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

Metastatic Tumors to the Ovary: Krukenberg Tumor

The ovary is a common site of metastasis from carcinomas of the gastrointestinal tract, breast, and other sites. Metastatic tumors account for ~5% of ovarian tumors and are frequently bilateral (versus most primary ovarian tumors which are unilateral).

Krukenberg Tumor:
• Defined specifically as bilateral metastatic signet-ring cell carcinoma of the ovary
• Origin: classically from gastric adenocarcinoma (diffuse type, poorly cohesive); also from colorectal, appendiceal, breast, and biliary carcinomas
• Mechanism of spread: hematogenous (blood-borne), lymphatic, or transcoelomic; the bilateral nature and ovarian tropism suggest hormonal or surface receptor-mediated implantation
• Gross: bilateral, solid (not cystic), preserved ovarian shape ("kidney-shaped"), firm white-grey masses
• Micro: signet-ring cells — mucin-filled cells that displace the nucleus to the periphery, creating a crescent ("signet ring") appearance — embedded in a cellular edematous fibromatous stroma (reactive stroma derived from ovarian stroma, not desmoplasia)
• Marker: positive for mucin stains (PAS, Alcian blue); CK20+, CDX2+, CK7± (gastric primary); negative for ovarian markers (WT1, PAX8)

Clinical importance:
• A woman presenting with bilateral ovarian masses must be worked up for a GI primary before assuming a primary ovarian tumor
• Prognosis: very poor (reflects the metastatic gastric primary)

Other common metastatic tumors to the ovary:
• Colorectal carcinoma: CK20+, CDX2+, CK7−; "garland pattern" glands with dirty necrosis
• Breast carcinoma: lobular type most common (discohesive cells mimicking signet rings); ER+, GATA3+
• Appendiceal mucinous neoplasm → pseudomyxoma peritonei (discussed under mucinous tumors)

Educational diagram showing high-power histology of Krukenberg tumor with signet-ring cells in fibromatous ovarian stroma, a magnified signet-ring cell, and gross bilateral solid ovarian tumors. — **Panel A:** High-power histology showing signet-ring cells, intracytoplasmic mucin, displaced crescent-shaped nuclei, and fibromatous ovarian stroma.. **Panel B:** Magnified signet-ring cell showing intracytoplasmic mucin vacuole and peripherally displaced nucleus.. **Panel C:** Gross correlation showing bilateral enlarged solid white-grey ovaries with preserved ovarian shape..

Diagram showing bilateral enlarged solid white-grey Krukenberg tumor ovaries with preserved contour, compared with other ovarian tumor gross patterns and linked to the need to search for a primary malignancy elsewhere. — **Panel A:** Bilateral enlarged ovaries, kidney-shaped masses, preserved ovarian contour, solid white-grey cut surface. **Panel B:** Krukenberg tumor: solid preserved shape; high-grade serous carcinoma: cystic-solid with papillary excrescences; mucinous tumor: multiloculated cystic mass. **Panel C:** Bilateral solid ovarian masses, female pelvis, stomach and colon as possible primary sites, search for primary elsewhere.

CLINICAL PEARL

Bilateral ovarian tumor = Krukenberg until proven otherwise is an examination mantra — but it requires nuance. Bilateral ovarian tumors can be: (1) bilateral primary (HGSC is bilateral in 65%; borderline serous ~30%; dysgerminoma 5–10%), OR (2) bilateral metastatic (Krukenberg, colorectal, breast). The key discriminators: Krukenberg tumors are solid and preserve ovarian shape; HGSC is cystic-solid with papillary excrescences; mucinous tumors are multiloculated. Always look for a primary elsewhere when bilateral solid ovarian masses are found.

