Search

Human papillomavirus (HPV) infection is an indicator of good response to chemoradiotherapy in oropharyngeal squamous cell carcinoma (OPSCC), and epidermal growth factor receptor (EGFR) is a molecular-therapeutic target in head and neck squamous cell carcinoma. Here we investigated the prevalence and prognostic significance of HPV infection and EGFR alteration in OPSCC. We analyzed the presence of high-risk HPV using in situ hybridization, protein expressions of p16 and EGFR using immunohistochemistry, and the EGFR gene copy number gain using chromogenic in situ hybridization (CISH) in 105 cases of OPSCC. The biopsy specimens before chemoradiotherapy were used for these analyses. HPV infection and p16 protein overexpression were detected in 53.3% and 52.4% of the OPSCCs, and each factor was associated with better overall survival (P = .0026 and P = .0026) and nonkeratinizing histology (P = .0002 and P = .0004), respectively. EGFR gene copy number gain (high polysomy or amplification) was detected in 12.4% of the OPSCCs and was correlated with EGFR protein overexpression (P = .0667) and worse overall survival (P < .0001). HPV infection and EGFR gene copy number gain (EGFR CISH positive) were mutually exclusive. The HPV-negative/EGFR CISH-positive OPSCCs had significantly worse overall survival than did the HPV-positive/EGFR CISH-negative OPSCCs and HPV-negative/EGFR CISH-negative OPSCCs (P < .0001 and P < .0001, respectively). The EGFR CISH-negative OPSCCs had favorable prognosis irrespective of HPV infection. Our results suggest that EGFR gene copy number gain-positive tumors represent an HPV-negative, aggressive subgroup of OPSCCs. The molecular subclassification of OPSCCs based on HPV infection and EGFR status may serve as important information for appropriate therapeutic strategy.

Background and Objective: The gingival epithelium is the physiologically important interface between the bacterially colonized gingival sulcus and periodontal soft and mineralized connective tissues, requiring protection from exposure to bacteria and their products. However, of the three epithelia comprising the gingival epithelium, the junctional epithelium has much wider intercellular spaces than the sulcular epithelium and oral gingival epithelium. Hence, the aim of the present study was to characterize the cell adhesion structure in the junctional epithelium compared with the other two epithelia. Material and Methods: Gingival epithelia excised at therapeutic flap surgery from patients with periodontitis were examined for expression of adhesion molecules by immunofluorescence. Results: In the oral gingival epithelium and sulcular epithelium, but not in the junctional epithelium, desmoglein 1 and 2 in cell–cell contact sites were more abundant in the upper than the suprabasal layers. E-cadherin, the main transmembranous molecule of adherens junctions, was present in spinous layers of the oral gingival epithelium and sulcular epithelium, but was scarce in the junctional epithelium. In contrast, desmoglein 3 and P-cadherin were present in all layers of the junctional epithelium as well as the oral gingival epithelium and sulcular epithelium. Connexin 43 was clearly localized to spinous layers of the oral gingival epithelium, sulcular epithelium and parts of the junctional epithelium. Claudin-1 and occludin were expressed in the cell membranes of a few superficial layers of the oral gingival epithelium. Conclusion: These findings indicated that the junctional epithelium contains only a few desmosomes, composed of only desmoglein 3; adherens junctions are probably absent because of defective E-cadherin. Thus, the anchoring junctions connecting junctional epithelium cells are lax, causing widened intercellular spaces. In contrast, the oral gingival epithelium, which has a few tight junctions, functions as a barrier.

In cases of multiple primary cancers, the combination of head/neck cancer and upper digestive tract cancer is often found. However, it is extremely rare for maxillary sinus cancer and esophageal cancer to occur simultaneously. This paper reports on an autopsy case of double primary cancers of the maxillary sinus and esophagus. The patient had been suffering from carcinoma of the maxillary sinus for about 12 months but the lesion was uncontrollable. At autopsy, the following two primary carcinomas were found : one was a moderately differentiated squamous cell carcinoma originated from the maxillary sinus infiltrating into the hard palate and tongue, with metastases in several regional lymph nodes, a para-aortic lymph node and bilateral lungs. The other was a progressive, well-differentiated squamous cell carcinoma originated from the esophagus transformed mucosa with epithelial dysplasia. Furthermore, two masses of gastrointestinal mesenchymal tumors (GIMT) of the stomach were noted.

Autopsy cases of tongue cancer in Japan were statistically analyzed. Autopsy cases were collected from the Annual of Pathological Autopsy Cases in Japan over the past five years (1997-2001). Tongue cancer was reported in 321 autopsy cases(M:241, F:79, Unknown: 1). The autopsy rate was 6.0% of 5,320 patients who died of tongue cancer in Japan. 103 of the autopsied patients (32.2%) were in their seventh decade, 74 (23.1%) were in their eighth decade, and 54 (16.9%) were in their sixth. Histologically, almost all the cases showed squamous cell carcinoma (96.8%). The cancer arose most frequently in the lateral borders (66.1%) of the tongue. Multiple primary cancers, affecting both the tongue and other organs, were found in 113 cases. The mean ages of only the autopsied cases of squamous cell carcinoma excluding the cases of multiple primary cancers were 63.8±10.1 (1997), 57.7±12.3 (1998), 65.4±13.6 (1999), 61.7±15.4 (2000) and 62.1±14.9 (2001) years old. However, the mean ages of multiple primary cancers, affecting both the tongue and the other organs, were 69.2±9.9 (1997), 70.5±11.2 (1998), 66.6±10.2 (1999), 68.2±11.6 (2000) and 69.9±15.5 (2001) years old. In cases of double cancers including tongue cancer, commonly occurring cancers were lung, liver, esophagus, thyroid and adrenal. Metastasis to other organs was frequently found in the tracheobronchus and lungs, liver, heart and aorta, bones, adrenals and thyroid. Metastasis to the lymph node was found in the cervix, lung hilum, periesophagus and peritrachea, left supraclavicula, and axilla. The most common cause of death was pulmonary infection.

