Robbins - Unit 1 - Female Genital Tract

Question 1

1 A 24-year-old woman experiences sudden onset of severe lower abdominal pain. Physical examination shows no
masses, but there is severe tenderness in the right lower quadrant. A pelvic examination shows no lesions of the cervix or
vagina. Bowel sounds are detected. An abdominal ultrasound scan shows a 4-cm focal enlargement of the proximal right
fallopian tube. A dilation and curettage procedure shows only decidua from the endometrial cavity. Which of the following
laboratory findings is most likely to be reported for this patient?
□ (A) Cervical culture positive for Neisseria gonorrhoeae
□ (B) 69,XXY karyotype on decidual tissue
□ (C) Positive result of serum pregnancy test
□ (D) Positive result of serologic testing for syphilis
□ (E) Pap smear showing Candida

Answer 1

c) Positive result of serum prgnancy test

(C) The patient has an ectopic pregnancy. Conditions predisposing to ectopic pregnancy include chronic salpingitis
(which may be caused by gonorrhea, but a culture would be positive only with acute infection), intrauterine tumors, and
endometriosis. In about half of cases, there is no identifiable cause. Gestational trophoblastic disease associated with a
triploid karyotype, such as a complete or partial mole developing outside the uterus, is rare. Syphilis is not likely to
produce a tubal mass with acute symptoms (a gumma is a rare finding). Candida produces cervicitis and vaginitis and is
rarely invasive or extensive in immunocompetent patients.

Question 2

2 A 30-year-old, sexually active woman has had a mucopurulent vaginal discharge for 1 week. On pelvic examination, the
cervix appears reddened around the os, but no erosions or mass lesions are present. A Pap smear shows numerous
neutrophils, but no dysplastic cells. A cervical biopsy specimen shows marked follicular cervicitis. Which of the following
infectious agents is most likely to produce these findings?
□ (A) Chlamydia trachomatis
□ (B) Candida albicans
□ (C) Gardnerella vaginalis
□ (D) Herpes simplex virus
□ (E) Human papillomavirus
□ (F) Neisseria gonorrhoeae
□ (G) Trichomonas vaginalis

Answer 2

a) Chlamydia trachomatis

(A) The redness of the cervix, the inflammatory cells in the cervical discharge, and the biopsy findings indicate that the
patient has cervicitis. Chlamydia trachomatis is the most common cause of cervicitis in sexually active women.
Candidiasis, gonorrhea, and trichomoniasis also are common. Candidiasis often produces a scant, white, curdlike vaginal
discharge; gonorrhea may have an associated urethritis; and Trichomonas may produce a profuse homogeneous, frothy,
and adherent yellow or green vaginal discharge. Gardnerella is found in bacterial vaginosis, a common condition caused
by overgrowth of bacteria. Gardnerella infection produces a moderate, homogeneous, low-viscosity, adherent vaginal
discharge that is white or gray and has a characteristic “fishy” odor; “clue” cells are seen on a wet mount. Herpetic
infections are more likely to manifest as clear vesicles on the skin in the perineal region. Infection with human
papillomavirus is associated with condylomata, dysplasias, and carcinoma.

Question 3

3 A 36-year-old woman has had menorrhagia and pelvic pain for several months. She had a normal, uncomplicated
pregnancy 10 years ago. She has been sexually active with one partner for the past 20 years and has had no
dyspareunia. On physical examination, she is afebrile. A pelvic examination shows a symmetrically enlarged uterus, with
no apparent nodularity or palpable mass. A serum pregnancy test result is negative. What is the most likely diagnosis?
□ (A) Endometriosis
□ (B) Leiomyoma
□ (C) Endometrial hyperplasia
□ (D) Adenomyosis
□ (E) Chronic endometritis

Answer 3

d) adenomyosis

In adenomyosis, endometrial glands extend from the endometrium down into the myometrium. The process may be
superficial, but occasionally it is extensive, and the uterus becomes enlarged two to four times its normal size because of a
reactive thickening of the myometrium. In endometriosis, endometrial glands and stroma are found outside the uterus in
such sites as peritoneum, ovaries, and ligaments. A leiomyoma is a myometrial tumor mass that, if large, produces an
asymmetric mass. Endometrial hyperplasias do not increase the size of the uterus. Chronic endometritis does not extend
to the myometrium and does not increase uterine size.

Question 4

4. A 45-year-old woman has had menometrorrhagia for the past 3 months. On physical examination, there are no
   remarkable findings. The microscopic appearance of an endometrial biopsy specimen is shown in the figure. The patient
   undergoes a dilation and curettage, and the bleeding stops, with no further problems. What condition is most likely to
   produce these findings?
   □ (A) Ovarian mature cystic teratoma
   □ (B) Chronic endometritis
   □ (C) Failure of ovulation
   □ (D) Pregnancy
   □ (E) Use of oral contraceptives

Answer 4

c) Failure of ovulation

(C) This patient has endometrial hyperplasia, which results from excessive estrogenic stimulation. This lesion often
occurs with failure of ovulation about the time of menopause. Estrogen-secreting ovarian tumors also may produce
endometrial hyperplasia, but teratomas are not known for this phenomenon. Hyperplasias do not develop from
endometritis. A secretory pattern of the endometrium is seen in pregnancy, not the proliferative pattern shown in the figure.
Oral contraceptives contain small doses of estrogenic compounds that do not lead to hyperplasia.

Question 5

5. A 31-year-old woman has had dull, constant abdominal pain for 6 months. On physical examination, the only finding is a
   right adnexal mass. CT scan of the pelvis shows a 7-cm circumscribed mass that involves the right ovary and contains
   irregular calcifications. The right fallopian tube and ovary are surgically excised. The gross appearance of the ovary,
   which has been opened, is shown in the figure. What is the most likely diagnosis?
   □ (A) Mucinous cystadenoma
   □ (B) Choriocarcinoma
   □ (C) Dysgerminoma
   □ (D) Serous cystadenoma
   □ (E) Mature cystic teratoma

Answer 5

e) Mature cystic teratoma

(E) This patient has a cystic tumor with a mass of hair in the lumen. This is the typical appearance of a mature cystic
teratoma. This tumor also is known as a dermoid cyst because it is cystic and filled with hair and sebum derived from
ectodermal structures. Dermoid cysts are benign tumors of germ cell origin, and they can contain various ectodermally,
endodermally, and mesodermally derived tissues. A mucinous cystadenoma is often multiloculated and filled with mucoid
fluid, but it does not contain hair or calcifications. A choriocarcinoma is gestational in origin and is an aggressive neoplasm
that usually has a hemorrhagic appearance. A dysgerminoma is a solid, lobulated, tan-white mass; it is the female
equivalent of a male testicular seminoma. A serous cystadenoma is usually a unilocular cyst filled with clear fluid and little
else.

Question 6

6 A healthy 52-year-old woman has had a feeling of pelvic heaviness for the past 11 months. There is no history of
abnormal bleeding, and her last menstrual period was 8 years ago. Her physician palpates an enlarged nodular uterus on
bimanual pelvic examination. A Pap smear shows no abnormalities. Pelvic CT scan shows multiple solid uterine masses;
there is no evidence of necrosis or hemorrhage. A total abdominal hysterectomy is performed. Based on the gross
appearance of the mass shown in the figure, what is the most likely diagnosis?
Robbins & Cotran Review of Pathology Pg. 453
□ (A) Metastases
□ (B) Endometriosis
□ (C) Infiltrative leiomyosarcoma
□ (D) Multiple leiomyomas
□ (E) Adenomyosis

Answer 6

d) Multiple leiomas

(D) The masses shown are well circumscribed, suggesting the presence of multiple benign tumors. Leiomyomas
(“fibroids”) can be present in one third to one half of all women. They tend to enlarge during the reproductive years, and then stop growing or involute after menopause. Most are asymptomatic. They are a common incidental finding in a uterus
removed for another reason. Metastases of this size and location are unlikely to occur in a healthy-appearing individual.
The small implants of endometriosis rarely exceed 1 to 2 cm in diameter; when a large mass forms, it is cystic and filled
with “old” blood (“chocolate cyst”). A leiomyosarcoma is a rare tumor and is usually a large, solitary mass. Endometrial
glands and stroma that extend into the myometrium constitute adenomyosis, a process that tends to enlarge the uterus
diffusely, without nodularity.

