Transcript Pathology of Female Genital System And Breast

Pathology of
Female Genital System
And Breast
2008
Contents:
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Pathology of
Vulva
Vagina
Cervix
Body of Uterus
Fallopian Tubes
Ovaries
Diseases of Pregnancy
Breast
VULVA
Diseases of vulva:
 Vulvitis (more common but not serious).
 Non-Neoplastic epithelial disorders.
 Carcinomas (uncommon but life threatening).
 Painful bartholin cysts (caused by obstruction
of the excretory ducts of the glands).
 Imperforate hymen in children.
 Impeding secretions and menstrual flow later
in life.
Vulvitis
Most important forms of vulvitis related
to sexually transmitted disease:
 HPV: produce condylomata acuminata and
vulvar intraepithelial neoplasia.
 Herpes genitalis (HSV1 or 2): causing
vesicular eruption.
 Gonococcal suppurative infection
 Syphilis: produce primary chancre at site of
inoculation.
 Candidal vulvitis.
Vulvitis
Contact dermatitis: the most dommon causes of
vulvar pruritus is a reactive inflammation to an
exogenous stimulus, whether an irritant or an
allergen.
 Contact irritant dermatitis: presents as welldefined erythematous weeping and crusting
papules and plaques. May be a reaction to urine,
sops, detergents, antiseptics, or alcohol.
 Contact allergic dermatitis: has similar gross
appearance and may result from allergy to
perfumes and other additives in creams, lotions,
and soaps, chemical treatments on clothing and
other antigens.
Non-Neoplasic epithelial disorders
 The epithelium of vulvar mucosa may
undergo atrophic thinning or hyperplastic
thickening
 There are two forms of non-neoplastic
epithelial disorders: lichen sclerosus and
lichen simplex chronicus.
 Both may coexist in different areas in the
same person, and both may appear
macroscopically as depigmented white
lesions, referred to as leukoplakia.
Non-Neoplastic epithelial disorders
 Lichen Sclerosus:
Characterized by atrophic epithelium, usually with dermal
fibrosis.
Pathogenesis is uncertain, autoimmune reaction may
involved
Carries an increased risk of developing squamous cell
carcinoma.
 Lichen Simplex Chronicus
End reaction of many inflammatory dermatoses, marked
by epithelial thickening, expansion of stratum
granulosum and surface hyperkeratosis.
Generally, there is no inrecased predisposition to cancer,
but suspiciously, lichen simplex chronicus is often
present at margins of established cancer of the vulva.
Non-Neoplastic epithelial disorders
Lichen Sclerosus
Lichen simplex
chronicus
Lichen Planus
It’s benign dermatoses
Tumors
 Condylomas and low-grade vulvar
intraepithelial Neoplasian (VIN)
Condylomas fall into two distinctive biologic forms:
- Condylomata lata: (not commonly seen today), are
flat, moist, minimally elevated lesions that occur in
secondary syphilis
- 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.
Condylomas
Giant condyloma accuminata
A vulva chancre and
condylomata
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
occorus in older women; It is well differentiated
and unifocal, and is associated with lichen sclerosus
or other inflammatory conditions.
Extramammary Paget Disease
 Like that of breast, is essentially a form of
intraepithelial carcinoma.
 Unlike breast, vulvar Paget disease have no
demonstrable underlying carcinoma.
 Microscopically, red, scaly plaque;
characterized by spread of malignant cells
within the epithelium, occasionally with
invasion of underlying dermis
Review Questions
1.
A.
B.
C.
D.
E.
A 62 year old woman
presented with stenosis
(narrowing) of her introitus
and symmetrical atrophic
changes of the labia. A
biopsy showed thinning of
the epidermis with
replacement of the
underlying dermis by dense
connective tissue. These
findings are most
consistent with:
Moderate dysplasia (VIN II)
Squamous hyperplasia
Condyloma acuminatum
Verrucous carcinoma
Lichen sclerosis
2.
A.
B.
C.
D.
E.
A 75-year old woman
presents with a pruritic
vulvar lesion. Physical
examination reveals an
irregular white, rough area
involving her vulva. If this
leukoplakia is due to lichen
sclerosis, then biopsies will
most likely reveal
Atrophy of epidermis with
dermal fibrosis
Epidermal atypia with
dysplasia
Epithelial hyperplasia and
hyperkeratosis
Individual malignant cells
invading the epidermis
Loss of epidermis pigment
VAGINA
 The vagina is seldom the site of primary
disease; more often it is secondarily involved in
the spread of cancer or infection arising in
cervix, vulva, bladder, or rectum.
 The only primary disorders discussed here are
a few congenital anomalies, vaginitis, and
primary tumors.
 Congenital anomalies are uncommon and
include entities such as total absence of
vagina, a separate or double vagina, and
congenital small lateral Gartner duct cysts
arising from persistent embryonic remnants.
Vaginitis
 Relatively common clinical problem that is usually
transient and not serious.
 A large variety of organisms are implicated; in
adults, primary gonorrheal infection of the vagina
is uncommon; However, it may occur in newborn
born to infected mothers.
 The frequent organisms are Candida Albicans and
Trichomonas vaginalis. Candidal vaginitis
produces a curdy white discharge, it is present in
about 5% of normal adults, and so the
appearance of symptomatic infection always
involves predisposing influences or sexual
transmission of new aggressive strains.
