Table 1 Age and sex distribution
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1 Histological and immunohistochemical studies on nevocellular nevi in the dermis With special reference to the histogenesis of nevus cells Kiyoshi Nishihara Department of Dermatology (Chief: Prof. Mitsuyoshi Honda, Director: Associate Prof. Shin-ichi Nakamura), Nippon Medical School The author has performed study on the histogenesis of the nevus cells in the nevocellular nevi. In the study, specimens of the intradermal nevi in 124 cases were evaluated histologically and immunohistochemically and the following results were obtained: 1) Findings of hematoxylin eosin staining It was observed that three types of cells, including type A cells (epidermoid type cells), type B cells lymphoid type cells), type C cells (neuroid type cells) were found to run through an intermediate stage from ( the upper part to the lower part of the nevocellular structure, although they disclosed different histological structures. In 39 (31.5%) of the 124 cases, Meissner's corpuscle-like cells were confirmed. 2) Findings of immunohistochemical staining i. Of the type A, type B and type C cells, the S-100 a protein stain was essentially negative. Meissner's corpuscle-like cells were selectively positive by this stain. ii. Although no particular difference was noted in the staining of S-100 protein between the type A and type B cells, a somewhat greater proportion of positive cells was noted in type C cells. In the Meissner's corpuscle-like cells, a notably higher positive conversion of cells was observed as compared to those of the three other types of cells. iii. Type A, type B and type C cells compared more or less similarly for the positive ratio of neuronspecific enolase but the ratio was unusually high in the Meissner's corpuscle-like cells. 3) Findings from routine electron microscopic staining i. Similar to the light microscopic findings, the nevus cells were found to change in shape uninterruptedly from the upper layer to the lower layer of the dermis. Unusually marked changes were noted both in the number and shape of the melanosome and premelanosome in the cytoplasm. ii. In the Meissner's corpuscle-like cells both melanosomes and premelanosomes were missing but a finding suggestive of a neuroid structure was affirmed. As noted above, the results of the histological, immunohistological and electron microscopic studies were in support of the general findings suggestive of a gradual shift of the nevus cells from the upper layer to the lower layer in the dermis, which prompted the author to support the so-called "neural crest origin hypothesis". Key words: intradermal nevocellular nevus, S-100 protein, neuron-specific enolase, electron microscopy Correspondence to Kiyoshi Nishihara, Department of Dermatology, Nippon Medical School First Hospital, 3-5-5, Iidabashi, Chiyoda-ku, Tokyo, 102 Japan
2 Table 1 Age and sex distribution
3 Table 2 Imrnunohistochemical staining of S-100 protein, S-100 a protein and S-100 protein in dermal nevus cell types Ĉ
4 Table 3 Immunohistochemical staining of NSE in dermal nevus cell types
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7 1) Miescher, G. et von Albertini, A.: Histologie de 100 cas de naevi pigmentaires d'apres les m6thodes de Masson. Bull. Soc. franc. de Dermat. syph., 42, , ) Traub, E.F. and Keil, H.: "Common mole" ; Its clinicopathologic relations and question of malignant degeneration. Arch. Dermat. Syph., 41, , ) Masson, P.: My conception of cellular nevi. Cancer, 4, 9-38, ) Winkelmann, R.K.: Cholinesterase in pigmented tumors of the skin. Arch. Dermatol., 82, 17-23, ) Mishima, Y. and Schaub, F.F.: Cholinesterase in junction nevus. J. Invest. Dermatol., 41, , ) Thorne, E. G., Mottaz, J. H. and Zelickson, A. S.: Tyrosinase activity in dermal nevus cell. Arch. Dermatol., 104, , ) Mishima, Y., Mevorah, B.L. and Schaub, F.F.: Electron microscopy of melanin synthesis in intradermal nevus 15) Nakajima, T., Watanabe, S., Sato, Y., Kameya, T., Shimosato, Y. and Ishihara, K.: Immunohistochemical demonstration of S-100 protein in malignant melanoma and pigmented nevus, and its diagnostic application. Cancer, 50, , ) Dhillon, A. P., Rode, J. and Leathem, A.: Neuronspecific enolase ; An aid to the diagnosis of melanoma and neuroblastoma. Histopathology, 6, 81-92, 1982, 18) Springall, D. R., Gu, J., Cocchia, D., Michetti, F., Levene, A., Levene, M. M., Marangos, P. J., Bloom, S. R. and Polak, cell, J. Invest. Dermatol., 39, , 1962, 11) Breathnach, AS.: Electron microscopy of a small pigmented cutaneous lesion. J. Invest. Dermatol., 42, 21-25, 12) Gottlieb, B., Brown, A. L. and Winkelmann, R. K.: Fine structure of the nevus cell. Arch. Dermatol., 92, 81 `87, 1965.
