title: Proliferative Nodules vs Melanoma Arising in Giant Congenital Melanocytic Nevi During Childhood.
abstract: The differential diagnosis between proliferative nodules (PNs) and melanoma arising in congenital melanocytic nevi (CMN) is crucial, as patients with PNs most often experience no increased risk of melanoma with metastases and death.
  
  
  
  To analyze the utility of immunohistochemistry and fluorescence in situ hybridization (FISH) in distinguishing PNs from childhood and adult-onset melanoma arising in CMN.
  
  
  
  A case series was conducted from June 29, 1989, to November 12, 2009, of 13 children with PNs arising in CMN in childhood and 5 children with melanomas arising in CMN in childhood. Five patients with giant CMN with no nodules were included as negative controls, and 6 patients with melanomas arising in CMN in adulthood were included as positive controls. Follow-up ranged from 3 to 21 years in all children (mean, 9.9 years) and from 3 months to 7 years in adults. Specimens were selected for immunohistochemistry and FISH. All histopathologic sections were reviewed by 2 dermatopathologists who examined all nodules arising at different ages in the same patient and, in the case of melanoma, all locations. Data analysis was performed from January 1, 2013, to January 31, 2015.
  
  
  
  The ability to distinguish melanoma from PN using immunohistochemistry and/or FISH.
  
  
  
  Of the 13 patients (5 boys and 8 girls) with PNs present at birth, all PNs were stable (mean follow-up, 9 years). Eight patients with PNs and 4 of 5 patients with childhood-onset melanoma showed homogeneous staining for HMB45, while heterogeneous staining for HMB45 was seen in 3 of 6 patients with adult-onset melanoma. Expression of p16 was strongly positive in most patients with childhood-onset PNs (10 of 11 patients) and melanoma (all patients) but negative in 4 patients with adult-onset melanoma. Patients with PNs and the 5 patients with childhood-onset melanoma had numerical chromosomal aberrations never observed in the adjacent CMN. The 2 children with FISH-positive PNs are melanoma free after 7 and 4 years. Only 1 patient with childhood-onset melanoma had a FISH aberration compared with 4 patients with adult-onset melanoma.
  
  
  
  Immunohistochemistry and the 4-probe FISH melanoma analysis are not useful for distinguishing PN from childhood-onset melanoma as opposed to adult-onset melanoma. Numerical anomalies seen in PNs but not in the adjacent CMN could be the result of a chromosomal segregation malfunction resulting in the development of nodules.
authors.affiliation: Department of Pathology and Molecular Pathology, Hôpital Haut-Lévêque, Centre Hospitalier Universitaire Bordeaux, Pessac, France2Institut National de la Santé et de la Récherche Médicale U1053-UMR, Bordeaux Research In Translational Oncology, Bordeaux University, Bordeaux, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Vergier
authors.affiliation: Department of Pathology and Molecular Pathology, Hôpital Haut-Lévêque, Centre Hospitalier Universitaire Bordeaux, Pessac, France2Institut National de la Santé et de la Récherche Médicale U1053-UMR, Bordeaux Research In Translational Oncology, Bordeaux University, Bordeaux, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Laharanne
authors.affiliation: Department of Pathology and Molecular Pathology, Hôpital Haut-Lévêque, Centre Hospitalier Universitaire Bordeaux, Pessac, France2Institut National de la Santé et de la Récherche Médicale U1053-UMR, Bordeaux Research In Translational Oncology, Bordeaux University, Bordeaux, France.
authors.forename: Martina
authors.initials: M
authors.lastname: Prochazkova-Carlotti
authors.affiliation: Department of Pathology, Centre Léon Bérard, Lyon, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: de la Fouchardière
authors.affiliation: Department of Pathology and Molecular Pathology, Hôpital Haut-Lévêque, Centre Hospitalier Universitaire Bordeaux, Pessac, France2Institut National de la Santé et de la Récherche Médicale U1053-UMR, Bordeaux Research In Translational Oncology, Bordeaux University, Bordeaux, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Merlio
authors.affiliation: Unit of Maxillofacial and Plastic Surgery, Necker-Enfants Malades Hospital, Paris, France.
authors.forename: Natacha
authors.initials: N
authors.lastname: Kadlub
authors.affiliation: Department of Dermatology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, Paris-Descartes-Sorbonne University, Paris, France.
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: Avril
authors.affiliation: Department of Dermatology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, Paris-Descartes-Sorbonne University, Paris, France6Department of Dermatology, Necker-Enfants Malades Hospital, Paris, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Bodemer
authors.affiliation: Department of Dermatology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, Paris-Descartes-Sorbonne University, Paris, France7Department of Pathology, Necker-Enfants Malades Hospital, Paris, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Lacoste
authors.affiliation: Department of Dermatology, Centre Hospitalier Universitaire Bordeaux, Bordeaux University, Pessac, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Boralevi
authors.affiliation: Department of Dermatology, Centre Hospitalier Universitaire Bordeaux, Bordeaux University, Pessac, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Taieb
authors.affiliation: Department of Dermatology, Centre Hospitalier Universitaire Bordeaux, Bordeaux University, Pessac, France.
authors.forename: Khaled
authors.initials: K
authors.lastname: Ezzedine
authors.affiliation: Department of Dermatology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, Paris-Descartes-Sorbonne University, Paris, France7Department of Pathology, Necker-Enfants Malades Hospital, Paris, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Fraitag
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism*; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D002648:Child; D002675:Child, Preschool; D003937:Diagnosis, Differential; D005260:Female; D005500:Follow-Up Studies; D005602:France; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D008297:Male; D016347:Medical Records Systems, Computerized; D008545:Melanoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D018330:Nevus, Intradermal / Q000473:pathology; D009508:Nevus, Pigmented / Q000378:metabolism / Q000473:pathology*; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor