Granular Cell Variant of Epithelioid Cell Histiocytoma

Abstract

Classic granular cell tumors (GCTs) stain strongly and uniformly positive for S100 protein and are believed to show Schwann cell derivation. Polypoid cutaneous tumors composed of cells with large nuclei and abundant granular cytoplasm that do not stain for S100 protein or show apparent Schwannian differentiation have been reported by several groups under names including "primitive polypoid granular cell tumors," "dermal nonneural granular cell tumor," and "primitive nonneural granular cell tumors of skin." We report a polypoid tumor composed of S100-negative epithelioid cells with abundant eosinophilic granular cytoplasm that meets diagnostic criteria for (primitive polypoid dermal) nonneural GCT but also meets criteria for a granular cell variant of epithelioid cell histiocytoma. We have identified a single previous report of a similar lesion. We report the immunohistochemical characteristics of these lesions and address how they are best classified.

A subset of so‐called dermal non‐neural granular cell tumours are underlined by ALK fusions, further supporting the idea that they represent a variant of epithelioid fibrous histiocytoma

“…Interestingly, the resemblance between NN-GCT and the granular cell variant of EFH has been previously noted. 4,5 The presence of well-circumscribed borders, epidermal collarettes, a low mitotic rate and mild/no atypia are features shared between our cases and these isolated reports, hinting at their diagnosis. It is, however, worth mentioning that, in the largest series of NN-GCTs, these aspects were not ubiquitously present, indicating the heterogeneity of this category of tumours and that our findings may not be extrapolated to all cases.…”

“…Following these efforts, two isolated case reports suggested that NN-GCT might correspond to a granular cell variant of epithelioid fibrous histiocytoma (EFH). 4,5 However, these statements were mostly based on morphological features, without the support of more specific ancillary techniques.…”

Granular cell differentiation: A review of the published work

“…These histological findings simulate those of Spitz's nevi and, to a lesser degree, pyogenic granuloma, reticulohistiocytoma, atypical fibrous histiocytoma, epithelioid hemangioma, neurothekeoma, cutaneous rhabdoid tumor, non‐lipidized xanthogranuloma and epithelioid sarcoma . ECH is S100 protein negative, and stains positively with factor XIIIa and CD68 . These tumors can also fit the profile of NN‐GCT …”

“…38 ECH is S100 protein negative, and stains positively with factor XIIIa and CD68. 39 These tumors can also fit the profile of NN-GCT. 39…”

S-100 Negative Granular Cell Tumor of the Oral Cavity

“…There are numerous histologic variants of FH with unique microscopic and immunohistochemical features [38]. Cases of common FH and variants exhibiting granular cell change have been described on the skin [39][40][41][42][43][44], as well as in the oral cavity [19]. The histologic features of a common FH are described as a mixture of fibroblastic and histiocytic cells in a storiform pattern with collagen trapping [19], and typically a grenz zone is present beneath the overlying epidermis [38].…”