. As with
rhabdomyosarcoma, the use of neoadjuvant or adjuvant chemotherapy has been
effective in children with osteogenic sarcoma but not in adults.

AIDS-RELATED DISORDERS
HIV infection and its consequence, AIDS, produce a large number of abnormalities in
the head and neck region, both neoplastic and nonneoplastic.

Symbiotic Infections
The generalized immunosuppression allows normally symbiotic or latent organisms to
cause serious disease and morbidity. Oral candidiasis is sometimes one of the earliest
manifestations of AIDS. The combination of xerostomia, which may be related to the
chronic fibrosis of the salivary glands or benign lymphoepithelial lesions seen in HIV-
positive patients, and the disturbance of normal flora of the oral cavity results in the
proliferation of yeast and other fungi to pathogenic levels. Herpes simplex virus
infections, resulting in painful ulcerations of the lips, oral mucosa, and oropharynx, as
well as varicella-zoster, with its painful distribution along the fifth cranial nerve, also
are common in patients afflicted by AIDS, again probably a result of generalized
immunosuppression. Other infectious disorders less commonly seen are human
papillomavirus, cytomegalovirus, cat-scratch disease, tuberculosis, and opportunistic
bacterial infection localized to the oral cavity and oropharynx.

Leukoplakia
Oral hairy leukoplakia is similar to the leukoplakia seen in chronic smokers except
that it has a shaggy or more nodular appearance and is more likely to present on the
lateral border of the tongue, frequently as a bilateral lesion. Cellular hyperplasia with
parakeratosis is seen, and there is a high correlation, both serologically and by
electron microscopy, with the Epstein-Barr virus. This lesion is sometimes an early
sign of ultimate HIV positivity, again as an expression of decreased
immunosurveillance.

Lymphoproliferative Disorders
Lymphoproliferative disorders are characteristic of AIDS and frequently occur in the
head and neck. Obstruction of the nasopharynx secondary to overgrowth in the
Waldeyer's ring area has been reported. Cervical lymphadenopathy is commonly a
part of the AIDS-related complex (ARC), and involvement of the intraparotid and
submandibular lymph nodes, with cystic degeneration and symptomatic accumulation
of fluid within them, causes enlargement of the nodes and is an early indicator of the
full-blown disease. Malignant lymphomas, most commonly of the B-cell type, also
have been reported and are second only to Kaposi's sarcoma in frequency, occurring
in up to 10 percent of AIDS patients. These lymphomas usually are extranodular, with
an unusual frequency of primary central nervous system disease. Lymphoma also has
been reported in the neck, oral cavity, and paranasal sinuses. Although the tendency to
disseminate is lower than in other lymphomas, the disease course is rapid and lethal.
Lymphoma occurs more commonly in intravenous drug users than in patients who
have developed AIDS from other sources. Again there is a high correlation of
lymphoma with elevated antigen titers for Epstein-Barr virus and electron
microscopic evidence of its presence. T-cell lymphomas also occur but are less
common. For disease localized to one area, radiotherapy may be an effective
treatment. Multidrug systemic chemotherapy also is effective but places the already
immunosuppressed patient at higher risk for disseminated infection.
Kaposi's Sarcoma
Kaposi's sarcoma is the most common malignancy in AIDS, arising in 15 percent of
patients. There is probably a sexual mode of transmission, since it is much more
common in homosexual AIDS patients than in those acquiring the disease from
intravenous drug use or contaminated blood products. Unlike the classical form of
Kaposi's sarcoma, which occurs in elderly males usually on the lower extremities, this
form of the disease occurs in oral or perioral mucosa in 55 percent of the cases. The
palate is the most common site, although the tongue, pharynx, and larynx have been
described as sites as well. Usually multifocal within the region, it may arise in or
metastasize to the cervical lymph nodes or the salivary glands. The tumor initially
presents as a flat blue to purple patch and may appear to be a submucosal hematoma
secondary to trauma. Later in the course of growth it becomes nodular. Biopsy
examination reveals endothelial cell and fibroblast proliferation, with increased
capillary growth, prominent spindle cells, few mitoses, and extravasation of
erythrocytes. The causation of Kaposi's sarcoma is unclear, although there is some
evidence linking it to cytomegalovirus infection or viral induction of local angiogenic
factors.

