LAUSR

For patients with Lynch Syndrome (LS) (formerly known as hereditary nonpolyposis colorectal cancer or HNPCC), inheritance of one of several mutated mismatch repair genes (MMR) results in an increased risk for a variety of malignancies including colon, rectal, endometrial, urinary tract, gastric, small bowel and others [1]. Confirmation of increased risk of particular malignancies for patients harboring an MMR germline mutation has typically been the result of population studies of families tracked for the development of the possible associated cancer. When cancer results from inheritance of a particular mutated MMR gene, the malignancy has a characteristic fingerprint referred to as microsatellite instability-high (MSI-H), which results from deficient expression of the inherited MMR gene product (dMMR). Therefore, if sporadic tumors of a particular tissue of origin are only rarely dMMR, identifying a tumor as dMMR in a known LS family member suggests that, in that particular family, inheritance of the mutated MMR gene does predispose to that malignancy. Here we describe a patient diagnosed with a germline mutation in the MMR gene MSH6 who developed an oral pharynx cancer. Oral pharynx cancers are not known to be associated with LS. By confirming that the tumor was not dMMR and not MSI-H, it was concluded that his oral pharynx cancer was sporadic, rather than LS-related, and other family members carrying the mutated MSH6 are unlikely to be at above-average risk for the development of oral cancers, as a result of the LS. In additional, he would not be eligible for the so-called FDA agnostic approved immunotherapy which is endorsed for dMMR or MSI-H tumors [2].