Name of the project; tumors
Dr Barkam Nagaraju
TUMORS OF THE OVARY
Ovarian cancer is the fifth most common cancer in
US women. It is also the fifth leading cause of
cancer death in women.
Three cell types make up the normal ovary: the
multipotential surface (coelomic) covering
epithelium, the totipotential germ cells, and the
multipotntial sex cord/stromal cells. Each of these
cell types gives rise to a variety of tumors.
Neoplasms of the surface epithelial origin account
for almost 90% of ovarian cancers.
epithelial – 65-70%
stromal – 15-20%
Germ cell tumors – 5-10%
Metastatic tumors – 5%
TUMORS OF THE OVARY (CONTINUED…)
Pathogenesis: several risk factors for epithelial ovarian
cancers have been recognized.
Two of the most important are nulliparity and family history.
Prolonged use of oral contraceptives reduce the risk
A majority of hereditary ovarian cancers seem to be caused
by mutations in the BRCA1 and BRCA2 ge.
K-RAS protein is overexpressed in up to 30% of
tumors, mostly mucinous cystadenocarcinoma
SURFACE EPITHELIAL TUMORS
all types can be benign, borderline , or malignant, depending
Benign ; - gross: mostly cystic - microscopic; fine papillae,
single layer covering (no stratification), no nuclear atypia, no
Borderline ; - gross; cystic / solid foci - microscopic;
papillary complexity, stratification, nuclear atypia, no stromal
Malignant ; - gross; mostly solid & hemorrhage / necrosis
- microscopic; papillary complexity, stratification, nuclear atypia,
These are the most frequent of the ovarian tumors.
Benign lesions are usually encountered between ages 30 and 40
years, and malignant serous tumors are more commonly seen
between 45 and 65 years of age.
Serous tumors are the most common malignant ovarian
tumors, account for 60% of all ovarian cancers.
Grossly, may be small, but most are large, spherical to
ovoid, cystic structures.
The prognosis for the individual with clearly invasive serous
The differ essentially from serous tumors in that the epithelium
consists of mucin-secreting cells simlar to those of the
10% of them are malignant, 10% are of low malignant
potential, 80% are benign.
The prognosis is of mucinous tumors is better than for the
serous counterpart, but the stage is the major determinant of
They may be solid or cystic, but sometimes they develop as a mass
projecting from the wall of a cyst filled with chocolate-colored fluid.
Microscopically, formation of tubular glands, similar to those of the
They are usually malignant tumors, although benign and borderline
forms also exist.
15-30% of women with these ovarian tumors have a concomitant
Similar to endometrial cancer, endometrioid carcnoma have
mutations in PTEN suppressor gene.
Solid / cyst filled by
GRANULOSA CELL TUMOR
Hormonally active tumor
The most common estrogenic ovarian neoplasm.
The adult form occurs mainly in postmenopausal
women, associated with endometrial hyperplasia and
The juvenile type occurs in the first two decades, cause
precocious sexual development.
They are uncommon, most are benign, solid, usually unilateral
tumors, consisting of an abundant stroma containing nest of
transitionl-like epithelium resembling that of the urinary tract.
Occasionally, the nests are cystic and are lined by columnar
They are generally somoothly encapsulated.
They may arise from the surface epithelium or from urogenital
epithelium trapped within the germinal ridge.
Rarely, they are formed as nodules within the wall of a
of germ-cell origin constitute 15% to
20% of ovarian tumors
However, more than 90% of these germ-cell are
benign mature cystic teratomas. The immature
malignant variant is rare.
BENIGN (MATURE) CYSTIC TERATOMAS
They are marked by differentiation of totipotential germ cells into mature
tissues representing all three germ cell layers.
Usually there is cysts lined by recognizable epidermis replete.
On transection, they are often filled with sebaceous secretion and matted
hair, when removed, reveal a hair-bearing epidermal lining. Sometimes teeth
protrude from nodular projection.
