Mind your head: two cases of mucosal metastasis of BRAF-mutated melanoma of the scalp

Abstract

Mucosal melanomas are rare and only a small portion bear BRAF mutations while cutaneous melanomas have a much higher prevalence and often harbor BRAF mutations. We present two cases in which, after a malignant melanocytic mucosal lesion with a BRAF mutation was found, the primary cutaneous source was identified and clonality confirmed between the lesions. In both cases, primary lesions occurred on the scalp, an often-overlooked site. Both lesions showed signs of regression implying that in due time these lesions could have been fully regressed and might never have been detected. In that case, the metastatic mucosal lesion would erroneously be identified as a BRAF-mutated mucosal melanoma. These cases give warrant; a careful dermatological inspection should be instigated when confronted with a BRAF-mutated mucosal melanoma. We hypothesize that some BRAF-mutated mucosal melanomas might actually represent metastases of regressed cutaneous melanomas.

Keywords: BRAF mutations; Melanoma; Metastatic melanoma; Mucosal melanoma; Oncologic genetics.

Fig. 1

Case 1: (A) H&E stain of the skin lesion demonstrating a almost fully regressive melanoma; a small cluster of atypical melanocytes residing in a larger field of fibrosis (arrow) can be seen in the top right corner. These melanocytes showed strong immunohistochemical positivity for PReferentially expressed Antigen in MElanoma (PRAME, insert B). Macroscopically the lesion manifested as a small, slightly asymmetrical pigmented lesion on the scalp (C)

Fig. 2

Case 1: SNP array analysis of the atypical melanocytes in the skin (A) and the melanoma in the maxillary sinus (B). A Upper panel shows intensity (Log R Ratio) and lower panel shows B allele frequency (BAF). CNV analysis shows partial loss of 2q, partial copy number neutral LOH (CN-LOH) of chromosome 5, loss of chromosome 6q and 10q, CN-LOH of chromosome 8p, gain of chromosome 8q, and heterozygous loss of 9p21 (including CDKN2A). B Upper panel shows intensity (Log R Ratio) and lower panel shows B allele frequency (BAF). CNV analysis shows CN-LOH of chromosome 1p, partial loss of chromosome 2q, partial CN-LOH of chromosome 5, loss of chromosome 6q, 8p, 10q, and 18p, trisomy of chromosome 7 and 20, gain of chromosome 8q, CN-LOH of chromosome 9, and monosomy of chromosome X

Fig. 3

Case 2: (A) H&E stain of a pedunculated melanoma with regressive changes. A pre-existing dermal nevus can be seen (single arrow) and under on the right can be seen and under the pedunculated lesion regressional changes are observed (double arrow). Macroscopically the lesion manifested on scalp, clinically appearing like an angioma (B)