Definition/General

Introduction:
-Ovarian secretory carcinoma is an extremely rare malignant tumor characterized by abundant eosinophilic secretions and distinctive morphology
-Represents less than 0.1% of all ovarian malignancies
-More commonly seen in breast, salivary glands
-Shows ETV6-NTRK3 fusion in many cases
-Contains intracytoplasmic and extracellular secretions.
Origin:
-Arises from surface epithelium or inclusion cysts of the ovary
-May develop from pre-existing cystadenoma
-Shows similar molecular features to mammary secretory carcinoma
-Results from ETV6-NTRK3 translocation t(12;15)
-Represents rare variant with unique molecular signature.
Classification:
-Classified under WHO 2020 as variant of surface epithelial tumor
-Low to intermediate grade typically
-Most cases are Grade I-II
-Characterized by ETV6-NTRK3 fusion (when present)
-FIGO staging follows standard ovarian cancer protocols.
Epidemiology:
-Peak incidence in 4th-6th decades (30-60 years)
-Younger age group compared to other ovarian carcinomas
-Unilateral presentation typical (>90%)
-Early stage at presentation common
-Indian population shows similar demographics
-Pediatric cases rarely reported.

Clinical Features

Presentation:
-Pelvic mass (most common presentation in 90% cases)
-Incidental finding during routine examination
-Abdominal distension mild to moderate
-Early stage presentation typical (80% Stage I)
-Unilateral disease in >90% cases
-Often asymptomatic until large.
Symptoms:
-Pelvic discomfort (mild in most cases)
-Abdominal fullness sensation
-Urinary frequency due to mass effect
-Minimal constitutional symptoms
-Normal menstrual cycles typically
-Pelvic pressure sensation occasionally.
Risk Factors:
-Age 30-60 years (younger than typical ovarian cancer)
-No specific genetic predisposition identified
-Nulliparity not consistently associated
-Hormonal factors unclear
-Environmental factors not established
-Family history typically negative.
Screening:
-Transvaginal ultrasound shows complex cystic-solid mass
-CA-125 typically normal or mildly elevated
-CT/MRI pelvis for characterization
-Tissue biopsy required for diagnosis
-Molecular testing for ETV6-NTRK3 fusion
-No specific tumor markers available.

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Gross Description

Appearance:
-Well-circumscribed cystic-solid tumor
-Gray-white cut surface with secretory material
-Smooth external surface typically
-Mucoid or serous secretions in cystic areas
-Solid areas firm with secretory material.
Characteristics:
-Soft to firm consistency
-Gray-white to tan coloration
-Well-defined margins
-Abundant secretory material
-Minimal necrosis or hemorrhage
-Cystic spaces contain eosinophilic secretions.
Size Location:
-Size ranges from 2-15 cm (median 8 cm)
-Unilateral involvement in >90% cases
-Can arise from any part of ovary
-Surface involvement rare
-Bilateral disease extremely rare (<5%)
-Well-localized to ovary.
Multifocality:
-Unifocal presentation typical (>95% cases)
-Bilateral involvement extremely rare
-Extraovarian spread uncommon at presentation
-Peritoneal implants rare
-Lymph node involvement uncommon
-Confined to ovary in most cases.

Microscopic Description

Histological Features:
-Epithelial tumor with abundant eosinophilic secretions
-Microcystic and solid patterns
-Intracytoplasmic secretions (PAS-positive)
-Extracellular secretory material
-Low-grade nuclear features typically
-Minimal mitotic activity (<5/10 HPF).
Cellular Characteristics:
-Cuboidal to columnar cells with eosinophilic cytoplasm
-Abundant intracytoplasmic secretions
-Round to oval nuclei with fine chromatin
-Inconspicuous nucleoli
-Uniform nuclear morphology
-Secretory vacuoles prominent.
Architectural Patterns:
-Microcystic pattern predominates
-Solid areas with secretory cells
-Tubular architecture may be present
-Papillary pattern occasionally seen
-Cystic spaces filled with secretions
-Infiltrative growth uncommon.
Grading Criteria:
-Low-grade tumor typically (Grade I-II)
-Grade I: Well-formed architecture, minimal pleomorphism
-Grade II: Moderate nuclear features
-Grade III extremely rare
-Nuclear uniformity characteristic
-Low mitotic activity typical.

