Female Genital Pathology 23

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Chapter 23 • Female Genital Pathology

USMLE Step 1 • Pathology

3.Leiomyomas (fibroids) are benign smooth muscle tumors ofthe myome­ trium and are the most commontumors ofthe female genital tract. These tumors have a high incidence in African Americans (but are also common generally) and are responsive to estrogen.

a.Pathology. They grossly form well-circumscribed, rubbery, white­ tan masses with whorl-like trabeculated appearance on cut section. Leiomyomas arecommonlymultiple andmayhavesubserosal,intramural, and submucosal location. The malignantvariant is leiomyosarcoma.

b.The clinical presentation may be with menorrhagia; abdominal mass; pelvic pain, back pain, or suprapubic discomfort; or infertility and spontaneous abortion.

4.Endometrial carcinoma is the most common malignant tumor of the lower female genital tract, and the tumor most commonly affects post­ menopausalwomen who typically present with vaginal bleeding.

a.Risk factors are mostly related to estrogen, and include early menarche and late menopause; nulliparity; hypertension and diabetes; obesity; chronic anovulation; estrogen-producing ovarian tumors (granulosa cell tumors); ERT and tamoxifen; endometrial hyperplasia (complex atypical hyperplasia); and Lynch syndrome (colon, endometrial, and ovarian can­ cers).

b.Pathology. Endometrial carcinoma typically forms a tan polypoid endometrialmass; invasion ofmyometrium is prognostically important. Endometroid adenocarcinoma is the most common histological type.

5. Less common types of uterine malignancy. Leiomyosarcoma is a malig­ nant smooth muscle tumor. Malignant mixed mtillerian tumors contain both malignant stromal cells and endometrial adenocarcinoma.

6.Adenomyosis is an invagination ofthe deeper layers ofthe endometrium into the myometrium, which causes menorrhagia and dysmenorrhea.

OVARY

1. Polycystic ovarian disease (Stein-Leventhal syndrome) is an endocrine disorder of unknown etiology showing signs of androgen excess (clinical or biochemical), oligoovulation and/or anovulation, and polycystic ovaries. When making the diagnosis, it is important to exclude other endocrine dis­ orders that might affect reproduction. Patients are usuallyyoung females of reproductive age who present with oligomenorrhea or secondary amenor­ rhea, hirsutism, infertility, or obesity. Treatment is with oral contraceptives or Provera.

a.Evaluation. Laboratory studies show elevated luteinizing hormone (LH), low follicle-stimulating hormone (FSH), and elevated testoster­ one. Gross examination is notable for bilaterally enlarged ovaries with multiple cysts; microscopic examination shows multiple follicle cysts.

2.Epithelial ovarian tumors arise from the ovarian surface epithelium and are the most common form ofovarian tumor.

a.Cystadenoma is specifically the most common benign ovarian tumor, and forms a unilocular, smooth-walled cyst that has a simple serous or mucinous lining.

b.Borderline tumors are tumors oflow malignant potential.

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Chapter 23 • Female Genital Pathology

c.Cystadenocarcinoma is the most common malignant ovarian tumor. Hereditary risk factors include BRCA- 1 (breast and ovarian cancers) and Lynch syndrome. CA 125 can be used as a tumor marker.

i.Pathology. Cystadenocarcinoma forms a complex multiloculated cyst with nodular and solid areas. Microscopically, the tumor shows strati­ fied serous or mucinous cyst lining with tufting, papillary structures with psammoma bodies, and stromal invasion. The disease com­ monly spreads by seeding the peritoneal cavity, and it is often detected at a late stage with a poor prognosis.

3.Ovariangerm celltumors.

a.Teratoma (dermoid cyst). The vast majority (>95%) of ovarian (but not testicular) teratomas are benign. These tumors commonly occur in the early reproductive years. Elements from all three germ cell layers are present, including ectoderm (skin, hair, adnexa, and neural tissue), mesoderm (bone and cartilage), and endoderm (thyroid and bronchial tissue). Complications include torsion, rupture, and malignant trans­ formation ( 1%, usually squamous cell carcinoma).

i.The dermoid cyst can contain hair, teeth, and greasy material. The term struma ovarii is used when there is a preponderance of thyroid tissue.

ii.Immatureteratoma is characterized by histologically immature tissue.

b.Dysgerminoma is a malignant germ cell tumor that is common in young adults. Risk factors include Turner syndrome and pseudoher­ maphrodites. Gross and microscopic features are similar to seminomas. Dysgerminomas are radiosensitive and have a good prognosis.

c.Other germ cell tumors include yolk sac tumor (endodermal sinus tumor) and choriocarcinoma.