The biologic behavior of and optimal treatment for oral verrucous carcinoma (VC) remain controversial. We analyzed the clinicopathological characteristics of 12 patients with oral VC. Immunohistochemical techniques were used to evaluate p53 protein, CD44 variant 9, and proliferating cell nucleus antigen. The TNM classification (UICC, 1997) was T1 in 1 patient, T2 in 3, T3 in 4, and T4 in 4. All patients were classified as N0M0. Four patients were treated by surgery alone and 8 by surgery after chemotherapy, radiotherapy, or both. After surgery, two patients had primary recurrence of disease. Immunohistochemically, the proliferative activity of tumor cells as evaluated by proliferating cell nuclear antigen labeling index and p53 protein expression was similar in VC and well-differentiated squamous cell carcinoma. However, CD44 varient 9 expression was positive in 8 of 10 VC, suggesting that oral VC is associated with a low risk of lymph node metastasis. Positive CD44 variant 9 expression by most oral VCs, indicating a low risk of cervical lymph node metastasis, suggests that most cases can be controlled by surgical intervention.

Pathological examinations undertaken in our department in 2002 were statistically reviewed. There were 602 examinations for 460 cases (Male 227, Female 233) Cases were most frequent in patients in their sixth decade (99 cases) According to histological classifications of the lesions (mean age±SD), odontogenic tumors consisted of 2 ameloblastomas (65 5±12 5), 4 odontomas (24 3±12 2) and 1 odontogenic ghost cell carcinoma (22) The non-odontogenic benign lesions were 29 fibrous hyperplasias (57 0±17 4), 23 hyperkeratoses (leukoplaskia) (57 3±16 2), 10 papillomas (62 1±143), 9 irritation fibromas (63 0±13 4), 8 hemangiomas (57 5±9 2), 6 papillary hyperplasias (65 7±13 7), 5 osteomas (exostosis, enostosis) (55 2±8 0), 4 epithelial dysplasias (60 8±13 3) and 4 penapical cemental dysplasias (45 3±5 7), 3 pleomorphic adenomas (44 3±5 7) Non-odontogenic malignant tumors consisted of 56 squamous cell carcinomas (658±126), 3 malignant lymphomas (68 7±20 1) The odontogenic cysts consisted of 37 radicular cysts (42 8± 15 7), 27 dentigerous cysts (42 9±186) and 16 primordial cysts (43 4±18 7) The non-odontogenic cysts consisted of 30 mucous retention cysts (mucoceles) (22 5±13 7), 18 postoperative maxillary cysts (56 7±9 1), 5 incisive canal cysts (49 8±3 7) and 2 simple bone cysts (13 0±1 4). Also found were 35 chronic inflammatory (granulation) tissues (54 7±14 1), 20 chronic localized hyperplastic gingivitises (epuhses) (50 4±16 8), 13 Sjogren syndromes (54 7±13 0), 10 sialohthiases (56 8±13 3), 7 lichen planuses (64 3±83), 7 dental granulomas (32 7±6 8) and 5 chronic (inflammatory) ulcers (61 0±7 5).

Dermoid cysts of the jaw are exceedingly rare, and only six such cases have been documented. The present paper reports a case with multiple microcysts showing histological characteristics of dermoid cyst in the surgically resected mandibular bone. These cysts were located near the inferior border of the mandibular bone, and histologically composed of an inner thin layer of squamous epithelium with marked hyperorthokeratinization and an outer layer of fibrous tissue containing numerous mature sebaceous glands. In addition, a hair follicle-like epithelial sphere was seen in part. The present microcysts suggest that it arises de novo, and one possible cause of jaw cysts could be sequestration of the stomadeal ectoderm that may have been trapped deep in the surface and embedded in the developing mandibular bone during embryogenesis. It may not be possible that such cysts developed from the odontogenic epithelial remnant undergoing dermoid metaplasia.

An unusual case of sialolith with bone formation, occurring in the submandibular gland of a 33-year-old woman, is reported. In addition to the irregularly laminated structure of sialolith, sparsely scattered foci of bone tissue were found. Some of them were mature, lamellar bone with lacunae containing osteocytes, endosteum and a bone marrow-like element. Others were immature bone associated with or without multinucleated giant cells. Foci of bone tissue were in contact with caliculi or fibrous tissue, and no epithelial component was seen around them. These observations suggest that bone formation in the present case may be in the nature of pathological ossification, and that in the earlier stage, the bone that is deposited is woven and is replaced through successive remodeling cycles by lamellar bone. This is the first case of sialolith with bone formation, although sialolithiasis is a common disease of the salivary glands.

We analyzed clinicopathologically patients with upper gingival carcinoma, especially those with cervical lymph node metastasis. This study included 35 patients who had undergone treatment for upper gingival carcinoma from 1975 to 2001. Clinically suspected node positive (N(+)) cases were appeared in 7 of the cases (20.0%). The TNM classification (UICC) was T4N1 and T4N2 in 3 each patients, with all patients classified as M0. Histopathologically confirmed node positive (pN(+)) cases appeared in 4 of 7 N(+) cases and 4 cases of secondary metastasis, for a total of 8 cases. A high prevalence of pN(+) cases were found among the endophytic, and 4C types. Regarding treatment modality, preoperative chemotherapy was administered to 30 of the cases. Chemotherapy was administered intra-venously in 8 cases and intra-arterially in 13 cases. Among patients treated intra-venously, there were no cases demonstrating neck metastasis ; however, among those treated intra-arterially, there was secondary metastasis in 3 cases. The 5-year cumulative survival rate was 81.3% overall and 62.5% among the pN(+) cases. Uncontrolled sites in pN(+) cases consisted of cervical lymph node metastasis in one case, and distant metastasis in another case.