Question 7

A 33-year-old woman comes to the physician for a routine health maintenance examination. On physical examination,
there are no abnormal findings. A Pap smear shows abnormalities; colposcopy and a biopsy are performed. The figure
shows the microscopic appearance of the biopsy specimen. Which of the following factors is likely to have contributed
most to the development of this lesion?
□ (A) Diethylstilbestrol (DES) exposure
□ (B) Recurrent Candida infections
□ (C) Early age at first intercourse
□ (D) Multiple pregnancies
□ (E) Postmenopausal estrogen therapy

Answer 7

c) early age at first intercourse

The figure shows cervical intraepithelial neoplasia (CIN) III because the dysplasia involves the full thickness of the
cervical epithelium. Such lesions arise more frequently in women who have had first intercourse at an early age, have
multiple sexual partners, or have a male partner with multiple sexual partners. These factors are believed to increase the
risk of infection with human papillomavirus (HPV), particularly types 16 and 18. HPV-16 and HPV-18 are associated with
dysplasias and carcinomas of the cervix. Diethylstilbestrol (DES) exposure in utero is strongly associated with clear cell
adenocarcinomas of the vagina and cervix. Recurrent Candida infections are a nuisance, but they are not premalignant.
Pregnancy does not play a role in the development of cervical neoplasia. Most cervical dysplasias occur in premenopausal
women. Estrogen therapy and the use of oral contraceptives do not increase the risk of cervical dysplasia.

Question 8

8 A 62-year-old, obese, nulliparous woman had an episode of vaginal bleeding, which produced only about 5 mL of blood.
On pelvic examination, there appears to be no enlargement of the uterus, and the cervix appears normal. A Pap smear
shows cells consistent with adenocarcinoma. Which of the following conditions is most likely to have contributed to the
development of this malignancy?
□ (A) Endometrial hyperplasia
□ (B) Chronic endometritis
□ (C) Use of oral contraceptives
□ (D) Human papillomavirus infection
□ (E) Adenomyosis

Answer 8

a) endometrial hyperplasia

(A) The patient has an endometrial carcinoma. Estrogenic stimulation from anovulatory cycles, nulliparity, obesity, and
exogenous estrogens (in higher amounts than found in birth control pills) gives rise to endometrial hyperplasia and can
progress to endometrial carcinoma if the estrogenic stimulation continues. Atypical endometrial hyperplasias progress to
endometrial cancer in about 25% of cases. Chronic endometritis and human papillomavirus infection (which is associated
with squamous epithelial dysplasias and neoplasia) do not cause cancer. Adenomyosis increases the size of the uterus
and is not a risk for endometrial carcinoma.

Question 9

9 A 36-year-old primigravida developed peripheral edema late in the second trimester. On physical examination, her blood
pressure was 155/95 mm Hg. Urinalysis showed 2+ proteinuria, but no blood, glucose, or ketones. At 36 weeks, the
patient gives birth to a normal viable, but low-birth-weight, infant. Her blood pressure returns to normal, and she no longer
has proteinuria. Which of the following is most likely to be found on examination of the placenta?
□ (A) Chronic villitis
□ (B) Partial mole
□ (C) Hydrops
□ (D) Multiple infarcts
□ (E) Choriocarcinoma

Answer 9

d) multiple infarcts

(D) This patient has toxemia of pregnancy. Her condition is best classified as preeclampsia because she has
hypertension, proteinuria, and edema, but no seizures. The placenta tends to be small because of reduced maternal blood
flow and uteroplacental insufficiency; infarct and retroplacental hemorrhages can occur. Microscopically, the decidual
arterioles may show acute atherosis and fibrinoid necrosis. A chronic villitis is characteristic of a congenital infection such
as cytomegalovirus. In a partial mole, a fetus is present, but it is malformed and rarely liveborn. Placental hydrops often
accompanies fetal hydrops in conditions such as infections and fetal anemias. A fetus is not present in a choriocarcinoma

Question 10

10 A 22-year-old woman, G2, P1, is in the early second trimester. She has noted a small amount of vaginal bleeding for
the past week and has had marked nausea and vomiting for several weeks. On physical examination, the uterus measures
large for dates. Ultrasound shows intrauterine contents with a “snowstorm appearance,” and no fetus is identified. The
gross appearance of tissue obtained by dilation and curettage is shown in the figure. Which of the following substances is
most likely to be increased in the serum?
□ (A) α-Fetoprotein
□ (B) Thyroxine
□ (C) Estradiol
□ (D) Lactate dehydrogenase
□ (E) Human chorionic gonadotropin
□ (F) Human placental lactogen
□ (G) Acetylcholinesterase

Answer 10

e) HCG

(E) The figure shows a hydatidiform mole, or complete mole, with enlarged, grapelike villi that form the tumor mass in
the endometrial cavity. These trophoblastic tumors secrete human chorionic gonadotropin. Molar pregnancies result from
abnormal fertilization. In a complete mole, only paternal chromosomes are present. α-Fetoprotein is a marker for some
germ cell tumors that contain yolk sac elements. Thyroxine can be produced by the rare struma ovarii, which is a teratoma
composed predominantly of thyroid tissue. Estrogens can be elaborated by various ovarian stromal tumors, including
thecomas and granulosa cell tumors. More ominously, a decrease in maternal serum estriol suggests incipient abortion.
Lactate dehydrogenase may be increased in many conditions, such as liver and cardiac disease, but it is unknown as a
marker for genital tract lesions. Human placental lactogen is produced in small quantities in the developing placenta, and
serum levels typically are not measured. Neural tube defects can be distinguished from other fetal defects (e.g., abdominal
wall defects) by use of the acetylcholinesterase test on amniotic fluid obtained by amniocentesis. If acetylcholinesterase
and maternal serum α-fetoprotein are elevated, a neural tube defect is likely. If the acetylcholinesterase is not detectable,
another fetal defect is suggested

Question 11

11 A 46-year-old perimenopausal woman has had pelvic discomfort for 5 months. On physical examination, the uterus
appears slightly enlarged, and there are no adnexal masses. The cervix and vagina appear normal. A total abdominal
hysterectomy is performed. The figure shows the gross (A) and microscopic (B) features of the uterus. Which of the
following is most likely prevented by the hysterectomy performed on this patient?
□ (A) Iron deficiency
□ (B) Malignant transformation
□ (C) Endometriosis
□ (D) Osteoporosis
□ (E) Invasive mole
□ (F) Preeclampsia

Answer 11

A) Iron deficiency

(A) The figure shows a uterus with two well-circumscribed, gray-white masses in the myometrium. Microscopically, the
lesions show spindle-shaped cells in whorled bundles. The cells are uniform in size and shape, and mitotic figures are
scarce. These features are characteristic of a benign neoplasm—a leiomyoma. A leiomyosarcoma is not as well
demarcated, and its cut surface is not as homogeneous as that of a leiomyoma. Although leiomyomas are often
asymptomatic, leiomyomas that are submucosal in location may produce menometrorrhagia and chronic blood loss,
leading to iron deficiency anemia. A leiomyosarcoma arises de novo, not from a leiomyoma, and is usually a larger, more
irregular mass composed of more pleomorphic spindle cells with many mitoses. Endometriosis may cause pelvic pain, but
usually has an onset at an earlier age, and the hemorrhagic lesions are located outside the uterus. Decreased ovarian
Robbins & Cotran Review of Pathology Pg. 467
function after menopause accelerates bone loss, which may be severe enough to be termed osteoporosis, but this
process is not related to female genital tract neoplasia. About 10% of complete moles are complicated by invasive mole,
which is unlikely to produce a large, circumscribed mass. Preeclampsia with hypertension and proteinuria is associated
with abnormal decidual vascularization and placental ischemia.

