An Unusual Case of Sporadic Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome

Cutis. 2015 February;95(2):E7-E9

February 6, 2015|Cutis

Priyadharsini Nagarajan, MD, PhD;Barton Kenney, MD;Paul Drost, MD

Hereditary leiomyomatosis and renal cell carcinoma syndrome (HLRCCS) is a rare, highly penetrant, autosomal-dominant disorder that has been reported in approximately 200 families worldwide. More than 90% of patients with HLRCCS develop multiple cutaneous leiomyomata, frequently in a segmental distribution, that increase in number and size with age. Patients may present initially to dermatologists; therefore, it is important to recognize the cutaneous manifestations of these conditions because early diagnosis of renal cancer may provide to be lifesaving.

Figure 3. Proposed mechanism of tumorigenesis in hereditary leiomyomatosis and renal cell carcinoma syndrome. In the presence of functional fumarate hydratase (FH), hypoxia-inducible factor (HIF) is degraded, resulting in normoxia (top panel). In the absence of functional FH, there is accumulation of fumarate, while malate levels decrease, and the glucose metabolism through Krebs cycle shifts toward anaerobic glycolysis, even when sufficient oxygen is present to support respiration (bottom panel). Increased fumarate inhibits HIF prolyl hydroxylase (HPH), which leads to stabilization of HIF, a transcription factor, that enhances anaerobic glycolysis, cellular proliferation, and angiogenesis, leading to tumor growth.

Patients with renal tumor–associated hereditary syndromes may present initially to dermatologists; therefore, it is important to recognize the cutaneous manifestations of these conditions because early diagnosis of renal cancer may prove to be lifesaving.

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