Vaginitis
(continued…)
 T. vaginalis produces a watery, copious
green discharge, in which parasite can be
identified microscopically.
 However, T. vaginalis can also be identified
in 10% of asymptomatic women, and so
symptomatic infection usually represent a
sexually transmitted new strain.
 Nonspecific atrophic vaginitis may be
encountered in postmenopausal women
with preexisting atrophy and thinning of the
squamous vaginal mucosa.
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.
Review Questions
3. The most frequent
malignancy of the
vagina is:
A. Embryonal
rhabdomyosarcoma
B. Clear cell
adenocarcinoma
C. Vaginal adenosis
D. Sarcoma botryoides
E. Squamous cell
carcinoma
4. Vaginal adenosis is
most likely to precede
the development of
A. Condyloma
acuminatum
B. Cervical carcinoma
C. Clear cell carcinoma
D. Carcinoma of the
endometrium
E. Squamous carcinoma
of the vagian
CERVIX
 Cervix is often the seat of disease.
 Fortunately, most cervical lesions are
relatively banal inflammation
 But cervix is also the site of the most
common cancers in women;
squamous cell carcinoma.
Cervicitis
 At birth, the columnar mucus-secreting
epithelium of the endocervix meets the sqamous
epithelial covering of the exocervix at the
external os; not visible by naked eye.
 In young women, squmocolumnar junction
comes to lie visibly on the exocervix (condition
called extropion).
 In adult, regeneration of both squamous and
columnar epithelium in region known as the
transformation zone. Frequently, overgrowth of
these epithelium blocks the orifices of
endocervical glands in the transformation zone to
produce small nabothian cysts.
Cervicitis
(contiued …)
 Inflammation of the cervix are extremely common,
and are associated with purulent vaginal discharge.
 These inflammation can be infectious or
noninfectious cervicitis.
 Microorganisms often present are indigenous,
incidental vaginal aerobes and anaerobes,
streptococci, staphylococci, enterococci, Escherichia
coli, Chlamydia trachomatis, Ureplasma urelyticum,
T. vaginlais, Candida spp., Neisseria gonorrheae,
herpes simplex genitalis, and HPV.
 Many of these organisms are transmitted sexually,
so cervicitis may represent sexually transmitted
disease. Among these organisms, C. trachomatis
represent 40% of cases of cervicitis encountered in
sexually transmitted disease clinics.
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
plummeted.
 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 changes CIN.
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 invasive carcinoma.
 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
carcinoma are:
-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.
Cervical intraepithelial Neoplasia
Normal squamous
epithelium of the cervix.
There is weak positive
cytoplasmic staining
Left, normal epithelium.
Right, CIN2/3
Strongly positive staining
nuclie
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 RB, respectively.
 Low-risk HPV types: 6, 11, 42, 44 which produce
condylomas; the viral DNA does not integrate into the
host genome.
 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 carcinoma 5%.
 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
(continued…)
 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 direct palpation.
Review Questions
5. Risk factors for cervical
cancer include all of the
following except:
A. Multiple sexual partners
B. A male partner with
multiple previous sexual
partners
C. Endocervical polyps
D. Early age at first
intercourse
E. Cigarette smoking
6. All of the following are
significant causes of
acute or chronic
cervicitis EXCEPT:
A. Gonococci
B. Lactobacilli
C. Chlamydia
D. Mycoplasma
E. Herpes
Review Questions
7.
A.
B.
C.
D.
E.
Which of the following
statements concerning
carcinoma of the cervix is
true?
Stage II disease is confined
to the cervix
Distant metastases accounts
for most deaths
Peak incidence is 20 to 25
years
85% associated with human
papillomavirus
Definitive diagnosis is made
by Pap smear
8.
A.
B.
C.
D.
E.
A 31 year old woman was
found to have abnormal cells
on pap smear a separate
sample of which were sent
for HPV (human
papillomavirus) typing. Which
of the following HPV types
would put her at highest risk
for subsequent development
of squamous cell carcinoma
of the cervix? (From
additional information)
6
11
16
42
44
Review Questions
9. Multiple small
mucinous cysts of the
endocervix that result
from blockage of
endocervical glands by
overlying sqmaous
metaplastic epithelium
are called:
A) Bartholines cysts
B) Chocolate cyst
C) Follicular cyst
D) Gartners duct cyst
E) Nabothian cyst
BODY OF UTERUD
Many disorders of this organ are common,
often chronic and recurrent, and sometimes
disastrous. Only the more frequent and
significant ones are considered here.
 Endometritis
 Adenomyosis
 Endometriosis
 Dysfunctional uterine bleeding and
endometrial hyperplasia
 Tumors
Endometritis
 Can be seen with pelvic inflammatory disease.
 It may be associated with foreign bodies or
retained tissue subsequent to miscarriage or
delivery. They act as a nidus for infection.
Removal of the foreign body and offending
tissue typically results in resolution.
 Endometritis is classified as acute or chronic
based on whether there is a predominant
neutrophilic or lymphoplasmacytic response,
Generally the diagnosis of chronic endometritis
requires the presence of plasma cells. Acute
endometritis is frequently due to N.
gonorrhoeae or C. trachomatis.
Endometritis
(continued …)
 Endometritis may present with fever,
abdominal pain, menstrual
abnormalities, infertility and ectopic
pregnancy due to damage to the
fallopian tubes.
