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THYROID CARCINOMA

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					THYROID CARCINOMA
                      Anatomy


   Weight 20-25 gm
   Isthmus of the thyroid is situated anterior to the second
    and third tracheal rings.
   Histologically the structure of thyroid gland consists of
    follicles of varying size.
   Follicle consist of cuboidal epithelium in inactive phase
    and columnar epithelium in active phase.
   Colloid storage the hormone in the form of thyroglobulin
    molecules.
       Development of Thyroid Gland

   Earliest endocrine glands to develop.
   3rd week, it out-pouches from the midline of the anterior
    pharyngeal floor.
   5th week, ultimobranchial bodies develop to form
    parafollicular C-cells.
   6th week, Thyroglossal duct obliterates
   9th week, Thyroid follicle form
   10th week, active uptake of iodine starts
                 Blood Supply


   Superior thyroid artery arise from ipsilateral external
    carotid arteries and divide into anterior and posterior
    branches at the apices.


   Inferior thyroid artery from thyrocervical trunk which
    arise from subclavian artery.


   Thyroidea ima from aorta or innominate.
            Lymphatic Drainage

• Extensive, lymphatic, network within the gland.

• Sub capsular plexus drains to the juxtathyroid (level 6)
  I.e. pretracheal, paratracheal and nodes on the superior
  and inferior thyroid veins.

• Then to deep cervical and mediastinal group.
Lymphnodes in the neck
Lymph nodes divided in seven regions
           EPIDEMIOLOGY
•   1% of all cancers
•   0.5 % of mortality due to cancer
•   Most common endocrine malignancy
•   Occurs mainly in patients of 25-65 year old
•   Annual incidence 20-70 new cases /106
•   Annual mortality ~ 4 cases /106
• More common in women
• Associated with radiation exposure and endemic
    goiters
•   10% of individuals will have a palpable thyroid
    nodule in their life time
•   8-17% of surgically treated nodules are
    carcinomas
•   Overall 5 year survival rate 90%
•   The unique property of the differentiated thyroid
•   carcinoma is its ability to concentrate iodine,
    albeit in lesser degree than the normal thyroid
• It is one of the few malignancies where radionuclides are
    extensively used not only for the diagnosis of primary
    tumor and distant metastasis but also for therapy of the
    disease
•   It is generally accepted that the TC in endemic zone has
    more follicular histology and higher incidence of
    Anaplastic differentiation.
             Incidence


