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More recent version available under https://oparu.uni-ulm.de/xmlui/123456789/30311

A diagnostic algorithm to distinguish desmoplastic from spindle cell melanoma

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Veröffentlichung
2015-07-21
DOI
10.18725/OPARU-3645
Dissertation


Authors
Weißinger, Stephanie
Faculties
Medizinische Fakultät
Peer review
ja
License
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https://oparu.uni-ulm.de/xmlui/license_v3
Abstract
Spindle cell melanoma and desmoplastic melanoma differ clinically in prognosis and therapeutic implications; however, due to partially overlapping histopathological features, diagnostic distinction of spindle cell from desmoplastic melanoma is not always straightforward. A direct comparison of diagnostic and therapeutic biomarkers has not been performed. Meta-review of the literature discloses key clinicopathological differences between spindle cell and desmoplastic melanoma, including immunophenotypes. Using 50 biomarkers available in routine diagnostics we examined 38 archival cases (n = 16 spindle, 18 desmoplastic, 4 mixed spindle/desmoplastic melanoma). S100 remains as the most reliable routine marker to reach the diagnosis of melanoma in spindle cell and desmoplastic melanoma. We identified 9 distinctly labeling markers with spindle cell melanoma showing positivity for laminin, p75, HMB45, c-kit, and MelanA, and desmoplastic melanoma preferentially labeling with collagen IV, trichrome, CD68, and MDM2. Based on comparisons of test performance measures, MelanA and trichrome were used to devise a 94 % sensitive diagnostic algorithm for the distinction of desmoplastic from spindle cell melanoma. Gene amplification and expression status was assessed for a set of potentially drugable targets (HER2, EGFR, MET, MDM2, TP53, ALK, MYC, FLI-1, KIT). Fluorescent in situ hybridizations did not reveal a significant number of gene abberations/rearrangements; however, protein overexpression for at least one of these markers was identified in 35 of 38 cases (92 %). In addition, we found BRAF mutations in 36 % of spindle cell and 5 % of desmoplastic melanoma with an overall mutation frequency of 16 % (n = 6/38). We present the first comprehensive screening study of diagnostic and therapeutic biomarkers in spindle cell and desmoplastic melanoma. The devised algorithm allows diagnostic distinction of desmoplastic from spindle cell melanoma when routine histology is not decisive.
Date created
2013
Original publication
Modern Pathology 27 (2014), 1, S. 524 - 534; doi:10.1038/modpathol.2013.162
http://www.nature.com/modpathol/journal/v27/n4/full/modpathol2013162a.html
Later version(s)
https://oparu.uni-ulm.de/xmlui/123456789/30311
Subject Headings
Amelanotisches Melanom [GND]
Kernspindel [GND]
BRAF protein, human [MeSH]
Melanoma, amelanotic [MeSH]
Keywords
Neurotropic agents
Dewey Decimal Group
DDC 610 / Medicine & health

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Weißinger, Stephanie (2015): A diagnostic algorithm to distinguish desmoplastic from spindle cell melanoma. Open Access Repositorium der Universität Ulm. Dissertation. http://dx.doi.org/10.18725/OPARU-3645

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