 Granulomatous endometritis: seen in
immunocompromised individuals in
U.S, and in other countries where
tuberculosis is endemic.
Adenomyosis
 It is the growth of basal layer of the
endometrium down into the myometrium.
 Endometrial stroma, glands are found well in
the myometrium between the muscle bundles.
 The uterine wall often becomes thickened and
the uterus is enlarged.
 Because they are drived from the stratum
basalis of the endometrium, they do not
undergo cyclical bleeding. Nevertheless,
adenomyosis may produce menorrhagia,
dysmenorrhea, and pelvic pain before the
onset of menstruation.
Endometriosis
 It is characterized by endometrial glands and
stroma in a location outside the
endomyometrium. It may present as a pelvic
mass filled with degenerating blood.
 Regurgitation theory: (currently most accepted
theory) proposes menstrual backflow through
the fallopian tubes with subsequent
implantation. Indeed, menstural endometrium
is viable and survives when injected into the
anterior abdominal wall.
Endometriosis
(continued …)
 Manifestations depend on the distribution of
the lesions. Extensive scaring of the oviducts
and ovaries produces discomfort in the lower
abdominal quadrants, and eventually causes
sterility. Pain on defecation reflects rectal wall
involvement, and dyspareunia (painful
intercourse) and dysuria reflect involvement of
the uterine and bladder serosa, respectively.
 Almost in all cases, there is severe
dysmenorrhea and pelvic pain as a result of
intrapelvic bleeding and periuterine adhesions.
Common locations of endometriosis
within the pelvis and abdomen
Dysfunctional uterine bleeding
 Abnormal bleeding in the absence of a well-defined
organic lesion in the uterus is called dysfunctional
uterine bleeding. It depends somewhat on the age of
the women.
 Various causes can be segregated into four groups:
- Failure of ovulation. Leads to an excess of estrogen
relative to progesterone.
- Inadequate luteal phase. Corpus luteum fail to
mature normally, leading to relative lack of
progesterone.
- Contraceptive-induced bleeding. Induce a variety of
endometrial responses, e.g. decidua-like stroma and
inactive, non-secretory glands.
- Endomyometrial disorders. Including chronic
endometritis, endometrial polyps, and leiomyomas.
Endometrial hyperplasia
 An excess of estrogen relative to progestin, induce
hyperplasia, which can be preneoplastic.
 They can be classified into simple hyperplasia,
complex hyperplasia and atypical hyperplasia. The
risk of developing carcinoma is dependent of the
severity of the hyperplastic changes.
 Potential contributors include failure of ovulation,
prolonged administration of estrogenic steroids,
polycystic ovaries (estrogen-producing ovarian
lesion) cortical stromal hyperplasia, and granulosatheca cell tumors of the ovary.
 Common risk factor is obesity, because adipose
tissue processes steroid precursors into estrogens.
Tumors
 They tend to produce bleeding as the earliest
manifestation.
 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
architecture.
They may occur at any age, but more commonly,
they develop at time of menopause.
clinical significance:
- production of abnormal uterine bleeding.
- risk of giving rise to a cancer (rare).
Tumors
(continued…)
 Leiomyoma:
- The most common benign tumor in females and are
found in 30% to 50% of women during reproductive
life. More frequent in blacks than in whites.
- 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.
Tumors
(continued…)
 Liomyosarcomas:
- Typically arise de novo from mesenchymal cells of
the myometrium.
- Almost always solitary tumors.
- They are frequently soft, hemorrhagic and necrotic.
- Diagnostic features include tumor necrosis,
cytologic atypia, and mitotic activity.
- They present a wide range of differentiation
- Recurrence after removal is common with these
cancers.
- Many metastasize, typically to the lungs. Yielding a
5-years survival rate of about 40%.
Tumors
(continued…)
 Endometrial carcinoma: The most frequent cancer
occurring in the female genital tract in the U.S and other
Western countries.
- Appears most frequently between the ages of 55 and 65
years.
- 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, respectively).
- Well-defined risk factors for endometroid carcinoma:
obesity-diabetes-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 this cancer.
Tumors
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
hyperplasia.
- These tumors are termed endometrioid because of
their similarity to normal endometrial gland.
- Breast cancer occurs more frequently in women with
endometrial cancer than by chance alone.
- Two familial cancer syndromes that have an increased
risk of the endometrioid type of endometrial
carcinoma:
1. hereditary nonpolyposis colon cancer syndrome.
2. Cowden’s syndrome (carries an increased risk of
carcinoma of the breast, thyroid, and endometrium,
have mutations in PTEN, a tumor suppressor gene).
Tumors
Endometrial carcinoma: (continued…)
-
-
Serous carcinoma of the endometrium typically
arises in a background of atrophy, sometimes in the
setting of an endometrial polyps.
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 latemetastasizing neoplasms, but dissemination
eventually occurs.
Review Questions
10. _______Causes
enlargement of the
uterine wall
A. Endometriosis
B. Adenomyosis
C. Both
D. Neither
11. _____ May result
in pelvic adhesions
A. Endometriosis
B. Adenomyosis
C. Both
D. Neither
Review Questions
12.Endometrial
carcinoma risk
factors include all
except:
A Obesity
B Hypertension
C Diabetes mellitus
D HPV infection
E Infertility
FALLOPIAN TUBES
 Salpingitis is the most common disease of the
fallopian tubes, almost always as a component of
pelvic inflammatory disease. It is almost always
microbial in origin.