Occasionally, foci of bone and cartilage, nests of bronchial or GIT
epithelium, and other recognizable lines of development are also present.
Sometimes, they produce infertility for unknown reasons.
In about 1% of cases there is malignant transformation, usually taking form
of a squamous cell carcinoma.
IMMATURE MALIGNANT TERATOMAS
They are found early in life, the mean age is 18 years.
Differ from benign teratomas insofar as they are often bulky, and
predominantly solid or near-solid on transection, and are punctuated by
areas of necrosis.
Uncommonly, one of the cystic foci may contain sebaceous
secretion, hair, and other feature similar to those in the mature teratoma.
Microscopically, the distinguishing feature is an immature areas of
differentiation toward cartilage, bone, muscle, nerve, and other
Particularly ominous are foci of neuropithelial differentiation, because
they are aggressive and metastasize widely.
Stroma ovarii is composed entirely of mature thyroid
tissue that may hyperfunction and produce
They appear as small, solid, unilateral brown ovarian
Stroma ovarii and carcinoid may combined in the same
ovary, One of these elements may become malignant.
Endometrial polyps: sessile, usually hemispheric.
Histologically, composed of endometrium
resembling the basalis, frequently with small
muscular arteries. More often they have cystic
dilated glands, but some have normal endometrial
They may occur at any age, but more commonly,
they develop at time of menopause.
- production of abnormal uterine bleeding.
- risk of giving rise to a cancer (rare).
Endometrial carcinoma: The most frequent cancer occurring
in the female genital tract in the U.S and other Western
Appears most frequently between the ages of 55 and 65
There are two clinical stettings in which endometrial
carcinomas arise: in perimenopausal women with estrogen
excess and in older women with endometrial atrophy.
(endometroid and serous carcinoma of the endometrium,
Well-defined risk factors for endometroid carcinoma: obesitydiabetes-hypertension-infertility
These risk factors poin to increased estrogen stimulation, and
it is well recognized that prolonged estrogen replacement
therapy and estrogen-secreting tumors increase the risk of
ENDOMETRIAL CARCINOMA: (CONTINUED…)
Many of these risk factors are the same as those for
endometrial hyperplasia, and endometrial carcinoma
frequently arises on a background of endometrial
These tumors are termed endometrioid because of their
similarity to normal endometrial gland.
Two familial cancer syndromes that have an increased risk
of the endometrioid type of endometrial carcinoma:
hereditary nonpolyposis colon cancer syndrome.
Cowden‟s syndrome (carries an increased risk of
carcinoma of the breast, thyroid, and endometrium, have
mutations in PTEN, a tumor suppressor gene).
ENDOMETRIAL CARCINOMA: (CONTINUED…)
Serous carcinoma of the endometrium typically arises in
a background of atrophy, sometimes in the setting of an
Mutations in DNA mismatch repair genes and PTEN are
rare in serous carcinoma; however, nearly all cases
have mutations in the p53 tumor suppressor gene.
Marked leukorrhea and irregular bleeding are the fist
clinical indication of all endometrial carcinoma.
With progression, uterus may be palpably enlarged, and
in time it becomes fixed to surrounding structures by
extension of the cancer beyond the uterus. Fortunately,
these are usually late-metastasizing neoplasms, but
dissemination eventually occurs.
The most common benign tumor in females and are found in 30% to
50% of women during reproductive life. More frequent in blacks than
They are often referred to as fibroids because they are firm.
Estrogens and oral contraceptives stimulate their growth;
conversely, they shrink postmenopausally.
They may be entirely asymptomatic, discovered on routine pelvic
examination. The most frequent manifestation, when present, is
menorrrhagia, with or without metrorrhagia. They may become
palpable to the woman or may produce a dragging sensation.
They rarely transform into sarcomas.
