title: Histomorphologic spectrum of BAP1 negative melanocytic neoplasms in a family with BAP1-associated cancer susceptibility syndrome.
abstract: BACKGROUND
  Multiple BAP1 negative melanocytic neoplasms are a hallmark of familial cancer susceptibility syndrome caused by BAP1 germline mutation. The syndrome is characterized by increased incidence of renal cell carcinoma, mesothelioma, cholangiocarcinoma, cutaneous and uveal melanoma and some other neoplasms.
  
  
  METHODS
  We report histomorphologic characteristics of six cutaneous melanocytic neoplasms with loss of BAP1 expression in two members of a family with BAP1-associated cancer susceptibility syndrome.
  
  
  RESULTS
  The neoplasms were dermal melanocytic nevi characterized by a proliferation of large epithelioid (spitzoid) melanocytes, and adipocytic metaplasia. Nuclear pseudoinclusions and multinucleated melanocytes were present in most neoplasms. In two of the cases, a nodular melanoma was found associated with a dermal nevus. None of the melanomas recurred or metastasized after 6 and 3 years of follow up.
  
  
  CONCLUSIONS
  We report two new cases of melanoma arising in a BAP1-deficient melanocytic nevus in the setting of familial tumor predisposition syndrome. Adipocytic metaplasia and nuclear pseudoinclusions may be additional morphologic clues to a BAP1-deficient nevus. It remains to be seen whether these features are more common in familial than sporadic lesions.
authors.affiliation: Ljudevit Jurak Department of Pathology, Clinical Hospital Center "Sestre milosrdnice", Zagreb, Croatia.
authors.forename: Zlatko
authors.initials: Z
authors.lastname: Marušić
authors.affiliation: Department of Dermatology, Clinical Hospital Center "Sestre milosrdnice", Zagreb, Croatia.
authors.forename: Marija
authors.initials: M
authors.lastname: Buljan
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Klaus J
authors.initials: KJ
authors.lastname: Busam
mesh_terms: D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000453:epidemiology / Q000473:pathology; D018281:Cholangiocarcinoma / Q000453:epidemiology / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008544:Melanocytes / Q000378:metabolism* / Q000473:pathology*; D008545:Melanoma / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008654:Mesothelioma / Q000453:epidemiology / Q000473:pathology; D008875:Middle Aged; D009386:Neoplastic Syndromes, Hereditary / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase / Q000235:genetics / Q000378:metabolism*; D014604:Uveal Neoplasms / Q000453:epidemiology / Q000473:pathology; D000096142:Cutaneous Malignant Melanoma; D000098943:Uveal Melanoma
chemical_list: C400134:BAP1 protein, human; D014408:Biomarkers, Tumor; D025521:Tumor Suppressor Proteins; D043222:Ubiquitin Thiolesterase
keywords: BAP1; cancer; hereditary; melanocytic; neoplasm