PMID- 21496703 OWN - NLM STAT- MEDLINE DCOM- 20110630 LR - 20220309 IS - 1097-6787 (Electronic) IS - 0190-9622 (Linking) VI - 64 IP - 5 DP - 2011 May TI - Atypical Spitzoid melanocytic tumors: a morphological, mutational, and FISH analysis. PG - 919-35 LID - 10.1016/j.jaad.2010.05.043 [doi] AB - 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%). 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 BRAF(V600E) and H-RAS mutations in this setting remains unclear. CI - Copyright (c) 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved. FAU - Massi, Daniela AU - Massi D AD - Division of Pathological Anatomy, Department of Critical Care Medicine and Surgery, University of Florence, Florence, Italy. Daniela.massi@UNIFI.IT FAU - Cesinaro, Anna Maria AU - Cesinaro AM FAU - Tomasini, Carlo AU - Tomasini C FAU - Paglierani, Milena AU - Paglierani M FAU - Bettelli, Stefania AU - Bettelli S FAU - Dal Maso, Luigino AU - Dal Maso L FAU - Simi, Lisa AU - Simi L FAU - Salvianti, Francesca AU - Salvianti F FAU - Pinzani, Pamela AU - Pinzani P FAU - Orlando, Claudio AU - Orlando C FAU - De Giorgi, Vincenzo AU - De Giorgi V FAU - Lukic, Silvana AU - Lukic S FAU - Maiorana, Antonio AU - Maiorana A FAU - Santucci, Marco AU - Santucci M FAU - Canzonieri, Vincenzo AU - Canzonieri V LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Am Acad Dermatol JT - Journal of the American Academy of Dermatology JID - 7907132 RN - 0 (lymph node revealing solution) RN - 0F5N573A2Y (Ether) RN - 1HG84L3525 (Formaldehyde) RN - 3K9958V90M (Ethanol) RN - EC 2.7.11.1 (BRAF protein, human) RN - EC 2.7.11.1 (Proto-Oncogene Proteins B-raf) RN - Q40Q9N063P (Acetic Acid) SB - IM MH - Acetic Acid MH - Adolescent MH - Adult MH - Child MH - Child, Preschool MH - Chromatography MH - Dermoscopy MH - Ethanol MH - Ether MH - Female MH - Formaldehyde MH - Genes, ras/genetics MH - Humans MH - Immunohistochemistry MH - In Situ Hybridization, Fluorescence MH - Infant MH - Male MH - Middle Aged MH - Nevus, Epithelioid and Spindle Cell/*genetics/*pathology MH - Prognosis MH - Proto-Oncogene Proteins B-raf/genetics MH - Skin Neoplasms/*genetics/*pathology MH - Young Adult EDAT- 2011/04/19 06:00 MHDA- 2011/07/01 06:00 CRDT- 2011/04/19 06:00 PHST- 2010/03/04 00:00 [received] PHST- 2010/04/26 00:00 [revised] PHST- 2010/05/13 00:00 [accepted] PHST- 2011/04/19 06:00 [entrez] PHST- 2011/04/19 06:00 [pubmed] PHST- 2011/07/01 06:00 [medline] AID - S0190-9622(10)00686-9 [pii] AID - 10.1016/j.jaad.2010.05.043 [doi] PST - ppublish SO - J Am Acad Dermatol. 2011 May;64(5):919-35. doi: 10.1016/j.jaad.2010.05.043.