Definition/General
Introduction:
Ovarian adenocarcinoma represents the most common malignant epithelial tumor of the ovary
It constitutes 85-90% of all ovarian cancers
These tumors arise from surface epithelium or inclusion cysts
They demonstrate glandular differentiation and mucin production
The prognosis varies by stage, grade, and histological subtype.
Origin:
Originates from ovarian surface epithelium or fallopian tube epithelium
May arise from endometriosis (clear cell, endometrioid types)
Develops through multistep carcinogenesis
Shows müllerian differentiation
Acquires capacity for invasion and metastasis.
Classification:
Classified by WHO 2020 guidelines
High-grade serous carcinoma (70%)
Endometrioid carcinoma (10%)
Clear cell carcinoma (10%)
Mucinous carcinoma (3%)
Low-grade serous (5%)
Other rare types (2%).
Epidemiology:
Peak incidence in 6th-7th decades
Leading cause of gynecologic cancer death
BRCA mutations in 15-20% cases
Lynch syndrome association (endometrioid type)
Indian population shows increasing incidence with urbanization.
Clinical Features
Presentation:
Abdominal distension and pain
Pelvic mass
Ascites (advanced cases)
Constitutional symptoms
Bowel obstruction (late stage)
Pleural effusion
Early satiety
Urinary symptoms.
Symptoms:
Persistent abdominal bloating
Pelvic or abdominal pain
Loss of appetite
Fatigue and weakness
Urinary urgency or frequency
Constipation
Unexplained weight loss
Postmenopausal bleeding (rare).
Risk Factors:
Age >50 years
BRCA1/2 mutations
Family history
Nulliparity
Infertility
Endometriosis
Lynch syndrome
Hormone replacement therapy.
Screening:
CA-125 (elevated >35 U/mL)
HE4
ROMA index
Transvaginal ultrasound
CT/MRI for staging
PET scan
Genetic testing (BRCA, Lynch).
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Gross Description
Appearance:
Solid and cystic masses
Bilateral involvement common
Surface nodularity
Papillary excrescences
Necrosis and hemorrhage
Friable consistency
Capsular rupture
Peritoneal deposits.
Characteristics:
Gray-white solid areas
Cystic components with papillae
Areas of necrosis
Hemorrhagic regions
Calcifications
Mucoid areas (mucinous type)
Chocolate-colored cysts (endometrioid)
Clear fluid (serous type).
Size Location:
Size typically >5 cm
Bilateral disease in 60-70%
Surface involvement common
Adherent to pelvic organs
Omental involvement
Peritoneal studding
Lymph node enlargement.
Multifocality:
Peritoneal carcinomatosis
Omental cake
Diaphragmatic deposits
Liver surface implants
Bowel serosal involvement
Lymph node metastases
Pleural deposits.
Microscopic Description
Histological Features:
Malignant glandular epithelium
Complex papillary architecture
Solid growth patterns
High-grade nuclear atypia
Increased mitotic activity
Stromal invasion
Necrosis
Lymphovascular invasion.
Cellular Characteristics:
Pleomorphic epithelial cells
Enlarged hyperchromatic nuclei
Prominent nucleoli
High N:C ratio
Loss of polarity
Atypical mitoses
Apoptotic bodies
Multinucleated cells.
Architectural Patterns:
Papillary pattern (serous)
Glandular pattern (endometrioid)
Solid sheets (poorly differentiated)
Cribriform pattern
Micropapillary areas
Single cell infiltration
Stromal desmoplasia.
Grading Criteria:
Two-tier system: Low-grade vs High-grade
Nuclear atypia
Mitotic rate
Architectural complexity
High-grade: >95% of serous carcinomas
Grade predicts behavior and treatment response.
Immunohistochemistry
Positive Markers:
PAX8 (müllerian marker)
WT1 (serous type)
p53 (mutant pattern, HGSC)
CK7
CA-125
p16 (HGSC)
ER/PR (variable)
Napsin A (clear cell).
Negative Markers:
CK20 (usually negative)
CDX2 (negative except mucinous)
TTF-1
Inhibin
Calretinin
CD45
Melanoma markers
Neuroendocrine markers.
Diagnostic Utility:
PAX8 confirms ovarian origin
WT1 distinguishes serous type
p53 pattern determines grade
CK7/CK20 profile aids classification
Subtype-specific markers guide classification
Excludes metastases.
Molecular Subtypes:
HGSC: p53 mutant, p16+, WT1+
LGSC: p53 wild-type
Endometrioid: ER+, PR+, β-catenin abnormal
Clear cell: Napsin A+, HNF-1β+
Mucinous: CK20+, CDX2+.
Molecular/Genetic
Genetic Mutations:
TP53 mutations (HGSC, >95%)
BRCA1/2 mutations (20-25%)
KRAS mutations (LGSC, mucinous)
PIK3CA mutations (endometrioid, clear cell)
ARID1A mutations (clear cell, endometrioid)
PTEN mutations (endometrioid).
Molecular Markers:
p53 overexpression
High Ki-67 (>40%)
PARP expression
PD-L1 expression
HRD score
Microsatellite status
TMB (tumor mutational burden).
Prognostic Significance:
Stage most important
Grade affects survival
BRCA mutations predict platinum response
HRD predicts PARP inhibitor response
Subtype influences outcome
Debulking status crucial.
Therapeutic Targets:
Platinum chemotherapy
PARP inhibitors (BRCA/HRD)
Bevacizumab
Immunotherapy (PD-1/PD-L1)
Folate receptor targeted therapy
VEGF inhibitors.
Differential Diagnosis
Similar Entities:
Metastatic adenocarcinoma
Primary peritoneal carcinoma
Fallopian tube carcinoma
Endometrial carcinoma
Borderline tumor
Sex cord-stromal tumor.
Distinguishing Features:
Primary ovarian: PAX8 positive
Bilateral large masses
Metastatic: Small bilateral nodules
Clinical history
Organ-specific markers
Primary peritoneal: Normal ovaries.
Diagnostic Challenges:
Primary vs metastatic
Subtype classification
Grade assignment
Synchronous primaries
Origin determination (ovary vs tube vs peritoneum)
Sampling adequacy.
Rare Variants:
Micropapillary variant
Transitional cell carcinoma
Squamous differentiation
Carcinosarcoma
Small cell carcinoma
Undifferentiated carcinoma.
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
Total hysterectomy, bilateral salpingo-oophorectomy, omentectomy
Diagnosis
Ovarian adenocarcinoma, [subtype], [grade]
Final Diagnosis
High-grade serous adenocarcinoma, FIGO Stage [stage]