Springer Science and Business Media LLC Acta Medica Okayama 2168-8184 17 7 2025 The Challenge of Diagnosing Scirrhous Gastric Cancer by Endoscopic Biopsy: A Case Report e87334 EN Yuka Ikeda Department of Internal Medicine, Clinic IkedaDepartment of Internal Medicine, Clinic Ikeda Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tadashi Yoshino Department of Pathology, Okayama University Takehiro Tanaka Department of Pathology, Okayama University Hospital Nobumasa Ikeda Department of Internal Medicine, Clinic Ikeda Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Scirrhous gastric cancer, also known as linitis plastica, is a rare and aggressive subtype of gastric carcinoma that poses significant diagnostic challenges due to its submucosal infiltration and often normal-appearing mucosa. We report a case involving a 30-year-old Japanese woman who presented with a six-month history of epigastric pain and postprandial vomiting. Initial endoscopic examination revealed erythema and mucosal swelling, with limited antral distensibility and resistance during duodenal intubation. Despite 12 mucosal biopsies, histopathological examination revealed no evidence of malignancy. Given the strong clinical and endoscopic suspicion of scirrhous gastric cancer, additional deep sections and immunohistochemical staining were performed. These revealed scattered signet-ring cell carcinoma and poorly differentiated adenocarcinoma, with positive immunostaining for p53 and Ki67. The patient underwent total gastrectomy, and the diagnosis of scirrhous gastric cancer was confirmed on the resected specimen. This case highlights the importance of a high index of clinical suspicion, close collaboration between endoscopists and pathologists, and the utility of ancillary diagnostic tools, such as immunohistochemistry, in identifying subepithelial gastric malignancies that may be missed on conventional biopsy. No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 1472-6831 24 1 2024 Histological differences related to autophagy in the minor salivary gland between primary and secondary types of Sjögren's syndrome 1099 EN Hitomi Ono-Minagi Department of Cytology and Histology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Tsutomu Nohno Department of Cytology and Histology, Okayama University Medical School Kiyofumi Takabatake Department of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takehiro Tanaka Department of Pathology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takayuki Katsuyama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Hospital Kohta Miyawaki Division of Precision Medicine, Kyushu University School of Medicine Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Seiji Iida Department of Oral and Maxillofacial Reconstructive Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tadashi Yoshino Department of Pathology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hitoshi Nagatsuka Department of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takayoshi Sakai Department of Rehabilitation for Orofacial Disorders, Osaka University Graduate School of Dentistry Hideyo Ohuchi Department of Cytology and Histology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Some forms of Sjögren’s syndrome (SS) follow a clinical course accompanied by systemic symptoms caused by lymphocyte infiltration and proliferation in the liver, kidneys, and other organs. To better understand the clinical outcomes of SS, here we used minor salivary gland tissues from patients and examine their molecular, biological, and pathological characteristics. A retrospective study was performed, combining clinical data and formalin-fixed paraffin-embedded (FFPE) samples from female patients over 60 years of age who underwent biopsies at Okayama University Hospital. We employed direct digital RNA counting with nCounter® and multiplex immunofluorescence analysis with a PhenoCycler™ on the labial gland biopsies. We compared FFPE samples from SS patients who presented with other connective tissue diseases (secondary SS) with those from stable SS patients with symptoms restricted to the exocrine glands (primary SS). Secondary SS tissues showed enhanced epithelial damage and lymphocytic infiltration accompanied by elevated expression of autophagy marker genes in the immune cells of the labial glands. The close intercellular distance between helper T cells and B cells positive for autophagy-associated molecules suggests accelerated autophagy in these lymphocytes and potential B cell activation by helper T cells. These findings indicate that examination of FFPE samples from labial gland biopsies can be an effective tool for evaluating molecular histological differences between secondary and primary SS through multiplexed analysis of gene expression and tissue imaging. No potential conflict of interest relevant to this article was reported.

Japanese Society for Lymphoreticular Tissue Research Acta Medica Okayama 1346-4280 64 1 2024 Analysis of Notch1 protein expression in methotrexate-associated lymphoproliferative disorders 1 9 EN Takeshi Okatani Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Midori Filiz Nishimura Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Yuria Egusa Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Sayako Yoshida Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Yoshito Nishimura Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Asami Nishikori Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Tadashi Yoshino Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hidetaka Yamamoto Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yasuharu Sato Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Methotrexate (MTX)-associated lymphoproliferative disorder (MTX-LPD) is a lymphoproliferative disorder in patients treated with MTX. The mechanism of pathogenesis is still elusive, but it is thought to be a complex interplay of factors, such as underlying autoimmune disease activity, MTX use, Epstein-Barr virus infection, and aging. The NOTCH genes encode receptors for a signaling pathway that regulates various fundamental cellular processes, such as proliferation and differentiation during embryonic development. Mutations of NOTCH1 have been reported in B-cell tumors, including chronic lymphocytic leukemia/ lymphoma, mantle cell lymphoma, and diffuse large B-cell lymphoma (DLBCL). Recently, it has also been reported that NOTCH1 mutations are found in post-transplant lymphoproliferative disorders, and in CD20-positive cells in angioimmunoblastic T-cell lymphoma, which might be associated with lymphomagenesis in immunodeficiency. In this study, to investigate the association of NOTCH1 in the pathogenesis of MTX-LPD, we evaluated protein expression of Notch1 in nuclei immunohistochemically in MTX-LPD cases [histologically DLBCL-type (n = 24) and classical Hodgkin lymphoma (CHL)-type (n = 24)] and de novo lymphoma cases [DLBCL (n = 19) and CHL (n = 15)]. The results showed that among MTX-LPD cases, the expression of Notch1 protein was significantly higher in the DLBCL type than in the CHL type (P < 0.001). In addition, among DLBCL morphology cases, expression of Notch1 tended to be higher in MTX-LPD than in the de novo group; however this difference was not significant (P = 0.0605). The results showed that NOTCH1 may be involved in the proliferation and tumorigenesis of B cells under the use of MTX. Further research, including genetic studies, is necessary. No potential conflict of interest relevant to this article was reported.

The Japanese Society for Lymphoreticular Tissue Research Acta Medica Okayama 1346-4280 63 4 2023 Sutimlimab suppresses SARS-CoV-2 mRNA vaccine-induced hemolytic crisis in a patient with cold agglutinin disease 246 250 EN Hiroki Kobayashi Department of Internal Medicine, Tsuyama Chuo Hospital Tomoki Ouchi Department of Internal Medicine, Tsuyama Chuo Hospital Wataru Kitamura Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shoji Asakura Department of Internal Medicine, Okayama Rosai Hospital Tomofumi Yano Department of Internal Medicine, Okayama Rosai Hospital Hiromasa Takeda Department of Internal Medicine, Tsuyama Chuo Hospital Yoshiyuki Tokuda Department of Internal Medicine, Tsuyama Chuo Hospital Tadashi Yoshino Department of Pathology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshinobu Maeda Department of Hematology, Oncology, and Respiratory Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Cold agglutinin disease (CAD) is a rare form of acquired autoimmune hemolytic anemia driven mainly by antibodies that activate the classical complement pathway. Several patients with CAD experience its development or exacerbation of hemolysis after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or after receiving the SARS-CoV-2 mRNA vaccine. Therefore, these patients cannot receive an additional SARS-CoV-2 mRNA vaccination and have a higher risk of severe SARS-CoV-2 infection. Sutimlimab is a monoclonal antibody that inhibits the classical complement pathway of the C1s protein and shows rapid and sustained inhibition of hemolysis in patients with CAD. However, whether sutimlimab could also inhibit hemolysis caused by SARS-CoV-2 mRNA vaccination is uncertain. Here, we present the case of a 70-year-old man with CAD who repeatedly experienced a hemolytic crisis after receiving SARS-CoV-2 mRNA vaccines. The patient eventually underwent SARS-CoV-2 mRNA vaccination safely, without hemolytic attack, under classical pathway inhibition therapy with sutimlimab. This report suggests that appropriate sutimlimab administration can suppress SARS-CoV-2 mRNA vaccination-induced CAD exacerbation, and that it could be a preventive strategy to minimize hemolytic attacks in susceptible populations. No potential conflict of interest relevant to this article was reported.

