A 63-year-old woman, gravida 0, para 0 comes to the physician because of a 3-month history of abdominal distension, constipation, and weight loss. She has a history of endometriosis. Pelvic examination shows a nontender, irregular, left adnexal mass. Her serum level of CA-125 is elevated. Serum concentrations of human chorionic gonadotropin and alpha-fetoprotein are within the reference ranges. Microscopic examination of the mass is most likely to show which of the following findings?

Atypical epithelial cells along with psammoma bodies

Large undifferentiated germ cells with clear cytoplasm

Spindle-shaped stromal cells along with signet ring cells

Small, round cells that form Call-Exner bodies

Flattened, cuboidal cells along with Schiller-Duval bodies

A 55-year-old postmenopausal woman comes to the physician for a screening Pap smear. She has no history of serious illness. Her last Pap smear was 10 years ago and showed no abnormalities. She has smoked one-half pack of cigarettes daily for 20 years and drinks 3 bottles of wine per week. She is sexually active with multiple male partners and uses condoms inconsistently. Her paternal grandmother had ovarian cancer and her maternal aunt had breast cancer. Pelvic examination shows multiple red, fleshy polypoid masses on the anterior vaginal wall. A biopsy is obtained and histology shows large cells with abundant clear cytoplasm. Which of the following is the most significant risk factor for this diagnosis?

Diethylstilbestrol exposure in utero

Family history of breast and ovarian cancer

A 54-year-old woman comes to the physician because of an ulcer on her left ankle for 6 years. She has had multiple ulcers over her left lower extremity during this period that have subsided with wound care and dressing. She has type 2 diabetes mellitus and gastroesophageal reflux disease. Current medications include metformin, sitagliptin, and omeprazole. She appears anxious. She is 162 cm (5 ft 4 in) tall and weighs 89 kg (196 lb); BMI is 34 kg/m2. Vital signs are within normal limits. Examination shows a 7.5-cm (3-in) ulcer with elevated, indurated margins and a necrotic floor above the left medial malleolus. There are multiple dilated, tortuous veins along the left lower extremity. There is 2+ pretibial edema of the lower extremities bilaterally. The skin around the left ankle appears darker than the right and there are multiple excoriation marks. Cardiopulmonary examination shows no abnormalities. Which of the following is the most appropriate next step in management of this patient's current condition?

Digital subtraction angiography

Female reproductive pathology for USMLE Step 3: High-Yield Pathology Lessons

Cervix - HPV's Unwanted Hug

Human Papillomavirus (HPV) is the primary cause.
- High-risk: 16, 18 → squamous cell & adenocarcinoma.
- Low-risk: 6, 11 → condyloma acuminatum.
Oncogenesis via viral proteins:
- E6: degrades p53 (tumor suppressor).
- E7: inhibits Rb (retinoblastoma protein).
Koilocytes: Pathognomonic sign of HPV; wrinkled nucleus with a perinuclear halo.

Koilocytic atypia in cervical cells

⭐ Most HPV infections are transient. Persistent infection with high-risk strains is required for malignant transformation.

Uterus - Womb for Improvement

Adenomyosis: Endometrial tissue within the myometrium. Presents with dysmenorrhea, menorrhagia, and a uniformly enlarged, boggy uterus.
Leiomyoma (Fibroid): Benign smooth muscle tumor. Often asymptomatic; can cause bleeding, pain. Estrogen-sensitive. Multiple, well-demarcated, whorled masses.

Endometrial Adenocarcinoma Histopathology

Feature	Endometrial Hyperplasia	Endometrial Carcinoma
Pathology	Proliferation of glands	Malignant glandular proliferation
Cause	Unopposed estrogen	Unopposed estrogen, genetics
Key Gene	-	PTEN inactivation
Progression	Precursor to carcinoma	Invades myometrium, metastasizes

📌 Endometrial Carcinoma Risk Factors: OLD AUNT → Obesity, Late menopause, Diabetes, Age, Unopposed estrogen, Nulliparity, Tamoxifen.

Ovary - Egg-citingly Bad Eggs

Surface Epithelial Tumors (most common)
- Derived from coelomic epithelium; CA-125 marker.
- Serous: Often bilateral. Psammoma bodies common in malignant types.
- Mucinous: Can be very large. Risk of pseudomyxoma peritonei.
- Endometrioid: Associated with endometriosis and endometrial carcinoma.
- Brenner: Transitional cell (urothelial) type, usually benign.
Germ Cell Tumors (younger women < 25)
- Teratoma: Most common germ cell tumor. Mature (“dermoid cyst”) is benign. Immature is malignant potential.
- Dysgerminoma: Malignant; ↑ LDH. Radiosensitive.
- Yolk Sac (Endodermal Sinus) Tumor: ↑ AFP. Schiller-Duval bodies (look like glomeruli).
- Choriocarcinoma: ↑ hCG. Aggressive, early hematogenous spread.
Sex Cord-Stromal Tumors
- Granulosa Cell Tumor: ↑ Estrogen (endometrial hyperplasia). Call-Exner bodies (rosettes).
- Sertoli-Leydig Cell Tumor: Produces androgens (virilization).

⭐ Krukenberg Tumor: Bilateral ovarian metastasis, typically from gastric adenocarcinoma, characterized by signet-ring cells.

Schiller-Duval body in ovarian yolk sac tumor

Gestation & Placenta - Pregnancy's Plot Twists

Spontaneous Abortion (<20 wks): Usually due to chromosomal anomalies. Recurrent losses suggest maternal factors (e.g., antiphospholipid syndrome).
Ectopic Pregnancy: 90% in fallopian tube ampulla. Key risk is prior PID. Presents with pain & bleeding.
Placental Pathologies:
- Previa: Implants over cervical os → painless bleeding.
- Accreta/Increta/Percreta: Abnormal myometrial attachment → massive hemorrhage.
- Abruption: Premature separation → painful bleeding.

⭐ Complete hydatidiform moles show a classic "snowstorm" or "bunch of grapes" pattern on ultrasound.

Ultrasound: Complete hydatidiform mole, snowstorm appearance

High‑Yield Points - ⚡ Biggest Takeaways

High-risk HPV (16, 18) is the main driver of cervical intraepithelial neoplasia (CIN) and invasive carcinoma.

Endometriosis is defined by ectopic endometrial glands/stroma, leading to dysmenorrhea, pain, and infertility.

PCOS diagnosis requires 2 of 3: oligo/anovulation, hyperandrogenism, and polycystic ovaries.

Epithelial ovarian cancers often present late with vague abdominal symptoms and peritoneal spread.

Hydatidiform moles show edematous, avascular chorionic villi ("bunch of grapes").

PID is a critical risk factor for infertility and ectopic pregnancy.

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