As with all malignancies in AIDS patients, the use of conventional multidrug
systemic therapy is somewhat hazardous because of chronic infection. Single-drug
treatment with vinblastine or etoposide, systemically or by intralesional injection,
results in partial regression of tumor and significant palliation in up to 30 percent of
patients. Interferon-a, systemically or as an intralesional injection, also has been
moderately effective. Local radiotherapy with an energy source, such as electrons,
that has low penetration, in total doses of 800 to 1,500 cGy, delivered in ten fractions,
also is effective in shrinking lesions and allowing significant palliation. With all
therapies, median survival of patients is 2 years, with a 5-year survival rate of only 10
percent.

Carcinoma
Squamous cell carcinoma of the upper aerodigestive tract has been reported in the
mouth, tongue, larynx, and other sites in AIDS patients. Although the true risk is
uncertain, squamous cell carcinoma has appeared in patients of earlier age and
without the usual risk factors of smoking and ethanol intake. This pattern is
suggestive of a defect in immunosurveillance similar to that seen in patients having
undergone organ transplantation. In AIDS patients, the median age of presentation of
squamous cell carcinoma is 32 years, in contrast to 60 years in the noninfected
patient, and the clinical course seems to be somewhat more aggressive.

SALIVARY GLANDS
Physiology
The production and excretion of the mixture of mucus, water, and electrolytes known
as saliva into the entrance to the upper aerodigestive tract are the function of the
salivary glands. The major salivary glands are the symmetrically paired parotid,
submandibular, and sublingual glands, which discharge saliva into the oral cavity via
Stensen's ducts, Wharton's ducts, and the numerous small orifices in the floor of the
mouth, respectively. Clustered primarily in the soft and hard palates but also found in
the sinuses and other sites of the upper aerodigestive tract are the minor salivary
glands, which produce mucus for lubrication. Saliva consists of varying
concentrations of numerous substances. To some degree its composition reflects the
osmolality and electrolyte concentration of the extracellular fluid, but its specific
functions require other components as well.

The normal volume of salivary secretion in the adult male ranges from 1,000 to 1,500
mL per day, mainly as serous fluid from the parotid and submandibular glands (95
percent) but also composed of mucus (5 percent) from the sublingual and minor
salivary glands. Active water resorption, sodium and potassium ion exchange, and
bicarbonate production couple with passive diffusion of urea and uric acid to
determine the inorganic content of saliva. Immunoglobulins A, G, and M, albumin,
lysozyme, and other enzymes also are secreted. In addition to its lubricating
properties, which allow food to be moved through the mouth, saliva has antibacterial
and antiviral properties, which protect the soft tissues of the oral cavity as well as the
teeth.

The neurogenic control of salivary secretion depends on reflex arcs that carry afferent
stimuli from the specialized sense organs via cranial nerves I, V, VII, and IX to the
brainstem and hypothalamus, and efferent signals, both sympathetic and
parasympathetic, along the branches of the external carotid artery, the superficial
petrosal nerve, and the chorda tympani.

Anatomy
Parotid Gland
The parotid gland is shaped like a flattened pyramid, with its apex in the
parapharyngeal space behind the mandible adjacent to the pterygoid muscles and its
base extending into the preauricular area from below the angle of the mandible in the
neck, sometimes as low as the mid–sternocleidomastoid muscle, to just below the
zygomatic arch. The medial extent of the gland usually reaches over the masseter
muscle and the vertical ramus of the mandible. The parotid gland is surrounded by the
continuation of the investing layer of the cervical fascia, the superficial layer of which
is continuous with the platysma. The parotid gland parenchyma is arbitrarily divided
into the deep and superficial lobes by the facial nerve, which exits the skull via the
stylomastoid foramen and passes through the substance of the gland. Approximately
70 percent of the gland lies superficial to the plane of the nerve and 30 percent deep to
it.

The lymphatic drainage of the midface, forehead, and anterior portion of the scalp
empties into lymph nodes that lie superficial to the fascia of the parotid and within the
gland itself before sending efferent channels to the jugulodigastric area. Sensory
supply to the gland derives from branches of the trigeminal nerve and from the great
auricular nerve, carrying cervical plexus axons. Stensen's duct, the parotid duct,
condenses from the larger intralobular ducts and passes adjacent to the buccal branch
of the facial nerve on a line between the tragus of the ear and the midline of the upper
lip. It enters the oral cavity adjacent to the second maxillary molar tooth.