8 J. M.: The value of S-100 immunostaining as a diagnostic tool in human malignant melanomas ; A comparative study using S-100 and neuron-specific enolase antibodies. Virchows Arch. [A], 400, , 1983, 19) Sueki, H., Iwai, M., Kato, H. and Nishida, H.: Immunohistochemical and electron microscopic observations of nevic corpuscle. J. Cutan. Pathol., 11, , ) Tapia, F. J., Polak, J. M., Barbosa, A. J. A., Marangos, P. J., Dermody, C. and Pearse, AGE.: Neuron-specific enolase is produced by endocrine tumors. Lancet, 1 (8224), , ) Haimoto, H., Takahashi, Y., Koshikawa, T., Nagura, H. and Kato, K.: Immunohistochemical localization of y-enolase in normal human tissues other than nervous and neuroendocrine tissues. Lab. Invest., 52, , ) Dranoff, G. and Signer, D. D.: A word of caution in the 24) Hachisuka, H., Sakamoto, F., Nomura, H., Mori, O. and Sasai, Y.: Immunohistochemical study of S-100 protein and neuron-specific enolase (NSE) in melanocytes and related tumors. Acta Histochem. (Jena), 89, , ) Hsu, S.-M., Raine, L. and Fanger, H.: The use of antiavidin antibody and avidin-biotin-peroxidase complex in immunoperoxidase technics. Am. J. Clin. Pathol., 75, , ) Moore, B. W.: A soluble protein characteristic of the nervous system. Biochem. Biophys, Res. Commun., 19, , ) Isobe, T., Ishioka, N. and Okuyarna, T.: Structural relation of two S-100 proteins in bovine brain ; Subunit composition of S-100 protein. Eur. J. Biochem., 115, , ) Bredshow, R. A.: Proteins of the Nervous System. 2nd ed., p , Raven Press, New York, ) Nakajima, T., Yamaguchi, H. and Takahashi, K.: S-100 protein in folliculostellate cell of the rat pituitary anterior lobe. Brain Res., 191, , ) Nakajima, T., Sato, Y., Watanabe, S., Shimosato, Y., Ishihara, K. and Isobe, T.: Immunoelectron microscopical demonstration of S-100 protein in epidermal Langerhans cell. Biomed. Res., 3, , ) Takahashi, K., Yamaguchi, H., Ishizeki, J., Nakajima, T. and Nakazato, Y, : Immunohistochemical and immunoelectron microscopic localization of S-100 protein in the interdigitating reticulum cells of the human lymph node, Virchows Arch. [B], 37, , ) Nakajima, T., Watanabe, S., Sato, Y., Kameya, T., Hirota, T. and Shimosato, Y.: An immunoperoxidase study of S-100 protein distribution in normal and neoplastic tissues. Am. J. Surg. Pathol., 6, , ) Stefansson, K., Wollmann, R.L. and Moore, B.W.: protein in human chondrocytes. Nature, 295, 63-64, ) Iwanaga, T., Fujita, T., Takahashi, Y. and Nakajima, T.: Meissner's and Pacinian corpuscles as studied by immunohistochemistry for S-100 protein, neuron-specific enolase and neurofilament protein. Neurosci. Lett., 31, , ) Moore, B. W. and McGregor, D.: Chromatographic and electrophoretic fractionation of soluble proteins of brain and liver. J. Biol. Chem., 240, , ) Schmechel, D., Marangos, P.J. and Brightman, M.: Neuron-specific enolase is a molecular marker for peripheral and central neuroendocrine cells. Nature, 276, , use of neuron-specific enolase expression in tumor diagnosis. Arch. Pathol. Lab. Med., 108, 535, ) Matsunou, H., Shimoda, T., Kakimoto, S., Yamashita, H., Ishikawa, I. and Mukai, M.: Histologic and immunohistochemical study of malignant tumors of peripheral nerve sheath (Malignant schwannoma). Cancer, 56, , ) Pease, D. C.: Electron microscopy of human skin. Am. J. Anat., 89, , ) Birbeck, M. S. C., Mercer, E. H. and Barnicot, N. A.: The structure and formation of pigment granules in human hair. Exp. Cell Res., 10, , Legends Photo 1 Nevocellular nevus in the dermis. (HE stain, ~ 40) Photo 2 A type cells in the upper dermis. (HE stain, 100) Photo 3 B type cells in the middle dermis. (HE stain, ~ 160) Photo 4 C type cells in the lower dermis. (HE stain, 160) Photo 5 Meissner's corpuscle-like cells in the lower dermis. (HE stain, ~ 200) Photo 6 Ultrastructure of nevocellular nevus cells in the upper dermis. (Uranyl acetate and lead citrate stain, ~ 6, 000) Photo 7 Nevocellular nevus cells in the upper dermis which show numerous melanosomes, premelanosomes and pinocytic vesicles in the cytoplasm. (Uranyl acetate and lead citrate stain, ~ 60, 000) Photo 8 Ultrastructure of nevocellular nevus cell in the lower dermis. (Uranyl acetate and lead citrate stain. ~ 8.000) ~ ~
9 123 (37) 37 Plate (1)
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11 (39) 39 Plate (3) 6789
12 40 (40) Plate (4)
13 Photo 9 Nevocellular nevus cells in the lower dermis which show a few organellae and pre - melanosomes. (Uranyl acetate and lead citrate stain, ~ 14, 000) Photo 10 Ultrastructure of Meissner's corpuscle -like cells in the lower dermis. (Uranyl acetate and lead citrate stain, ~ 30, 000) Photo 11 Meissner's corpuscle-like cells which show lead citrate stain, ~ 30, 000) Photo 12 Ultrastructure of Meissner's corpuscle-like cells which show mitochondria and myelinlike structure in the axon. (Uranyl acetate and lead citrate stain, ~ 40, 000) axon and laminar cells. (Uranyl acetate and
1) Asa, S. L., et al.: Immunohistochemical localization of neuron-specific enolase in the human hypophysis and pituitary adenoma, Arch. Pathol. Lab. Med., 108: 40 `43, 1984. 2) Chi, B. H. and Kim, R. C.:
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