American Society of Hematology Acta Medica Okayama 2473-9529 7 24 2023 Distribution and clinical impact of molecular subtypes with dark zone signature of DLBCL in a Japanese real-world study 7459 7470 EN Tomohiro Urata Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Naoi Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Aixiang Jiang British Columbia Cancer, Centre for Lymphoid Cancer Merrill Boyle British Columbia Cancer, Centre for Lymphoid Cancer Kazutaka Sunami Department of Hematology, NHO Okayama Medical Center Toshi Imai Department of Hematology and Blood Transfusion, Kochi Health Sciences Center Yuichiro Nawa Division of Hematology, Ehime Prefectural Central Hospital Yasushi Hiramatsu Department of Hematology and Oncology, Japanese Red Cross Society Himeji Hospital Kazuhiko Yamamoto Department of Hematology and Oncology, Okayama City Hospital Soichiro Fujii Department of Hematology, Japanese Red Cross Okayama Hospital Isao Yoshida Department of Hematologic Oncology, NHO Shikoku Cancer Center Tomofumi Yano Department of Internal Medicine, Okayama Rosai Hospital Ryota Chijimatsu Center for Comprehensive Genomic Medicine, Okayama University Hospital Hiroyuki Murakami Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Ikeuchi Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroki Kobayashi Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuma Tani Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideki Ujiie Center for Comprehensive Genomic Medicine, Okayama University Hospital Hirofumi Inoue Clinical Genomic Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Shuta Tomida Center for Comprehensive Genomic Medicine, Okayama University Hospital Akira Yamamoto Department of Hematology and Oncology, Okayama University Hospital Takumi Kondo Department of Hematology and Oncology, Okayama University Hospital Hideaki Fujiwara Department of Hematology and Oncology, Okayama University Hospital Noboru Asada Department of Hematology and Oncology, Okayama University Hospital Hisakazu Nishimori Department of Hematology and Oncology, Okayama University Hospital Keiko Fujii Department of Hematology and Oncology, Okayama University Hospital Nobuharu Fujii Department of Hematology and Oncology, Okayama University Hospital Ken-ichi Matsuoka Department of Hematology and Oncology, Okayama University Hospital Keisuke Sawada Department of Pathology, Saitama Medical Center, Saitama Medical University Shuji Momose Department of Pathology, Saitama Medical Center, Saitama Medical University Jun-ichi Tamaru Department of Pathology, Saitama Medical Center, Saitama Medical University Asami Nishikori Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Yasuharu Sato Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Tadashi Yoshino Department of Pathology, Okayama University Yoshinobu Maeda Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences David W. Scott British Columbia Cancer, Centre for Lymphoid Cancer Daisuke Ennishi Department of Hematology and Oncology, Okayama University Hospital The distribution and clinical impact of cell-of-origin (COO) subtypes of diffuse large B-cell lymphoma (DLBCL) outside Western countries remain unknown. Recent literature also suggests that there is an additional COO subtype associated with the germinal center dark zone (DZ) that warrants wider validation to generalize clinical relevance. Here, we assembled a cohort of Japanese patients with untreated DLBCL and determined the refined COO subtypes, which include the DZ signature (DZsig), using the NanoString DLBCL90 assay. To compare the distribution and clinical characteristics of the molecular subtypes, we used a data set from the cohort of British Columbia Cancer (BCC) (n = 804). Through the 1050 patient samples on which DLBCL90 assay was successfully performed in our cohort, 35%, 45%, and 6% of patients were identified to have germinal center B-cell–like (GCB) DLBCL, activated B-cell–like (ABC) DLBCL, and DZsig-positive (DZsigpos) DLBCL, respectively, with the highest prevalence of ABC-DLBCL, differing significantly from the BCC result (P < .001). GCB-DLBCL, ABC-DLBCL, and DZsigpos-DLBCL were associated with 2-year overall survival rates of 88%, 75%, and 66%, respectively (P < .0001), with patients with DZsigpos-DLBCL having the poorest prognosis. In contrast, GCB-DLBCL without DZsig showed excellent outcomes after rituximab-containing immunochemotherapy. DZsigpos-DLBCL was associated with the significant enrichment of tumors with CD10 expression, concurrent MYC/BCL2 expression, and depletion of microenvironmental components (all, P < .05). These results provide evidence of the distinct distribution of clinically relevant molecular subtypes in Japanese DLBCL and that refined COO, as measured by the DLBCL90 assay, is a robust prognostic biomarker that is consistent across geographical areas. No potential conflict of interest relevant to this article was reported.

Cell Press Acta Medica Okayama 2405-8440 9 7 2023 Expression and clinicopathological characteristics of PDX1, PTF1A, and SALL4 in large and small ducts of ectopic pancreas located in gastro-duodenum and jejunum e18241 EN Mengxi Chen Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takehiro Tanaka Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuro Igawa Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yanyan Han Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fangli Peng Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Zaishun Jin Department of Pathology, Mudanjiang Medical University Tadashi Yoshino Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences An ectopic pancreas is defined as pancreatic tissue outside its normal location, anatomically separated from the pancreas.<br> 　The transcription factor pancreas/duodenum homeobox protein 1 (PDX1) is involved in maintaining the pancreas and functions in early pancreatic development, beta cell differentiation, and endocrine non beta cells. Pancreatic transcription factor 1 subunit alpha (PTF1A) affects exocrine cell formation and regulation of acinar cell identity, and is expressed in exocrine cells as a transcription factor. The depletion of SALL4 disrupts self-renewal and induces differentiation.<br> 　To clarify which of PDX1, PTF1A, or SALL4 determines the difference in Heinrich's classification, we examined the localization and number of positive cells. We analyzed the differential expression of PDX1, PTF1A, and SALL4 in large and small ducts in ectopic pancreas by immunohistochemistry. Results showed that the number of PTF1A-positive cells in large ducts was more widespread in type I than in type II in the gastro-duodenum, and more SALL4-positive cells were noticed in large ducts than in small ducts in the gastro-duodenum of type II. Our results revealed that PTF1A might promote exocrine differentiation in developing the pancreatic tissues, and that those with widespread expression differentiate into exocrine cells. No potential conflict of interest relevant to this article was reported.

The Japanese Society for Lymphoreticular Tissue Research Acta Medica Okayama 1346-4280 63 1 2023 Benefit of prednisolone alone in nodal peripheral T-cell lymphoma with T follicular helper phenotype 37 42 EN Wataru Kitamura Department of Hematology, National Hospital Organization Iwakuni Clinical Center Hiroki Kobayashi Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Medical School Tomohiro Urata Department of Hematology, National Hospital Organization Iwakuni Clinical Center Yumiko Sato Department of Pathology, National Hospital Organization Iwakuni Clinical Center Yusuke Naoi Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tadashi Yoshino Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yoshinobu Maeda Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Medical School Shoichi Kuyama Department of Respiratory Medicine, National Hospital Organization Iwakuni Clinical Center A 71-year-old Japanese man presented with severe thrombocytopenia. A whole-body CT at presentation showed small cervical, axillary, and para-aortic lymphadenopathy, leading to suspicion of immune thrombocytopenia due to lymphoma. Biopsy was difficult to perform because of severe thrombocytopenia. Thus, he received prednisolone (PSL) therapy and his platelet count gradually recovered. Two and a half years after PSL therapy initiation, his cervical lymphadenopathy slightly progressed without other clinical symptoms. Hence, a biopsy from the left cervical lymph node was performed, and he was diagnosed with nodal peripheral T-cell lymphoma (PTCL) with T follicular helper (TFH) phenotype. Due to various complications, we continued treatment with prednisolone alone after the diagnosis of lymphoma; however, there was no further increase in lymph node enlargement and no other lymphoma-related symptoms for one and a half years after diagnosis. Although immunosuppressive therapy has been reported to produce a response in some patients with angioimmunoblastic T-cell lymphoma, our experience suggests that a similar subset may exist in patients with nodal PTCL with TFH phenotype, which has the same cellular origin. Immunosuppressive therapies may constitute an alternative treatment option even in the era of novel molecular-targeted therapies, especially for elderly patients who are ineligible for chemotherapy. No potential conflict of interest relevant to this article was reported.