Question 12

12 A 62-year-old childless woman noticed a blood-tinged vaginal discharge twice during the past month. Her last
menstrual period was 14 years ago. Bimanual pelvic examination shows that the uterus is normal in size, with no palpable
adnexal masses. There are no cervical erosions or masses. Her body mass index is 33. Her medical history indicates that
for the past 30 years she has had hypertension and type 2 diabetes mellitus. An endometrial biopsy specimen is most
likely to show which of the following?
□ (A) Adenomyosis
□ (B) Leiomyosarcoma
□ (C) Adenocarcinoma
□ (D) Squamous cell carcinoma
□ (E) Choriocarcinoma
□ (F) Malignant mixed müllerian tumor

Answer 12

c) adenocarcinoma

(C) Postmenopausal vaginal bleeding is a “red flag” for endometrial carcinoma. Such carcinomas often arise in the
setting of endometrial hyperplasia. Increased estrogenic stimulation is thought to drive this process, and risk factors
include obesity, type 2 diabetes mellitus, hypertension, and infertility. Adenomyosis is an extension of endometrial glands
and stroma into the myometrium, generally resulting in symmetric uterine enlargement. A submucosal leiomyosarcoma
could produce vaginal bleeding, but the uterus would be enlarged because leiomyosarcomas tend to be large masses.
Squamous carcinomas of the endometrium are rare. Choriocarcinomas are gestational in origin. Malignant mixed müllerian
tumors are much less common than endometrial carcinomas, but they could produce similar findings.

Question 13

13 A 23-year-old woman, G3, P2, has a spontaneous abortion at 15 weeks’ gestation. The male fetus is small for
gestational age and is malformed and has syndactyly of the third and fourth digits of each hand. The placenta also is
small, and shows 0.5-cm grapelike villi scattered among morphologically normal villi. Chromosomal analysis of placental
tissue is most likely to show which of the following karyotypes?
□ (A) 69,XXY
□ (B) 46,XX
□ (C) 23,Y
□ (D) 45,X
□ (E) 47,XXY
□ (F) 47,XY,+18

Answer 13

a) 69, XXY

(A) This patient has a partial hydatidiform mole, which results from triploidy (69 chromosomes). In contrast to a
complete mole, in which no fetus is present, a partial mole has a fetus because maternal chromosomes are present.
Survival of the fetus to term is rare. A partial mole may contain some grapelike villi or none. The fetus is usually malformed.
A 46,XX karyotype could be present in a complete mole or a normal male fetus. The 23,Y karyotype is typical of a sperm. A
fetus with Turner syndrome has a 45,X karyotype. Most female fetuses with loss of an X chromosome undergo
spontaneous abortion. Klinefelter syndrome has a 47,XXY karyotype, and male infants are liveborn. A 47,XY,+18
karyotype of trisomy 18 is associated with multiple congenital malformations, but not with a partial mole.

Question 14

14. A 54-year-old woman has had weight loss accompanied by abdominal enlargement for the past 6 months. She is
    concerned because of a family history of ovarian carcinoma. On physical examination, there are no lesions of the cervix,
    and the uterus is normal in size, but there is a left adnexal mass. An abdominal ultrasound scan shows a 10-cm cystic
    mass in the left adnexal region, with scattered 1-cm peritoneal nodules. Cytologic studies of peritoneal fluid show
    malignant cells consistent with a cystadenocarcinoma. Which of the following mutated genes is most likely a factor in the
    development of this neoplasm?
    □ (A) RAS
    □ (B) BRCA1
    □ (C) ERBB2 (HER2)
    □ (D) MYC
    □ (E) RB1

Answer 14

b) BRCA 1

(B) Some familial cases of ovarian carcinoma (usually serous cystadenocarcinoma) are associated with the
homozygous loss of the BRCA1 gene. This tumor-suppressor gene also plays a role in the development of familial breast
cancers. Familial syndromes account for less than 5% of all ovarian cancers, however. Mutations of the RAS and MYC
oncogenes occur sporadically in cancers. The ERBB2 gene may be overexpressed in ovarian cancers; however,
mutations of this gene do not give rise to familial tumors. The RB1 gene can be involved in familial forms of retinoblastoma
and osteosarcoma.

Question 15

15 A 4-year-old girl is brought to the physician by her parents, who noticed blood-stained underwear and “something”
protruding from her external genitalia. On physical examination, there are polypoid, grapelike masses projecting from the
vagina. Histologic examination of a biopsy specimen from the lesion shows small, round tumor cells, some of which have
eosinophilic straplike cytoplasm. Immunohistochemical staining shows desmin in these cells. What is the most likely
diagnosis?
□ (A) Neuroblastoma
□ (B) Embryonal rhabdomyosarcoma
□ (C) Condyloma acuminatum
□ (D) Vulvar intraepithelial neoplasm
□ (E) Infiltrating squamous cell carcinoma

Answer 15

B) Embryonal rhabdomyosarcoma

(B) Embryonal rhabdomyosarcoma is an uncommon vaginal tumor found in girls younger than 5 years old. Because it
forms polypoid, grapelike masses, it is sometimes called sarcoma botryoides. Histologically, it is a small, round, blue-cell
tumor that shows skeletal muscle differentiation in the presence of muscle-specific proteins such as desmin.
Neuroblastomas also are small blue-cell tumors, but they occur in the adrenal glands or extra-adrenal sympathetic chain.
Condylomata acuminata are caused by sexually transmitted human papillomavirus and rarely occur in such young
patients. Vulvar intraepithelial neoplasm is a carcinoma in situ of the vulvar skin. It occurs in older patients. Invasive
squamous cell carcinomas are rare in very young patients, and they show histologic evidence of squamous epithelial
differentiation.

Question 16

16 A 42-year-old woman has had menometrorrhagia for the past 2 months. She has no history of irregular menstrual
bleeding, and she has not yet reached menopause. On physical examination, there are no vaginal or cervical lesions, and
the uterus appears normal in size, but there is a right adnexal mass. An abdominal ultrasound scan shows the presence of
a 7-cm solid right adnexal mass. Endometrial biopsy shows hyperplastic endometrium, but no cellular atypia. What is the
most likely diagnosis?
□ (A) Mature cystic teratoma
□ (B) Endometrioma
□ (C) Corpus luteum cyst
□ (D) Metastasis
□ (E) Granulosa-theca cell tumor
□ (F) Struma ovarii

Answer 16

e) granulosa-theca cell tumor

(E) The mass is probably producing estrogen, which has led to endometrial hyperplasia. Estrogen-producing tumors of
the ovary are typically sex cord tumors, such as a granulosa-theca cell tumor or a thecoma-fibroma, the former more often
being functional. Teratomas can contain various histologic elements, but not estrogen-producing tissues. Endometriosis
can give rise to an adnexal mass called an endometrioma, which enlarges over time. Endometrial glands are hormonally
sensitive, but they do not produce hormones. Corpus luteum cysts are common, but they are unlikely to produce
estrogens. Metastases to the ovary do not cause increased estrogen production. A struma ovarii is a variant of a teratoma
in which more than half the mass is thyroid tissue, which may be functional and cause hyperthyroidism.

Question 17

17 A 19-year-old woman has had pelvic pain for 1 week. A pelvic examination shows mild erythema of the ectocervix. A
Pap smear shows many neutrophils, but no dysplastic cells. A cervical culture grows Neisseria gonorrhoeae. If the
infection is not adequately treated, the patient will be at increased risk for which of the following complications?
□ (A) Ectopic pregnancy
□ (B) Dysfunctional uterine bleeding
□ (C) Cervical carcinoma
□ (D) Endometrial hyperplasia
□ (E) Endometriosis
□ (F) Placenta previa

Answer 17

a) ectopic pregnancy

(A) Gonorrheal infections can lead to salpingitis and pelvic inflammatory disease with scarring. This predisposes to
ectopic pregnancy. Gonorrhea and other genital tract infections do not cause dysfunctional bleeding. Gonorrhea does not
carry the risk of dysplasias or carcinomas that human papillomavirus infection does. Gonorrhea and other infections do not
contribute to endometrial hyperplasia. The actual cause of endometriosis is unknown, but infection does not seem to play
Robbins & Cotran Review of Pathology Pg. 468
a role in this process. Placenta previa results from low-lying implantation of the placenta and is not related to sexually
transmitted diseases.

