POLE-Mutant Colon Adenocarcinoma-Case Presentation and Histopathological Evaluation

Tamás Pancsa; Béla Vasas; Zsombor Melegh; Erika Tóth; László Torday; Anita Sejben

doi:10.1007/s12029-023-01004-4

POLE-Mutant Colon Adenocarcinoma-Case Presentation and Histopathological Evaluation

J Gastrointest Cancer. 2024 Jan 4. doi: 10.1007/s12029-023-01004-4. Online ahead of print.

Authors

Tamás Pancsa¹, Béla Vasas¹, Zsombor Melegh², Erika Tóth², László Torday³, Anita Sejben⁴

Affiliations

¹ Department of Pathology, University of Szeged, Állomás U. 1, Szeged, 6725, Hungary.
² Center of Tumor Pathology, Department of Surgical and Molecular Pathology, National Institute of Oncology Hungary, Ráth György U. 7-9, Budapest, 1122, Hungary.
³ Department of Oncotherapy, University of Szeged, Korányi fasor 12, Szeged, 6720, Hungary.
⁴ Department of Pathology, University of Szeged, Állomás U. 1, Szeged, 6725, Hungary. sejben.anita@gmail.com.

PMID: 38175383
DOI: 10.1007/s12029-023-01004-4

Abstract

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.

Keywords: Immune-checkpoint inhibition therapy; Next-generation sequencing; POLE mutation; POLE-mutant colon adenocarcinoma.