•   Papillary 60- 80%
•   Follicular 15-30 %
•   Medullary 2-10 %
•   Anaplastic 1-10 %
History
• Symptoms
• The most common presentation of a thyroid
    nodule, benign or malignant, is a painless mass in
    the region of the thyroid gland (Goldman, 1996).
•   Symptoms consistent with malignancy
        • Pain
        • dysphagia
        • Stridor
        • hemoptysis
        • rapid enlargement
        • hoarseness
History (continued...)
• Risk factors
• Thyroid exposure to irradiation
     • low or high dose external irradiation (40-50 Gy
       [4000-5000 rad])
     • especially in childhood for:
        – large thymus, acne, enlarged tonsils, cervical adenitis,
          sinusitis, and malignancies
     • Schneider and co-workers (1986) studied, with long
       term F/U, 3000 patients who underwent childhood
       irradiation.
        – 1145 had thyroid nodules
        – 318/1145 had thyroid cancer (mostly papillary)
History (continued...)
• Risk factors (continued…)
• Age and Sex
     • Benign nodules occur most frequently in women 20-
       40 years
     • 5%-10% of these are malignant
     • Men have a higher risk of a nodule being malignant
     • Belfiore and co-workers found that:
        – the odds of cancer in men quadrupled by the age of 64
        – a thyroid nodule in a man older than 70 years had a 50%
          chance of being malignant
History (continued…)
 • Family History
   – History of family member with medullary
     thyroid carcinoma
   – History of family member with other
     endocrine abnormalities (parathyroid,
     adrenals)
   – History of familial polyposis (Gardner’s
     syndrome)
Evaluation of the thyroid Nodule
(Physical Exam)
• Examination of the thyroid nodule:
     • consistency - hard vs. soft
     • size - < 4.0 cm
     • Multinodular vs. solitary nodule
        – multi nodular - 3% chance of malignancy (Goldman, 1996)
        – solitary nodule - 5%-12% chance of malignancy
          (Goldman, 1996)
     • Mobility with swallowing
     • Mobility with respect to surrounding tissues
     • Well circumscribed vs. ill defined borders
Physical Exam (continued…)
• Examine for ectopic thyroid tissue
• Indirect or fiberoptic laryngoscopy
     • vocal cord mobility
     • evaluate airway
     • preoperative documentation of any unrelated
       abnormalities
• Systematic palpation of the neck
     • Metastatic adenopathy commonly found:
        – in the central compartment (level VI)
        – along middle and lower portion of the jugular vein
          (regions III and IV) and
• Attempt to elicit Chvostek’s sign
  Classification of Malignant Thyroid
  Neoplasm's
• Papillary carcinoma       • Medullary Carcinoma
     • Follicular variant   • Miscellaneous
     • Tall cell                 • Sarcoma
     • Diffuse sclerosing        • Lymphoma
     • Encapsulated              • Squamous cell carcinoma
• Follicular carcinoma           • Mucoepidermoid
     • Overtly invasive            carcinoma
     • Minimally invasive        • Clear cell tumors
• Hurthle cell carcinoma         • Plasma cell tumors
                                 • Metastatic
• Anaplastic carcinoma              –   Direct extention
     • Giant cell                   –   Kidney
     • Small cell                   –   Colon
                                    –   Melanoma
                  Role of Genes
• RET protooncogene plays significant role in the
    pathogenesis of thyroid cancers.
•   RET/ PTC 3 is associated with a solid type
    papillary thyroid cancer that appears at a higher
    stage and to be more aggressive.
•   Mutated ras oncogeenes identified in upto 40%
    of thyroid follicular adenomas and carcinomas ,
    MNG and papillary and anaplastic ca.
•   Mutations of p53 are rare in PTCs , but common
    in undifferentiated thyroid cancers and thyroid
    cancer cell lines.
WDTC - Papillary Carcinoma
• 60%-80% of all thyroid cancers (Geopfert, 1998,
  Merino, 1991)

• Histologic subtypes
       • Follicular variant
       • Tall cell
       • Columnar cell
       • Diffuse sclerosing
       • Encapsulated
• Prognosis is 80% survival at 10 years (Goldman,
  1996)

• Females > Males
• Mean age of 35 years (Mazzaferri, 1994)
•   Large proportion of papillary Ca. in
    areas of higher Iodine intake
•   Associated with radiation exposure
•   Usually well differentiated
•   Slow growing
•   In young indolent
•   In old more aggressive
• Multifocal in 20-80%
• Tumor encapsulated in 4-22%
• Extension beyond capsule - 5-16%
• Distant metastases - 3-7%
• Good prognosis - >90% survival rate
• Cancer death in 20 year period - 4-12%
• Usually contain elements of follicular
  differentiation
• Tend to infiltrate locally
 WDTC - Papillary Carcinoma
 (continued…)


