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Flashcards in RUbins - Unit 1 - Female Repro/Pregnancy Pathology Deck (52)
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1 A 36-year-old woman presents with infertility. She complains
of having had dull pelvic pain for 9 months, which is accentuated
during menstruation. Physical examination and endocrinologic
studies are normal. Laparoscopy reveals multiple,
small hemorrhagic lesions over the surface of both ovaries and
fallopian tubes and abundant pelvic scarring. Which of the
following is the most likely diagnosis?
(A) Borderline serous tumor
(B) Ectopic pregnancy
(C) Endometriosis
(D) Metastatic cervical carcinoma
(E) Pelvic infl ammatory disease


The answer is C: Endometriosis. Endometriosis refers to the
presence of benign endometrial glands and stroma outside the
uterus. It affl icts 5% to 10% of women of reproductive age
and regresses following menopause. The sites most frequently
involved are the ovaries (>60%); other uterine adnexae; and
the pelvic peritoneum covering the uterus, fallopian tubes,
rectosigmoid colon, and bladder. With repeated cycles, hemorrhage,
and the onset of fi brosis, the affected surface may
take on a grossly brown discoloration (“powder burns”) and
form cysts up to 15 cm in diameter, which contain chocolatecolored
material (“chocolate cysts”). The other choices do not
present as small hemorrhagic lesions in these anatomic sites.
Diagnosis: Endometriosis


2 A 58-year-old woman complains of recent swelling in her
vagina. There is a past medical history of prenatal exposure
to diethylstilbestrol. Physical examination reveals a 3-cm fi rm
mass in the anterior wall of the upper vagina. Biopsy of the
vaginal mass will most likely show which of the following
pathologic fi ndings?
(A) Clear cell adenocarcinoma
(B) Endodermal sinus tumor
(C) Granular cell tumor
(D) Mucinous adenocarcinoma
(E) Squamous cell carcinoma


The answer is A: Clear cell adenocarcinoma. Of women
exposed in utero to diethylstilbestrol, 0.1% develop clear cell
adenocarcinoma. The tumor is most common between ages
17 and 22 years and is most frequent on the anterior wall
of the upper third of the vagina. Almost all clear cell adenocarcinomas
are associated with vaginal adenosis, but very few
women with adenosis develop this cancer. The abundant clear
cytoplasm, refl ecting the presence of glycogen, accounts for
the name “clear cell.” The other choices are not associated
with prenatal exposure to diethylstilbestrol.
Diagnosis: Clear cell adenocarcinoma of vagina


3. A 60-year-old woman presents with a 3-week history of a painful
genital lesion and bleeding. Physical examination reveals
an exophytic, ulcerated 1-cm polypoid mass near the external
end of the urethra. What is the most likely diagnosis?
(A) Bartholin gland cyst
(B) Caruncle
(C) Condyloma acuminatum
(D) Lichen sclerosis
(E) Lymphogranuloma venereum


The answer is B: Caruncle. This polypoid infl ammatory lesion
near the female urethral meatus elicits pain and bleeding. It
occurs exclusively in women, most frequently after menopause.
Urethral caruncle presents as an exophytic, often ulcerated,
polypoid mass of 1 to 2 cm in diameter. Microscopically,
the lesion exhibits acutely and chronically infl amed granulation
tissue and ulceration and hyperplasia of transitional-cell
or squamous epithelium. The other choices do not typically
involve the urethral meatus.
Diagnosis: Caruncle


4 A 30-year-old woman presents with a 5-month history of
increasing abdominal girth and pelvic discomfort. Imaging
studies reveal a mass replacing the left ovary. A multilocular
tumor fi lled with thick, viscous fl uid is removed (shown in
the image). Tumor spaces are lined by mucinous, columnar
epithelial cells, showing no evidence of atypia. There are no papillary structures and no evidence of stromal invasion. Which
of the following is the appropriate pathologic diagnosis?
(A) Endometrioid adenoma of ovary
(B) Granulosa cell tumor
(C) Mucinous cystadenocarcinoma
(D) Mucinous cystadenoma
(E) Serous cystadenocarcinoma


The answer is D: Mucinous cystadenoma. Benign common
epithelial tumors of the ovary are almost always serous or mucinous
adenomas and generally arise in women between the ages
of 20 and 60 years. The neoplasms are frequently large and often
15 to 30 cm in diameter. Some of these tumors, particularly the
mucinous variety, reach truly massive proportion, exceeding
50 cm in diameter. As opposed to their malignant counterparts,
benign ovarian epithelial tumors tend to have thin walls and
lack solid areas. Lack of stromal invasion and atypia in this case
exclude mucinous cystadenocarcinoma (choice C).
Diagnosis: Mucinous cystadenoma of the ovary


