Rubins - Female Reproductive System

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 inflammatory disease

1. The answer is C: Endometriosis. Endometriosis refers to the presence of benign endometrial glands and stroma outside the uterus. It afflicts 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 fibrosis, the affected surface may take on a grossly brown discoloration ("powder burns") and form cysts up to 15 cm in diameter, which contain chocolate-colored material ("chocolate cysts"). The other choices do not present as small hemorrhagic lesions in these anatomic sites. Diagnosis: Endometriosis

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 calcified focus (psammoma body). This neoplasm most likely originated from which of the following ovarian cells/tissues? (A) Germ cells (B) Granulosa cells (C) Sertoli-Leydigcells (D) Surface epithelium (E) Theca cells

28. 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 afflict 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.

29.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

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

3. The answer is B: Caruncle. This polypoid inflammatory 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 inflamed granulation tissue and ulceration and hyperplasia of transitional-cell or squamous epithelium. The other choices do not typically involve the urethral meatus. Diagnosis: Caruncle

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 salpingooophorectomy. 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

30. 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 hormones. Diagnosis: Granulosa cell tumor of the ovary

31. A 40-year-old woman presents with 6 months of increasing abdominal girth. Gynecologic examination reveals large bilateral ovarian masses. The patient undergoes bilateral oophorectomy. The pathology report reads "Krukenberg tumor," and the histopathologic findings are shown in the image. Which of the following tests would likely provide the highest diagnostic yield? (A) Serum AFP level (B) Biopsy of the cervix and endometrial curettage (C) Laparoscopy (D) Serum hCG level (E) Gastric endoscopy

31. The answer is E: Gastric endoscopy. Krukenberg tumors are ovarian metastases in which the tumor appears as nests of mucin-filled "signet ring" cells within a cellular stroma derived from the ovary. The stomach is the primary site in 75% of cases, and most of the other Krukenberg tumors are from the colon. Bilateral ovarian involvement and multinodularity are important clues to the diagnosis of metastatic carcinoma. Diagnosis: Krukenberg tumor of the ovary, gastric adenocarcinoma

32. A 15-year-old girl presents with left lower abdominal pain. She has noted recent enlargement of her breasts. Her last menstrual period was 10 weeks ago. She denies having had sexual intercourse. Serum levels of hCG are markedly elevated. Which of the following is the most likely diagnosis? (A) Choriocarcinoma (B) Hydatidiform mole (C) Mature cystic teratoma (D) Serous cystadenocarcinoma (E) Yolk sac carcinoma

32. The answer is A: Choriocarcinoma. Choriocarcinoma of the ovary is a rare tumor that mimics the epithelial covering of placental villi (cytotrophoblast and syncytiotrophoblast). Choriocarcinoma of germ cell origin manifests in young girls as precocious sexual development, menstrual irregularities, and rapid breast enlargement. In women of reproductive age, ovarian choriocarcinoma may represent metastasis from an intrauterine gestational tumor. Microscopically, it displays an admixture of malignant cytotrophoblast and syncytiotrophoblast. The syncytial cells of choriocarcinoma secrete hCG, which accounts for the frequent finding of a positive pregnancy test result. The tumor is highly aggressive but responds to chemotherapy. Hydatidiform mole secretes hCG but is a gestational trophoblastic disease. The other choices do not secrete hCG. Diagnosis: Choriocarcinoma of the ovary

33. A 20-year-old woman presents with increasing abdominal girth of 3 months in duration. Physical examination reveals ascites. A pelvic examination discloses a right ovarian mass. A 7-cm ovarian mass is removed at surgery. The histologic appearance of this ovarian neoplasm (shown in the image) most closely resembles which of the following malignant neoplasms seen in males? (A) Choriocarcinoma (B) Embryonal carcinoma (C) Immatureteratoma (D) Seminoma (E) Sertoli cell tumor

33. The answer is D: Seminoma. Dysgerminoma is the ovarian counterpart of testicular seminoma and is composed of activated germ cells. The neoplasm demonstrates large nests of monotonously uniform cells, which have a clear glycogen-filled cytoplasm and irregularly flattened central nuclei. Fibrous septa containing lymphocytes traverse the tumor. The other choices are also found in both sexes but do not show this histologic appearance. Diagnosis: Dysgerminoma