• Lymph node involvement is common
    • Major route of metastasis is lymphatic
    • 46%-90% of patients have lymph node
      involvement Clinically undetectable lymph
      node involvement does not worsen prognosis
  WDTC - Papillary Carcinoma
  (Continued…)
• Microcarcinomas - a manifestation of
 papillary carcinoma
    • Definition - papillary carcinomas smaller than 1.0 cm
    • Most are found incidentally at autopsy
    • Autopsy reports indicate that these may be present in
      up to 35% of the population
    • Usually clinically silent
    • Most agree that the morbidity and mortality from
      microcarcinoma is minimal and near that of the
      normal population
    • One study showed a 1.3% mortality rate
 WDTC - Papillary Carcinoma
 (continued…)
• Pathology
    • Gross - vary considerably in size
              - often multi-focal
              - unencapsulated but often have a
      pseudocapsule
    • Histology - closely packed papillae with little colloid
                 - psammoma bodies
                  - nuclei are oval or elongated, pale staining
      with ground glass appearance - Orphan Annie cells
Cut surface of papillary
carcinoma.
The
coarsely granular surface reflects the
microscopic morphologic features of
branching processes
Papillary carcinoma.
Branching processes
composed of fibrovascular
stalks supporting low
columnar cells with optically
clear nuclei (inset).
Psammoma bodies are also
evident.
• Poor prognosis:
   •   Male gender
   •   > 50 year old
   •   Tumor larger than 4 cm
   •   Less differentiated
   •   Local invasion or distant metastases
Molecular and genetic markers for poor prognosis



  DNA aneuploidy,
  Decreased cAMP response to TSH
  Increased EGFB,
  Presence of N ras and gsp mutation,
  Over expression of c myc,
  p53 mutation
Papillary carcinoma of thyroid showing multifocal
            tumour(85% are multifocal)
WDTC - Follicular Carcinoma
• 20% of all thyroid malignancies
• Women > Men (2:1 - 4:1)
• Mean age of 39 years
• Prognosis - 60% survive to 10 years
• Metastasis - angioinvasion and
 hematogenous spread
    • 15% present with distant metastases to bone and
      lung
• Lymphatic involvement is seen in 13%
Follicular Carcinoma

• Greater degree of TSH responsiveness
• Low incidence in iodine-rich areas
• High incidence in iodine-depleted
 countries
• Mostly unifocal
• Closely resemble follicular adenomas
• Involves cervical nodes in 6% of cases
• Angio -invasive (unlike Papillary
 carcinomas)
WDTC - Follicular Carcinoma
(Continued…)
• Pathology
    • Gross - encapsulated, solitary
    • Histology - very well-differentiated (distinction
     between follicular adenoma and carcinoma is
                    difficult)
     - Definitive diagnosis - evidence of vascular
            and capsular invasion
    • FNA and frozen section cannot accurately distinguish
               between benign and malignant lesions
• Prone to give distant metastases (lungs, bones)
• The older the patient- the lesser the
    differentiation
•    Overall 20 year survival – 80%
•    Poor prognosis associated with
      age > 45 year old
      local extracapsular invasion
      distant metastases
Follicular neoplasm of thyroid presenting as an isolated swelling
WDTC - Hurthle Cell Carcinoma
• Aggressive Variant of follicular carcinoma
• First described by Askanazy
       • “Large, polygonal, eosinophilic thyroid follicular cells
         with abundant granular cytoplasm and numerous
         mitochondria” (Goldman, 1996)
• Definition (Hurthle cell neoplasm) - an
    encapsulated group of follicular cells with at least a
    75% Hurthle cell component
•   Carcinoma requires evidence of vascular and
    capsular invasion
• 4%-10% of all thyroid malignancies            (Sessions, 1993)
    Hurthle cell Carcinoma

•    Composed of "modified follicular cells"
•    Up to 25% Multifocal
•    Does not tend to take up radioactive iodine
•    Prognosis similar to that of follicular carcinoma
     Therefore not diagnosed by FNAC as there is
    capsular and vascular invasion
  Medullary Thyroid Carcinoma
• 10% of all thyroid malignancies
• 1000 new cases in the U.S. each year
• Arises from the parafollicular cell or C-cells
  of the thyroid gland
     • derivatives of neural crest cells of the branchial
       arches
     • secrete calcitonin which plays a role in calcium
       metabolism
 Medullary Thyroid Carcinoma
 (Continued…)


• Develops in 4 clinical settings:
     • Sporadic MTC (SMTC)
     • Familial MTC (FMTC)
     • Multiple endocrine neoplasia IIa (MEN IIa)
     • Multiple endocrine neoplasia IIb (MEN IIb)
 Medullary Thyroid Carcinoma
 (continued…)