The facial nerve, which supplies motor innervation to the muscles of facial expression
and several other muscles, exits the base of the skull from the stylomastoid foramen,
passing deep to superficial and caudad to cephalad before branching at the pes
anserinus into an upper and lower division. Although there is some variability in
branching patterns, particularly of the buccal branch, the upper division usually
includes the temporal, zygomatic, and buccal branches, and the lower division, the
mandibular and cervical branches.

Submandibular Gland
The submandibular salivary gland is surrounded by a condensation of the cervical
fascia that lies beneath the platysma muscle, connecting to the parotid fascia and
known as the pars interglandularis, separating the parotid and jugulodigastric areas
from the submandibular triangle. The anatomic boundaries of the submandibular
triangle are the anterior belly of the digastric muscle medially, the posterior belly
laterally, and the mandible superiorly. The gland lies on the hyoglossus muscle and
wraps both superficial and deep to the mylohyoid muscle medially. The
submandibular ganglion of the lingual nerve carries efferent nerve supply via the
chorda tympani. Wharton's duct conveys the secretions of the submandibular salivary
gland into the oral cavity.

Sublingual Glands
The sublingual salivary glands lie immediately beneath the mucosa of the floor of the
mouth, intimately related to the lingual artery, and release their mucous secretions
into the oral cavity through numerous orifices along the alveololingual sulcus.

Inflammatory and Infectious Disorders
Inflammation usually presents as diffuse enlargement or firmness of the gland,
unilateral or bilateral, associated with tenderness and erythema. Bacterial infection
usually is the result of duct obstruction and retrograde infection with oral bacteria.
Acute bacterial parotitis may be seen in the elderly postoperative patient who
becomes dehydrated and is usually caused by Staphylococcus aureus. Although
rehydration and antibiotic therapy may be successful, drainage of localized abscesses
and even total parotidectomy may be required for resolution. Because of the septate
nature of the parotid, simple drainage of the gland is frequently unsuccessful. Acute
sialadenitis of the submandibular gland also may necessitate gland resection.

Mumps, coxsackievirus, and echoviruses also may cause acute parotitis, usually
panglandular but occurring as unilateral gland enlargement. Tuberculosis,
actinomycosis, and cat-scratch disease also may present with enlargement of the
salivary glands or of their adjacent lymph nodes. Systemic disorders such as
sarcoidosis, Sjögren's syndrome, and cirrhosis with liver failure also result in salivary
gland enlargement. Mikulicz's syndrome, enlargement of the gland with histologic
changes reflecting loss of acinar epithelium and replacement with chronic
inflammatory cells, is a nonspecific accompaniment of several diseases, such as
leukemia, lymphoma, and tuberculosis.

Tumors
Pathology
The clinical problem most frequently presented to the surgeon is that of a discrete
mass in the salivary gland, particularly the parotid gland. Of salivary gland tumors, 70
to 80 percent present in the parotid gland. Of parotid gland tumors, 70 to 80 percent
are benign and, of the benign tumors, 80 percent are pleomorphic adenomas.
Although lymph nodes, lipomas, cysts, or other benign entities may present as solitary
masses, the benign pleomorphic adenoma is by far the most common mass. Occurring
most frequently in the fifth decade, with a slight female predominance, the benign
mixed tumor or pleomorphic adenoma is the proliferation of epithelial and
myoepithelial cells of the ducts as well as an increase in the stromal component,
which histologically may appear similar to cartilage. A true epithelial benign
neoplasm, it may grow to a large size without causing facial nerve symptoms (Fig. 15-
45). Pleomorphic adenomas usually present as a solitary painless mass in the
superficial lobe of the gland. Deep lobe growth may present as an intraoral pharyngeal
mass as growth extends into the pharynx via the parapharyngeal space. Malignant
degeneration of pleomorphic adenomas occurs in 2 to 10 percent of adenomas
followed for long periods, with carcinoma ex pleomorphic adenoma occurring most
frequently as adenocarcinoma.

