Photo Challenge
Erythematous Nodular Plaque Encircling the Lower Leg
A 66-year-old woman presented with red to violaceous, rapidly growing nodules on the skin. Her medical history was remarkable for diabetes...
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.
