LAUSR

To the Editor, In a recent study, Fernandez-Flores et al characterized non-neural granular cell tumors (NNGCTs) as neoplasms with differentiation of the fibrous root sheath. In particular, 4 of 5 cases of NNGCTs demonstrated folliculocentric growth, while the fifth specimen was too small to be investigated. Moreover, the immunoprofile of the tumors was similar to those of the fibroblasts of the normal fibrous root sheath, including increased CD10 expression. Regrettably, in the study, the authors did not consider the pre-existing literature cases of the glabrous mucosal lesions; particularly, 5 NNGCT cases of the oral cavity have been previously reported. Although the fact that NNGCTs can arise in the glabrous mucosa can reject the conclusion by Fernandez-Flores et al, in my review of the literature, some of these oral cases might have been incorrectly diagnosed. At least 1 of the 5 oral cases could be a histiocytic lesion, as histiocytoid cytomorphology was observed and immunohistochemical analysis was insufficient. In addition, another oral case might be a cellular neurothekeoma because uncertain granularity in the cytoplasm of the tumor cells and lobulated architecture separated by thin collagen bands were observed. Therefore, it still remains uncertain whether the suggestion of Fernandez-Flores et al is true, unless further studies confirm that NNGCTs cannot arise in the glabrous mucosa, such as the oral cavity; nevertheless, this paper really increased my interest about the relationship between NNGCT and granular cell fibrous papule (FP). FP is a common benign lesion arising on the face, especially on the lower part of the nose, which is considered by some authorities as a hamartomatous condition including the fibrous sheath of the hair follicle. FP is a polypoid or domed, superficial lesion with an angiofibromatous stroma and spindle or satellite mesenchymal cell proliferation, showing a folliculocentric distribution. In the rare variant of FP where the mesenchymal cells could exhibit granular cytoplasm, it would be histopathologically difficult to distinguish FPs from NNGCTs. The mesenchymal cells of granular cell FPs are positive for NKI/C3 and CD68. In addition, the stromal cells in FPs are negative for S100 protein and smooth muscle actin, but could be positive for CD10 (author’s unpublished observations). Although CD10 expression is not specific for these 2 conditions, the histomorphological and immunohistochemical characteristics of granular cell FPs are similar to those of NNGCTs. According to Fernandez-Flores et al, this similarity between the granular cell FPs and NNGCTs might be explained by their common cell differentiation. However, most cases of NNGCTs have been reported to be on the extra-facial locations, while FPs arise on the facial sites. Moreover, NNGCT could show varying degrees of nuclear atypia and lymph node metastasis, while FP is widely accepted as a benign condition. Therefore, NNGCT and granular cell FP do not seem to be part of a spectrum of the same entity. However, it could be considered that NNGCT is the neoplastic counterpart of granular cell FP, which is thought as a hamartomatous condition including root sheath fibroblasts. In order to verify this, further analysis is needed, especially of the glabrous mucosal lesions that have been reported as NNGCT of the oral cavity.