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A case of paraneoplastic pemphigus (PNP) associated with Castleman's disease in the retroperitoneal region is reported. A 54-year-old woman presented at our hospital because of multiple regions of severe oral mucositis. Biopsy of the buccal mucosa was performed, and the histopathological diagnosis was a lichenoid lesion. The results of indirect immunofluorescence and immunoblotting strongly suggested PNP. General screening by CT scanning, endscopy of the upper and lower gastrointestinal tracts, and nuclear medical examinations was performed to search for the cause of PNP. A 60×43mm mass was found in the right retroperitoneal region on CT. The tumor was extirpated by urologists at our university hospital. The histopathological diagnosis of the mass was Castleman's disease. The oral lesion was diagnosed as PNP and was treated with high-dose prednisolone and cyclosporine A gargle. After treatment, the oral lesion resolved completely. The clinical course of the patient has been good, with no evidence of recurrence 1 year after discharge from our hospital.

Lethal midline granuloma is a T/natural killer cell lymphoma characterized by progressive ulcerationand necrosis of the nasal cavity or pharynx along the midline facial tissues. A case of lethalmidline granuloma in the palate of a 63-year-old woman is reported. The patient had a low-grade fever anda large ulcer with hemorrhage in the palate. Clinically, a malignant tumor was initially suspected becauseof rapid progressive ulceration, but inflammatory disease was pathologically diagnosed on examination ofa tissue specimen stained with hematoxylin and eosin. The definite diagnosis was made by in situ hybridizationwith Epstein-Barr virus RNA (EBV encoded small RNA- 1: EBER 1)-specific oligonucleotideprobes, which showed positive signals in small lymphocytes. The patient's condition became critical becauseof frequent hemorrhage, and she soon died.

Objective To evaluate the existence of Epstein-Barr virus (EBV) infection in the synovial tissue of patients with rheumatoid arthritis (RA). Methods Synovial tissues were obtained at synovectomy or arthroplasty from 32 patients with RA and 30 control patients with osteoarthritis (OA). EBV DNA was detected by Southern blot hybridization and/or polymerase chain reaction (PCR) amplification. To localize the EBV-infected cells, tissue sections were studied by RNA in situ hybridization (ISH) for the EBV-encoded small RNA 1 (EBER-1), by DNA ISH for the Bam HI W region of EBV DNA, and by immunohistochemistry for EBV lytic proteins BZLF1 and gp350/220. Results EBV DNA was detected by PCR in 15 of the 32 samples from RA patients (47%), but in none of those from the 30 OA patients (P 1 EBV copy/1,000 cells (referred to as EBV 2+), and 6 contained 1 copy/1,000–5,000 cells (EBV 1+). Among the 9 EBV 2+ samples, 3 were also positive for EBV DNA by Southern blot hybridization, 5 were positive for EBER-1 by RNA ISH, and 3 were positive for EBV DNA by DNA ISH. Immunohistochemical analysis showed positive signals in all samples for BZLF1 and in 7 samples for gp350/220. In each examination, the positive signals were detected not only in lymphocytes, but also in synovial lining cells. Conclusion EBV was frequently detected in the synovial tissue of RA patients. The infected cells were both lymphocytes and synovial cells, and expressed EBV proteins associated with virus replication. These findings suggest that EBV may play a role in the pathogenesis of RA.

In this study, we investigated the presence of Epstein–Barr virus (EBV) in liver tissue from 35 patients with hepatocellular carcinoma (HCC). EBV DNA was detected in 13 patients (37%) by Southern blot hybridization. In 10 of these patients, EBV DNA was present in tumor tissue only, whereas in the other 3, it was detected in both tumor and nontumor tissues. The quantity of EBV DNA detected was equivalent to 1–10 viral DNA molecules/100 cells. EBV-determined nuclear antigen was detected in 7–13% of the carcinoma cells in three tumor tissue samples that contained approximately one copy of the EBV genome/10 cells. A single terminal fragment of EBV DNA was identified in these tissues, suggesting that the EBV-infected cells in HCC represent clonal proliferation. Western blotting and reverse transcription–polymerase chain reaction analyses demonstrated that these three tumor tissue specimens were positive for EBV-determined nuclear antigen 1 and BamHI A transcripts but were negative for the other latent EBV products, including EBV-encoded small RNA. The results indicated that there is a high EBV load in HCC tissue and that all of the HCC tissue examined showed a novel pattern of EBV latency characterized by absence of EBV-encoded small RNA expression.

