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PA29.4 | Ovarian Tumors — SDL Guide (Part 2)

Surface Epithelial Tumors: Mucinous Tumors and Pseudomyxoma Peritonei

Mucinous tumors are lined by mucin-secreting columnar cells resembling endocervical or intestinal epithelium.

Mucinous Cystadenoma (benign):
• Second most common benign ovarian tumor after serous cystadenoma
• Usually unilateral, multiloculated ("honeycomb" appearance), filled with thick viscous mucin
• Can be enormous — reported up to 50 kg!
• Micro: single layer of tall columnar cells with basal nuclei and abundant apical mucin (intestinal or endocervical type)

Borderline Mucinous Tumor:
• Epithelial stratification and mild atypia without stromal invasion
• Two subtypes: intestinal type (common) and endocervical (Müllerian) type

Mucinous Carcinoma (primary ovarian, rare):
• Truly primary ovarian mucinous carcinomas are uncommon — most bilateral mucinous tumors are metastatic (from appendix, colorectum, stomach, pancreas)
• A practical rule: bilateral mucinous ovarian tumor = think metastatic until proven otherwise

Pseudomyxoma Peritonei (PMP):
• A rare but dramatic complication defined as mucin accumulation throughout the peritoneal cavity ("jelly belly")
• Classically associated with a low-grade mucinous neoplasm of the appendix (low-grade appendiceal mucinous neoplasm, LAMN) — the ovary is secondarily involved, not the primary
• Peritoneal cavity fills with gelatinous mucin, causing progressive abdominal distension
• Histologically, the mucin pools may contain sparse, bland epithelial cells
• Prognosis: indolent but incurable with standard chemotherapy; treatment is cytoreductive surgery + HIPEC (hyperthermic intraperitoneal chemotherapy)

A cut-open multiloculated ovarian mucinous cystadenoma shows locules filled with thick mucin separated by fibrous septae. — **Panel A:** Cut-open multiloculated ovarian cystic mass showing locules, thick mucin, and fibrous septae.. **Panel B:** Magnified cut surface showing viscous mucin within locules separated by fibrous septum..

Histology diagram of ovarian mucinous cystadenoma showing a cyst wall lined by a single layer of tall columnar mucin-secreting cells with goblet cells, pale apical mucin, and basal nuclei. — **Panel A:** Medium-power H&E-style cyst wall showing cyst lumen, fibrous cyst wall, single layer of tall mucin-secreting columnar cells, pale apical mucin, goblet cells, and basal nuclei.. **Panel B:** High-power goblet/intestinal-type mucinous epithelium showing goblet cells, pale apical mucin, basal nuclei, basement membrane, and tall columnar cell shape.. **Panel C:** Schematic diagnostic comparison showing benign single-layer mucinous epithelial lining with no stromal invasion, contrasted with a simplified abnormal invasive pattern labeled as not seen in benign mucinous cystadenoma..

Surface Epithelial Tumors: Endometrioid, Clear Cell, and Brenner Tumors

Endometrioid Carcinoma:
• Second most common ovarian carcinoma (~10–20%)
• Histologically resembles endometrial adenocarcinoma: glands lined by stratified columnar epithelium with squamoid differentiation (squamous morules)
• Strongly associated with endometriosis (20–30% arise in an endometriotic cyst — "chocolate cyst") and with synchronous endometrial carcinoma (present in 15–30% of cases — may be independent primary tumors, not metastases)
• Molecular profile: CTNNB1 (β-catenin), PTEN, PIK3CA mutations; microsatellite instability (Lynch syndrome link)
• Prognosis: better than HGSC when diagnosed at early stage

Clear Cell Carcinoma:
• ~5–10% of ovarian carcinomas
• Also strongly associated with endometriosis (EAOC); highest frequency in Japan and East Asia
• Gross: solid-cystic mass, often arising within an endometriotic cyst
• Micro: two distinctive cell types — (1) clear cells: large cells with abundant clear cytoplasm (glycogen-rich, washed out in H&E processing) — (2) hobnail cells: cells with nuclei bulging into the lumen like a hobnail boot
• ARID1A mutation is the molecular hallmark (~50%); also PIK3CA
• Notably chemo-resistant to standard platinum–taxane regimens — a major clinical challenge
• Paraneoplastic hypercalcemia occurs in ~10% (PTHrP secretion)

Brenner Tumor:
• Uncommon; usually benign (>95%)
• Contains nests of transitional epithelium (resembles urothelium / bladder lining) embedded in dense fibrous stroma — "coffee bean" nuclei
• Often an incidental finding; may be associated with mucinous cystadenoma in the same ovary
• Gross: small, firm, white-grey; may be calcified
• Malignant Brenner tumor: rare; aggressive behavior

High-power schematic histology of ovarian clear cell carcinoma showing clear cells, hobnail cells, and tubular lumina in a tubulocystic pattern. — **Panel A:** High-power ovarian clear cell carcinoma showing tubulocystic pattern, clear cells, hobnail cells, and tubular lumen. **Panel B:** Magnified clear cells with pale cytoplasm and distinct cell borders. **Panel C:** Magnified hobnail cells with nuclei protruding into tubular lumen.

