Reevaluation of established and new criteria in differential diagnosis of Spitz nevus and melanoma

Arch Dermatol Res. 2018 May;310(4):329-342. doi: 10.1007/s00403-018-1818-8. Epub 2018 Feb 7.


The histopathologic differentiation between Spitz nevus and melanoma is of particular interest in routine diagnostic procedures of melanocytic tumors. Atypical Spitz nevi are sometimes difficult to distinguish from melanoma. There is still no single criterion that ensures a distinction of melanoma and atypical Spitz nevus. The aim of this study was to reevaluate established and new criteria to differentiate Spitz nevus from melanoma more reliably. We analyzed 25 melanomas with a Breslow index ≥ 1 mm and 18 classical compound Spitz nevi concerning their histopathologic, immunohistochemical and molecular genetic characteristics. Moreover, clinical follow-up data for 5 years were collected. We found statistically significant differences between Spitz nevus and melanoma for the following features: pagetoid spread, atypia, maturation, elastosis, Kamino bodies, p16 expression, and the staining pattern of HMB45. BRAF was positive in 7/21 melanomas and in 1/14 Spitz nevi. Fluorescence in situ hybridization confirmed the histopathologic diagnosis in 36/37 cases. The established clinical, histopathologic, and immunohistochemical criteria to differentiate Spitz nevus and melanoma could be reproduced in our collective. Especially, the expression of p16, BRAF analysis and fluorescence in situ hybridization proved to be helpful tools to improve the differentiation of Spitz nevus and melanoma in our study. Nevertheless, there is-until now-no reliable histopathologic and immunohistochemical parameter which can discriminate Spitz nevus and melanoma with absolute certainty.

Keywords: BRAF; Fluorescence in situ hybridisation; Immunohistochemistry; Melanoma; P16; Spitz nevus.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • Diagnosis, Differential
  • Female
  • Follow-Up Studies
  • Humans
  • Immunohistochemistry
  • MART-1 Antigen / metabolism
  • Male
  • Melanoma / diagnosis*
  • Melanoma / pathology
  • Melanoma-Specific Antigens / metabolism
  • Middle Aged
  • Nevus, Epithelioid and Spindle Cell / diagnosis*
  • Nevus, Epithelioid and Spindle Cell / pathology
  • Severity of Illness Index
  • Skin Neoplasms / diagnosis*
  • Skin Neoplasms / pathology
  • gp100 Melanoma Antigen


  • Biomarkers, Tumor
  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • MART-1 Antigen
  • Melanoma-Specific Antigens
  • PMEL protein, human
  • gp100 Melanoma Antigen