• Sporadic MTC:
  – 70%-80% of all MTCs (Colson, 1993, Marzano, 1995)
     • Mean age of 50 years (Russell, 1983)
     • 75% 15 year survival (Alexander, 1991)
     • Unilateral and Unifocal (70%)
     • Slightly more aggressive than FMTC and MEN
      IIa
    • 74% have extrathyroid involvement at
      presentation (Russell, 1983)
Medullary Thyroid Carcinoma
(Continued…)

• Familial MTC:
    • Autosomal dominant transmission
    • Not associated with any other endocrinopathies
    • Mean age of 43
    • Multifocal and bilateral
    • Has the best prognosis of all types of MTC
    • 100% 15 year survival
Medullary Thyroid Carcinoma
(continued…)

• Multiple endocrine neoplasia IIa (Sipple’s
 Syndrome):
     • MTC, Pheochromocytoma, parathyroid hyperplasia
     • Autosomal dominant transmission
     • Mean age of 27
     • 100% develop MTC (Cance, 1985)
     • 85%-90% survival at 15 years (Alexander, 1991, Brunt,
      1987)
Medullary Thyroid Carcinoma
(continued…)

• Multiple endocrine neoplasia IIb (Wermer’s
 Syndrome, MEN III, mucosal syndrome):
    • Pheochromocytoma, multiple mucosal neuromas,
      marfanoid body habitus
    • 90% develop MTC by the age of 20
    • Most aggressive type of MTC
    • 15 year survival is <40%-50%
                                   (Carney, 1979)
Medullary Thyroid Carcinoma
(continued…)
• Diagnosis
     • Labs: 1) basal and pentagastrin stimulated serum
                       calcitonin levels (>300 pg/ml)
             2) serum calcium
             3) 24 hour urinary catecholamines
                       (metanephrines, VMA, nor-
       metanephrines)
             4) carcinoembryonic antigen (CEA)
     • Fine-needle aspiration
     • Genetic testing of all first degree relatives
            RET   proto-oncogene
                 Histologically


• Medullary carcinoma.
          The tumor is composed of spindle cells
  with moderate amount of eosinophilic cytoplasm,
  some assuming plasmacytoid appearance.
  Focal deposits of amyloid are seen in upper left
  corner.
    Anaplastic Carcinoma of the
    Thyroid
•   Highly lethal form of thyroid cancer
•   Median survival <8 months
•   1%-10% of all thyroid cancers
•   Affects the elderly (30% of thyroid cancers in
    patients >70 years)
•   Mean age of 60 years
•   53% have previous benign thyroid disease
•   47% have previous history of WDTC
•   Long standing neck mass, which rapidly enlarges
    may be painful
Anaplastic Carcinoma of the Thyroid
• Pathology
    • Classified as large cell or small cell .
    • Large cell is more common and has a worse
      prognosis .
    • Histology - sheets of very poorly differentiated
      cells .
                  little cytoplasm
                   numerous mitoses
                   necrosis
                   extrathyroidal invasion
• Highly fatal
• Grows rapidly, spreads locally ,invades the
    trachea, esophagus , mediastinum by direct
    invasion
•      Grave prognosis
•      Most die within one year
               Lymphomas

