Osteoblast differentiation is regulated by various hormones and local factors such as estrogen, parathyroid hormone , bone morphogenetic proteins ( BMPs ) and hedgehogs . Estrogendeficiency increases systemic factors that stimulate osteoblast differentiation, resulting in a high turnover bone remodeling with accelerated bone formation. Parathyroid hormone has diverse effects on osteoblast differentiation depending on the exposure time in vitro mediated through different signal transduction systems. Among local factors, BMPs are the most potent inducers and stimulators of osteoblast differentiation: BMPs not only stimulate osteoprogenitors to differentiate into mature osteoblasts but also induce non-osteogenic cells to differentiate into osteoblast lineage cells. Sonic and Indian hedgehogs also play important roles in regulation of osteoblast differentiation by interacting with BMPs. Cbfa1, a transcription factor belonging to the runt-domain gene family, is essential for osteoblast differentiation and bone formation because Cbfa1-deficient mice completely lack bone formation due to maturational arrest of osteoblasts. BMPs are important local factors that up-regulate Cbfa1 expression. The phenotype of heterozygous Cbfa1 mutation is similar to that of cleidocranial dysplasia. The intimate interaction between the local factors including hedgehogs and BMPs as well as the transcription factor Cbfa1 play crucial roles in the process of osteoblast differentiation and bone formation. Further progress in bone research will provide information important not only in the field of cell biology but also for clinical research of various bone diseases.

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Sixty cases of non-Hodgkin's lymphoma (NHL) originating in the oral cavity and maxillofacial lymph nodes were investigated concerning clinicopathological features. The incidence of extranodal oral NHL (56.7%) was slightly greater than that of maxillofacial nodal NHL (43.3%). Histopathologically, all of the extranodal oral NHL showed diffuse pattern, and maxillofacial nodal NHL showed diffuse pattern in 21 cases and follicular pattern in 5 cases. Immunohistochemistry showed that T-cell lymphoma was 8.8% in the extranodal oral NHL and 15.4% in the maxillofacial nodal NHL. The 3-year survival for extranodal oral NHL (28.0%) is lower than that of maxillofacial nodal NHL (52.9%). Epstein-Barr virus (EBV) was found in 2 extranodal oral NK/T-cell lymphomas, 2 maxillofacial nodal peripheral T-cell lymphomas and 1 diffuse large B-cell lymphoma. All other cases were negative. These findings indicate that extranodal oral NHL is different from maxillofacial nodal NHL. There is an older age preponderance, a greater incidence of diffuse growth pattern, a higher T/B ratio, and a worse prognosis in the extranodal oral NHL.

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Histopathological diagnoses for palatal pleomorphic adenomas are often impossible because of inadequate biopsy procedures. In order to adduce reasons for the high ratio of unsuccessful palatal biopsies, we reexamined palatal biopsy specimens to assess depth and volume of tissue samples and sites of incision. The depth of unsuccessful biopsy specimens was 4.2 ± 0.4 mm (mean ± S.E.), which was significantly shorter than successful biopsy ones. The volume of unsuccessful biopsy samples was 142.5 ± 38.6 mm³, whichwas less than half of successful ones. The ratio of biopsy specimen volume to the total tumor volume in unsuccessful biopsies was 0.86 ± 0.2%, which was three times less than that in successful ones. Erroneous biopsies were more often performed in the posterior and lateral sides of tumors. The results indicate that incisional biopsies for palatal tumors should be performed in the anterior side of tumors with an incision depth of 5 mm including the palatal mucosa and with a 3% volume of tumors.

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Oral carcinogenesis is dependent upon cumulative effects within cells. Besides smoke, alcohol and solar radiation, many potentially carcinogenic noxious products in foods, medications andb the environment come into contact with the oral mucosa. Recently, a technique for bleaching vital teeth involving the application of 10% carbamide peroxide in trays by patients at home, the “nightguard vital bleaching technique,” has been introduced. Significant controversy has been generated over the risk of tissue damage from ingestion of carbamide peroxide during the bleaching process. In the current study, the effects of two bleaching agents, based on a 10% carbamide peroxide solution with and without Carbopol, were evaluated by the 9, 10-dimethyl-1, 2-benzanthracene (DMBA)-induction experimental model of carcinogenesis. For 20 weeks, 7 experimental groups were evaluated. Each group contained 10 hamsters and the following products were painted on the middle of the lateral border of the tongue: acetone, non-Carbopolcontaining 10% carbamide peroxide, Carbopol containing 10% carbamide peroxide, DMBA+10% carbamide peroxide with Carbopol, DMBA+10% carbamide peroxide without Carbopol, DMBA 0.5% in acetone and distilled water. The groups receiving acetone, 10% carbamide peroxide with and without Carbopol and distilled water showed no dysplastic alterations. In the group receiving DMBA alone, 4 animals developed dysplasias and 6 developed carcinomas, 3 being micro-invasive and 3 invasive carcinomas. For the group receiving DMBA and 10% carbamide peroxide with Carbopol, all 9 animals developed carcinomas, 2 being micro-invasive and 7 invasive. When DMBA and 10% carbamide peroxide without Carbopol was applied, 1 out of 9 animals presented intense hyperplasia and the other 8 invasive carcinomas. It was concluded that bleaching agents enhance the effect of other carcinogenic agents, probably by acting as promoters.

