The Lymphatic System

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					Cell Biology and Cancer

                   Differentiate    Apoptosis        Proliferate

• All cells have three ‘programs’ that they can perform. Proliferation or cell
replication, differentiation or specialization, and apoptosis or cell death.
Only one of these programs can ‘run’ at any given time.
• Once cells engage in a differentiation program, they cannot normally enter
into a proliferation phase.
• Apoptosis is a controlled way to control cell number and eliminate
damaged cells.
The Cell Cycle
• The cell cycle consists of four phases that
cells undergo while they are dividing. The
stage of the cycle where cells divide into
two ‘daughter’ cells is called mitosis (M).
When cells are not dividing, they are in
interphase. Another term for cells division is
cell proliferation.
• Interphase has two growth phases (G1
and G2) interrupted by an S phase where
DNA synthesis occurs.
• Most cells in our body halt their cell cycle
in G1 during some point in their lifespan.                                      (1)

This allows cells to differentiate for specialized functions. This differentiation
phase is often called Go. Under normal circumstances, cells that have
differentiated cannot proliferate, and cells that are proliferating cannot perform
specialized functions.
• Cells that have the ability to proliferate are often called stem cells. There are
vast numbers of stem cells during embryonic development.
Cellular Adaptation and Transformation


Cells can adapt to their environment in a number of ways:
• Atrophy: Decreased cell size.
• Hypertrophy: Increased cell size.
• Hyperplasia: Increased cell number.
• Dysplasia: Cells display increased mitosis and are varying sizes and shapes. They are
considered pre-cancerous.
• Neoplasia: Cells are dividing out of control. They are said to have been transformed into
cancerous cells.
Cancer and Cancer Therapy
•   Cancer is the 2nd leading cause of death in Canada and the U.S..
•   Neoplasm or tumor is an abnormal mass of cells which grow and divide
    without response to normal regulatory controls.
•   Although the cause of cancer is considered unknown, the current theory
    of cancer formation involves multiple and sequential genetic mutations
    that impair a cell’s ability to control its cell cycle and replication.
•   In general, two types of tumors exist: Benign and malignant.
•   Malignant cells usually share the following characteristics:
    1) Proliferation without limits
    2) Evasion of apoptosis
    3) Acquisition of vasculature (ie. angiogenesis)
    4) Invasion of other tissue and metastasis (ie. travel to distant sites)
Cancer Epidemiology
Malignant and Benign Tumors                                                   (3)

• Malignant (cancerous) tumors
usually consist of less differentiated,
abnormal cells which also proliferate
at a high rate; cells form an
irregularly shaped mass; cells
infiltrate (spread) into surrounding
tissue and break away to form new
tumors at distant sites (i.e.
• Benign tumors usually consist of differentiated, relatively normal cells
which proliferate at a higher than normal rate; cause damage to adjacent
tissue by compression; do not spread and are usually not life-threatening.

Malignant Neoplasms
Malignant cells:
• Are believed to develop from genetic mutations resulting in a transformed
  cell mass.
• These cells are highly undifferentiated and are very different from the
  normal tissue cells surrounding them, especially with respect to nuclear
  size and shape.
• They lack contact inhibition, cohesiveness, and adhesiveness, which leads
  to invasion and metastasis.

Benign tumor of                                                Malignant tumor
the breast,                                                    of the breast;
encapsulated                                                   invasive
and distinct from                                              carcinoma
the whiter breast
Local Effects of Tumors
Locally, malignant tumors cause death to surrounding tissues in the following
1) They tend to compress blood vessels and outgrow their blood supply
   causing ischemia, inflammation, and tissue necrosis. This can lead to
   infection in areas where the normal flora can become opportunistic.
2) They rob normal surrounding cells of nutrients (nutrient trapping).
3) Replace normal tissue leading to loss of function.
4) They liberate toxins and enzymes that destroy both normal and tumor
5) They can obstruct a passageway.
6) They can cause pain if they put pressure on sensory nerves or a visceral
   structure. Inflammation and bleeding also contribute to pain. Pain is rarely
   an early sign.

