CPC12 A metastatic melanoma mimic: malignant peripheral nerve sheath tumour in the setting of a rare germline BAP1 disease-causing variant
Authors: Cunliffe Amy , Hawari Rand , Mitra Angana , Mathew Bipin , Merchant William , Smith Hayley , Muinonen-Martin Andrew , Sharma Maulina 
Published: June 2024

BAP1 tumour predisposition syndrome (BAP1-TPDS) is a newly recognized cancer syndrome that predisposes patients to uveal melanoma, malignant mesothelioma, renal cell carcinoma, cutaneous melanomas and an emerging range of other cancers. We previously presented a 48-year-old patient with an isolated melanoma metastasis on his wrist arising on a background of a germline BAP1 mutation. We wish to provide an update on his diagnosis, which has been revised to a malignant peripheral nerve sheath tumour (MPNST). To our knowledge, there is only one published similar case in a patient with BAP1-TPDS (Kaszuba MC, Pulido JS, Folpe AL et al. Malignant peripheral nerve sheath tumor in a patient with BAP1 tumor predisposition syndrome. World Neurosurg 2018; 109: 362–4). The patient initially presented to the hand surgeons with a 5-year history of a subcutaneous swelling on his right wrist associated with paraesthesia and pain. Excision biopsy of the lesion revealed a perineural encapsulated pleomorphic tumour with large atypical cells and small neurofibroma-appearing cells at the periphery. Immunohistochemistry showed expression of S100, SOX10 and calretinin, and negative melan-A. Next-generation sequencing revealed BAP1 loss with high variant allele frequency. The patient’s mother died from metastatic uveal melanoma, his maternal grandmother had a history of mesothelioma and his aunt died of a brain tumour. Germline testing showed the patient to be heterozygous for the pathogenic BAP1 sequence variant c.122+1del. We initially presented this case as a stage IV metastatic melanoma deposit on the right wrist originating from a pT4a BAP1 inactivated primary melanoma on the back. This skin lesion had been present for 10 years without change and there was no visceral organ involvement. Due to the unusual nature of the presentation further input from a specialist skin cancer multidisciplinary team with an interest in BAP1-TPDS led to a revised diagnosis of an MPNST on the wrist. The primary melanoma diagnosis was changed to a low-risk BAP1 melanocytoma, based on histological and immunohistochemical findings. Two other low-risk melanocytomas were also excised. The patient was referred to the sarcoma multidisciplinary team, for wide local excision of the MPNST, staging scans and surveillance, including annual ophthalmology review, dermatology review and renal imaging. BAP1 loss in MPNST has only been described once before, interestingly with a splice receptor germline disease-causing variant (Kaszuba et al.). Our case highlights the potential diagnostic complexity associated with BAP1-TPDS for the dermatologist and dermatopathologist. Clinicians should be aware of the proposed surveillance guidelines, while being mindful that the spectrum of associated cancers is expanding. For complex cases like ours, gaining input from centres with experience managing patients with BAP1-TPDS can refine the diagnosis, with important implications for prognosis and patient outcomes.