    Accounts for <1%
- Most of them are non-Hodgkin's B cell type
- Mostly develop in patients with Chronic lymphocytic
thyroiditis or as a part of generalised lymphomatous
conditions.
- Signs and symptoms - Similar to anaplastic ca - rapidly
enlarging neck mass often painless.
- Patients may present with acute respiratory distress
• Treatment - respond rapidly to CHOP
 regimen
• Combined treatment with radiotherapy
 also recommended.
• Overall survival rate is 50%.
Metastasis from Ca thyroid in   Metastasis from Ca thyroid in
Humerus                         left parietal bone
Evaluation of the Thyroid
Nodule
(Blood Tests)
• Thyroid function tests
     • thyroxine (T4)
     • triiodothyronin (T3)
     • thyroid stimulating hormone (TSH)
• Serum Calcium
• Thyroglobulin (TG)
• Calcitonin
Evaluation of the Thyroid
Nodule
(Radio imaging)
• Radio imaging usually not used in initial work-up
  of a thyroid nodule
      • Chest radiograph
      • Computed tomography
      • Magnetic resonance imaging
Evaluation of the Thyroid
Nodule
(Ultrasonography)
• Advantages
• Most sensitive procedure for identifying lesions
    in the thyroid (2-3mm)
•   90% accuracy in categorizing nodules as solid,
    cystic, or mixed (Rojeski, 1985)
•   Best method of determining the volume of a
    nodule (Rojeski, 1985)
•   Can detect the presence of lymph node
    enlargement and calcifications
•   Noninvasive and inexpensive
Ultrasonography (Continued…)
• When to use Ultrasonography:
• Long term follow-up for the following:
     • to evaluate the involution of a multinodular gland or
       a solitary benign nodule under suppression therapy
     • monitor for reaccumulation of a benign cystic lesion
     • follow thyroid nodules enlargement during
       pregnancy
• Evaluation of a thyroid nodule:
     • help localize a lesion and direct a needle biopsy
       when a nodule is difficult to palpate or is deep-
       seated
     • Determine if a benign lesion is solid or cystic
Ultrasonography (Continued…)

• Disadvantages
   • Unable to reliably diagnose true cystic lesions
   • Cannot accurately distinguish benign from malignant
    nodules
Evaluation of the Thyroid
Nodule
(Thyroid-Stimulating Hormone Suppression)
• Mechanism/Rationale
    • Exogenous thyroid hormone feeds back to the
      pituitary to decrease the production of TSH
    • Cancer is autonomous and does not require TSH for
      growth whereas benign processes do
    • Thyroid masses that shrink with suppression therapy
      are more likely to be benign
    • Thyroid masses that continue to enlarge are likely to
      be malignant
Thyroid Suppression (continued…)
Limitations:
    • 16% of malignant nodules are suppressible
    • Only 21% of benign nodules are suppressible
    • Provides little use in distinguishing benign
     from malignant nodules
    Evaluation of the Thyroid
    Nodule
    (Radioisotope Scanning)
• Prior to FNA, was the initial diagnostic procedure
    of choice
•   Performed with: technetium 99m pertechnetate
    or radioactive iodine
        • Technetium 99m pertechnetate
             cost-effective
             readilyavailable
             short half-life
             trapped but not organified by the thyroid - cannot
              determine functionality of a nodule
Radioisotope Scanning (Continued…)

   • Radioactive iodine
         radioactive iodine (I-131, I-125, I-123)
         is trapped and organified
         can determine functionality of a thyroid
          nodule
Radioisotope Scanning (continued...)
• Limitations
  – Not as sensitive or specific as fine needle
    aspiration in distinguishing benign from
    malignant nodule
        – 90%-95% of thyroid nodules are hypofunctioning, with
          10%-20% being malignant
        – Campbell and Pillsbury (1989) performed a meta-analysis
          of 10 studies correlating the results of radionuclide scans in
          patients with solitary thyroid nodules with the pathology
          reports following surgery and found:
             17% of cold nodules, 13% of warm or cool nodules,
              and 4% of hot nodules to be malignant
Radioisotope Scanning (continued…)
Specific uses of thyroid scanning:
    • Preoperative evaluation
      – When patients have benign (by FNA), solid (by
        U/S) lesions
      – When patients have nonoxyphilic follicular
        neoplasm's
    • Postoperative evaluation
      – immediately postop for localization of residual
        cancer or thyroid tissue
      – follow-up for tumor recurrence or metastasis
 Evaluation of the Thyroid
 Nodule
 (Fine-Needle Aspiration)
• Currently considered to be the best first-line
  diagnostic procedure in the evaluation of
  the thyroid nodule:
• Advantages:
     • Safe
     • Cost-effective
     • Minimally invasive
     • Leads to better selection of patients for surgery than
      any other test   (Rojeski, 1985)
Fine-Needle Aspiration (continued…)
• Limitations
       • skill of the aspirator
                Sampling  error in lesions <1cm, >4cm, multinodular
                 lesions, and hemorrhagic lesions
                Error can be diminished using ultrasound guidance