Systemic Effects of Tumors and Paraneoplastic
1) Weight loss, tissue wasting (ie. cachexia), and fatigue: Caused by
   anorexia, increased catabolism, inflammation, and nutrient trapping. The
   immune response associated with malignancy releases cytokines that
   contribute to the increased catabolism and muscle wasting. This is called
2) Bleeding: Tumor necrosis and erosion of blood vessels leads to bleeding.
   Bone marrow suppression can occur as a systemic effect of a specific
   tumor, invasion of the marrow, or secondary to therapy. GI bleeds can be
   especially difficult to treat.
3) Anemia: Can result from blood loss, iron deficiency, or bone marrow
4) Infections: Result from bone marrow suppression/invasion. However,
   immobility, muscle wasting, and fatigue can cause pooling of respiratory
   secretions and stasis of urine, which predispose to opportunist infections.
5) Paraneoplastic syndromes: Characterized by symptoms that occur that
   cannot be attributed to the direct effects of the tumor or metastasis.
   Examples include abnormal hormone or cytokine secretion by a tumor (eg.
   ACTH, ADH, PTH), bone marrow suppression, dementia, abnormal
   clotting, fever, and cachexia.
Spread of Malignant Tumors
Malignant tumors spread by producing
    secondary tumors that are identical to
    the original primary tumor.
Tumors spread by three ways:
1) Invasion of neighbouring tissues.
2) Metastasis.
3) Seeding.
•   Invasion occurs when tumor cells
    grow into adjacent tissue. Tumor cells
    lack adhesion molecules and can
    secrete enzymes that allow them to
    break down confining connective

• Metastasis occurs when
tumor cells break free of a
tissue and are circulated to
distant tissues in the blood
and/or lymph.
• Secondary tumors can be
contained by local lymph
nodes or attach to capillary
beds they come across.
• The lungs are a common
site of metastasis because
pulmonary capillaries are
often the first beds
encountered by systemic
tumor cells.

• Seeding involves the spreading of tumor cells along membranes or
within fluids other than blood or lymph.

Development of Cancer (Carcinogenesis)
Carcinogenesis: the process by which normal cells become transformed
   into malignant cells. This initially involves changes in the DNA (ie.
   mutation). Most cancers require multiple changes in DNA, caused by
   several factors.
Stages of Carcinogenesis:
1) Initiation: Exposure to carcinogenic agents that causes the initial
   irreversible genetic modifications. These agents may be chemical,
   physical, or biologic.
2) Promotion: Previously initiated cells are induced into unregulated
   proliferation by various promoter chemicals and growth factors or
   hormones. This stage is reversible if promoter is removed, and may
   occur after long latency period after initiation. Characterized by
3) Progression: Tumor cells acquire malignant changes that promote
   invasiveness, metastatic properties, and autonomous growth.
Oncogenes and Tumor Suppressor Genes
There are two main classes of genes responsible for controlling cell growth
   and replication: Proto-oncogenes and Tumor Suppressor Genes.
1) Proto-oncogenes promote controlled division. When genetically altered,
   proto-oncogenes become oncogenes, which confer unregulated
   proliferative and invasive properties on the cells. Proteins encoded by
   proto-oncogenes include surface membrane proteins, cytoplasmic
   signaling proteins, and proteins that bind to DNA and regulate gene
   transcription (ie. Transcription factors).
2) Tumor Suppressor genes normally inhibit growth and proliferation. When
   they are genetically altered, control functions are lost leading to
   unregulated proliferation. Proteins encoded by tumor suppressor genes
   include cell cycle regulators, surface receptors, cell adhesion proteins,
   transcription factors, DNA repair proteins.
Research suggests that many human neoplasms result from a
   combination of oncogene activation and tumor suppressor gene
Ras: An example of an Oncogene
• Proliferation of many cell types is regulated by
growth factors or mitogens secreted locally into
the tissues. Examples include: Insulin-like
growth factor, vascular endothelium growth
factor, fibroblast growth factor, and transforming
growth factor.
• These growth factors exert their effects by
binding to membrane receptors and activating
an intracellular signalling cascade that                               MAPK: mitogen
                                                                       activated protein
ultimately increases the production of proteins                        kinase.
                                                                       TF: transcription
responsible for cell cycle progression.                                factor.

