title: Melanomas Associated With Blue Nevi or Mimicking Cellular Blue Nevi: Clinical, Pathologic, and Molecular Study of 11 Cases Displaying a High Frequency of GNA11 Mutations, BAP1 Expression Loss, and a Predilection for the Scalp.
abstract: Melanomas associated with blue nevi (MABN) or mimicking cellular blue nevi (MMCBN) represent exceptional variants of malignant cutaneous melanocytic tumors. Uveal and leptomeningeal melanomas frequently have somatic mutations of GNAQ or GNA11, which are believed to be early driver mutations. In uveal melanomas, monosomy 3, linked to the BAP1 gene, is an adverse prognostic factor. We have studied the clinical, histologic, BAP1 expression profile, and molecular data of 11 cases of MABN/MMCBN and 24 cellular blue nevi. Most of the cases of MABN/MMCBN occurred on the scalps of adult patients and presented as rapidly growing nodules, typically >1 cm, often arising at the site of a preexisting melanocytic lesion. The MABN/MMCBN were composed of dense nests of large dermal atypical melanocytes, in some cases lying adjacent to a blue nevus. Four patients developed metastatic disease, and 2 died from their disease. A GNA11 mutation was found in 8/11 cases and a GNAQ mutation in 1 case. Seven of 11 cases showed loss of nuclear BAP1 immunohistochemical (IHC) expression in the malignant component, sparing the adjacent nevus. Array comparative genomic hybridization revealed recurrent deletions of chromosomes 1p, 3p, 4q, 6q, 8p, 16q, and 17q and recurrent gains of chromosomes 6p, 8q, and 21q. The 24 cases of cellular blue nevi frequently occurred on the sacrum, had GNAQ mutations, and showed normal positive IHC staining for BAP1. These results underscore overlapping features in all blue-like malignant melanocytic tumors. Loss of BAP1 IHC expression was restricted to melanomas, including all metastatic cases.
authors.affiliation: *Department of Biopathology, Leon Berard Center, Lyon †Department of Anatomical Pathology, Royal North Shore Hospital, Sydney, NSW, Australia ‡Department of Dermatology, Lyon Sud Hospital Center, Pierre-Benite, CRCL and CHU of Lyon, Lyon §Department of Dermatology, CHU Besançon, Besançon ∥Department of Medical Oncology, Eugene Marquis Center, Rennes ¶Department of Dermatology, Robert Debre´ University Hospital, Reims #Department of Dermatology, CHU of Dijon, Dijon **Department of Dermatology CHRU of Lille, Lille ††Department of Dermatology, Institut Gustave Roussy, Villejuif ‡‡Department of Dermatocancerology, Hotel Dieu, Nantes §§Department of Pathology, Lyon Sud Hospital Center, Pierre-Benite ∥∥Department of Pathology, CHU of Bordeaux, Hospital Haut-Leveque, Pessac, France.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Costa
authors.forename: Michelle
authors.initials: M
authors.lastname: Byrne
authors.forename: Daniel
authors.initials: D
authors.lastname: Pissaloux
authors.forename: Veronique
authors.initials: V
authors.lastname: Haddad
authors.forename: Sandrine
authors.initials: S
authors.lastname: Paindavoine
authors.forename: Luc
authors.initials: L
authors.lastname: Thomas
authors.forename: Francois
authors.initials: F
authors.lastname: Aubin
authors.forename: Thierry
authors.initials: T
authors.lastname: Lesimple
authors.forename: Florent
authors.initials: F
authors.lastname: Grange
authors.forename: Bertille
authors.initials: B
authors.lastname: Bonniaud
authors.forename: Laurent
authors.initials: L
authors.lastname: Mortier
authors.forename: Christine
authors.initials: C
authors.lastname: Mateus
authors.forename: Brigitte
authors.initials: B
authors.lastname: Dreno
authors.forename: Brigitte
authors.initials: B
authors.lastname: Balme
authors.forename: Beatrice
authors.initials: B
authors.lastname: Vergier
authors.forename: Arnaud
authors.initials: A
authors.lastname: de la Fouchardiere
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D001706:Biopsy; D055028:Comparative Genomic Hybridization; D004252:DNA Mutational Analysis; D015536:Down-Regulation; D005260:Female; D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006258:Head and Neck Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008545:Melanoma / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D009154:Mutation; D018329:Nevus, Blue / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D010641:Phenotype; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012535:Scalp; D012878:Skin Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D047368:Tumor Burden; D025521:Tumor Suppressor Proteins / Q000032:analysis*; D043222:Ubiquitin Thiolesterase / Q000032:analysis*; D055815:Young Adult
chemical_list: C400134:BAP1 protein, human; D014408:Biomarkers, Tumor; C554062:GNA11 protein, human; D044385:GTP-Binding Protein alpha Subunits; D025521:Tumor Suppressor Proteins; D043222:Ubiquitin Thiolesterase