Japanese Society for Lymphoreticular Tissue Research Acta Medica Okayama 1346-4280 63 1 2023 Comparison of serum sIL-2R and LDH levels in patients with intravascular large B-cell lymphoma and patients with advanced stage diffuse large B-cell lymphoma 25 31 EN Yuki Hirami Department of Nursing, Okayama University Graduate School of Health Sciences Midori Filiz Nishimura Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Tomohiro Urata Department of Hematology and Oncology, Okayama University Hospital Michiko Morimoto Department of Nursing, Okayama University Graduate School of Health Sciences Yukina Maekawa Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Tadashi Yoshino Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yoshito Nishimura Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yasuharu Sato Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences Intravascular large B-cell lymphoma (IVL) is a rare type of lymphoma characterized by tumor growth selectively within the vessels. The 5th edition of the World Health Organization classification defines IVL as a large B-cell lymphoma, the same as diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS). Since the clinical manifestations of IVL are nonspecific, the diagnosis is time-consuming, and the course is often fatal. Serum soluble interleukin-2 receptor (sIL-2R) and serum lactate dehydrogenase (LDH) levels are known to be elevated in a variety of lymphomas. However, the mechanism of sIL-2R elevation in B-cell lymphomas is not fully understood. In this study, we analyzed the serum level of laboratory findings, including sIL-2R and LDH, as well as the presence of B symptoms in 39 patients with IVL, and compared them with 56 patients with stage IV DLBCL. Both sIL-2R and LDH levels were significantly higher in IVL than in DLBCL (p = 0.035 andp = 0.002, respectively). In IVL, there were no significant differences in both sIL-2R and LDH levels between patients with and without B symptoms (p = 0.206 andp = 0.441, respectively). However, in DLBCL, both sIL-2R and LDH levels were significantly higher in the presence of B symptoms (p = 0.001 andp < 0.001, respectively). The high sIL-2R and LDH levels in IVL may be related to the peripheral blood microenvironment, but further studies are needed to verify this. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 134 1 2022 ３学会開催報告（第67回日本病理学会特別総会，第12回アジア太平洋病理学会，第61回日本リンパ網内系学術総会） 54 55 EN Tadashi Yoshino Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 1 2023 Effect of a Cyclooxygenase-2 Inhibitor in Combination with (−)-Epigallocatechin Gallate or Polyphenon E on Cisplatin-Induced Lung Tumorigenesis in A/J Mice 65 70 EN Ken Sato Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nagio Takigawa Department of General Internal Medicine 4, Kawasaki Medical School Toshio Kubo Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideki Katayama Department of Medicine, Yamaguchi-Ube Medical Center Daizo Kishino Department of Medicine, Yamaguchi-Ube Medical Center Toshiaki Okada Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akiko Hisamoto Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Junko Mimoto Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuaki Ochi Department of General Internal Medicine 4, Kawasaki Medical School Tadashi Yoshino Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Ueoka Department of Medicine, Yamaguchi-Ube Medical Center Mitsune Tanimoto Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshionobu Maeda Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuyuki Kiura Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/64363 We investigated the effects of celecoxib combined with (−)-epigallocatechin-3-gallate (EGCG) or polyphenon E in a cisplatin-induced lung tumorigenesis model. Four-week-old female A/J mice were divided into seven groups: (i) Control, (ii) 150 mg/kg celecoxib (150Cel), (iii) 1,500 mg/kg celecoxib (1500Cel), (iv) EGCG+150 mg/kg celecoxib (EGCG+150Cel), (v) EGCG+1,500 mg/kg celecoxib (EGCG+1500Cel), (vi) polyphenon E+150 mg/kg celecoxib (PolyE+150Cel), and (vii) polyphenon E+1,500 mg/kg celecoxib (PolyE+1500Cel). All mice were administered cisplatin (1.62 mg/kg of body weight, i.p.) 1×/week for 10 weeks and sacrificed at week 30; the numbers of tumors on the lung surface were then determined. The tumor incidence and multiplicity (no. of tumors/mouse, mean±SD) were respectively 95% and 2.15±1.50 in Control, 95% and 2.10±1.29 in 150Cel, 86% and 1.67±1.20 in 1500Cel, 71% and 1.38±1.24 in EGCG+150Cel, 67% and 1.29±1.38 in EGCG+1500Cel, 80% and 1.95±1.36 in PolyE+150Cel, and 65% and 1.05±0.10 in PolyE+1500Cel. The combination of high-dose celecoxib with EGCG or polyphenon E significantly reduced multiplicity in cisplatin-induced lung tumors. No potential conflict of interest relevant to this article was reported.

The Japanese Society for Lymphoreticular Tissue Research Acta Medica Okayama 1346-4280 62 4 2022 Immunohistochemistry for IRTA1 and MNDA helps differentiate gastric MALT lymphoma from chronic gastritis/reactive lymphocyte hyperplasia 195 201 EN Yoshiyuki Ayada Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takuro Igawa Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yusuke Naoi Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kyosuke Horikawa Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tetsuya Tabata Department of Pathology, National Hospital Organization Okayama Medical Center Takehiro Tanaka Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tadashi Yoshino Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences It is difficult to histologically differentiate extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) from chronic gastritis (CG)/ reactive lymphoid hyperplasia (RLH). To determine whether immunohistochemistry for IRTA1 and MNDA can differentiate gastric MALT lymphoma from CG/RLH, we investigated 81 stomach biopsy specimens [Wotherspoon grade (WG) 1, 11 cases; WG 2, 9 cases; WG 3, 20 cases; WG 4, 31 cases; and WG 5, 10 cases]. According to a previously reported algorithm involving PCR for immunoglobulin heavy (IgH) chain locus rearrangement, all 81 cases were divided into three groups: CG/RLH (55 cases), MALT lymphoma (19 cases) groups, and IgH undetectable group (7 cases). We analyzed the CG/RLH and MALT lymphoma groups. The median percentage of IRTA1-positive cells was 0% (range 0%-90.6%) in the CG/RLH group and 43.5% (range 0%-97.6%) in the MALT lymphoma group (p < 0.0001). The median percentage of MNDA-positive cells was 32.4% (range 0%-97.6%) in the CG/RLH group and 55.1% (range 0%-97.6%) in the MALT lymphoma group (p = 0.0044). These results indicate that immunohistochemistry for IRTA1 and MNDA can help dif-ferentiate gastric MALT lymphoma from CG/RLH. No potential conflict of interest relevant to this article was reported.

Karger Acta Medica Okayama 1662-6575 15 3 2022 Sequential Combination of FLAM and Venetoclax plus Azacitidine to Bridge to Cord Blood Transplantation in a Patient with Primary Induction Failure Acute Myeloid Leukemia 974 979 EN Hiroyuki Murakami Department of Hematology and Oncology, Okayama University Hospital Ken-Ichi Matsuoka Department of Hematology and Oncology, Okayama University Hospital Takeru Asano Department of Hematology and Oncology, Japanese Red Cross Society Himeji Hospital Takashi Moriyama Department of Hematology and Oncology, Okayama University Hospital Akifumi Matsumura Department of Hematology and Oncology, Okayama University Hospital Hideaki Fujiwara Department of Hematology and Oncology, Okayama University Hospital Noboru Asada Department of Hematology and Oncology, Okayama University Hospital Daisuke Ennishi Department of Hematology and Oncology, Okayama University Hospital Hisakazu Nishimori Department of Hematology and Oncology, Okayama University Hospital Keiko Fujii Department of Hematology and Oncology, Okayama University Hospital Nobuharu Fujii Department of Hematology and Oncology, Okayama University Hospital Tomohiro Toji Department of Pathology, Okayama University Hospital Tadashi Yoshino Department of Pathology, Okayama University Hospital Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Hospital Venetoclax (VEN) is an oral B-cell lymphoma-2 (BCL-2) inhibitor that has been widely used to treat various hematological disorders. Recent studies have demonstrated that VEN in combination with fludarabine-enhanced high-dose cytarabine (FLA) is effective for treating relapsed or refractory acute myeloid leukemia (AML). In the combination therapy, salvage chemotherapy and VEN are basically concurrently administrated; however, further optimization may enable the treatment to apply to larger numbers of patients with various clinical backgrounds. Here, we describe a case of refractory AML treated with a sequential combination of the intensive chemotherapy (fludarabine, cytarabine, and mitoxantrone; FLAM) and VEN/AZA to bridge to an unrelated cord blood transplantation (uCBT). By continuously adding VEN/AZA after FLAM, the patient achieved morphologic leukemia free state with only minor toxicities. Blood cell counts did not recover until the time of transplantation because of the deep myelosuppression caused by the treatment sequence, but the infection risk was safely managed during this period. After engraftment, maintenance therapy with VEN/AZA was performed, and the patient has survived without disease recurrence for over 9 months after transplantation. Our case suggests that bridging therapy with VEN and AZA from the time of the last chemotherapy to allogeneic transplantation may provide an effective and tolerable treatment strategy for refractory AML. Further studies of larger numbers of cases are needed to validate the effectiveness of this treatment. No potential conflict of interest relevant to this article was reported.

The Japanese Society for Lymphoreticular Tissue Research Acta Medica Okayama 1346-4280 2022 Historical and pathological overview of Castleman disease 21036 EN Midori Filiz Nishimura Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yoshito Nishimura Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Asami Nishikori Division of Pathophysiology, Okayama University Graduate School of Health Sciences Tadashi Yoshino Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yasuharu Sato Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Castleman disease consists of several lymphoproliferative subtypes that share some histological features in the lymph nodes. On the other hand, numerous clinical findings and etiologies make the disease challenging to understand. The origin of the disease is the hyaline vascular-type unicentric Castleman disease (UCD), first reported by Benjamin Castleman et al. in 1954. Although UCD is characterized by localized lesions and lack of symptoms, multicentric Castleman disease (MCD) with multiple lesions and systemic symptoms was reported by Frizzera in 1983. MCD is further divided according to KSHV/HHV8 infection status. In KSHV/HHV8-related MCD, viral infection signals lead to excessive cytokine production, and cause clinical and pathologic abnormalities. Some cases of plasma cell-type KSHV/HHV8-negative MCD can be found in association with POEMS syndrome (polyneuropathy, organomegaly, cndocrinopathy, M-protcins, and skin changes), which is a paraneoplastic syndrome. The others are idiopathic MCD, which are currently considered a heterogeneous group of diseases with overlapping pathological and clinical features. In this article, we summarize the historical evolution of Castleman disease to help understand the disease concept. We also review the latest ideas and definitions of the subtypes within the MCD spectrum and summarize the histopathological findings. No potential conflict of interest relevant to this article was reported.