Immunohistochemistry

Positive Markers:
-CK7 (95-100% cases)
-PAX8 (90-95% cases)
-Mammaglobin (80-90% cases)
-S-100 (70-80% cases)
-STAT5A (60-70% cases)
-PAS positive secretions
-Mucicarmine positive secretions.
Negative Markers:
-CK20 (negative)
-CDX2 (negative)
-TTF1 (negative)
-WT1 (typically negative)
-Calretinin (negative)
-Inhibin (negative)
-GCDFP15 (negative).
Diagnostic Utility:
-PAX8 positivity confirms ovarian origin
-Mammaglobin positivity supports secretory phenotype
-S-100 positivity characteristic
-PAS-positive secretions diagnostic
-ETV6-NTRK3 FISH confirmatory when positive
-Molecular testing recommended.
Molecular Subtypes:
-ETV6-NTRK3 fusion positive subtype (when present)
-Low-grade molecular profile
-NTRK expression positive in fusion cases
-Low Ki-67 proliferation (<10%)
-p53 wild-type pattern
-Unique molecular signature.

Molecular/Genetic

Genetic Mutations:
-ETV6-NTRK3 translocation t(12;15) (when present)
-NTRK3 gene rearrangements
-PIK3CA mutations (10-15% cases)
-TP53 mutations uncommon (<5%)
-ARID1A mutations rare
-Low mutational burden typically.
Molecular Markers:
-ETV6-NTRK3 fusion (diagnostic when present)
-NTRK3 protein expression
-Low Ki-67 proliferation index (<10%)
-p53 wild-type pattern
-STAT5A expression
-Mammaglobin expression.
Prognostic Significance:
-Excellent prognosis when diagnosed early
-Stage at presentation most important factor
-Early-stage disease has >95% 5-year survival
-Low-grade biology associated with good outcomes
-ETV6-NTRK3 fusion may predict NTRK inhibitor response.
Therapeutic Targets:
-NTRK inhibitors (larotrectinib, entrectinib) for fusion-positive cases
-Standard chemotherapy for advanced cases
-Hormonal therapy limited role
-Anti-angiogenic agents investigational
-Targeted therapy based on molecular profile.

Differential Diagnosis

Similar Entities:
-Metastatic breast secretory carcinoma
-Mucinous adenocarcinoma of ovary
-Endometrioid adenocarcinoma with secretions
-Clear cell carcinoma
-Serous cystadenoma with atypia
-Yolk sac tumor (in young patients).
Distinguishing Features:
-vs Breast metastasis: PAX8 positive in ovarian
-Clinical correlation essential
-vs Mucinous: Different secretion quality
-Mammaglobin positive
-vs Clear cell: Lacks hobnail morphology
-Different IHC profile
-vs Yolk sac: Age difference
-AFP negative.
Diagnostic Challenges:
-Rare entity with limited experience
-Morphological overlap with other secretory tumors
-Molecular testing may be required
-Distinction from breast metastasis
-Small biopsy samples challenging
-ETV6-NTRK3 FISH confirmatory.
Rare Variants:
-Secretory carcinoma with solid areas
-Mixed secretory-endometrioid pattern
-Cystic secretory carcinoma
-Secretory carcinoma with clear cells
-Each variant requires molecular confirmation.

Sample Pathology Report

Template Format

Sample Pathology Report

Complete Report: This is an example of how the final pathology report should be structured for this condition.

Specimen Information

Right/Left ovary and fallopian tube, measuring [X x Y x Z] cm

Gross Description

Well-circumscribed [X] cm cystic-solid mass with secretory material

Microscopic Description

Epithelial tumor with abundant intracytoplasmic and extracellular secretions

Immunohistochemistry

CK7: Positive, PAX8: Positive, Mammaglobin: Positive, S-100: Positive

Molecular Studies

ETV6-NTRK3 FISH: [Positive/Negative/Not performed]

Diagnosis

Ovarian Secretory Carcinoma, Grade [I/II], Stage [stage]

Final Diagnosis

Right/Left Ovarian Secretory Carcinoma, Grade [X], FIGO Stage [X]