• Ras is involved in growth factor signalling by
activating the mitogen activated signalling
cascade, which increases proliferation.

• When the gene that codes for Ras is mutated, the Ras protein can
continuously activate cellular proliferation, even in the absence of growth
factors. This mutation is a common finding in lung, colon, and pancreatic
p53: An example of a Tumor Suppressor Gene
• p53 is a protein that has the ability to stop the cell
cycle in the G1 phase.                                     Repairable     Nonrepairable
                                                             DNA          DNA damage
• p53 is activated when DNA damage occurs. By               damage
stopping the progression into the S phase, p53
prevents damaged DNA from being replicated and                                 p53
passed on to daughter cells.                                activation      activation
• If the DNA damage can be repaired, p53 is
inactivated and the cell proceeds into the S phase.         Pause in       Apoptosis
• If the DNA cannot be repaired, p53 activates the            cell
cellular apoptosis program and the cell is destroyed.
• Mutations in the p53 gene prevents this ‘safety             DNA
switch’ from being turned on, and allows DNA                 Repair
mutations to be passed on to the daughter cells. p53
mutations are found in virtually all neoplasms.                p53
• Another tumor suppressor gene is the breast
cancer gene (ie. BRCA-1). This protein is believed to
be involved in DNA repair. Mutations in this gene are       Cell cycle
found in rare breast and ovarian cancers.                  progression
Risk Factors In Cancer Development (Carcinogens)
• In over 50 different types of cancer altered oncogenes or tumor-suppressor
  genes are inherited (e.g. BRCA-1 in breast cancer).
• Chronic irritation and inflammation: Associated with cell transformation.
  Examples include ulcerative colitis increasing the risk of colon cancer and
  chronic heartburn increasing the risk of esophageal cancer.
• Age: Many cancers are more common in elderly, perhaps due to exposure to
  reactive oxygen species (free radicals) that damage DNA.
• Hormones: Increased exposure to estrogen increases the risk of breast
  cancer. Testosterone may contribute to prostate cancer.
• Viruses: Some have transforming properties where they alter host cell DNA.
  Examples include hepatitis B virus increases the risk of liver cancer, and
  human papillomavirus that increases the risk of cervical cancer.
Carcinogens Continued
• Smoking: Cigarette smoke increases the risk of lung, larynx, esophagus,
  pancreas, kidney, cervix, and bladder cancers.
• Chewing tobacco: Increases the risk of oral cavity and esophagus cancer.
• Diet: Smoked, salted, highly refined foods, high fat, protein, and red meats,
  and low fiber diets may increase the risk of stomach and colon cancers.
• Many chemicals in the industrial workplace and in pollution have been
  identified as carcinogens. Asbestos increases the risk of lung cancer, and
  herbicides increases the risk of lymphoma.
• High energy radiation and radioactive chemicals cause chromosomal
  damage. Ultraviolet rays from sun exposure increases the risk of skin
Naming Tumors
• Tumors are named by a root based on the cell type of origin, and a suffix that
  indicates a benign tumor or a malignant tumor.
    Roots                Suffixes                      Examples
 Fatty tissue:            benign:             lipoma: benign tumor of fatty
      lip-                 -oma*                         tissue
 Gland tissue:      malignant epithelial       adenoma: benign tumor of
    adeno-                tissue:                   glandular cells
    Fibrous             -carcinoma                 adenocarcinoma:
 tissue: fibro-    malignant connective       malignant tumor of epithelial