A uterine leiomyosarcoma is a rare malignant (cancerous) tumor that
arises from the smooth muscle lining the walls of the uterus
(myometrium). Smooth muscles react involuntarily in response to various
stimuli. For example, the myometrium stretches during pregnancy
Leiomyosarcoma is classified as a soft tissue sarcoma. Sarcomas are
malignant tumors that arise from the connective tissue
The nuclei of the tumor cells are round, oval or spindle with high pleomorphism
and condensed chromatin and occasional prominent nucleoli.
Adenocarcinoma is a cancer of an epithelium that originates
in glandular tissue. Epithelial tissue includes, but is not limited
to, the surface layer of skin, glands and a variety of other
tissue that lines the cavities and organs of the body.
Epithelium can be derived embryologically from ectoderm,
endoderm or mesoderm. To be classified as Adenocarcinoma
Leiomyoma of the fallopian tube is extremely rare. Most
cases are asymptomatic and found incidentally at autopsy or
unrelated operation. These leiomyomas tend to be singular,
small, and unilateral, with a resultant rare preoperative
Fibroadenomas are round, firm, rubbery masses that arise from
excess growth of glandular and connective tissue. These masses
can grow to the size of a small plum, but they're benign and usually
painless. If you have a fibroadenoma, it may bounce or move slightly
when you press the area.
fibroadenoma. Mammography and ultrasound may help with the
diagnosis, but the only way to be certain of a fibroadenoma is to take
a sample of tissue for lab analysis (biopsy). Your doctor may also
recommend surgery to remove the lump completely.
Gross examination of the fallopian tubes revealed no masses or
lesions; however, 2 small foci of granulosa cells were identified
microscopically within one of the fallopian tubes. These foci were
suspicious for granulosa cell tumor metastases. The patient
subsequently underwent a bilateral oophorectomy, which revealed no
primary granulosa cell tumor
TUMORS OF THE CERVIX
Cervical carcinoma is one of the major causes of
cancer-related deaths in women, despite
improvements in early diagnosis and treatment.
Since introduction of the Papanicolaou (Pap) smear
50 years ago, the incidence of cervical cancer has
The pap smear remains the most successful cancer
screening test ever developed.
Over the same period, the incidence precursor
cervical intraepithelial neoplasia (CIN) has
increased to more than 50,000 cases annually. It is
important to know that nearly all invasive cervical
squamous cell carcinoma arise from epithelial
CERVICAL INTRAEPITHELIAL NEOPLASIA
Cytologic examination can detect epithelial changes (CIN)
before the development of an overt cancer by many years.
However, only a fraction of cases of CIN progress to
The peak incidence of CIN is about 30 years, whereas that
of invasive carcinoma is about 45 years.
Risk factors for the development of CIN and invasive
-Early age at first intercourse
-Multiple sexual partners
-Male partner with multiple previous sexual partners
-persistent infection by „„High-risk‟‟ HPV
They point to the likelihood of sexual transmission of a
causative agent, in this case HPV.
HPV (ADDITIONAL INFORMATION)
High-risk HPV types: 16, 18, 45, and 31, account for the
majority of carcinomas, smaller contributions by
HPV33, 35, 39, 45, 52, 56, 58, and 59. The viral DNA
integrates into the host genome and express E6 and E7
proteins which inactivate tumor suppressor genes p53 and
Low-risk HPV types: 6, 11, 42, 44 which produce
condylomas; the viral DNA does not integrate into the host
The recently introduced HPV vaccine is very effective in
preventing HPV infections and cervical cancers.
Many women harbor these viruses, only few develop
cancer, suggesting other influences like cigarette smoking
and exogenous or endogenous immunodeficiency.
INVASIVE CARCINOMA OF THE CERVIX
The most common cervical carcinoma are sqamous cell
carcinoma 75%, adenocarcinoma and adenosquamous
carcinoma 20%, and small cell neuro-ednocrine
In some individual with aggressive intraepithelial
changes, the time interval may be considerably shorter,
whereas in other women CIN precursors may persist for
life. The only reliable way to monitor the course of the
disease is with careful follow-up and repeat biopsies.
