Oral Med Pathol 14 (2009) 65

Proceeding of the 20th Annual Meeting of The Japanese Society of Oral Pathology

Meeting Period: July 29-31, 2009 Meeting Venue: Royton Sapporo, Sapporo, Hokkaido, Japan Organizing Committee: Chairperson: Professor Tohru Kaku, Division of Clinical Oral Pathology, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido, Japan Program Opening Address: T. Kaku (Health Sciences University of Hokkaido) Special Lecture: Speaker: T. Himi (Sapporo Medical University) Scientific Symposium: Symposium Ⅰ: Diagnostic Pitfall of Oral Pathology Organizer; I. Ogawa (Hiroshima University Hospital), H. Harada (Iwate Medical University) Symposium Ⅱ: Approaches to correct diagnosis of the Oral - Concepts of clinical status and histopathology - Organizer; H. Maeda (Aichi-Gakuin university), K. Komiyama (Nihon University) Symposium Ⅲ: Surgical Conference Organizer; Y. Tanaka (Tokyo Dental College), G. Sekine (Shimane University) Case Discussion: 13 Titles Case Report: 21 Titles (poster) General Session: 32 Titles (poster) Slide Seminar: 1. Cytology: K. Kayo & T. Utsunomiya (Nihon University, School of Dentistry at Matsudo) 2. Autopsy: T. Yamada (Nihon University, School of Medicine) 3. Macroscopy: M. Toida (Gifu University, School of Medicine) Closing Address: T. Kaku (Health Sciences University of Hokkaido)

Abstracts Symposium: Diagnostic Pitfall of Oral Pathology or synovial sarcoma. Herein a reference on diagnostic problems especially focused on double-layered ducts or SⅠ-1. Morphological characteristics of salivary biphasic morphology is made. gland tumors: a reference focused on double- layered ducts and biphasic differentiation SⅠ-2. Non-odontogenic lesions of the jaw bone: Harada H bone tumors and tumor-like lesions Department of Oral Pathology, School of Dentistry, Iwate Utsunomiya T Medical University Department of Oral Pathology, Nihon University School of The most striking histological feature of salivary gland Dentistry at Matsudo tumors is the participation of modified (neoplastic) There are various types of tumors and tumor-like lesions myoepithelial cells, which is typically reflected in double- in the jaws. For making the definitive diagnosis, it is so layered ducts commonly seen in , important to understand the characteristic features of tumor or epithelial-myoepithelial carci­ cells and extra- (inter-) cellular matrices in these lesions. For . In these structures, myoepithelial cells are arranged in instance, osteosarcoma, one of the most major bone tumors, the outer layer and reveal cellular morphology equivalent to consists of proliferation of atypical mesenchymal cells with basaloid or clear cells in most instance. Although lacking osteoid and/or bone formation as the typical characteristics, ductal structures, myoepithelioma or myoepithelial carci­ the tumor, however, often shows minimum cellular atypism, noma could show biphasic morphology, but does not directly marked cartilage and/or myxoid matrix formation, or impart dual directional differentiation, unlike carcinosarcoma unremarkable evidence of osteoid and bone formation. In 66 Proceeding of the 20th Annual Meeting of The Japanese Society of Oral Pathology such cases, it is so difficult to distinguish the osteosarcoma different etiologies with a common clinical and histological from the chondrosarcoma, fibrosarcoma and fibro-osseous appearance. Oral lichen planus (OLP), lichenoid contact lesions. The diagnostic problems of the tumors and tumor- reactions (LCR), lichenoid drug reactions (LDR) and graft like lesions in jaws are present and discussed herein, from versus host disease (GVHD) can affect the and viewpoints of morphology of these tumor cells and formation belong to the group of lichenoid reactions (LR). Thus, LR of the extra- (inter-) cellular matrices. does not represent one disease entity but should be considered as a pathological reaction pattern instigated by SⅠ-3. Histological diversity in ameloblastoma different etiological entities. Immunological mechanisms Nagatsuka H play an important role in the pathogenesis of all members of Department of Oral Pathology and Medicine, Graduate School the LR-group. OLP is a mucocutanous disease which of Medicine, Dentistry and Pharmaceutical Sciences, Okayama presumably involves autoreactive T-cells. LCR are seen in University oral mucosa in contact with dental materials, and is Ameloblastoma is the most common , considered to be a delayed hypersensitivity reaction against which is characterized by proliferation of odontogenic the filling material. Recently it has been suggested that epithelium. However, its diagnosis may sometimes be diffi­ bacterial antigens may also induce LCR. LDR are elicited by cult or misguided by its histological diversity. We should pharmacological drugs which may act as haptens linked to note that the epithelial component which appears in self-proteins. GVHD is observed in patients treated with ameloblastoma is also observed in other odontogenic allogeneic stem cell transplantation. Immune cells from the tumors, and vice versa, the feature of other odontogenic donor recognize the recipient’s tissue as foreign causing a T tumors also may be appears in ameloblastoma. Also the cell dominated inflammatory cell infiltrate in the mucosa estimation of malignancy in ameloblastoma is problematic. underlying the oral epithelium. In the diagnosis of ameloblastoma, it is absolutely imperative The explanation behind the different clinical to inform the proper information to the clinicians, contem­ manifestations of OLP is related to the magnitude of the plating its histology, invasiveness and clinical behavior. subepithelial inflammation. A mild degree of inflammation may provoke the epithelium to produce hyperkeratosis, SⅠ-4. Lymphoid lesions in the head and neck- MALT whereas more intense inflammation will lead to partial or lymphoma and related lesions- complete deterioration of the epithelium, histopathologically Izumo T perceived as atrophy, erosion or ulceration. This corroborates Department of Pathology, Saitama Cancer Center with the fact that most erythematous and ulcerative lesions In new WHO classification (2008) histopathological are surrounded by white reticular or papular structures. An examination plays only a part in determining the final inflammatory gradient may be formed where the central part diagnosis. In this symposium I comment on a diagnostic comprise an intense inflammatory process while the procedure about lymphoid lesions at present, mainly MALT periphery is less affected and the epithelial cells are able to lymphoma (MZBL). MZBL affects almost all extranodal respond with hyperkeratosis. sites, common site in head and neck are salivary glands, To differentiate between the four types of lichenoid thyroid gland, ocular adnexa, oral mucosa and tonsil. It was reactions, a histopathologic examination is of modest known that MZBL had a history of chronic inflammatory diagnostic value. The reason is that the four lesions display disorder, such as Sjögren’s syndrome, Mikulicz’s disease, the same histopathologic features. Undoubtedly, histopa­ Hashimoto’s disease, but it was recently reported that MZBL thology is a valuable tool when lichenoid reactions are to be can also arise from IgG4-related sclerosing disease. MZBL discriminated from other mucosal lesions. The necessity of a consists of various cells, has varieties by organs and there is biopsy to arrive at an accurate diagnosis of olp has been no specific marker, so distinguishing morphologically discussed but explicit guidelines have not been universally between the early phase and chronic inflammatory lesions is approved. When the diagnosis is uncertain, biopsies should very difficult. In the future MZBL may be divided into always be taken. subtypes that can not be distinguished histopathologically. Since the etiology behind OLP is unknown, basic conditions are lacking for development of causal therapies. Symposium: Approaches to correct diagnosis of the Thus, all current treatment strategies are aiming at reducing Oral Lichen Planu - Concepts of clinical status and or eliminating symptoms. Several topical drugs have histopathology been suggested including steroids, calcineurin-inhibitors (ciclosporin and tacrolimus), retinoids, and UV-phototherapy. SⅡ-2. Clinical characteristics and treatment Among these, topical steroids are widely used and accepted strategies of oral lichenoid reactions with special as the primary treatment of choice. Some reports have reference to oral lichen planus advocated very potent steroids as clobetasol propionate in Jontell M favour of intermediate steroids as triamcinolone acetonide. Department of Oral Medicine and Pathology. Institute of However, no randomized clinical trials exist where different Odontology, Sahlgrenska Academy, University of Gothenburg, formulas, strengths and classes of topically applied steroids Sweden have been compared. Topical application of ciclosporin, Lichenoid reactions represent a family of lesions with tacrolimus and retinoids has been suggested as a second line Oral Med Pathol 14 (2009) 67 therapy for OLP. Ciclosprorin has been reported to be less expansive and infiltrative growth. Microscopically, the effective than clobetasol propionate and not significantly tumor mainly consisted of sheet-like arrangement of the better than 1% triamcinolone paste. In a comparison of cells, which had oval to polygonal shaped nuclei and pale topical application of clobetasol and ciclosporin, the former cytoplasm accompanying with squamous eddies. In some has been found to be more effective in inducing clinical part of the tumor, ductal formation with stromal myxo­ improvement, but the two drugs have comparable effects on chondroid matrix and hyalinization were observed. Mitotic symptoms. Clobetasol was found to give less stable results figure was rarely seen. MIB-1 labeling index was varying than ciclosporin when therapy ended and was ascribed a from 0.5% to 6.5% (ave. 3.5%) in the lesion. After the higher incidence of side-effects but none of these were operation, we found out that the patient had undergone severe enough to require discontinuation of therapy. Topical surgery on the left submandibular gland tumor 38 years ago. tacrolimus 0.1% ointment has been reported to have a better Pathological diagnosis of the tumor was unknown. initial therapeutic response than triamcinolone acetonide 0.1% ointment. However, this drug has been labelled with D-3. Tumor of the submandibular gland FDA’s Black Box Warning: “Possibility of increased risk of Kishino M1, Ishibashi M1, 2, Sato S1, Murakami S3, malignancy (squamous cell carcinoma and lymphoma) in Fukuda Y4, Okura M2, Ogawa Y1, Kogo M2, Toyosawa S1 patients using topical tacrolimus/pimecrolimus for cutaneous Department of 1Oral Pathology, 2Oral & Maxillofacial Surgery psoriasis these agents should be used in limited circumstances, 1, 3Oral & Maxillofacial Radiology and 4Clinical Laboratory, and patients made aware of these concerns”. In conclusion, Osaka University Graduate School of Dentistry topical steroids should be used as the primary therapeutic A 65-year-old man was referred to our hospital because choice for symptomatic OLP. Ciclosporin may be considered of submandibular swelling and pain. From clinical and as a second choice although the efficacy has been questioned. radiological examination, the lesion was diagnosed as Tacrolimus should only be used by experts when symptomatic malignant submandibular tumor with multiple metastases. OLP lesions are recalcitrant to topical steroids. The tumor excision and radical neck dissection were It is widely accepted that patients with OLP are performed. The tumor consists of a hyalinized nodule with predisposed to develop oral carcinomas although it should calcification and diffusely proliferative tumor nests. The be emphasized that the risk is low and presumably does not tumor nests were composed of large atypical cells with large exceed an incidence of 0.2 % per year. Albeit this low risk nuclei and prominent nucleoli, containing PAS-positive for patients with OLP to contract oral squamous cell substance. Immunohistochemically, these tumor cells were carcinomas, a minimum of annual monitoring has been positive for AE1/AE3, CK7, CK18, EMA and CEA, and suggested. negative for CK14, α-SMA, S-100, GFAP, Chromogranin A.