We studied overexpression of p53, Bcl-2, Bcl-6, c-Myc and Mdm2 proteins by immunohistochemistry for a total of 27 primary central nervous system B cell lymphomas (CNS lymphomas) in immunocompetent patients and one CNS lymphoma in an AIDS patient. The expression of Epstein-Barr (EB) virus-encoded small RNA-1 (EBER-1) was also analysed using in situ hybridisation. Overexpression (more than 20% of cells stained) of p53 protein was detected in 8 of 27 immunocompetent cases (30%); 6 cases showed a nuclear stain and 2 cases showed cytoplasmic stain (nuclear exclusion). Strong Bcl-2 or Bcl-6 immunoreactivity suggestive of overexpression was seen, respectively, in 5 (19%) and 6 (22%) cases; 2 cases were positive for both immunoreactivities. Interestingly, overexpression of Bcl-2 or Bcl-6 was not seen in the cases which showed p53 overexpression (P < 0.03; chi-square test). EBER-1 expression was not detected in any of the 27 immunocompetent cases, but was found in the AIDS-related CNS lymphoma, which also showed an overexpression of Bcl-6, but not Bcl-2. None of the cases showed c-Myc or Mdm2 overexpression. Taken together, it is suggested that CNS lymphoma in immunocompetent hosts is a distinct disease that has a different molecular profile from those of systemic lymphoma and/or AIDS-related CNS lymphoma.

Although the presence of Epstein-Barr virus has been documented in approximately 7% of patients with gastric carcinoma, the clinical features of Epstein-Barr virus-associated carcinoma have not been well documented. We studied the histologic and endoscopic characteristics of Epstein-Barr virus-associated gastric carcinoma.We tested 124 gastric carcinomas from 117 patients using in situ hybridization for Epstein-Barr virus encoded small RNA1. The histologic and endoscopic findings in the Epstein-Barr virus-associated groups and the negative control groups were analyzed and compared.Twelve tumors (9.7%) were identified as Epstein-Barr virus associated. These lesions were located mainly in the upper part of the stomach (p.05) and had a diffuse-type histology (p.05) compared with those in the control group. Six of seven (85.7%) early Epstein-Barr virus-associated lesions were type 0 IIc (superficial depressed) or a combined type, and 42.9% were accompanied by submucosal nodules of carcinoma with lymphoid stroma. Four of five (80%) advanced Epstein-Barr virus-associated tumors were type 3 (ulcerated without definite limits), thought to be the advanced shape of superficial depressed lesions.Epstein-Barr virus-associated gastric carcinomas often appear as superficial depressed or ulcerated lesions in the upper part of the stomach and have a diffuse-type histology with lymphoid infiltration.

At the Department of Oral and Maxillofacial Surgery, Yamaguchi University Hospital, 43 tracheotomies were performed between 1985 and 1994.Tracheotomies were classified as elective or emergency. Elective tracheotomies were performed in 37 cases (86.0%) and emergency tracheotomies in 6 cases (14.0%). The elective tracheotomies included 34 cases of oral cancer, 2 cases of multiple fractures of the jaws, and 1 case of benign tumor. Of these 34 cases of oral cancer, 17 underwent total or subtotal resection of maxilla, and 16 underwent immediate reconstruction with a pectoralis major myocutaneous flap after the resection of oral cancer.Six emergency tracheotomies were performed in patients with advanced oral cancer because of obstruction of the upper respiratory track or bleeding from the mouth or cervical region.The duration of intubation ranged from 3 to 214 days, with an average of 23.8 days. The tubes were used up to 10 days in 25 cases (58.1%).No serious complications occured during the operative or the early and late postoperative phases after tracheotomy.

