Familial adrenocortical carcinoma in association with Lynch syndrome

 adrenocortical carcinoma
 


open access
 

Case:

 A 54-year-old female, with a history of ovarian and colorectal malignancy, was found to have an ACC. A detailed family history revealed her mother had died of ACC and her sister had previously been diagnosed with endometrial and colorectal cancers. A unifying diagnosis of Lynch syndrome was considered, and immunohistochemical analyses demonstrated loss of MSH2 and MSH6 expression in both adrenocortical carcinomas (proband and her mother), and in the endometrial carcinoma of her sister. Subsequent genetic screening confirmed the presence of a germline MSH2 mutation (resulting in deletions of exons 1–3) in the proband and her sister.

Conclusion:

Our findings provide strong support for the recent proposal that ACC should be considered a Lynch syndrome associated tumour and included in the Amsterdam II clinical diagnostic criteria. We also suggest that screening for ACC should be considered in cancer surveillance strategies directed at individuals with germline mutations in DNA mismatch repair genes.

In summary, we report the first description of familial ACC in conjunction with a germline MSH2 mutation and provide support for MMR genes as candidates in hereditary ACC. We advocate ACC be now included in clinical diagnostic criteria for LS and considered in cancer surveillance strategies for individuals with germline mutations in DNA MMR genes. Moreover, in the absence of clinical management guidelines for ACC surveillance in patients with inherited cancer syndromes, including LS, we recommend individualized screening protocols coupled with ongoing clinical vigilance.