Case Discussion D-4. Tumor of the Ogawa I1, Maejima T2, Kitajima S3, Miyauchi M3, D-1. , presentation of three cases Takata T3 Takeda Y 1Center of Oral Clinical Examination, Hiroshima University Department of Oral Pathology, School of Dentistry, Iwate Hospital, 2Department of Pathology and Laboratory Medicine, Medical University National Hospital Organization Nagano National Hospital and Two cases of usual type of oncocytoma arisen in the 3Department of Oral and Maxillofacial Pathobiology, Graduate parotid gland and a clear cell oncocytoma arisen in the School of Biomedical Sciences, Hiroshima University submandibular gland were presented. Thses tumors were A 36-year-old male had noticed a swelling in right side composed of well circumscribed mass of densely arranged of the palate for about 2 months. Physical examination cells showing solid, trabecular and tubular patterns. The revealed a solid tumor with ulceration. The resected tumor, relation between oncocytoma and oncocytosis (diffuse measuring 13 × 8 × 7mm, was solid with grayish-white color hyperplastic oncocytosis, multifocal oncocytic adenomatous and well demarcated. Histopathologically, the tumor hyperplasia is discussed. proliferated in relatively well-circumscribed nodular growth pattern, but was not encapsulated, and consisted of tubular, D-2. Metastatic tumor of the sternum cribriform and trabecular nests with abundant hyaline Urano M1, Kuroda M1, Mizoguchi Y2, Abe M3 matrices. Luminal and abluminal cells were identified and Fujita Health University, School of Medicine, 1Department of the latter showed the various degrees of positivity for Diagnostic Pathology, 2Second Department of Pathology and neoplastic myoepithelial cell markers and isolated into the 3School of Health Science, Department of Pathology hyaline stroma. Cellular atypia and more or less high A 58-year old male had noticed a swelling for two years proliferative activity were noticed. on his anterior chest. CT and MRI examination revealed a tumor, 6×6cm in size, existed in the sternum. Wide resection of the tumor was performed. The gross finding showed an ill-defined solid tumor, which occupied sternum and sternocleido joint. The tumor lacked fibrous capsule and had 68 Proceeding of the 20th Annual Meeting of The Japanese Society of Oral Pathology

D-5. Unusual lesion of painful swelling for one month in her right mandibular Irie T1, 6, Ogawa I2, Takata T3, Toyosawa S4, Tachikawa T1, region. MRI showed a 28-mm mass lesion with ill-defined Saitou N5, Akiba M5, Suzuki Y6 margin and intermediate signal intensity in T2-weighted 1Department of Oral Pathology, Showa University School of imaging in the right mandible. Histopathologically, the Dentistry, 2Center of Oral Clinical Examination, Hiroshima tumor was composed of fibroblasts / myofibroblasts and University Hospital, 3Department of Oral and Maxillofacial collagen fibers with hemorrhage. Mitotic figures were Pathobiology, Graduate School of Biomedical Sciences, infrequent and never atypical. Immunohistochemically, Hiroshima University, 4Department of Oral Pathology, Osaka tumor cells were positive for vimentin, focally positive for University Graduate School of Dentistry, 5Department of Oral SMA, and negative for desmin and CD34. Ki-67 LI was and Maxillofacial Surgery, Asahi General Hospital, 6Department 5.4%. of Pathology, Asahi General Hospital A 67-year-old male had a paresthesia of the left side of D-8. A case of the right maxillary tumor with post- lower and mental region of the skin and was admitted to operative lung metastases Asahi General Hospital. Radiographically, the lesion showed Kusafuka K approximately well-defined but partially ill-defined radiolu­ Pathology Division, Shizuoka Cancer Center Hospital and cency intermingled with foci of radioopacity. Diagnosis of Research Institute biopsy was consistent with cement-ossifying fibroma. At the The patient was a 60-year-old Japanese female, who operation, the lesion was fragile, therefore, curettage was noticed a swelling of the right alveolar mucosa. This carried out as entirely as possible. Histologically, most of maxillary tumor consisted of the dense proliferation of pieces of resected materials were composed of trabecular or atypical spindle-shaped cells with the fascicular pattern, but round hard tissue and fibrous tissue. In the majority of these no hard tissue formation was found. The primary tumor was hard tissues had no lamellar structure with or without focally positive for ASMA, and desmin. She was followed osteoblast rimming. Only a part of resected materials up with CT. Three years after operation, one lung metastasis contained dispersed thin cords and small nests of epithelial was found, and histologically, this metastatic tumor was cells accompanied by fibrous tissue. Cellular atypia and similar to the primary tumor. Eight months after VATS, mitotic figure were not conspicuous. These epithelial cells another lung metastasis was found. Histologically this showed negative for PAS and mucicarmine stain and metastatic tumor consisted of the atypical oval cells with immunohistochemically positive for AE1/AE3, negative for osteoid and calcified chondroid formation. S-100 protein, CEA, carletinin, CD34, CD44 and KP-1. MIB-1 positive nuclei were not remarkable. D-9. A case of the lower gingival tumor with the upper lip tumor D-6. Tumor of mandible Kusafuka K Kobayashi T1, Maruyama S1, Cheng J2, Fujita H3, Pathology Division, Shizuoka Cancer Center Hospital and Takagi R3, Hayashi T4, Saku T1, 2 Research Institute 1Oral Pathology Section, Department of Surgical Pathology, The patient was a 69-year-old Japanese female, who Niigata University Hospital; Divisions of 2Oral Pathology, Oral noticed a swelling of the lower anterior gum. A bulky tumor and Maxillofacial 3Surgery and 4Radiology, Niigata University was found in the right to the left molar region of the gingiva. Graduate School of Medical & Dental Sciences Histologically, the tumor consisted of the proliferation of the A 79-year-old male had noticed a swelling in his right atypical squamous cells, and of the reticular or vessel-like cheek region for 2 months. At his first visit to our hospital, a proliferation of atypical eosinophilic ovoid/short spindle- diffuse swelling was recognized in the right molar region of shaped cells. Another tumor was also found in the right mandible. Clinical examinations including CT, MRI revealed upper lip. Grossly, it was a papillomatous tumor, and a well-demarcated multilocular lesion with solid and cystic histologically, it consisted of the proliferation of the areas. The tumor was surgically removed under general squamous cells with minimal cytological atypia, and it anesthesia. Histopathologically, the tumor was composed of showed the hyperparakeratosis, keratin plugs, and bulbous stellate reticulum-like tumor cell nests in fibrous stroma. The rete ridges. tumor cells had eosinophilic cytoplasm with nuclear pleomorphism, scattering mitotic figures. They showed D-10. A malignant tumor of the mandibular some invasive growth into the capsule, with which most of gingiva the cortical bone was replaced. Some of the tumor cell nests Ito N1, Muramatsu Y2, Nagayama M1, Sato M1, reached to the submucosal layer of the covering gingival Takeuchi H1 mucosa. 1Division of Oral Pathology, 2Division of Oral and Maxillofacial Surgery, Asahi University School of Dentistry D-7. A case of mandibular tumor We have a case (81-year-old-female) of malignant tumor Yada N , Kashima K, Daa T, Yokoyama S which showed rapid growth with ulceration of lower gingiva Department of Diagnostic Pathology, Faculty of Medicine, Oita and irregular resorption of mandibular bone. Biopsy showed University histologically fibrous spindle shaped tumor cells have Patient was a 2-year-old female who had noticed a characterized herring bone cellular growth pattern, and high Oral Med Pathol 14 (2009) 69 number of cellular mitosis. Immunohistochemcal study Case Report revealed positive reaction for vimentin, α-SMA , HHF35 muscle actin, S-100 protein and Ki-67, but negative reaction C-1. A case of multiple MALT lymphoma of upper for cytokeratin AE1/AE3, Runx2, DMP-1 and desmin, and lower lip resulted to be diagnosed as leiomyosarcoma. Kenmotsu M1, Miwa T1, Kimura Y1, Matsuoka K1, Matsuzaka K1, Hashimoto S2, Inoue T1 D-11. A case of gingival neoplasm 1Department of Clinical Pathophysiology, Tokyo Dental College, Matsumoto M1, Mukae S1, Omagari D1, Arai S2, 2Department of Pathology, Tokyo Dental College Tanaka T2, Asano M1, Ohki H2, Komiyama K1. We report a case of multiple MALT lymphoma of upper 1Department of Pathology, 2First department of oral and and lower lip. A 14 year-old man was admitted to the Chiba maxillofacial surgery Hospital of Tokyo Dental College with swelling of lower lip. A 15 year-old male was referred to our hospital for The lesion was resected under general anesthesia. Histo­ evaluation of gingival ulceration with cortical bone erosion pathologically, the lesion consisted of proliferation of involving left lower premolar region. Several clinical lymphoid cells with foliole pattern and mild dysplasia. examinations including tumor markers were within normal Immunohistochemically, these cells were positive for Ki-67, limits. An incisional biopsy specimen showed small islands L26, and MB1, and slightly positive for UCHL1 and MT1. and cords beneath covering epithelium. They lacked The final pathological diagnosis was MALT lymphoma. peripheral palisading pattern and had occasional squamous Two years after the operation, similar lesion