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To investigate the role of apoptosis in the development of odontogenic keratocysts (OKCs), apoptosis-related factors and apoptotic cells were examined immunohistochemically and by in situ DNA nick end-labeling. Expression of bcl-2 protein was detected in the cytoplasm of basal cells of OKC lining epithelium, and parakeratinized OKCs showed higher expression than orthokeratinized OKCs. P53 protein was detected sporadically in nuclei of OKC lining epithelium, and expression of Lewisy antigen was detected in the cell membranes of superficial cells of OKC lining epithelium. Ki-67 reactivity in bcl-2 or p53 positive cases was higher than in negative cases, but the correlation between these apoptosis-related factors and apoptotic cells was unclear. Ki-67 antigen was expressed in nuclei of basal and parabasal cells of OKC lining epithelium, while apoptotic cells were found among superficial flattened cells. Many Ki-67 positive and apoptotic cells were observed in basal cell nevus syndrome (BCNS)-associated OKCs.

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The term pseudotumor is used for a broad category of tumorous proliferations that are considered to be reactive rather than neoplastic and that can simulate malignant tumors. Presently, its nosologic position in the pathological diagnosis is still largely elusive and disputable. In this report, we present a comprehensive review of so-called inflammatory pseudotumor and its related lesions in the oral and maxillofacial region with different diagnostic considerations. The spectrum of these pseudotumors undoubtedly encompasses a diverse group of inflammatory fibrohistiocytic / myofibroblastic lesions with different causes, pathogeneses, and clinical and pathological implications.

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A case of tumor occurring in the palate of a 74-year-old Japanese female is reported. Although histological and immunohistochemical features of the tumor were identical to those of pleomorphic adenoma, except for scarce pleomorphic or “mixed” appearance, diffuse cellular and nuclear pleomorphism and relatively high proliferative cellular activity were observed. However, there was no metastasis or recurrence, indicative of its low-grade malignancy. Preexisting benign pleomorphic adenoma was not recognized. Due to these characteristics, we consider that the tumor should be diagnosed as “malignant pleomorphic adenoma” or “lowgrade malignant mixed tumor” and propose to separate such types of tumor from ordinary types of pleomorphic adenoma and carcinoma in pleomorphic adenoma.

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A case of acute myelocytic leukemia with unusual oral manifestation characterized by nodular lesion of the tip of the tongue is reported. The patient was a 31-year-old woman who had been admitted for treatment of recurrent leukemia. Pathologically, the lesion was diagnosed as leukemic cell infiltration. The possible reasons for this localized specific leukemic cell infiltration are discussed.

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The presence of phage in A. actinomycetemcomitans isolated from a Brazilian Papillon-Lefèvre syndrome patient was reported. Phage infection was detected by negative staining with phosphotungstic acid for electron microscopy. The phage infection might explain the strong periodontal destruction observed in this patient. The PLS patient is still in a plaque control program.

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A peripheral calcifying odontogenic cyst (PCOC) was observed in a 9 year-old Japanese boy. The patient visited our hospital with a chief complaint of swelling on the palatal aspect of the oral mucosa. He had felt the slowly growing lesion without pain for 3 months. Physical examination showed a firm submucosal mass approximately 1 cm in diameter in the palatal mucosa between the maxillary right central and lateral incisors. Based on clinical data, the lesion was thought to be an epulis; however, histological examination revealed a calcifying odontogenic cyst (COC). Follow-up examinations for over 1 year indicated no recurrence of the tumor. Although many cases of COC have been reported, this is the first case of PCOC in Japan suggesting racial differences in the incidence.

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We report a case of spindle cell type myoepithelioma arising from the submandibular gland initially examined by fine needle aspiration cytology (FNAC). The patient was a 47-year-old man who noticed a mass gradually enlarging in right submandibular region four years before consulting the Social Insurance Saitama Hospital. The cytological specimens revealed numerous massive clusters of spindle-shaped cells. The cells were comparatively spindle- and oval-shaped nuclei were centrally localized in them and their nuclear membrane was homogeneously hyperplasmic. Cytoplasms were slightly dense-stained with light green. Histologically, the tumor cells were uniform in spindle or elliptic shapes showing herringbone patterns. Immunohistologically, S-100, vimentin and α-SMA were positive reactions, and electron microscopically, desmosomes were indicated. In distinguishing myoepithelioma from soft tumors such as leiomyoma and neurinoma, it seems important to consider cytological findings comprehensively because they are different from each other in cell density, size and arrangement of cell populations, cell margins and cytoplasm features.

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