5 The ovarian tumor described in Question 4 most closely
resembles which of the following patterns of müllerian-type
(A) Endometrial glands in pregnancy
(B) Epithelium of the fallopian tube
(C) Glandular epithelium of the endometrium
(D) Mucosa of the bladder
(E) Mucosa of the endocervix


The answer is E: Mucosa of the endocervix. During embryonic thelial lining gives rise to müllerian ducts, from which the
fallopian tubes, uterus, and vagina arise. Common epithelial
tumors of the ovary, in order of decreasing frequency, include:
serous tumors that resemble the epithelium of the fallopian
tube (choice B); mucinous tumors that mimic the mucosa of
the endocervix (choice E); endometrioid tumors that are similar
to glands of the endometrium (choice C); clear cell tumors
that display glycogen-rich cells that resemble endometrial
glands in pregnancy (choice A); and transitional cell tumors
that resemble the mucosa of the bladder (choice D). These
tumors are broadly classifi ed as benign, borderline (atypical
proliferative), and malignant.
Diagnosis: Mucinous cystadenoma of the ovary


6 A 19-year-old student presents to the university health service
with lower abdominal pain and a painful swollen right
knee. She denies any trauma to the knee. Pelvic examination
is exquisitely painful and reveals an ill-defi ned thickening
in the right and left adnexae. A vaginal discharge is noted.
The patient is febrile (38.7°C/103°F). Examination of her
right knee reveals an enlarged, tender, and warm joint. The
WBC count is 18,500/μL (normal = 4,000 to 11,000/μL). If
untreated, which of the following would be the most likely
complication in this patient?

(A) Bronchopneumonia
(B) Lung abscess
(C) Meningitis
(D) Tubo-ovarian abscess
(E) Vaginal ulceration


The answer is D: Tubo-ovarian abscess. Gonorrhea is caused
by Neisseria gonorrhoeae, a Gram-negative diplococcus. The
infection is a frequent cause of acute salpingitis and pelvic
infl ammatory disease. The organisms ascend through the
cervix and the endometrial cavity, where they cause an acute
endometritis. The bacteria then attach to mucosal cells in
the fallopian tube and elicit an acute infl ammatory reaction,
which is confi ned to the mucosal surface (acute salpingitis).
From the tubal lumen, the infection spreads to involve the
ovary, sometimes resulting in a tubo-ovarian abscess. Systemic
complications of gonorrhea include septicemia and septic
arthritis. The healing process distorts and destroys the plicae
of the fallopian tube, often leading to sterility. Infections by
N. gonorrhoeae at other sites (choices A, B, C, and E) are rare.
Diagnosis: Gonorrhea, pelvic infl ammatory disease


7 A 59-year-old woman presents with a 2-year history of vulvar
itching and burning. Physical examination reveals a red,
moist lesion of the labium major. Biopsy reveals clusters of
pale vacuolated cells within the epidermis that stain positively
for periodic acid-Schiff (PAS) and carcinoembryonic
antigen (CEA). Which of the following is the most likely
(A) Extramammary Paget disease
(B) HPV-induced papilloma
(C) Verrucous carcinoma
(D) Vulvar intraepithelial neoplasia
(E) Vulvar melanoma


The answer is A: Extramammary Paget disease. Paget disease
of the vulva is named after similar-appearing tumors in
the nipple and extramammary sites, such as the axilla and
perianal region. The typical Paget cell has a pale, vacuolated
cytoplasm that contains glycosaminoglycans. It stains with
PAS and mucicarmine and expresses CEA. The disorder usually
occurs on the labia majora in older women. Women with
Paget disease of the vulva complain of pruritus or a burning
sensation for many years. The other choices do not feature
these specifi c histologic fi ndings.
Diagnosis: Extramammary Paget disease


8. A 52-year-old woman with hypothyroidism presents with a
2-year history of vulvar itching and painful intercourse. Physical
examination reveals vulval white plaques, atrophic skin,
and a parchment-like appearance. Biopsy of the lesion (shown
in the image) demonstrates hyperkeratosis, loss of rete ridges,
and a homogeneous, acellular zone in the upper dermis. This
patient’s vulvar dermatitis is most commonly associated with
which of the following underlying conditions?
(A) Amyloidosis
(B) Autoimmune disease
(C) Diabetes mellitus
(D) Hyperlipidemia
(E) Prenatal exposure to diethylstilbestrol


The answer is B: Autoimmune disease. Lichen sclerosis is
an infl ammatory disease of the vulva, which is often associated
with autoimmune disorders such as vitiligo, pernicious
anemia, and thyroiditis (e.g., Hashimoto thyroiditis). The
condition is represented by white plaques, atrophic skin, a
parchment-like or crinkled appearance, and, occasionally,
marked contracture of the vulvar tissues. Histologically, there
is hyperkeratosis, loss of rete ridges, and a homogeneous, acellular
zone in the upper dermis. A band of chronic infl ammatory
cells typically lies beneath this layer. Itching is the most
common symptom, and dyspareunia is frequent. Women with
symptomatic lichen sclerosis have a 15% chance of developing
squamous cell carcinoma. The other choices are not associated
with lichen sclerosis.
Diagnosis: Lichen sclerosus