was appeared in differentiation. The neoplastic cells were small and have the upper lip. Histopathological findings of resected material round pale nuclei with faintly eosinophilic cytoplasm. showed similar pattern. Immunohistochmistry demonstrate diffuse reactivity for cytokeratins 8, 13, 17, 18, 19, and focal reactivity for alpha- C-2. A case of malignant lymphoma accompanies smooth muscle actin, S-100 protein and vimentin. Ki-67 neurofibroma in the palate labeling index reached approximately 40%. Michifuri Y, Nakamori K, Sasaki T, Hiratsuka H Department of Oral Surgery, Sapporo Medical University D-12. Ulcerative lesion of gingival mucosa School of Medicine Kuyama K1, Endo H2, Matsumoto T3, Sun Y1, We report a case of malignant lymphoma with accom­ Yamamoto H1 panying neurofibroma in the palate. The patient noticed a Departments of 1Oral Pathology, 2Periodontology, 3Clinical gradual swelling of the left side of the palate. Upon Laboratory, Nihon University School of Dentistry at Matsudo examination, a soft elastic mass arising in the left anterior A 57-year-old male had a slight haphalgesia in the left border of the palate, and a hard elastic mass, which included lower gingival mucosa of molar area for 2 years. After 2 an ulcer in the left anterior ridge, were recognized. A tumor years, symptom and pain had enlarging. Macroscopically, excision was performed with under general anesthesia. The the lesion had erosive/ulcerative appearance with bleeding resected specimen was composed of two different types of and irregular border. Cytologically, eosinophilic surface the tumors. The lesion which included the ulcer was cells showed nuclear enlargement, irregular shape and deep diagnosed as diffuse large B-cell lymphoma, and the colored cytoplasm. Intermediate cells were nuclear enlarge­ surrounding lesion was diagnosed as neurofibroma. ment, N/C ratio increasing and prominent nucleoli. C-3. A case of metastatic malignant lymphoma seen D-13. A case of upper lip tumor in the tongue Ohuchi T1, Taira H2, Kaku T1 Enoki N, Ohno J, Iwahashi T, Okamura K, Taniguchi K 1Division of Clinical Oral Pathology, 2Division of Oral and Division of Pathology, Department of Morphological Biology, Maxillofacial Surgery, Health Sciences University of Hokkaido Fukuoka Dental College A 70-year-old Japanese male had a swelling of central We report a case of metastatic malignant lymphoma seen region in the upper lip for the past 4 years. The resected oval in the tongue. A 70-year-old-male visited our hospital with a tumor with smooth surface was 17 × 14 × 12 mm in size. In chief complaint of repeated aphtha in the sublingual region. imprint cytology from cut surface of the tumor, epithelial Histopathological diagnosis of biopsy revealed T cell cells were arranged in cohesive large clusters with sheets- lymphoma in the tongue. We supposed the lesion would be like and ductal structures. Various cell clusters were the primary focus, so mycosis fungoides-like T cell composed of atypical large polygonal cells with abundant lymphoma was mostly suspected. However, it turned out cytoplasm, round - oval nucleus and large number of spindle that the patient had the history of enteropathy type T cell shaped cells without marked atypia. Nucleoli were prominent lymphoma. Together with results of scrutinizing the intestinal in some atypical cells. Metachromatic stainings were specimen, present case was suspected to be a metastatic observed in several cell clusters with Giemsa staining. malignant lymphoma. 70 Proceeding of the 20th Annual Meeting of The Japanese Society of Oral Pathology

C-4. A case of lymphoepithelial carcinoma arising Panoramic examination indicated a radiopaque lesion, and in the parotid gland this was confirmed by an incisional biopsy. A histopathological Ehara M, Iwasaki S, Nakashima A examination revealed a tumor exhibiting spindle cells with Saiseikai Fukuoka General Hospital, Division of Pathology nuclear hyperchromasia and no mitotic activity as well as an A 69-year-old female was visited to our hospital because irregular osteoid formation. The tumor was diagnosed as of left parotic region swelling for 2 month. The lesion was LGOS. The patient was treated surgically, and there was no diagnosed as the parotid gland benign tumor by MRI and evidence of recurrence after operation. US, and the tumor was resected. Macroscopically, tumor measuring 3.3 × 2.9 cm, showed white to yellowish white C-8. A case of intraosseous mass with capsule. Histopathologically, the tumor was arising from the composed of the cells that are a little more large-scale than Sugita Y1, 2, Kubo K1, 2, Sato E1, Yoshida W1, Nakatsuka lymphocytes and lymphoid stroma. Immunohistochemically, K3, Abe A3, Kurita K3, Maeda H1, 2 cancer cells were positive for AE1/AE3 and EMA, and Department of 1Oral Pathology, 2Diagnostic Oral Pathology, negative for LCA. 3Oral and Maxillofacial Surgery, Aichi Gakuin University We report a rare lesion in which, intraosseous verrucous C-5. Histopathological analysis of metastatic malig­ carcinoma arising from the odontogenic cyst. nant tumor of mandible from distant organs A 35-year-old male patient had noticed swelling of the Kanri Y1, Ohkubo Y1, Okada Y1, 2 maxillary gingiva. Clinical examination revealed an odonto­ 1Nippon Dental University, School of Life Dentistry at Niigata, genic cyst, mass in the part extended from the left maxilla Department of Pathology, 2Nippon Dental University, Niigata anterior teeth to the first molar. The mass was enucleated Hospital, Department of Clinical Laboratory surgically. Here we report 3 cases of metastatic malignant tumor in Histopathological examination revealed verrucous mandible from distant organs: rectum, prostate, and carcinoma. The tumor is composed of an exophytic lesion mammary gland. Case 1: A 65 years old male. Metastatic comprised of thickened, papillary squamous epithelium and tumor of mandibular from rectal malignant tumor (moderately also an endophytic growth of well differentiated squamous to well differentiated tubular ). Case 2: A 74 epithelium with cytologic atypia and mitotic activity. It is years old male. Metastatic tumor of mandibular from mandatory to correlate the clinical and histopathologic prostatic tumor (adenocarcinoma). Case 3: A 43 years old findings to establish a diagnosis. female. Metastatic tumor of mandibular from breast cancer. (Medullary carcinoma >solid tubular carcinoma) C-9. Basaloid squamous cell carcinoma of tongue, 2 case report. C-6. Lung large cell carcinoma with metastasis to Shimao Y1, Hayashi N2, Itoh M2, Nishikubo M2 the upper jaw: case report 1Department of pathology, 2Department of dental surgery, Namikoshi S1, Watanabe M1, Harada T2, Chiba H1 Miyazaki Prefectural miyazaki hospital 1Department of Oral and Maxillofacial Surgery, Tokyo Medical Basaloid squamous cell carcinoma, a rare variant of University, 2Departemnt of Pathology, Jikei University School squamous cell carcinoma, is a high grade malignant tumor. of Medicine This report presents two case of basaloid squamous cell Large cell carcinoma is a very rare type of tumor. We carcinoma arising at the posterior region and the back of the will report the case of a 79-year-old man that the lung large tongue. cell carcinoma metastasized to the upper jaw and other organs. This patient was referred to our department with C-10. Three cases of oral squamous cell carcinoma complaints of bleeding from the left upper gingiva. Biopsy which had been followed as a diagnosis of oral was performed so that histopathological finding was poorly lichen planus differentiated. Immunohistochemistry of both CAM5.2 and Yamashita M1, Jinbu Y1, Itoh H1, Kusama M1, TTF1 was positive, while that of NapsinA was negative. Matsumoto N2, Komiyama K2 When we compared them with lung specimen, these 1Department of Dentistry, Oral and Maxillofacial Surgery, Jichi resembled extremely so that it was clear that this gingival Medical University, 2Department of Pathology Nihon University large cell carcinoma metastasized from the lung. School of Dentistry We report 3 cases of oral squamous cell carcinoma. In C-7. Low grade osteosarcoma in the Mandible; these 3 patients, clinical diagnosis and histopathological report of a case. diagnosis of the initial biopsy specimens was oral lichen Nakamori K, Sasaki T, Michifuri Y, Hiratsuka H planus. We re-examined these biopsy specimens retrospec­ Department of Oral Surgery, Sapporo Medical University tively and we discuss on the diagnostic criteria of oral lichen School of Medicine planus. Low grade osteosarcoma (LGOS) is a malignant neoplasm occurring in the bones, and is relatively rare in the oral region. In this study, we report a case of LGOS of the mandible. A tumor was located in the body of mandible. Oral Med Pathol 14 (2009) 71