Histology diagram of Brenner tumor showing transitional epithelial nests with coffee-bean nuclear grooves embedded in abundant fibrous stroma. — **Panel A:** Medium-power Brenner tumor showing epithelial nests and abundant fibrous stroma. **Panel B:** High-magnification inset showing coffee-bean nuclei with longitudinal nuclear grooves. **Panel C:** Simplified diagnostic pattern showing transitional-type epithelial nests embedded in collagen-rich fibrous stroma.

SELF-CHECK

A 62-year-old woman presents with bilateral adnexal masses, ascites, and CA-125 of 520 U/mL. Histology shows complex papillary architecture with high nuclear grade, frequent mitoses, and gritty calcified spherules within the papillae. BRCA1 germline mutation is confirmed. What are the calcified spherules called, and what is the molecular hallmark of this tumor type?

A. Schiller-Duval bodies; AFP overexpression

B. Psammoma bodies; near-universal TP53 mutation

C. Call-Exner bodies; inhibin secretion

D. Asteroid bodies; KRAS mutation

Reveal Answer

Answer: B. Psammoma bodies; near-universal TP53 mutation

The gritty calcified spherules are psammoma bodies — concentrically laminated calcifications formed at papillary tips — classic for high-grade serous carcinoma (HGSC). HGSC shows near-universal TP53 mutation (>96%) and is strongly associated with BRCA1/2 mutations. Schiller-Duval bodies are found in yolk sac tumor (with AFP). Call-Exner bodies with inhibin characterize granulosa cell tumor. KRAS/BRAF mutations are the hallmark of low-grade serous carcinoma.

Germ Cell Tumors: Mature Cystic Teratoma and Immature Teratoma

Germ cell tumors (GCTs) arise from primordial germ cells and reproduce the developmental potential of the egg — hence, they may contain derivatives of all three germ layers (ectoderm, mesoderm, endoderm). GCTs are the most common ovarian tumors in women under 20.

Mature Cystic Teratoma ("Dermoid Cyst"):
• Most common benign ovarian tumor in reproductive-age women and the most common germ cell tumor overall
• Contains well-differentiated tissues from ≥2 germ layers: most commonly skin (dermis, hair follicles, sebaceous glands — hence "dermoid"), teeth, bone, cartilage, thyroid tissue, neural tissue, respiratory epithelium
• Gross: cyst filled with yellow-grey sebaceous material and hair; may contain teeth visible on X-ray/imaging
• A specific structure: the Rokitansky protuberance (dermoid plug) — a solid nodule projecting into the cyst from which the diverse tissue elements arise
• Micro: all tissues are well-differentiated (mature) — this is the key distinction from immature teratoma
• Usually unilateral; 10–15% bilateral
• Complications: torsion (most common complication; presents as acute abdomen in young women), rupture (chemical peritonitis from sebaceous content), malignant transformation (<1%, usually to squamous cell carcinoma from the skin component)
• Struma ovarii: a monodermal teratoma composed predominantly of thyroid tissue; may cause hyperthyroidism; radioiodine scan shows pelvic uptake

Immature Teratoma:
• Contains immature (embryonic) tissue, especially immature neural tissue (neuroepithelial tubules/rosettes)
• Grading (I–III) based on the proportion of immature neural elements per slide (Grade III = most aggressive)
• Elevated AFP and LDH as markers
• Treatment: surgical + chemotherapy (BEP: bleomycin–etoposide–cisplatin); good prognosis with treatment

Diagram of a cut-open ovarian mature cystic teratoma showing greasy yellow sebaceous material, hair, and a solid Rokitansky protuberance. — **Panel A:** Cut-open ovarian mature cystic teratoma showing cyst wall, greasy yellow sebaceous material, hair, and solid Rokitansky protuberance.. **Panel B:** Magnified view of the solid Rokitansky protuberance projecting from the cyst wall.. **Panel C:** Magnified view of cyst contents showing sebaceous material and hair..

Low-power histology diagram of a mature cystic teratoma showing stratified squamous epithelium with sebaceous glands, cartilage, and respiratory mucosa. — **Panel A:** Low-power mature cystic teratoma showing keratinizing stratified squamous epithelium, sebaceous gland, cartilage, and respiratory mucosa.. **Panel B:** Magnified skin-type differentiation showing keratin layer, stratified squamous epithelium, hair follicle, and sebaceous gland.. **Panel C:** Magnified non-skin tissues showing cartilage with chondrocytes in lacunae and respiratory mucosa with ciliated epithelium and goblet cells..