The Japanese Society for Lymphoreticular Tissue Research Acta Medica Okayama 1346-4280 62 1 2022 Transformed diffuse large B-cell lymphoma from marginal zone lymphoma in the anterior mediastinum: A case report and review of the literature 35 40 EN Wataru Kitamura Department of Hematology and Oncology, Okayama University Hospital Noboru Asada Department of Hematology and Oncology, Okayama University Hospital Tetsuya Tabata Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Rei Shibata Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tatsuya Nishi Department of Respiratory and Allergy, Okayama University Hospital Yuka Kato Center for Innovative Clinical Medicine, Okayama University Hospital Hiroki Takasuka Department of Hematology and Oncology, Okayama University Hospital Hideaki Fujiwara Department of Hematology and Oncology, Okayama University Hospital Daisuke Ennishi Center for Comprehensive Genomic Medicine, Okayama University Hospital Hisakazu Nishimori Department of Hematology and Oncology, Okayama University Hospital Nobuharu Fujii Department of Transfusion Medicine, Okayama University Hospital Ken-Ichi Matsuoka Department of Hematology and Oncology, Okayama University Hospital Katsuyuki Kiura Department of Respiratory and Allergy, Okayama University Hospital Tadashi Yoshino Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Hospital Marginal zone lymphoma (MZL) arising from the anterior mediastinum is rare. In the majority of reported cases, the tumor was incidentally discovered, reflecting its indolent clinical features. We present a 38-year-old woman who had no medical history, and presented with a bulky anterior mediastinal tumor complicated by life-threatening compression of the vasculature and bronchi. Biopsy specimens of the neoplasm suggested transformed diffuse large B-cell lymphoma (DLBCL) from MZL. To our best knowledge, this is the first case report of anterior mediastinum MZL associated with an aggressive clinical course and life-threatening complications likely due to transformation to DLBCL. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 133 3 2021 「十二指腸型」濾胞性リンパ腫の疾患単位の確立 166 168 EN Tadashi Yoshino Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmacenticul Sciences No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2072-6694 13 22 2021 Primary Gastrointestinal T-Cell Lymphoma and Indolent Lymphoproliferative Disorders: Practical Diagnostic and Treatment Approaches 5774 EN Midori Filiz Nishimura Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yoshito Nishimura Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Asami Nishikori Division of Pathophysiology, Okayama University Graduate School of Health Sciences Tadashi Yoshino Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yasuharu Sato Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Simple Summary: It is challenging for pathologists to diagnose primary gastrointestinal T-cell neoplasms. Besides the rarity of the diseases, the small biopsy material makes it more difficult to differentiate between non-neoplastic inflammation and secondary involvement of extra gastrointestinal lymphoma. Since this group of diseases ranges from aggressive ones with a very poor prognosis to indolent ones that require caution to avoid overtreatment, the impact of the diagnosis on the patient is enormous. Although early treatment of aggressive lymphoma is essential, the treatment strategy is not well established, which is a problem for clinicians. This review provides a cross-sectional comparison of histological findings. Unlike previous reviews, we summarized up-to-date clinically relevant information including the treatment strategies as well as practical differential diagnosis based on thorough literature review. <br> <br> Abstract: Primary gastrointestinal (GI) T-cell neoplasms are extremely rare heterogeneous disease entities with distinct clinicopathologic features. Given the different prognoses of various disease subtypes, clinicians and pathologists must be aware of the key characteristics of these neoplasms, despite their rarity. The two most common aggressive primary GI T-cell lymphomas are enteropathy-associated T-cell lymphoma and monomorphic epitheliotropic intestinal T-cell lymphoma. In addition, extranodal natural killer (NK)/T-cell lymphoma of the nasal type and anaplastic large cell lymphoma may also occur in the GI tract or involve it secondarily. In the revised 4th World Health Organization classification, indolent T-cell lymphoproliferative disorder of the GI tract has been incorporated as a provisional entity. In this review, we summarize up-to-date clinicopathological features of these disease entities, including the molecular characteristics of primary GI T-cell lymphomas and indolent lymphoproliferative disorders. We focus on the latest treatment approaches, which have not been summarized in existing reviews. Further, we provide a comprehensive review of available literature to address the following questions: How can pathologists discriminate subtypes with different clinical prognoses? How can primary GI neoplasms be distinguished from secondary involvement? How can these neoplasms be distinguished from non-specific inflammatory changes at an early stage? No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2075-4418 11 11 2021 Clinical and Pathological Characteristics of Hyaline-Vascular Type Unicentric Castleman Disease: A 20-Year Retrospective Analysis 2008 EN Midori Filiz Nishimura Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yoshito Nishimura Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Asami Nishikori Division of Pathophysiology, Okayama University Graduate School of Health Sciences Yukina Maekawa Division of Pathophysiology, Okayama University Graduate School of Health Sciences Kanna Maehama Division of Pathophysiology, Okayama University Graduate School of Health Sciences Tadashi Yoshino Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yasuharu Sato Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences The first case of hyaline vascular type of unicentric Castleman disease (HV-UCD) was reported more than six decades ago. Since patients with HV-UCD are often asymptomatic and this condition is generally discovered incidentally on imaging tests, most of the previous reports were of mediastinal origin detected by chest radiography. In recent years, improved access to imaging modalities has provided new insights in the diagnosis of this condition. In this study, we reviewed the detailed clinical and pathological findings of 38 HV-UCD cases (20 males and 18 females, mean age: 42.8 years). The most common site involved was the abdominal cavity (34.2%), followed by mediastinum (23.7%) and retroperitoneum (15.8%). In the abdominal cavity, mesenteric origin was the most common. The mean size of masses was 4.8 cm. Pathologically, thick hyalinized collagen fibers surrounding large blood vessels and calcification were observed (81.6% and 23.7%, respectively). Multinucleated giant cells resembling Warthin-Finkeldey cell were also observed in occasional cases (23.7%). This is a unique paper that summarizes detailed clinical and pathological findings of a large series of a rare disease. The clinical information presented in this paper is more plausible than previous views and is useful for accurate diagnosis and understanding of the disease. No potential conflict of interest relevant to this article was reported.

WILEY Acta Medica Okayama 2045-7634 2021 00 2021 PD-L1 expression is associated with the spontaneous regression of patients with methotrexate-associated lymphoproliferative disorders 1 EN Yuka Gion Division of Pathophysiology, Okayama University Graduate School of Health Sciences Misato Doi Division of Clinical Laboratory, Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital Yoshito Nishimura Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoka Ikeda Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Midori Filiz Nishimura Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Misa Sakamoto Division of Pathophysiology, Okayama University Graduate School of Health Sciences Yuria Egusa Division of Pathophysiology, Okayama University Graduate School of Health Sciences Asami Nishikori Division of Pathophysiology, Okayama University Graduate School of Health Sciences Azusa Fujita Division of Pathophysiology, Okayama University Graduate School of Health Sciences Noriko Iwaki Department of Hematology, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University Naoya Nakamura Department of Pathology, Tokai University School of Medicine Tadashi Yoshino Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuharu Sato Division of Pathophysiology, Okayama University Graduate School of Health Sciences Background Most patients with methotrexate-associated lymphoproliferative disorder (MTX-LPD) show diffuse large B-cell lymphoma (DLBCL) or classic Hodgkin lymphoma (CHL) types. Patients with MTX-LPD often have spontaneous remission after MTX discontinuation, but chemotherapeutic intervention is frequently required in patients with CHL-type MTX-LPD. In this study, we examined whether programmed cell death-ligand 1 (PD-L1) expression levels were associated with the prognosis of MTX-LPD after MTX discontinuation.<br> Methods A total of 72 Japanese patients diagnosed with MTX-LPD were clinicopathologically analyzed, and immunohistochemical staining of PD-L1 was performed in 20 DLBCL-type and 24 CHL-type MTX-LPD cases to compare with the clinical course. <br> Results PD-L1 was expressed in 5.0% (1/20) of patients with DLBCL-type MTX-LPD, whereas it was expressed in 66.7% (16/24) of the patients with CHL-type MTX-LPD in more than 51% of tumor cells. Most CHL-type MTX-LPD patients with high PD-L1 expression required chemotherapy owing to exacerbations or relapses after MTX discontinuation. However, no significant differences in clinicopathologic findings at diagnosis were observed between PD-L1 high- and low-expression CHL-type MTX-LPD. <br> Conclusion PD-L1 expression was significantly higher in patients with CHL-type than DLBCL-type MTX-LPD, suggesting the need for chemotherapy in addition to MTX discontinuation in CHL-type MTX-LPD patients to achieve complete remission. No association was observed between PD-L1 expression levels and clinical findings at diagnosis, suggesting that PD-L1 expression in tumor cells influences the pathogenesis of CHL-type MTX-LPD after MTX discontinuation. No potential conflict of interest relevant to this article was reported.