34. A 60-year-old woman presents with a 1-year history of vulvar itching, bleeding, and inflammation. Physical examination reveals a 1-cm exophytic mass on the labium major. Biopsy of the mass is shown in the image. These neoplastic cells would most likely express which of the following tumor markers? (A) Alpha-fetoprotein (B) Carcinoembryonic antigen (C) Cytokeratins (D) Estrogen/progesteronereceptors (E) Her2/neu polypeptides

34. The answer is C: Cytokeratins. The tumor depicted is a well- differentiated squamous cell carcinoma with keratin pearls. Squamous cell carcinoma is the most common primary malignant neoplasm of the vulva, and these tumors commonly express cytokeratins. Squamous cell carcinoma of the vulva is the end result of a multistep process that has its origin in vulvar intraepithelial neoplasia. Two thirds of larger tumors are exophytic; the others are ulcerative and endophytic. The tumors grow slowly and then extend to the contiguous skin, vagina, and rectum. They metastasize to the superficial inguinal and then the deep inguinal, femoral, and pelvic lymph nodes. The other tumor markers are not expressed by vulvar squamous cell carcinoma. Diagnosis: Squamous cell carcinoma

35. A 22-year-old woman presents to the emergency room with a 2-hour history of acute abdominal pain and vaginal bleeding. Her vital signs are normal. Physical examination reveals blood oozing from the vaginal opening. Laparotomy shows an enlarged right fallopian tube with hemorrhage and rupture. What is the most likely cause of hemorrhage in this patient? (A) Choriocarcinoma (B) Ectopic pregnancy (C) Infarcted tubal polyp (D) Intramural leiomyoma (E) Tubal adenocarcinoma

35. The answer is B: Ectopic pregnancy. Over 95% of ectopic pregnancies occur in the fallopian tube. Ectopic pregnancy results when the passage of the conceptus along the fallopian tube is impeded, for example, by mucosal adhesions or abnormal tubal motility secondary to inflammatory disease or endometriosis. The trophoblast readily penetrates the mucosa and tubal wall. The thin tubal wall usually ruptures by the 12th week of gestation. Tubal rupture is life threatening because it can result in rapid exsanguination. The other choices are rare. Diagnosis: Ectopic pregnancy

36. A 25-year-old woman in the last trimester of her first pregnancy presents for a routine obstetric evaluation. Her blood pressure is 160/100 mm Hg, and her pulse is 75 per minute. Physical examination shows pitting edema of the extremities. Urinalysis demonstrates 3+ proteinuria. Which of the following is the most dangerous complication of preeclampsia in this patient? (A) Amniotic fluid embolism (B) Chorioamnionitis (C) Choriocarcinoma (D) Disseminated intravascular coagulation (E) Rupture of the fallopian tube

36. The answer is D: Disseminated intravascular coagulation. Preeclampsia usually begins insidiously after the 20th week of pregnancy with (1) excessive weight gain occasioned by fluid retention, (2) increased maternal blood pressure, and (3) the appearance of proteinuria. As the disease progresses from mild to severe preeclampsia, the diastolic pressure persistently exceeds 110 mm Hg. Proteinuria is greater than 3 g per day, and renal function declines. Disseminated intravascular coagulation (DIC) often supervenes. DIC is a prominent feature of preeclampsia, manifested as fibrin thrombi in the liver, brain, and kidneys. The definitive therapy is the removal of the placenta, hopefully by normal delivery. The other choices are not complications of preeclampsia. Diagnosis: Preeclampsia

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 identified 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

15. 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 findings (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

16. 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 dis- tant 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 fistula 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 flow 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) Chronicendometritis (D) Complexhyperplasia (E) Glandular metaplasia

17. 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 difficult 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.

18. 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 (B) PTEN (C) Rb (D) RET (E) WT-1

18. 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 fifth 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 flow 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

19. 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 stimula- tion 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 carcinoma. Diagnosis: Endometrial hyperplasia

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 firm mass in the anterior wall of the upper vagina. Biopsy of the vaginal mass will most likely show which of the following pathologic findings? (A) Clear cell adenocarcinoma (B) Endodermal sinus tumor (C) Granular cell tumor (D) Mucinous adenocarcinoma (E) Squamous cell carcinoma

2. 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, reflecting 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

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 fleshy 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

20. The answer is E: Uterine leiomyoma. Leiomyoma is a benign tumor of smooth muscle origin that is colloquially known as a fibroid. 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 firm, pale gray, whorled, and without encapsulation. Most leiomyomas are intramural, but some are submucosal, subserosal, or pedunculated. Submucosal leio- myomas 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

