Ambiguous Melanocytic Tumors With Loss of 3p21

Abstract

Germline loss of function mutations in BAP1 are associated with the development of cutaneous melanocytic tumors with some histopathologic characteristics seen in Spitz nevi. Similar melanocytic tumors occurring in a sporadic setting have been demonstrated to have biallelic loss of BAP1. In some of these sporadic tumors, loss of BAP1 occurs through mutation of one allele and genomic loss of the other. We screened our database of comparative genomic hybridization profiles of ambiguous melanocytic tumors to identify cases with a single genomic event involving loss of the BAP1 locus. The prevalence of tumors with a single genomic event involving loss of BAP1 was 6.7% in our study population. We further characterized the BAP1 status in 17 of these tumors with available additional material, confirming loss of BAP1 in all cases. We describe BAP1 loss in a blue nevus like melanoma and further expand the histopathologic spectrum of spitzoid melanocytic neoplasms with BAP1 loss.

Gene of the month:BAP1

“…Cytoplasm is well-demarcated and amphophilic. Tumour-infiltrating lymphocytes and multinucleated tumour cells are commonly seen 28. A background banal naevus component may be present 29.…”

Histopathology of melanocytic lesions in a family with an inherited BAP1 mutation

“…Nuclear pseudoinclusions were noted, although distributed more sparsely within this lesion. To our knowledge, there is only one other reported case of a 64‐year‐old female with a BAP1 germline mutation who had a malignant blue nevus‐like melanoma of the scalp 2. Our patient was also found to have a meningioma on computed tomography (CT) scanning.…”

Wiesner nevus

“…These range from completely benign (e.g., Wiesner nevus), 2 as in this patient, to melanocytic borderline atypical intradermal tumours 3 and to overtly malignant tumours. A BRAFV600E mutation, detectable with the VE1 immunostain, is present in about 70% of BAPomas.…”

“…A BRAFV600E mutation, detectable with the VE1 immunostain, is present in about 70% of BAPomas. 3 Wiesner nevus grows slowly, and no further action is necessary after excision of the nevus. However, the patient should be checked for the presence of multiple fibroma-like nevi.…”

“…These nevi are the hallmarks of the uncommon familial tumour predisposition syndrome (Online Mendelian Inheritance in Man; OMIM:614327) caused by germline BAP1 inactivating mutations, which is associated with atypical Spitz tumours/melanocytic borderline atypical intradermal tumours, cutaneous and uveal melanoma, and internal neoplasms (e.g., mesothelioma, renal clear cell carcinoma, lung adenocarcinoma, squamous cell carcinoma of the head and neck, breast carcinoma, myelodysplasia, medulloblastoma and meningioma). 1,3 Any cutaneous papulonodular lesion reported to be growing should be excised. If Wiesner nevus is diagnosed histopathologically and is associated with multiple cutaneous (fibroma-like) melanocytic tumours, the patient should receive genetic testing for tumour predisposition syndrome.…”