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

Introduction: POLE mutant phenotype in colon adenocarcinomas represents a rare molecular subtype. These tumours are generally responsive to immune-checkpoint inhibition therapy and, therefore, are currently considered as a subtype with good prognosis. We hereby present the first detailed case presentation of a POLE mutant colon adenocarcinoma with useful microscopic features.
Case Report: A 53-year-old male patient's colon adenocarcinoma histologically showed wide variety of growth patterns and massive intra- and peritumoural lymphocytic infiltrate. The majority of the tumour consisted of a high-grade component resembling medullary carcinoma of the colon, while approximately one-third of the tumour was composed of conventional areas exhibiting a tubular pattern. A minority of the tumour was constituted by poorly cohesive rhabdoid cells. Immunohistochemistry was performed, and colorectal origin was proven with CDX-2 and SATB2. Furthermore, proficiency in mismatch repair proteins and SMARCB1 deficiency was observed. The unusually high-grade colon adenocarcinoma, with areas mimicking medullary carcinoma, and generally aggressive morphology raised suspicion of microsatellite instability. The diverse morphology and the SMARCB1 deficiency also raised suspicion of ultramutation caused by POLE alteration. Next-generation sequencing panel confirmed a pathogenetic mutation in POLE exon 9: p.Pro286Arg, c.857C > G.
Discussion: The diverse, high-grade morphology and increased intratumoural lymphoid infiltration should raise suspicion for POLE-mutated adenocarcinoma during everyday histopathological practice. Mismatch repair proficiency results on immunohistochemistry should not determine the final diagnosis, as only a minor percentage of these tumours are MSI. In every case suspicious for POLE-mutated adenocarcinoma, a 500-cancer gene panel should be carried out.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)