    Bone:                 tissue:                   lining of a gland
    oste-               -sarcoma
                                                osteoma: benign mass of
    Nervous                                          lamellar bone
 tissue: neur-
                                                osteosarcoma: malignant
   *Note: “-oma” suffix is sometimes              tumor of osteoblasts
   used for specific malignant tumors
   e.g. lymphomas, melanoma
Staging and Treating Cancers
• Staging is a classification system that is useful in determining the prognosis
of a cancer, and the most appropriate therapy.
• Cancers are placed in one of four stages (ie. I, II, III, IV); where stage I
tumors are small and well localized, and stage IV tumors are larger and have
metastasized to other sites.
• Cancers are assessed according to the TNM system. T indicates the nature
and the size of the primary tumor. N indicates the involvement of regional
lymph nodes. M indicates the spread or metastasis of the tumor. The TNM
score determines the stage of the cancer. The specifics of this nomenclature
are different for every cancer.
• Treatment of cancer involves surgery, chemotherapy, or radiation. Often a
combination of these is required. If a cancer is known to be hormone sensitive,
hormone manipulation or hormone antagonist drugs may be of benefit.
Biological therapy with interleukins and interferon can sometimes be used to
increase the activity of the immune system to help destroy transformed cells.
• Nutritional supplementation is often useful to prevent malnutrition and slow
Drug Treatment
Chemotherapy is the use of drugs to destroy tumor cells. Chemotherapy
   agents are classified based on the following categories.
1) Alkylating Agents: These agents affect all cells in the body; therefore, they
   are considered non-specific. Alkylating agents chemically bind to DNA and
   other cellular molecules. Alkylated DNA becomes cross-linked and can no
   longer replicate.
2) Antimitotics: Inhibit mitosis and stop cycle in the M phase.
3) Antimetabolites: Tumors have high metabolic, and are therefore more
   susceptible to these drugs. An example is methotrexate,
   which inhibits folic acid-mediated
   nucleic acid synthesis. Disrupting this
   metabolic pathway prevents DNA
   replication and inhibits mitosis.
4) Antibiotics: These drugs were originally
   used to kill bacteria; however, they
   have significant effects on human cells
   (ie. They are not selectively toxic). Most
   of these drugs bind to DNA and prevent
   DNA and/or RNA synthesis.
Drug Treatment Continued
• Combinations of chemotherapeutic drugs (ie. from different classes) are
  often used in order to destroy the maximum number of cells. Combining
  medications often has synergistic effects, so the dosages can be reduced,
  and side effects minimized. Treatment is also repeated to allow recovery
  periods and to maximize destruction of as many cells as possible.
• Combination drugs have:
         • Different actions and time of onset.
         • Affect different metabolic pathways.
         • Act at different points in the cell cycle.
         • Have different side effects.
         • An example is the ABVD regimen. Adriamycin and bleomycin are
         antibiotics, vinblastine is an antimitotic, and dacarbazine is an
         alkylating agent. Used for treating Hodgkin’s lymphoma.
• Chemotherapeutic drugs tend to also damage normal cells, especially
  rapidly dividing cells (e.g. skin and mucosal epithelia, bone marrow,
  gonads). Dosage and treatment duration are adjusted to maximize tumor
  destruction but avoid potentially critical complications.
• Side effects include: anorexia, nausea, vomiting, diarrhea, anemia,
  leukopenia, thrombocytopenia, fatigue, and hair loss.
Radiation Treatment                                                         (4)