9 A 29-year-old woman is evaluated for an abnormal cervical
Pap smear. Colposcopy reveals condyloma acuminatum of
the exocervix. A biopsy of the cervix is shown in the image.
PCR amplifi cation of this biopsy specimen will most likely
demonstrate evidence of which of the following infectious

(A) Cytomegalovirus
(B) Herpes simplex virus
(C) Human papillomavirus
(D) Molluscum contagiosum
(E) Treponema pallidum


The answer is C: Human papillomavirus (HPV). Condyloma
acuminatum is a benign, exophytic, papillomatous lesion on
the skin or mucous membranes of the lower female genital tract. HPV is a DNA virus that infects a variety of skin and mucosal
surfaces to produce condylomata, which are also referred to as
verrucae. The median time from infection to fi rst detection of
HPV is 3 months. HPV types 6 and 11 are detected in over 80%
of macroscopically visible condylomata. Several strains of HPV
are now considered the major etiologic factor in the development
of squamous cell cancer in the female lower genital tract.
Types 16, 18, 31, and 45 are the most representative high-risk
types linked to intraepithelial neoplasia and invasive cancer.
The vacuolated cells in the cervical biopsy (see photomicrograph)
are typical of HPV infection and are termed koilocytes.
The other pathogens do not infect the cervix and do not produce
this histopathologic appearance.
Diagnosis: Condyloma acuminatum


10 A 31-year-old Haitian woman is evaluated for infertility. Pelvic
examination shows a markedly enlarged vulva, inguinal
lymph node enlargement, and rectal stricture. Biopsy of an
inguinal lymph node reveals necrotizing granulomas, neutrophilic
infi ltrates, and inclusion bodies within macrophages.
Which of the following is the most likely etiology of infertility
in this patient?
(A) Chlamydia trachomatis
(B) Gardnerella vaginalis
(C) Molluscum contagiosum
(D) Mycobacterium tuberculosis
(E) Treponema pallidum


The answer is A: Chlamydia trachomatis. Lymphogranuloma
venereum is a sexually transmitted infection that is endemic
in tropical countries but rare in developed ones. The disease
is caused by C. trachomatis, which is a Gram-negative obligate,
intracellular rickettsia. This organism has been found in the
genital tract of about 8% of asymptomatic women and in 20%
of women presenting with symptoms of a lower genital tract
infection. After a few days to a month, a small painless vesicle
forms at the site of inoculation. It heals rapidly, and in many
instances, the vesicle is not even noticed. The second stage
presents with bilaterally enlarged inguinal lymph nodes that
may rupture and form suppurative fi stulas. In some untreated
patients, a third stage appears, which causes lymphatic obstruction
and resulting genital elephantiasis and rectal strictures.
Mycobacterium tuberculosis (choice D) induces granulomatous
infl ammation but does not feature inclusion bodies. Gardnerella
vaginalis (choice B) causes nonspecifi c vaginitis. Molluscum
contagiosum (choice C) does not involve the lymph nodes.
Treponema pallidum (choice E) does not cause granulomas.
Diagnosis: Lymphogranuloma venaereum


11 A 35-year-old woman in Africa presents with fever, chills, and
malaise. She further complains of a painful genital sore. She
had sexual intercourse 5 days previously. Physical examination
reveals vesiculopustular lesions on the labium major and
cervix. There is bilateral inguinal lymphadenopathy. A lymph
node biopsy reveals granulomatous infl ammation. Which of
the following is the most likely etiology of this constellation of
signs and symptoms?
(A) Cytomegalovirus
(B) Gardnerella vaginalis
(C) Haemophilus ducreyi
(D) Mycobacterium tuberculosis
(E) Neisseria gonorrhoeae

The answer is C: Haemophilus ducreyi. Chancroid, also called
soft chancre, is caused by H. ducreyi, a Gram-negative bacillus.
This disease is rare in the United States but is common in underdeveloped
countries. Usually 3 to 5 days after sexual congress
with an infected partner, single or sometimes multiple small,
vesiculopustular lesions appear on the cervix, vagina, vulva, or
perianal region. Histologic examination reveals a granulomatous
infl ammatory reaction. The lesion often ruptures to form a purulent
ulcer that is painful and bleeds easily. There may be associated
inguinal lymphadenopathy, fever, chills, and malaise. A
major complication is scar formation during the healing phase,
which is an outcome that sometimes causes urethral stenosis.
Mycobacterium tuberculosis (choice D) causes granulomatous salpingitis
but is not transmitted acutely, as in this case. The other
choices do not elicit granulomatous infl ammation.
Diagnosis: Chancroid


12 A routine cervical Pap smear taken during a gynecologic
examination of a 31-year-old woman shows numerous, loosely
arranged cells with high nuclear-to-cytoplasmic ratio. Colposcopy
shows white epithelium, punctation, and a mosaic pattern
in the transformation zone (shown in the image). Which
of the following is the most likely diagnosis?

