To the Editor:
Dermatofibrosarcoma protuberans (DFSP) is a rare, locally infiltrative, low-grade sarcoma that rarely metastasizes in its conventional form.1 It characteristically harbors a translocation of t(17;22) (q22;q13) leading to the formation of collagen type alpha 1 and platelet-derived growth factor β fusion transcripts. The detection of this translocation has become a useful diagnostic tool for DFSP because greater than 90% of cases are reportedly positive.2 Rarely, DFSP contains intermixed pigmented cells with dendritic processes in an otherwise typical DFSP known as Bednar tumor or pigmented storiform neurofibroma of Bednar. This pigmented variant comprises approximately 1%–5% of all cases of DFSP.3 The histogenesis of the pigmented cells in Bednar tumor remains disputed. Bednar regarded them as neurogenic4; however ultrastructural studies by Fletcher et al5 failed to demonstrate neuroectodermal (especially perineural fibroblastic) differentiation in these cells, and hence, a theory of melanocytic colonization was raised. In this article, we reported a unique case of DFSP with areas of melanocytic differentiation in the absence of melanin production.
A 42-year-old woman presented with a skin plaque located on her left chest for unknown duration. A 4-mm punch biopsy was performed and sent to our institution for consultation. Routine hematoxylin-/eosin-stained sections revealed a spindle cell proliferation involving dermis with infiltration of subcutis. These cells were arranged loosely and haphazardly with a subset of them exhibiting wavy nuclei and a mild degree of cytologic atypia including hyperchromasia, nuclear enlargement, and irregularity. Mitotic activity was inconspicuous; necrosis was absent (Fig. 1). Melanin pigment was not observed. A panel of immunohistochemical stains were performed at the referring institution and revealed diffuse positivity for CD34, CD68, and MiTF. A subset of the tumor cells, especially those located superficially, stained positive for Melan-A, SOX10, and, very focally, S100 (Fig. 1). The tumor was negative for HMB45, actin, and desmin. Fluorescence in situ hybridization for t(17;22) (q22;q13) performed in our institution was positive, confirming a diagnosis of DFSP.
DFSP has an overall annual incidence of 4.2 per million with peak age incidence between 25 and 45 years. It can occasionally present in kids with cases of congenital onset documented as well. Women are slightly more likely to be affected than men.6 DFSP tends to occur at trunk, proximal extremities, and head and neck regions.3 The treatment is wide local excision. Conventional DFSP very rarely metastasize unless there is fibrosarcomatous transformation (rate of metastasis: 1.1% vs. 14.7% for DFSP and DFSP with fibrosarcomatous transformation, respectively). The proportion of fibrosarcomatous component does not correlate with clinical outcome.1 Although the clinical and epidemiological characteristics of conventional DFSP have been well studied, the same is not true for Bednar tumor, likely due to its rarity. Nonetheless, existing data indicates that the clinical features of Bednar tumor are comparable with its nonpigmented counterpart.3,7 There have been debates regarding the line of differentiation of the pigmented cells in Bednar tumor. A neural crest origin was initially suspected, which is reflected by its original name—storiform neurofibroma.4 Electron microscopy studies later confirmed the presence of melanosomes and premelanosomes in the pigmented cells3; however, neuroectodermal differentiation was not identified in the nonpigmented cells based on the absence of perineural fibroblastic differentiation.5 These findings have led to a conclusion that the pigmented cells in Bednar tumor are simply nonneoplastic bystanders that get secondarily entrapped or colonized in the tumor.5 Some regard DFSP in general as fibroblastic or histiocytic in nature.8,9 In our case, the tumor demonstrates areas of melanocytic differentiation, supported by immunoreactivity to melanocytic markers including MiTF, Melan-A, SOX-10, and, very focally, S100. Interestingly, these cells are nonpigmented and show similar morphological features, including comparable degree of nuclear atypia, to the rest of the tumor cells that are not labeled. This is important because it suggests that the immunoreactive cells are neoplastic instead of being coincidentally incorporated during tumorigenesis. Our findings are more consistent with the original claim made by Bednar that DFSP may be derived from neural crest.4 This argument is echoed by a recent case reported by Goncharuk et al10 that pigmented DFSP arises from a region of preexisting dermal melanocytosis. The authors argued that it is difficult to explain the source of the pigmented cells in Bednar tumor by colonization alone because of the absence of melanocytes normally in the dermis where the tumor usually arises. In addition, the multidirectional differentiation capabilities of neuromesenchyme to express fibrogenic, melanogenic, or neurosustentacular phenotypes could explain the mixed cellular phenotypes found in pigmented DFSP.10 It is possible that our current case represents an interim between conventional Bednar tumor and DFSP in a sense that a subset of the neoplastic cells gain melanocytic phenotype but fail to fully assume dendritic morphology and the capability to produce melanin pigment. Our findings lend support to the argument that DFSP may be of neuromesenchyme origin.
Our case is diagnostically challenging because of small sample size (punch biopsy) and that the tumor coexpressed CD34 and melanocytic markers (MiTF, Melan A, S100 and SOX10). CD34 is a nonspecific marker and has been shown to label a myriad of nonneoplastic (hematopoietic stem cells, endothelial cells, etc.) and neoplastic cells (solitary fibrous tumor, gastrointestinal stromal tumor, etc.).11–13 Rare cases of melanoma have been reported to aberrantly express CD34.14 DFSP occasionally lacks CD34 immunoreactivity.2 The absence of atypical junctional melanocytes and presence of t(17;22) (q22;q13) translocation in our case argue against a diagnosis of atypical melanocytic lesion.
In conclusion, we reported a case of DFSP with melanocytic differentiation, which raises a possibility of potential neuroectodermal origin of these tumors. The differential diagnosis of a CD34-positive cutaneous spindle cell proliferation should always include DFSP, especially in immunohistochemically and morphologically equivocal cases, with the knowledge that aberrant melanocytic differentiation may occur.
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2. Salgado R, Llombart B, M Pujol R, et al. Molecular diagnosis of dermatofibrosarcoma protuberans: a comparison between reverse transcriptase-polymerase chain reaction and fluorescence in situ hybridization methodologies. Genes Chromosomes Cancer. 2011;50:510–517.
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