C-11. A Case of Primary Intra-osseous Carcinoma C-14. Solitary fibrous tumor of the lower lip: a case Suspected the Malignant Change from the Epithe­ report lium of the Mandibular Cyst Wall ; Histopathological Kamino Y1, 2, Ohuchi T2, Abiko Y2, 3, Kaku T2 Analysis 1Sapporo Oral and Maxillofacial Surgery Clinic, 2Division of Ohkubo Y1, Kanri Y1, Moride M1, Hasegawa H1, Clinical Oral Pathology, 3Division of Oral Medicine and Okada Y1, 2 Pathology, School of Dentistry, Health Sciences University of 1Department of Pathology, School of Life Dentistry at Niigata, Hokkaido The Nippon Dental University, 2Clinical Laboratory, Niigata Solitary fibrous tumors (SFTs), first reported in the Hospital, The Nippon Dental University pleura by Klemperer and Rabin in 1931, are rare lesions in We present a case of intra-osseous carcinoma occurring the oral cavity. We report a case of SFT arising from the in the right mandible of a 36-year-old woman. Radiographic lower lip of a 67-year-old woman. She consulted a dentist examination showed a radiolucent lesion from the second for examination of a mass at the right lower lip with 3 month molar to the ramus in the right mandible. Based on our medical history. It was excised under a diagnosis of benign diagnosis as well-differentiated squamous cell carcinoma in tumor. Tumor was composed of microvessels and small the partial biopsy, block resection of the mandible and neck spindle cells involved in small salivary glands. Immuno­ dissection were perfomed. From the histopathological histochemical investigation showed that the spindle shaped examination of the specimen, no continuity between tumor tumor cells were positive for CD34 and vimentin, and and oral mucosal epithelium was observed, but the views negative for smooth muscle actin and S-100 protein. suspected that the epithelium of the mandibular cyst wall showed malignant change were provided. C-15. Leiomyomatous hamartoma of the tongue: 2 cases arising in the newborn infants. C-12. Primary intraosseous squamous cell carci­ Kayamori K, Nagumo K, Okada N noma derived from calcifying cystic odontogenic Tokyo Medical & Dental University, Graduate School, tumor Diagnostic Oral Pathology Matsuoka K1, Matsuzaka K1, Muramatsu T2, Hashimoto In the oral regions, hamartomatous lesion is relatively S2, Kimura Y1, Hashimoto K1, Miwa T1, Kenmotsu M1, uncommon, especially leiomyomatous hamartoma is Khan SZ1, Haku G1, Shimono M2, Inoue T1 extremely rare in the oral cavity. 1Department of Clinical Pathophysiology, 2Department of We present 2 cases of leiomyomatous hamartoma arising Pathology, Tokyo Dental College on the tongue of newborn infants. Clinically, these tumors A 61-years-old female admitted to the TDC with showed well-demarcated,pedunculated lesions. Covering spontaneous pain at third molar legion. On the examination epithelium appeared normal. Histologically, many bundles of CT, the legion revealed soft tissue density with irregular or aggregates of smooth muscle fibers were recognized in border around the impacted tooth. Histopathologically, the the subepithelial fibrous tissues, and not admixed with tumor was mainly composed of atypical squamous epithelial striated muscle fibers. Immunohistochemically, these tumor cells, and ghost cells were sometimes observed. Immuno­ cells were positive for smooth-muscle Actin, and negative histochemically, the tumor cells were positive for AE1AE3, for S-100 protein. As a final diagnosis, we made a diagnosis CK13, Ki-67 and ghost cells were positive for CK13. of leiomyomatous hamartoma. Diagnosis was primary intraosseous squamous cell carcinoma derived from calcifying cystic odontogenic tumor. C-16. A case of oncogenic osteomalacia associated with a tumor in the mandible. C-13. A case of dentinogenic ghost cell tumor Sasaki T, Michifuri Y, Nakamori K, Hiratsuka H Usami Y1, Ohnishi M2, Iwaki F2, Hashimoto K3 Department of Oral Surgery, Sapporo Medical University 1Division of Diagnostic Pathology, Kobe University Hospital, School of Medicine 2Department of Oral Surgery, Nishikobe Medical Center, Oncogenic osteomalacia is a rare paraneoplastic 3Department of Pathology, Nishikobe Medical Center syndrome associated with mesenchymal tumors. We herein A case of dentinogenic ghost cell tumor (DGCT) is describe the extremely rare case of a 39-year-old man with presented. DGCT is a rare tumor, also referred as odontogenic oncogenic osteomalacia due to a tumor in the mandibular ghost cell tumor, classified as a neoplastic variant of gingiva, who was suffering from chronic general bone pain calcifying odontogenic cyst in the latest criteria proposed by that was gradually worsening. The patient’s laboratory the World Health Organization. In radiographic examination, findings revealed hypophosphatemia due to renal phosphate the tumor shows multilocular radiolucent area containing a wasting and an unusually high serum level of fibroblast mass of radiopaque material. Histologically, it was composed growth factor 23 (FGF-23). After surgery, FGF-23 and of ameloblastoma-like epithelial component and mass of serum phosphate levels normalized rapidly. The pathologic osteodentinoid material with trapped pale cells. Diagnosis of diagnosis of the tumor indicated a fibroma. Six months after DGCT was made by characteristic ghost cells found in the operation, the bone pain was improved. odontogenic epithelium. We report a unique case of DGCT with some of available literature. 72 Proceeding of the 20th Annual Meeting of The Japanese Society of Oral Pathology

C-17. An autopsy case of pyogenic liver abscess were non acid-fast. with periodontal bacteria: implication of the In the DNA analysis, DNA sequence of the PCR product potential association of periodontal infection was compared with the 16S ribosomal RNA gene of Ohyama H, Yamanegi K Actinomyces israelii (GeneBank: X82450). Department of Pathology, Hyogo College of Medicine By using PCR and direct sequencing, we can get a more A 59-year-old female suddenly developed cardiopul­ definite diagnosis. The combination use of PCR and usual monary arrest and died as a result of pyogenic liver abscess stainings makes a progress in diagnosis of actinomycosis. (PLA). Despite macroscopic and microscopic examinations, the infectious routes and source of infection were unidentified. C-19. Two cases of necrotizing sialometaplasia Since this patient had suffered severe periodontitis for a long Kimura Y1, Matsuoka K1, Miwa T1, Khan SZ1, period of time, we investigated the involvement of Kenmotsu M1, Haku G1, Muramatsu T2, Hashimoto S2, periodontal infection in PLA formation by performing Matsuzaka K1, Inoue T1 immunohistochemical analyses. We identified several 1Department of Clinical Pathophysiology, 2Department of periodontopathic bacterial species in the PLA of this patient, Pathology, Tokyo Dental College including Fusobacterium nucleartum, Treponema denticola, Necrotizing sialometaplasia is a rare salivary glands Prevotella intermedia and Porphyromonas gingivalis. lesion. To help the diagnosis, we report the histopathological Thus, we demonstrate here that periodontal infection is a findings and immunohistochemical findings of the two potential source of infection in the formation of PLA. cases. Case 1: Twenty years old female was admitted to TDC with bilateral ulcer formation of palatal mucosa. Case 2: C-18. Actinomycosis of the upper lip with tumor- Fifty-two years old male was admitted to TDC with ulcer like appearance formation at the right side of palatal mucosa after the Sun Y1, Kuyama K1, Fukui K2, Iwadate K2, Yamamoto H1 resection of mandibular squamous cell carcinoma. Immuno­ 1Department of Oral Pathology, Nihon University Graduate histochemical findings of the two cases are acinar part was School of Dentistry at Matsudo, 2Department of Forensic positive for S100(+), GFAP(+), α-SMA(+). Squamous Medicine, The Jikei University School of Medicine metaplasia part was positive for Pankeratin(+), GFAP(+), Actinomycosis, which has tumor-like features,of the CK7(−), S100(−). oral mucosa is very uncommon. Orofacial actinomycosis mimicking the clinical appearance of a tumor of the upper C-20. Pathological study of biopsied minor salivary lip was reported. A 68-year-old woman who suffered from a glands in IgG4-related sclerosing disease. -Report tumor of the upper-lip had visited our hospital and underwent of a case- surgical removal of the mass. The specimen showed a Kiyoshima T, Kobayashi I, Fujiwara H, Sakai H granuloma including bacterial colonies in the submucosa. Laboratory of Oral Pathology and Medicine, Faculty of Oral Actinomyces israelli was detected using PCR and DNA Science, Kyushu University sequencing. Finally, the diagnosis was actinomycosis. A 72-year-old woman had bilateral swelling in the Using PCR is effective for early and accurate diagnosis lacrimal glands for 10 years and presented four years ago. of oral lesions infected with microorganisms. Because of the gradual growth in size, she was admitted for A 68-year-old woman who suffered a tumor of the upper a detailed evaluation of the lesion. IgG4-related dacryoad­ lip visited our hospital. The clinical diagnosis was an upper enitis was clinically suspected. Biopsy specimen of her labial tumor with induration. The patient had underwent minor salivary gland showed interstitial fibrosis and surgical removal of the mass and recovered fine after 4 years formation of lymphoid follicles. Diffuse interstitial follow-up. infiltration of IgG4-positive plasmacytes is noted. Periductal The surgically-removed soft tissue was routinely made infiltration of CD3-positive lymphocytes is also noted. This in paraffin embedding and was stained with hematoxylin and specimen is diagnosed as sialoadenitis in IgG4-related eosin (HE). Serial sections were used for periodic acid schiff sclerosing disease. In addition, periductal infiltration of T reaction (PAS), Ziehl-Neelsen staining and MacCallum- lymphocytes suggested that this case might be associated Goodpasture method for gram positive and gram negative with other autoimmune disease. bacteria (gram stain). DNA was extracted from 3 sections of 10-μm formalin-fixed, paraffin-embedded tissues by using C-21. A case of epidermoid cyst in the mental DXPAT. PCR was performed with the primers for 16S region ribosomal RNA gene of Actinomyces israelii. DNA sequence Kuraguchi J1, Satomi T2, Shimizu H1, Kaku3, Chiba H2 of the PCR products were determined by direct sequencing. 