A) Adenocarcinoma of endocervix
(B) Chronic cervicitis
(C) Clear cell adenocarcinoma
(D) Dysplasia of the cervix
(E) Herpes simplex virus infection


The answer is D: Dysplasia of the cervix. Cervical intraepithelial
neoplasia is defi ned as a spectrum of intraepithelial changes
that begins with minimal atypia and progresses through stages
of more marked intraepithelial abnormalities to invasive
squamous cell carcinoma. Dysplasia and carcinoma in situ can
often be detected on colposcopic examination by signs associated
with their altered epithelial and vascular changes: epithelial
mosaicism (irregular surface resembling inlaid woodwork)
and vascular dots differentiated from the surrounding tissue thelial lining gives rise to müllerian ducts, from which the
fallopian tubes, uterus, and vagina arise. Common epithelial
tumors of the ovary, in order of decreasing frequency, include:
serous tumors that resemble the epithelium of the fallopian
tube (choice B); mucinous tumors that mimic the mucosa of
the endocervix (choice E); endometrioid tumors that are similar
to glands of the endometrium (choice C); clear cell tumors
that display glycogen-rich cells that resemble endometrial
glands in pregnancy (choice A); and transitional cell tumors
that resemble the mucosa of the bladder (choice D). These
tumors are broadly classifi ed as benign, borderline (atypical
proliferative), and malignant.
Diagnosis: Mucinous cystadenoma of the ovary


A 36-year-old woman is evaluated for an abnormal Pap smear.
A cervical biopsy shows atypical squamous cells throughout
the entire thickness of the epithelium, with no evidence of epithelial
maturation (shown in the image). The basal membrane
appears intact. What is the appropriate diagnosis?
(A) Clear cell adenocarcinoma
(B) Invasive squamous cell carcinoma
(C) Mild dysplasia (cervical intraepithelial neoplasia [CIN]-1)
(D) Severe dysplasia (CIN-3)
(E) Squamous metaplasia of the transformation zone


The answer is D: Severe dysplasia (CIN-3). The normal process
by which the cervical squamous epithelium matures is
disturbed in CIN, as evidenced morphologically by changes
in cellularity, differentiation, polarity, nuclear features, and
mitotic activity. In CIN-1 (mild dysplasia), the most pronounced
changes are seen in the basal third of the epithelium.
However, in this case, abnormal cells are present throughout
the entire thickness of the epithelium. In CIN-2 (moderate
dysplasia, choice C), most of the cellular abnormalities are
in the lower and middle thirds of the epithelium. CIN-3 is
synonymous with severe dysplasia and carcinoma in situ and
shows abnormal cells occupying the full thickness of the epithelium,
with no evidence of epithelial maturation. Invasive
carcinoma (choice B) features extension of neoplastic cells
through the basal membrane. Dysplasia is not synonymous
with squamous metaplasia (choice E).
Diagnosis: Cervical intraepithelial neoplasia


14 A 35-year-old woman presents with a 6-week history of
vaginal discharge, which is occasionally blood tinged. Pelvic
examination reveals a 2-cm pedunculated, lobulated, and
smooth cervical growth; it is excised. Histologic examination
of the specimen would most likely reveal which of the
(A) Condyloma acuminatum
(B) Embryonal rhabdomyosarcoma
(C) Endocervical polyp
(D) Leiomyosarcoma
(E) Microglandular hyperplasia


The answer is C: Endocervical polyp. Endocervical polyp, the
most common cervical growth, appears as a single smooth or
lobulated mass, typically smaller than 3 cm in greatest dimension.
It typically manifests as vaginal bleeding or discharge.
The lining epithelium is mucinous, with varying degrees of
squamous metaplasia, but may feature erosions and granulation
tissue in women with symptoms. Simple excision or
curettage is curative. Cancer rarely arises in an endocervical
polyp (0.2% of cases). The other choices are rare causes of an
endocervical polyp.
Diagnosis: Endocervical polyp


15 A 28-year-old woman, who is 28 weeks pregnant, presents
with vaginal bleeding. She does not have a history of uterine
contractions. Pelvic examination reveals bright red blood in
the endocervical canal. An ulcerated exophytic mass is identifi
ed on the left side of the cervix. There is no evidence of direct
tumor extension into the parametrium. The pelvic lymph
nodes are slightly enlarged, raising the possibility of nodal
involvement by the tumor. A Caesarian section is performed,
followed by a radical hysterectomy. The cervix is shown in the
image. Which of the following is the best prognostic indicator
of survival in this patient?
(A) BRCA gene mutation
(B) Degree of keratinization
(C) Nodal involvement
(D) Presence of carcinoembryonic antigen (CEA) in serum
(E) Small cell rather than large cell carcinoma

