Mixed Endometrioid and Clear Cell Carcinoma of the Endometrium: A Plethora of Issues for the Diagnostic Pathologist Ovarian Cancer and Us OVARIAN CANCER and US Ovarian Cancer and Us

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Sunday, July 24, 2016

Mixed Endometrioid and Clear Cell Carcinoma of the Endometrium: A Plethora of Issues for the Diagnostic Pathologist



abstract
 Mixed Endometrioid and Clear Cell Carcinoma of the Endometrium: A Plethora of Issues for the Diagnostic Pathologist

A case of mixed endometrioid and clear cell (CCC) endometrial carcinoma with ovarian and peritoneal metastasis of the CCC component is presented. This raised several diagnostic issues, beginning with the morphological recognition of CCC. It is increasingly recognized that CCC is a rare subtype in the endometrium, raising questions regarding its clinical connotations. Traditionally regarded as a type 2 aggressive histotype, there are current efforts to assess its true incidence and place within the clinical and molecular spectrum of endometrial carcinomas. Both mixed carcinomas and CCC fall into the category of tumors currently acknowledged to show “ambiguous” morphology, that is, those in which morphology does not reliably indicate clinical behavior. As the 4 major molecular subgroups of endometrial carcinoma, as revealed by The Cancer Genome Atlas, become better characterized, there are indications that these ambiguous tumors may fall into those groups with a high mutation rate: “ultramutated” (harbouring mutations in polymerase epsilon, POLE) or “hypermutated” (characterised by microsatellite instability, MSI). Testing such or all tumors for mismatch repair gene proteins remains variable with no universally accepted guidance. Aside from screening for Lynch syndrome, this testing also indicates the neoplasm as belonging to the MSI subgroup and may have predictive value for immunotherapy. Finally, there are recent insights into synchronous endometrial and ovarian carcinoma; although traditionally considered to be independent primary carcinomas, these are clonally related as demonstrated by 2 independent recent studies, that is, representing an indolent form of metastasis.

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