The spectrum of clinical and genetic findings in hereditary leiomyomatosis and renal cell cancer (HLRCC) with relevance to patient outcomes: a retrospective study from a large academic tertiary referral center

Thomas Scharnitz; Mio Nakamura; Erika Koeppe; Marie-Louise Henry; Lori Lowe; Tobias Else; Kelly B Cha

The spectrum of clinical and genetic findings in hereditary leiomyomatosis and renal cell cancer (HLRCC) with relevance to patient outcomes: a retrospective study from a large academic tertiary referral center

Am J Cancer Res. 2023 Jan 15;13(1):236-244. eCollection 2023.

Authors

Thomas Scharnitz¹, Mio Nakamura², Erika Koeppe³, Marie-Louise Henry⁴, Lori Lowe⁵, Tobias Else³, Kelly B Cha²

Affiliations

¹ Dermatology and Laser Center of Charleston SC 29414, USA.
² Department of Dermatology, University of Michigan MI 48109, USA.
³ Department of Internal Medicine, University of Michigan MI 48109, USA.
⁴ Cancer Center, University of Michigan MI 48109, USA.
⁵ Department of Pathology, University of Michigan MI 48109, USA.

PMID: 36777509
PMCID: PMC9906083

Abstract

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant condition attributed to pathogenic variants in fumarate hydratase (FH) and presents with cutaneous leiomyomas (CLMs), uterine leiomyomas (ULMs) and renal cell cancer (RCC). The objective of this study was to characterize the spectrum of clinical and genetic findings in HLRCC at a large academic tertiary care referral center with a focus on dermatologic manifestations. Fifty-seven patients, 41 female and 16 male, with 27 unique pathogenic or likely-pathogenic FH variants were identified from 38 families. Mean age of HLRCC diagnosis was 44.4 years (range 8-82). CLMs were the primary reason for referral in 49.1% (n=28). CLMs were present in 43/56 patients who underwent full skin examination. Three of these 56 patients were diagnosed with cutaneous leiomyosarcoma. Incidence of ULMs was 37/41 female patients; no uterine leiomyosarcomas were observed. RCC was observed in 6/57 patients (mean age of diagnosis: 47.3 years (range 28-79)). CLMs predated RCC in the 3 patients diagnosed with both. Dermatologists have an opportunity to recognize cutaneous manifestations of HLRCC, including cutaneous leiomyomas and rarely cutaneous leiomyosarcomas, and refer for genetic evaluation to provide definitive diagnosis. Identification of HLRCC can promote family cascade testing and screening for RCC.

Keywords: Hereditary leiomyomatosis and renal cell cancer; cutaneous leiomyoma; cutaneous leiomyosarcoma; fumarate hydratase; genetic variants; reed syndrome; renal cell cancer; uterine leiomyoma.