The second most frequent benign neoplasm of the salivary glands is the papillary
cystadenoma lymphomatosum or Warthin's tumor. With a marked male
predominance, it usually occurs in the tail of the parotid gland and presents with a
lymphocytic infiltrate as well as cystic epithelial proliferation. There is a 10 percent
incidence of bilaterality and multicentricity. A subset of the group of monomorphic
adenomas, Warthin's tumors comprise 4 to 8 percent of all parotid tumors. Other
benign monomorphic adenomas include oxyphilic adenoma, oncocytoma, basal cell
adenoma, sebaceous adenoma, sialadenoma papilliferum, and canalicular adenoma,
all of which are rare. Pleomorphic adenoma is the most common benign tumor of the
parotid, submandibular, and minor salivary glands.

Malignant tumors of the salivary glands occasionally (4 percent) present as a diffuse
enlargement of a gland, almost always as a discrete mass. Pain is associated with
malignancy in 12 to 24 percent of cases. Other symptoms include formication (a
paresthesia that is described as the feeling of ants crawling on the skin), facial nerve
dysfunction (8 to 26 percent), or complete paresis of the nerve (7 to 9 percent). All of
these symptoms and signs carry a poorer prognosis than asymptomatic disease (Fig.
15-46). Facial nerve palsy is almost never seen with benign disease, so the presence of
nerve palsy, even without a discrete mass, must be considered a possible sign of
malignancy.

Fixation to the masseter muscle or pterygoid muscles occurs in approximately 17
percent of cases, and skin ulceration in 9 percent. The risk of clinical or subclinical
metastases to the cervical lymph nodes from salivary gland cancers depends on the
histology and grade of the primary tumor. High-grade mucoepidermoid
adenocarcinoma and squamous cell carcinoma have a high risk of metastatic disease
(Fig. 15-47), whereas adenoid cystic acinic cell and lower grades of mucoepidermoid
and squamous cell have a low risk of metastasis. Approximately 20 percent of parotid
gland neoplasms are malignant. The risk of malignancy is inversely proportion to
gland size, with the submandibular glands having 40 percent malignant tumors and
the minor salivary glands 60 percent.

Diagnosis
The discrete mass in the salivary gland must be considered a possible malignancy.
History and physical examination may provide some indication that the lesion is
malignant. Complete resolution after 10 days of antibiotics and clinical features
consistent with inflammation may constitute an adequate therapeutic trial. Definitive
histologic diagnosis, however, is ultimately necessary. Fine-needle aspiration may be
helpful in planning surgery, but any uncertainty should be treated with adequate
surgical excision. CT scan of the parotid is helpful in determining extension of the
tumor into the deep lobe. MRI can be formatted in both axial and coronal planes,
giving even better anatomic information. When carefully performed and analyzed
MRI can provide information about the facial nerve and its anatomic relationship to
the tumor. Contrast-enhanced studies may allow discrimination between the gland and
metastatic lymph nodes, particularly in the submandibular area, differentiating
metastases from the head and neck site to an intraglandular or epiglandular lymph
node from intrinsic malignancy of the salivary gland. Sialography, or injection of
contrast material into Stensen's or Wharton's ducts, is useful in demonstrating the
chronic stenotic changes of a benign lymphoepithelial lesion or chronic parotitis and
in showing complete occlusion from stones. Eighty percent of parotid duct stones are
radiolucent. Eighty percent of submandibular gland stones are radiopaque.

Treatment
The surgical approach to a salivary gland mass is predicated on the assumption that it
is malignant. The major confounding factor is the presence of the facial nerve in the
parotid gland. Since the facial nerve passes through the gland, the usual surgical
oncologic approach to head and neck malignancy—en bloc resection—would require
excision of the nerve in all cases. This approach, however, is not appropriate in most
situations. If there is no evidence of nerve involvement, the tumor should be excised
by superficial lobectomy, removal of the parenchyma above the nerve with a margin
of normal tissue, preserving the nerve.

If the tumor is malignant, total parotidectomy with preservation of the nerve is
indicated, though it is a piecemeal procedure (Fig. 15-48). Involvement of a branch of
the nerve requires removal of that branch. In young patients, nerve graft should be
used to replace the resected nerve segment in the hope of avoiding the long-term
sequelae of facial nerve palsy. In the event of invasion of the nerve by tumor, any
proximal extension of the malignancy to the base of the skull should be evaluated, and
in some cases resection of the nerve to clear margin in the stylomastoid foramen or
the facial canal may improve survival. If the facial nerve is not involved by
malignancy but preservation of the nerve would result in gross disruption of the
tumor, the nerve should be removed and replaced with a nerve graft.

