Definition/General
Introduction:
Ovarian serous carcinoma is the most common malignant epithelial tumor of the ovary
It accounts for 70-80% of all ovarian cancers
It arises from the ovarian surface epithelium or fallopian tube epithelium
It demonstrates papillary architecture with serous differentiation.
Origin:
Originates from ovarian surface epithelium or fallopian tube epithelium
Recent evidence suggests many arise from the fimbrial end of fallopian tube
The neoplastic transformation involves p53 mutations in most cases
It leads to loss of cellular differentiation
It results in acquisition of invasive properties.
Classification:
Classified as low-grade or high-grade serous carcinoma
Low-grade shows mild nuclear atypia and low mitotic rate
High-grade demonstrates marked nuclear pleomorphism and high mitotic activity
FIGO staging system is used
Stage I (confined to ovaries)
Stage II (pelvic extension)
Stage III (peritoneal implants)
Stage IV (distant metastases).
Epidemiology:
Peak incidence in 6th-7th decades
Risk factors include age
BRCA1/2 mutations (hereditary cases)
Family history
Nulliparity
Early menarche
Late menopause
Hormone replacement therapy
Indian population shows increasing incidence with improved detection and aging population.
Clinical Features
Presentation:
Abdominal distension due to ascites (most common)
Pelvic mass on examination
Abdominal pain
Early satiety
Weight loss
Elevated CA-125 (>90% cases)
Often presents at advanced stage (III-IV).
Symptoms:
Bloating and abdominal discomfort (80% cases)
Urinary frequency (50% cases)
Loss of appetite (40% cases)
Bowel symptoms (constipation, change in habits)
Fatigue and weakness
Dyspnea (pleural effusion)
Back pain.
Risk Factors:
Age >50 years
BRCA1 mutation (40% lifetime risk)
BRCA2 mutation (20% lifetime risk)
Family history of ovarian/breast cancer
Lynch syndrome
Nulliparity
Infertility
Hormone replacement therapy
Endometriosis (low-grade serous).
Screening:
No effective screening for general population
High-risk patients: transvaginal ultrasound and CA-125
BRCA carriers: risk-reducing salpingo-oophorectomy
Genetic counseling for familial cases
Clinical awareness of symptoms important.
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Gross Description
Appearance:
Solid and cystic masses with papillary excrescences
Bilateral involvement in 60-70% cases
Surface shows nodular implants
Cut surface reveals friable papillary tissue
Areas of necrosis and hemorrhage common.
Characteristics:
Gray-white to tan solid areas with cystic components
Papillary projections into cyst cavities
Soft, friable consistency
Calcifications may be present (psammoma bodies)
Adherent to surrounding structures.
Size Location:
Variable size (2-30 cm, average 10-15 cm)
Bilateral ovarian involvement in majority
Peritoneal implants throughout abdomen
Omental caking characteristic finding
Fallopian tube involvement common.
Multifocality:
Multifocal disease is characteristic
Peritoneal carcinomatosis common at presentation
Lymph node metastases (pelvic and para-aortic)
Pleural involvement in advanced cases
Liver surface implants frequent.
Microscopic Description
Histological Features:
Branching papillary architecture with fibrovascular cores
Malignant epithelial cells lining papillae
Slit-like spaces between papillae
Psammoma bodies (calcified spherules) characteristic
Solid areas with sheet-like growth.
Cellular Characteristics:
Epithelial cells with pleomorphic nuclei
Prominent nucleoli in high-grade tumors
Increased nuclear-cytoplasmic ratio
Abundant mitotic figures
Cytoplasm eosinophilic to amphophilic
Ciliated cells may be present.
Architectural Patterns:
Papillary pattern predominant
Glandular pattern with slit-like lumina
Solid pattern in poorly differentiated areas
Cribriform pattern
Micropapillary pattern
Transitional-like pattern.
Grading Criteria:
Binary grading system: Low-grade vs High-grade
Low-grade: uniform nuclei, low mitotic rate (<12/10 HPF)
High-grade: marked nuclear pleomorphism, high mitotic rate (>12/10 HPF)
High-grade constitutes 90% of cases.
Immunohistochemistry
Positive Markers:
PAX8 (95-100%)
WT1 (90-95%)
p53 (overexpression in high-grade, 80-90%)
CK7 (100%)
CA-125 (90-95%)
Calretinin (focal)
BerEP4
MOC31.