Spread, Staging, and Clinical Features of Ovarian Carcinoma

Routes of spread (most important for pathological and clinical staging):

1. Transcoelomic (transperitoneal) seeding — the dominant and most important route
• Malignant cells shed from the ovarian surface into the peritoneal cavity
• Circulate via peritoneal fluid
• Implant preferentially on: omentum ("omental caking" — solid replacement of the greater omentum by tumor), peritoneum, bowel serosa, diaphragm (especially right hemidiaphragm), paracolic gutters, pouch of Douglas
• Ascites develops from obstruction of lymphatic drainage and tumor fluid secretion

Lymphatic spread: to para-aortic nodes (via gonadal lymphatics) and pelvic nodes

Direct extension: to fallopian tube, uterus, broad ligament

Hematogenous spread: late; to liver parenchyma, lung (liver surface deposits = transcoelomic, not blood-borne)

FIGO Staging (simplified):

Stage	Description
I	Confined to ovary/ovaries
Ia	One ovary, intact capsule, no surface tumor
Ib	Both ovaries, intact capsule
Ic	Ia/Ib + capsule rupture or surface tumor or positive peritoneal cytology
II	Pelvic extension (uterus, tubes, other pelvic organs)
III	Peritoneal/omental metastasis beyond pelvis, or retroperitoneal lymph nodes
IIIc	Peritoneal metastases >2 cm; or pelvic/para-aortic nodes
IV	Distant metastasis (pleural effusion with positive cytology; liver/spleen parenchyma)

Why 75% present at Stage III–IV:
• The ovary is intraperitoneal — shed cells immediately encounter the peritoneal surface
• Early disease is asymptomatic; by the time symptoms appear (bloating, early satiety, pelvic pressure, altered bowel habits), transcoelomic spread has usually occurred
• Screening with CA-125 + transvaginal ultrasound has NOT proven mortality benefit in general population (UKCTOCS trial, 2016)

Tumor Markers — Summary Table:

Marker	Primary Tumor
CA-125	Serous carcinoma (>80%); also endometrioid, clear cell
AFP (alpha-fetoprotein)	Yolk sac tumor; immature teratoma (component)
hCG (beta)	Choriocarcinoma; dysgerminoma (if syncytiotrophoblastic cells)
Inhibin	Granulosa cell tumor; thecoma
PLAP + LDH	Dysgerminoma
CEA / CA19-9	Mucinous carcinoma; metastatic GI tumor

Diagram showing ovarian carcinoma spreading through ascitic fluid to form bilateral ovarian masses, peritoneal deposits, and omental cake. — **Panel A:** Anterior abdominopelvic overview showing bilateral ovarian masses, primary ovarian tumor, ascites, peritoneal deposits, and omental cake.. **Panel B:** Close-up of greater omentum showing normal fatty omentum replaced by solid nodular tumor mass labeled omental cake.. **Panel C:** Mechanism inset showing exfoliated ovarian carcinoma cells spreading through ascitic fluid and implanting on peritoneum and omentum..

Complications of Ovarian Tumors

Ovarian tumors — benign or malignant — can produce several acute and chronic complications that require rapid recognition.

1. Torsion (Ovarian Torsion):
• Most common complication of benign cystic tumors, particularly mature cystic teratoma and paraovarian cysts
• The ovarian pedicle (containing ovarian vessels and fallopian tube) twists, causing venous congestion → arterial compromise → ischemia → infarction
• Clinical: sudden onset severe lower abdominal pain, often with nausea/vomiting, in a reproductive-age woman
• Ultrasound: absent Doppler flow to the ovary
• Treatment: surgical untwisting (detorsion) ± oophorectomy; can recur if underlying tumor not removed

2. Rupture:
• Dermoid cysts: rupture releases sebaceous material → chemical (granulomatous) peritonitis with severe pain
• Serous cystadenoma: rupture releases watery fluid — less inflammatory
• Malignant tumors: rupture upstages the tumor from Ia to Ic (FIGO)

3. Ascites:
• Malignant tumors: from transcoelomic seeding → lymphatic obstruction + tumor fluid secretion
• Meigs syndrome: benign ovarian fibroma with ascites + pleural effusion (resolves with tumor removal)
• Pseudo-Meigs syndrome: any benign pelvic tumor (not just fibroma) with ascites + pleural effusion

4. Infection (Dermoid cyst):
• Secondary infection of dermoid cysts → abscess; rare

5. Malignant transformation:
• Mature teratoma → squamous cell carcinoma (<1%)
• Borderline tumor → invasive carcinoma (rare; years later)

