Original ArticlesImmunohistochemical Characterization of Fumarate Hydratase (FH) and Succinate Dehydrogenase (SDH) in Cutaneous Leiomyomas for Detection of Familial Cancer SyndromesCarter, Cody S. MD*; Skala, Stephanie L. MD*; Chinnaiyan, Arul M. MD, PhD*,†,‡; McHugh, Jonathan B. MD*; Siddiqui, Javed MS‡; Cao, Xuhong MS‡; Dhanasekaran, Saravana M. PhD*,‡; Fullen, Douglas R. MD*,§; Lagstein, Amir MD*; Chan, May P. MD*,§; Mehra, Rohit MD*,†,‡Author Information Departments of *Pathology §Dermatology †Comprehensive Cancer Center, University of Michigan Health System ‡Michigan Center for Translational Pathology, Ann Arbor, MI Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Rohit Mehra, MD, Department of Pathology, University of Michigan Health System, Room 2G332 UH, 1500 E. Medical Center Drive, Ann Arbor, MI 48109 (e-mail: email@example.com). The American Journal of Surgical Pathology: June 2017 - Volume 41 - Issue 6 - p 801-809 doi: 10.1097/PAS.0000000000000840 Buy Metrics Abstract Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) 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). Absent immunohistochemical expression of fumarate hydratase (FH) has previously been used to diagnose HLRCC-associated RCC, but immunohistochemical staining of leiomyomas is not standard practice. We performed immunohistochemistry (IHC) on whole sections from consecutive cutaneous leiomyomas from our archives 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. Ninety-six cutaneous leiomyomas from 87 patients were identified; 12 of these specimens were from 7 patients with documented HLRCC. FH expression by IHC was absent in 9 specimens and retained in 85 specimens; 2 cases were equivocal with minimal FH expression. Seven of the 9 absent expression specimens were from patients with HLRCC, as were both of the equivocal specimens. The overall sensitivity and specificity of absent 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. Loss of 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. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.