![]() ![]() One approach to resolve this diagnostic challenge has been the introduction of an intermediate category (termed ‘mixed’ or ‘combined’ spindle/desmoplastic melanoma) that suggests a seemingly continuous biological spectrum. 1 Diagnostic distinction of spindle cell from desmoplastic melanoma is not always straightforward because of partially overlapping features and heterogeneity in collagen content. 9, 13, 14īecause of these differences, diagnostic distinction of spindle cell and desmoplastic melanoma is clinically relevant however, currently mainly rests on the amount of scar-like tissue (ie, collagen content). This is why knowledge of specific immunophenotypes in spindle cell and desmoplastic melanoma can be helpful. Histologically, spindle cell melanoma is often confused with other (eg, mesenchymal or neural) tumors. 9, 13 In contrast, spindle cell melanoma is frequently amelanotic, can occur essentially anywhere on the body, and presents typically with widespread metastatic disease. 6, 7, 8, 9, 10, 11, 12 The overall prognosis in desmoplastic melanoma tends to be better when compared stage by stage with conventional melanoma. 2, 3, 4, 5 There is an ongoing debate whether sentinel lymph node biopsy should be performed in desmoplastic melanoma because its metastatic rate is somewhat lower when compared with conventional melanoma and spindle cell melanoma. This specific growth pattern of desmoplastic melanoma is likely responsible for the higher rate of local recurrences, when compared with other melanoma subtypes. Desmoplastic melanoma is usually not well circumscribed and malignant cells track along pre-existing structures such as skin appendages or nerves (eg, neurotropic melanoma). Anatomically, desmoplastic melanoma usually occurs in the head and neck region and presents clinically with a flat or nodular, scar-like lesion. In desmoplastic melanoma, these malignant cells are intimately admixed with ropy and dense collagen fibrils. 1 Histologically, both spindle cell and desmoplastic melanoma are characterized by atypical, spindled, malignant melanocytes. Spindle cell and desmoplastic melanoma are two distinct subtypes of malignant melanoma that differ by clinical, histopathological, and prognostic features. The devised algorithm allows diagnostic distinction of desmoplastic from spindle cell melanoma when routine histology is not decisive. We present the first comprehensive screening study of diagnostic and therapeutic biomarkers in spindle cell and desmoplastic melanoma. In addition, we found BRAF mutations in 31% of spindle cell and 5% of desmoplastic melanoma, with an overall mutation frequency of 16% ( n=6/38). Fluorescent in situ hybridizations did not reveal a significant number of gene aberrations/rearrangements however, protein overexpression for at least one of these markers was identified in 35 of 38 cases (92%). Gene amplification and expression status was assessed for a set of potentially drugable targets (HER2, EGFR, MET, MDM2, TP53, ALK, MYC, FLI-1, and KIT). On the basis of 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. We identified nine 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. S100 remains as the most reliable routine marker to reach the diagnosis of melanoma in spindle cell and desmoplastic melanoma. Using 50 biomarkers available in routine diagnostics, we examined 38 archival cases ( n=16 spindle, 18 desmoplastic, 4 mixed spindle/desmoplastic melanoma). Meta-review of the literature discloses key clinicopathological differences between spindle cell and desmoplastic melanoma, including immunophenotypes. A direct comparison of diagnostic and therapeutic biomarkers has not been performed. Spindle cell melanoma and desmoplastic melanoma differ clinically in prognosis and therapeutic implications however, because of partially overlapping histopathological features, diagnostic distinction of spindle cell from desmoplastic melanoma is not always straightforward. ![]()
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