The relative proportion of adenocarcinoma has been
increasing in recent decades; glandular lesions are not
detected well by Pap smear.
INVASIVE CARCINOMA OF THE CERVIX
advanced cases of cervical cancer are invariably seen in
women who either have never had a Pap smear or have
waited many years since the prior smear. Such tomors may
be symptomatic, called to attention by unexpected vaginal
bleeding, leukorrhea, painful coitus, and dysuria.
Detection of precursors by cytologic examination and their
eradication by laser vaporization or cone biopsy is the most
effective method of cancer prevention.
Invasive carcinomas range from microscopic foci of early
stromal invasion to grossly conspicuous tumors encircling
the os. Tumors encircling the cervix and penetrate into the
stroma produce a “barrel cervix”, which can be identified by
Condylomas and low-grade vulvar intraepithelial
Condylomas fall into two distinctive biologic forms:
Condylomata lata: (not commonly seen today), are flat,
moist, minimally elevated lesions that occur in
Condylomata accuminata: (more common) may be
papillary and distinctly elevated. They occur anywhere
on the anogenital surface. Significant characteristic
cellular morphology is: perinuclear cytoplasim
vacuolization. Vulvar cndylomas are not pre-cancerous
but coexist with foci of intraepithelial neoplasia in vulva
(VIN grade 1) and cervix.
Giant condyloma accuminata
A vulva chancre and
TUMORS (CONTINUED …)
High-grade vulvar intraepithelial neoplasia and
carcinoma of the vuvla
Carinoma of vulva represent about 3% of all genital tract
cancers in women.
90% of vulvar carcinomas are squamous cell
carcinomas; and 90% of them are HPV related, and
most common seen in relatively younger patients.
Non-HPV-related vulvar squamous cell carcinoma
occrus in older women; It is well differentiated and
unifocal, and is associated with lichen sclerosus or other
VAGINAL INTRAEPITHELIAL NEOPLAISA AND
SQUAMOUS CELL CARCINOMA
Extremely uncommon, usually occur in women older
than age 60 years.
Risk factors are similar to those for carcinoma of the
cervix (discussed later).
Associated with HPV infection in most cases.
Vaginal clear cell adenocarcinoma, usually encountered
in young women in their late teens whose mothers took
diethylstilbestrol during pregnancy; overall risk is 1 per
1000 of those exposed in utero.
Vaginal adenosis, are small glandular or microcystic
inclusions appear in vaginal mucosa, appear as red
glandular foci lined by mucus-secreting cell; from such
inclusions rare clear cell adenocarciona arises.
TUMORS OF THE BREAST
is the most common benign neoplasms of the
female breast. They almost never become
malignant. Usually appear in young women; the
peak incidence is in the third decade of life.
An increase in estrogen activity is thought to
contribute to its development.
Similar lesions may appear with fibrocystic
They usually present as solitary, discrete,
movable mass. They may enlarge late in the
menstrual cycle and during pregnancy.
They are much less common than fibroadenomas.
Arise from the periductal stroma and from preexisting fibroadenomas.
They may be small or grow to large massive size, distending the breast.
Some become lobulated and cystic; on gross section they exhibit leaflike
clefts and sliits, that is why they called phylodes tumors.
In the past they had the name cystosarcoma phyllodes, an unfortunate
name because they are benign.
The most ominous change is the appearance of increased stromal
cellularity with anaplasia and high mitotic activity, accompanied by rapid
increase in size, and invasion of adjacent breast tissue by malignant
they remain localized and are cured by excision;even malignant tumors
also tend to remain localized. Only the most malignant (15% of cases)
metastasize to distant sites.
It is a neoplastic papillary growth within a duct.
Most are solitary, found within the principal
lactiferous ducts or sinuses.