The answer is C: Nodal involvement. Squamous cell carcinoma
is by far the most common type of cervical cancer. In
the earliest stages of cervical cancer, patients complain most
frequently of vaginal bleeding after intercourse or douching.
With more advanced tumors, the symptoms are referable to
the route and degree of spread. The clinical stage of cervical
cancer is the best prognostic index of survival. Radical hysterectomy
is favored for localized tumor, especially in younger
women; radiation therapy or combinations of the two are used
for more advanced tumors. Histologic or cytologic fi ndings
(choices B and E) are of secondary importance. CEA (choice D)
is not typically expressed by squamous carcinoma cells.
Diagnosis: Cervical cancer


16 Imaging studies establish a diagnosis of stage IV cervical cancer.
If untreated, which of the following will be the most likely
cause of death in the patient described in Question 15?
(A) Adrenal cortical failure
(B) Brain metastases
(C) Lung metastases
(D) Renal failure
(E) Vertebral fractures


The answer is D: Renal failure. Cervical cancer spreads by
direct extension and through lymphatic vessels and only
rarely by the hematogenous route, which would result in distant
metastases (choices A, B, C, and E). Local extension into
surrounding tissues (parametrium) results in ureteral compression.
The corresponding clinical complications of local extension
are hydroureter, hydronephrosis, and renal failure, the
last being the most common cause of death (50% of patients).
Bladder and rectal involvement may lead to fi stula formation.
Metastases to regional lymph nodes involve the paracervical,
hypogastric, and external iliac nodes.
Diagnosis: Cervical cancer


17 A 50-year-old nulliparous woman with a history of diabetes
complains that her menstrual blood fl ow is more abundant
than usual. During the last two menstrual cycles, she noticed
spotting throughout the entire cycle. The patient is obese
(BMI = 32 kg/m2), and her blood pressure is 160/100 mm Hg.
An ultrasound examination reveals a thickened endometrial
stripe with a polypoid mass in the uterine fundus. The patient
undergoes a hysterectomy. The uterus is opened to reveal a
partially necrotic mass (shown in the image). A biopsy of
the mass shows moderately differentiated adenocarcinoma.
Which of the following represents the most likely precursor of
this patient’s malignant disease?

A) Adenomyosis
(B) Atypical hyperplasia
(C) Chronic endometritis
(D) Complex hyperplasia
(E) Glandular metaplasia


The answer is B: Atypical hyperplasia. Endometrial hyperplasia
refers to a spectrum that ranges from simple glandular
crowding to conspicuous proliferation of atypical glands,
which are diffi cult to distinguish from early carcinoma. The risk
of developing endometrial cancer increases with progressively
higher degrees of endometrial hyperplasia. The progression
from hyperplasia free of atypia (complex type, choice D) to
invasive cancer requires some 10 years, but the corresponding
time for hyperplasia with atypia is only 4 years. Atypical
hyperplasia is characterized by cytologic atypia and marked
glandular crowding, frequently as back-to-back glands. The
epithelial cells are enlarged and hyperchromatic and have
prominent nucleoli and an increased nuclear-to-cytoplasmic
ratio. One fourth of these cases progress to adenocarcinoma.
Adenomyosis (choice A) and chronic endometritis (choice C)
are not premalignant conditions.
Diagnosis: Endometrial adenocarcinoma


Neoplastic cells obtained from the patient described in Question
17 would most likely show loss of function of which of
the following cell cycle control proteins?
(A) p53
(C) Rb
(E) WT-1


The answer is B: PTEN. The PTEN tumor suppressor gene,
which is hormonally regulated in normal endometrium, is an
informative biomarker for endometrial carcinogenesis. Loss of
this gene function occurs in two thirds of endometrial carcinomas.
PTEN knockout mice uniformly develop “endometrial
hyperplasia” that evolves to carcinoma in one fi fth of the
animals. Loss of Rb function (choice C) has been implicated
in HPV-induced cervical carcinoma. Mutations in p53 (choice
A) are found in many tumors, but loss of p53 function is not
associated with endometrial carcinoma. Loss of WT-1 tumor
suppressor protein (choice E) is related to Wilms tumor.
Diagnosis: Endometrial adenocarcinoma


19 A 45-year-old obese woman (BMI = 32 kg/m2) with a history
of diabetes and poorly controlled hypertension complains of
increased menstrual blood fl ow of 3 months in duration. An
endometrial biopsy is shown in the image. Which of the following
most likely accounts for the pathogenesis of endometrial
hyperplasia in this patient?
(A) Excess estrogen stimulation
(B) Exposure to exogenous progestational agents
(C) History of chronic endometritis
(D) History of oral contraceptive use
(E) Prenatal exposure to diethylstilbestrol