4.Ovarian sex cord-stromal tumors.

a.Ovarianfibroma is the most common stromal tumor, and forms a firm, white mass. Meigs syndrome refers to the combination of fibroma, asci­ ties, and pleural effusion.

b.Granulosa cell tumor is a potentially malignant, estrogen-producing tumor.

i.Clinically, the presentation depends on age:

•Prepuberal patients present with precocious puberty

•Reproductive age patients present with irregular menses

•Postmenopausal patients present with vaginal bleeding Complications include endometrial hyperplasia and cancer.

u.Pathology. The tumor forms a yellow-white mass that microscopically shows polygonal tumor cells and formation of follicle-like structures (Call-Exner bodies).

c.Sertoli-Leydig cell tumor (androblastoma) is an androgen-producing tumor that presents with virilization; a complication is risk of female pseudohermaphroditism.

5.Primary sites for metastatic tumor to the ovary include breast cancer,

colon cancer, endometrial cancer, and gastric "signet-ring cell" cancer (Krukenberg tumor).

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USMLE Step 1 • Pathology

Table 23-2. Origins ofCommon Ovarian Neoplasms

GESTATIONALTROPHOBLASTIC DISEASE AND

PLACENTAL DISEASE

1.Hydatidiform mole (molar pregnancy) is a tumor of placental tropho­ blastic tissue. The incidence of hydatidiform mole in the United States is 1 per 1,000 pregnancies, with molar pregnancy being more common in Asia than in the United States. There is increased risk in women ages <15 and >40.

a.Complete mole results from fertilization of an ovum that lost allits chromosomal material, so that allchromosomal material is derived from sperm. 90% ofthe time, the molar karyotype is 46,XX; 10% ofthe time, the molar karyotype includes a Y chromosome. The embryo does not develop.

b.Partial mole results from fertilization of an ovum that has not lost its

chromosomal material by two sperms, one 23,X and one 23,Y. This results in a triploid cell 69, XXY (23,X [maternal] + 23,X [one sperm] + 23,Y [the other sperm]). The embryo may develop for a fewweeks.

c.Clinically,thepresentation is typically with excessive uterine enlarge­ ment ("size greater than dates"); vaginal bleeding; passage of edema­ tous, grapelike soft tissue; and elevated beta-human chorionic gonado­ tropin ( -HCG). Diagnosis is by ultrasound, and treatment is with endometrial curettage and following of -HCG levels.

d.Microscopically, molar tissue willshow edematous chorionic villi; tro­ phoblast proliferation; and fetal tissue (only in partial mole).

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USMLE Step :t • Pathology

Chapter Summary

•Lesions ofthe vulva include condyloma acuminatum, papillary hidradenoma, extramammary Paget disease, squamous cell carcinoma, melanoma, Bartholin gland abscess, lichen sclerosis, and lichen simplex chronicus.

•Lesions ofthe vagina include vaginal adenosis, clearcell adenocarcinoma, embryonal rhabdomyosarcoma, squamous cell carcinoma, rhabdomyoma, Gartner duct cyst, and Rokitansky-Kuster-Hauser syndrome.

•Pelvic inflammatory disease is an ascending infection that is often due to gonorrhea and/or Chlamydia, from the cervix to the endometrium, fallopian tubes, and pelvic cavity. Pelvic inflammatory disease is an important cause of pelvic and even peritoneal inflammation, abscess formation, and scarring.

•Cervical carcinoma is the third most common malignant tumor ofthe female genital tract and typically arises from HPV-types 16, 18, 31, and 33. Cervical polyps and cervicitis can also affect the cervix.

•Acute endometritis is usually due to an ascending infection ofthe cervix, sometimes associated with pregnancy or abortions. Chronic endometritis is associated with PID and intrauterine devices.

•Endometriosis is the presence of endometrial glands and stroma outside the

uterus, and may cause red-brown nodules or cysts in a wide variety of sites.

•Leiomyomas are benign smooth muscle tumors that are the most common tumors ofthe female tract.

•Endometrial adenocarcinoma is the most common malignant tumor of the female genital tract and usually presents as postmenopausal bleeding. Less common tumors ofthe uterus include leiomyosarcoma and malignant mixed mUllerian tumors.

•Polycystic ovarian disease is a cause of infertility and hirsutism in young women.

•Ovarian tumors are subclassified as epithelial, germ-cell, orsex cord origin. Epithelial ovarian tumors include cystadenoma, borderline tumors, and cystadenocarcinoma. Ovarian germ-cell tumors include teratoma, dysgerminoma, yolk sac tumor, and choriocarcinoma. Ovarian sex cord-stromal tumors include ovarian fibroma, granulosa cell tumor, and Sertoli-Leydig cell tumor. The ovaries are also a site of metastatic disease, with common primarysites including breast, colon, endometrium, and stomach.

•Gestational trophoblastic disease includes benign and malignant tumors derived from trophoblast, including hydatidiform mole, invasive mole, and choriocarcinoma.

•Abnormalities ofthe placenta include ectopic pregnancy, enlarged placentas, succenturiate lobes, placental abruption, placenta previa, placenta accreta, and twin placentas.

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