Present clinically as a result of
- Appearance of serous or blody nipple discharge
- Precence of small subareolar tumor
- Nipple retraction (rare).
In some cases there are multiple papillomas in
several ducts (intraductal papillomatosis). These
lesion sometimes become malginant, wherease the
solitary papilloma almost always remain benign.
Despite advances in diagnosis and treatment, almost onefourth of women who develop these neoplasms will die of
75% of women with breast cancer are older than age 50.
only 5% are younger than the age 40.
Oral contraceptives: they have been suspected of increasing
the risk of breast cancer.
Ionizing radiation to the chest increases the risk of breast
cancer. Only women irradiated before age 30, seem to be
affected. 20% to 30% of women irradiated for Hodgkin
lymphoma in their teens and 20s develop breast cancer, but
the risk for women treated later in life is not elevated.
Other less well-established risk factors: obesity, alchohol
consumption, and a diet high in fat.
Pathogenesis: as with all cancers, the cause of breast
cancer remain unknown. however, three set of influences
seem to be important:
- Mutations affecting proto-oncogenes and tumor supressor
genes in breast epithelium contribute to the oncogenic
A large number of genes including the estrogen receptor may be
inactivated by promoter hypermethylation.
- Most likely, multiple acquired genetic alterations are involved in the
sequential transormation of a normal epithelial cell into a cacerous
- Endogenous estrogen excess or hormonal imbalance has a
significant role. Many risk factors (mentioned before) imply
increased exposure to estrogen peaks during the menstrual cycle.
- They are suggested by the variable incidence of breast cancer in
genetically homogeneous groups and the geographic differences in
prevalence. Important environmental variables include irradiation
and exogenous estrogens.
Spread of breast cancer:
Occurs through lymphatic and hematogenous channels.
Lymph node metastasis are present in about 40% of cancers
presenting as a palpable masses.
Outer quadrant and centrally located lesions typically spread to
the axillary nodes. Those in the inner quadrants often involve the
lymph node along the internal mammary arteries.
The supraclavicular nodes are sometimes the primary site of
spread, but they become involved only after the axillary and
internal mammary nodes are affected.
Metastatic involvement maybe to any organ, such as
lungs, skeleton, liver, adrenals brain, spleen, and pituitary.
Matastases may appear many years after apparent therapeutic
control of the primary lesion, sometimes 15 years later.
Prognosis is influenced by the following variables:
The size of the primary carcinoma. Invasive carcinoma
smaller than 1cm have an excellent prognosis in the
absence of lymph node metastases.
Lymph node involvement and the number of lymph nodes
involved by metastases.
Distant metastases. Patient who develop hematogenous
spread are rarely curable.
The grade of the carcinoma. The most common grading
system for breast cancer evaluates tubule formation,
nuclear grade, and mitotic rate to divide carcinomas in to
The histologic type of carcinoma. All specialized types of
breast carcinoma (tubular, medullary, cribriform, adenoid
cystic, and mucinous) have a better prognosis than
carcinomas of no special type (ductal carcinoma).
The presence or absence of estrogen or progesterone
receptors. The reason for determining their presence is to
predict the response to anti-estrogen therapy.
The proliferation rate of the cancer. High proliferative rates are
associated with a poorer prognosis.
Aneuploidy. Carcinoma with an abnormal DNA content have a
slightly worse prognosis.
Overexpression of HER2/NEU. Ovexpression is associated
with poorer prognosis. However, the importance of evaluating
HER2/NEU is to predict resposne to monoclonal antibody
“Herceptin” to the gene product.