When clinical examination, with or without fine-needle aspiration cytology, does not
clearly define the problem, a biopsy specimen should be obtained by superficial
lobectomy, with identification and preservation of the main trunk of the facial nerve
and its branches. Benign tumors of the superficial lobe should be removed with a
clear margin by superficial lobectomy. If the deep lobe is involved, total
parotidectomy may be required even for benign disease, although partial
parotidectomy is sometimes possible.

Treatment of the neck in patients with malignant disease of the parotid depends on the
histologic type and the grade of the tumor and its risk of metastatic disease or the
presence of the metastatic disease itself. Node- positive necks are treated by the
appropriate neck dissection—radical neck dissection if there is involvement in the
sternocleidomastoid muscle or the jugular vein, or modified or selective neck
dissection depending on the site of metastasis. Although elective or prophylactic neck
dissections are not as frequently necessary as in mucosal malignancy, they are
indicated in high- grade mucoepidermoid carcinoma, squamous cell carcinoma, and
high- grade adenocarcinoma.

Neoadjuvant (preoperative) or adjuvant chemotherapy has not been effective in
treating malignancy of the salivary glands—parotid, submandibular, or minor glands.
Adjuvant postoperative radiotherapy, however, is effective. Radiation portals should
include the entire site of surgery, the foramen ovale, the base of the skull, including
the mastoid process and the stylomastoid foramen, and the ipsilateral neck depending
on the risk of metastasis.

The risk of recurrent disease and the pattern of recurrence also depend on histology
and grade. Mucoepidermoid carcinoma, squamous cell carcinoma, and high-grade
adenocarcinoma have a high frequency of cervical and distant metastasis as well as
local recurrence. Adenoid cystic carcinoma is characterized by an indolent course but
relentless local progression and perineural invasion, with disease eventually extending
to the base of the skull and the brain. Both adenoid cystic and mucoepidermoid
carcinoma may demonstrate extensive pulmonary metastasis that remains
asymptomatic for relatively prolonged periods, and the patient's death may be caused
by locoregional disease rather than by disseminated disease. Just as adjuvant
chemotherapy has been unsuccessful, so is treatment of disseminated disease,
although both doxorubicin and cisplatin have demonstrated finite response rates
without prolongation of survival. Local recurrence may be successfully treated by
radical resection with or without adjuvant radiotherapy.

The treatment of submandibular gland abnormalities follows the same basic rule as
for the parotid gland. If definitive diagnosis cannot be made before surgery, total
excision of the gland, with preservation of the uninvolved marginal mandibular,
hypoglossal, and lingual nerves, is indicated and is adequate therapy for benign
tumors and inflammatory or autoimmune disorders. Radical resection of the nerves,
platysma, skin, and underlying muscle is reserved for extensive local invasion.
Adenoid cystic carcinoma is the most common malignant histology of the
submandibular gland, and pleomorphic adenoma the most common benign tumor.
Adjuvant postoperative radiotherapy appears to be helpful in the malignant tumor.

Minor salivary gland disorders reflect the spectrum seen in the major salivary glands.
Mucocele is a cystic enlargement of the intraoral glands usually seen in the lip or the
floor of the mouth. Sjögren's syndrome of keratoconjunctivitis sicca is diagnosed by
lip biopsy and histologic confirmation of the chronic inflammatory changes seen in
the minor salivary glands. Necrotizing sialometaplasia, an ulcerative but self-limited
disorder affecting the junction of the hard and soft palates, clinically mimics
malignancy but eventually heals; biopsy examination reveals no evidence of
malignant change.

Tumors of the minor salivary glands, either benign or malignant, may occur in any of
the mucosa-lined areas of the upper aerodigestive tract but are most common in the
hard and soft palates. Their presentation may be as a submucosal or an ulcerative
mass. Pleomorphic adenoma is the most common benign tumor, and mucoepidermoid
and adenoid cystic carcinoma (Fig. 15-49) occur with roughly the same frequency as
malignancies. Therapy is wide local resection, including subjacent bone if the hard
palate is involved, with adjuvant radiotherapy for malignancy. Since subclinical
metastases to the neck are rare, cervical lymphadenectomy is reserved for patients
with histologically proved lymph node metastases. Palatal defects usually can be
rehabilitated with dental prostheses, though local or distant tissue transfer may be
necessary for extensive disease.


(Bibliography omitted in Palm version)

				
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