Minor salivary gland tumors were clinicopathologically evaluated. Between 1990 and 2000, 31 patients with minor salivary gland tumors (10 males and 21 females between 12 and 75 years of age, mean age : 49.9 years) were treated in our department. Minor salivary gland tumors most frequently occurred in the palate in 19 patients, followed by 5 in the buccal mucosa, 4 in the lips, and 1 in the oropharynx. Histopathological examinations revealed 20 benign and 11 malignant tumors. Pleomorphic adenoma accounted for the majority (19 cases) of the benign tumors. Malignant tumors consisted of 3 mucoepidermoid carcinomas, 3 adenoid cystic carcinomas, 1 adenocarcinoma, 1 acinic cell carcinoma, 1 salivary duct carcinoma, 1 tubular adenocarcinoma, and 1 basal cell adenocarcinoma. All cases of benign tumors were successfully treated by extirpation without tumor recurrence. Of the 11 cases of malignant tumors, 7 were treated by surgery alone, 1 was treated by surgery after chemotherapy, and 3 were treated by surgery after chemotherapy and radiotherapy. Primary lesions recurred in 2 of these patients. The outcomes of patients with malignant tumors were as follows : 6 patients survived without other complications, 3 died of uncontrollable tumors, and 2 died of other diseases. Of the 3 patients who died of uncontrollable tumors, 2 died of primary lesions and 1 died of cervical lymph node metastasis.

Pathological examinations diagnosed at our department in 2001 were statistically reviewed. There were 641 examinations for 516 cases (Male: 244, Female 272). Cases were most frequent in patients in their seventh decades (106 cases). In histological classifications of the lesions (mean age ±SD), odontogenic tumors consisted of 5 ameloblastomas (40.4±25.2), 2 odontomas (20.2±8.0), and one malignant ameloblastoma (33.0). The non-oclontogenic benign lesions were 44 fibrous hyperplasias (55.2±18.9), 28 hyperkeratosis (leukoplakia) (55.7±13.4), 7 hemangiomas (65.6±5.9), 6 pleomorphic adenomas (56.7±11.5), 6 osteomas (exostosis, enostosis), 4 papillomas (80.7±7.4), 4 epithelial dysplasias (61.5±11.9) and 3 periapical cemental dysplasias (30.1±13.7). Non-odontogenic malignant tumors consisted of 53 squamous cell carcinomas (68.1±12.6) and 3 verrucous carcinomas (71.7±4.8). The odontogenic cysts consisted of 45 radicular cysts (45.2±14.3), 21 dentigerous cysts (41.4±19.9) and 8 primordial cysts (29.9±11.3). The non-odontogenic cysts consisted of 44 mucoceles (30.3±22.6), 18 postoperative maxillary cysts (56.1±11.4), 3 incisive canal cysts (54.3±9.9) and 2 dermoid cysts (16.5±2.5). In addition, 10 Sjogren syndromes (53.9±11.0), 7 lichen planus (69.1±12.9), 26 chronic localized hyperplastic gingivitis (epulis) (60.1±15.7) and 6 dental granulomas (50.5±16.9) were revealed.

Background: Lobular capillary hemangioma (LCH) usually occurs in the skin or mucous membranes as a rapidly growing red nodule. LCH is one of the most common vascular lesions in the oral mucosa. Tie2 is a novel, human endothelial receptor tyrosine kinase which may play an important role in blood vessel formation. In this study, we investigated its immunohistochemical expression in LCH of the oral mucosa. Methods: Double immunostaining with anti-CD34 and antiα smooth muscle actin (SMA) antibodies was performed to characterize the cellular expression of Tie2 in 15 cases of this condition. Results: We found Tie2 immunoreactivity in the ovoid cells only, which were frequently intermingled with αSMA-positive cells, especially in the hypercellular portion of LCH. Conclusions: These results suggest that the expression of Tie2 in ovoid cells and the interaction between ovoid cells and αSMA-positive cells play an important part in the development and progression of LCH.

Infiltration of eosinophils io the stroma is occasionally seen in malignant tumors, and there is some relation between eosinophilic infiltration and prognosis of squamous cell carcinoma (SCC) originating in the esophagus, lung and other organs. However there are few reports of oral SCC with infiltration of eosinophils. The present paper reports a case of oral SCC with a severe degree of eosinophilic infiltration. The patient was a 71-year-old female whose chief complaint was a white lesion in her tongue. Histologic examination revealed the lesion to he well differentiated SCC with infiltration of numerous eosinophils in the stroma. A few eosinophils had infiltrated in the parenchyma. Infiltration of eosinophils was clearly demonstrated by Luna stain. Chemotherapy had effect on the lesion and surgically resected material showed complete disappearance of SCC.

我々の施設では, 口腔癌に対して機能温存, 形態温存を目的に動注, 放射線同時併用療法を行っている。今回は, 一次治療時で腫瘍が消失し外科療法を行わずに良好な経過が得られている下顎歯肉癌の1例について報告する。患者は65歳女性で, 初診時, 左側下顎歯槽部を中心に38×26mmの腫瘍を認め, X線所見にて下顎管におよぶ骨吸収を認めた。入院後, 浅側頭動脈カニュレーションを行い, PEP (総量48mg) , MTX (総量200mg) およびCDDP (総量100mg) の3剤併用化学療法と放射線療法 (Linac総線量40Gy) を行った。治療後臨床的に腫瘍は縮小, 消失し, positoron emission tomographyによる機能的画像診断による治療効果の評価でもCRと判定した。治療後2年2か月経過した現在, 再発, 転移は認めていない。

