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Familial Adrenocortical Carcinoma in Association With Lynch Syndrome.

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Challis, Benjamin G 
Kandasamy, Narayanan 
Powlson, Andrew S 
Koulouri, Olympia 
Annamalai, Anand Kumar 


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 tumor predisposition exists for the development of ACC in adults. Here, we report the first occurrence of familial ACC in a kindred with Lynch syndrome resulting from 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 AACs (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 tumor 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.



Adrenal Cortex Neoplasms, Adrenocortical Carcinoma, Colorectal Neoplasms, Hereditary Nonpolyposis, Female, Genetic Predisposition to Disease, Genetic Testing, Germ-Line Mutation, Humans, Middle Aged, MutS Homolog 2 Protein, Neoplastic Syndromes, Hereditary

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J Clin Endocrinol Metab

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The Endocrine Society
National Institute for Health Research (NIHR) (unknown)
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.