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The light microscopic, electron microscopic and immunohistochemical features of a small cell undifferentiated carcinoma of the minor salivary gland are presented. The tumor was composed predominantly of undifferentiated small cells with focally admixed neuroendocrine, exocrine and squamous cells, occasionally arranged in an organoid manner. The presence of vasoactive intestinal polypeptide in the tumor was found immunohistochemically. In addition, the tumor cells stained with Grimelius' impregnation. Immunohistochemically the tumor contained cells that reacted positively with the antibodies to carcinoembryonic antigen, 66K keratin polypeptide, or human salivary amylase. These findings indicate that a small cell undifferentiated carcinoma of the minor salivary gland, reported here, exhibits focally multidirectional differentiation as well as neuroendocrine cell derivation.

The adenocarcinoma produced by transplantation into nude mice of a neoplastic human salivary intercalated duct cell line was treated with 0.1 ml of minimal essential medium (MEM) containing 12-0-tetradecanoyl-phorbol-1Iacetate (TPA) at a final concentration of lo-' mol/l daily for 28 days and examined morphologically and immunohistochemically. The TPA treatment resulted in an enhancement of tumor growth. In addition, tumor cells containing secretory granules positively reactive to antiamylase serum were observed in the treated tumors, but not in untreated controls. These findings lead us to suggest that neoplastic intercalated duct cells treated with TPA can be induced to differntiate into acinar cells in heterotransplanted athymic nude mice.Cancer 6O:lOOO-1008,1987. NEOPLASTIC intercalated duct cell line initially es-A tablished in culture from a human submandibular salivary gland that existed in the field of therapeutic irradiation for carcinoma of the floor of the mouth can be used in our laboratories to study various aspects of the salivary gland cell differentiation.'-' Tumors grown in nude mice are histopathologically interpreted as adenocarcinomas. ' Cells of both tumors grown in nude mice and monolayer cell culture in vitro have phenotypes similar to that of the intercalated duct cell present in human salivary glands. 1,2 When, however, the cells are cultured in the presence of dibutyryl cyclic adenosine 3',5'-monophosphate (dB-CAMP) or the tumors grown in nude mice are treated with dB-CAMP, the cells assume morphologic characteristics and biologic markers that resemble that of myoepithelial cell^.'^^ From the *Department of Laboratory Medicine and the tSecond Department of Oral and Maxillofacial Surgery, Tokushima University School of Dentistry, Tokushima, Japan.Supported in part by a grant-in-aid for scientific research (6 1440083) from the Ministrv of Education. Science and Culture of JarJan.Moreover, commitment to differentiation into myoepithelial cells occurs in the neoplastic salivary intercalated duct cell line following the treatment with sodium butyrate. ' Many investigators, however, have suggested that human epithelial tumors of salivary glands arise solely from the intercalated duct cells,'-1° although Eversole' ' proposed that two cell types, the intercalated duct cells and the excretory duct reserve cells, might function as possible progenitors in the occurrence of the various salivary gland tumors. Thus, we are interested in whether cells with phenotypes other than that of the myoepithelial cell are induced in the neoplastic intercalated duct cells that have been isolated and characterized in our laboratories. Since it has been reported that 12-0-tetradecanoyl-phorbol-13-acetate (TPA) can induce terminal differentiation in a variety of cell syswe have studied the effects of TPA on the morphologic characteristics and biologic markers of neoplastic human salivary intercalated duct cells grown in athymic nude mice. During this experiment, we have found that treatment with TPA of the tumors...

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