The World Health Organization (WHO) classifies endometrial carcinoma (EC) into several histological subtypes, each with distinct characteristics and implications for diagnosis and treatment.
1. Endometrioid Carcinoma
Prevalence: Endometrioid carcinoma is the most common form, representing 75-80% of all EC cases.
Histopathology: This type features tall columnar cells that line closely packed glands, often without intervening stroma, indicating possible invasion. The glandular structures typically have smooth luminal contours, and cribriform patterns are frequently observed. Variants may include squamous differentiation, mucinous differentiation (marked by significant intracellular mucin), and secretory patterns characterized by prominent cytoplasmic vacuoles.
Myometrial Invasion Patterns: Invasive patterns may be infiltrative, associated with stromal fibrosis and inflammation, or a more subtle pushing pattern where neoplastic cells extend into the myometrium without significant stromal reaction. The microcystic elongated and fragmented pattern (“MELF”) in grade 1 tumors is linked to lymphovascular invasion and metastases.
Grading: Endometrioid carcinomas are graded according to the FIGO system:
- Grade 1: Less than 5% solid growth.
- Grade 2: 6-50% solid growth.
- Grade 3: More than 50% solid growth.
Nuclear atypia can influence grading; marked nuclear atypia can elevate the grade.
Molecular Subtypes: These tumors can fall into any of the four molecular subtypes, highlighting genetic diversity. Many grade 3 tumors exhibit profiles similar to serous carcinomas and may harbor significant genomic alterations and TP53 mutations.
Prognosis: Generally, endometrioid carcinomas are low-grade, diagnosed early, and have favorable outcomes. However, approximately 5% of low-grade tumors may exhibit p53 abnormalities, correlating with poorer prognosis.
2. Serous Endometrial Carcinoma
Prevalence: Serous carcinoma is the second most common type, accounting for around 10% of cases.
Histopathology: Characterized by papillary structures and serrated gland outlines, serous carcinoma cells display significant nuclear atypia and numerous mitotic figures. Psammoma bodies may also be present.
Molecular Subtypes: A large majority fall under the p53-abnormal subtype. Some cases exhibit HER2 overexpression, which may be targeted therapeutically.
Prognosis: This carcinoma often shows extrauterine disease at diagnosis and can infiltrate the myometrium extensively, resembling ovarian carcinoma. However, early-stage serous carcinoma confined to the endometrium may have a good prognosis.
3. Clear Cell Carcinoma
Prevalence: Clear cell carcinoma is rare, comprising less than 5% of EC cases, often seen in older, postmenopausal women.
Histopathology: These tumors display various architectural patterns, including papillary and tubulocystic formations. The cells often have abundant clear cytoplasm, although eosinophilic and hobnail cell types may also be present.
Molecular Subtypes: Clear cell carcinomas may represent any molecular subtype. Those with POLE mutations generally have better outcomes, while p53-abnormal cases are more aggressive. MMR-deficient tumors may present mixed morphologies.
Prognosis: Clear cell carcinomas typically show negative estrogen receptor status and positive Napsin A, aiding in differential diagnosis.
4. Mixed Carcinoma
Description: These tumors exhibit at least two distinct histologic components, typically combining endometrioid and high-grade nonendometrioid patterns, such as serous or clear cell. They often share the same molecular characteristics.
5. Undifferentiated/Dedifferentiated Carcinoma
Description: This group lacks glandular or squamous differentiation. Dedifferentiated variants often feature grade 1 or 2 endometrioid components alongside undifferentiated areas. They may frequently show MMR deficiency and have specific genetic mutations.
6. Carcinosarcoma
Prevalence: Previously known as malignant mixed Müllerian tumor, carcinosarcoma accounts for less than 5% of EC cases and is considered aggressive.
Histopathology: It comprises both high-grade sarcomatous and carcinomatous components, with the former originating from uterine tissue types and the latter often being difficult to classify.
Molecular Subtypes: The majority are categorized as p53-abnormal, with some showing features of other molecular subtypes.
7. Rare Subtypes
Description: Rare types include mesonephric and mesonephric-like adenocarcinomas, which have distinct immunophenotypes and aggressive behavior. Pure squamous cell carcinomas of the endometrium are also rare and must be differentiated from endometrioid carcinomas with squamous differentiation.
Pathology Reporting
The International Collaboration on Cancer Reporting (ICCR) provides guidelines for essential factors to include in EC pathology reports, emphasizing the importance of histology and grading. Recommendations for molecular marker testing include:
- Mismatch Repair (MMR) Testing: Conduct MMR immunohistochemistry or MSI assays for all EC cases to aid in Lynch syndrome screening.
- p53 Testing: Perform on high-grade and atypical low-grade cases to determine treatment options.
- POLE Testing: Consider for cases with specific risk factors or in clinical trials.
- Estrogen Receptor (ER) Testing: Useful for prognosis and treatment decision-making.
- HER2 Assessment: Evaluate for potential therapeutic targeting.
These guidelines aim to enhance the accuracy of diagnoses and optimize treatment strategies for patients with endometrial carcinoma.