The answer is A: Excess estrogen stimulation. Endometrial
hyperplasia and adenocarcinoma are frequently associated
with exogenous or endogenous estrogen excess. For example,
endometrial hyperplasia may result from anovulatory cycles,
polycystic ovary syndrome, an estrogen-producing tumor, or
obesity. In such cases, therapy aimed at the primary disease
may alleviate the estrogenic stimulation. Estrogenic stimulation
of the endometrium beyond the 2-week interval of a normal
proliferative menstrual cycle causes progressive changes
that have been associated with a 2- to 10-fold increased risk of
endometrial cancer. In contrast to benign hyperplasia, endometrial
intraepithelial neoplasia (EIN) is recognized as monoclonal
neoplastic growth of genetically altered cells. The other
choices do not predispose to endometrial hyperplasia, EIN, or
Diagnosis: Endometrial hyperplasia


20 A 33-year-old woman with a history of menorrhagia presents
with a 6-month history of increasing fatigue. A CBC reveals
a hypochromic, microcytic anemia (hemoglobin = 8 g/dL).
Bimanual pelvic examination reveals an enlarged uterus with
multiple, irregular masses. A hysterectomy is performed, and a
sharply circumscribed fl eshy tumor is found within the uterine
wall (shown in the image). Which of the following is the most
likely cause of vaginal bleeding and anemia in this patient?
(A) Adenomyosis
(B) Cervical cancer
(C) Endometrial carcinoma
(D) Endometriosis
(E) Uterine leiomyoma


The answer is E: Uterine leiomyoma. Leiomyoma is a benign
tumor of smooth muscle origin that is colloquially known
as a fi broid. These tumors are rare before age 20 years, and
most regress after the menopause. Estrogen promotes the
growth of leiomyomas, although it does not initiate them.
Grossly, leiomyomas are fi rm, pale gray, whorled, and without
encapsulation. Most leiomyomas are intramural, but some are
submucosal, subserosal, or pedunculated. Submucosal leiomyomas
may cause bleeding, which is an effect due to ulceration
of the thinned, overlying endometrium. Adenomyosis
(choice A)does not present as a discrete mass. Endometrial
carcinoma (choice C) is much less common than leiomyoma.
Diagnosis: Leiomyoma of the uterus


21 A 52-year-old woman presents with chronic pelvic discomfort.
A CT scan of the pelvis shows a 10-cm, well-circumscribed
uterine mass. A hysterectomy is performed. On gross examination,
the mass is soft with areas of necrosis and irregular
borders extending into the myometrium. Histologic examination
demonstrates large zones of necrosis surrounded by a rim
of disorganized spindle cells that display numerous mitoses.
Immunohistochemical staining for smooth muscle actin is
positive. Which of the following is the most likely diagnosis?
(A) Adenomyosis
(B) Carcinosarcoma
(C) Endometrial stromal sarcoma
(D) Leiomyoma
(E) Leiomyosarcoma


The answer is E: Leiomyosarcoma. Leiomyosarcoma is a
malignant tumor of smooth muscle cell origin. It should be suspected
if an apparent leiomyoma is soft, shows areas of necrosis
on gross examination, has irregular borders, or does not bulge
above the surface when cut. The following features are considered
evidence for the diagnosis of leiomyosarcoma: (1) ten or
more mitoses per high-powered fi eld (HPF); (2) fi ve or more
mitoses per 10 HPFs, with nuclear atypia and necrosis; and
(3) myxoid and epithelioid smooth muscle tumors with fi ve
or more mitoses per 10 HPFs. Adenomyosis (choice A) refers
to the presence of benign endometrial glands and stroma in
the myometrium. Carcinosarcoma (choice B) is a mixed tumor
with malignant epithelial and stromal components. Endometrial
stromal sarcomas (choice C) show a vascular supporting
framework with neoplastic cells concentrically arranged around
blood vessel; they are much rarer than leiomyosarcoma.
Diagnosis: Leiomyosarcoma of the uterus


22. A 50-year-old woman complains of having intermenstrual
bleeding for 4 months. A Pap smear is normal. An ultrasound
examination shows a mass in the endometrial cavity.
The patient elects to undergo a hysterectomy. A large polyp
is found upon opening the endometrial cavity (shown in the
image). Histologic examination of this polyp will most likely
show which of the following pathologic fi ndings?