The major prognostic factors are used by the American
Joint Committee on Cancer to devide breast cancer into
clinical stages as follows:
Stage 0. DCIS or LCIS (5-year survival rate: 92%)
Stage 1. invasive carcinoma 2cm, without nodal
involvement (5-year survival rate: 87%)
Stage 2. invasive carcinoma 5cm, with up to 3 involved
axillary nodes (5-year survival rate: 75%)
Stage 3. invasive carcinoma 5cm with four or more
involved axillary nodes. (5-year survival rate: 43%)
Stage 4. breast cancer with distant metastases (5-year
survival rate: 13%)
Only two disorders occur in male breast with sufficient frequency.
Gynecomastia: male breast are also subject to hormonal influences, but
they are less sensitive than are female breasts. Gynecomastica may
occur in response to estrogen excess. The most important cause is
cirrhosis of the liver, with consequent inability of the liver to metabolize
estrogens. Other causes include Klinefelter syndrome, estrogen-secreting
tumors, estrogen therapy, digitalis therapy. Physiologic gynecomastia
occurs in puberty and in old age. Morphologic features are simlar to
Carcinoma: frequency ratio to breast cancer in the female of 1:125. It
occurs in advanced age. Because of scant amount of breast substance in
males, the tumor rapidly infiltrates the skin and underlying thoracic wall.
They resemble invasive carcinoma in females both morphologically and
MALE REPRODUCTIVE SYSTEM
MOST IMPORTANT CAUSE OF PAINLESS
ENLARGEMENT OF TESTIS
INCREASED FREQUENCY IN SIBLINGS
PEAK INCIDENCE 15-34 YRS
MOST ARE MALIGNANT
ASSOCIATED WITH GERM CELL
95% ARISE FROM GERM CELLS
ISOCHROMOSOME 12, i(12p), IS A COMMON FINDING
INTRATUBULAR GERM CELL NEOPLASMS
RARELY ARISE FROM SERTOLI CELLS OR LEYDIG
THESE ARE OFTEN BENIGN
WHO CLASSIFICATION OF TESTICULAR
ONE HISTOLOGIC PATTERN (40%)
YOLK SAC TUMOR
MULTIPLE HISTOLOGIC PATTERNS (60%)
EMBRYONAL CA + TERATOMA
CHORIOCARCINOMA + OTHER
Most are malignant
Excellent results with treatment.
Must look for „markers‟ before removal
Germ line (actual reproductive cells)
Specialized supportive cells
Leydig, may be hormonally active
Some tumors produce agents measurable in the
Embryonic tissue markers
We measure this in pregnancy tests
Marker associated with embryonic gut
Arises from sperm
fried egg looking cells.
No production of Bet-HCG or Alpha-fetoprotein
distinct cell types
part of a
„mixed lineage‟ tumor.
This element spreads
LEYDIG CELL TUMOR
One of several so-called „specialized stromal
Sometimes even corticosteroids
filled scrotal cyst.
Often with inguinal
Fluid will recollect if
Can be large
GERM CELL TUMOURS OF THE TESTIS
mainly 15-40 yrs
more common in undescended testes & in testicular
dysgenesis (Klinefelter‟s syndrome)
usually presents as painless mass
almost always malignant
seminoma and “non-seminoma” are two main types
precursor lesion = ITGCN
INTRATUBULAR GERM CELL NEOPLASIA
CIS in other organs
seen adjacent to most tumours
also often seen where germ cell tumours
may arise, e.g. cryptorchidism, Klinefelter‟s
progresses to invasive tumour in ~ 50%
cases over ~ 5 years
may be bilateral
important to follow up/treat (e.g.
GERM CALL TUMOURS - SEMINOMA
(seminoma = ovarian dysgerminoma)
(rarely arise elsewhere - mediastinum,
can metastasise– especially nodes and
radiosensitive - 95% cure in early stages
pale homogenous tumour
big cells, lymphocytes, few mitoses
contain PLAP (placental alkaline phosphatase)
BENIGN PROSTATIC HYPERPLASIA
Nodular growth pattern
Some chronic inflammation
Glands always have a double layer of epithelium
Rare in Asians
LN and Bone mets
Some are dangerous