Desmoplastic melanoma with sarcomatoid dedifferentiation

Abstract

Desmoplastic melanoma (DM) is a variant of melanoma, which typically affects chronically sun-damaged skin of elderly patients. Pure DM displays a low density of fusiform melanocytes in a collagen-rich matrix. In mixed DM, tumor cell density is higher, and parts of the tumor lack abundant stromal fibrosis. Both pure and mixed DMs usually express S100 protein homogenously. We report herein an unusual biphenotypic tumor characterized by the association of a pure DM with an undifferentiated solid spindle cell nodule. It occurred on the scalp of a 66-year-old man. A biopsy of the undifferentiated spindle cell nodule was initially interpreted at a commercial laboratory as atypical fibroxanthoma. The pure DM was seen only in the excisional specimen. All cells of the pure DM stained for S100 protein and SOX10. The adjacent solid sarcomatoid spindle cell nodule lacked expression of S100 protein, SOX10, as well as melan-A, gp100, and microphthalmia-associated transcription factor in >95% of its tumor cells. Although focal expression of melanocyte differentiation antigens in the solid tumor component made us favor a combined DM with sarcomatoid dedifferentiation, we also considered the possibility of a collision scenario, that is, a pleomorphic dermal sarcoma incidentally colliding with a DM. To further assess a possible relationship of the sarcomatoid nodule with the DM, we performed next-generation sequencing analysis on each component separately. The analysis revealed shared chromosomal copy number changes and a high number of common mutations, thereby supporting the concept of a DM with a dedifferentiated sarcomatoid component. An interesting finding is the presence of mutations of the neurofibromin 1 (NF1) gene in both tumor components.

Figure 1

Tumor with hemorrhagic crust on the scalp of a 66 year-old man.

Figure 2

Shave biopsy from the edge of the tumor. Ulcerated spindle cell proliferation (A). Adjacent pigmented melanocytic proliferation (B; Hematoxylin and eosin stain; C: Immmunohistochemistry for microphthalmia-associated transcription factor).

Figure 3

A spindle cell nodule associated with desmoplastic melanoma. Spindle cell nodule protruding above the skin surface and adjacent fibrosing process in dermis and subcutis (A). Desmoplastic melanoma is highlighted by an immunostain for S100 protein while the cellular spindle cell nodule is negative for S100 protein (B). The desmoplastic melanoma shows a pauci-cellular infiltrate of hyperchromatic spindle cells in a fibrous stroma (C). The large nodule is composed of densely cellular pleomorphic spindle cells (D).

Figure 4

Mutant allele frequencies observed in the desmoplastic melanoma and the spindle cell nodule. Mutations are colored according to their presence in one or both samples.

Figure 5

Copy number changes in the desmoplastic melanoma (A) and the spindle cell nodule (B).