 Non-gonococcal infections are more invasive,
penetrate the wall of the tubes, and give rise to
blood-borne infections and seeding of the
meninges, joint spaces, and sometimes the heart
valves.
 Salpingitis increase risk of tubal ectopic pregnancy.
 All forms of salpingitis may produce fever, lower
abdominal or pelvic pain, and pelvic masses. They
may result in tubo-ovarian abscess, or tubo-ovarian
complex. And damage or obstruction of the tubal
lumina may produce permanent sterility.
FALLOPIAN TUBES
(continued…)
 Primary adenocarcinomas: may be
of papillary serous or endometrioid
histology. They seem to be increased
in women with BRCA mutations.
Because the lumen and fimbria of the
fallopian tube have access to the
peritoneal cavity, fallopian tube
carcinomas frequently involve the
omentum and peritoneal cavity at
presentation.
OVARIES
(contents):
 Follicle and luteal cysts
 Polycystic ovaries
 Tumors of the ovary
- Surface epithelial-stromal tumors
- Serous tumors
- Mucinous tumors
- Endometrioid tumors
- Brenner tumor
- Other tumors
- Teratomas
*Benign (mature) cystic teratomas
*Immature malignant teratomas
*Specilized teratomas
OVARIES
 Follicle and luteal cysts:
- Common place of physiologic variants.
- Originate in unruptured graafian follicles or in
follicles that have ruptured and immediately sealed.
- They may become palpable masses and produce
pelvic pain, when they achieve diameters of 4-5cm.
- When small thy are lined by granulosa lining cells
or luteal cells, but as the fluid accumulates,
pressure may cause atrophy of these cells.
- Sometimes these cysts rupture, producing
intraperitoneal bleeding and acute abdominal
symptoms.
OVARIES
(continued…)
 Polycystic ovaries:
- Oligomenorrhea, hirsutism, infertility, and sometimes
obesity may appear in girls after menarche secondary
to excessive production of estrogens and androgens
by multiple cystic follicles in the ovaries.
- They are also called Stein-Leventhal syndrome.
- Ovaries usually twice normal in size, gray-white
cortex, studded with subcortical cysts.
- Histologically, thickened outer tunica, with
hypertrophic and hyperplastic luteinized theca interna.
And corpora lutea is absence.
- The principal biochemical abnormalities are excessive
production of androgens, high concentration of LH,
low concentration of FSH.
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.
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
somewhat.
- A majority of hereditary ovarian cancers seem to be
caused by mutations in the BRCA1 and BRCA2 genes.
- HER2/NEU protein is overexpressed in 35% of ovarian
cancers, with poor prognosis.
- K-RAS protein is overexpressed in up to 30% of
tumors, mostly mucinous cystadenocarcinomas.
- P53 is mutated in about 50% of all ovarian cancers.
Surface epithelial-stromal tumors
 They are derived from the coelomic mesothelium
that covers the surface of the ovary.
 With repeated ovulation and scarring the surface
epithelium is pulled into the cortex of the ovary,
forming small epithelial cysts.
 Benign lesions are usually cystic (cystadenoma) or
have a stromal component (cystadenofibroma).
 Malignant tumors may also be cystic
(cystadenocarcinoma) or solid (carcinoma).
 There are also intermediate, borderline category,
tumors of low malignant potential. They are lowgrade cancers with limited invasive potential.
Serous Tumors
 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 cystadenocarcinoma after treatment is poor
and depends on the stage of the disease at the time
of diagnosis.
Mucinous tumors
 The differ essentially from serous tumors in that
the epithelium consists of mucin-secreting cells
simlar to tthose of the endocervical mucosa.
 Their incidence is much lower and they are less
likely to be malignant than serous tumors,
accounting for about 10% of all ovarian cancers.
 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 treatment success.
Endometrioid tumors
 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 endometrium.
 They are usually malignant tumors, although
benign and borderline forms also exist.
 15-30% of women with these ovarian tumors
have a concomitant endometrial carcinoma.
 Similar to endometrial cancer, endometrioid
carcnoma have mutations in PTEN suppressor
gene.
Brenner tumor
 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 mucus-secreting cell.
 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 mucinous cystadenoma.
Teratomas
 Neoplasms of germ-cell origin constitute
15% to 20% of ovarian tumors.
 They arise in the first two decades of life.
 Thy younger the person, the greater is the
likelihood of malignancy
 However, more than 90% of these germcell 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 hairbearing 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.
For unknown reasons, these tumors are prone to undergo
torsion, producing an acute surgical emergency.
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 structure.
 Particularly ominous are foci of neuropithelial
differentiation, because they are aggressive and
metastasize widely.
Specialized teratomas
 Struma ovarii is composed entirely of mature
thyroid tissue that may hyperfunction and
produce hyperthyroidism.
 They appear as small, solid, unilateral brown
ovarian masses.
 Struma ovarii and
carcinoid may combined
in the same ovary.
One of these elements
may become malignant.
Specialized teratoma
Tomors of the ovary
Serous tumor
Endometrioid tumor
Mucinous ovarian tumor
Mature (benign) teratoma
Brenner tumor
Immature (malignant)
teratoma
Review Questions
13. A 27 year old nulliparous
woman presents with
hirsutism and
oligomenorrhea.