We developed a SiPM based MR-compatible DOI-TOF-PET detector. The detector consists of a scintillator block, a light guide, a 64-channels SiPM array, and front-end electronics (FEE) boards. The scintillator block consists of 2.9 mm × 2.9 mm × 20 mm LGSO crystals in a 16 × 16 array containing light reflectors arranged for four-layer DOI encoding by Anger logic calculation. The FEE including a full-custom mixed-signal ASIC was optimized for SiPM readout and TOF capability. 64-SiPM channels are segmented into four-blocks (16-ch/block) and a trigger signal is generated in each block for reducing degradation of timing resolution caused by dark counts. The ASIC consists of 16-readout channels, 16-DAC channels, an Anger type position encoder, a fast summing amplifier for timing signals, and a slow summing amplifier for energy signals. The readout channel is connected to AC-coupling to the anode of the SiPM and is composed of a fast voltage amplifier (>200 MHz), a slow voltage amplifier (shaper), and an offset controller. A two-dimensional position histogram, which was obtained under uniform irradiation from a 22Na point source, showed that all crystal positions, including DOI direction, were clearly identified and an energy resolution of 13.4 % was achieved. A timing histogram obtained from a quarter block (16-ch) of the developed detector in coincidence with a PMT based detector showed that a timing resolution of 495 ps is expected in the actual system. Based on the developed detectors, we are now developing an MR-compatible DOI-TOF-PET system.

Keratoameloblastoma is an extremely rare variant of ameloblastoma, and a review of the English language literature yields only several documented cases of ketatoameloblastoma. This paper reports a keratoameloblastoma showing unique histological architecture. The patient was a 76-year-old Japanese man with a multilocular radiolucent lesion of the mandible extending from the left canine to the second molar area. Microscopically, the lesion was characterized by multicystic spaces lined by papillary projections of proliferating odontogenic epithelium with extensive surface parakeratinization in a lamellar accumulation of keratin. In addition, "hair-like" extensions of keratin were frequently found. There was no ghost cell type keratinization. Histological features of the odontogenic epithelium were similar to those of conventinal ameloblastoma. An additional prominent feature of the present ameloblastoma was formation of hard tissue in continuation, in part, of the accumulated keratin in the fibrous tissue. These hard tissues showed a woven bone- or cellular cementum-like appearance and were not in contact with odontogenic epithelium. The present case was finally diagnosed as "keratoa meloblastoma," although such a type of keratoameloblastoma has not been documented previously in the spectrum of ameloblastoma.

We established two gingival epithelial cell lines (GE1 and GE6), originating from transgenic mice harboring the temperature-sensitive simian virus 40 large T-antigen gene. GE1 and GE6 grew at a permissive temperature (33 degrees C) in a pavement arrangement and solely formed multilayers that exhibited morphological features similar to those of the stratified oral epithelium, with neither the use of stromal equivalents nor feeder layers. Both GE cells underwent apoptosis at a non-permissive temperature (39 degrees C). Characteristic keratin peptides, keratin 4 and 13, for mucosal epithelium were obviously expressed in the suprabasal cells, and keratohyalin granules and involucrin were present in the surface flat cells in the multilayered culture. Keratin 10 (one of the markers for higher keratinized gingival epithelium) was rarely found in some uppermost cells, and filaggrin (a component of keratohyalin granules) appeared sparsely in uppermost desquamating cells in the older cultures. These observations indicated that GE1 and GE6 cells exhibited the phenotype characterizing nonkeratinized sulcular epithelium, which possessed the potency undergoing keratinization in such highly stratified cultures as oral gingival epithelium. GE cells increased the expression levels of mRNA of interleukin-1beta and tumor necrosis factor alpha by the stimulation of lipopolysaccharide and extracellular substances of oral streptococci. The GE cell lines thus could serve as an excellent experimental system for further studies on the physiology of gingival epithelium and corresponding diseases, such as periodontal disease, epithelial hyperplasia, and gingival tumors.

This paper reports about an ameloblastic fibrodentinoma with macroscopically visible pigmentation, resulting in the clinical appearance of a melanotic lesion in a 21-year-old Japanese male. In addition to the characteristic histopathologic features of ameloblastic fibrodentinoma, various-formed and -sized cells, which were considered to be melanophages containing numerous aggregates of melanin pigment in their cytoplasm, were densely distributed throughout the mesenchymal component. In addition, melanin pigment was deposited in dentin. Some of the pigmented cells showed dendritic form and were regarded as melanocytes. Furthermore, pigmented cells were frequently distributed in the epithelial component, and melanin pigment was seen in some epithelial cells. Perusal of the English language literature revealed 30 cases of pigmented odontogenic tumors: 18 were calcifying odontogenic cysts, three were ameloblastic fibro-odontomas, three were adenomatoid odontogenic tumors, two were odontomas, one was an ameloblastic fibroma and one was an odontogenic fibroma. However, all of these reported lesions did not show macroscopically visible pigmentation. The possible histogenesis of melanocytes in the odontogenic lesions is discussed, although no firm conclusion could be drawn.

The cellular localization and roles of bone morphogenetic protein (BMP)-2 and apoptosis-associating factors in human orofacial development remain unclear. In this study, BMP-2, osteocalcin, and TGF-beta, which are bone-differentiating markers, apoptosis-associating factors (i.e., Bcl-2, Bax, Fas, and Fas ligand), apoptotic cells detected by the in situ 3'-end labeling method (TUNEL), and proliferating cell nuclear antigen (PCNA) were immunohistochemically examined in the heads (in particular, the jaw bone and tooth germs) of human fetuses of 11-week pregnancy. BMP-2 was positive in osteoblasts and newly formed osteoid of the incisive and palatal bone of the maxilla and the mandible, which indicated that BMP-2 was exclusively involved in intramembranous ossification in the human fetal head. Fas was positive in the cytoplasm of osteocytes and a few osteoblasts. In contrast, Fas ligand was positive in the cytoplasm of osteoblasts and abundant in the stroma of the osteoblastic layer, periosteum, and perichondrium. The Fas ligand in the stroma was recognized as the soluble form, which was possibly produced by osteoblasts. TUNEL-positive apoptotic cells were found in a few osteocytes and a few osteoblastic cells in new bone, and in monocytes of degenerate Meckel's cartilage. The induction of apoptosis observed in monocytes seems to be caused via a Fas-Fas ligand cell death system, because some of these monocytes were Fas-positive, and most of them were Fas ligand-positive. Interestingly, the abundant soluble Fas ligand observed in the periosteum probably protects the bone-formative zone from the invasion of the activated lymphocytes by binding to Fas expressing in these lymphocytes and killing these cells. Fas and Fas ligand were focally positive in the dental lamina and inner enamel epithelium and cusps of the enamel organ, nevertheless, the presence of TUNEL-positive cells was very rare. Bcl-2 was clearly and Bax was weakly positive in the cells throughout the dental lamina and enamel organ. These findings indicated that Fas-mediated apoptosis was inhibited by the Bcl-2 family in the development of teeth.