Radiation causes breaks in chemical bonds,
   destroys blood vessels that supply tumors, and
   generates free radicals that damage cells by:
1) Damaging cell membranes (lipid alteration).
2) Damaging proteins including enzymes critical to
   cell function.
3) Damaging DNA leading to cell death or prevent replication.
The radiation damage can kill cells immediately, or causes DNA damage that
   results in cell death after replication. Radiation therapy affects the less
   differentiated, rapidly proliferating cells of cancerous tumors more than the
   slowly dividing cells of normal tissue. However, all proliferating cells are
   susceptible to radiation therapy especially those of skin, bone marrow and
   mucosal lining of of the G.I. tract. Side effects include: anorexia, nausea,
   emesis, diarrhea, fatigue, profuse perspiration, chills, susceptibility to
   infection, bleeding, dry mouth, and hair loss. Normal tissue usually
   recovers more readily than cancerous tissue.
Radiosensitivity describes the tumor’s responsiveness to radiation. Fast
   growing cells are more radiosensitive; whereas, slow growing cells are
   more radioresistant.
Breast Disorders                                                              (4)

• The breast consist 15-20
lobes interspersed with adipose
tissue, and are supported by
ligaments. The functional unit of
the breast is the acini, that are
comprised of epithelial cells
that secrete milk and
contracting cells that move milk
into a duct system.
• The duct system collects and ejects milk through the openings in the nipple
under the influence of oxytocin from the pituitary. Development of the breast
tissue requires estrogens for the proliferation of the mammary ducts, and
progesterone for the development of the lobules. Complete differentiation of
the mammary epithelium requires stimulation by prolactin.
• Although lactation normally does not occur until the end of pregnancy, there
are cyclic changes in the breast during the menstrual cycle. During the 10 days
preceding menstruation many women experience breast swelling, tenderness,
and pain. This is likely due to distention of the ducts, increased blood flow, and
edema caused by elevated estrogens and progesterone during this time.
These changes usually regress during menstruation.
Fibrocystic Breast Disease
Fibrocystic disease refers to benign nodules or masses in the breast that
    change during the menstrual cycle. Development of fibrous tissue in the
    breast results in cysts forming during the secretory or luteal phase of the
    menstrual cycle. Cysts enlarge over time and can cause degeneration of
    normal tissue.
Fibrocystic disease is very common, and usually occurs between ages 30 and
    50 years. It is very rare in postmenopausal women not receiving hormone
Three categories of lesions have been developed based on the risk of breast
    cancer development.
1) Nonproliferative lesions: Include microcysts and fibroadenomas, which are
    not considered precancerous. Most cysts are of this type. They often
    appear as singular, movable masses.
2) Proliferative lesions: Consist of hyperplasia of the epithelia of the ducts.
    There is a risk of developing breast cancer only if there is a positive family
    history of breast cancer.
3) Proliferative atypical: Increases the risk of cancer, but only represents a
    small number of cases.
Carcinoma of the Breast
• Breast cancer represents the most frequent cancer in women, and is the
second leading cause of cancer deaths in women. The mortality rate is roughly
30%. Breast cancer is rare in males, but is generally more aggressive when
• The highest incidence rate of breast cancer occurs between 50 and 60 years
of age. Other risk factors include family history in first-degree relatives, atypical
hyperplasia, and estrogen exposure (ie. Early menarche, late menopause,
nulliparity, delay of first pregnancy). Other risks include HRT, use of oral
contraceptives, high postmenopausal BMI, and increased breast density.
Breast feeding decreases the risk. It is interesting that most women with breast
cancer have no identifiable risk factors.
• Approximately 8% of breast cancers are inherited through a mutation in the
BRCA-1 or BRCA-2 genes. These gene products are considered tumor
suppressors. 56% of women with these mutant genes develop breast cancer.
• Most breast cancers develop from ductal epithelium; although, there are
many different types. The majority of tumors are unilateral and in the upper
outer quadrant. In the early stages they may be movable, but generally
become fixed later in their course.
Breast Cancer Continued                                (4)

• Cancer of the breast may manifest as a single hard
mass, a puckering due fixation of the tumor, a
retracted nipple, or an unusual discharge. Many
tumors are detected by self-examination; however,
mammography can detect tumors too small for
palpation. Self-exam should be conducted
immediately following menses to avoid cyclic
changes in hormones, or at a consistent time of the
month for postmenopausal women.
• Biopsy must be conducted to confirm the diagnosis
and rule out benign tumors.

