Co‐existence of BRAF V600E‐mutated malignant melanoma and BRAF V600E‐mutated Langerhans cell histiocytosis: A case report

Abstract

Langerhans cell histiocytosis (LCH) is a neoplastic condition of Langerhans cells, and can be associated with other neoplasms, especially BRAF-mutant hematological tumors and papillary thyroid carcinoma. Here we present the first case of co-existing LCH and low cumulative sun damage (low-CSD) melanoma, both of which had a BRAF V600E mutation. A 49-year-old man had a 45 Â 43 Â 15 mm semi-pedunculated, pigmented tumor in his back but had no other systemic symptoms. Histopathology revealed a 2-mm-sized incidental focus of LCH within a large lesion of low-CSD melanoma. Diffuse immunoexpression of CD1a, langerin/CD207, S100 protein, and BRAF (VE1) was observed in the focus of LCH. Sanger sequencing with microdissection confirmed BRAF V600E mutation in the component of LCH. Interestingly, the advanced melanoma also harbored the same BRAF V600E mutation, although the significance of this tumor combination is still unknown.

An Unexpected Diagnosis Uncovered by Quantitative Molecular Findings: A Case Report

“…1 Common genetic alterations involve the MAPK/ERK pathway, with BRAF V600E occurring in approximately 50% of cases. [1][2][3][4] Cases of LCH co-occurring with malignancies, including cutaneous melanoma, have been previously reported (Table 1), [5][6][7][8][9] with one case describing similar findings to ours, in which a cutaneous melanoma was associated with a very small focus of adjacent/intermixed LCH. 9 Notably, a few cases of LCH associated with nonmalignant melanocytic lesions have also been previously reported in children (Table 1).…”

“…[1][2][3][4] Cases of LCH co-occurring with malignancies, including cutaneous melanoma, have been previously reported (Table 1), [5][6][7][8][9] with one case describing similar findings to ours, in which a cutaneous melanoma was associated with a very small focus of adjacent/intermixed LCH. 9 Notably, a few cases of LCH associated with nonmalignant melanocytic lesions have also been previously reported in children (Table 1). 10,11 In the current case, which would be the first to describe a case of LCH associated with mucosal melanoma, the amount of LCH was minimal and objectively challenging to detect with histologic evaluation.…”

Langerhans Cells—Revising Their Role in Skin Pathologies

“…In this patient, a diffuse expression of CD1a, langerin/CD207, S100 protein, and BRAF (VE1) was found within LCH. Nevertheless, the link between the occurrence of melanoma and LCH in the same patient is unknown [49]. Furthermore, a recent case report of poly-neoplastic syndrome showed that in a patient with eight different cancers, five of them exhibited a BRAF V600E mutation (i.e., LCH, chronic lymphocytic leukemia, histiocytic sarcoma, melanoma, adenocarcinoma of the lung), in contrast to the other neoplasms (i.e., multiple myeloma, basal cell carcinoma, and papillary thyroid cancer).…”