POLE-Mutant Colon Adenocarcinoma-Case Presentation and Histopathological Evaluation.

Area of Science:

• Oncology
• Gastroenterology
• Molecular Pathology

Background:

• POLE mutations define a rare colon adenocarcinoma subtype, often responsive to immunotherapy and associated with a good prognosis.
• This case presents detailed microscopic features of a POLE-mutated colon adenocarcinoma, contributing to the understanding of this rare entity.

Observation:

• A 53-year-old male presented with colon adenocarcinoma exhibiting varied growth patterns, including high-grade medullary carcinoma-like areas, conventional tubular components, and rhabdoid cells.
• Immunohistochemistry confirmed colorectal origin and revealed mismatch repair proficiency alongside SMARCB1 deficiency.
• Next-generation sequencing identified a pathogenic POLE mutation (p.Pro286Arg, c.857C>G).

Findings:

• The diverse, high-grade morphology and significant intratumoral lymphoid infiltrate are key indicators for suspecting POLE-mutated adenocarcinoma.
• Mismatch repair proficient (MMR-P) status does not exclude POLE mutation, as only a minority of these tumors are microsatellite unstable (MSI).

Implications:

• Histopathological features like diverse high-grade morphology and lymphoid infiltration should raise suspicion for POLE-mutated colon cancer.
• Comprehensive molecular testing, such as a 500-cancer gene panel, is crucial for diagnosing POLE-mutated adenocarcinomas, irrespective of MMR status.
• Accurate identification of this subtype can guide therapeutic strategies, potentially improving patient outcomes.