1Department of Oral and Maxillofacial Surgery, Kamma Microscopically, the tissues showed various large and Memorial Hospital, 2Department of Oral and Maxillofacial well-defined intertwining filamentous colonies and the Surgery, Tokyo Medical University, 3Division of Clinical Oral periphery of the colonies revealed numerous club-shaped Pathology, Health Sciences University of Hokkaido filaments. The HE staining showed tangled meshes of In the oral cavity, epidermoid cysts usually arise in the actinomyces with paler staining radiating filaments which oral floor and rarely occur in the lower lip. The patient was a were positive in gram staining compatible with actinomycetes 66-year-old man. A painless mass developed slowly on the infection. The Ziehl-Neelsen staining showed the bacteria mental region close to the lower lip 6 months ago. MRI and Oral Med Pathol 14 (2009) 73 ultrasonic examinations showed that the lesion was 30mm in G-3. Histopathological relationship between diameter in the subcutaneous tissue of the mental region. pseudocysts and true duct-like structures in adenoid The lesion was extirpated under general anesthesia. The cystic carcinoma excised material was 20x15mm in diameter and filled with a Shahidul AM1, Yamazaki M1, Uddin S1, Cheng J1, yellowish bean- curd-refuse (okara) -like material. The Kobayashi T2, Maruyama S2, Saku T1, 2 specimen was histologically diagnosed to be an epidermoid 1Division of Oral Pathology, Niigata University Graduate cyst. School of Medical and Dental Sciences, 2Surgical Pathology Section, Niigata University Hospital Background: Adenoid cystic carcinoma (ACC) is General Session histopathologically characterized by cribriform structures which are composed of two types of luminal spaces. One is G-1. The clinico-pathological analysis of lymphoe­ true duct-like (TD) structures and the other pseudocystic pithelial carcinoma (LEC) of the parotid gland: (PS) ones. We have shown that the PS spaces are formed by three cases report an excessive deposition of such extracellular matrix (ECM) Kusafuka K molecules as perlecan produced by ACC cells, while there Pathology Division, Shizuoka Cancer Center Hospital and have been no investigations about the histopathological Research Institute relationship between TD and PS structures. To study their This report presents three cases of lymphoepithelial histopathogenetic processes, we examined immunohis­ carcinoma (LEC) of the parotid gland. Case 1 was a 51 tochemical distribution modes of two ECM receptors, year-old male, case 2 was a 66 year-old male and case 3 was integrin b1 and α-dystroglycan, in comparison with those of a 31 year-old male. Clinically, all cases were Japanese and their ligands and some other related molecules. free of disease after surgery. All cases showed the irregular Materials and methods: Surgical specimens of 11 nest proliferation of undifferentiated epithelial cells with cases of adenoid cystic carcinoma filed in the Oral Pathology marked lymphoid stroma. Although two cases (case 1 & 2) Section, Niigata University Hospital were examined by revealed the positive for EBER, all cases revealed high immunohistochemistry for ECM molecules, their receptors, MIB-1 labeling index. LEC is an EBV-associated cancer, their lyases, myoepithelial markers, and cell junction and the differential diagnosis with parotid gland metastasis molecules. of the nasopharyngeal cancer and lymphadenoma (non- Results & Discussion: Tumor cells forming the PS were sebaceous) is needed. positive for p63 protein and integrin β1. The PS space was positive for perlecan, laminin, and agrin. Tumor cells G-2. Geminin expression level is an important forming TD structures were positive for CK19, which was prognostic factor of salivary gland carcinomas: a not demonstrated in the PS-lining cells. They were also tissue microarray analysis positive for α-dystroglycan and MMP-9 in dot-like patterns Yamazaki M1, 2 in the apical and lateral surface of TD cells. Claudin 1, 1Division of Oral Pathology, Niigata University Graduate which is predominantly expressed in the basal side of normal School of Medical and Dental Sciences, Niigata, 2Pathology ducts, was positive in most of the cell surfaces but most Division, Research Center for Innovative Oncology, National enhanced in the narrow TD luminal space, which was Cancer Center Hospital East simultaneously positive for laminin and agrin, but not for To seek for more reliable prognostic factors of salivary perlecan. The results indicated that both of the two luminal gland carcinomas, whose grades of malignancy are not structures contained ECM but with different compositions, always obvious because of their low frequencies, expression and that the TD lumen was not a true ductal space. In the levels of Ki-67 and geminin were evaluated by using the transitional process from TD to PS structures, integrin β1 tissue microarray technique, and the results were related to may come to be an exclusive receptor for PS ECMs by the clinical outcome. The higher expression of geminin was taking the place of dystroglycan, which plays some role for more strongly correlated with reduced overall and relapse- TD ECMs but may be degradated by MMP-9 in the free survivals than that of Ki-67. As a result of multivariate process. analyses, pathological T factor and geminin expression were the most significant and independent factors for the patient G-4. Podoplanin expression in odontogenic tumors survival and tumor relapse. Tsuneki M1, Maruyama S2, Yamazaki M1, Kobayashi T2, Cheng J1, Saku T1, 2 1Division of Oral Pathology, Niigata University Graduate School of Medical and Dental Sciences; 2Oral Pathology Section, Department of Surgical Pathology, Niigata University Hospital Podoplanin, a transmembrane glycoprotein, is one of the most highly expressed proteins in the lymphatic endothelial cells. Recently, podoplanin has been localized in carcinoma cells and thought to serve as a marker for cancer development. 74 Proceeding of the 20th Annual Meeting of The Japanese Society of Oral Pathology

To study its function, we determined the immunohistochemical findings of the DN at any time or any place via broadband expression mode for podoplanin in odontogenic tumors. Internet. A successful implementation of digital note system Podoplanin was immunolocalized in the peripheral zone of has been observed for the education of oral pathology. ameloblastoma foci, in spindle cells between pseudocystic or whirl-like structures of adenomatoid odontogenic tumor, G-8. The outline of “ specialist and in the basal and parabasal cells of calcifying cystic program” at graduate school of Dentistry, Tokyo odontogenic tumor and keratocystic odontogenic tumor. The Dental College present result showed that podoplanin was expressed in Kawachi H1, 3, Saito H1, 4, Ikawa H1, 4,Oono K1, 3, odontogenic tumor cells, and the positioning of podoplanin- Yoshida Y1, 4, Yamamura K1, 4, Sekine R1, 3, Sato K2, positive cells suggested that podoplanin was associated with Yamauchi T2, Katakura A1, 2, 3, Yamane G1, 2, 4, Shibahara S3, molecules, which were sometimes related to cell proliferation, Tanaka Y5 in the intercellular space. 1Department of oral Oral Cancer specialist program, 2Department of Oral Cancer Center, 3Department of Oral and G-5. Immunohistochemical study of keratocystic Maxillofacial Surgery, 4Department of Oral Medicine, Oral and odontogenic tumor and orthokeratinized odonto­ Maxillofacial Surgery, 5Clinical Laboratory, Division of genic cyst. Surgical Pathology, Ichikawa General Hospital, Tokyo Dental Wato M1, Kokubu M2, Masuno K1, Tominaga K1, College Nishikawa T1, Tanaka A1 Our college is the only dental school taking a part in a 1Department of oral pathology, 2Graduate School of Dentistry medical consortium, “Cancer specialist program,” supported (Pathology), Osaka Dental University by Ministry of Education, Culture, Sports, Science and In order to clarify the characteristics between keratocystic Technology, which started in 2007. Our school undertakes odontogenic tumor (KCOT) and orthokeratinized odonto­ its Oral Cancer division. The curriculum aims to train genic cyst (OOC), we elucidated the immunohistochemical dentists who can demonstrate leadership in oral cancer localization of CK10, CK13, Bcl-2 and Bax. CK13 was treatments. The training includes 3 months of laboratory expressed in KCOT and DC, but was not in OOC. Bcl-2 was work in Pathology in the Hospital Clinical Laboratory at observed in OOC and DC, but was not in KCOT. The Ichikawa General Hospital. I would like to introduce the expression of Bax in OOC and DC was the same. These outline of the program and its achievement. results suggest that there is the difference in the entity between KCOT and OOC. G-9. The establishment of oral cancer detecting system and its development - According to inspection G-6. Immunohistochemical study on origin of of its campaign in Ichikawa city, Chiba prefecture. irritation fibroma Yamashina M1, Tanaka Y3, Ryuzaki M5, Gibo K3, Tsukinoki K1, Sato K1, Kubota N1, Miyoshi Y1, Saruta J2, Fukuda M3, Saito J3, Sato K2, Yamauchi T2, Katakura A2, 4, Kondo Y1 Ikawa H1, Ichijima T1, Saito H1, Noguchi S1, Yoshida K1, 1Department of Maxillofacial Diagnostic Science Division of Tonogi M1, Yamane G1, 2 Pathology, 2Department of Craniofacial Growth and 1Department of Oral Medicine, Oral and Maxillofacial surgery, Development Dentistry, Kanagawa Dental College Tokyo Dental College, 2Oral Cancer Center, Tokyo Dental