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 findings? (A) Atypical endometrial hyperplasia (B) Chronic endometritis (C) Complex endometrial hyperplasia (D) Endometrial glands and fibrous stroma (E) Multiple foci of squamous metaplasia

The answer is D: Endometrial glands and fibrous 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 fibrous endometrial stroma; and (3) thick-walled, coiled, dilated blood vessels. The other choices may be observed occasionally in an endometrial polyp. Diagnosis: Endometrial polyp

41. A 33-year-old woman presents after 3 weeks of a painful genital lesion. Physical examination reveals a tender, erythematous, submucosal lesion of the labium minor (shown in the image). Which of the following is the most likely diagnosis? (A) Bartholin gland cyst (B) Caruncle (C) Condyloma acuminatum (D) Extramammary Paget disease (E) Lichen sclerosis

41. The answer is A: Bartholin gland cyst. The Bartholin glands produce a clear mucoid secretion that continuously lubricates the vestibular surface. The ducts are prone to obstruction and cyst formation. Infection of the cyst leads to abscess formation. Bartholin gland abscess was formerly associated with gonorrhea, but staphylococci, chlamydia, and anaerobes are now more frequently the cause. The other choices do not present as discrete submucosal nodules. Diagnosis: Bartholin gland abscess

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 infiltrates, 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

10. 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 fistulas. 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 inflammation but does not feature inclusion bodies. Gardnerella vaginalis (choice B) causes nonspecific 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 inflammation. 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

11. 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 under- developed 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 inflammatory 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 inflammation. 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

12. The answer is D: Dysplasia of the cervix. Cervical intraepithelial neoplasia is defined 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 surface by color and texture. The other choices do not demonstrate these gross morphologic features, although they may share dysplastic morphology. Diagnosis: Cervical intraepithelial neoplasia

13. 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

13. 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 epi- thelium, 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 following? (A) Condyloma acuminatum (B) Embryonal rhabdomyosarcoma (C) Endocervical polyp (D) Leiomyosarcoma (E) Microglandular hyperplasia

14. 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

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

21. 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 field (HPF); (2) five or more mitoses per 10 HPFs, with nuclear atypia and necrosis; and (3) myxoid and epithelioid smooth muscle tumors with five 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

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 pathology? (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 abortion (E) Premalignant uterine lesion composed of smooth muscle

23. The answer is B: Displacement of endometrial glands and stroma. Adenomyosis refers to the presence of endometrial glands and stroma within the myometrium. One fifth 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 fibrosis. 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) Pleomorphicadenoma (E) Rhabdomyosarcoma

24. 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 findings? (A) Bilateral endometriomas (B) Cystic teratoma (C) Mucinous cystadenoma (D) Serous cystadenoma (E) Subcapsular cysts

25. 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 serum? (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

26. 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 the abdomen indicates ascites. Aspiration cytology of the ascites fluid 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? (A) BRCA1 (B) p53 (C) Rb (D) VHL (E) WT-1

27. The answer is A: BRCA1. Malignant papillary structures and psammoma bodies (laminated calcified 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

37. A 17-year-old woman presents to her gynecologist with a 5-day history of vaginal bleeding. A home pregnancy test had been positive 1 week previously. This morning, the patient passed tissue with the appearance of small grapes. An ultrasound shows a dilated endometrial cavity but no evidence of a fetus. Endometrial evacuation of the uterus by suction curettage reveals grapelike clusters, with individual units measuring up to 5 mm in diameter (shown in the image). Cytogenetic examination of this tissue will most likely demonstrate which of the following genetic patterns? (A) Aneuploidy (B) Diploidy (C) Haploidy (D) Polyploidy (E) Triploidy

37. The answer is B: Diploidy. The term gestational trophoblastic disease embraces the spectrum of trophoblastic disorders that exhibit abnormal proliferation and maturation of trophoblast, as well as neoplasms derived from the trophoblast. Complete hydatidiform mole is a placenta that has grossly swollen chorionic villi, resembling bunches of grapes, in which there are varying degrees of trophoblastic proliferation. Complete mole results from the fertilization of an empty ovum that lacks functional DNA. The haploid (23,X) set of paternal chromosomes duplicates to 46,XX. Hence, most complete moles are homozygous 46,XX, but all of the chromosomes are of paternal origin. Since the embryo dies at a very early stage, fetal parts are absent. Malignant transformation (choriocarcinoma) develops in about 2% of cases. Triploidy (choice E) is encoun- tered in partial hydatidiform mole, but this diagnosis is ruled out by the absence of fetal tissue. Diagnosis: Complete hydatidiform mole

