Definition/General
Introduction:
Endometrial serous carcinoma is an aggressive high-grade adenocarcinoma of the endometrium characterized by papillary architecture, high nuclear grade, and frequent p53 mutations
It represents 10% of endometrial carcinomas but accounts for 40% of deaths.
Origin:
Arises from atrophic endometrium, often in the setting of endometrial intraepithelial carcinoma (EIC)
Develops via p53-mutated pathway (Type II endometrial cancer).
Classification:
WHO Classification: High-grade endometrial adenocarcinoma, serous type
Part of Type II endometrial cancers
FIGO grade 3 by definition.
Epidemiology:
Peak incidence 65-75 years
More common in African American women
Not estrogen-related
Associated with p53 mutations (>90%)
Poor prognosis with early metastatic spread.
Clinical Features
Presentation:
Postmenopausal bleeding
Enlarged uterus
May present with advanced stage disease
Abnormal endometrial biopsy or curettage.
Symptoms:
Vaginal bleeding (most common)
Pelvic pain
Abdominal distension
Weight loss
Ascites (advanced cases)
Constitutional symptoms.
Risk Factors:
Advanced age
African American ethnicity
Personal history of breast/ovarian cancer
BRCA mutations
Lynch syndrome (rare)
Not associated with obesity/diabetes.
Screening:
No specific screening recommended
Diagnosed on endometrial biopsy
CA-125 may be elevated
Imaging shows complex endometrial lesion.
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Gross Description
Appearance:
Polypoid or papillary endometrial mass
Friable and hemorrhagic
Cut surface shows solid and cystic areas
Necrosis common.
Characteristics:
Size variable (1-10 cm)
Gray-white to tan coloration
Soft consistency
Papillary or cauliflower-like surface
Areas of necrosis.
Size Location:
May involve entire endometrial cavity
Extension to cervix common
Myometrial invasion frequent
Adnexal involvement possible.
Multifocality:
May be multifocal within endometrium
Peritoneal implants common
Lymph node metastases frequent
Distant metastases early.
Microscopic Description
Histological Features:
Papillary architecture with complex branching
High nuclear grade with marked pleomorphism
Prominent nucleoli
Abundant mitotic activity including atypical forms.
Cellular Characteristics:
Large cells with eosinophilic cytoplasm
High nuclear-to-cytoplasmic ratio
Marked nuclear pleomorphism
Macronucleoli
Frequent bizarre giant cells.
Architectural Patterns:
Papillary (most common)
Glandular
Solid
Mixed patterns frequent
Surface involvement characteristic
Deep myometrial invasion common.
Grading Criteria:
High-grade by definition (FIGO grade 3)
Nuclear grade 3
Architecture may be papillary, glandular, or solid
All patterns are high-grade.
Immunohistochemistry
Positive Markers:
p53 overexpression (>75% strong nuclear) or complete loss
WT1 positive (nuclear)
p16 diffuse positive
CK7 positive
EMA positive.
Negative Markers:
ER/PR usually negative or weak
CK20 negative
CDX2 negative
Vimentin negative
MSH proteins intact (usually).
Diagnostic Utility:
p53 pattern (overexpression or loss) diagnostic
WT1 supports serous differentiation
p16 helps distinguish from endometrioid
MSH intact excludes Lynch.
Molecular Subtypes:
p53-mutated subtype (Type II)
High microsatellite stable
High chromosomal instability
Copy number high.
Molecular/Genetic
Genetic Mutations:
TP53 mutations (>90%)
PIK3CA mutations (20-30%)
FBXW7 mutations
PPP2R1A mutations
CCNE1 amplification
Complex karyotype.
Molecular Markers:
p53 protein accumulation or loss
High Ki-67 proliferation index (>50%)
Her2/neu overexpression (20%)
Chromosomal instability.
Prognostic Significance:
Poor prognosis overall
p53 status correlates with behavior
Stage at presentation most important
Lymphovascular invasion predicts spread.
Therapeutic Targets:
Platinum-based chemotherapy standard
Anti-angiogenic agents (bevacizumab)
HER2-targeted therapy if overexpressed
Immune checkpoint inhibitors.
Differential Diagnosis
Similar Entities:
High-grade endometrioid carcinoma
Clear cell carcinoma
Carcinosarcoma
Metastatic serous carcinoma from ovary/fallopian tube
Endometrial intraepithelial carcinoma.
Distinguishing Features:
Serous: p53+, WT1+, papillary
Endometrioid: p53 wild-type, squamous areas
Clear cell: Napsin A+, clear cytoplasm
Metastatic: Clinical correlation.
Diagnostic Challenges:
Distinction from ovarian primary
Small biopsy specimens
Mixed histologies
Distinction from EIC (invasion required).
Rare Variants:
Mixed serous-endometrioid
Serous with clear cell features
Micropapillary variant
Solid variant
Transitional-like morphology.
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
[specimen type], uterus measuring [size] cm
Diagnosis
Endometrial serous carcinoma
Classification
Classification: WHO serous carcinoma, FIGO grade 3
Histological Features
Shows [papillary/glandular/solid] architecture with high nuclear grade
Size and Extent
Size: [X] cm, myometrial invasion: [depth] ([percentage]%)
Lymphovascular Invasion
Lymphovascular invasion: [present/absent]
Cervical Involvement
Cervical involvement: [present/absent]
Adnexal Involvement
Adnexal involvement: [present/absent]
Special Studies
IHC: p53 [overexpressed/lost], WT1 positive
Molecular: [if performed]
[other study]: [result]
Prognostic Factors
Prognostic factors: [stage, invasion depth, LVI]
Final Diagnosis
Final diagnosis: Endometrial serous carcinoma, FIGO stage [X]