Ultrasound shows
bilateral 8 cm ovaries
with multiple small
cortical cysts. The most
likely diagnosis:
A Granulosa cell tumor
B Polycystic ovary disease
C Thecal luteal cysts
D Bilateral cysts of
Morgagni
E Bilateral Brenner tumors
DISEASES OF PREGNANCY
 Diseases of pregnancy and pathologic conditions of
the placenta are important causes of intrauterine or
perinatal death, premature birth, congenital
malformations and growth retardation, maternal
death, and morbidity for both mother and child.
 Some disorders:
- Placental inflammations and infections
- Ectopic pregnancy
- Gestational trophoblastic disease
* hydatidifrom mole: complete and partial
* invasive mole
* choriocarcinoma
* placental site trophoblastic tumor
- Preeclampsia/eclampsia (toxemia of pregnancy)
Placental inflammations and
infections
 Infections reach placenta by two pathways:
 Ascending infections through the birth
canal. The most common, they are
bacterial and are associated with premature
birth. Choriomnion shows polymorph
leukocytic infiltration with edema and
congestion of the vessels. When it extends
beyond the membranes, it may cause acute
vasculitis of the cord. They are caused by
mycoplasms, Candida, and bacteria of the
vaginal flora.
Placental inflammations and
infections (continued…)
 Hematogenous spread.
- Histologically, the villi are most often
affected (villitis).
- Syphilis, tuberculosis, listeriosis,
toxoplasmosis, rubella and cytomeglaovrius
and herpes simplex viruses can all cause
placental villitis.
- Transplacental infections can affect the
fetus and give rise to the so-called TORCH
complex.
Ectopic pregnancy
 It is implantation of the fertilized ovum in any site
other than the normal uterine location.
 Occurs as many as 1% of pregnancies.
 In 90% of these cases, implantation is in the oviducts
(tubal pregnancy) other sites include the ovaries, the
abdominal cavity, and the intrauterine portion of the
oviduct.
 Any factor that retard the passage of an ovum from
oviduct to uterus predispose to ectopic pregnancy. In
adult half of the cases, such obstruction is based on
chronic inflammatory changes in the oviduct, although
tumors and endometriosis may also retard passage of
the ovum.
 In half of tubal pregnancy no anatomic cause can be
demonstrated.
Ectopic pregnancy
(continued…)
 Ovarian pregnancies result when ovum is fertilized
within its follicle just at time of rupture.
 Gestation within the abdominal cavity occurs when
the fertilized eggs drops out of the oviduct and
implants on the peritoneum.
 Until rupture occurs, an ectopic pregnancy may be
indistinguishable from a normal one.
 Under the influence of the placental hormones, the
endometrium (in 50% of cases) undergoes the
characteristic changes. (although there is absence
of elevated gonadotropin levels).
 Rupture of an ectopic pregnancy may be with
sudden onset of intense abdominal pain, often
followed by shock. Prompt surgical intervention is
necessary.
Gestational trophoblastic disease
 They are divided into three overlapping morphologic
categories:
- Hydatidiform mole
- Invasive mole
- Choriocarcinoma
 They range in aggressiveness from the dydatidiform
moles, most of which are benign, to the highly
malignant choriocarcinomas.
 All elaborate human chorionic gonadotropin (hCG),
which can detected considerably higher than those
found during normal pregnancy. The titers
progressively rising from hydatidiform mole to
invasive mole to choriocarcinoma.
 The fall or rise in the level of the hormone can be
used to monitor the effectiveness of treatment.
Hydatidiform mole
It is a voluminous mass of swollen, sometimes cystically
dilated, chorionic villi, appears as grapelike structures.
 The swollen villi are covered by varying amounts of normal
to highly atypical chorionic epithelium.
 Two distinctive subtypes of moles have been charaterized:
- Complete hydatidiform: does not permit embryogenesis
therefore never contain fetal parts. All of the chorionic villi
are abnormal, and the chorionic epithelial cells are diploid
(46,XX or, uncommonly, 46,XY).
- Partial hydatidiform: compatible with early embro
formation, has some normal chorionic villi, and is almost
always triploid (69,XXY), rarely give rise to choriocarcinoma
 Moles are most common before age 20 years and after age
40 years, and a history of the condition increases the risk in
subsequent pregnancies.
 Elevation of hCG in the maternal bllod and absence of fetal
parts or fetal heart sound are typical.

Invasive mole
 They are complete moles that are more aggressive
locally but do not have the aggressive metastatic
potential of a choriocarcinoma.
 An invasive mole retains hydropic villi, which
penetrate the uterine wall deeply, causing rupture and
sometime life-threatenining hemorrhage.
 Local spread to the broad ligament and vagina may
also occur.
 Hydropic villi may embolize to distant organs, such as
lungs or brain, but they do not constitute true
metastases and may actually regress spontaneously.
 Because of the greater depth of invasion into the
myometrium, an invasive mole is difficult to remove
completely by curettage, and therefore serum hCG
may remain elevated.
Choriocarcinoma
 It is very aggressive malignant tumor.
 Arises from gestational chorionic epithelium or, less
frequently, from totipotential cells within the
gonads or elsewhere.
 Rare in western countries, and much more common
in Asian and African countries.
 The risk is greater before age 20 years and after
age 40.
