Abstract.We immunohistochemically investigated the localization of activin A and follistatin in various human tissues with specific antibodies to recombinant human (rh-) activin A and rh-follistatin.

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The nature of the cells in neurofibromas was studied by electron microscopy and immunoelectron-microscopic examination of S-100 protein. Ultrastructurally, all five neurofibromas studied were found to be composed of Schwann cells, perineurial cells, and intermediate cells, which had features of both perineurial cells and fibroblasts. The Schwann cells had complex, branched cytoplasmic processes and a continuous basal lamina. The perineurial cells were distinguishable from Schwann cells by the presence of numerous pinocytotic vesicles, unbranched slender cytoplasmic processes and a discontinuous basal lamina. The intermediate cells had no basal lamina, but were topographically related to Schwann cells and had a similar fine structure to that of perineurial cells. Thus, they seemed to be modified neoplastic perineurial cells. Immunoelectron-microscopic studies showed the presence of cells with and without S-100 protein in the neurofibromas: cells with S-100 protein resembled Schwann cells ultrastructurally, and those without S-100 protein were perineurial and intermediate cells. Some Schwann cells with S-100 protein in one neurofibroma had numerous pinocytotic vesicles characteristic of perineurial cells, suggesting that Schwann cells and perineurial cells are functional variants of the same cell type. Thus this study showed that neurofibromas were composed of Schwann cells with S-100 protein and perineurial and intermediate cells, including so-called endoneurial fibroblasts, without S-100 protein. Morphological and functional transition seems to occur between Schwann cells and perineurial cells, and between perineurial cells and intermediate cells.

Angioleiomyoma is a solitary subcutaneous tumor characterized by pain in about half of patients with this tumor, and the pathogenesis of this pain has been a cause of much debate. To clarify the mechanism of pain and cytoskeletal property of tumor cells, 50 angioleiomyomas were studied clinicopathologically and immunohistochemically. The tumors occurred preferentially on the extremities, particularly the lower leg (46%), and the female to male ratio was 1.9:1. They were classified into three histological subtypes: (i) solid (30 cases); (ii) venous (15 cases); and (iii) cavernous (five cases). The pain and/or tenderness were present in 26 out of 49 patients (52%), in which small nerve fibers immunoreactive for S-100 protein and PGP9.5 were identified within the capsule of 20 tumors (77%) and the tumor stroma of 18 (69%), irrespective of the histological subtypes. In 24 patients where the pain was absent or unknown, nerves were observed within the capsule of 19 tumors (79%) and tumor parenchyma of 10 (42%). Many cells in all 50 tumors were positive for alpha-smooth muscle actin, and a relatively large number of cells in many tumors were positive for vimentin, desmin and collagen type IV. Also, cytokeratin (CAM5.2) reactivity was scattered in a few cells of four tumors. From these findings, the peculiar pain of angioleiomyomas could be mediated by the nerve fibers especially located within the tumor parenchyma. Although the expression of intermediate filaments in angioleiomyomas was heterogeneous, the overall cytoskeletal features were of smooth muscle cell differentiation.

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