POLE-mutated Endometrial "Carcinosarcoma".

Area of Science:

• Gynecologic Oncology
• Molecular Pathology
• Cancer Genomics

Background:

• The molecular classification of endometrial carcinoma has advanced disease understanding.
• Integrating histotype and molecular data remains challenging for specific diagnoses.
• Distinguishing between endometrial carcinoma subtypes and carcinosarcoma requires precise criteria.

Observation:

• Two cases presented with morphological features suspicious for endometrial carcinosarcoma but did not meet diagnostic criteria.
• Subsequent molecular testing identified pathogenic POLE mutations in both cases.
• These findings prompted a revised diagnosis of low-grade endometrioid endometrial carcinoma with a homologous sarcoma component.

Findings:

• Pathogenic POLE mutations were detected in cases morphologically resembling carcinosarcoma.
• The presence of POLE mutations in these cases questions the validity of diagnosing POLE-mutated endometrial carcinosarcoma.
• A descriptive diagnosis integrating histopathology and molecular findings is proposed.

Implications:

• This study highlights the importance of molecular testing in refining endometrial carcinoma diagnoses.
• The findings necessitate a re-evaluation of diagnostic criteria for endometrial carcinosarcoma, particularly in POLE-mutated cases.
• Accurate classification impacts treatment strategies and prognostic assessments for endometrial cancer patients.