       • expertise of the cytologist
       • difficulty in distinguishing some benign cellular
         adenomas from their malignant counterparts
         (follicular and Hurthle cell)
• False negative results = 1%-6% (Mazzeferri, 1993)
• False positive results = 3%-6% (Rojeski, 1985,
  Mazzeferri, 1993, Hall, 1989)
Fine-Needle Aspiration (continued…)
• Pathologic results are categorized as:
     • positive,
     • negative, or
     • indeterminate
• Hossein and Goellner (1993) use four
 categories. They pooled data from seven
 series and came up with the following rates:
     • benign - 69%
     • suspicious -10%
     • malignant - 4%
     • nondiagnostic - 17%
AJCC Cancer staging
Primary tumour (T)

TX        Primary tumour cannot be assessed

T0        No evidence of primary tumor

T1        Tumor < 2 cm in diameter, limited to thyroid

T2        Tumor >2 cm but <4 cm in diameter, limited to thyroid
T3        Tumor >4 cm in diameter, limited to thyroid, or any tumor
          with minimal extrathyroidal invasion
T4a       Any size tumor extending beyond capsule to invade
          subcutaneous soft tissue, larynx, trachea, esophagus, or
          recurrent laryngeal nerve, or intrathyroidal anaplastic cancer
T4b       Tumor invading prevertebral fascia, or encasing carotid
          artery or mediastinal vessels, or extrathyroidal anaplastic
          cancer.
Regional lymph nodes (N) include central, lateral, cervical, and upper
mediastinal nodes
Nx          Regional lymph nodes cannot be assessed
N0          No regional lymph node metastasis
N1          Regional lymph node metastasis
N1a         Metastases to level VI (pretracheal, paratracheal and
            prelaryngeal/delphian lymph nodes)
N1b         Metastases to unilateral, bilateral, or contralateral cervical
            or superior mediastinal lymph nodes
Distant metastasis (M)
MX          Distant metastases cannot be assessed
M0          No distant metastasis
M1          Distant metastasis
   WDTC - Prognosis
• Based on age, sex, and findings at the time
  of surgery (Geopfert, 1998)
• Several prognostic schemes represented by
  acronyms have been developed by different
  groups:
     • AMES (Lahey Clinic, Burlington, MA)
     • GAMES (Memorial Sloan-Kettering Cancer Center,
       New York, NT)
     • AGES (Mayo Clinic, Rochester, MN)
Prognostic Risk Classification for Patients with
Well-Differentiated Thyroid Cancer
(AMES or AGES)
                Low Risk                High Risk
• Age           <40 years               >40 years
• Sex           Female                  Male
• Extent        No local extension,     Capsular invasion, extra-
                intrathyroid, no caps   thyroidal extension
                invasion
• Metastasis    None                    Regional/distant
• Size          <2 cm                   >4 cm
• Grade         Well diff               Poorly diff
Management
• Surgery is the definitive management of
 thyroid cancer, excluding most cases of ATC
 and lymphoma
• Other Modalities
• RADIO-IODINE
• THYROID HORMONE
• Types of operations
• Lumpectomy
      Removal of nodule with minimal surrounding tissue

• Partial thyroidectomy
      Removal of nodule and large margin of surrounding
  thyroid tissue

• Subtotal thyroidectomy
      Bilateral removal of more than
      half of the thyroid + isthmus