An autopsy case of malignant ameloblastoma in a 64-year-old Japanese woman is presented, which started as a benign ameloblastoma with plexiform and follicular patterns, and transformed into a malignant histology with atypical and mitotic tumor cells in the course of several recurrences. An autopsy revealed several relatively large metastases in the lungs bilaterally consisting of malignant ameloblastoma and intracranial invasion of malignant tumor cells to the left temporal lobe. Immunohistochemical staining of proliferating cell nuclear antigen (PCNA) demonstrated a significant increase in the proliferative activity of neoplastic cells between the primary tumor and two recurrent ones (P < 0.01, Newman-Keul's test). This data provides evidence of malignant transformation in a benign ameloblastoma in the course of multiple recurrences. Immunostaining of PCNA may be useful in determining the possibility of malignant transformation in recurrent cases of ameloblastoma.

Radicular cysts arising from deciduous teeth are rare, although they are the most common cysts of the jaws. During the 20-year period between 1976 and 1995, we studied four cases (three boys, one girl) of radicular cysts arising from deciduous teeth at our hospital. These cases were diagnosed clinically and histologically. The patients' ages ranged from 9 years to 12 years, with a mean age of 11 years 4 months, and they were all in Hellman's Dental Age III B. Three patients had gingival swelling as a primary symptom, and the other had no symptoms. All lesions were located in the second premolar area of the mandible. Three cases were unilateral, and one was bilateral. All lesions showed swelling on the buccal side of the mandibular bone in the areas of the cysts. In all the lesions, X-ray examination showed cyst-like radiolucency at the apex of the second deciduous molars. Extirpation or mar supialization of the cysts was the treatment of choice for all lesions. There has been no recurrence, and all permanent teeth erupted at their normal positions in all patients.

Bone morphogenetic proteins (BMPs) are crucial factors of osteogenesis. We investigated the expressions of BMP subtypes in human salivary adenocarcinoma cell line (HSG-S8), tongue squamous cell (HSC-4) and gingival squamous cell (Ca9-22) carcinoma cell lines, gastric poorly differentiated adenocacinoma cell (MNK45) and signet ring cell (KATOIII) carcinoma cell lines, rectal adenocarcinoma (RCM-1, RCM-2, and RCM-3), and thyroid (8505C) and bladder (T24) carcinoma cell lines by reverse transcription-polymerase chain reaction (RT-PCR). RT-PCR disclosed that BMP-1 was expressed in all cell lines examined, and BMP-2 was amplified in almost all cells except MKN45. Two squamous cell carcinomas, HSC-4 and Ca9-22, and KATOIII expressed only BMP-1 and BMP-2. MKN45 did not express BMP-2, but expressed BMP-7 and weakly BMP-4 and BMP-5. In addition to the expression of BMP-1 and BMP-2, three rectal adenocarcinoma cell lines commonly expressed BMP-7, and HSG-S8 expressed BMP-6. These findings indicated that the neoplastic epithelial cells possessed a rather great potency to express BMP mRNAs. On the other hand, among these carcinoma cells, HSG-S8 solely induced bone in nude mouse tumors, and HSC-4 and KATOIII contained many calcified masses in tumors while the rest did not induce either.

The gingival epithelium is the physiologically important interface between the bacterially colonized gingival sulcus and periodontal soft and mineralized connective tissues requiring protection from exposure to bacteria and their products. However, the molecules comprising the gingival epithelial cell junction remain poorly characterized. Thus, the aim of the present study was to characterize the desmosome-associating proteins (desmoglein 1 and 3), desmosome-associating cytoskeleton (keratins), and tight junction-associating protein (claudin-1) within the oral gingival epithelium (OGE), sulcular epithelium (SE), and junctional epithelium (JE). Gingival epithelia excised at therapeutic flap surgery from patients with periodontitis were used to examine expression of adhesion molecules by immunofluorescence. In the OGE and SE, but not JE, desmoglein 1 was more abundant in the cell-cell contact sites of the upper than the suprabasal layer, while desmoglein 3 and desmoplakin were present in the cell-cell contact sites in all layers of the JE as well as the OGE and SE. Keratin 14 and 19, but not keratin 13 and 4, were present in the JE. Claudin-1 was expressed only in the intermediate layers in the uppermost flat layers in the OGE. These data indicated that the JE contained only few desmosomes composed of desmoglein 3. Thus, it is thought that the anchoring junction connecting JE cells is not firm, causing widened intercellular spaces in the JE. In contrast, the OGE, which has tight junctions, functions as a barrier.

