Cysts of the Ovary - Pathology

Classification

I. Non-Neoplastic (Functional) Cysts

1. Follicular Cyst

• Most common functional cyst
• Arises from a Graafian follicle that fails to rupture or regress
• Defined as pathologic when diameter exceeds 3 cm; rarely larger than 8 cm
• Gross: Thin-walled, unilocular, filled with clear serous fluid
• Micro: Lined by granulosa cells (inner) and theca cells (outer); if large, the epithelium may be flattened or absent
• Clinical: Usually asymptomatic; may rupture causing transient pelvic pain or dyspareunia; rarely associated with hemorrhage
• Resolution: Typically within 4-8 weeks with expectant management
• Cigarette and marijuana smoking increase risk; oral contraceptives reduce risk

2. Corpus Luteum Cyst

• Less common than follicular cysts
• Forms when the corpus luteum fails to regress after ovulation, or persists after conception
• Gross: Often filled with hemorrhagic (blood-stained) fluid; thick yellow-orange wall (due to luteinization)
• Micro: Lined by large luteinized granulosa cells and theca-lutein cells
• Clinical: May range from asymptomatic to chronic dull pelvic pain; rupture can cause significant hemoperitoneum (more so than follicular cyst)
• Ruptures more commonly on the right side, often on cycle days 20-26; may be triggered by intercourse, trauma, or pelvic examination
• Patients on anticoagulants are at particular risk for hemorrhage

3. Theca-Lutein Cysts

• Least common functional cyst
• Typically bilateral and multiple
• Caused by excessive hCG stimulation of the theca-lutein cells
• Associated with: molar pregnancy, choriocarcinoma, multiple gestations, ovulation induction drugs (clomiphene, hMG-hCG), GnRH analogs
• Up to one-quarter of complete molar pregnancies have theca-lutein cysts
• Regress spontaneously once the hCG stimulus is removed
• Gross: Often large, multilocular, bilateral; pale yellow walls

II. Neoplastic Cysts

WHO Classification (Surface Epithelial Origin - most common ~70%)

4. Serous Cystadenoma / Cystadenocarcinoma

• Most common epithelial ovarian tumor; constitutes ~25% of all ovarian tumors
• Gross: Unilocular or multilocular cyst; thin-walled; filled with watery (serous) fluid; may have papillary excrescences
• Micro (benign): Lined by a single layer of low cuboidal to columnar tubal-type (ciliated) epithelium; psammoma bodies may be present
• Borderline: Increased architectural complexity, nuclear stratification (2-3 layers), no stromal invasion
• Malignant (High-grade serous carcinoma): Solid and cystic; papillary architecture; high nuclear grade; TP53 mutations in nearly all; BRCA1/BRCA2 germline mutations in ~10-15%; thought to arise from fallopian tube epithelium (serous tubal intraepithelial carcinoma - STIC)
• Bilateral in ~30% of serous cystadenomas; higher bilaterality in carcinomas

5. Mucinous Cystadenoma / Cystadenocarcinoma

• Second most common epithelial tumor
• Gross: Often large (can reach 50+ cm), multilocular ("honeycomb" appearance); filled with viscous, mucoid material; smooth inner surface
• Micro (benign): Lined by tall columnar mucin-secreting cells resembling endocervical or intestinal epithelium; goblet cells may be present
• Borderline: Epithelial stratification up to 3 layers, tufting, mild atypia; no stromal invasion
• Malignant: Glandular structures invading stroma; often intestinal type; KRAS mutations common
• Typically unilateral
• A rare but serious complication: rupture can seed the peritoneum with mucin-secreting cells causing pseudomyxoma peritonei

6. Endometrioma ("Chocolate Cyst")

• Ovarian cyst arising from endometriosis within the ovary
• Gross: Unilocular cyst containing thick, dark-brown ("chocolate") fluid - old hemorrhagic debris from cyclical bleeding; can grow 6-8 cm
• Micro: Wall lined by endometrial-type glandular epithelium and stroma, with hemosiderin-laden macrophages; epithelium may be attenuated or absent in older lesions
• Clinical: Pelvic pain (often cyclical/menstrual), dyspareunia; rupture causes acute generalized peritoneal irritation; associated with infertility
• Dense adhesions are characteristic
• Diagnosis by histology (since chocolate fluid may also be found in hemorrhagic corpus luteum cysts)

III. Germ Cell Tumors with Cystic Morphology

7. Mature Cystic Teratoma (Dermoid Cyst)

• Most common germ cell tumor of the ovary; accounts for ~15-25% of all ovarian tumors in young women
• Age: Young adult females (reproductive age)
• Bilateral in 10-15%
• Karyotype: 46,XX; arises from an ovum after the first meiotic division

• Unilocular cyst filled with sebaceous material and hair
• Wall is opaque, gray-white, wrinkled epidermis with protruding hair shafts
• Contains teeth and areas of calcification (visible on plain X-ray)
• A Rokitansky protuberance (dermoid plug) - a nodule of tissue at one pole of the cyst - is characteristic

• Wall lined by stratified squamous epithelium with sebaceous glands, hair shafts, and skin adnexa
• Tissues from all three germ layers can be found: cartilage, bone, thyroid (struma ovarii), neural tissue, respiratory epithelium
• ~1% undergo malignant transformation, most commonly to squamous cell carcinoma

• Usually asymptomatic; discovered incidentally
• May rupture causing chemical peritonitis (sebaceous material is highly irritating)
• Torsion is a common complication
• Struma ovarii - if thyroid tissue predominates, may cause hyperthyroidism
• Rarely associated with anti-NMDA receptor encephalitis (paraneoplastic)

8. Immature (Malignant) Teratoma

• Rare; mean age 18 years (prepubertal/adolescent)
• Contains immature embryonal/fetal tissue - chiefly immature neuroepithelium
• Gross: Bulky, smooth external surface, predominantly solid with areas of necrosis and hemorrhage
• Micro: Graded I-III based on proportion of immature neuroepithelium - grade determines prognosis
• More aggressive than mature teratoma; risk of spread correlates with histologic grade

IV. Other Cystic Ovarian Lesions

9. Brenner Tumor (Transitional Cell Tumor)

• Usually benign (~10% of ovarian epithelial tumors); typically unilateral (90%)
• Gross: Solid or cystic; variable size (< 1 cm to 20-30 cm); fibrous, white-gray cut surface
• Micro: Nests of urothelium-like (transitional) epithelial cells within a dense fibrous stroma; mucinous glands often present in centers of nests
• Often detected incidentally; even when large, usually behaves benignly

10. Polycystic Ovary (PCOS)

• Bilateral, enlarged ovaries with multiple small follicular cysts (< 1 cm each; ≥12 per ovary) in the cortex with a thickened, white fibrous cortex
• Not a true cyst - represents a syndrome of anovulation (LH:FSH imbalance, insulin resistance, hyperandrogenism)
• Rotterdam criteria: >10 mL ovarian volume or ≥12 subcentimeter antral follicles per ovary

Summary Table

• Robbins, Cotran & Kumar Pathologic Basis of Disease - Classification, Morphology of Teratomas, Epithelial Tumors, Brenner Tumors
• Berek & Novak's Gynecology - Functional Cysts, Theca-Lutein Cysts, Endometriomas, PCOS
• Rosen's Emergency Medicine - Follicular and Corpus Luteum Cysts, Clinical Features
• Schwartz's Principles of Surgery - Benign Ovarian Lesions