Oral irritation fibroma (OIF) is benign fibroblast College, 3Division of Clinical Laboratory, Ichikawa General proliferating lesion. This lesion is non-neoplastic lesion and Hospital, Tokyo Dental College, 4Department of Oral and causes by chronic irritation in the oral mucosa including the Maxillofacial surgery, Tokyo Dental College, 5Ichikawa Dental tongue, buccal mucosa and lower lip. Although OIF is Association common lesion in the dental field, details of histopathogenesis Examination for oral cavity is useful to detect early oral and immunohistochemical profiles are not well understood cancer, but there is little effective detecting system that any in the spindle cells of main component. Thirty three cases of dentists can easily access. In 2008, we started a system, fibroblast proliferating lesion including solitary fibrous called OCDSIN (Oral Cancer Detecting System Ichikawa tumor, true fibroma, peripheral odontogenic fibroma, Network), could support dentists in practicing oral cancer fibromatosa, OIFs, fibrous epulis were investigated. examination in their dental offices, and this system has screened a person who suffered from early oral cancer in G-7. The establishment of digital note for dental about 100 cases. Thin Prep®, liquid based cytology system, education. gives dentists stress free operation. Public oral cancer Kubo K1, 2, Yoshida W1, Sugita Y 1, 2, Sato E1, 2, Maeda H1, 2 examination in Ichikawa city, starting with 2009, adopts 1Department of Oral Pathology, School of Dentistry, Aichi- techniques based on OCDSIN, including Thin Prep®. Gakuin University, 2Research Institute of Advanced Oral Science, Aichi-Gakuin University In the oral pathology education, the development of contents as the support of education is essential. We constructed the oral pathology digital note system (DN) using the original software, and the students can review the Oral Med Pathol 14 (2009) 75

G-10. Telomere length and chromosomal instability Notch1 may participate in pathogenesis of OED and OSCC. in oral orthokeratotic dysplasia (OKD) ; Analysis by the quantitative fluorescence in situ hybridization G-13. HPV infection in oral precancerous lesion (Q-FISH) method and squamous cell carcinoma Aida J1, Kobayashi T2, Maruyama S2, Cheng J3, Saku T2, 3, Ishibashi M1, 2, Kisihino M1, Sato S1, Ogawa Y1, Kogo M2, Takubo K1 Toyosawa S1 1Research Team for Geriatric Pathology, Tokyo Metropolitan 1Department of Oral Pathology and 2Oral & Maxillofacial Institute of Gerontology, 2Oral Pathology Section, Department Surgery 1, Osaka University Graduate School of Dentistry of Surgical Pathology, Niigata University Hospital, 3Division of Human papillomavirus (HPV) infection is associated Oral Pathology, Niigata University Graduate School of Medical with tumorigenesis of cervical cancer, while its association & Dental Sciences is not clear in oral cancer. In this study, we reinvestigated the Orthokeratotic dysplasia (OKD) is a histopathological HPV prevalence in oral precancerous lesions, oral squamous entity that is often recognized in cases of multiplicity or cell carcinoma (OSCC)s, compared to cervical lesions by recurrence of oral squamous cell carcinoma, being charac­ PCR and HPV genotyping methods. The p16 expression as terized by hyperorthokeratosis with the presence of a surrogate marker of HPV infection and the p53 accumulation granular layer. The telomere lengths of individual cells in were immunohistochemically detected. The incidence of these lesions were analyzed by quantitative fluorescence in HPV-DNA detection and p16 expression in oral lesions was situ hybridization (Q-FISH). Telomeres in OKD were much lower than that in cervical lesions. The intensity of uniformly and significantly shorter than in normal control p53 expression in oral lesions was higher than that in samples or squamous cell carcinoma in situ (CIS (JSOP)). cervical lesions. These findings indicated that p53 mutation Extremely short telomeres are considered to cause rather than HPV infection would be related to the chromosomal instability and to be related to cancerization. carcinogenesis of OSCC.

G-11. Abnormal expression of desmosomal proteins G-14. Nuclear Export of HuR in oral cancer cells in border-line malignancies of oral mucosa Kuroshima T, Higashino F, Hasegawa H, Kakuguchi W, Aizawa S1, Ochiai T2, Nakano K1, 2, Kimura A1, 2, Kitamura T, Kitagawa Y, Totsuka Y, Shindoh M Kawakami T1, 2, Hasegawa H1, 2 Department of Oral Pathology and Biology, Hokkaido University 1Hard Tissue Pathology Unit, Matsumoto Dental University Graduate School of Dental Medicine Graduate School, 2Department of Oral Pathology, Matsumoto HuR is an RNA-binding protein which has potential to Dental University stabilize AU-rich element containing-mRNAs. Here we We examined the immunohistochemical localization of show that HuR is exported oral cancer cells. HuR existed in desmoglein1 (Dsg1) and desmocollin3 (Dsc3) in 27 cases of the cytoplasm in oral cancer cells, whereas almost all HuR oral SIN3, which included basaloid, verrucous and acanthotic was located in the nucleus in normal cells. In those cells, types. In 30% cases of basaloid type, lower atypical cells of ARE-mRNAs were exported and those half-lives were two-phase structure showed Dsg1 (-) /Dsc3 (+), but prolonged. HuR and ARE-mRNAs were exported in CRM1- superficial cells demonstrated Dsg1 (+)/Dsc3 (+). However, independent manner and knockdown of Transportin2 affect in most cases of three types, the full-thickness layers were the stabilization of ARE-mRNAs. These findings suggest positive for both Dsg1 and Dsc3. These results might that HuR and ARE-mRNAs are exported in oral cancer cells suggest that Dsg1 and Dsc3 immunostainings gave us useful in a different manner from that of normal cells. information on abnormal differentiation of atypical cells in SIN. G-15. Loss of heterozygosity analysis of Dkk-3 in head and neck squamous cell carcinoma G-12. Notch1 is downregulated in oral epithelial Katase N1, Gunduz M1, Tsujigiwa H2, Tamamura R1, dysplasia and squamous cell carcinoma Matsuda H1, Lefeuvre M1, Liu H1, 3, Nagatsuka H1 Sakamoto K1, Katsube K1, Okada N2, Yamaguchi A1 1Department of Oral Pathology and Medicine, 2Department of 1Section of Oral Pathology, 2Section of Diagnostic Oral Virology, Graduate School of Medicine, Dentistry and Pathology2, Tokyo Medical and Dental University Pharmaceutical Sciences, Okayama University, 3Department of We previously demonstrated that keratin 4 (K4) and K13 Oral Biology, Collage of Stomatology, Dalian Medical were consistently downregulated in oral epithelial dysplasia University (OED) and oral squamous cell carcinoma (OSCC). To We previously performed genome wide loss of understand the mechanism for the dysregulation of the heterozygosity (LOH) analysis in head and neck squamous keratins expression, we immunohistochemically examined cell carcinoma (HNSCC) and Dkk-3 was found out as a the expression of several factors that were suggested to candidate tumor suppressor. To investigate its role in regulate epithelial differentiation, and found that Notch1 HNSCC, LOH analysis with statistical analysis were expression was associated with those of K4 and K13; performed. Pretty high LOH ratio was detected, and Notch1 was expressed in the basal cell layer of the normal statistical analysis revealed that LOH(+) group showed oral epithelium, but was downregulated in OED (60%, fewer lymph nodal metastasis and longer over-all survival. 12/20) and OSCC (87%, 26/30). These results implicate that All the results suggested that Dkk-3 was possibly related to 76 Proceeding of the 20th Annual Meeting of The Japanese Society of Oral Pathology the carcinogenesis and lymph nodal metastasis in HNSCC. G-19. HSulf-1 promotes the invasion of head and neck cancer G-16. Expression of Hsp47 in oral squamous cell Yoshida M1, Kudo Y1, Thao NTP1, Ogawa I2, Takata T1 carcinoma cell line 1Department of Oral and Maxillofacial Pathobiology, Hiroshima Okuyama N, Sakurai Y, Sugiura J, Ito H, Yamasaki A University Graduate School of Biomedical Sciences, 2Center of Department of Oral Medical Science, Oral Pathology, Ohu Oral Clinical Examination, Hiroshima University Hospital University of Dentistry HSulf-1 is known as an endosulfatase removing sulfate Heat shock protein 47 (Hsp47) participates in the from the 6-O-position of glucosamine within heparan sulfate synthesis of various types of collagen as a collagen-specific proteoglycan (HSPG). Importantly, HSPGs bind various molecular chaperone. Hsp47 is expressed not only in the factors through the 6-O-sulfation of glucosamine. Here we collagen-producing but also normal and neoplastic focused on HSulf-1 in the head and neck squamous cell keratinocytes, but the role of Hsp47 in keratinocytes is not carcinoma (HNSCC). HSulf-1 was highly expressed in clear. To elucidate this problem, we examined the expression HNSCC cases and cell lines. The invasion of HNSCC cells pattern of Hsp47 in human oral squamous cell carcinoma was promoted by HSulf-1 overexpression and was suppressed cell line, HSC-3, by Western blot and RT-PCR analyses. The by HSulf-1 knockdown. Moreover, injection of HSulf-1 expression of both Hsp47 protein and Hsp47 mRNA overexpressed cells into nude mice showed bigger tumors increased with the proliferation of cells and became than that of control cells. These findings suggest that HSulf-1 decreased after confluent, the expression pattern being with may play important roles for tumor progression through the that of type IV collagen and laminin 5. promotion of invasion in HNSCC.