The answer is D: Endometrial glands and fi brous stroma.
Endometrial polyps occur most commonly in the perimenopausal
period and are virtually unknown before menarche.
They are thought to arise from endometrial foci that are
hypersensitive to estrogenic stimulation or unresponsive to
progesterone. In either case such foci do not slough during
menstruation and continue to grow. Microscopically, the core
of a polyp is composed of (1) endometrial glands, which often
are cystically dilated and hyperplastic; (2) a fi brous endometrial
stroma; and (3) thick-walled, coiled, dilated blood
vessels. The other choices may be observed occasionally in an
endometrial polyp.
Diagnosis: Endometrial polyp


23 A 40-year-old woman presents with a 5-year history of dysmenorrhea.
Physical examination and endocrine studies are
normal. A hysterectomy is performed. Histologic examination
of the uterine wall reveals areas of extensive adenomyosis.
Which of the following best describes this patient’s uterine
(A) Benign neoplasm of glandular epithelial cells
(B) Displacement of endometrial glands and stroma
(C) Endometrial intraepithelial neoplasia
(D) Hyperplasia of trophoblast as a sequel of incomplete
(E) Premalignant uterine lesion composed of smooth muscle


The answer is B: Displacement of endometrial glands and
stroma. Adenomyosis refers to the presence of endometrial
glands and stroma within the myometrium. One fi fth of all
uteri removed at surgery show some adenomyosis. Microscopic
examination of these lesions reveals glands lined by
mildly proliferative to inactive endometrium and surrounded
by endometrial stroma with varying degrees of fi brosis. Many
patients with adenomyosis are asymptomatic; however, it is
not uncommon for patients to exhibit varying degrees of pelvic
pain, dysfunctional uterine bleeding, dysmenorrhea, and
dyspareunia. Adenomyosis does not represent a neoplastic
process (choices A, C, and E).
Diagnosis: Adenomyosis


24 A 60-year-old women presents with a 2-week history of uterine
bleeding. Gynecologic examination reveals an enlarged
uterus. The hysterectomy specimen shows a large polypoid
mass involving the endometrium and myometrium. Histologic
examination reveals malignant glands and malignant stromal
elements, including striated muscle and cartilage. What is the
appropriate diagnosis?
(A) Carcinosarcoma
(B) Endometrioid adenocarcinoma
(C) Leiomyosarcoma
(D) Pleomorphic adenoma
(E) Rhabdomyosarcoma


The answer is A: Carcinosarcoma. Carcinosarcoma is an
aggressive, mixed mesodermal tumor, in which the epithelial
and stromal components are both highly malignant. These
neoplasms are derived from multipotential stromal cells. The
overall 5-year rate survival is 25%. Pleomorphic adenoma
(choice D) is a mixed tumor of salivary gland. The other
choices do not feature biphasic components.
Diagnosis: Carcinosarcoma


25 A 25-year-old woman is referred to the gynecologist for treatment
of infertility. The patient is obese (BMI = 32 kg/m2) and
has pronounced facial hair. She states that she has always had
irregular menstrual periods. On gynecologic examination,
both ovaries are found to be symmetrically enlarged. This
patient’s ovaries would likely show which of the following
pathologic fi ndings?
(A) Bilateral endometriomas
(B) Cystic teratoma
(C) Mucinous cystadenoma
(D) Serous cystadenoma
(E) Subcapsular cysts


The answer is E: Subcapsular cysts. Polycystic ovary syndrome,
also known as Stein-Leventhal syndrome, describes
(1) clinical manifestations related to the secretion of excess
androgenic hormones, (2) persistent anovulation, and (3) ovaries
containing many small subcapsular cysts. It was described initially as a syndrome of secondary amenorrhea, hirsutism,
and obesity. The clinical presentation is now recognized to
be far more variable and includes amenorrheic women who
appear otherwise normal and, even rarely, have ovaries lacking
polycystic features. Up to 7% of women experience the
polycystic ovary syndrome, making this condition a common
cause of infertility. Unopposed acyclic estrogen secretion
in women with polycystic ovary syndrome results in an
increased incidence of endometrial hyperplasia and adenocarcinoma.
On gross examination, both ovaries are enlarged. On
cut section, the cortex is thickened and discloses numerous
cysts (typically 2 to 8 mm in diameter) arranged peripherally
around a dense core of stroma. The other choices are not typically
associated with Stein-Leventhal syndrome.
Diagnosis: Polycystic ovary syndrome


26 Endocrine studies of the woman described in Question 25
would most likely show which of the following results in the
(A) High levels of corticosteroids
(B) High levels of follicle-stimulating hormone
(C) High levels of luteinizing hormone
(D) Low levels of estrogens
(E) Low levels of corticosteroids


The answer is C: High levels of luteinizing hormone. Polycystic
ovary syndrome represents a state of functional ovarian
hyperandrogenism associated with increased levels of luteinizing
hormone (LH), although the increase in LH is probably a
result rather than a cause of the ovarian dysfunction. The central
abnormality is thought to be increased ovarian production
of androgens, but adrenal hypersecretion of androgens may
also contribute to the clinical manifestations.
Diagnosis: Polycystic ovary syndrome