Negative Markers:
CK20 (negative)
CDX2 (negative)
TTF1 (negative)
Estrogen receptor (usually negative in high-grade)
Progesterone receptor (usually negative)
Inhibin (negative)
Calponin (negative).
Diagnostic Utility:
Essential for distinguishing from metastases
PAX8 and WT1 confirm Müllerian origin
p53 pattern helps grade determination
CK7+/CK20- pattern typical
CA-125 useful for monitoring treatment response.
Molecular Subtypes:
High-grade serous (p53 mutated, chromosomally unstable)
Low-grade serous (KRAS/BRAF mutated, chromosomally stable)
BRCA-associated (homologous recombination deficient)
CCNE1 amplified subtype.
Molecular/Genetic
Genetic Mutations:
TP53 mutations (95% of high-grade)
BRCA1/2 mutations (15-20% overall, 40% familial)
KRAS mutations (low-grade serous)
BRAF mutations (low-grade serous)
PIK3CA mutations (10-15%)
CCNE1 amplification (20%).
Molecular Markers:
p53 overexpression (high-grade) or null pattern
Ki-67 high proliferation index
PARP expression
Homologous recombination deficiency (HRD score)
Microsatellite stability (most cases)
PD-L1 expression (variable).
Prognostic Significance:
BRCA1/2 mutations predict better response to platinum therapy
HRD status predicts PARP inhibitor sensitivity
p53 pattern correlates with grade and prognosis
CCNE1 amplification associated with poor prognosis
Platinum sensitivity important prognostic factor.
Therapeutic Targets:
PARP inhibitors: BRCA-mutated and HRD-positive cases
Anti-angiogenic agents: bevacizumab
Immune checkpoint inhibitors: PD-1/PD-L1 inhibitors
Folate receptor alpha: mirvetuximab soravtansine
HER2: trastuzumab (HER2-positive cases).
Differential Diagnosis
Similar Entities:
Endometrioid carcinoma (endometrioid glands, squamous elements)
Clear cell carcinoma (clear cells, hobnail pattern)
Mucinous carcinoma (mucinous differentiation)
Transitional cell carcinoma (transitional morphology)
Metastatic carcinoma (breast, GI tract).
Distinguishing Features:
Serous: PAX8+, WT1+, p53 mutated pattern
Endometrioid: ER/PR positive, β-catenin nuclear
Clear cell: HNF1β positive, napsin A positive
Mucinous: CK20+, CDX2+
Metastatic breast: ER+, GCDFP-15+, mammaglobin+
Metastatic GI: CK20+, CDX2+.
Diagnostic Challenges:
Distinguishing high-grade serous from endometrioid
Separating primary from metastatic carcinoma
Identifying fallopian tube primary vs ovarian
Low-grade vs high-grade serous distinction
Borderline tumors with microinvasion.
Rare Variants:
Serous carcinoma with SET features (solid, endometrioid-like, transitional-like)
Micropapillary variant
Solid variant
Psammocarcinoma (extensive psammoma bodies)
Malignant Brenner tumor with serous features.
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
Bilateral salpingo-oophorectomy with omentectomy, measuring [size] cm
Diagnosis
High-grade serous carcinoma of ovary
Classification and Grade
High-grade serous carcinoma, FIGO Grade [grade]
Histological Features
Shows papillary architecture with slit-like spaces, psammoma bodies, and marked nuclear pleomorphism
Size and Extent
Tumor size: [X] cm, FIGO Stage: [stage], bilateral ovarian involvement
Lymphovascular Invasion
Lymphovascular invasion: [present/absent]
Lymph Node Status
Pelvic lymph nodes: [X] positive out of [X] examined; Para-aortic lymph nodes: [X] positive out of [X] examined
Special Studies
IHC: PAX8 (+), WT1 (+), p53 (overexpression pattern), CK7 (+), CK20 (-)
Molecular: BRCA1/2 [result], HRD score [result] if performed
CA-125: [level] if performed
Prognostic Factors
Grade: High-grade; Stage: [FIGO stage]; Residual disease: [status]; BRCA status: [result]
Final Diagnosis
High-grade serous carcinoma of bilateral ovaries, FIGO Stage [stage]