Cutaneous clear-cell granular cell tumors: the histologic description of an unusual variant

Granular cell tumors (GCTs) are neoplasms showing nerve sheath differentiation that can arise in the skin but, to our knowledge, have not been associated with significant clear-cell morphology.

Two patients developed four separate GCTs with distinctive, diffuse clear-cell change, which completely camouflaged the primary differentiation. The morphology, histochemistry and immunohistochemistry of the lesions are described and are compared with the presence and extent of clear-cell change in 14 other cases of GCTs.

The index cases were relatively broad proliferations with uniform diffuse clear-cell change and only minimal overlying epidermal hyperplasia. Prominent lymphoid nodules were present at the periphery. These clear-cell granular tumors were positive for S-100 protein, p75, CD68, NKI/C3 and neuron-specific enolase and were negative for epithelial mucin, periodic acid-Schiff, carcinoembryonic antigen, HMB-45, Melan-A, smooth muscle actin, Leu7, synaptophysin, CD34, factor XIIIa, epithelial membrane antigen and cytokeratin. Three of the fourteen comparison cases were found to have no clear-cell change, eight showed focal clear-cell change and three showed moderate clear-cell change.

The distinctive morphology and the immunohistochemical results are discussed in the context of the differential diagnosis of clear-cell cutaneous tumors.