• Malignant cells spread at an early stage,
usually to the axillary nodes. Widespread
metastases follows quickly to the lungs, brain,
bone and liver.
• The tumors are graded based on their degree
of differentiation, then staged based on the size
of the primary tumor, the involvement of the
lymph nodes, and the presence of metastases.
Breast Cancer Continued
Treatment and Prognosis:
• Treatment methods include surgery, chemotherapy, radiation, and hormonal
therapy. Radical mastectomy (ie. Removal of the entire breast, underlying
muscle, and all axillary nodes) is rarely used unless breast cancer is
advanced at the time of diagnosis. More conservative mastectomy and
lumpectomy accompanied by chemotherapy, radiation, or hormonal therapy
is the preferred method.
• Tumors are often checked for the presence of estrogen and progesterone
receptors. This is useful in predicting the tumors responsiveness to hormone
therapy, and improves the prognosis and likelihood of remission. Tamoxifen is
an estrogen receptor blocker commonly used to treat estrogen responsive
• Overall prognosis is related to the extent of nodal involvement. 5-year
survival rate for localized tumors is 96%, with nodal involvement it’s 75%, and
is 21% with distant metastasis.
Cervical Carcinoma
• Tumors of the cervix can be benign (cervical dysplasia), noninvasive
neoplasia (carcinoma in situ), or an invasive cancer that spreads to
neighboring organs. Although cervical dysplasia is benign, it usually
progresses to invasive cancer if left untreated. This process takes about 10
Epidemiology: A high percentage of cervical dysplasias and cancers are
associated with sexually transmitted strains of human papillomvirus (HPV).
Cervical cancer almost never occurs in women who have not engaged in
sexual intercourse, and the risk increases with the number of sexual partners
a women has had, and the number of other female partners a male partner
has had. Use of condoms or diaphragms decreases the risk. Some evidence
suggests that males who are circumcised or less likely to transmit HPV to their
female sexual partners. Smoking also increases the risk.
The Papanicolaou smear is a cytologic examination of the cervical cells.
Widespread use of this test has dramatically decreased the incidence of
invasive cancer; however, the incidence of cervical dysplasia has increased.
This is probably due to widespread screening leading to early diagnosis,
increased transmission of HPV. Cervical dysplasia is graded based on the
degree of dysplasia, while in carcinoma in situ the cells appear disorganized,
undifferentiated and abnormal.
Cervical Carcinoma Continued
Manifestations: Carcinoma in situ is usually
   asymtomatic, but can be detected by
   routine cytologic screening (ie. Pap
   smear). Manifestations and complications
   of invasive carcinoma include:
1) Abnormal uterine bleeding and vaginal
   discharge. Metrorrhagia and postcoital
   spotting occur frequently with cervical
   carcinoma. The discharge is often
   described as bloody or purulent, odorous,
   and nonpruritic.
2) Invasive spread of the cancer. The cancer
   usually spreads down the vagina first,
   then laterally to the ureters. Fistulas can
   form creating pain and allowing the
   cancer to spread to the bladder and/or
   rectum. Metastic spread to the lymph
   nodes can occur at any time throughout
   the course, but spreading to distant sites
   does not occur until very late.
Cervical Carcinoma Continued
3) Hydroureter and hydronephrosis. Occurs with lateral spread of the
    cancer. Flank and lower back pain radiating to the groin is common,
    along with postrenal azotemia (ie. Renal failure). Uremia can occur with
    a bilateral obstruction.
Treatment: Usually involves some form of surgery. Hysterectomy and/or
    radiation are the treatments of choice for invasive cancers. Five-year
    survival rate depends of the stage at diagnosis: Stage 0 (in situ) = 100%,
    Stage I = 75%, Stage II = 55%, Stage III = 30%, Stage IV = 7%.
Endometrial Cancer
• Adenocarcinoma of the uterus is the fourth most common cancer in women.
It occurs most often in women 50-70 years of age. Risk factors include:
Obesity, nulliparity, diabetes, prolonged periods of anovulation (eg. Polycystic
ovaries), extended use of tamoxifen or unopposed estrogen therapy, and
possibly oral contraceptives. Most risk are related to estrogen exposure or
prolonged periods without endometrial shedding.
Manifestations: Abnormal vaginal bleeding is the presenting symptom in most
cases. Cancers are typically in the lower uterus and can obstruct the cervix.
When this occurs blood and pus can accumulate in the uterus can cause
lower abdominal pain. Other causes of lower abdominal pain include
metastasis and infection. Cancers can penetrate through the uterine wall
spread along the peritoneum, or spread through the lymph to distant organs.
Prevention and treatment: Endometrial sampling (Dilation and Curettage) for
patients with abnormal or postmenopausal bleeding can reveal precancerous
hyperplasic changes. Treatment with oral progestins to promote endometrial
shedding has been shown to decrease the incidence of adenocarcinoma.
Hysterectomy and radiation are the usual treatments for neoplastic changes.
With early diagnosis the five-year survival rate is 85%.
Myoma of the Uterus (Fibroids or Leiomyomas)
• Myomas are benign smooth muscle tumors of the myometrium that are often
infiltrated with connective tissue. They are the most common benign tumor of
the female reproductive tract and are hormone responsive. They often occur
during the reproductive years and tend to subside following menopause. Also,
during pregnancy they can become quite enlarged. Occasionally, a
submucosal myoma can become pendunculated and descend through the
Manifestations: In a nonpregnant women, myomas are frequently
asymptomatic. They often cause irregular enlargement of the uterus, and can
cause symptoms due to pressure on neighboring organs, like urinary
frequency. They can also cause dysmenorrhea (painful menstruation),
menorrhagia (heavy bleeding) often with anemia. Intense pain can occur if the
tumor becomes twisted or infarcted. Infertility can occur if the myoma
significantly distorts the uterine cavity.
• In pregnant women a growing myoma can cause additional problems like
abortion, malpresentation, failure of engagment, premature labour, and
postpartum hemorrhage.
Treatment: Emergency surgery is required for torsion of a pendunculated
myoma. GnRH analogues can preoperatively reduce the size of the myoma
before myomectomy or hysterectomy.
Ovarian Cysts                                                                (3)

