Immunohistochemical Detection of HLRCC Markers


Dr. Rohit Mehra led a study on hereditary leiomyomatosis and renal cell carcinoma (HLRCC) that is caused by germline mutations in the FH gene, and is associated with increased incidence of leiomyomas and a potentially aggressive variant of renal cell carcinoma (HLRCC-associated RCC). Absence of fumarate hydratase (FH) expression as determined by immunohistochemistry has previously been used to diagnose HLRCC-associated RCC, but immunohistochemical staining of leiomyomas is not standard practice. Here, Dr. Mehra and colleagues performed immunohistochemistry (IHC) on whole sections from consecutive cutaneous leiomyomas from archived samples (96 samples from 87 patients) to evaluate for both FH and succinate dehydrogenase B expression, in addition to clinicopathologic data collection and review of all hematoxylin and eosin-stained slides for blinded morphologic evaluation of features reported to be seen in HLRCC-associated uterine leiomyomas. The overall sensitivity and specificity of negative FH expression in leiomyomas for detection of patients with HLRCC were 70.0% and 97.6%, respectively. Inclusion of cases classified as equivocal increased sensitivity to 75.0%. Succinate dehydrogenase B expression was retained in 95 specimens and equivocal in 1 specimen. None of the evaluated morphologic features showed any association with leiomyomas in HLRCC. Absent FH immunohistochemical expression in cutaneous leiomyomas is a sensitive and specific marker for detection of HLRCC, thus suggesting a role for prospective FH IHC in patients with these tumors to screen for HLRCC. The results of this study was published in Am J Surg Pathol (2017 Jun;41(6):801-809).

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Immunohistochemical assays for FH and SDH-B are routinely performed for clinical use as/when indicated to detect syndromic neoplasia at Michigan Medicine Department of Pathology.