Granular cell tumors (GCTs) are rare, soft tissue tumors, and their histogenesis is still controversial, although the neurogenic theory, especially Schwann cell derivation, is considered the most plausible at present.
We studied eight cases of GCT clinicopathologically and immunohistochemically. The results were as follows:
1. Granular cells of GCT had a variety of sizes and shapes, were filled with fine eosinophilic granules, and showed lysosome-like characteristics, also with a variety of sizes and shapes, on electron microscopic observation.
2. Immunohistochemically, the intracytoplasmic granules showed positive reactions for S-100 protein, NSE, Kp-1 and diastase-resistant PAS staining but a negative reaction for a 1-antichymotrypsin. Additional lipid staining, such as oil red O, Sudan black B, and Nile blue, was performed in two cases, but was all negative.
3. In three cases, an appearance of transition from striated muscle fibers to granular cells, and the accumulation of intracytoplasmic granules with the shape of striated muscle fibers remaining were seen at the margin of GCT masses. In addition, four cases out of eight showed weakly positive reactions for myoglobin.
Thus, several cases were suggested to have a myogenic origin, and neither 5-100 protein nor NSE provided conclusive evidence of neurogenic origin due to their poor specificity. It was, therefore difficult to limit their derivation to neurogenic origin, and further examinations are required.
The accumulation of intracytoplasmic granules in other tumors, such as neurofibroma, which was referred to as granular cell neurofibroma by Enzinger and Weiss (1983), and leiomyoma, were previously reported. The neoplastic proliferation of granular cells seems unlikely in view of their few cell organelles on electron microscopic observation.
In order to explain our results and those of previous studies, it is most reasonable to consider that GCT is not a neoplastic lesion, that the accumulation of intracytoplasmic granules in GCT is the result of degenerative or reprocessing changes (Whitten, 1968), and that such “granular cell changes” occur in various tissues (Shear, 1960 and Millar, 1977).
Furthermore, previously reported “malignant” GCTs, which showed histological malignancy and remote metastasis and were often diagnosed with much difficulty, may include pre-existing malignant tumors with “granular cell changes”.
