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BAP1-inactivated melanocytic tumor (BIMT) is a group of melanocytic neoplasms with epithelioid cell morphology molecularly characterized by the loss of function of BAP1, a tumor suppressor gene located on chromosome 3p21, and a mutually exclusive mitogenic driver mutation, more commonly BRAF. BIMTs can occur as a sporadic lesion or, less commonly, in the setting of an autosomal dominant cancer susceptibility syndrome caused by a BAP1 germline inactivating mutation. Owing to the frequent identification of remnants of a conventional nevus, BIMTs are currently classified within the group of combined melanocytic nevi. "Pure" lesions can also be observed. We studied 50 BIMTs from 36 patients. Most lesions were composed of epithelioid melanocytes of varying size and shapes, resulting extreme cytomorphological heterogeneity. Several distinctive morphological variants of multinucleated/giant cells were identified. Some hitherto underrecognized microscopic features, especially regarding nuclear characteristics included nuclear blebbing, nuclear budding, micronuclei, shadow nuclei, peculiar cytoplasmic projections (ant-bear cells) often containing micronuclei and cell-in-cell structures (entosis). In addition, there were mixed nests of conventional and BAP1-inactivated melanocytes and squeezed remnants of the original nevus. Of the 26 lesions studied, 24 yielded a BRAF mutation, while in the remaining two cases there was a RAF1 fusion. BAP1 biallelic and singe allele mutations were found in 4/22 and 16/24 neoplasms, respectively. In five patients, there was a BAP1 germline mutation. Six novel, previously unreported BAP1 mutations have been identified. BAP1 heterozygous loss was detected in 11/22 lesions. Fluorescence in situ hybridization for copy number changes revealed a related amplification of both RREB1 and MYC genes in one tumor, whereas the remaining 20 lesions studied were negative; no TERT-p mutation was found in 14 studied neoplasms. Tetraploidy was identified in 5/21 BIMTs. Of the 21 patients with available follow-up, only one child had a locoregional lymph node metastasis. Our results support a progression of BIMTs from a conventional BRAF mutated in which the original nevus is gradually replaced by epithelioid BAP1-inactivated melanocytes. Some features suggest more complex underlying pathophysiological events that need to be elucidated.

Introduction: Dissecting cellulitis of the scalp, or Hoffman disease, is described as an extremely rare condition. Clinically, it is represented by recurrent painful nodules, purulent drainage, interconnected sinus tracts and keloid formation, leading to scaring and cicatricial alopecia. Without a precise diagnosis and an adequate treatment, the repercussions consist of severe infectious complications along with psychological negative effects and serious aesthetic alterations. There is no standard treatment. In refractory cases, surgical management is reported. Patient concerns: We report a case of a 65-year-old Caucasian male patient, with a 5-year history of Hoffman disease, who presented with multiple abscesses and sinus tracts of the scalp and patches of alopecia. The lesions were non-responsive to medical treatment. Diagnosis: The diagnosis of DCS has been established on the basis of the clinical appearance and has been confirmed histopathologically. Interventions: The patient underwent wide excision of the scalp, followed by reconstruction using free latissimus dorsi flap and covered by meshed split-thickness skin graft. Outcomes: Eighteen-month follow-up revealed complete remission of symptoms and lesions along with satisfactory cosmetic result. Conclusion: The scope of this case report is to raise awareness of the following aspects: Hoffman disease has an extremely low occurrence rate, a difficult differential diagnosis and no standard therapeutical strategy. It also highlights the effectiveness of scalpectomy and free latissimus dorsi flap covered by meshed split-thickness skin graft in treating a very advanced stage of the disease together with providing a natural contouring of the scalp. Ultimately, it discusses the other treatment alternatives.