Question 18

18 A 28-year-old, sexually active woman comes to her physician for a routine health maintenance examination. There are
no abnormal findings on physical examination. The patient has been taking oral contraceptives for the past 10 years. A
Pap smear shows a moderate dysplasia, or cervical intraepithelial neoplasia (CIN) II. What is the major significance of this
finding?
□ (A) A cervicitis needs to be treated
□ (B) The patient has an increased risk of cervical carcinoma
□ (C) Condylomata acuminata are probably present
□ (D) An endocervical polyp needs to be excised
□ (E) The patient should stop taking oral contraceptives

Answer 18

b) pt. has increased risk of cervical carcinoma

Dysplasias of the cervix should not be ignored because they naturally progress to more severe dysplasias and to
invasive carcinomas. Although not all cases progress, the physician should not take this chance. Dysplasias are strongly
related to human papillomavirus (HPV) infections, and HPV DNA can be found in about 90% of cases. In about 10% to
15% of cases, there is no evidence of HPV, and other factors may play a role in the development of the dysplasia. A
condyloma acuminatum also is an HPV-associated lesion, but it is usually caused by a distinct, low-risk type of HPV. With
such HPV infection, the Pap smear may show changes of cervical intraepithelial carcinoma (CIN) I. Cervicitis usually is due
to bacterial or fungal organisms and is not a significant risk of dysplasia or carcinoma. Endocervical polyps may produce
some bleeding, but typically show no dysplasia. Oral contraceptive use does not increase the risk of dysplasia
significantly.

Question 19

19 A 40-year-old, G5, P5 woman has noticed lower abdominal pain with fever for the past 2 days. She delivered a normal
term infant 1 week ago. On examination, she has a temperature of 37.4°C. There is a foul-smelling vaginal discharge.
Which of the following pathologic findings is she most likely to have?
□ (A) Cervical epithelial dysplasia
□ (B) Endometrial neutrophilic infiltrates
□ (C) Myometrial smooth muscle neoplasm
□ (C) Myometrial smooth muscle neoplasm
□ (D) Ovarian endometrioma
□ (E) Tubal granulomatous inflammation
□ (F) Vaginal trichomonads

Answer 19

b) endometrial neutrophilic infiltrates

(B) Acute endometritis in this case is the result of retained products of conception after delivery. Endometritis may
follow premature rupture of membranes with ascending infection to the uterine cavity. There is often polymicrobial infection
with organisms found in the vagina. Some cases of chronic endometritis may be associated with Neisseria and Chlamydia
infections and produce lymphoplasmacytic infiltrates within the endometrium. Cervical dysplasias are confined to the
epithelium and are asymptomatic so that detection is by Pap smear. A myometrial neoplasm is unlikely to produce acute
inflammation. An ovarian endometrioma is a mass lesion resulting from continued hemorrhage into a focus of
endometriosis, but this mass lesion is not associated with pregnancy, and endometriosis is a cause for infertility.
Mycobacterium tuberculosis infection may spread to the female genital tract, most often the fallopian tube, but acute signs
are unlikely to be present, and inflammation of the tube can be a cause for infertility. Vaginitis may produce acute
inflammation with discharge, but trichomonal infections typically are associated with a watery gray-to-green discharge.

Question 20

20 A 25-year-old woman has experienced discomfort during sexual intercourse for the past month. On physical
examination, there are no lesions of the external genitalia. Pelvic examination shows a focal area of swelling on the left
posterolateral inner labium that is very tender on palpation. A 3-cm cystic lesion filled with purulent exudate is excised. In
which of the following structures is this lesion most likely to develop?
□ (A) Bartholin’s gland
□ (B) Gartner duct
□ (C) Hair follicle
□ (D) Urogenital diaphragm
□ (E) Vestibular bulb

Answer 20

a) Bartholin’s gland

(A) Bartholin’s glands may become obstructed, inflamed, and cystic because of abscess formation. A Gartner duct cyst
may form in the lateral vaginal wall from the remnant of a wolffian duct; the cyst is filled with fluid and is not inflamed. Hair
follicles are not present at the inner labia. The Bartholin’s gland lies just inferior to the fascia of the urogenital diaphragm
and just anterior to the vestibular bulb, which is not glandular and does not become cystic.

Question 21

21 A 58-year-old woman has had dull pain in the lower abdomen for the past 6 months and minimal vaginal bleeding on
three occasions. Her last menstrual period was 14 years ago. Pelvic examination shows a right adnexal mass, and the
uterus appears normal in size. An abdominal ultrasound scan shows an 8-cm solid mass. A total abdominal hysterectomy
is performed, and the mass is diagnosed as an ovarian granulosa-theca cell tumor. Which of the following additional
lesions is most likely to be found in the excised specimen?
□ (A) Condylomata acuminata of the cervix
□ (B) Endometrial hyperplasia
□ (C) Metastases to the uterine serosa
□ (D) Bilateral chronic salpingitis
□ (E) Partial mole of the uterus

Answer 21

b) endometrial hyperplasia

Most granulosa-theca cell tumors are hormonally active and secrete estrogens that can lead to endometrial
hyperplasia or carcinoma. Most of these tumors also are benign and do not metastasize. A condyloma acuminatum is
related to infection with human papillomavirus and is more likely to occur in younger, sexually active women. In most
cases, chronic salpingitis is related to sexually transmitted infections, such as gonorrhea. A partial mole is an uncommon
form of gestational trophoblastic disease and occurs only in reproductive-age women.

Question 22

22 A 43-year-old woman has had postcoital bleeding for 6 months. She experienced menarche at age 11 and has had 12
sexual partners during her life. She continues to have regular menstrual cycles without abnormal intermenstrual bleeding.
Pelvic examination shows a focal, slightly raised area of erythema on the cervix at the 5 o’clock position. A Pap smear
shows high-grade cervical intraepithelial neoplasia (CIN III). In situ hybridization performed on cells from the cervix shows
the presence of human papillomavirus type 16. If the cervical lesion is not treated, which of the following malignancies is
she at greatest risk of developing?
□ (A) Clear cell carcinoma
□ (B) Immature teratoma
□ (C) Krukenberg tumor
□ (D) Leiomyosarcoma
□ (E) Papillary serous cystadenocarcinoma
□ (F) Sarcoma botryoides
□ (G) Squamous cell carcinoma

Answer 22

g) squamous cell carcinoma

(G) This woman has several risk factors for the development of cervical squamous cell carcinoma, including multiple
sexual partners, documented infection of the cervix with high-risk human papillomavirus (HPV) type 16, and diagnosis of a
high-grade squamous intraepithelial neoplasm. The remaining choices are not related to HPV infection. Clear cell
carcinomas of the cervix are uncommon; some are associated with maternal use of diethylstilbestrol (DES) in pregnancy.
An immature teratoma arises in the ovary. A Krukenberg tumor is a form of metastasis to the ovary. Leiomyosarcomas are
rare and typically arise in the myometrium, although they can form in the cervix. Cystadenocarcinomas arise in the ovary.
Sarcoma botryoides is a vaginal lesion that typically occurs in young girls.

Question 23

23 An 18-year-old woman has had pelvic discomfort for several months. On pelvic examination, there is a 10-cm right
adnexal mass. An abdominal CT scan shows the mass to be solid and circumscribed. On surgical removal, the mass is
solid and white, with small areas of necrosis. Microscopically, it contains mostly primitive mesenchymal cells along with
some cartilage, muscle, and foci of neuroepithelial differentiation. What is the most likely diagnosis?
□ (A) Brenner tumor
□ (B) Dysgerminoma
□ (C) Granulosa cell tumor
□ (D) Immature teratoma
□ (E) Leiomyosarcoma
□ (F) Malignant mixed müllerian tumor
□ (G) Sarcoma botryoides

Answer 23

d) immature teratoma

(D) Immature teratomas are not cystic similar to mature teratomas. Tissues derived from multiple germ cell layers are
present, however, as in all teratomas. The presence of neuroectodermal tissues in immature teratomas is typical. The less
differentiated and more numerous the neuroepithelial elements, the worse is the prognosis. Brenner tumors of the ovary
are uncommon solid tumors that contain epithelial nests resembling transitional cells of the urinary tract; most are benign.
Dysgerminomas are the female equivalent of male testicular seminomas. Granulosa cell tumors have cells that resemble
those in ovarian follicles and may secrete estrogens. Leiomyosarcomas are solid tumors of smooth muscle origin that are
Robbins & Cotran Review of Pathology Pg. 469
found most often in the myometrium. Malignant mixed müllerian tumors are typically uterine neoplasms that have glandular
and stromal elements; the malignant stromal component can be “heterologous” and may resemble mesenchymal cells not
ordinarily found in the myometrium, such as cartilage. Sarcoma botryoides resembles an embryonal rhabdomyosarcoma
and is typically a vaginal tumor of young girls.