• Lobectomy or hemithyroidectomy
     Removal of one lobe + isthmus
• Near total Thyroidectomy
      Total lobectomy & Isthmusectomy leaving <10% of
      the posterior lateral portion of the contralateral lobe

• Total Thyroidectomy
      Removal of both lobes and isthmus
Management of Papillary Carcinoma

• Near-total or total thyroidectomy is
  recommended if:
   –   Tumor > 1-1.5cm
   –   Contralateral nodules
   –   Local or regional metastasis
   –   + FHx in 1st degree relative
   –   + history of radiation exposure
   –   Age >45 yr
• Increased extent of surgery lowers recurrence
  rates and has improved survival in high-risk
  patients
Management of Papillary Cancer
When is lobectomy an acceptable surgical
 procedure for FNA proven papillary cancer?

• According to the American Thyroid
 Association Guidelines Taskforce, lobectomy
 with isthmusectomy may be sufficient
 treatment for microcarcinoma ( 1cm), low-
 risk patients, intrathyroidal cancer without
 involvement of cervical LN
Management of Papillary Cancer
Will you plan on performing a lymph node
 dissection?
• A central compartment (Level VI) neck dissection should be
    considered
•   If nodal disease is evident clinically then a more extensive
    cervical lymphadenectomy should be performed
•   LN sampling not recommended
 Management of FNA suspicious for
 follicular neoplasm
• Patients diagnosed by FNA biopsy as having a follicular
  lesion should undergo thyroid lobectomy because at
  least 80 % of these patients will have benign adenomas.

• Some surgeons recommend total thyroidectomy in older
  pts with follicular lesions larger than 4 cm because of the
  higher risk of cancer. ( 50 % ).

• Total thyroidectomy should be performed when thyroid
  ca. is diagnosed.
 Management (WDTC) - Papillary and
 Follicular (continued)

• Postoperative therapy/follow-up
  – Radioactive iodine (administration)
     • Scan at 4-6 weeks postop
     • repeat scan at 6-12 months after ablation
     • repeat scan at 1 year then...
     • every 2 years thereafter
 Management (WDTC) - Papillary and
 Follicular (continued)
• Postoperative therapy/follow-up
  – Thyroglobulin (TG) (Gluckman)
     • measure serum levels every 6 months
     • Level >30 ng/ml are abnormal
  – Thyroid hormone suppression (control TSH
    dependent cancer) (Goldman, 1996)
     • should be done in - 1) all total thyroidectomy
      patients
                        2) all patients who have had
                                radioactive ablation of
             any remaining thyroid tissue
Management (WDTC) - Hurthle Cell
Carcinoma (continued)


• Total thyroidectomy is recommended
 because:
    • 1) Lesions are often Multifocal
    • 2) They are more aggressive than WDTCs
    • 3) Most do not concentrate iodine
Management (WDTC) - Hurthle Cell
Carcinoma (continued)

• Postoperative management
    • Thyroid suppression
    • Measure serum thyroglobulin every 6 months
    • Postoperative radioactive iodine is usually not
     effective (10% concentrate iodine)   (Clark, 1994)
 Medullary Thyroid Carcinoma
 (Management)
• Recommended surgical management
    • total thyroidectomy
    • central lymph node dissection
    • lateral jugular sampling
           if   suspicious nodes - modified radical neck dissection

• If patient has MEN syndrome
    • Remove pheochromocytoma before thyroid surgery
Anaplastic Carcinoma
(Management)

• Most have extensive extrathyroidal
 involvement at the time of diagnosis
     • surgery is limited to biopsy and tracheostomy
• Current standard of care is:
     • maximum surgical debulking, possible
     • adjuvant radiotherapy and chemotherapy (Jereb
      and Sweeney, 1996)
              Complications of surgery