The Japanese Society of Internal Medicine Acta Medica Okayama 0918-2918 60 19 2021 Nodal Peripheral T-cell Lymphoma with T Follicular Helper Phenotype Presenting as Chorea During Treatment: A Case Report and Literature Review 3155 3160 EN Wataru Kitamura Department of Hematology and Oncology, Okayama University Hospital Daisuke Ennishi Center for Comprehensive Genomic Medicine, Okayama University Hospital Ryoya Yukawa Department of Hematology and Oncology, Okayama University Hospital Ryo Sasaki Department of Neurology, Okayama University Hospital Chikamasa Yoshida Department of Hematology, Okayama City Hospital Hiroki Takasuka Department of Hematology and Oncology, Okayama University Hospital Hideaki Fujiwara Department of Hematology and Oncology, Okayama University Hospital Noboru Asada Department of Hematology and Oncology, Okayama University Hospital Hisakazu Nishimori Department of Hematology and Oncology, Okayama University Hospital Keiko Fujii Division of Clinical Laboratory, Okayama University Hospital Nobuharu Fujii Division of Blood Transfusion, Okayama University Hospital Ken-Ichi Matsuoka Department of Hematology and Oncology, Okayama University Hospital Koji Abe Department of Neurology, Okayama University Hospital Tadashi Yoshino Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Hospital A 72-year-old man presented with chorea while undergoing treatment for recurrence of nodal peripheral T-cell lymphoma with T follicular helper (TFH) phenotype. An examination by brain N-isopropyl-p-iodoamphetamine (I-123-IMP)-single photon emission computed tomography (SPECT) revealed no abnormalities other than a decreased cerebral blood flow (CBF) in the left striatum. After four courses of salvage chemotherapy, his clinical symptoms and asymmetric cerebral perfusion improved, suggesting that the decreased CBF had caused chorea. The significance of brain SPECT has not been fully clarified in patients with chorea-associated malignant lymphoma, warranting further investigations. Brain SPECT is an alternative approach to identify abnormalities in such patients. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2571-841X 4 3 2021 Lymphoepithelial Carcinoma in the Lateral Tongue: The Case Report 24 EN Sawako Ono Department of Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hidenori Marunaka Department of Otolaryngology Head and Neck Surgery, Okayama University Hospital Hiroyuki Yanai Department of Pathology, Okayama University Hospital Hotaka Kawai Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kiyofumi Takabatake Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kenji Nishida Department of Pathology, Okayama University Hospital Tomohiro Toji Department of Pathology, Okayama University Hospital Keisuke Nakano Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hitoshi Nagatsuka Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tadashi Yoshino Department of Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Lymphoepithelial carcinoma (LEC) of the tongue is a rare subtype of squamous cell carcinoma. Histologically, it is an undifferentiated carcinoma with rich lymphocyte and plasma cell infiltration. The most common location for LEC in the head and neck is the salivary glands, and LEC of the oral cavity is extremely rare. The second case report of LEC in the lateral tongue is presented. In addition, a review of the literature was performed, and the relationship between LEC and Epstein-Barr virus infection was considered. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2571-841X 4 1 2021 A Case Report of Primordial Odontogenic Tumor That Required Distinction from a Dentigerous Cyst 4 EN Sawako Ono Department of Pathology, Okayama University Hospital Hotaka Kawai Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shintaro Sukegawa Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kiyofumi Takabatake Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keisuke Nakano Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hitoshi Nagatsuka Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tadashi Yoshino Department of Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Primordial odontogenic tumor (POT) is a rare odontogenic tumor characterized by a variably cellular loose fibrous tissue with areas similar to the dental papilla and covered by cuboidal to columnar epithelium. We herein report a case of POT in a 14-year-old boy. Computed tomography (CT) exhibited a round cavity with a defined cortical border circumscribing the tooth of the second molar. However, the gross finding was a solid mass, not a cyst. Histologically, the tumor consisted of dental papillalike myxoid connective tissue covered by columnar epithelium. Therefore, although the clinical diagnosis was dentigerous cyst (DC), we diagnosed POT based on histologic findings. Clinical findings of POT resemble DC, but the clinical behavior of POT is different to DC, such as cortical expansion and root resorption of teeth. Therefore, histological differentiation of POT from DC is critical for accurate diagnosis. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2075-4418 11 5 2021 Diagnostic Utility of SOX4 Expression in Adult T-Cell Leukemia/Lymphoma 766 EN Atsuko Nasu Division of Pathophysiology, Okayama University Graduate School of Health Sciences Yuka Gion Division of Pathophysiology, Okayama University Graduate School of Health Sciences Yoshito Nishimura Department of General Medicine, Okayama University Hospital Asami Nishikori Division of Pathophysiology, Okayama University Graduate School of Health Sciences Misa Sakamoto Division of Pathophysiology, Okayama University Graduate School of Health Sciences Yuria Egusa Division of Pathophysiology, Okayama University Graduate School of Health Sciences Azusa Fujita Division of Pathophysiology, Okayama University Graduate School of Health Sciences Tadashi Yoshino Department of Pathology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yasuharu Sato Division of Pathophysiology, Okayama University Graduate School of Health Sciences Differentiation between adult T-cell leukemia/lymphoma (ATLL) and peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), is often challenging based on pathological findings alone. Although serum anti-HTLV-1 antibody positivity is required for ATLL diagnosis, this information is often not available at the time of pathological diagnosis. Therefore, we examined whether the expression of SOX4 and p16 would be helpful for differentiating the two disease entities. We immunohistochemically examined SOX4 and p16 expression (which have been implicated in ATLL carcinogenesis) in 11 ATLL patients and 20 PTCL-NOS patients and classified them into four stages according to the percentage of positive cells. Among the ATLL cases, 8/11 (73%) were SOX4-positive, while only 2/20 (10%) PTCL-NOS cases expressed SOX4. The mean total score was 4.2 (standard deviation (SD): 0.61) in the ATLL group and 0.50 (SD: 0.46) in the PTCL-NOS group (p < 0.001). Positive expression of p16 was noted in 4/11 (36%) patients with ATLL and 3/20 (15%) patients with PTCL-NOS, with mean total scores of 1.9 (SD: 0.64) and 0.70 (SD: 0.48) in the ATLL and PTCL-NOS groups, respectively (p = 0.141). These results suggest that SOX4 may be strongly expressed in ATLL compared to PTCL-NOS cases. Therefore, it may be helpful to perform immunohistochemical staining of SOX4 when pathologists face challenges discriminating between ATLL and PTCL-NOS. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1422-0067 22 8 2021 Upregulated Expression of Activation-Induced Cytidine Deaminase in Ocular Adnexal Marginal Zone Lymphoma with IgG4-Positive Cells 4083 EN Asami Nishikori Division of Pathophysiology, Okayama University Graduate School of Health Sciences Yoshito Nishimura Department of General Medicine, Okayama University Hospital Rei Shibata Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Koh-Ichi Ohshima Department of Ophthalmology, National Hospital Organization Okayama Medical Center Yuka Gion Division of Pathophysiology, Okayama University Graduate School of Health Sciences Tomoka Ikeda Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Midori Filiz Nishimura Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tadashi Yoshino Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yasuharu Sato Division of Pathophysiology, Okayama University Graduate School of Health Sciences Immunoglobulin G4-related disease (IgG4-RD) is a systemic disorder characterized by tissue fibrosis and intense lymphoplasmacytic infiltration, causing progressive organ dysfunction. Activation-induced cytidine deaminase (AID), a deaminase normally expressed in activated B-cells in germinal centers, edits ribonucleotides to induce somatic hypermutation and class switching of immunoglobulin. While AID expression is strictly controlled under physiological conditions, chronic inflammation has been noted to induce its upregulation to propel oncogenesis. We examined AID expression in IgG4-related ophthalmic disease (IgG4-ROD; n = 16), marginal zone lymphoma with IgG4-positive cells (IgG4+ MZL; n = 11), and marginal zone lymphoma without IgG4-positive cells (IgG4- MZL; n = 12) of ocular adnexa using immunohistochemical staining. Immunohistochemistry revealed significantly higher AID-intensity index in IgG4-ROD and IgG4+ MZL than IgG4- MZL (p < 0.001 and = 0.001, respectively). The present results suggest that IgG4-RD has several specific causes of AID up-regulation in addition to inflammation, and AID may be a driver of oncogenesis in IgG4-ROD to IgG4+ MZL. No potential conflict of interest relevant to this article was reported.