G-17. HMGB1-related signal in oral squamous cell G-20. Clinicopathological analysis of the diffuse carcinoma large B-cell lymphoma. — Comparison of germinal Sasahira T1, Kurihara M1, Yamamoto K2, Kuniyasu H2 center B-cell type and non-germinal center B-cell 1Department of Molecular Pathology, 2Department of Oral and type in head and neck region. Maxillofacial surgery, Nara Medical University Kawano R1, 3, Shimoyama T1, Hanzawa K2, Tokuhira M2, We examined HMGB1-RAGE/MIA signal in oral Momose S3, Higashi M3, Tamaru J3, Itoyama S3 squamous cell carcinoma. RAGE expression was associated 1Department of Oral and Maxillofacial Surgery, 2Department of with local progression and RAGE positive cases showed Hematology 3Department of Pathology, Saitama Medical worse prognosis than RAGE negative cases. RAGE also Center, Saitama Medical University induced angiogenesis via VEGF. Whereas, expression of Diffuse large B-cell lymphoma (DLBCL) is a most MIA was associated with HMGB1 expression, lymphangio­ frequent subtype of lymphomas in the head and neck region. genesis, nodal metastasis, and VEGF-C/D expression. We evaluated 57 patients with DLBCL primed in this region, HMGB1-NFkB complex induced MIA expression and using antibodies against CD10, Bcl-6 and MUM1 immuno­ HMGB1 siRNA treatment reduced expression of MIA. MIA histologically. Among 57 cases, 40 cases (70%) showed neutralization by MIA antibody treatment decreased p38 non-germinal center B-cell (GCB) immunophenotype, and phosphorylation and VEGF-C/D expression. These results the others did GCB type (30%). In this study, we also suggested that HMGB1 related signal might be a useful analyzed the DLBCL cases clinicopathologically. target of oral squamous cell carcinoma. G-21. Mechanism of inhibition of JNK by mutant G-18. Expression of HuD in oral squamous cell p53 carcinoma Kitamura T Kurihara M1, Sasahira T1, Yamamoto K2, Kirita T2, Department of Oral Pathology and Biology, Division of Oral Kuniyasu H1 Pathobiological Science, Hokkaido University Graduate School 1Department of Molecular Pathology, 2Department of Oral and of Dental Medicine Maxillofacial Surgery, Nara Medical University Daxx, originally identified as a Fas death domain- We examined HuD expression in oral squamous cell binding protein, interacts with ASK1, a mitogen-activated carcinoma (OSCC). HuD immunoreactivity was observed in protein kinase (MAP kinase) kinase kinase and enhances the nucleus of the cancer cells, and HuD expression was Fas-induced apoptosis by activating JNK pathway. Ohiro et significantly associated with tumor progression, clinical al. reported that some p53 mutants, but not wild-type p53, stage, and nodal metastasis. In in vitro study, cell growth and interacted with Daxx and inhibited ASK1 activation. invasive activity were inhibited by HuD siRNA treatment in Here, we show here that Daxx is essential for sustained HSC3 cells (metastatic cell line), whereas HSC4 cells (non- JNK activation and cell death induced by TNF. metastatic cell line) did not affect by HuD siRNA treatment. Phosphorylation of Daxx by ASK1 stabilizes Daxx, which in These findings suggested that HuD is a good metastatic turn contributes to ASK1 activation, resulting sustained ability marker and inhibition of HuD might be a new JNK. This positive feedback-loop is disrupted by tumorigenic therarpeutic target in OSCCs. p53, which interferes with the complex formation between Daxx and ASK1. Oral Med Pathol 14 (2009) 77

G-22. Expression of angiogenic factors by salivary transcription-polymerase chain reaction (RT-PCR). BDNF adenoid cystic carcinoma protein was clearly detected in saliva by western blot after Fujita G1, 2, Sato S1, Kishino M1, Toyosawa S1, Ogawa Y1 exposure of noise stress. Departments of 1Oral Pathology and 2Oral and Maxillofacial This study demonstrates that BDNF are present in Surgery II, Osaka University Graduate School of Dentistry human saliva and salivary gland. To explain the causes of vascular abnormalities in salivary adenoid cystic carcinoma (ACC), expression of G-25. Chronic stress affects the expression of angiogenic factors in the fresh tumor tissues were analyzed neurotrophins in the rat salivary glands by real-time RT-PCR. The factors analyzed were VEGF-A, Saruta J1, Kondo Y2, Tsukinoki K2 VEGF-C, PDGF-B, angiopoietin-1 (Ang-1) and angio­ 1Department of Craniofacial Growth and Development poietin-2 (Ang-2). VEGF-A mRNA expression by the ACCs Dentistry, 2Department of Maxillofacial Diagnostic Science was similar to that by normal salivary glands. Either Division of Pathology, Kanagawa Dental College VEGF-C mRNA or VEGF-D mRNA was often not detected. In our previous study, we reported that BDNF was PDGF-B mRNA level was elevated 3-fold. The ratio of produced from salivary glands under acute immobilization Ang-1:Ang-2 shifted in favor of Ang-2 (1/6 of normal stress. Additionally, salivary glands were the origin of salivary glands). VEGF-A, PDGF-B and Ang-2 were mainly plasma BDNF in that condition; however, the association expressed by the tumor cells. These results appear to explain between the expression of BDNF and the salivary gland the causes of vascular abnormalities in ACC. under chronic stress conditions is not well understood. In the present study, we investigated whether plasma BDNF levels G-23. Survival and proliferation of pleomorphic were influenced by chronic stress in the salivary gland. adenoma in hypoxic condition Expressions of BDNF mRNA and protein were identified in Maruyama S1, Cheng J2, Yamazaki M2, Kobayashi T1, the submandibular glands when male rats were exposed to Saku T1, 2 chronic stress, as demonstrated by multiple technics. 1Oral Pathology Section, Department of Surgical Pathology, Niigata University Hospital 2Division of Oral Pathology, G-26. Role of ameloblastin for bone formation and Niigata University Graduate School of Medical and Dental application for regeneration of bone tissues Sciences Iizuka S1, Kitagawa M2, Kudo Y1, Ogawa I2, Miyauchi M1, Salivary pleomorphic adenoma is characterized by its Takata T1 colorful stroma which is poorly vascularized. Based on this 1Department of Oral and Maxillofacial Pathobiology, Graduate histopathological architecture, we had a hypothesis that School of Biomedical Sciences, Hiroshima University, 2Center pleomorphic adenoma cells are able to survive in hypoxic of Oral Clinical Examination, Hiroshima University Hospital conditions. To approve it, we examined expressions of It has recently been reported that ameloblastin (AMB) is hypoxia-related molecules in SM-AP1/4, human pleomorphic expressed during craniofacial development and may play the adenoma cell systems, cultivated under hypoxic conditions. significant role not only in tooth development but alsoin In hypoxic conditions, SM-AP cells showed higher gene bone formation. In the present study, we demonstrated that expression levels for VEGF but did not for those for HIF-1α the effects of AMB on the differentiation of osteoblasts and and vHL in hypoxia, while HIF-1α protein was kept in regeneration of bone tissues both in vitro and in vivo by higher levels and localized more significantly in nuclei. The using full-length AMB and synthetic peptides of N-terminal results indicate that pleomorphic adenoma cells are able to of AMB (AMB-N), a genetically well conserved among proliferate even in hypoxic conditions, in which HIF-1α is various species. Overall, we suggest that AMB plays not degraded by vHL but induces expressions of VEGF or important roles for bone formation, and that AMB-N peptide the other target genes of HIF-1α. may be useful for bone regeneration.

