Hereditary Syndromes Manifesting as Endometrial Carcinoma: How Can Pathological Features Aid Risk Assessment?

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2) Histological Evaluation. Endometrial carcinomas associated with LS have been shown to exhibit a tendency to occur in the lower uterine segment (LUS) with up to third of such tumors attributed to this syndrome [38]. Histologically, LS-associated tumors have a diverse morphological appearance. The most common subtype is endometrioid carcinoma but serous carcinoma, clear cell carcinoma, and carcinosarcoma are also well accounted for [39]. Nonendometrioid carcinomas such as clear cell carcinoma, serous cell carcinoma, and carcinosarcoma are known to occur in LS patients at a younger age than is commonly seen in non-LS patients [40]. There is also a well-documented predisposition for LS-associated tumors to exhibit high grade features with a mixed histology which can at times represent a huge challenge to anatomic pathologists attempting to subtype the tumor components into the various neat categorical variants [41, 42]. Difficulty in separating the various tumor components comprising endometrioid, serous, and/or clear cell carcinomas is not uncommon in such situations [42]. Interestingly, tumors seen arising in the LUS have been shown to occasionally disclose histological and immunohistochemical features which are difficult to ascertain if the tumor is an endometrial or endocervical primary adenocarcinoma [38].

 Table 1: A summary of the epidemiological, mutational, clinical, and pathological characteristics and features encountered in hereditary syndromes manifesting as endometrial carcinoma. The indicators noted by pathologists to augur a need to notify clinicians on the possible need for referral to a geneticist for further clinical assessment and confirmatory gene mutational testing. Highlighted in the extreme right column are the histological features seen on microscopy and ancillary tests including immunohistochemistry and polymerase chain reaction- (PCR-) based tests such as microsatellite instability analysis and MLH-1 methylation study.