Question 24

24 A 32-year-old woman has cyclic abdominal pain that coincides with her menses. Attempts to become pregnant have
failed over the past 5 years. There are no abnormal findings on physical examination. Laparoscopic examination shows
numerous hemorrhagic 0.2- to 0.5-cm lesions over the peritoneal surfaces of the uterus and ovaries. Which of the
following ovarian lesions is most likely to be seen during the laparoscopic procedure?
□ (A) Fibroma
□ (B) Brenner tumor
□ (C) Endometriotic cyst
□ (D) Krukenberg tumor
□ (E) Mature cystic teratoma
□ (F) Mucinous cystadenocarcinoma

Answer 24

c) endometriotic cyst

(C) This woman has endometriosis, a condition in which functional endometrial glands are found outside the uterus.
Common sites include ovaries, uterine ligaments, rectovaginal septum, and pelvic peritoneum. These glands respond to
ovarian hormones; cyclic abdominal pain coincides with menstruation. Recurrent hemorrhages are followed by scarring
and the formation of fibrous adhesions in the pelvis. This may cause distortion of the ovaries and fallopian tubes and may
lead to infertility. One common variation is formation of an endometrioma, or “chocolate cyst,” which represents a focus of
endometriosis that becomes a cystic lesion, its center filled with chocolate-brown sludge from the recurrent hemorrhage.
The remaining choices are not associated with endometriosis, although endometrioid tumors may form in foci of
endometriosis.

Question 25

25 A 37-year-old woman has noted increasing size of a red, pruritic lesion on her left labium over the past 7 months. On
examination, this rough, scaly lesion is 0.4 × 0.9 cm. On physical examination, the lesions are slightly raised, soft pink to
white in color, and 0.2 to 1 cm in diameter. The perineum appears normal; there is no lymphadenopathy, and there are no
rectal lesions. A Pap smear shows no abnormal findings. The lesion is excised; on microscopic examination, there is
infiltration of the lower dermis by large cells having pale blue to granular cytoplasm. What is the most likely diagnosis?
□ (A) Condylomata acuminata
□ (B) Extramammary Paget disease
□ (C) Lichen sclerosus et atrophicus
□ (D) Lichen simplex chronicus
□ (E) Vulvar intraepithelial neoplasia

Answer 25

b) Extramammary Paget dz

25 (B) In most cases, extramammary Paget disease is not associated with an underlying malignancy, in contrast to Paget
disease of the breast. In many cases, the Paget cells remain in the epithelium, often for years, creating an annoying itchy
red lesion, but local invasion and even metastases are possible. A condyloma is the result of HPV infection and leads to
koilocytotic atypia, but the cells of a condyloma are not malignant. Lichen sclerosis is a white patch of epithelial thinning
with dermal fibrosis and chronic inflammation that can be extensive enough to constrict the vaginal orifice; it may have an
autoimmune basis, and there is an increased risk for future development of a squamous carcinoma. Lichen simplex
chronicus is an area of epithelial hyperplasia that has no atypia and no association with malignancy. Vulvar intraepithelial
neoplasia has neoplastic cells extending the full thickness of the epithelium; it is related to HPV infection.

Question 26

26 A 31-year-old woman has had a whitish, globular, vaginal discharge for the past week. On pelvic examination, the
cervix appears erythematous, but there are no erosions or masses. A Pap smear shows budding cells and pseudohyphae.
No dysplastic cells are present. Which of the following infectious agents is most likely to produce these findings?
□ (A) Trichomonas vaginalis
□ (B) Ureaplasma urealyticum
□ (C) Candida albicans
□ (D) Chlamydia trachomatis
□ (E) Neisseria gonorrhoeae

Answer 26

c) Candida albicans

26 (C) The presence of pseudohyphae indicates a fungal infection. Candidal (monilial) vaginitis is common; this organism
is present in about 5% to 10% of women. The inflammation tends to be superficial, and there is typically no invasion of
underlying tissues. Infection with Trichomonas vaginalis can produce a purulent vaginal discharge, but the organisms are
protozoa and do not produce hyphae. Ureaplasma is a bacterial agent, as is Chlamydia, and both can produce cervicitis.
Neisseria gonorrhoeae, a gram-negative diplococcus, is the causative agent of gonorrhea

Question 27

27 A 57-year-old woman comes to the physician because she recently noticed a pale area of discoloration on the labia.
Pelvic examination shows the presence of a 0.7-cm flat, white area on the right labia majora. A biopsy specimen shows
Robbins & Cotran Review of Pathology Pg. 459
dysplastic cells that occupy about half the thickness of the squamous epithelium, with minimal underlying chronic
inflammation. In situ hybridization shows human papillomavirus type 16 DNA in the epithelial cells. What is the most likely
diagnosis?
□ (A) Lichen sclerosus et atrophicus
□ (B) Condyloma acuminatum
□ (C) Squamous hyperplasia
□ (D) Vulvar intraepithelial neoplasia
□ (E) Chronic vulvitis
□ (F) Contact dermatitis

Answer 27

d) vulvular intraepithlial neoplasia

27 (D) The presence of dysplastic cells occupying half of the thickness of the epithelium suggests vulvar intraepithelial
neoplasia (VIN). The incidence of these lesions has been increasing, probably because of more cases of human
papillomavirus (HPV) infections. Some VIN lesions may progress to invasive cancers. Lichen sclerosus is a vulvar
dystrophy characterized by thinning of the squamous epithelium and sclerosis of the dermis. A condyloma is usually a
raised, nodular lesion. It also is caused by HPV, principally HPV-6 and HPV-11. Similar to VIN, squamous hyperplasia,
another form of vulvar dystrophy, can appear as an area of leukoplakia, but no dysplastic changes are present. Chronic
inflammation does not produce dysplasia. A contact dermatitis typically produces reddish “bumps” of various sizes, with
irritation and itching that may persist for days or as long as 2 weeks.

Question 28

28 A 19-year-old, sexually active woman has had dyspareunia followed by vaginal bleeding for the past month. On pelvic
examination, a red, friable, 2.5-cm nodular mass is seen on the anterior wall of the upper third of the vagina. The
microscopic appearance of a biopsy specimen is shown in the figure. Which of the following conditions is likely to have
contributed most to the origin of this neoplasm?
□ (A) Diethylstilbestrol (DES) exposure
□ (B) Trichomonas vaginitis
□ (C) Polycystic ovaries
□ (D) Human papillomavirus infection
□ (E) Congenital adrenal hyperplasia

Answer 28

a) DES exposure

28 (A) The microscopic appearance is that of a malignant tumor containing cells with a clear cytoplasm. Vaginal clear cell
carcinomas are associated with exposure of the patient’s mother to diethylstilbestrol (DES) during pregnancy. These
tumors are generally first diagnosed in the late teenage years. Trichomonal infections do not give rise to neoplasia.
Polycystic ovary disease can lead to hormonal imbalances from excess androgen production, but vaginal neoplasms do
not arise in this setting. Infection with human papillomavirus is associated with squamous epithelial dysplasias and
malignancies, not with clear cell adenocarcinomas. Congenital adrenal hyperplasia can produce masculinization in girls,
manifesting in early childhood.

