IMMUNOREACTIVITY OF S100 PROTEIN, ALPHA-1-ANTITUYPSIN, AND CD68 IN ADULT AND CONGENITAL GRANULAR-CELL TUMORS

Some benign tumors categorized as ''granular cell tumors'' (GCTs) may have heterogeneous origins despite their uniform morphologic appearanc e. Adult GCTs (the usual type), presumed to be of Schwannian origin, a re reported to be positive for S100 protein (S100) and neuron-specific enolase (NSE). Congenital GCTs are S100- and NSE-negative and of unkn own but probable non-Schwannian origin. To elucidate the histogenesis of adult and congenital GCT, we undertook a comparative immunohistoche mical study using paraffin-embedded tissue from 10 cases of GCTs, of w hich 3 were the congenital type, 6 were the adult type, and 1 was an u nusual multiple GCT involving the colonic mucosa. All of the GCTs tver e negative for keratin, smooth muscle actin, muscle-specific actin, de smin, CD57, CD15, and MAC387. All of the adult and multifocal GCTs inv olving the colonic mucosa were positive for S100, NSE, alpha-1-antitry psin (A1AT), CD68, and vimentin. Congenital GCTs, on the other hand, w ere negative for S100 and NSE but positive for A1AT, CD68, and vimenti n. Our study suggests that these two types of GCT have different histo geneses because S100 and NSE are positive in the adult type but negati ve in the congenital type. They share, however, a common immunophenoty pe of positive A1AT, CD68, and vimentin. Although this may seem to ind icate a common histiocytic origin for adult and congenital GCT, anothe r macrophage marker, MAC387, is negative. Furthermore, CD68 is closely related to the glycoprotein of the lysosomal membrane and is not comp letely specific for histiocytic cells; for example, it is positive in reactive and neoplastic Schwann cells. Thus, we conclude that positive immunoreactivity for A1AT and CD68 in GCT may be a reflection of the intracytoplasmic accumulation of phagolysosomes and that it does not i mply a histiocytic origin for this tumors. We confirm that adult GCT i s of Schwannian origin and that congenital GCT is of uncommitted mesen chymal cell origin.