38. A 41-year-old immigrant woman from Asia presents for prenatal care. Her uterus is significantly larger than expected, and her serum hCG level is much higher than expected for her due date. No fetus is found on ultrasound examination. The abnormal placenta is removed. One month later, this patient presents to the emergency room with abdominal pain. Explor- atory laparotomy reveals rupture of the posterior uterine fundus with grape-like tissue extruding from the defect. Two liters of blood are present in the abdominal cavity. Histologic examination of the uterine mass is shown in the image. The arrows point to syncytial cells. Which of the following is the most likely diagnosis? (A) Carcinosarcoma (B) Choriocarcinoma (C) Embryonal carcinoma (D) Endometrial adenocarcinoma (E) Yolk sac carcinoma

38. The answer is B: Choriocarcinoma. Choriocarcinoma occurs in 1 in 30,000 pregnancies in the United States. In Asia, the frequency is far greater. Choriocarcinoma develops in about 2% of patients after a complete hydatidiform mole has been evacuated. Abnormal uterine bleeding is the most frequent initial indication that heralds choriocarcinoma. Occasion- ally, the first sign relates to metastases to the lungs or brain. In some cases, choriocarcinoma only becomes evident 10 or more years after the last pregnancy. The other choices are not sequelae of gestational trophoblastic disease. Diagnosis: Choriocarcinoma

39. A 34-year-old woman in the third trimester of her second pregnancy presents with a 1-week history of vaginal bleeding. The patient subsequently gives birth to a healthy female at 35 weeks of gestation. Immediately after delivery, the patient begins to hemorrhage transvaginally. The bleeding cannot be controlled, and the patient undergoes emergency hysterectomy. Examination of the hysterectomy specimen reveals penetration of chorionic villi deep into the myometrium, causing failure of the placental tissue to fully separate from the uterine wall. Which of the following best describes the uteroplacental abnormality seen in this patient? (A) Gestational choriocarcinoma (B) Abruptio placentae (C) Placenta increta (D) Placenta previa (E) Preeclampsia

39. The answer is C: Placenta increta. Abnormal adherence of the placenta to the underlying uterine wall is subclassified according to the depth of villous invasion into the myometrium. Placenta accreta refers to the attachment of villi to the myometrium without further invasion. Placenta increta (correct answer) defines villi invading the underlying myometrium. Placenta percreta describes villi penetrating the full thickness of the uterine wall. Most patients with placenta acreta have a normal pregnancy and delivery. However, bleeding in the third trimester is the most common presenting sign before delivery. In patients with placenta increta and percreta, substantial fragments of placenta may remain adherent to the uterine wall after delivery and are a source of postpartum hemorrhage. Abruptio placentae (choice B) refers to retroplacental hemorrhage in the absence of clinical hemorrhage. A deficiency of decidua at the implantation site may result from implantation of the placenta close to or over the cervix (placenta previa, choice D). Diagnosis: Placenta increta

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 filled with thick, viscous fluid 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

4. 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

40. A 30-year-old pregnant woman asks for information regarding mechanisms of sex determination during development. You explain that the Y chromosome determines male phenotype and that specific genital organs are inhibited from developing by hormones secreted by the developing testes. For example, müllerian-inhibiting substance released by Sertoli cells causes the involution of which of the following urogenital organs? (A) Breast (B) Clitoris (C) Ovary (D) Uterus (E) Vulva

40. The answer is D: Uterus. A central tenet of genital tract development in both sexes holds that the müllerian tubes will develop along female lines unless specifically impeded by embryonic testicular factors. In males, Sertoli cells in the developing testis produce müllerian-inhibiting substance, a protein that causes the müllerian ducts to regress. These ducts are the precursors of the fallopian ducts, uterus, and upper third of the vagina. Formation of the ovary (choice C) and vulva (choice E) is not affected by this hormone. Diagnosis: Sex determination, müllerian-inhibiting substance