 50% of choriocarcinoma arise in complete
hydatidiform moles, 25% after abortion, and the
remainder occur during a normal pregnancy. The
more abnormal the conception the greater is the
risk of developing gestational choriocarcinoma.
 In most cases there is a bloody, brownish
discharge, accompanied by a rising titer of hCG.
Choriocarcinoma
(continued…)
 By the time most choriocarcinomas are discovered,
there is usually widespread dissemination via the
blood most often to lungs, vagina. Lymphatic invasion
is uncommon.
 despite extreme aggressiveness of these neoplasms,
which made them nearly fatal in the past, present-day
chemotherapy has achieved remarkable results.
Nearly 100% of cases can be cured
 By contrast, there is relatively poor response to
chemotherapy in chocriocarcinoma that arise in the
gonads (ovary or testis). This striking difference may
related to the presence of paternal antigens on
placental choriocarcinoma but not gonal lesion,
maternal immune response against paternal antigens
helps by acting as an adjunct to chemotherapy.
Placental site trophoblastic tumor
 These uncommon tumors are diploid, are often
XX in karyopte, derived from the placental site or
intermediate trophoblast.
 Typically arise a few months after pregnancy.
 Intermediate trophoblasts do no produce large
amount of hCG, so hCG concentration is only
slightly elevated.
 They produce human placental lactogen.
 They are indolent and have favorable outcome if
confined to endometrium. However, they are not
sensitive to chemotherapy, and the prognosis is
poor if they spread beyond the uterus.
Preeclampsia/eclampsia (toxemia
of pregnancy)
 Preeclampsia is the development of
hypertension, accompanied by proteinuria and
edema in third trimester of pregnancy.
 Occurs in 5% to 10% of pregnancies,
particularly with first pregnancies in women
older than age 35 years.
 In those severely affected, renal function is
impaired, the blood pressure mounts,
convulsive seizures may appear, the symptom
complex is then termed eclampsia.
 Preeclampsia and eclampsia are referred to as
toxemia of pregnancy.
Preeclampsia/eclampsia (toxemia
of pregnancy) (continued…)
 Full-blown eclampsia may lead to disseminated
intravascular coagulation, with widespread ischemic
organ injuries, and so eclampsia is potentially fatal.
However, early recognition and treatment of
preeclampsia has now made eclampsia rare.
 The basic feature underlying all cases is inadequate
maternal blood flow to the placental secondary to
inadequate development of spiral arteries of the
uteroplacental bed.
 Recent studies suggest imbalance between
proangiogenic and antiangiogenic factors. Increase in
the antiangiogenic factor sFlt1 and reduction in the
level of the proangiogenic factor VEGF have been
noted.
Review Questions
14.Triploid Karyotype
A. Complete mole
B. Partial mole
C. Both A and B
D. Neither
15.Fetal parts may be
present
A. Complete mole
B. Partial mole
C. Both A and B
D. Neither
Review Questions
16.Edematous changes of
all the villi
A. Partial hydatiform
mole
B. Complete hydatiform
mole
C. Invasive mole
D. Choriocarcinoma
E. Placental site
trophoblastic tumor
17. _____ Admixture of
edematous and
normal villi
A. Complete mole
B. Partial mole
C. Both
D. Neither
Review Questions
18.Elevated HCG in
serum
A. Complete mole
B. Partial mole
C. Both A and B
D. Neither
BREAST
Fibrocystic changes:
 Different changes range from those that are
innocuous to patterns associated with an increased
risk of breast carcinoma.
 Some of them produce palpable “lumps”.
 This range of changes is the consequence of an
exaggeration and distortion of the cyclic breast
changes that occur normally in the menstrual cycle.
Estrogenic therapy and oral contraceptives do not
seem to increase the incidence of these alterations.
 They may cause nodularity; only a small minority
represent forms of epithelial hyperplasia that are
clinically important.
 Lumps that are produced by the various patterns of
fibrocystic change must be distinguished from cancer.
Fibrocystic changes
(continued…)
 They can be subdivided into nonporliferative and
proliferative patterns.
- The nonproliferative lesions include cysts and/or
fibrosis without epithelial cell hyperplasia (simple
fibrocystic change).
- The proliferative lesions include a range of
innocuous to atypical duct or ductular epithelial cell
hyperplasias and sclerosing adenosis.
 They tend to arise during reproductive period of life
but may persist after menopause.
 Nonproliferative changes are so common, being
found at autopsy in 60% to 80% of women, that
they almost constitute physiologic variants.
Nonproliferative change
Cysts and fibrosis:
 Characterized by an increase in fibrous
stroma associated with dilation of ducts and
formation of cysts of various size.
 The stroma is usually compressed fibrous
tissue, having lost in their normal delicate,
myxomatous appearance.
 A stromal lymphocytic infiltration is
common in this and other variants of
firbrocystic change.
Proliferative change
Epithelial hyperplasia:
 It is proliferative lesion within the ductules, the
terminal ducts, and sometimes the lobules of the
breast.
 Some of the epithelial hyperplasia are mild and
orderly, and carry little risk of carcinoma.
 But there is more florid atypical hyperplasia that carry
significantly greater risk.
 The epithelial hyperplasia are often accompanied by
other histologic variants of fibrocystic change.
 Occasionally it produces microcalcifications on
mammography, rising fears about cancer.
Proliferative change
(continued…)
Sclerosing adenosis:
 This variant is less common than cysts and
hyperplasia, but it is significant because its
clinical features are smilar to those of
carcinoma.
