What is Endometrioid Carcinoma?
Endometrioid carcinoma is the most common histologic subtype of endometrial cancer, accounting for 75-90% of all cases, characterized by glands that microscopically resemble normal proliferative endometrium and classified as Type I endometrial cancer. 1, 2, 3
Histologic and Clinical Characteristics
Endometrioid carcinoma is composed of glands that resemble those of the normal endometrium, at least in well-differentiated forms 4, 5. The tumor is graded architecturally based on the ratio of solid to glandular components:
- Grade 1: <5% solid component
- Grade 2: 5-50% solid component
- Grade 3: >50% solid component 4
Important caveat: The traditional three-tier grading system is evolving toward a two-tier system that combines grades 1 and 2 as "low grade" and designates grade 3 as "high grade" 2.
Type I vs Type II Classification
Endometrioid carcinoma represents the prototypical Type I endometrial cancer, which differs fundamentally from Type II cancers 3:
Type I (Endometrioid) characteristics:
- Estrogen-dependent and associated with hyperestrogenism
- Linked to obesity, metabolic syndrome, diabetes, and hypertension
- Often preceded by endometrial hyperplasia
- Expresses estrogen and progesterone receptors (>90% express moderate to high levels)
- Generally well to moderately differentiated
- Better prognosis when low grade 3, 6
Type II cancers (serous, clear cell, carcinosarcoma) are estrogen-independent, occur in atrophic endometrium, and behave more aggressively 1, 4.
Molecular Profile
Endometrioid carcinomas harbor characteristic genetic alterations 1:
- PTEN mutations (most common)
- KRAS mutations
- PIK3CA mutations
- CTNNB1 (β-catenin) mutations (especially in tumors with squamous differentiation)
- MLH1 promoter hypermethylation leading to microsatellite instability
- FGFR2 mutations 7, 6
Critical distinction: While most endometrioid carcinomas are low grade with favorable prognosis, approximately 25% of high-grade (grade 3) endometrioid carcinomas harbor TP53 mutations and behave like aggressive Type II serous carcinomas 1. This molecular heterogeneity underscores why molecular classification is increasingly important beyond traditional histologic typing.
Clinical Context
Endometrioid carcinoma typically presents with:
- Postmenopausal bleeding (90% of cases) 4
- Early-stage disease at diagnosis (80% stage I) 1
- Excellent 5-year survival rates >95% for stage I disease 1
- Median age at diagnosis of 63 years 1
Prognostic Factors Beyond Histology
Key prognostic determinants include 2:
- Myometrial invasion depth (>50% invasion indicates higher risk)
- Lymphovascular space invasion (substantial LVSI defined as ≥4 vessels is particularly adverse)
- Cervical stromal invasion
- Lymph node metastases
- Tumor diameter (>2 cm)
- Molecular subtype (POLE-mutated has excellent prognosis; p53-aberrant has poor prognosis)
Modern approach: The 2022 ESMO guidelines emphasize that molecular classification (POLE ultramutated, microsatellite unstable, copy-number high/p53-abnormal, or no specific molecular profile) should supplement traditional histologic assessment to refine risk stratification and guide treatment decisions 2.