Recently, various PET-MRI systems with silicon photomultiplier (SiPM) arrays have been developed by many research groups [1–3]. We previously proposed the concept of a multi-modal compatible “flexible” PET scanner [4]. The scanner consists of adjustable two detector heads and scans a patient lying on a bed equipped with another medical device such as CT, MR and radiotherapy device. In this study, we have developed a proof-of-concept (POC) MR-compatible PET system that consists of two detector heads and the data acquisition (DAQ) system. The single detector module consists of 16 × 16 LGSO crystal array, a light guide and a 6 × 6 SiPM array. The size of each crystal element was 2.9 mm × 2.9 mm × 20.0 mm with a special reflector arrangement for four-layer DOI encoding. Two detector heads each consists of six detector modules are positioned in front of a permanent magnet (1.5 T) open MRI scanner. We evaluated the mutual interference between PET and MRI by the sequential PET/MRI experiments, and finally performed small animal imaging studies. These results showed MR-compatibility of our detectors and encouraged the concept of the “flexible” PET.

Cementogenesis of the molars with aging was studied using senescence accelerated mouse (SAM) which included SAMP2/Iw and SAMP8@Iw as prone strains, and SAMR1/Iw as a resistant strain. Morphometric analysis was done for the cementum thickness at 2, 6, 12 and 16 months of age on 4 parts of the mice, i.e. at the mesial (M), the distal (D), the apical (A) and the furcational (F) cementum of the maxillary first molar. SAMR1/Iw was also studied at 20 months of age. Mean cementum thickness was statistically analyzed for age and strain differences. Mean thicknesses of the M and the D cementum in SAMP2/Iw and in SAMP8@Iw were usually higher than those in SAMR1/Iw. Furthermore, there were significant differences between SAMP2/Iw and SAMR1/Iw, and between SAMP8/Iw and SAMR1/Iw, both at 12 and 16 months of age. There was no difference in mean thickness in the F cementum in either strain and at any age. In the A cementum, SAMP2/Iw displayed significantly thicker cementum than SAMR1/Iw at 6, 12 and 16 months of age. The degree of molar eruption was thought to be more accelerated in SAMP2/Iw than in SAMR1/Iw. However, the thickness of the A cementum was not different for SAMP8@Iw and SAMR1/Iw in any age group. In this study, 2 conclusions were drawn as follows: first, that SAMP2/Iw and SAMP8@Iw exhibited more accelerated cementogenesis than SAMR1/Iw in the M and the D cementum. Secondly, several factors such as intrinsic factors, occlusal forces and degree of attrition affected the cementogenesis of the M and the D, the F and the A cementum, respectively.

A case of amyloidosis presenting with multiple nodules in the tongue is reported. A 70-year-old woman with a history of chronic renal insufficiency and receiving long-term hemodialysis complained of tenderness along the margin of her tongue. Clinical examination and palpation demonstrated multiple, firm ash-yellow nodules. Microscopic examination of a biopsy specimen stained with alkaline Congo red revealed orange staining. Under a polarization microscope, green disdiaclast refraction of amyloid proteins was identified. The histopathological diagnosis of the specimen was amyloidosis. The patient has not noticed any symptoms after biopsy and is currently being observed.

The localization of bone morphogenetic protein (BMP)-1, -2, -3 and transforming growth factor (TGF)-beta in normal salivary gland and pleomorphic adenoma of the salivary gland has been examined immunocytochemically. Tumor cells with BMP immunostaining in pleomorphic adenoma were associated with some solid cellular and tubuloglandular patterns, and with stellate cells in the myxoid area. In addition, in the chondroid area of three pleomorphic adenomas, chondrocyte-like cells were positive for BMPs. It is speculated that BMPs secreted by the tumor cells play a role in the formation of the chondroid component in pleomorphic adenoma by inducing some tumor cells, probably neoplastic myoepithelial cells, to differentiate to chondrocytes by metaplastic change. No tumor cells specifically immunostained with TGF-beta were found. TGF-beta was positive in fibrous and hyalinized stroma. In the submandibular gland, only anti-BMP-1 antibody specifically reacted to apical portions of degenerated serous acinar cells.

5′-Nase-ALPase 二重染色法の開発により, 毛細リンパ管と毛細血管の光顕的識別が可能となった。この方法を口腔癌の臨床病理学的研究の分野へ応用できないものかと考え, 基礎的実験データに基づき, 標本作製条件について検討した。対象は1992年12月から1993年1月までの2カ月間に当科外来を受診し, 口腔癌が疑われた一次症例5名で, 生検時, 標本の1/2に通常のHE染色, 残りの1/2に5′-Nase-ALPase 二重染色法を施した。検討の結果, 冷ホルムアルデヒド塩化カルシウム固定液の濃度は4%で, 前固定, 後固定を各30分間施行し, 一定の反応液濃度で30分間反応させると, 口腔癌における毛細リンパ管を容易に同定することができた。

For a data processing circuit using Anger positioning method on a high-resolution PET detector, it is difficult to measure precisely the position of the interaction, because a signal baseline fluctuates by causes such as temperature dependence of the detector sensitivity and the circuit drift, pulse pileup at high count rates, and scintillator afterglow. Particularly in the case of the number of scintillator elements much greater than the number of photo detector elements, both high signal precision and stability are required because the positioning error is caused by a slight baseline change. Usually AC-coupled circuit is utilized to reduce the influence of the baseline change, but may not work at high count rates. Then we adopted a DC coupling and have developed a DBLR (Digital Baseline Restorer) method to correct the baseline shift in real time. The amount of baseline shift is periodically estimated during the acquisition based on the shrinkage of a 2D position histogram map of the detector. The ratios of the total count of the outermost region and the inner region for each direction of the 2D map are fed back to correct the position calculation on FPGA. We evaluated the proposed method with a four-layer DOI (depth of interaction) detector that consists of 4,096 LGSO crystal elements and a 64-channel PS-PMT (position sensitive photomultiplier tube). The DBLR can effectively correct the baseline shift and reduce the map shrinkage to less than 0.3% even at a high count rate of 243 kcps.