Approximately 60% of all actinomycotic infections occur in the cervicofacial area. The submandibular region is the most frequent site, and actinomycosis of bone is rare. We report a rare case of actinomycosis arising in the maxilla.The patient was a 51-year-old woman who presented with a diffuse swelling and purulent fistulas in the left maxillary molar region. Radiography revealed an irregular radiopaque mass surrounded by a radiolucent area in the left maxillary molar region. The left maxillary sinus was cloudy. Computed tomography showed hone destruction appearing to be a sequestrum in the left maxillary molar region with severe mucosal thickening of the left maxillary sinus.The clinical diagnosis was chronic osteomyelitis of the maxilla with spontaneous sequestration and chronic maxillary sinusitis. The sequestrum was removed, and radical antrum operation was performed with the patient under general anesthesia. The histopathological diagnosis was actinomycosis with a sequestrum.

The Epstein-Barr virus (EBV) has been reported to be detectable in about 10% of gastric carcinomas. We performed a comparative study of endosonographic findings of EBV-positive and -negative early gastric carcinomas. Epstein-Barr virus was detected in 11.8% (four of 34) of endosonographically observed early gastric carcinoma lesions. Endoscopic ultrasonography (EUS) revealed a hypoechoic mass in the third layer, which reflected submucosal nodules, in 75% (three of four) of EBV-associated lesions. Endoscopically, in 66.7% (two of three) of EBV-associated carcinomas, the depressed lesion was surrounded by a raised margin covered with normal mucosa and was similar to a submucosal tumour (P < 0.05). Histologically, all three cases of EBV-associated lesions with submucosal tumour invasion had submucosal nodules of carcinoma with lymphoid stroma and 75% (three of four) were located in the gastric body. The ratio of maximal thickness to width of EBV-associated lesions was significantly larger than that of EBV-negative lesions, and this tendency was marked in lesions with submucosal tumour invasion (P < 0.05). This study indicated that EUS and endoscopy are of great use for the determination of EBV association with early gastric carcinoma.

Gastric tissue specimens from 20 patients with chronic atrophic gastritis, one of whom also had an early gastric carcinoma, were studied for evidence of Epstein–Barr virus (EBV) infection by Southern blot analysis, DNA and RNA in situ hybridization, and immunohistochemistry for the presence of the EBV-determined nuclear antigen 1 (EBNA-1) and the latent membrane protein 1 (LMP-1). EBV DNA was detected in two cases with chronic atrophic gastritis and in the case with early gastric carcinoma by Southern blot hybridization. DNA in situ hybridization showed EBV genomes in the epithelial cells of two other cases with chronic atrophic gastritis and in non-carcinomatous and carcinomatous epithelial cells of the early gastric carcinoma case. EBNA-1 was detected in all cases. LMP-1 was detected in areas of intestinal metaplasia in eight patients with chronic atrophic gastritis. EBV-encoded small RNA 1 (EBER-1) expression was limited to carcinoma cells. These results show that gastric epithelium is frequently infected with EBV and suggest that prolonged EBV persistence may contribute to the development of gastric carcinoma. © 1997 John Wiley & Sons, Ltd.

To elucidate the association of Epstein-Barr virus (EBV) and salivary gland tumors, 114 cases of tumors of major salivary glands were investigated. EBV DNA was detected in all 6 cases of undifferentiated carcinoma and all 3 cases of T-cell lymphoma, but not in other tumor tissues. In situ hybridization studies for EBV DNA and EBV-encoded small RNA 1 (EBER1) showed specific localization of the EBV sequences to the undifferentiated carcinoma cells and T-lymphoma cells. Moreover, intense DNA signals were detected on nonneoplastic epithelial cells of T-lymphoma tissues. These epithelial cells were negative for EBER1 and expressed BZLF1, BALF2, and gp350/220 proteins associated with virus production. In contrast, nonmalignant epithelial cells surrounded by undifferentiated carcinoma cells showed no evidence of EBV infection or virus replication. These results indicate that there is an unusual association of salivary gland T-cell lymphomas with lytic EBV replication of nonmalignant epithelial cells.