• Ovarian cysts can be formed
from a ruptured or unruptured
follicle or from a corpus luteum.
• Ovarian cysts are the most
common form of ovarian tumor.

• Each month, several follicles begin to develop. One will become the
dominant follicle and will rupture releasing its ovum (ie. Ovulation). Cysts can
develop when an immature follicle’s duct becomes blocked, and produces a
fluid-filled mass. Also, dominant follicles can persist and continue to grow.
Luteal cysts develop when the corpus luteum becomes enlarged and fails to
regress in the absence of pregnancy.
• Most cysts are asymptomatic, but on occasion, the cyst may become large
enough to cause discomfort, urinary retention, or menstrual irregularities.
Follicle cysts often disappear after 2 months of oral contraception. Bleeding or
rupture of a cyst can cause serious peritonitis. Large cysts can also cause
torsion of the ovary resulting in ischemia and necrosis.
• Polycystic ovarian syndrome is an endocrine disorder that results in multiple
cysts of the ovaries.
Ovarian Cancer
• The incidence of ovarian cancer increases with age, being greatest between
65 and 80 years of age. Difficulty detecting this cancer early makes it very
lethal, as 75% of women have considerable metastasis before the time of
• 90% of cancers develop from epithelial cells within the ovary.
• The most significant risk factor for ovarian cancer appears to be the length
of time during a women’s life when her ovarian cycle is not suppressed by
pregnancy, lactation, or oral contraceptive use (ie. Ovulatory age). This can
be observed in cultures where women bear numerous children, the incidence
of ovarian cancer is quite low.
• Family history is also a significant risk factor. Women who have two or more
first- or second-degree relatives who have had ovarian cancer have a 50%
risk of developing the disease. As well, inherited mutations in the BRCA-1 or
BRCA-2 genes predisposes to ovarian and breast cancer.
• Most ovarian cancers are asymptomatic, or produce symptoms so vague
that the patient fails to seek medical advise until the disease is far advanced.
Vague signs often include: abdominal discomfort, flatulence, bloating or
ascites, altered bowel or bladder function.
Ovarian Cancer Continued                       (3)