Question 29

29 A 35-year-old woman presents with infertility. She has had dysmenorrhea, dyspareunia and pelvic pain on defecation
for 4 years. Laparoscopic examination reveals red-blue nodules on the surface of the uterus and extensive adhesions
between ovaries and the fallopian tubes. Histologic examination of a biopsy from one of the nodules shows hyperplastic
endometrial glands and hemorrhage in the stroma. Molecular analysis of the biopsy material reveals hypomethylation of
the promoter regions of the genes that encode steroidogenic factor-1 and estrogen receptor-β. There are no mutations in
the PTEN, KRAS and hMLH1 genes. Which of the following is an appropriate treatment modality in this case?
□ (A) Aromatase inhibitors
□ (B) Chemotherapy
□ (C) Estrogen
□ (D) Progesterone
□ (E) Surgical removal

Answer 29

a) aromatase inhibitors

(A) This woman has classical symptoms and signs of endometriosis. Thirty to 40% of women present with infertility,
menstrual irregularities, and pelvic pain. The presence of endometrial tissue in the nodules confirms this diagnosis. The
glands in the nodules are hyperplastic but show no evidence of malignancy; in addition all the genes implicated in
Robbins & Cotran Review of Pathology Pg. 470
endometrial cancer are normal. Hypomethylation of the two genes, steroidogenic factor-1 and estrogen receptor-β is found
in endometriosis. These lead to over-production of prostaglandins and estrogens. Aromatase inhibitors are used to
suppress estrogen production. Lesions of endometriosis are not neoplastic and chemotherapy is not indicated.

Question 30

30 A 36-year-old woman has noticed that warty vulvar lesions have been increasing in size and number over the past 5
years. On physical examination, there are several 0.5- to 2-cm, red-pink, flattened lesions with rough surfaces present on
the vulva and perineum. One of the larger lesions is excised; its microscopic appearance is shown in the figure. Which of
the following infectious agents is most likely to produce these lesions?
□ (A) Human papillomavirus
□ (B) Chlamydia trachomatis
□ (C) Treponema pallidum
□ (D) Haemophilus ducreyi
□ (E) Candida albicans

Answer 30

a) HPV

(A) The epithelium shows typical features of infection with human papillomavirus—specifically, prominent perinuclear
vacuolization (koilocytosis) and angulation of nuclei. These lesions, called condylomata acuminata, may occur anywhere
on the anogenital surface, as single lesions or, more commonly, as multiple lesions. They are not precancerous.
Condylomata are associated with HPV infection, often types 6 and 11. Chlamydial infections may produce urethritis,
cervicitis, and pelvic inflammatory disease. Treponema pallidum is the infectious agent of syphilis, characterized by the
gross appearance of a “hard” chancre. Haemophilus ducreyi is the agent that produces the “soft” chancre of chancroid.
Candidal infections produce a vaginitis or cervicitis with exudate and erythema.

Question 31

31 A 35-year-old woman has a routine Pap smear for the first time. The results indicate that dysplastic cells are present,
and the lesion is consistent with cervical intraepithelial neoplasia (CIN) III. The patient is referred to a gynecologist, who
performs colposcopy and takes several biopsy specimens that all show CIN III. Conization of the cervix shows a focus of
microinvasion at the squamocolumnar junction. Based on these findings, what is the next step in treating this patient?
□ (A) Course of radiation therapy
□ (B) Hysterectomy
□ (C) Bone scan for metastatic lesions
□ (D) Pelvic exenteration
□ (E) No further therapy is indicated

Answer 31

E) No further therapy

(E) Microinvasive squamous cell carcinomas of the cervix are stage I lesions that have a survival rate similar to that of
in situ lesions. Such minimal invasiveness does not warrant more aggressive therapies. The likelihood of metastasis or
recurrence is minimal.

Question 32

32 A 20-year-old woman experienced menarche at age 14 and had regular menstrual cycles for several years. For the
past year, she has had oligomenorrhea and has developed hirsutism. She has noticed a 10-kg weight gain in the past 4
months. On pelvic examination, there are no vaginal or cervical lesions, the uterus is normal in size, and the adnexa are
prominent. A pelvic ultrasound scan shows that each ovary is about twice normal size, whereas the uterus is normal in
size. Which of the following conditions is most likely to be present?
□ (A) Immature teratomas
□ (B) Polycystic ovaries
□ (C) Krukenberg tumors
□ (D) Tubo-ovarian abscesses
□ (E) Ovarian cystadenocarcinomas

Answer 32

b) polycystic ovaries

(B) Polycystic ovarian disease is a disorder of unknown origin that is typically associated with oligomenorrhea, obesity,
and hirsutism. It is thought to be caused by abnormal regulation of androgen synthesis. Teratomas are mass lesions that
can be bilateral, but usually are not symmetric. Krukenberg tumors represent metastatic disease involving the ovaries,
usually from a primary site in the gastrointestinal tract, and are rare among patients of this age. Abscesses are usually
unilateral and do not account for the hormonal changes seen in this patient. Cystadenocarcinoma can be bilateral;
however, androgen production by ovarian tumors is rare except by the rare Sertoli-Leydig cell tumors.

Question 33

33 A 28-year-old woman sees her physician because she has had fever, pelvic pain, and a feeling of pelvic heaviness for
the past week. Pelvic examination shows a palpable left adnexal mass. Laparoscopy shows an indistinct left fallopian tube
that is part of a 5-cm circumscribed, red-tan mass involving the left adnexal region. Which of the following infectious
agents is most likely to produce these findings?
□ (A) Human papillomavirus
□ (B) Mycobacterium tuberculosis
Robbins & Cotran Review of Pathology Pg. 461
□ (C) Treponema pallidum
□ (D) Chlamydia trachomatis
□ (E) Candida albicans
□ (F) Herpes simplex virus
□ (G) Haemophilus ducreyi

Answer 33

d) Chlamydia

(D) Sexually transmitted diseases are the most common cause of inflammation of the fallopian tube. When the
incidence of gonorrhea caused by Neisseria gonorrhoeae decreases in a population, the proportion of cases of salpingitis
caused by Chlamydia and Mycoplasma increases. The fallopian tube can become distended and adherent to the ovary
and may form a tubo-ovarian abscess. These are features of pelvic inflammatory disease. Infection with human
papillomavirus is associated with squamous epithelial dysplasia and neoplasia of the genital tract. Mycobacterium
tuberculosis is an uncommon cause of salpingitis. Treponema pallidum infection causes syphilis, which does not produce
florid inflammation with mass effect. Candida infections are typically limited to the vagina and cervix and are superficial,
without invasion. Herpes simplex virus most often involves the external genitalia, but it may produce vaginal or cervical
lesions; it is unlikely to advance farther. Haemophilus ducreyi causes chancroid, which can produce erythematous
papules of the external genitalia or vagina, but grossly visible lesions may not be present in women.

Question 34

34 A 42-year-old woman has a Pap smear as part of a routine health maintenance examination. There are no remarkable
findings on physical examination. The Pap smear shows cells consistent with a high-grade squamous intraepithelial lesion
(HSIL) with human papillomavirus subtype 18. Cervical biopsy specimens are obtained, and microscopic examination
confirms the presence of extensive moderate dysplasia (CIN II) along with intense chronic inflammation with squamous
metaplasia in the endocervical canal. What is the most likely explanation for proceeding with cervical conization for this
patient?
□ (A) She is at risk for invasive carcinoma
□ (B) Human papillomavirus infection cannot be treated
□ (C) She is perimenopausal
□ (D) She has chronic cervicitis
□ (E) Her reproductive years are over

Answer 34

a) At risk for invasive carcinoma

(A) This patient’s cervical intraepithelial neoplasia (CIN) II may progress to invasive carcinoma in several years if not
treated, particularly because she has a high-risk subtype of HPV. Infection with HPV often drives this process, but the
presence of HPV alone does not determine therapy. HPV infection cannot be eradicated. Chronic cervicitis with squamous
metaplasia is not a malignant lesion and does not determine therapy in this case. The conization can preserve fertility in
women who are of childbearing age.