HINDAWI LTD Acta Medica Okayama 2090-6528 2021 2021 A Case of Myoepithelial Hamartoma: Morphological Variation Supported by OCT4 Expression 6617370 EN Takehiro Tanaka Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kenji Nishida Department of Pathology, Okayama University Hospital Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Satoru Kikuchi Department of Gastroenterological Surgery, Okayama University, Graduate School of Medicine, Dentistry, and Pharmaceutical Science Tadashi Yoshino Department of Pathology, Okayama University, Graduate School of Medicine, Dentistry, and Pharmaceutical Science In this report, we describe a patient with myoepithelial hamartoma, which is regarded as synonymous with adenomyosis and heterotopic pancreas. Endoscopy revealed a submucosal tumor in the antrum of the stomach. Subsequently, distal gastrectomy with Roux-en-Y reconstruction was performed. Histological findings of adenomyomatous lesion and heterotopic pancreatic tissue were observed in this lesion. The distribution of OCT4, which is a pluripotency marker, varied in each part. No potential conflict of interest relevant to this article was reported.

Japanese Society for Lymphoreticular Tissue Research Acta Medica Okayama 1346-4280 60 4 2020 Differential diagnosis of chronic lymphocytic leukemia/small lymphocytic lymphoma and other indolent lymphomas, including mantle cell lymphoma 124 129 EN Tadashi Yoshino Department of Pathology, Okayama University Graduate School Takehiro Tanaka Department of Pathology, Okayama University Graduate School Yasuharu Sato Department of Pathology, Okayama University Graduate School Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) accounts for approximately 1% of all lymphomas in our department. In this article, we describe the differential diagnosis of CLL/SLL from other indolent lymphomas, with special reference to follicular lymphoma, marginal zone B-cell lymphoma, lymphoplasmacytic lymphoma, and mantle cell lymphoma, although the latter is considered to be aggressive. CLL/SLL often exhibits proliferation centers, similar to follicular lymphoma. Immunohistological examination can easily distinguish these two lymphomas. The most important characteristic of CLL/SLL is CD5 and CD23 positivity. Mantle cell lymphoma is also CD5-positive and there are some CD23-positive cases. Such cases should be carefully distinguished from CLL/SLL. Some marginal zone lymphomas are also positive for CD5 and such cases are often disseminated. Lymphoplasmacytic lymphoma should also be a differential diagnosis for CLL/SLL. It frequently demonstrates MYD88 L265P, which is a key differential finding. By immunohistological examination, the expression of lymphoid enhancer-binding factor 1 is specific for CLL/SLL and can be a good marker in the differential diagnosis. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1422-0067 22 3 2021 Epstein-Barr Virus-Positive Mucocutaneous Ulcer: A Unique and Curious Disease Entity 1053 EN Tomoka Ikeda Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuka Gion Division of Pathophysiology, Okayama University Graduate School of Health Sciences Yoshito Nishimura Department of General Medicine, Okayama University Hospital Midori Filiz Nishimura Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tadashi Yoshino Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuharu Sato Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Epstein-Barr virus (EBV)-positive mucocutaneous ulcer (EBVMCU) was first described as a lymphoproliferative disorder in 2010. EBVMCU is a unifocal mucosal or cutaneous ulcer that often occurs after local trauma in patients with immunosuppression; the patients generally have a good prognosis. It is histologically characterized by proliferating EBV-positive atypical B cells accompanied by ulcers. On the basis of conventional pathologic criteria, EBVMCU may be misdiagnosed as EBV-positive diffuse large B-cell lymphoma or other lymphomas. However, its prognosis differs from that of EBV-associated lymphomas, in that patients with EBVMCU frequently show spontaneous regression or complete remission without chemotherapy. Therefore, EBVMCU is now recognized as a low-grade malignancy or a pseudo-malignant lesion. Avoiding unnecessary chemotherapy by distinguishing EBVMCU from other EBV-associated lymphomas will reduce the burden and unnecessary harm on patients. On the basis of these facts, EBVMCU was first described as a new clinicopathological entity by the World Health Organization in 2017. In this review, we discuss the clinicopathological characteristics of previously reported EBVMCU cases, while focusing on up-to-date clinical, pathological, and genetic aspects. No potential conflict of interest relevant to this article was reported.

The Japanese Society for Lymphoreticular Tissue Research Acta Medica Okayama 1346-4280 60 1 2020 Hemosiderin deposition in lymph nodes of patients with plasma cell-type Castleman disease 1 6 EN Yanyan Han Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takuro Igawa Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kyohei Ogino Department of Pathology, Fukuyama City Hospital Asami Nishikori Division of Pathophysiology, Okayama University Graduate School of Health Sciences Yuka Gion Division of Pathophysiology, Okayama University Graduate School of Health Sciences Tadashi Yoshino Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yasuharu Sato Division of Pathophysiology, Okayama University Graduate School of Health Sciences Plasma cell-type Castleman disease (PCD) is a rare idiopathic atypical lymphoproliferative disorder. It is difficult to differentiate between PCD and IgG4-related disease (IgG4-RD) based on histology alone. As PCD often presents with abundant hemosiderin deposition, lymph node lesions obtained from 22 PCD patients and 12 IgG4-RD patients were analyzed using Prussian blue staining to clarify whether hemosiderin deposition is effective in distinguishing between these two diseases. The analysis disclosed that hemosiderin was more densely deposited in PCD than in IgG4-RD. The median number of Prussian blue-positive cells ± standard deviation (SD) in PCD and IgG4-RD cases was 13 ± 36 cells/3HPFs and 4 ± 8 cells/3HPFs (P = 0.034), respectively. In addition, we analyzed the relationship between hemosiderin deposition and levels of serum interleukin (IL)-6, serum C-reactive protein (CRP), and anemia-related biomarkers. We found that hemosiderin deposition was significantly correlated with the level of serum CRP (P = 0.045); however, no significant correlation was observed between hemosiderin deposition and serum IL-6 levels (P = 0.204). A non-significant positive correlation was observed between hemosiderin deposition and serum hemoglobin levels (P=0.09). Furthermore, no significant correlation was observed between hemosiderin deposition and serum iron levels (P = 0.799). In conclusion, hemosiderin deposition characteristically observed in PCD may be related to the inflammatory aggressiveness of the disease and could be used for its differential diagnosis. No potential conflict of interest relevant to this article was reported.

The Japanese Society for Lymphoreticular Tissue Research Acta Medica Okayama 1346-4280 60 3 2020 Clinicopathological significance of CD79a expression in classic Hodgkin lymphoma 78 86 EN Akio Sakatani Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences akuro Igawa Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Takeshi Okatani Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Megumu Fujihara Department of Pathology, Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital Hideki Asaoku Department of Hematology, Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital Yasuharu Sato Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tadashi Yoshino Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Classic Hodgkin lymphoma (CHL) is a lymphoid neoplasia characterized by the presence of large tumor cells, referred to as Hodgkin and Reed-Sternberg (HRS) cells, originating from B-cells in an inflammatory background. As the clinical significance of B-cell markers has yet to be fully elucidated, this study aimed to clarify the clinicopathological significance of CD79a in 55 patients with CHL. They were immunohistochemically divided into two groups, comprising of 20 CD79a-positive and 35 CD79a-negative patients. There was no significant correlation between CD79a and CD20 expression (rs = 0.125, P = 0.362). CD79a-positive patients were significantly older at onset (P = 0.011). There was no significant correlation between CD79a-positivity and clinical stage (P = 0.203), mediastinal involvement (P = 0.399), extranodal involvement (P = 0.749), or laboratory findings, including serum levels of lactate dehydrogenase (P = 1) and soluble interleukin-2 receptor (P = 0.251). There were significant differences in overall survival (OS) (P = 0.005) and progression-free survival (PFS) (P = 0.007) between CD79a-positive and CD79a-negative patients (5-year OS: 64.6% and 90.5%; 5-year PFS: 44.0% and 76.6%, respectively). Five patients in whom the majority (> 80%) of HRS cells expressed CD79a consisted of 4 males and 1 female aged between 52 and 81 years; 4 of them were in a limited clinical stage. We concluded that CD79a-positive CHL may have unique clinicopathological features. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2075-4426 10 4 2020 Pulmonary Manifestations of Plasma Cell Type Idiopathic Multicentric Castleman Disease: A Clinicopathological Study in Comparison with IgG4-Related Disease 269 EN Midori Filiz Nishimura Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takuro Igawa Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yuka Gion Division of Pathophysiology, Okayama University Graduate School of Health Sciences Sakura Tomita Department of Pathology, Tokai University School of Medicine Dai Inoue Department of Radiology, Kanazawa University Graduate School of Medical Sciences Akira Izumozaki Department of Radiology, Kanazawa University Graduate School of Medical Sciences Yoshifumi Ubara Nephrology Center, Toranomon Hospital Kajigaya Yoshito Nishimura Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tadashi Yoshino Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yasuharu Sato Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Plasma cell type idiopathic multicentric Castleman disease (PC-iMCD) occasionally manifests as parenchymal lung disease. This study aimed to elucidate the detailed clinicopathological features of lung lesions in PC-iMCD and compare the findings with those in immunoglobulin (Ig) G4-related disease (IgG4-RD), the most difficult differential diagnosis of PC-iMCD. We analyzed the clinicopathological findings and immunohistochemical expression patterns of interleukin-6 (IL-6) and Igs in lung specimens from 16 patients with PC-iMCD and 7 patients with IgG4-RD. Histologically, pulmonary PC-iMCD could not be differentiated from IgG4-RD based on lesion distribution patterns, the number of lymphoid follicles and obliterative vasculitis, or fibrosis types. The eosinophil count was higher in the IgG4-RD group than in the PC-iMCD group (p = 0.004). The IgG4/IgG-positive cell ratio was significantly higher in the IgG4-RD group (p < 0.001). The IgA-positive cell count and IL-6 expression intensity were higher in the PC-iMCD group than in the IgG4-RD group (p < 0.001). Based on these findings, we proposed a new diagnostic approach to differentiate lung lesions of PC-iMCD and IgG4-RD. Our approach can be utilized to stratify patients with suspected lung-dominant PC-iMCD to identify candidates for strong immunosuppressive treatment, including IL-6 blockade, at an early stage. No potential conflict of interest relevant to this article was reported.

