15.8 Reproductive System Pathology: Endocrine, Inflammatory, and Neoplastic Disorders of the Reproductive Tract

15.8 Reproductive System Pathology

Reproductive pathology is the largest single-system disease list in the blueprint. This section groups the conditions by category and emphasizes the mechanism-to-vignette link.

1. Reproductive Endocrine Conditions

Amenorrhea is primary (no menses by age 15) or secondary (cessation for ≥3 months). Common secondary causes include pregnancy, hypothalamic suppression (stress, low body weight, exercise), hyperprolactinemia, thyroid disease, and premature ovarian insufficiency. Anovulation and dysfunctional uterine bleeding result from unopposed estrogen cycling without ovulation. Polycystic ovary syndrome (PCOS) is the classic anovulatory syndrome: hyperandrogenism, insulin resistance, an elevated LH-to-FSH ratio (>2), and a string-of-pearls appearance of peripheral ovarian cysts on ultrasound; complications include type 2 diabetes, endometrial hyperplasia (from unopposed estrogen), and infertility. Menopause/perimenopause is ovarian follicle depletion (average age 51) with elevated FSH/LH and vasomotor symptoms; osteoporosis and cardiovascular risk rise. Ovarian insufficiency/failure before age 40 may be autoimmune, chromosomal (Turner), or idiopathic.

2. Inflammatory Diseases of the Reproductive Tract

Endometriosis is functioning endometrium outside the uterus (ovaries, pouch of Douglas, broad ligaments), producing cyclical pain, dyspareunia, dysmenorrhea, and infertility, with chocolate cysts (endometriomas) in the ovary. Pelvic inflammatory disease (PID) is ascending infection (often Chlamydia or gonorrhea) causing salpingitis, endometritis, and the risk of tubo-ovarian abscess, ectopic pregnancy, and infertility; Fitz-Hugh-Curtis perihepatitis is a complication producing right-upper-quadrant pleuritic pain. Cervicitis and vaginitis are common; candidal vaginitis produces a thick white discharge and pseudohyphae on microscopy.

3. Congenital and Genetic Disorders

Cryptorchidism is an undescended testis carrying elevated risk of infertility and testicular cancer. Hypospadias (urethral opening on the ventral penis) and epispadias (dorsal) are urethral malformations. Klinefelter syndrome (47,XXY) gives tall stature, gynecomastia, small firm testes, azoospermia. Turner syndrome (45,X) gives streak ovaries, short stature, webbed neck, coarctation of the aorta. Fragile X syndrome (CGG repeat in FMR1) is the most common inherited intellectual disability, with macroorchidism. Pseudohermaphroditism, imperforate hymen, septate vagina/uterus, phimosis and paraphimosis complete the congenital category.

4. Benign Conditions of Penis, Scrotum, and Breast

Scrotal collections: hydrocele (peritoneal fluid via patent processus vaginalis), spermatocele (epididymal retention cyst), varicocele (pampiniform venous plexus dilation, more on the left, a cause of infertility), hematocele (blood, post-trauma). Erectile dysfunction is common and often vascular, neurologic, or psychogenic.

Breast: fibrocystic change (cyclical nodularity, no increased cancer risk if non-proliferative), mastitis (lactational, Staph aureus), fat necrosis (post-trauma, calcification), duct ectasia, galactocele (milk retention). Fibroadenoma is the most common benign breast tumor of young women—mobile, well-circumscribed, stromal + epithelial.

5. Prostate and Ovarian Disease

Benign prostatic hyperplasia arises in the transition (periurethral) zone, causing urinary hesitancy and nocturia, distinct from cancer. Prostatitis is inflammation or infection. Prostate adenocarcinoma arises in the peripheral (posterior) zone, graded by Gleason score, tracked by PSA, and characteristically produces osteoblastic bone metastases.

Ovarian cysts include functional (follicular, corpus luteum) and polycystic; tubo-ovarian cysts follow PID. Ovarian tumors: epithelial (serous, most common; BRCA1 associated), germ cell (dermoid/teratoma most common germ cell; dysgerminoma analogous to seminoma; yolk sac with Schiller-Duval bodies and elevated AFP), and sex-cord stromal (granulosa cell with Call-Exner bodies and estrogen; Sertoli-Leydig with androgen; fibroma with Meigs syndrome = fibroma + ascites + pleural effusion).

6. Diseases of the Placenta

Hydatidiform mole: complete (46,XX all paternal, no fetus, markedly elevated hCG, theca-lutein cysts) versus partial (triploid, fetal parts present). Both carry risk of choriocarcinoma, a highly chemosensitive trophoblastic malignancy with high hCG. Invasive mole invades the myometrium. Preeclampsia (>20 weeks: hypertension + proteinuria; HELLP = Hemolysis, Elevated Liver enzymes, Low Platelets; eclampsia adds seizures).

7. Reproductive Neoplasms

Cervical intraepithelial neoplasia (CIN) precedes invasive squamous carcinoma, driven by HPV 16/18 (E6 → p53, E7 → Rb), with koilocytes on cytology. Endometrial hyperplasia (unopposed estrogen) precedes endometrial carcinoma (PTEN). Leiomyoma (fibroid) is the most common benign uterine tumor, estrogen-responsive; leiomyosarcoma is its malignant counterpart. Testicular tumors: germ-cell (seminoma most common, radiosensitive; embryonal; yolk sac → AFP; choriocarcinoma → hCG) and non-germ-cell (Leydig, Sertoli). Squamous cell carcinoma of the penis and vaginal/vulvar carcinoma and VIN complete the list.

8. Infectious Diseases of the Genitourinary System (Including STDs)

The sexually transmitted infections are best compared in a table, because the vignette usually hinges on the organism, the lesion character, and the microscopy.

Syphilis stages bear memorizing: primary chancre (painless), secondary (diffuse rash including palms/soles, condyloma latum), latent, and tertiary (gumma, tabes dorsalis, aortitis). Bacterial vaginosis shows clue cells and a positive amine/whiff test. Toxic shock syndrome is Staph TSST-1-mediated and tampon-associated.

Board signal: a 28-year-old with dysmenorrhea, dyspareunia, infertility, and a chocolate cyst → endometriosis; a woman with hirsutism, oligomenorrhea, and string-of-pearls ovaries → PCOS; a young woman with abnormal uterine bleeding and koilocytes → HPV-driven CIN; an older man with osteoblastic bone metastases and elevated PSA → prostate adenocarcinoma.