Atypical Spitzoid melanocytic tumors:A morphological, mutational, and FISH analysis

Background: Identification of the clinical behavior of atypical Spitzoid tumors with conflictinghistopathologic features remains controversial.Objective: We sought to assess whether molecular findings may be helpful in the diagnostic andprognostic assessment of atypical Spitzoid tumors.Methods: A total of 38 controversial, atypical Spitzoid lesions ($1 mm in thickness) were analyzed forclinicopathological features, chromosomal alterations by fluorescence in situ hybridization (FISH) analysis(RREB1/MYB/CCND1/CEP6), BRAFV600E mutation by allele-specific real-time polymerase chain reactionconfirmed 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). Ninepatients underwent sentinel lymph node biopsy and a sentinel lymph node micrometastasis was detectedin 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. Lesionsfrom 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 chromosomalalterations in 6 of 25 cases. Correlation with follow-up data showed that the only case with fatal outcomeshowed multiple chromosomal alterations by FISH analysis. BRAFV600E mutation was detected in 12 of 16cases (75%) and H-RAS mutation on exon 3 was found in 3 of 11 cases (27%).Limitations: 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 BRAFV600E and H-RAS mutations in this setting remains unclear. ( J Am AcadDermatol 2011;64:919-35.)