MITF Activation Is a Feature of Clear Cell and Conventional Fibrous Papule

Fibrous papule, also known as angiofibroma, is a common benign cutaneous lesion with a predilection for the nose and, to a lesser extent, other parts of the face. Most cases occur sporadically, although similar lesions occur in tuberous sclerosis where they are sometimes referred to as adenoma sebaceum. In addition to conventional fibrous papule, several morphologic subtypes have been described which are much less common and may be more challenging to recognize. Clear cell fibrous papule is distinguished by its voluminous clear cytoplasm and the expression of NKI-C3, a marker of lysosomes. Here we show that clear cell fibrous papule is characterized by MITF overexpression and activation, and is accompanied by overexpression of GPNMB, a direct transcriptional target of MITF. Surprisingly, MITF overexpression was also seen in both conventional fibrous papule and tuberous-sclerosis-associated fibrous papules, suggesting a potentially unifying cellular feature in all three subtypes of fibrous papule. Furthermore, since the mTOR pathway, which is dysregulated in tuberous sclerosis, regulates the MITF/TFE family of transcription factors, these findings also suggest a potential mechanistic link between sporadic and syndromic fibrous papules.