27 A 50-year-old woman who has a family history of breast cancer
presents with a 6-month history of increasing abdominal
girth. On close questioning, she volunteers a history of
vague abdominal pain dating back 1 year. She has no children
and has never been pregnant. Bimanual pelvic examination
reveals a 10-cm right adnexal mass. Percussion of theabdomen indicates ascites. Aspiration cytology of the ascites
fl uid reveals malignant papillary structures with psammoma
bodies. A mutation in which of the following genes is most
likely associated with this patient’s malignant disease?
(B) p53
(C) Rb
(E) WT-1


The answer is A: BRCA1. Malignant papillary structures and
psammoma bodies (laminated calcifi ed concretions) in a
patient with ascites is most compatible with the diagnosis of
papillary serous cystadenocarcinoma of the ovary. The same
gene implicated in hereditary breast cancers, namely BRCA1,
has been incriminated in the pathogenesis of familial ovarian
cancer. Women who bear BRCA1 gene mutations tend to
develop ovarian cancer considerably earlier than women who
have sporadic ovarian cancer, but their prognosis is considerably
better. Mutations in the WT-1 tumor suppressor gene
(choice E) are related to Wilms tumor.
Diagnosis: Ovarian cancer, papillary serous cystadenocarcinoma


28 The patient described in Question 27 undergoes surgery to
have the mass removed. Histologic examination of the surgical
specimen is shown in the image. The arrow points to a
calcifi ed focus (psammoma body). This neoplasm most likely
originated from which of the following ovarian cells/tissues?
(A) Germ cells
(B) Granulosa cells
(C) Sertoli-Leydig cells
(D) Surface epithelium
(E) Theca cells


The answer is D: Surface epithelium. The tumor depicted is
a papillary serous cystadenocarcinoma. The most frequently
encountered ovarian tumors (e.g., benign and malignant
serous and mucinous neoplasms) arise from the surface
epithelium and are termed common epithelial tumors. Epidemiologic
studies suggest that common epithelial neoplasms
are related to repeated disruption and repair of the epithelial
surface during normal cyclic ovulation. Thus, these tumors
most commonly affl ict women who are nulliparous and, conversely,
occur least often in women in whom ovulation has
been suppressed (e.g., by pregnancy or oral contraceptives).
Germ cells (choice A) give rise to benign teratomas and a
variety of malignant tumors. The other cells give rise to sex
cord/stromal tumors.
Diagnosis: Ovarian cancer, papillary serous cystadenocarcinoma


29 Which of the following statements best characterizes the endocrine
status of the malignant cells in the patient described in
Questions 27 and 28?
(A) They are hormonally inactive.
(B) They cause arterial hypertension.
(C) They cause polyuria and polydipsia.
(D) They secrete polypeptide hormones.
(E) They secrete steroid hormones.


The answer is A: They are hormonally inactive. Ovarian
tumors that arise from the surface (germinal or celomic)
epithelium are hormonally inactive and do not produce endocrine
syndromes. Ovarian masses rarely cause symptoms until
they are large. When they distend the abdomen, they cause pain, pelvic pressure, or compression of regional organs. By the
time ovarian cancers are diagnosed, many have metastasized
to the surfaces of the pelvis, abdominal organs, or bladder.
Overall 5-year survival is only 35%.
Diagnosis: Ovarian cancer


30 A 50-year-old woman presents with a 1-month history of
intermittent vaginal bleeding. A Pap smear is normal. Pelvic
examination reveals a left adnexal mass. A uterine curettage
shows complex endometrial hyperplasia without atypia.
A CT scan of the abdomen reveals a 5-cm mass replacing the
left ovary. The patient undergoes hysterectomy and bilateral
salpingo-oophorectomy. Histologic examination of the ovarian
mass is shown in the image. Which of the following is the
appropriate pathologic diagnosis?

A) Dysgerminoma
(B) Endometrioid carcinoma
(C) Granulosa cell tumor
(D) Mucinous cystadenocarcinoma
(E) Sertoli-Leydig cell tumor

The answer is C: Granulosa cell tumor. Granulosa cell tumor
is the prototypical functional neoplasm of the ovary associated
with estrogen secretion. The tumor is derived from sex
cord stromal cells. Most granulosa cell tumors occur after the
menopause. A juvenile form occurs in children and young
women and has distinct clinical and pathologic features
(hyperestrogenism and precocious puberty). Microscopically,
granulosa cell tumors display haphazard orientation of the
nuclei about a central degenerative space (Call-Exner bodies),
which results in a characteristic follicular histologic pattern.
Three fourths of granulosa cell tumors secrete estrogens.
Consequently, endometrial hyperplasia is a common presenting
sign. Hyperplasia may progress to endometrial adenocarcinoma
if the functioning granulosa cell tumor remains
undetected. Sertoli-Leydig cell tumors (choice E) typically
secrete weak androgens. The other choices do not secrete
Diagnosis: Granulosa cell tumor of the ovary