Figure 5. Model of synchronous endometrial and ovarian cancer development in the Lynch syndrome and sporadic settings.

One could hypothesize a model in the setting of Lynch syndrome, where the likelihood of transformation happening in the endometrium, either eutopic or ectopic, is high (⚡). Synchronous endometrial carcinomas (ECs) and ovarian carcinomas (OCs) can either constitute independent lesions, whereby the endometrium and the ectopic endometrial cells would transform independently and have no somatic genetic alterations in common (left) or be clonally related lesions in the form of a primary EC giving rise to the OC (middle). In the context of sporadic cancers, the likelihood of transformation of the eutopic or ectopic endometrium is lower; therefore, the majority of synchronous ECs/OCs are clonally related and likely derived from a primary EC “metastasizing” to the ovary (middle). It should be noted, however, that in the context of clonally related synchronous ECs/OCs, both in the sporadic and Lynch/CMMRD settings, another possibility that could be entertained includes one where the endometrium that gave rise to the endometriosis, albeit not entirely transformed, already harbored somatic genetic alterations acquired early in the development of ECs. In this case, there would be a subset of somatic genetic alterations shared between the EC and the OC, hence the lesions would be clonal, however a high number of genetic alterations that diverge between the two lesions would be expected. CMMRD, constitutional mismatch repair deficiency.