日本内科学会 Acta Medica Okayama 0918-2918 59 21 2020 Adult T-cell Leukemia-lymphoma with Primary Breast Involvement: A Case Report and Literature Review 2757 2761 EN Hiroki Kobayashi Department of Hematology and Oncology, Okayama University Hospital Noboru Asada Department of Hematology and Oncology, Okayama University Hospital Takuro Igawa Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masaya Abe Department of Hematology and Oncology, Okayama University Hospital Yusuke Meguri Department of Hematology and Oncology, Okayama University Hospital Daisuke Ennishi Department of Hematology and Oncology, Okayama University Hospital Hisakazu Nishimori Department of Hematology and Oncology, Okayama University Hospital Nobuharu Fujii Department of Transfusion Medicine, Okayama University Hospital Ken-ichi Matsuoka Department of Hematology and Oncology, Okayama University Hospital Tadashi Yoshino Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Hospital Breast involvement of Adult T-cell leukemia-lymphoma (ATLL) is extremely rare, and the data on the characteristics are limited. We herein describe a 49-year-old woman who presented with skin involvement of ATLL. Positron emission tomography/computed tomography showed bilateral breast lesions. Although the patient once achieved a complete metabolic response, a relapse of her ATLL occurred. The patient received subsequent allogeneic hematopoietic stem cell transplantation (HSCT). To our knowledge, only four cases of ATLL with breast involvement have previously been reported, and the prognoses have generally been poor. Breast lesions of ATLL have aggressive features, and intensive systemic chemotherapy and HSCT are required to improve survival. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 2215-0161 7 2020 Technique for single-step lymphocyte isolation from an endoscopic biopsy specimen for the diagnosis of gastrointestinal lymphoma 101095 EN Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takahide Takahashi Division of Medical Support, Okayama University Hospital Natsuki Watanabe Division of Medical Support, Okayama University Hospital Sizuma Omote Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsunori Matsueda Department of Gastrointestinal Oncology, Osaka International Cancer Institute Takehiro Tanaka Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Daisuke Ennishi Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tadashi Yoshino Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Okada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences In this paper, we introduce a simplified, one-step procedure for lymphocyte isolation from an endoscopically biopsied fragment. For lymphocyte isolation, an endoscopically harvested specimen and 5 mL of normal saline solution were placed in a wire mesh strainer set in a porcelain bowl. To obtain the lymphocyte suspension, the solid specimen was crushed using the rubber portion of a plunger of a 10 mL injection syringe. Flow cytometry was performed using the lymphocyte suspension. For validating our methods, the one-step lymphocyte isolation technique was used to perform flow cytometry on samples from 23 patients with (n = 12) or without (n = 11) gastrointestinal lymphoma. Flow cytometry of light chain expression was performed in all patient samples (feasibility: 100%). Sensitivity was 83.3% (10/12) and specificity was 100% (11/11). In conclusion, lymphocytes isolated from a single endoscopic biopsy specimen using our simplified and quick procedure are suitable for flow cytometry. Considering that flow cytometry has an important advantage of providing the results on the examination day itself, the results of this study suggest that flow cytometric analysis using our single-step lymphocyte isolation technique can be potentially used to diagnose lymphoma in the gastrointestinal mucosa. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 132 2 2020 ホジキンリンパ腫の治療により神経症状の改善を認めた傍腫瘍性神経症候群の1 例 87 90 EN Ryosuke Ikemachi Department of Hematology, Okayama Red Cross Hospital Kaho Kondo Department of Hematology, Okayama Red Cross Hospital Akihumi Matumura Department of Hematology, Okayama Red Cross Hospital Soichiro Fujii Department of Hematology, Okayama Red Cross Hospital Makoto Takeuchi Department of Hematology, Okayama Red Cross Hospital Kouta Sato Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koji Abe Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tadashi Yoshino Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 　An 86-year-old man was admitted to another hospital with ataxia and general fatigue. Brain MRI scan revealed a high-intensity area in the bilateral thalamus, and he was referred to Okayama University Hospital for detailed examination. Cerebrospinal fluid (CSF) and blood tests showed no evidence of infection or autoimmune encephalitis. An FDG-PET/CT scan revealed systemic lymphadenopathy, and cervical lymph node biopsy showed classical Hodgkin lymphoma. Neurological symptoms were suspicious of paraneoplastic neurological syndrome (PNS), but onco-neural antibodies were not detected in either serum or CSF. He was referred to our hospital, Okayama Red Cross Hospital, for treatment and administered 6 cycles of an ABVD regimen, and an FDG-PET/CT scan showed a complete remission. The brain lesion disappeared and neurological symptoms were improved, so he was diagnosed with PNS. PNS is rare complication associated with malignant lymphoma and early diagnosis is important because neurological symptoms can be improved with anti-cancer treatment. No potential conflict of interest relevant to this article was reported.

Public Library of Science Acta Medica Okayama 1932-6203 15 7 2020 Triple-negative pleomorphic lobular carcinoma and expression of androgen receptor: Personal case series and review of the literature e0235790 EN Kohei Taniguchi Department of Pathology, Okayama University Hospital Shinichi Takada Department of Pathology, Yuai Memorial Hospital Masako Omori Department of Pathology, Kurashiki Medical Center Takuro Igawa Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Midori Filiz Nishimura Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Toshiaki Morito Department of Pathology, National Hospital Organization Iwakuni Clinical Center Kouichi Ichimura Department of Pathology, Hiroshima City Hiroshima Citizens Hospital Tadashi Yoshino Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Pleomorphic lobular carcinoma (PLC) is a histological variant of invasive lobular carcinoma (ILC) and is associated with worse prognosis than classical ILC. It exhibits a greater degree of cellular atypia and pleomorphism and is occasionally accompanied with apocrine morphology. We investigated the immunohistochemical characteristics of samples from 31 Japanese patients with PLC to elucidate the clinicopathological characteristics of PLC including androgen receptor (AR) immunoreactivity. The surrogate molecular subtypes were luminal A-like, luminal B-like, luminal B-like/HER2, HER2-type, and triple-negative in 5, 4, 3, 5, and 14 cases, respectively. AR was positive in 92.8% (13/14) of the triple-negative PLC cases and 100% (10/10) of the non-triple-negative PLC cases. Disease-specific survival was worse in patients with histological grade 3 PLCs than in those with histological grade 2 PLCs (p = 0.007). However, there was no significant difference in the progression-free survival between the two groups (p = 0.152). No other clinicopathological characteristics were associated with prognosis. These results reveal that PLC exhibits various surrogate molecular subtypes and that the triple-negative subtype frequently expresses AR. The observed molecular apocrine differentiation implicates that triple-negative PLC can be categorized into the luminal AR subtype. Furthermore, AR-targeted therapy might be useful for patients with triple-negative PLC. No potential conflict of interest relevant to this article was reported.

