Cytopathological features associated with POLE mutation in endometrial cancer

Abstract Objective For patients with endometrial cancer, the POLE (polymerase epsilon) mutation ( POLE mut)‐subtype, one of four molecular‐analysis‐based categories in the Cancer Genome Atlas (TCGA), has the best prognosis. The following histological characteristics are typically observed in endometroid carcinoma cases with the POLE mut‐subtype: (1) the presence of tumour giant cells, (2) numerous tumour‐infiltrating lymphocytes (TILs) and/or peri‐tumoral lymphocytes, and (3) a high grade. However, in the context of cytology, the morphological characteristics of this subtype remain unknown. Methods DNA extracted from formalin‐fixed paraffin‐embedded (FFPE) tissues was subjected to next‐generation sequencing analysis and categorised according to the TCGA classifications. Genomic mutation, tumour mutation burden (TMB), and microsatellite instability were also assessed. Cytological specimens of resected uteri obtained using the Papanicolaou method were histologically separated into three types. Results Seven out of 112 patients (6%) with endometrial cancer were diagnosed with the POLE mut‐subtype between January 2019 and August 2021. Tumour giant cells were observed in three cases (43%) on histology and cytology. TIL and/or peritumoral lymphocytes with inflammatory cells were detected in five cases (71%) on histology and three cases (43%) on cytology. Cases in which these three characteristics were observed on both cytology and histology may have belonged to the POLE mut‐subtype. There were no cases in which these characteristics were absent on histology but present on cytology. TMB tended to be higher in cases when the three characteristics were observed in both cytological and histological findings. Conclusions Preoperative endometrial cytology highlighted the characteristics of the POLE mut‐subtype in the histological analysis of resected uterine specimens and has the potential to play an important role in treatment decisions.