Definition/General
Introduction:
Endometrial clear cell carcinoma is a rare high-grade adenocarcinoma characterized by cells with clear cytoplasm and hobnail morphology
It represents 1-6% of endometrial carcinomas but has a disproportionately poor prognosis.
Origin:
Arises from endometrial glandular epithelium
Part of Type II endometrial cancers (non-estrogen related)
May arise from atrophic endometrium.
Classification:
WHO Classification: High-grade endometrial adenocarcinoma, clear cell type
FIGO grade 3 by definition
Part of Type II pathway.
Epidemiology:
Peak incidence 60-70 years
Not associated with estrogen exposure
More common in Japanese women
Associated with Lynch syndrome in some cases.
Clinical Features
Presentation:
Postmenopausal bleeding
Enlarged uterus
Often advanced stage at presentation
Abnormal endometrial sampling.
Symptoms:
Vaginal bleeding
Pelvic pain
Abdominal distension
Constitutional symptoms in advanced cases.
Risk Factors:
Advanced age
Not associated with obesity or diabetes
Lynch syndrome (MLH1/MSH2 mutations)
Previous pelvic radiation.
Screening:
No specific screening
Diagnosed on endometrial biopsy
CA-125 may be elevated
Imaging shows complex mass.
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Gross Description
Appearance:
Polypoid or papillary mass
Friable consistency
Cut surface shows solid and cystic areas
Necrosis may be present.
Characteristics:
Variable size
Tan to gray coloration
Soft to firm consistency
May show hemorrhage.
Size Location:
May involve entire endometrial cavity
Myometrial invasion common
Cervical extension possible.
Multifocality:
Usually unifocal
May have multifocal disease
Metastatic spread to ovaries and peritoneum.
Microscopic Description
Histological Features:
Cells with clear to eosinophilic cytoplasm
Characteristic hobnail cells with apical nuclei
Papillary, tubulocystic, and solid patterns.
Cellular Characteristics:
Clear cytoplasm due to glycogen
Hobnail morphology with protruding nuclei
High nuclear grade
Prominent nucleoli.
Architectural Patterns:
Papillary (most common)
Tubulocystic
Solid
Mixed patterns frequent
Hyalinized stroma.
Grading Criteria:
High-grade by definition
Nuclear grade 3
All architectural patterns considered high-grade.
Immunohistochemistry
Positive Markers:
Napsin A positive (diagnostic)
CK7 positive
EMA positive
p53 variable (wild-type pattern)
ER/PR usually negative.
Negative Markers:
CK20 negative
CDX2 negative
TTF-1 negative
WT1 negative
p16 usually negative.
Diagnostic Utility:
Napsin A highly specific for clear cell carcinoma
Helps distinguish from serous carcinoma
p53 wild-type pattern typical.
Molecular Subtypes:
Microsatellite stable in most cases
POLE mutations rare
p53 wild-type typically.
Molecular/Genetic
Genetic Mutations:
PIK3CA mutations common
ARID1A mutations
PTEN mutations
TP53 mutations less common than serous
MLH1 promoter methylation possible.
Molecular Markers:
Microsatellite status important
POLE sequencing if young patient
PIK3CA mutations for targeted therapy.
Prognostic Significance:
Poor prognosis overall
Stage most important factor
MMR deficiency may predict immunotherapy response.
Therapeutic Targets:
PIK3CA inhibitors
mTOR inhibitors
Immune checkpoint inhibitors if MMR deficient.
Differential Diagnosis
Similar Entities:
Serous carcinoma
Secretory carcinoma
Yolk sac tumor
Clear cell carcinoma of ovary
Metastatic renal cell carcinoma.
Distinguishing Features:
Clear cell: Napsin A+, hobnail cells
Serous: p53+, WT1+
Secretory: S-100+
Yolk sac: AFP+, young age.
Diagnostic Challenges:
Distinction from serous carcinoma
Recognition of mixed patterns
Metastatic vs primary.
Rare Variants:
Mixed with endometrioid
Oxyphilic variant
Signet ring-like cells.
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 clear cell carcinoma
Final Diagnosis
Final diagnosis: Endometrial clear cell carcinoma, FIGO stage [X]