title: Atypical Spitzoid melanocytic tumors: a morphological, mutational, and FISH analysis.
abstract: BACKGROUND
  Identification of the clinical behavior of atypical Spitzoid tumors with conflicting histopathologic features remains controversial.
  
  
  OBJECTIVE
  We sought to assess whether molecular findings may be helpful in the diagnostic and prognostic assessment of atypical Spitzoid tumors.
  
  
  METHODS
  A total of 38 controversial, atypical Spitzoid lesions (≥ 1 mm in thickness) were analyzed for clinicopathological features, chromosomal alterations by fluorescence in situ hybridization (FISH) analysis (RREB1/MYB/CCND1/CEP6), BRAF(V600E) mutation by allele-specific real-time polymerase chain reaction confirmed by sequencing, and H-RAS gene mutation by direct sequencing.
  
  
  RESULTS
  Atypical Spitzoid lesions developed in 21 female and 17 male patients (mean age 22 years). Nine patients underwent sentinel lymph node biopsy and a sentinel lymph node micrometastasis was detected in 4 of these 9 cases. Four additional patients, who did not receive a sentinel lymph node biopsy, experienced bulky lymph node metastases and one experienced visceral metastases and death. Lesions from patients with lymph node involvement showed more deep mitoses (P < .01), less inflammation (P = .05), and more plasma cells (P = .04). FISH analysis demonstrated the presence of chromosomal alterations in 6 of 25 cases. Correlation with follow-up data showed that the only case with fatal outcome showed multiple chromosomal alterations by FISH analysis. BRAF(V600E) mutation was detected in 12 of 16 cases (75%) and H-RAS mutation on exon 3 was found in 3 of 11 cases (27%).
  
  
  CONCLUSIONS
  Our results require validation in a larger series with longer follow-up information.
  
  
  CONCLUSIONS
  FISH assay may be of help in the prognostic evaluation of atypical Spitzoid tumors. Diagnostic significance of BRAF(V600E) and H-RAS mutations in this setting remains unclear.
authors.affiliation: Division of Pathological Anatomy, Department of Critical Care Medicine and Surgery, University of Florence, Florence, Italy. Daniela.massi@UNIFI.IT
authors.forename: Daniela
authors.initials: D
authors.lastname: Massi
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Cesinaro
authors.forename: Carlo
authors.initials: C
authors.lastname: Tomasini
authors.forename: Milena
authors.initials: M
authors.lastname: Paglierani
authors.forename: Stefania
authors.initials: S
authors.lastname: Bettelli
authors.forename: Luigino
authors.initials: L
authors.lastname: Dal Maso
authors.forename: Lisa
authors.initials: L
authors.lastname: Simi
authors.forename: Francesca
authors.initials: F
authors.lastname: Salvianti
authors.forename: Pamela
authors.initials: P
authors.lastname: Pinzani
authors.forename: Claudio
authors.initials: C
authors.lastname: Orlando
authors.forename: Vincenzo
authors.initials: V
authors.lastname: De Giorgi
authors.forename: Silvana
authors.initials: S
authors.lastname: Lukic
authors.forename: Antonio
authors.initials: A
authors.lastname: Maiorana
authors.forename: Marco
authors.initials: M
authors.lastname: Santucci
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Canzonieri
mesh_terms: D019342:Acetic Acid; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002845:Chromatography; D046169:Dermoscopy; D000431:Ethanol; D004986:Ether; D005260:Female; D005557:Formaldehyde; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008297:Male; D008875:Middle Aged; D018332:Nevus, Epithelioid and Spindle Cell / Q000235:genetics* / Q000473:pathology*; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology*; D055815:Young Adult
chemical_list: C119829:lymph node revealing solution; D004986:Ether; D005557:Formaldehyde; D000431:Ethanol; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D019342:Acetic Acid