ABSTRACT
BACKGROUND: Activating mutations in BRAF have been observed in up to 60% of melanomas, indicating a pivotal role for kinase deregulation in tumor progression. Vemurafenib is a specific inhibitor of BRAF for treatment of melanomas with activating BRAF V600E mutations and has been a major advancement in melanoma treatment. Treatment with vemurafenib, and to a lesser extent, sorafenib, a relatively non-specific inhibitor of BRAF, has been associated with cutaneous squamous cell carcinoma (SCC). METHODS: Clinical and microscopic characteristics of cutaneous neoplasms were evaluated following vemurafenib administration. RESULTS: Twenty-four of 47 (51%) patients receiving vemurafenib at our institution developed 146 total cutaneous neoplasms, with 75% developing multiple lesions. The median number of lesions in affected patients was three. Body distribution included head/neck (29%), chest/back (21%), upper (23%) and lower extremities (27%). Lesions were biopsied and pathologically showed multiple types of epidermal tumors including, but not limited to, verrucous keratoses with/without partial thickness dysplasia, actinic keratoses and well-differentiated and invasive SCCs with/without keratoacanthomatous features. CONCLUSIONS: We describe the histopathologic findings of skin lesions potentially associated with vemurafenib. Additional investigation is necessary to further elucidate cutaneous neoplasms associated with vemurafenib; however, frequent dermatologic evaluation is warranted in all patients receiving BRAF inhibitors.
Subject(s)
Indoles/adverse effects , Keratoacanthoma/chemically induced , Keratoacanthoma/pathology , Melanoma/drug therapy , Neoplasms, Second Primary/pathology , Proto-Oncogene Proteins B-raf/antagonists & inhibitors , Skin Neoplasms/chemically induced , Skin Neoplasms/pathology , Sulfonamides/adverse effects , Adult , Aged , Aged, 80 and over , Humans , Indoles/administration & dosage , Keratoacanthoma/enzymology , Keratoacanthoma/genetics , Male , Melanoma/enzymology , Melanoma/genetics , Middle Aged , Mutation , Neoplasms, Second Primary/enzymology , Neoplasms, Second Primary/genetics , Proto-Oncogene Proteins B-raf/genetics , Skin Neoplasms/enzymology , Skin Neoplasms/genetics , Sulfonamides/administration & dosage , VemurafenibABSTRACT
Nevoid hyperkeratosis of the nipple and areola is a benign condition with fewer than 70 cases reported in the literature. We report a case of unilateral nevoid hyperkeratosis of the areola with intraepidermal lymphocytes that resembled Pautrier's microabscesses on histological examination. This is the third report of mycosis fungoides-like changes in nevoid hyperkeratosis of the nipple and areola. In addition, this is the first case to present immunohistochemical and T-cell gene rearrangement studies of the intraepidermal lymphocytes. This case highlights a potential histopathological pitfall in the diagnosis of nevoid hyperkeratosis of the nipple and areola.