 They contain marked intralobular fibrosis
and proliferation of small ductules and
acini.
 Although it is difficult to differentiate from
carcinoma, it is associated with only a
minimally increased risk of pregression to
carcinoma.
Inflammations
 They are uncommon, and during acute stages usually
cause pain and tenderness in the involved areas.
 In this category there are several forms of mastitis and
traumatic fat necrosis.
 They are not associated with increased risk of cancer.
 Mammary duct ectasia (periductal or plasma cell
mastitis) is nonbacterial chronic inflammation of the
beast associated with inspiration of breast secretions in
the main excretory ducts. It is uncommon, and
encountered in women in their 40s and 50s who have
borne children.
 Mammary duct ectasia is significant because it leads to
induration of the breast substance mimicking the
changes caused by some carcinomas.
Tumors of the breast
 They may arise from either
connective tissue or epithelial
structures. That latter give rise to
common breast neoplasms.
Fibroadenoma
 It 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 llife.
 An increase in estrogen activity is thought
to contribute to its development.
 Smiliar lesions may appear with fibrocystic
changes.
 They usually present as solitary, discrete,
movable mass. They may enlarge late in
the menstrual cycle and during pregnancy.
Phyllodes tumor







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 stroma.
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.
Intraductal papilloma
 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.
Carcinoma
 Despite advances in diagnosis and treatment, almost
one-fourth of women who develop these neoplasms
will die of the disease.
 75% of women with breast cancer are older than age
50. only 5% are younger than the age 40.
Epidemiology and risk factors:
 Geographic distribution: there are differences among
countries in the incidence and mortality rates of
breast cancer. The risk is significantly higher in North
America and northern Europe than in Asia and Africa.
These difference seems to be environmental rather
than genetic in origin.
 Age: uncommon in women younger than 30 ys, the
risk steadily increase throughout life, but after the
menopause the slope of the curve is almost plateous.
Carcinoma
(continued…)
 Getetics and family history:
- 5% to 10% of breast cancer are related to inherited
mutations.
- Women are more likely to carry a breast cancer
susceptibility gene if they develop breast cancer before
menopause, have bilateral cancer, have other
associated cancer like ovarian cancer, or have a family
history.
- Half of women with hereditary breast cancer have
mutations in gene BRCA1 and one-third have mutations
in BRCA2. These genes function in DNA repair.
- Less common genetic diseases associated with breast
cancer are the Li-Fraumeni syndrome (mutations in
p53), Cowden disease (mutations in PTEN), and carriers
of ataxia-telangiectasia gene.
Carcinoma




(continued…)
prolonged exposure to exogenous estrogens
postmenopausally: know as a hormone replacement therapy,
prevents or delays the onset of osteoporosis. However, use of
combined estrogen plus progestin hormone therapy is
associated with an increased risk of breast cancer, diagnosis at
more advanced stage, and more abnormal mammograms.
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.
Carcinoma
(continued…)
Pathogenesis: as with all cancers, the cause of breast
cancer remain unknown. however, three set of
influences seem to be important:
 Genetic change:
- Mutations affecting proto-oncogenes and tumor
supressor genes in breast epithelium contribute to the
oncogenic transformation process.
- Overexpression of the HER2/NEU proto-oncogene,
found to be amplified in up to 30% of invasive breast
cancers.
- Amplification of RAS and MYC genes has also been
reported in some breast cancer.
- Mutation of the tumor suppressor genes RB and p53
may also be present.
Carcinoma
-
(continued…)
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 cell.
- Gene expression profiling can stratify breast cancer into
five subtypes: luminal A, luminal B, HER2/NEU
overexpression, basal-like, and normal breast like. These
subtypes are reproducible and are associated with
difference outcomes.
 Hormonal influences:
- 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.
Carcinoma
-
(continued…)
Functioning ovarian tumors that elaborate estrogens
are associated with breast cancer in postmenopausal
women.
- Estrogens stimulate the production of growth factors
by normal breast epithelial cells and by cancer cells.
Estrogen and progesterone receptors are present in
breast epithelium and in breast cancer cells, may
interact with growth promoters to create an autocrine
mechanism of tumor development.
Enviornmental variables:
- 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.
Carcinoma
(continued…)
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.
Carcinoma
(continued…)
Clinical course:
 Breast cancer is often discovered by the woman or
physician as a discrete, solitary, painless, and
movable mass. At this time, involvement of regional
lymph nodes is already present in about half of
patients.
 With mammographic screening, carcinomas are
frequently detected before they become palpable, and
only 15% of these have nodal metastases.
 Magnetic resonance imaging is being studied in highrisk young patients with dense breasts that are
difficult to image by mammography.
Carcinoma

1.
2.
3.
4.
(continued…)
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. 5-year survival rate is
90% with no axillary node involvement. The survival
rate is decreases with each involved lymph node and is
less than 50% with 16 involved nodes.
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 three groups. Well-differentiated or poor
differentiated or moderately differentiated.
Carcinoma
5.
6.
7.
8.
9.
(continued…)
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 presence of receptors confers a slightly
better prognosis. 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.
Carcinoma
(continued…)
 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 (5year survival rate: 13%)
Male breast



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 intraductal hyperplasia.
