Familial adrenocortical carcinoma in association with Lynch syndrome
Annamalai, Anand Kumar
Marker, Alison J
Arends, Mark J
Familial ACC in Lynch Syndrome
Journal of Clinical Endocrinology and Metabolism
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Challis, B., Kandasamy, N., Powlson, A., Koulouri, O., Annamalai, A. K., Happerfield, L., Marker, A. J., et al. (2016). Familial adrenocortical carcinoma in association with Lynch syndrome. Journal of Clinical Endocrinology and Metabolism https://doi.org/10.1210/jc.2016-1460
Context: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a poor prognosis. Although the majority of childhood ACC arises in the context of inherited cancer susceptibility syndromes, it remains less clear whether a hereditary tumour predisposition exists for the development of ACC in adults. Here, we report the first occurrence of familial ACC in a kindred with Lynch syndrome due to a pathogenic germline MSH2 mutation. 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.
adrenocortical carcinoma, Lynch syndrome, MSH2
ASP, OK and MG are supported by the National Institutes for Health Research Cambridge Biomedical Research Centre. SNZ is a Wellcome Trust Intermediate Clinical Fellow (WT100183MA). We are grateful to Dr Joan Patterson for clinical advice and Dr Erik Schoenmakers for assistance with illustrations.
National Institute for Health Research ()
External DOI: https://doi.org/10.1210/jc.2016-1460
This record's URL: https://www.repository.cam.ac.uk/handle/1810/255981