•   Recurrent laryngeal nerve palsy 2-7%
•   Permanent hypoparathyroidism 1-3%
•   5-10% in difficult cases
•   Hematoma 1-2%
•   Wound infection < 1%
•   Hypertrophy of the scar
      Neck Dissection for Nodal Metastasis
• Central compartment lymph nodes :
        Frequently involved in patients with papillary ,
  medullary and Hurthle cells.
• Central neck dissection is particularly important in pts.
  with medullary and Hurthle cell ca. because of the high
  frequency of microscopic tumor spread and because
  these tumors cannot be ablated with 131 I .
• An Ipsilateral modified radical neck dissection is
  indicated in the presence of palpable cervical lymph
  nodes or prophylactically in patients with medullary ca.
  when the thyroid lesion is larger than 1.5 cm .
              I-131 Therapy




Remnant Ablation
Treatment of metastatic disease
             Remnant Ablation with I-131


          There is evidence that I-131:
•      Destroys residual microscopic thyroid cancer
•      Removes an effective competitor of metastatic
    disease
         Post-operative Radio-iodine Scan




•          To determine residual thyroid tissue
•         To determine metastatic disease
•         To determine the suitability for
    Radio-iodine therapy
                    Precautions before Test
• Discontinue thyroid hormone therapy for six weeks

• For first post-operative scan, thyroid hormone therapy
    is withheld for a period of 6 weeks following surgery
•
•    To stimulate endogenous TSH to the highest level
•
•    Exogenous rTSH
•
•    ?? TRH
•
•    Pre-study low iodine diet for a period of 1-2 weeks

• Avoid radiographic contrast studies
I-131 Treatment of Metastatic
Disease
• Patients with known or presumed residual thyroid cancer
  in the thyroid bed based on pathology or surgical report
  are treated widely with 100 mCi
• For non-palpable cervical lymph node metastases, 100
  to 150 mCi
• Lung metastases and bone metastases with 150 to 200
  mCi and 200 to 250 mCi,respectively.
• When feasible, palpable metastatic lymphadenopathy
  should be removed even if the nodes are well visualized
  to reduce the bulk of disease requiring treatment
Post iodine complications



•   Radiation thyroiditis
•   Painless edema
•   Radiation sialoadenitis
•   Haemorrhage in tumor
•   Radiation pneumonitis
Thyroid Suppression Therapy

• Maintained on thyroxine after surgery and
  ablation. Low TSH levels reduce tumor
  growth rates and reduce recurrence rates.
• Most recommend TSH levels of 0.1 mU/l.
• Follow-up q 6 months with thyroglobulin
  levels and repeat scans.it.
External beam radiotherapy and chemotherapy



•    Occasionally required to control unresectable,
    locally invasive, recurrent disease
• To treat metastasis in support bones to         decrease
the risk of fracture
    Helpful in treatment and control of pain from bony
metastasis when there is minimal or no RAIU
    Single and multidrug chemotherapy has been          used
with little success in disseminated thyroid scan.
    Adriamycin and Taxol are most commonly used agents
Current molecular investigations
•- Adenovirus mediated P53 gene therapy has shown
   to increase chemosensitivity to adriamycin and
   doxorubicin
•- Bone morphogenic protein (BMP-7) inhibits proliferation of
ATC cells by G1 arrest
•- Bovine seminal ribonuclease induced high rate of
   apoptosis in ATC
•- Use of histone deacylatase inhibition to promote
   apoptosis and differential cell cycle arrest.
•- Human sodium iodide sympoter when transfected into
ATC cells invitro/invivo establish uptake of      iodide.
•- National Cancer Institute phase II trials are going on
   for drugs Sorafenib tosylate which inhibit enzymes
   needed for cell growth and by inhibiting blood flow to
tumor.
       Prognosis


Overall prognosis is good
Long term survival is ~ 92%
• Thyroid cancer needs vigorous and drastic
 treatment like any other cancer
• Radio iodine improves quality of life
• Radio iodine prolongs life
• Thyroid cancer needs prolonged follow-up
• One of the preparations, before you start
  treating patients of thyroid cancer, is to
  develop the facility for keeping meticulous
  and long term follow-up records

				
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