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. Almost half have spread to
regional nodes and more distant sites by the time they are
discovered. They resemble invasive carcinoma in females both
morphologically and biologically.
Review Questions
19. The most likely cause
of 1 cm mass in the
upper outer quadrant
of the breast of 65
year old woman.
A) Fibrocystic change
B) Acute mastitis
C) Fibroadenoma
D) Carcinoma
E) Pagets disease of the
breast
20.All of the following are
associated with
carinoma of the
breast, except:
A) High-fat diet
B) Positive family history
C) Obesity
D) Early menarche
E) multiparity
Additional informations
Infectious disorders:
 Candidiasis: most common form of vagnitis
 Trichomoniasis: second most common type of vaginitis.
 Garnerella vaginitis: “clue cell” are characteristic cells
 Toxic shock syndrome: associated with use of tampons.
 Gonorrhea: frequent cause of pelvic inflammatory disease.
 Chlamydial infection: clymedial cervicitis –
lymphogranuloma venereum.
 Herpes simplex virus infection: produce small viscels and
shallow ulcers.
 Shyphilis: 1st stage: chancre, 2nd stage: condyloma lata.
 Chancroid: soft and painful ulcerated lesion. Caused by
haemophilus dureyi
 Granduloma inguinale: characterized by donovan bodies.
Cased by calmmatobacterium granulomatis.
Review Test
21. All of the following
condition correctly
matched with the
appropriate association,
except:
A) Endometriosis: severe
menstrual pain
B) Endometrial hyperplasia:
excess estrogen
stimulation
C) Leiomyoma:
postmenopausal decrease
in size
D) Endometrial carcinoma:
multiparity
E) Ectopic pregnancy:
hematosalpinx
22.HPV infection is not
associated with:
A Vulvar intra epithelial
neoplasia (VIN)
B Vaginal intra epithelial
neoplasia (VAIN)
C Cervical intra epithelial
neoplasia (CIN)
D Endocervical glandular
dysplasia
E Paget's disease of the
vulva
Review Test
23. Fishy odor, "clue cells”,
caused by (from
additional information)
A. Trichomonas
B. Gardnerella
C. Candida
D. Herpes
E. Gonorrhea
24. Which of the following
neoplasms of the vagina
has been associated with
in utero exposure to
diethylstilbestrol?
A. Vaginal intraepithelial
neoplasia (VAIN)
B. Squamous cell carcinoma
C. Embryonal
rhabdomyosarcoma
D. Clear cell
adenocarcinoma
E. Leiomyoma
Review Test
25.The most common site
of an ectopic
pregnancy:
A. ovary
B. peritoneal cavity
C. endocervical canal
D. endometrial cavity
E. fallopian tube
26. A 21 year old woman is at
week 25 of her first
pregnancy. Her gynecologist
tells you she has
pre_eclampsia. You would
expect to find which
constellation of findings on
your evaluation:
A Hypertension; otherwise
normal
B Hypertension and
proteinuria; otherwise normal
C Glucose intolerance;
otherwise normal
D Glucose intolerance, and
hypertension; otherwise
normal
E
Hypertension, proteinuria and
peripheral edema
Review Test
27. A 32-year-old woman
with a history of
hyperthyroidism was
found to have a left
adnexal tumor
composed entirely of the
tissue as depicted
microscopically. The
best diagnosis is:
A. Krukenberg tumor
B. Struma ovarii
C. Immature teratoma
D. Ovarian carcinoid
E. Strumal carcinoid
28. A 27 year old woman
had a palpable right
ovary which an x-ray was
found to contain a well
developed molar tooth.
The most likely diagnosis
would be:
A. Dysgeminoma
B. Yolk sac tumor
C. Sertoli-Leydig cell tumor
D. Mature cystic teratoma
E. Denturoma
Review Test
29.Elevated beta - HCG
A. Choriocarcinoma
B. Fibroma
C. Granulosa cell tumor
D. Endodermal sinus
tumor
E. Immature teratoma
30.A 21 year old woman
was diagnosed as
having pre-eclampsia.
Which of the following
would not be
consistent with that
diagnosis?
A. Hypertension
B. Convulsions
C. Proteinuria
D. Edema
Review Test
31. The most common
primary sites for the
oringin of Paget’s
disease are the nipple
and the
A. Anal canal
B. Liver
C. Nasopharynx
D. Penis
E. Vulva
32. A 26-year old female in
the third trimester of her
first pregnancy develops
persistent headaches and
swelling of her legs and
face. Her blood pressure is
170/105 mmHg and
urnialysis reveals slight
proteinuria. What is the
diagnosis
A. Eclampsia
B. Gestational trophoblastic
disease
C. Nehritic syndrom
D. Nehprotic syndrom
E. preeclampsia
Review Test
33.The most important
factor related to the
prognosis of breast
cancer is
A. the presence of
activated oncogenes
B. The histologic type and
grade
C. The size of the tumor
D. The status of axillary
lymph nodes
E. The presence of
estrogen receptors.
Answers
1-E.
2-A.
3-E.
4-C.
5-C.
6-B.
7-D.
8-C.
9-E.
10-B.
11-A.
12-D.
13-B.
14-B.
15-B.
16-B.
17-B.
18-C.
19-D.
20-E.
21-D.
22-E.
23-B.
24-D.
25-E.
26-E.
27-B.
28-D.
29-A.
30-B.
31-E.
32-A.
33-E.
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