Uveal melanoma (UM) is characterized by a small number of recurrent genetic alterations that determine metastatic propensity. BAP1 loss and PRAME expression define the dominant prognostic axes in UM, yet how they promote malignant progression remains unclear. We profiled 190,535 cells from normal uvea, uveal nevus, primary and metastatic UM using single-cell transcriptomics, T cell receptor sequencing, spatial transcriptomics and isogenic perturbation models. Normal melanocytes, nevus cells and UM cells formed a transcriptional continuum marked by loss of differentiation and emergence of neural crest-like, stress-responsive, hypoxic-glycolytic and immune-interacting states. BAP1 loss and PRAME expression imposed distinct but convergent immunoregulatory programs, inducing interferon and TNF-NF-κB signaling and MHC-I expression, with HLA-E showing the strongest response. These alterations were accompanied by macrophage and CD8 + T cell remodeling. PRAME-enriched tumor regions formed spatially organized niches enriched for macrophages and plasma cells. These findings define BAP1 loss and PRAME expression as distinct but convergent axes of tumor-immune coevolution and nominate HLA-E as a candidate mediator of immune resistance.

Wolf's isotopic response is defined as the appearance of a new, unrelated dermatosis within the borders of a healed prior skin injury. We report a seven-year-old boy who developed multiple verrucous papules confined to a healed partial-thickness thermal burn on the anterior trunk, with histopathologic findings consistent with epidermal nevus. The clear temporal and spatial relationship between skin injury and lesion development is suggestive of an isotopic response occurring within an immunocompromised cutaneous district, although causation cannot be definitively established. To our knowledge, based on a review of the available English-language literature, this case of epidermal nevus arising within a healed thermal burn expands the spectrum of burn-associated isotopic response.

Phakomatosis pigmentokeratotica (PPK) is a rare variant of epidermal nevus syndrome, classically characterized by the coexistence of nevus sebaceus and nevus spilus. Secondary neoplasms arising within nevus sebaceus, including syringocystadenoma papilliferum (SPAP), can cause persistent irritation, discomfort, and bleeding that negatively impact quality of life, particularly in patients with extensive disease. Due to the rarity of this condition, no standardized management protocol exists for symptomatic SPAPs, which poses a therapeutic challenge for this patient population. Herein, we present a case of multiple SPAPs in a patient with PPK successfully managed using multimodal therapy involving dermatologic surgery and ablative CO2 laser, adding to the limited literature on the management of recalcitrant SPAPs.

Giant congenital melanocytic naevi (GCMN) presenting over large surface areas pose significant reconstructive challenges following surgical excision. We report the case of a paediatric female with a symptomatic GCMN covering ~2% of total body surface area on the right thigh, causing recurrent ulceration and psychological distress. Following failed conservative management, excision under general anaesthetic was performed, with reconstruction of the thigh defect using NovoSorb™ Biodegradable Temporizing Matrix (BTM). Despite a series of sequential infectious and contamination episodes during integration-including bacterial infection with Escherichia coli, Pseudomonas aeruginosa, and Klebsiella variicola, urine contamination, and maggot infestation-BTM maintained integration with conservative management. Successful split-thickness skin grafting was achieved at 4 weeks, with complete wound healing at 4 months and a well-matured scar at 1 year. This case supports BTM as a robust option for paediatric GCMN reconstruction in anatomically challenging, high-contamination locations.

Eruptive disseminated Spitz nevus (EDSN) is an exceptionally rare condition characterized by widespread Spitz-spectrum melanocytic lesions. We report a 21-year-old woman with an estimated 50,000-60,000 lesions involving the entire cutaneous surface, predominantly the trunk and proximal extremities. Lesions began at age 17 with hundreds of lesions and increased dramatically over subsequent years. Initial HRAS sequencing and ROS1 FISH were negative; broader molecular profiling was performed at re-presentation. Seven representative lesions from distinct sites were sampled: five Spitz nevi and two atypical Spitz tumors, without melanoma. Strong, diffuse ALK expression was detected in three lesions, while RNA sequencing identified an identical TPM3 exon 8::ALK exon 20 fusion in two of seven lesions from anatomically separate sites. Although compatible with shared clonality, this finding does not establish a common clonal origin because TPM3::ALK is a recurrent Spitz driver and transcript-level concordance does not prove an identical genomic breakpoint. A constitutional NF1 p.S1249F variant was classified as a variant of uncertain significance and was also present in two clinically unaffected brothers, arguing against an independently sufficient pathogenic role. TPM3::ALK remains the only demonstrated oncogenic driver. To our knowledge, this represents the first longitudinal molecular follow-up of EDSN, with findings compatible with either clonal dissemination or recurrent independent acquisition of the same driver.