42. A 22-year-old woman presents to the emergency room with an 8-hour history of high fever, vomiting, diarrhea, and night sweats. Her temperature on admission is 38.7°C (103°F), blood pressure 100/60 mm Hg, and respirations 24 per minute. She has a diffuse desquamative erythematous rash. Upon pelvic examination, the patient is found to be menstruating, and a tampon is in place. A purulent exudate is found within the vagina, which is cultured and grows Staphylococcus aureus. The hemoglobin is 12 g/dL, and the platelet count is 40,000/μL. Which of the following represents the most com- mon life-threatening complication of this patient's systemic disorder? (A) Acute tubular necrosis (B) Anemia (C) Cardiacarrhythmia (D) Disseminated intravascular coagulation (E) Pulmonary thromboembolism

42. The answer is D: Disseminated intravascular coagulation. Toxic shock syndrome is an acute, sometimes fatal disorder characterized by fever, shock, and a desquamative erythematous rash. In addition, vomiting, diarrhea, myalgias, neuro- logic signs, and thrombocytopenia are common. Certain strains of Staphylococcus aureus release an exotoxin called toxic shock syndrome toxin-1. In addition to the pathologic alterations characteristic of shock, the lesions of disseminated intravascular coagulation (DIC) are usually prominent. The disease was first recognized when long-acting tampons were first introduced, providing sufficient time for the staphylococcal organisms to proliferate. The other choices are less common and may be secondary to DIC. Diagnosis: Toxic shock syndrome

43. A 35-year-old woman complains of vaginal discomfort for 2 weeks. Physical examination reveals a scanty vaginal discharge. The fluid develops a "fishy" odor after treatment with 10% potassium hydroxide. A Pap smear taken during the pelvic examination shows squamous cells covered by coccobacilli ("clue" cells). Which of the following is the most likely etiology of vaginal discomfort in this patient? (A) Chlamydia trachomatis (B) Gardnerella vaginalis (C) Herpes simplex virus (D) Humanpapillomavirus (E) Trichomonas vaginalis

43. The answer is B: Gardenerella vaginalis. Sexual transmission of G. vaginalis, a Gram-negative coccobacillus, causes a substantial proportion of cases classified as nonspecific vaginitis. The diagnosis of Gardnerella infection is best established by identifying the organisms either in a wet mount specimen of a vaginal discharge or in a Papanicolaou-stained smear. The "clue cell" is pathognomonic and shows squamous cells covered by coccobacilli. Other aids to the diagnosis are a thin, homogeneous, milk-like vaginal discharge, a vaginal pH above 4.5, and the presence of a "fishy" odor from the discharge once alkalinized with 10% potassium hydroxide. Viruses (choices C and D) do not produce vaginal discharge. Choices A and E are not associated with "clue" cells. Diagnosis: Vaginitis, cervicitis

44. A 56-year-old woman presents with a 3-month history of vaginal bleeding. A cervical Pap smear reveals malignant, glandular epithelial cells. This patient most likely has a neoplasm originating in which of the following anatomic locations? (A) Cervix (B) Endometrium (C) Ovary (D) Vagina (E) Vulva

44. The answer is A: Cervix. Adenocarcinoma of the endocervix accounts for 20% of malignant cervical tumors. An increased incidence of cervical adenocarcinoma has been reported recently, with a mean age at presentation of 56 years. Most of the tumors are of the endocervical cell (mucinous) type, but the various subtypes have little importance for overall survival. Adenocarcinoma shares epidemiologic factors with squamous cell carcinoma of the cervix and spreads similarly. The tumors are often associated with adenocarcinoma in situ and are frequently infected with HPV types 16 and 18. Malignant cells derived from endometrial carcinoma (choice B) may be identified occasionally by cervical Pap smear. Diagnosis: Adenocarcinoma of the exocervix

45. A 20-year-old woman presents for a complete physical examination. During the pelvic examination, a 5-cm cystic mass is found in the region of the right ovary. Radiographs show focal calcifications in the mass. The tumor is removed, and the surgical specimen is shown in the image. Which of the following is the most likely diagnosis? (A) Dysgerminoma (B) Mature teratoma (C) Mucinou scystadenoma (D) Serous cystadenocarcinoma (E) Teratocarcinoma

45. The answer is B: Mature teratoma. Mature teratoma is a tumor of germ cell origin that differentiates toward somatic structures. More than 90% contain skin, sebaceous glands, and hair follicles. Half of the tumors exhibit smooth muscle, sweat glands, cartilage, bone, teeth, and respiratory tract epithelium. Tissues such as gut, thyroid, and brain are encountered less frequently. Haploid (postmeiotic) germ cells are believed to auto-fertilize, yielding diploid tumor cells that are genetically female (46,XX). Teratocarcinoma (choice E) features immature embryonic tissues and malignant stem cells. Diagnosis: Mature cystic teratoma of the ovary