The expression of the ras p21 in oral squamous cell carcinoma was examined immunohistochemically with the use of a monoclonal antibody NCC-RAS-001 with the avidin-biotin-peroxidase complex method. The expression of ras p21 product was detected in 65.7% (44 of 67 cases) of cancer patients. On the basis of the degree of histologic differentiation of the cancer cells, the incidence of ras p21 was found to be as follows: 63.4% (26 of 41 cases) were well differentiated; 86.7% (13 of 15 cases) were moderately differentiated; and 45.5% (5 of 11 cases) were poorly differentiated. The highest incidence was found in patients in their sixties--80.0% (16 of 20 cases). The incidence decreased to 40% in patients over 80 years of age. The incidence of ras p21 on the basis of location was as follows: 81.8% (9 of 11 cases) involved the buccal region, 70.6% (12 of 17 cases) were in the gingiva, and 55.0% (11 of 20 cases) were in the tongue.

ヒト舌粘膜上皮におけるランゲルハンス (L) 細胞数とその分布を抗S-100蛋白抗体を用いて免疫組織化学的に検索した。L細胞は突起を持った細胞として舌粘膜上皮の有棘細胞層に容易に認めることが出来たが, 上皮内に均等に分布することはなく, 検索視野によってその密度は一定ではなかった。舌の表面長1mmあたりの粘膜上皮内におけるL細胞数は舌の前部, 中央部および後部の間で大差はみられず, 舌背と舌側部の上皮内における細胞数の間にも顕著な差はみられなかった。しかし, 舌粘膜上皮1mm2あたりでL細胞数を見ると舌背部に比較して舌側部でやや多い傾向が窺え, この部位の粘膜上皮が舌背部の上皮に比して抗原提示能力と免疫学的活性の高いことを示唆している所見と見なされた。

For diagnosis of very small lesions of breast cancer on very early stage, a dedicated breast positron emission tomography (PET) scanner consisting of four-layer depth of interaction (DOI) detectors is now under development. We are aiming for the spatial resolution of less than 1 mm across a large effective field of view (FOV), and acquisition time of less than 5 minutes for each breast and 10 minutes in total. The "C" shape of this scanner allows it to be positioned closely around the breast, effectively increasing both resolution and sensitivity. The C-shaped design of the scanner accommodates a variety of patient physiques, ensuring inclusion of the entire breast into the effective FOV. The detector consists of four-layer of a 32 × 32 Lu 1.8 Gd 0.2 SiO 5 (LGSO) crystal array, a light guide and a 64ch position-sensitive photomultiplier tube (H8500). The size of crystal element is 1.44 mm × 1.44 mm × 4.5 mm. The detector ring consists of 24 detector modules arranged in a 2-ring configuration with a diameter of 228 mm and an axial extent of 105 mm. We developed a prototype equipment of C-shaped breast PET scanner, and also developed a full-ring PET scanner for comparison. We report basic evaluation of each prototype, such as, sensitivity, count rate, resolution, and image quality of phantoms.

The expression of ras p 21 and its histological localization on 13 ameloblastomas has been immunohistochemically studied using monoclonal antibody NCC-RAS-001 as the primary antibody. The ras p 21 was detected in 10/13 (76.9%) ameloblastomas; 3/5 (60.0%) were of the follicular and 7/8 (87.5%) of the plexiform type. In addition, ras p 21 was also detected in the cytoplasm of metaplastic squamous cells. The result suggested that ras p21 may be closely related to the proliferation and the development of tumor cells in ameloblastoma.

The expression of c-myc oncogene products in oral squamous cell carci noma (34 cases) was immunohistochemically studied, and this was detected in 14 cases (41.2%). These results suggest that c-myc oncogene product may be related to the development and growth of oral squamo us cell carcinoma.

A pigmented nevus is defined as a hamartomatous proliferation of melaninproducing cells (nevus cells). A relatively rare case of the disease with involvement of the oral mucosa is reported.The patient was a 44-year-old woman who had a nevus on the alveolar mucosa of the maxilla for about 7 years. The nevus measured 33×23mm, but was asymptomatic. A biopsy showed the lesion to be an intradermal nevus. Because of the location of the nevus and the patient's past history of schizophrenia, the lesion was resected with the patient under general anesthesia. Postoperative healing was uneventful, and there was no evidence of recurrence as of 4 years 6 months after the operation.

For diagnosis of very small lesions of breast cancer on very early stage, a dedicated breast positron emission tomography (PET) scanner consisting of four-layer depth of interaction (DOI) detectors is now under development. We are aiming for the spatial resolution of less than 1 mm in this scanner and acquisition time is less than 5 minutes by one breast and 10 minutes in total. The “C” shape of this scanner allows it to be positioned closely around the breast, effectively increasing both resolution and sensitivity. The open end of the detector unit allows the arm to be placed there and the C-shaped design of the scanner accommodates a variety of patient physiques, ensuring inclusion of the entire breast into the effective field of view (FOV).

Time-of-flight position emission tomography (TOF-PET) is a promising technique for greatly improving image quality. It is well known that depth of interaction (DOI) information can reduce parallax error and uniform the spatial resolution in whole FOV. In this work, we developed three types of DOI detector (non-DOI, 2-layer and 4-layer) for TOF-PET and confirmed whether DOI information can also improve time resolution. The crystal blocks consist of a 16 × 16 Lu 1.8 Gd 0.2 SiO 5 (LGSO) array. To become the same sensitivity for all crystal blocks, they had the total length in depth direction of the crystal blocks are the same. The size of each crystal element was 3 mm square. The crystal blocks were optically coupled to a 64-channel position sensitive photomultiplier tube, which has 8 × 8 multi anodes at intervals of 6.08 mm. Irradiating 511 keV gamma rays uniformly, All crystal elements of each block are clearly separated on a two-dimensional position histogram. Energy resolutions of non-DOI, 2-layer and 4-layer DOI detectors are 11.1%, 12.0% and 13.0% and time resolutions are 450 ps, 455 ps and 476 ps, respectively.