G-24. Presence of BDNF in human salivary gland G-27. Wnt/β-catenin signaling is essential for and saliva chondrocyte maturation and ossification in devel­ Kondoh Y1, 2, Saruta J1, 3, Sato S3, Tsukinoki K1, 2 oping cranial base synchondroses 1Department of Maxillofacial Diagnostic Science Division of Nagayama M1, Shibukawa Y2, Koyama E3, Takeuchi H1 Pathology, 2Laboratory of salivary gland and health medicine, 1Division of Oral Pathology Asahi University School of 3Department of Craniofacial Growth and Development Dentistry, 2Department of Periodontology Tokyo Dental College, Dentistry, Kanagawa Dental College 3Department of Orthopaedic Surgery Thomas Jefferson Brain-derived neurotrophic factor (BDNF) promotes University survival and differentiation of nerves cell. BDNF has been Cartilage-specificβ-catenin deficient mice was created identified in non-neural tissue. In the present study, we and analyzed by μCT, histological and in situ hybridization investigated that an expression and presence in human to know the role of Wnt/β-catenin signaling is essential for salivary BDNF. BDNF was located in the serous cells of endochondral bone formation in developing cranial base salivary gland by immunohistochemistry (IHC) and in situ synchondroses. The antero-posterior length of the mutant hybridization (ISH). In human salivary gland tissue, mice cranial base was shorter than wild type and both expression of BDNF mRNA is identified with reverse endochondral and intramembranous bone formation was 78 Proceeding of the 20th Annual Meeting of The Japanese Society of Oral Pathology delayed. When Wnt/β-catenin signaling was activated in sialoprotein (BSP) and osteoprotegerin (OPG) mRNAs were chondrocytes, chondrocyte hypertrophy was induced in the detected using RT-PCR. Furthermore, immunohistochemistry, resting zone of the growth plate. Interestingly, Ihh mutant transmission electron microscopy (TEM) and mineralization synchondroses revealed the similar phenotype to those of analysis with alizarin red were also performed. Next, DFCS Wnt/β-catenin activated mice and were accompanied by was homo-transplanted into omentum of adult male rat. Rats severe reduction of Wnt antagonist secreted frizzled-related were sacrificed at 5 weeks after the transplantation and was protein-1 (sFRP-1). Ectopic chondrocyte differentiation was analyzed using either HE or immunohistochemical staining also found in the periodontal ligament inβ-catenin mutant with BSP, OCN and OPG as primary antibodies. mice. These data suggests that Wnt/β-catenin signaling is Result: The expression of Col I, ALP, Runx2, BSP and not only essential for endochondral bone formation in OPG mRNAs were significantly higher in the experimental cranial base synchondroses but also required for periodontal group than the control group after one week of culture. ligament development. Alizarin red positive calcified nodules were much more observed in the experimental group for 3 weeks. Immuno­ G-28. Influence of hyper-γ-glutamyl transpeptidase- histochemistry, ALP, BSP, OCN and OPG positive reactions emia on bone destruction were stronger than those of control groups at each of the Miyauchi M1, Kawazoe Y1, Furusyo H1, Niida S2, time periods. Ultrastructurally, more organelles, such as Takata T1 Golgi’s apparatus, rough endoplasmic reticulum (RER), 1Department of Oral and Maxillofacial Pathobiology, Hiroshima mitochondrion were observed in the experimental groups. In University 2Department of Geriatric Sciences, National Institute the transplantation experiment, -like tissue, which for Longevity Sciences was positive for BSP, OCN and OPG, and periodontal γ-glutamyl transpeptidase (GGT) is accepted as an ligament-like tissues were formed, while only the fibrous escape enzyme without effect on bone. We identified GGT tissues formation was observed in the control group. as a novel bone resorbing factor. The hyper-GGTemia may Conclusion: The DFCS had the ability of producing be responsible for reduction of bone mass. Influences of cementum- and periodontal ligament-like tissues in vivo, hyper-GGTemia on bone were analyzed using rat bile duct and could be conveniently applied in the field of periodontium ligation (BDL) model. In BDL-animals, serum GGT level regeneration therapy. and osteoclasts-number were significantly increased. Bone mineral density and bone mass were markedly reduced. G-30. Roles of Primary Cilia in Synchondrosis They were improved by anti-GGT antibody treatment. Development These findings indicated that the elevation of serum Ochiai T1, 3, Nagayama M2, Koyama E3, Hasegawa H1 GGT might be a critical causative factor of osteoporosis in 1Department of Oral Pathology, Matsumoto Dental University, patients with hyper-GGTemia. 2Department of Oral Pathology, Asahi University, 3Department of Orthopaedic Surgery, Thomas Jefferson University G-29. Cementum- and Periodontal Ligament-like Primary cilia regulate several developmental processes Tissues Formation by Dental follicle cell sheet and mediate hedgehog signaling. To study their roles in Haku G1, 2, Matsuzaka M1, Inoue T1 cranial base development and growth, we generated 1Department of Clinical Pathophysiology, 2Department of conditional mouse mutants deficient in Polaris, a critical Pediatric Dentistry, Tokyo Dental College primary cilium component, in cartilage. Cranial bases were Dental follicle cell sheet (DFCS) was made using a malformed and their synchondrosis growth plates were co-culture system with dental papilla cells (DPCs). The altered. Excessive ossification along perichondrium was expression of Col Ⅰ, ALP, Runx2, BSP and OPG mRNAs accompanied by excessive Ptch-1 expression, suggesting were higher than control. Then DFCS was homo-transplanted that Indian hedgehog (Ihh) protein distribution was wider into omentum of adult male rat. Five weeks after the and responsible for such response. Expression of heparan transplantation, cementum- and periodontal ligament-like sulfate proteoglycans was barely detectable in mutant tissues were formed, but only fibrous tissue was observed in synchondroses. The data provide the evidence for the the control group. In conclusion, DFCS could be conveniently essential roles of primary cilia and hedgehog signaling in utilized in periodontium tissue engineering. cranial base development. Purpose: The purpose of this study was to investigate Objectives: Primary cilia regulate several developmental the behavior of DFCS when transplanted into omentum. processes and mediate hedgehog signaling. To study their Materials and methods: Tooth germs were obtained roles in cranial base development, we created conditional from post natal 7 days SD rats. Dental papilla and follicle mouse mutants deficient inPolaris , a critical primary cilium, were separated by mechanical means. And then, DFCS was in cartilage. Methods: Cartilage-specific mutant mice were made using co-culture system. Dental follicle cells (DFCs) created by mating Col2a1-Cre with Polaris-floxed mice. were cultured in the lower and DPCs were cultured in the Skulls from mutant and wild type littermates were analyzed upper compartments of double chambers. Only cultured by μCT and anatomical, histological and in situ hybridization DFCs were used as control. For evaluation of DFCS, the procedures. Results: Cranial base was deformed in postnatal expression of collagen typeI (ColI), alkaline phosphatase Polaris-deficient mice, and synchondrosis growth plates (ALP), runt related transcription factor 2 (Runx2), bone were disorganized. Expression of Ihh, Patched-1 and Oral Med Pathol 14 (2009) 79 collagen X was reduced and accompanied by decreases in osmotic stress. We observed the expression levels of hBDs endochondral bone and marrow. Interestingly, there was mRNA and peptides by quantitative RT-PCR and an ELISA excessive intramembranous ossification along perichondrium assay. hBDs levels were increased with the stimulation of accompanied by excessive Patched-1 expression, suggesting sorbitol. Furthermore, AG1478, an inhibitor of epithelial that Ihh protein distribution became wider and responsible growth factor receptor (EGFR) tyrosine kinase inhibited that for such excessive response of the perichondrial tissues. levels. These finding indicated that osmotic stresses by food Indeed, expression of heparan sulfate proteoglycans and drink may induce upregulated the expression of hBDs (HS-PGs), normally involved in restricting hedgehog via EGFR activation. distribution, was barely detectable in mutant synchondroses. Conclusion: The data demonstrate for the first time that G-32. IL-22 induced expression of beta-defensins in Polaris and primary cilia are essential for hedgehog signaling oral epithelium and oral diseases. in cranial base development, and point to a close Nishimura M1, Yamazaki M1, Kaku T1, Abiko Y1, 2 interdependence between cilia and HS-PGs to delimit targets 1Division of Clinical Oral Pathology, 2Division of Oral of hedgehog action in synchondrosis growth plates. Medicine & Pathology, Institute of Personalized Medical Sciences, Health Sciences University of Hokkaido G-31. Osmotic Stress Induced Upregulated Expres­ Human beta-defensin (hBD)s belong to a group of sion of HBDs in HaCaT cells by an Epithelial antimicrobial peptides expressed mainly in epithelial cells, Growth Factor Receptor (EGFR)-mediated including oral and skin keratinocytes. Interleukin (IL)-22 is Process on effector cytokine produced by T cells and mediates Yamazaki M1, Nishimura M1, Uemura D1, Kaku T1, crosstalk between the immune system and epithelial cells. Abiko Y1, 2 To investigate the effects of IL-22 on the expression of 1Division of Clinical Oral Pathology, Health Sciences University hBD-2, -3 mRNA in human oral epithelial cells (HOECs) we of Hokkaido, 2Division of Oral Medicine and Pathology, Health conducted in-situ localization of hBDs, IL-22 and IL-22 Sciences University of Hokkaido receptor (IL-22R) expression in normal and diseased oral Human beta-defensin(hBD)s are a group of antimicrobial tissues. These results indicate that IL-22 upregulates hBD-2 peptides. The present study investigated whether osmotic and -3 mRNA in oral epithelial cells and co-localized with stress altered expression of hBD-1, -2 and -3 in HaCaT hBD-3 to the basal epithelium in oral lichen planus. keratinocytes. HaCaT cells were treated with sorbitol to add