46. A 43-year-old woman presents with a 6-month history of increasing abdominal girth. On physical examination, there is pronounced ascites. Pelvic examination reveals a left adnexal mass. A 6-cm ovarian tumor is removed. The tumor is solid and white. Histologically, it is composed of cells resembling normal ovarian stroma surrounded by collagen fibers. Which of the following is the appropriate diagnosis? (A) Fibroma (B) Granulosa cell tumor (C) Leiomyosarcoma (D) Papillarycystadenoma (E) Sertoli-Leydig cell tumor

46. The diagnosis is A: Fibroma. Fibromas are the most common ovarian stromal tumors, accounting for 75% of all stromal tumors and 7% of all ovarian tumors. They occur at all ages, with a peak in the perimenopausal period, and are virtually always benign. The tumors are solid, firm, and white. Microscopically, the cells resemble the stroma of the normal ovarian cortex, being composed of well-differentiated fibroblasts and variable amounts of collagen. Half of the larger tumors are associated with ascites and, rarely, with ascites and pleural effusions. Ascites is not a typical clinical feature of the other choices. Diagnosis: Fibroma of the ovary

51. A 55-year-old nulliparous woman presents for a physical examination. The patient is obese (BMI = 33 kg/m2) and has mild, adult-onset diabetes. Compared with multiparous women, this patient is at increased risk of developing a neoplasm in which of the following anatomic locations? (A) Cervix (B) Endometrium (C) Endosalpinx (D) Vagina (E) Vulva

51. The answer is B: Endometrium. The major form of endometrial cancer, endometrioid adenocarcinoma, is linked to prolonged estrogenic stimulation of the endometrium. In addition to treatment with exogenous estrogens, the most common risk factors are obesity, diabetes, nulliparity, early menarche, and late menopause. Each risk factor points to relative hyperestrinism. A high frequency of endometrial cancer is also found in women with estrogen-secreting granulosa cell tumors. In the case of obesity, the incidence correlates with body weight, with the risk being increased 10-fold for women who are more than 23 kg (50 lb) overweight. This effect of obesity is related to the enhanced aromatization of androstenedione to estrone in adipocytes. Cancers of the other organs are not related to estrogenic stimulation. Diagnosis: Endometrial adenocarcinoma

47. A 25-year-old woman presents with a 6-month history of increasing facial hair, deepened voice, and amenorrhea. Physical examination confirms virilization. A CT scan reveals a left ovarian mass. The tumor is surgically removed. It measures 10 cm in diameter and has a yellowish-tan appearance on cross section. The tumor is malignant and consists of two distinct cell populations. Some cells form solid nests, whereas others are arranged in trabecular and gland-like structures. Which of the following is the appropriate diagnosis? (A) Brennertumor (B) Dysgerminoma (C) Granulosa cell tumor (D) Mature cystic teratoma (E) Sertoli-Leydig cell tumor

47. The answer is E: Sertoli-Leydig cell tumor. Sertoli-Leydig cell tumor is a rare mesenchymal neoplasm of the ovary of low malignant potential that resembles the embryonic testis. It is the prototypical functional tumor associated with androgen secretion. The neoplastic cells typically secrete weak androgens (dehydroepiandrosterone), which accounts for the large tumor size required to achieve masculinizing signs. Sertoli- Leydig cell tumor occurs at all ages but is most common in young women of childbearing age. Nearly half of all patients with Sertoli-Leydig cell tumors exhibit androgenic effects (i.e., signs of virilization, evidenced by hirsutism, male escutcheon, enlarged clitoris, and deepened voice). The initial sign is often defeminization, which is manifested as breast atrophy, amenorrhea, and loss of hip fat. Once the tumor is removed, the signs disappear or are at least ameliorated. The other choices are not associated with virilization. Diagnosis: Sertoli-Leydig cell tumor

48. A 25-year-old woman presents with a 6-month history of breast enlargement and menstrual irregularities. An endometrial biopsy 3 months previously showed complex hyperplasia without atypia. A CT scan of the pelvis reveals a left ovarian mass, which is subsequently removed. The surgical specimen is solid and yellow, and measures 8 cm in diameter. Histologically, it is composed of lipid-laden theca cells. Following removal of this neoplasm, a marked decrease in serum levels of which of the following hormones would be expected in this patient? (A) Chorionic gonadotropin (B) Estrogen (C) Progesterone (D) Prolactin (E) Testosterone

