Copy Number Variations and Clinical Outcome in Atypical Spitz Tumors
Department of Internal Medicine, University of Michigan, Ann Arbor, USA.The American journal of surgical pathology (Impact Factor: 5.15). 02/2011; 35(2):243-52. DOI: 10.1097/PAS.0b013e31820393ee
Atypical Spitz tumors (ASTs) are rare spitzoid neoplasms of uncertain biological behavior. Our study was designed to characterize genetic abnormalities that may help to differentiate ASTs from melanoma or Spitz nevi. We examined copy number variation in formalin-fixed, paraffin-embedded samples using an Agilent 44k array comparative genomic hybridization platform. Sixteen patients with AST (8 with positive sentinel lymph node biopsy, 1 with distant metastasis), 8 patients with Spitz nevi, and 3 patients with melanoma (2 spitzoid, 1 superficial spreading) were evaluated. Chromosomal aberrations were found in 7 of 16 ASTs, 1 with fatal outcome, 2 spitzoid melanomas, and 1 conventional melanoma. We found no difference in chromosomal instability between AST patients with positive and negative sentinel lymph node biopsies. Our patient with widely metastatic AST lacked the most frequent aberrations in melanoma involving chromosomes 6 and 11q that are loci targeted by fluorescence in situ hybridization (FISH) probes developed to distinguish malignant melanoma from benign melanocytic lesions. The vast majority of chromosomal abnormalities observed in ASTs are not commonly found in melanomas, suggesting that AST may be a distinct clinical entity and raising additional questions regarding their malignant potential, prognosis, and clinical management. The current FISH probes failed to detect 1 spitzoid melanoma, 1 fatal metastatic AST case, and the other chromosomally aberrant ASTs in our series, but detected 1 spitzoid melanoma and 1 conventional melanoma. Thus, a comprehensive, genome-wide approach to chromosomal abnormalities offered greater sensitivity and specificity than current FISH probes in identifying spitzoid lesions of uncertain malignant potential in this series.
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ABSTRACT: Senetta R, Paglierani M & Massi D (2012) Histopathology 60, 706–714 Fluorescence in-situ hybridization analysis for melanoma diagnosis Melanocytic proliferation constitutes a heterogeneous group of lesions with remarkable differences in their biology and clinical outcome. Thus, accurate histological diagnosis of these cases is mandatory to establish the most appropriate surgical treatment and follow-up. Although histological examination alone is usually sufficient to identify melanomas among the greater number of nevi, the definition of the benign or malignant nature of a subset of melanocytic tumours, exhibiting atypical features, is a challenging task. Novel techniques that may assist in the histopathological diagnosis in difficult cases have been extensively researched over recent years. Fluorescence in-situ hybridization (FISH), performed with a panel of four probes, including three locus-specific identifier (RREB1, MYB, and CCND1) genes, seems to represent a sensitive and specific molecular tool for the diagnosis of non-ambiguous melanocytic lesions. Some studies have agreed that FISH may be an ancillary diagnostic instrument, but cannot replace light microscopy, to distinguish benign nevi from malignant melanomas in daily practice. However, in the context of ambiguous melanocytic tumours, results are still controversial, and additional and substantial work is needed to develop reliable probes that may identify, with high sensitivity, specific subsets of ambiguous melanocytic lesions, including spitzoid proliferation.Histopathology 10/2011; 60(5):706-14. DOI:10.1111/j.1365-2559.2011.03984.x · 3.45 Impact Factor
- Annales de Pathologie 11/2011; 31(5 Suppl):S115-6. DOI:10.1016/j.annpat.2011.09.006 · 0.29 Impact Factor
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ABSTRACT: Differentiating Spitz nevus (SN) from Spitzoid malignant melanoma (SMM) is one the most difficult problems in dermatopathology. SPECIFIC AIM: To identify differences on proteomic level between SN and SMM. We performed Imaging Mass Spectrometry analysis on formalin-fixed, paraffin-embedded tissue samples to identify differences on proteomic level between SN and SMM. The diagnosis of SN and SMM was based on histopathologic criteria, clinical features, and follow-up data, which confirmed that none of the lesions diagnosed as SN recurred or metastasized. The melanocytic component (tumor) and tumor microenvironment (dermis) from 114 cases of SN and SMM from the Yale Spitzoid Neoplasm Repository were analyzed. After obtaining mass spectra from each sample, classification models were built using a training set of biopsies from 26 SN and 25 SMM separately for tumor and for dermis. The classification algorithms developed on the training data set were validated on another set of 30 samples from SN and 33 from SMM. We found proteomic differences between the melanocytic components of SN and SMM and identified 5 peptides that were differentially expressed in the 2 groups. From these data, 29 of 30 SN and 26 of 29 SMM were recognized correctly based on tumor analysis in the validation set. This method correctly classified SN with 97% sensitivity and 90% specificity in the validation cohort. Imaging Mass Spectrometry analysis can reliably differentiate SN from SMM in formalin-fixed, paraffin-embedded tissue based on proteomic differences.The American Journal of dermatopathology 12/2011; 34(1):82-90. DOI:10.1097/DAD.0b013e31823df1e2 · 1.39 Impact Factor
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