Question 35

35 A 20-year-old woman notices a bloody, brownish vaginal discharge. The next day, she sees a physician because of
shortness of breath. On physical examination, a 3-cm, red-brown mass is seen on the lateral wall of the vagina. A chest
radiograph shows numerous 2- to 5-cm nodules in both lungs. A biopsy specimen of the vaginal mass shows malignant
cells resembling syncytiotrophoblasts. Which the following proteins is most likely to be elevated in the serum?
□ (A) Human chorionic gonadotropin
□ (B) α-Fetoprotein
□ (C) Estradiol
□ (D) Testosterone
□ (E) Thyroxine
□ (F) Carcinoembryonic antigen

Answer 35

a) HCG

(A) This patient has a choriocarcinoma, an aggressive malignant trophoblastic tumor. Some of these tumors can arise
without evidence of pregnancy. Metastases in the vaginal wall and lungs and a hemorrhagic appearance are
characteristic. The syncytiotrophoblastic cells produce human chorionic gonadotropin. The α-fetoprotein level is elevated
in yolk sac tumors; estrogens are elevated in granulosa-theca cell tumors; androgens such as testosterone are elevated in
Leydig cell tumors; and thyroxine can be elevated in specialized teratomas that contain thyroid tissue (e.g., struma ovarii).
Carcinoembryonic antigen is a tumor marker that is more characteristic of visceral malignancies, such as colonic
adenocarcinoma.

Question 36

36 A 14-year-old girl began menstruation 1 year ago. She now has abnormal uterine bleeding, with menstrual periods that
are 2 to 7 days long and 2 to 6 weeks apart. The amount of bleeding varies from minimal spotting to a very heavy flow. On
physical examination, there are no remarkable findings. A pelvic ultrasound scan shows no abnormalities. Which of the
following is most likely to produce these findings?
□ (A) Endometrial polyp
□ (B) Anovulatory cycles
□ (C) Ectopic pregnancy
□ (D) Uterine leiomyomata
□ (E) Endometrial carcinoma

Answer 36

B) Anovulatory cycles

(B) Anovulatory cycles are a common cause of dysfunctional uterine bleeding in young women who are beginning
menstruation and in women approaching menopause. There is prolonged estrogenic stimulation that is not followed by
secretion of progesterone. Polyps are more common in older women. An ectopic pregnancy has acute findings and does
not have a prolonged course. Submucosal leiomyomas are a cause of less variable bleeding and are more likely to be
seen in older women. Endometrial carcinomas are rare in patients this age.

Question 37

37 A 51-year-old woman is concerned about pale areas on her labia that have been slowly enlarging for the past year.
The areas cause discomfort and become easily irritated. Physical examination shows pale gray to parchment-like areas of
skin that involve most of the labia majora, labia minora, and introitus. The introitus is narrowed. A biopsy specimen shows
thinning of the squamous epithelium, a dense band of upper dermal hyaline collagen, and scattered upper dermal mononuclear inflammatory cells. What is the most likely diagnosis?
□ (A) Pelvic inflammatory disease
□ (B) Lichen sclerosus et atrophicus
□ (C) Vulvar intraepithelial neoplasia
□ (D) Extramammary Paget disease
□ (E) Human papillomavirus infection

Answer 37

b) lichen sclerosis et atrophicus

(B) This patient has lichen sclerosus et atrophicus, which is most common in postmenopausal women. Although this
lesion is not premalignant, there is a 1% to 4% risk for women with this condition developing a squamous cell carcinoma.
In contrast, lichen simplex chronicus appears grossly as leukoplakia from squamous hyperplasia and is not associated with
malignancy. Pelvic inflammatory disease results from infection of internal genital organs with organisms such as Neisseria
gonorrhoeae and Chlamydia trachomatis. Vulvar intraepithelial neoplasia is marked by dysplastic squamous epithelial
changes. Extramammary Paget disease is rare; it produces reddish areas of scaling and is caused by the presence of
adenocarcinoma-like cells at the dermal-epidermal junction. Human papillomavirus infection is associated with
condylomata acuminata and with squamous epithelial dysplasias.

Question 38

38 A 40-year-old, nulliparous woman has had menorrhagia for the past 6 months. On physical examination her blood
pressure is 150/90 mm Hg: there are no cervical lesions or adnexal masses, and the uterus is normal in size. She is
155 cm (5 feet 1 inch) tall and weighs 74.5 kg (body mass index 38). A Pap smear shows atypical glandular cells of
uncertain significance. Hemoglobin A1c concentration is 9.8%. Endometrial biopsy shows complex hyperplasia with atypia;
molecular analysis detects loss of PTEN gene heterozygosity and enhanced AKT phosphorylation. What is further
biochemical analysis of her endometrium most likely to reveal?
□ (A) Decreased glucose uptake
□ (B) Decreased prostaglandin synthesis
□ (C) Increased aerobic glycolysis
□ (D) Increased glycogen storage
□ (E) Increased oxidative phosphorylation

Answer 38

c) increased aerobic glycolysis

(C) She has obesity, diabetes mellitus, and nulliparity—factors that contribute to development of endometrial
hyperplasias and carcinomas caused by hyperestrinism. She has complex endometrial hyperplasia with atypicality of cells
—a precursor for type I endometrial carcinoma. These lesions often have loss of PTEN tumor suppressor genes. In many,
if not all, cancers there is activation of aerobic glycolysis (i.e. glycolysis even in the presence of enough oxygen)—the socalled
“Warburg effect.” This is linked to loss of PTEN and offers a growth advantage to tumor cells. When aerobic
glycolysis is stimulated there is a reciprocal decrease in oxidative phosphorylation. Tumors are metabolically active, so
glucose uptake and glycogen utilization is enhanced and not reduced. In many cancers the COX-2 enzyme is upregulated
(e.g. colon cancer) and this leads to increased prostaglandins, but this is not related to PTEN loss.

Question 39

39 A 35-year-old woman has had increasing abdominal enlargement for the past 6 months. She states that she feels like
she is pregnant, but results of a pregnancy test are negative. On physical examination, there is abdominal distention with a
fluid wave. A pelvic ultrasound scan shows bilateral cystic ovarian masses, 10 cm on the right and 7 cm on the left. The
masses are surgically removed. On gross examination, the excised masses are unilocular cysts filled with clear fluid, and
papillary projections extend into the central lumen of the cyst. Microscopic examination shows that the papillae are
covered with atypical cuboidal cells that invade underlying stroma. Psammoma bodies are present. What is the most likely
diagnosis?
□ (A) Endometrioid tumor
□ (B) Clear cell carcinoma
□ (C) Cystadenocarcinoma
□ (D) Dysgerminoma
□ (E) Granulosa cell tumor
□ (F) Malignant mixed müllerian tumor
□ (G) Mature cystic teratoma
□ (H) Sertoli-Leydig cell tumor

Answer 39

c) cystadenocarcinoma

(C) Cystadenocarcinomas are common ovarian tumors that are often bilateral. The serous type occurs more frequently
than the mucinous type and is typically unilocular, whereas mucinous tumors are multilocular. Serous
cystadenocarcinomas account for more than half of ovarian cancers. As the name indicates, they are cystic in appearance.
They may be benign, borderline, or malignant. Benign tumors have a smooth cyst wall with small or absent papillary
projections. Borderline tumors have increasing amounts of papillary projections. Endometrioid tumors resemble
endometrial carcinomas and may arise in foci of endometriosis. Clear cell carcinomas are uncommon malignancies of the
vagina and cervix. Dysgerminomas are solid tumors of germ cell origin. Granulosa cell tumors can be solid and cystic and
may produce estrogens. Malignant mixed müllerian tumors are typically uterine neoplasms that have glandular and stromal
elements; the malignant stromal component can be “heterologous” and may resemble mesenchymal cells that are not
ordinarily found in the myometrium, such as cartilage. Mature cystic teratomas typically contain abundant hair and gooey
sebaceous fluid within the cystic cavity; surrounding tissues are formed from various germ layers. Sertoli-Leydig cell
tumors are rare, yellow-brown, solid masses; they may secrete androgens or estrogens.

Question 40

40 A 45-year-old woman has had a small amount of vaginal bleeding and a brownish, foul-smelling discharge for the past
Robbins & Cotran Review of Pathology Pg. 463
month. On pelvic examination, there is a 3-cm lesion on the ectocervix, shown in the figure. Microscopic examination of the
lesion is most likely to show which of the following?
□ (A) Adenocarcinoma
□ (B) Cervical intraepithelial neoplasia
□ (C) Chronic cervicitis
□ (D) Clear cell carcinoma
□ (E) Extramammary Paget disease
□ (F) Squamous cell carcinoma

Answer 40

f) Squamous cell carcinoma

(F) The lesion shown in the figure is large and ulcerative and projects into the vagina. It is most likely an invasive
squamous cell carcinoma that has infiltrated into the subepithelial region. Dysplastic changes confined to the epithelium
represent cervical intraepithelial neoplasia and do not form mass lesions. Glandular invasive lesions indicate an
adenocarcinoma, which is much less common than squamous cell carcinoma of the cervix. Chronic cervicitis has
erythema, but no mass effect. Clear cell carcinomas are uncommon and most likely found arising in the vagina.
Extramammary Paget disease usually arises on the vulva, producing an eczematous lesion, not a mass, because the
neoplastic cells are confined to the epithelium and to adjacent skin adnexa.

