Context: Germline mutations in fumarate hydratase (FH) gene are known to cause hereditaryleiomyomatosis and renal cell carcinoma (HLRCC) and are occasionally accompanied withcutaneous and uterine leiomyoma or cortisol-producing adrenocortical hyperplasia. However,the association between FH mutations and cardiac or adrenocortical tumors has remainedunknown. Here, we identified a novel deletion in FH, exhibiting cardiac myxoma and subclinicalCushing syndrome due to adrenocortical tumor.Case Description: A 44-year-old man was referred to our hospital for cardiac and adrenaltumor evaluation. He had a history of multiple painful, dermal papules and nodules diagnosedas cutaneous leiomyoma. The surgically resected cardiac tumor was diagnosed as myxoma.The adrenal tumor was clinically diagnosed as subclinical Cushing syndrome. Laparoscopicallyresected adrenal tumor was pathologically diagnosed as adrenocortical adenoma harboringunique histological findings similar to primary pigmented nodular adrenocortical disease(PPNAD). DNA analysis revealed a germline deletion in FH c0.737delT (p. Phe225Leufs*31)and loss of heterozygosity (LOH) in cardiac myxoma. As a functional analysis of FH in cardiacmyxoma, low FH protein expression with elevated 2-succinocysteine (2SC), a marker of FHdysfunction, was immunohistochemically detected. However, in adrenocortical tumor, LOH of FHwas not detected, and FH or 2SC expression was not altered.Conclusions: This is the first case of HLRCC complicated by cardiac myxoma. LOH of FH deletionand its dysfunction were identified in cardiac myxoma. The association between FH deletion andadrenocortical lesion, however, needs to be further clarified.
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Clinical Biochemistry
- Biochemistry, medical