• Vague early symptoms have been
attributed to the anatomical position of the
ovaries. They are positioned is such a
way, that a growing mass does not impair
the function of neighboring organs until it
is quite large and advanced.
• This tumor spreads easily along the
peritoneal membranes (ie. Seeding) and
through the lymphatics to the liver, uterine
tubes, uterus, and pelvis.
• Surgical removal of all affected organs,
followed by chemotherapy is usually the
the treatment of choice.
• 5 year survival rate is 50%. However, if
ovarian cancer is detected and treated
early, the 5 year survival rate is 95%, but
this only occurs in 25% of the cases.
Testicular Cancer
• Testicular cancer in the most common cancer in men aged 20-35 year. The
cause is not known, but the most established risk factor is cryptorchism (ie.
Undescended testicle at birth). Other risk factors include exogenous
estrogen administration during pregnancy, trauma, and infection.
Manifestations: The typical presentation is a patient-identified painless
nodule or enlargement of the testicle. The feeling of heaviness in the effected
testicle is common. Tumors are usually unilateral. Pain resulting from
intratesticular hemorrhage occurs in about 10% of patients, and secondary
hydroceles are present in another 10%. Many testicular cancers secrete
nontesticular proteins (ie. Paraneoplastic syndrome). Examples include
human chorionic gonadotropin (hGC) and alpha-fetoprotein, which are useful
diagnostic markers. Gynecomastia can also occur as a result of abnormal
hormone secretion by the tumor. Diagnosis is usually confirmed by
orchiectomy, since biopsies can promote the spread and metastasis or the
• Metastasis usually occurs to lymph (retroperitoneal, mediastinal, or
subclavicular nodes), lungs, liver, bone, brain or vena cava.
Treatment: Surgical removal of the affected testicle (ie. Orchiectomy) and
Tumors of the Skin
• Nevi or moles, are the most common tumor of the
skin. They are generally benign.
• Most nevi involve abnormal growth of melanocytes
(ie. Pigment producing cells) and are therefore dark in
colour. Nevi can also be nonpigmented, flat, elevated,
hairy or nonhairy.

• Benign nevi are usually dark coloured, uniformly pigmented, with well-
defined borders.
• Dysplastic nevi have the capacity to transform into malignant melanomas.
Their appearance is usually flat with an irregular border. It is believed that
UV exposure plays a role in the development dysplastic nevi or in the
development of malignant cells from dysplasic cells.
Basal Cell Carcinoma
• Basal cell carcinoma is the most common
skin cancer in white-skinned individuals. It is
less common in dark-skinned individuals.
• A history of significant long-term sun
exposure is the major risk factor.
• Most tumors develop in sun-exposed areas of the body (ie. Head and neck).
• This tumor is generally nonmetastasizing, but can extent deep if untreated.
• Treatment is usually excision, but irradiation can also be used.
Malignant Melanoma
• This tumor develops from melanocytes, and
depends on genetic factors, exposure to UV
radiation, and hormoral influences.
• They develop from melanocytes in the basal layer
of skin or from a collection of melanocytes within a
• They appear as mulitcoloured lesions with irregular
borders. As they spread the colour may darken and
may bleed.

• Melanoma grow quickly and extend deep into the
tissues. They metastasize quickly to regional lymph
nodes and then to other organs.
• The prognosis is poor if untreated. 5-year survival
is 60%.
• Treatment is surgical, with chemotherapy and
Malignant Melanoma Continued
• Early detection is critical with malignant melanomas since these cancers
readily metastasize. Self-examination follows the ABCD pneumonic.
A – asymmetry.
B – border irregularity.
C – colour inconsistent throughout.
D – diameter greater than 6 mm.

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