Question 41

41 A healthy 30-year-old woman comes to the physician for a routine health maintenance examination. No abnormalities
are found on physical examination. A screening Pap smear shows cells consistent with a low-grade squamous
intraepithelial lesion (LSIL). Subsequent cervical biopsy specimens confirm the presence of cervical intraepithelial
neoplasia (CIN) I. Which of the following risk factors is most likely related to her Pap smear findings?
□ (A) Oral contraceptive use
□ (B) Diethylstilbestrol (DES) exposure
□ (C) Vitamin B12 (cobalamin) deficiency
□ (D) Prior treatment for squamous cell carcinoma
□ (E) Multiple sexual partners

Answer 41

e) multiple sex partners

(E) Cervical intraepithelial neoplasia (CIN) I represents minimal (mild) dysplasia and is a potentially reversible process.
Dysplasias are preneoplastic and may progress to carcinomas if not treated. Risk factors for cervical dysplasias and
carcinoma include early age at first intercourse, multiple sexual partners, and a male partner with multiple previous sexual
partners. These factors all increase the potential for infection with human papillomavirus. Use of oral contraceptives does
not cause cervical dysplasia or carcinoma. Diethylstilbestrol (DES) exposure is a factor in the development of clear cell
Robbins & Cotran Review of Pathology Pg. 472
carcinomas of the vagina and cervix. A vitamin B12 deficiency may produce some megaloblastic epithelial changes, but not
dysplasia. Treatment of carcinomas does not result in dysplasia.

Question 42

42 A 24-year-old woman has had lesions of the external genitalia that first appeared several years ago, after she
vacationed at a resort near Negril, Jamaica, where she goes every year. The figure shows the gross appearance of the
external genitalia (A) and histologic features (B) of an excised lesion. Which of the following factors is likely to have
contributed most to the development of these lesions?
□ (A) Lack of menstrual cycles
□ (B) Inheritance of a faulty tumor-suppressor gene
□ (C) Poorly controlled diabetes mellitus
Robbins & Cotran Review of Pathology Pg. 464
□ (D) Exposure to ultraviolet light
□ (E) Sexual intercourse

Answer 42

e) sex

(E) The lesions shown are condylomata acuminata, which are often multiple and can become several centimeters in
diameter. They also are known as genital or venereal warts and are the result of infection with human papillomavirus
(HPV) acquired during sexual intercourse. The presence of HPV-infected cells is indicated by koilocytotic change. These
cells have cytoplasmic vacuolation. Although not premalignant, condylomata acuminata can be present along with other
lesions caused by HPV, such as squamous dysplasias and carcinomas. Anovulatory cycles can lead to irregular menstrual
periods, but not to vulvar skin changes. The best-known association of a faulty tumor-suppressor gene and a genital tract
cancer is the BRCA1 gene and ovarian carcinoma. Diabetic patients are more prone to infections, typically bacterial or
fungal, that do not produce nodular masses. Portions of this data are best left to the imagination of the reader to interpret

Question 43

43 A 40-year-old woman has noticed progressive enlargement of the abdomen over the past 5 months, although her diet
has not changed, and she has been exercising more. Physical examination shows no palpable masses, but a fluid wave is
present. Paracentesis yields 500 mL of slightly cloudy fluid. Cytologic examination of the fluid shows malignant cells. An
abdominal ultrasound scan shows a 15-cm multilobular mass that involves the right adnexal region. The uterus is normal in
size. The mass is surgically removed; the figure shows the gross features of a section of the excised mass. What is the
most likely diagnosis?
□ (A) Immature teratoma
□ (B) Mucinous cystadenocarcinoma
□ (C) Granulosa cell tumor
□ (D) Choriocarcinoma
□ (E) Dysgerminoma

Answer 43

b) mucinous cystadenocarcinoma

(B) Mucinous tumors of the ovary are of epithelial origin, are less common than serous tumors, and tend to be
multiloculated. The appearance of ascites suggests metastases, which is most common with surface epithelial neoplasms
of the ovary. Immature teratomas tend to be solid masses, as do granulosa cell tumors and dysgerminomas.
Choriocarcinomas rarely reach this size because they metastasize early; they are typically hemorrhagic

Question 44

44 A 35-year-old primigravid woman is in the seventh month of an otherwise unremarkable pregnancy when she develops
worsening headaches along with a 3-kg weight gain over 1 week. This morning she had a generalized seizure. On
physical examination, she is afebrile, but her blood pressure is 190/110 mm Hg (it was 120/80 mm Hg at a prenatal visit 1
month ago). She has edema involving her head and all extremities. Fetal heart tones of 140/min and fetal movement are
present. Laboratory studies show hemoglobin, 12.5 g/dL; hematocrit, 37.6%; MCV, 92 μm3; platelet count, 199,000/mm3;
serum creatinine, 1 mg/dL; potassium, 4.2 mmol/L; and glucose, 101 mg/dL. Urinalysis shows 2+ proteinuria, but no
hematuria, RBCs, WBCs, or casts. Which of the following is the most likely underlying factor in the causation of her
disease?
□ (A) Gestational trophoblastic disease
□ (B) Disseminated intravascular coagulation
□ (C) Adrenal cortical hyperplasia
□ (D) Placenta ischemia
□ (E) Ovarian neoplasm producing estrogen

Answer 44

d) placenta ischemia

(D) This woman has classic features of eclampsia defined by hypertension, edema, and proteinuria, typically with
onset in the third trimester. The addition of seizures defines eclampsia. Primigravid women are at greater risk. There is no
evidence in this case that primary renal disease could cause her hypertension, and the onset was sudden. Although the
precise cause of preeclampsia/eclampsia is unknown, placental ischemia is believed to be the underlying mechanism. This
is associated with shallow placentation and incomplete conversion of decidual vessels into high-volume channels required
to perfuse the placenta adequately. Untreated patients may go on to DIC. Gestational trophoblastic disease predisposes
patients to preeclampsia, but hydatidiform mole is excluded by the presence of a fetus, and a partial mole would be
unlikely to persist into the third trimester. Cushing syndrome with adrenal cortical hyperplasia could lead to hypertension
with sodium retention, but she does not have hypokalemia or hyperglycemia. Functional ovarian tumors, most commonly
estrogen-secreting, such as a granulosa cell tumor or thecoma, do not produce hypertension and proteinuria.

Question 45

45 A study of patients with postmenopausal uterine bleeding reveals that some of them have malignant neoplasms that
arise from prior atypical hyperplastic lesions. The peak incidence is between 55 and 65 years of age in women who have
obesity, hypertension, and/or diabetes mellitus. Molecular analysis reveals mutations of the PTEN tumor suppressor gene
in most of them. Their malignancies tend to remain localized for years before spread to local lymphatics. Which of the
following neoplasms is most likely to have these characteristics?
□ (A) Clear cell carcinoma
□ (B) Endometrioid carcinoma
□ (C) Leiomyosarcoma
□ (D) Mixed mullerian tumor
□ (E) Serous carcinoma
□ (F) Stromal sarcoma

Answer 45

b) endometrioid carcinoma

(B) Most endometrial cancers have the endometrioid pattern and are classified as type I endometrial carcinomas. They
arise in the setting of unopposed estrogen stimulation and may also have KRAS and β-catenin mutations as well as
microsatellite instability. In contrast, type II endometrial carcinomas occur at an older age in the background of atrophic
endometrium; they usually have a serous carcinoma pattern, but may also exhibit clear cell and mixed mullerian patterns,
a n d p53 mutations are common. Leiomyosarcomas and stromal sarcomas are far less common than endometrial
carcinomas, and they have no known risk factors.