48. The answer is B: Estrogen. Thecomas are functional ovarian tumors that arise in postmenopausal women. In most cases, they produce signs of estrogen production. Thecomas are solid tumors of 5 to 10 cm in diameter. The cut section is yellow, owing to the presence of many lipid-laden theca cells. Microscopically, the cells are large and oblong to round, with a vacuolated cytoplasm that contains lipid. Bands of hyalinized collagen separate nests of theca cells. Thecomas are almost always benign. Because of estrogen output by the tumor, thecomas in premenopausal women commonly cause irregularity in menstrual cycles and breast enlargement. Endometrial hyperplasia and cancer are well-recognized complications. The other choices do not produce endometrial hyperplasia. Diagnosis: Thecoma

49. A 34-year-old woman presents with increasing abdominal girth of 3 months in duration. Physical examination reveals a left ovarian mass and mild ascites. The ovarian mass is removed, and the pathology report states "yolk sac carcinoma." Which of the following provides the best serologic marker to monitor the course of disease in this patient after surgery? (A) Alkaline phosphatase (B) Alpha-fetoprotein (C) Carcinoembryonic antigen (D) Human chorionic gonadotropin (E) Sex hormones (estrogen/progesterone)

49. The answer is B: Alpha-fetoprotein. Yolk sac tumor is a highly malignant tumor of women under the age of 30 years that histologically resembles mesenchyme of the primitive yolk sac. The tumor secretes alpha-fetoprotein (AFP), which can be demonstrated histochemically within eosinophilic droplets. Detection of AFP in the blood is useful both for diagnosis and for monitoring the effectiveness of therapy. The hormone human chorionic gonadotropin (choice D) is secreted by choriocarcinoma. Estrogen (choice E) is secreted by sex cord tumors. Diagnosis: Yolk sac carcinoma

5. The ovarian tumor described in Question 4 most closely resembles which of the following patterns of müllerian-type differentiation? (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

5. The answer is E: Mucosa of the endocervix. During embryonic life, the celomic cavity is lined by a mesothelium. This mesothelial 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 classified as benign, borderline (atypical proliferative), and malignant. Diagnosis: Mucinous cystadenoma of the ovary

50. A 20-year-old woman presents to her gynecologist with a 3-day history of vaginal bleeding. An ultrasound shows a dilated endometrial cavity. Evacuation of the uterus by suction curettage reveals grapelike clusters and fetal parts. Cytogenetic examination of this tissue will most likely demonstrate which of the following genetic patterns? (A) Aneuploidy (B) Diploidy (C) Euploidy (D) Haploidy (E) Triploidy

50. The answer is E: Triploidy. Cytogenetic examination of a partial hydatidiform mole will reveal triploidy. This abnormal chromosomal complement results from the fertilization of a normal ovum (23,X) by two normal spermatozoa, each carrying 23 chromosomes, or a single spermatozoon that has not undergone meiotic reduction and bears 46 chromosomes. The fetus associated with a partial mole usually dies after 10 weeks of gestation, and the mole is aborted shortly thereafter. In contrast to a complete mole, which exhibits diploidy (choice B), fetal parts are commonly present in a partial hydatidiform mole. Diagnosis: Partial hydatidiform mole

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-defined 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-ovarianabscess (E) Vaginal ulceration

6. 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 inflammatory 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 inflammatory reaction, which is confined 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 inflammatory disease

7. A 59-year-old woman presents with a 2-year history of vul- var 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 posi- tively for periodic acid-Schiff (PAS) and carcinoembryonic antigen (CEA). Which of the following is the most likely diagnosis? (A) Extramammary Paget disease (B) HPV-induced papilloma (C) Verrucouscarcinoma (D) Vulvar intraepithelial neoplasia (E) Vulvar melanoma

7. The answer is A: Extramammary Paget disease. Paget dis- ease 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 usu- ally 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 specific histologic findings. 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

8. The answer is B: Autoimmune disease. Lichen sclerosis is an inflammatory 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 inflammatory 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 amplification of this biopsy specimen will most likely demonstrate evidence of which of the following infectious agents? (A) Cytomegalovirus (B) Herpes simplex virus (C) Human papillomavirus (D) Molluscum contagiosum (E) Treponema pallidum

9. 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 first 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