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]