Oral senile amyloidosis in senescence accelerated mouse (SAM) was examined for two SAM sublines (P/2/Iw and R/1/Iw) and for various ages by light microscopy, immunohistochemistry, and electron microscopy. The amyloid deposition, identified by green birefrigence following Congo red stain, was observed only in P/2/Iw. In P/2/Iw, no amyloid deposition was found at age 6 months; however, frequency and extent of such deposits increased with advancing age. Distribution of amyloid deposition was as follows: along papillary layers of mucous epithelium in the tongue, the gingiva, the palate, and the buccal mucosa; foci in connective tissues; along vessels, muscles, and minor salivary glands. Immunohistochemically, the amyloid deposition was positive with anti-ASSAM serum being raised against a unique amyloid protein ASSAM which probably induced "senile systemic amyloidosis". P/2/Iw is useful as an animal model of oral senile amyloidosis.

We are now developing a sophisticated 32times32times4-layer depth of interaction (DOI) detector for a positron emission mammography (PEM) scanner which has both high resolution and high sensitivity. The candidate of scintillator is Lu1.8Gd0.2SiO5 (LGSO) or Lu1.9Y0.1SiO5 (LYSO) and each crystal size is 1.45 mm times 1.45 mm times 4.5 mm. The white plastic reflectors with thickness of 0.125 mm are inserted into a crystal block with different patterns for each DOI layer. The crystal block is coupled to a 256-channel flat panel position sensitive photomultiplier tube which has 16 times 16 at intervals of 3.04 mm. In this work, we evaluated the performance of a DOI detector with LGSO crystals by obtaining a two-dimensional (2D) position histogram of all crystal elements with 511 keV gamma-ray irradiation. Results show that 4,096 crystal elements (32 x 32 x 4) can be clearly identified on the 2D position histogram. As the average over all crystal elements, the energy resolution is 14.7% and the timing resolution is 849 ps in FWHM.

The incidence of mucous and ciliated cells in epithelial linings was examined among odontogenic inflammatory cysts (radicular cysts) and developmental cysts (dentigerous and primordial cysts). Mucous cells were found in 20.8% of all cysts examined, while ciliated cells were found in 11.4%; however, ciliated cells were always accompanied by mucous cells. The incidence of mucous cells in radicular cysts and dentigerous cysts and that of ciliated cells in radicular cysts was higher in the maxilla than in the mandible, while the incidence of mucous cells in primordial cysts and that of ciliated cells in dentigerous cysts and primordial cysts was higher in the mandible than in the maxilla. The present results regarding mucous cells and ciliated cells in the epithelial linings of intraosseous odontogenic cysts indicate a metaplasic origin, but the cause and biological significance of this phenomenon is not known. Mucous cells were present in the surface layer of epithelial linings, and intraepithelial gland-like structures lined with mucous cells were observed in the hyperplastic regions of epithelial linings of several radicular and dentigerous cysts. Such gland-like structures lined by mucous cells in the thickened epithelial lining, which have not been demonstrated previously, resembled the glandular structures of "glandular odontogenic cysts".

Background: Although it is known that retinoic acid (RA) regulates the cellular differentiation of skin keratinocytes, the effects of RA on the anchoring junction have not been clarified. The effects of all-trans RA on cell–cell and cell–matrix connections of gingival epithelial (GE)1 cells in a multilayered culture were investigated. Methods: Ultrastructures of GE1 cells were observed and immunohistochemistry was used to detect keratin 4, keratin 13, and desmoglein expression. Reverse transcription-polymerase chain reaction was performed to detect expression of desmosome and hemidesmosome-associating adhesion molecules, keratin 13, and keratin14. Results: Retinoic acid caused immunohistochemical diminution of keratin 4, keratin 13, and desmoglein. Ultrastructurally, RA induced drastic loss of typical desmosomes and complete loss of hemidesmosomes. RA significantly decreased the transcript levels of keratin 13, keratin 14, desmoglein 1, and desmocollin 1 in a dose-dependent manner. The 230-kD bullous pemphigoid antigen (BPAG1) gene expression was also reduced by RA, whereas transcript levels of integrin α6, integrin β4, the 180-kD bullous pemphigoid antigen (BPAG2), and laminin 5 were not affected. Conclusion: These results indicated that RA disintegrated not only desmosomes by depriving the cells of desmoglein 1, desmocollin 1, keratin 13, and keratin 4, but also hemidesmosomes by reducing the expression of BPAG1 and keratin 14 in basal keratinocytes.

This paper reports a pleomorphic adenoma with grossly visible pigmentation resulting in the macroscopic appearance of melanotic lesion in a 33-year-old Japanese male. In addition to the characteristic histopathological features of a benign pleomorphic adenoma, variously formed and -sized cells, many of which were considered to be melanocytes, containing melanin pigment in their cytoplasm, were distributed in the epithelial component. In addition, melanin pigment was deposited in tumor cells of duct structures. Furthermore, condensed secretory substances with marked pigmentation were frequently seen in the tubular lumina. Perusal of the English language literature revealed only two cases of parenchymal pigmentation of salivary gland tumors: both were mucoepidermoid carcinoma. The possible histogenesis of melanocytes in the salivary gland lesions is discussed, though no firm conclusion could be drawn.

The patient was a 20-year-old female who visited the Department of Dentistry and Oral Surgery of Hakodate Goryokaku Hospital complaining of slight pain in the bilateral upper molar regions.Radiographic examination showed radiopaque shadows at the bottom of the bilateral maxillary sinuses. The sinuses were surgically enucleated under a clinical diagnosis of osteoma. The lesions had the consistency and appearance of bone.Microscopic examination revealed lamellar bone with fatty marrow containing a slight infiltration of inflammatory cells. There were few osteoblasts or osteoclasts in this lesion. Near the cut surface, cystic formation characterized by an antral mucous membrane and mucus in the cystic cavity was observed. Due to a previous history of nasal bone fracture. these findings suggested that hone fragments formed an exostosis for reactive bone proliferation.