6. Paraneoplastic syndromes:
• Hypercalcemia: clear cell carcinoma (PTHrP), immature teratoma
• Subacute cerebellar degeneration: anti-Yo antibodies in HGSC (paraneoplastic neurological syndrome)
• Endometrial hyperplasia/carcinoma: from estrogen secretion by granulosa cell tumor / thecoma

7. Hormonal effects:
• Virilization: Sertoli-Leydig cell tumor, Leydig cell tumor
• Pseudo-precocious puberty in girls: granulosa cell tumor (juvenile type), choriocarcinoma (hCG)
• Isosexual pseudo-precocity: hCG-secreting tumors

SELF-CHECK

A 16-year-old girl presents with rapidly progressive abdominal distension and pain. Ultrasound shows a 12 cm solid unilateral right ovarian mass. Serum AFP is 2,400 ng/mL. Histology of the resected tumor shows glomeruloid vascular structures surrounded by tumor cells within a myxoid stroma, and eosinophilic hyaline globules. Which structure is pathognomonic of this tumor?

A. Psammoma body

B. Call-Exner body

C. Schiller-Duval body

D. Rokitansky protuberance

Reveal Answer

Answer: C. Schiller-Duval body

The described structure — a glomeruloid vascular tuft surrounded by tumor cells in a loose myxoid stroma — is a Schiller-Duval body, pathognomonic of yolk sac tumor (endodermal sinus tumor). The dramatically elevated AFP confirms the diagnosis. Psammoma bodies are concentric laminated calcifications in serous carcinoma. Call-Exner bodies are small follicle-like spaces in granulosa cell tumor. The Rokitansky protuberance is the solid nodule within a mature cystic teratoma (dermoid cyst).

Prognosis and an Integrated Approach to Ovarian Tumors

Prognostic factors for ovarian carcinoma:

Factor	Better Prognosis	Worse Prognosis
Stage	I–II	III–IV
Histological type	Endometrioid, clear cell (Stage I)	HGSC (usually late stage)
Residual disease	<1 cm (optimal cytoreduction)	>1 cm (suboptimal)
BRCA mutation	Better chemosensitivity (paradox)	Wild-type TP53 pathway
Differentiation	Well-differentiated	Poorly differentiated
Ascites volume	Absent/small	Large

5-year survival by stage (HGSC):
• Stage I: ~90–92%
• Stage II: ~70–75%
• Stage III: ~25–35%
• Stage IV: ~15%

BRCA paradox in treatment: Although BRCA1/2 mutations increase cancer risk, once HGSC develops in a BRCA carrier, it is paradoxically more chemosensitive (platinum–taxane) because BRCA-deficient cells cannot repair platinum-induced DNA crosslinks. PARP inhibitors (olaparib, niraparib) exploit this "BRCAness" as maintenance therapy.

Integrated diagnostic approach — when you see an ovarian mass:

Bilaterality → suggests epithelial (HGSC), Krukenberg, or borderline serous; not mature teratoma or sex cord–stromal
Age → young = germ cell; peri/post-menopausal = epithelial or GCT adult type
Hormonal features → virilization (Sertoli-Leydig), feminization/endometrial hyperplasia (granulosa cell, thecoma)
Marker → AFP (yolk sac), CA-125 (serous), inhibin (GCT), hCG (choriocarcinoma), PLAP (dysgerminoma)
Morphology → cystic + hair/teeth (dermoid), bilateral papillary-cystic (serous), solid kidney-shaped (Krukenberg), multiloculated mucinous (mucinous cystadenoma)
Spread pattern → transcoelomic = malignant epithelial; no spread = benign; lymphatic = advanced malignant

A single wide comparison table summarizes five key ovarian tumor types by age group, gross appearance, histological hallmark, tumor marker, and distinguishing feature. — **Panel A:** Side-by-side comparison of HGSC, mature cystic teratoma, granulosa cell tumor, yolk sac tumor, and Krukenberg tumor across age group, gross appearance, histological hallmark, tumor marker, and distinguishing feature; includes labeled insets for psammoma bodies, mature skin adnexa, Call-Exner bodies, Schiller-Duval body, and signet-ring cells..