Springer Nature Acta Medica Okayama 0893-3952 33 12 2020 Clinicopathological analysis of 34 Japanese patients with EBV-positive mucocutaneous ulcer 2437 2448 EN Tomoka Ikeda Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuka Gion Okayama University Graduate School of Health Sciences Misa Sakamoto Okayama University Graduate School of Health Sciences Tomoyasu Tachibana Department of Otolaryngology, Japanese Red Cross Society Himeji Hospital Asami Nishikori Okayama University Graduate School of Health Sciences Midori Filiz Nishimura Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tadashi Yoshino Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuharu Sato Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Epstein–Barr virus (EBV)-positive mucocutaneous ulcer (EBVMCU) is a unifocal mucosal or cutaneous ulcer that is histologically characterized by proliferating EBV-positive atypical B cells. While EBVMCU demonstrates a histology similar to that of EBV-positive diffuse large B-cell lymphoma (DLBCL), their clinical behavior differs. Thus, characterizing distinguishing features of EBVMCU and EBV-positive DLBCL is critical. To identify unique characteristics between EBVMCU and lymphoma, we analyzed the clinicopathological and genetic features of 34 Japanese patients with EBVMCU and compared them to those of 24 EBV-positive DLBCL patients and 25 EBV-negative DLBCL patients. All patients with EBVMCU had localized ulcerative lesions, and 31 patients (91%) were using immunosuppressants, such as methotrexate (MTX) or hydroxycarbamide. All patients that were followed up with exhibited good prognosis following immunosuppressant reduction or chemotherapy. In addition, 17 EBV-positive DLBCL patients, and 15 EBV-negative DLBCL patients, received chemotherapy (P < 0.001, P < 0.001, respectively). Our data showed that EBVMCU did not increase indicators associated with lymphoma prognosis, such as soluble interleukin 2 receptor (sIL-2R) and lactate dehydrogenase (LDH) compared to those in the EBV-positive DLBCL or EBV-negative DLBCL groups (sIL-2R, P < 0.001, P = 0.025; LDH, P = 0.018, P = 0.038, respectively). However, histologically, EBVMCU exhibited EBV-positive, variable-sized, atypical B-cell proliferation. Thus, EBVMCU was histologically classified as: (1) polymorphous; (2) large cell-rich; (3) classic Hodgkin lymphoma-like; and (4) mucosa-associated lymphoid tissue lymphoma-like. Moreover, genetic analysis showed that immunoglobin heavy chain (IGH) gene rearrangement did not differ significantly between EBVMCU and EBV-positive DLBCL (44% vs. 32%; P = 0.377), or between EBVMCU and EBV-negative DLBCL (44% vs. 58%; P = 0.280). Therefore, it is difficult to distinguish EBVMCU from EBV-positive DLBCL using only pathological and genetic findings, suggesting that clinical information is important in accurately distinguishing between EBVMCU and EBV-positive DLBCL. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 2213-0071 28 2019 Long-term spontaneous remission with active surveillance in IgG4-related pleuritis: A case report and literature review 100938 EN Go Makimoto Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kadoaki Ohashi Department of Allergy and Respiratory Medicine, Okayama University Hospital Kohei Taniguchi Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Junichi Soh Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akihiko Taniguchi Department of Allergy and Respiratory Medicine, Okayama University Hospital Nobuaki Miyahara Department of Medical Technology, Okayama University Graduate School of Health Sciences Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tadashi Yoshino Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshinobu Maeda Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuyuki Kiura Department of Allergy and Respiratory Medicine, Okayama University Hospital Pleural effusion is a relatively rare feature of IgG4-related disease (IgG4-RD). Here, we report a case of a 72-year-old woman who presented with pleural effusion. Although the pleural adenosine deaminase level was increased, surgical biopsy of the pleura and left inguinal lymph node indicated that the effusion was due to IgG4-RD. Active surveillance was initiated because serum IgG4 and pleural effusion naturally decreased and then completely disappeared. The patient has shown no recurrence for >4 years. This case suggests that pleural biopsy can be used to distinguish IgG4-RD from tuberculosis; moreover, some cases with pleural effusion could improve without treatment. No potential conflict of interest relevant to this article was reported.

Japanese Society for Lymphoratic Tissue Research Acta Medica Okayama 1346-4280 59 2 2019 A review of EBV-positive mucocutaneous ulcers focusing on clinical and pathological aspects 64 6471 EN Tomoka Ikeda Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuka Gion Division of Pathophysiology, Okayama University Graduate School of Health Sciences Tadashi Yoshino Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuharu Sato Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Epstein-Barr virus (EBV)-positive mucocutaneous ulcers (EBVMCUs) were first described as a lymphoproliferative disorder in 2010. Clinically, EBVMCUs are shallow, sharply circumscribed, unifocal mucosal or cutaneous ulcers that occur in immunosuppressed patients, including those with advanced age-associated immunosenescence, iatrogenic immunosuppression, primary immune disorders, and HIV/AIDS-associated immune deficiencies. In general, patients exhibit indolent disease progression and spontaneous regression. Histologically, EBVMCUs are characterized by the proliferation of EBV-positive, variable-sized, atypical B-cells. According to conventional histopathologic criteria, EBVMCUs may diagnosed as lymphomas. However, EBVMCUs are recognized as pseudomalignant lesions because they spontaneously regress without anti-cancer treatment. Therefore, overtreatment must be carefully avoided and multilateral differentiation is important. In this article, we reviewed previously reported EBVMCUs focusing on their clinical and pathological aspects in comparison with other EBV-positive B-cell neoplasms. No potential conflict of interest relevant to this article was reported.

Nature Publishing Group Acta Medica Okayama 2045-2322 9 2019 Up-regulation of activation-induced cytidine deaminase and its strong expression in extra- germinal centres in IgG4-related disease 761 EN Yuka Gion Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mai Takeuchi Department of Pathology, Kurume University School of Medicine Rei Shibata Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuyoshi Takata Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoko Miyata-Takata Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yorihisa Orita Department of Otolaryngology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoyasu Tachibana Department of Otolaryngology, Himeji Red Cross Hospital Tadashi Yoshino Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuharu Sato Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Immunoglobulin (Ig) G4-related disease (IgG4-RD) is a systemic disorder involving benign mass formation due to fibrosis and intense lymphoplasmacytosis; the chronic inflammation associated with the disease might also contribute to oncogenesis. Activation-induced cytidine deaminase (AID), normally expressed in germinal centre activated B-cells, is an enzyme that edits DNA/RNA and induces somatic hypermutation and Ig class switching. AID expression is strictly controlled under physiological conditions; however, chronic inflammation and some infectious agents induce its up-regulation. AID is overexpressed in various cancers and may be important in chronic inflammation-associated oncogenesis. We examined AID expression in IgG4-related sialadenitis (n = 14), sialolithiasis (nonspecific inflammation, n = 13), and normal submandibular glands (n = 13) using immunohistochemistry and quantitative real-time polymerase chain reaction (qPCR). Immunohistochemistry revealed significantly more AID-expressing cells in IgG4-related sialadenitis than in sialolithiasis or normal submandibular gland samples (P = 0.02 and P < 0.01, respectively); qPCR yielded similar results. Thus, AID was significantly more up-regulated and had higher expression in extra-germinal centres in IgG4-RD than in non-specific inflammation or normal conditions. This report suggests that IgG4-RD has several specific causes of AID up-regulation in addition to inflammation. Furthermore, chronic inflammation-associated AID-mediated oncogenesis is possible in IgG4-RD. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2049-4173 7 3 2019 Very rare solitary primary peripheral nerve onset cytotoxic molecule-positive peripheral T-cell lymphoma (PTCL) 146 149 EN Namiko Matsumoto Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kota Sato Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshiaki Takahashi Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuko Kawahara Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Taijun Yunoki Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Jingwei Shang Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mami Takemoto Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Nozomi Hishikawa Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasuyuki Ohta Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toru Yamashita Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Maiko Sakamoto Department of Hematology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Eisei Kondou Department of Hematology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Rei Shibata Department of Pathology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tadashi Yoshino Department of Pathology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshifumi Ozaki Department of Orthopedic Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koji Abe Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Here we present the first report of solitary primary peripheral nerve onset cytotoxic molecule (CM)-positive peripheral T-cell lymphoma (PTCL) diagnosed after nerve biopsy. An 84-year-old female with rheumatoid arthritis (RA) complained of asymmetric severe tenderness in her upper limbs. The biopsy pathology revealed a direct invasion of CM-positive PTCL. When RA patients complain of numbness, tenderness, or weakness, lymphomatic peripheral nerve invasion should be considered. No potential conflict of interest relevant to this article was reported.

CANCER INTELLIGENCE Acta Medica Okayama 1754-6605 13 2019 Two cases of gastric mucosa-associated lymphoid tissue (MALT) lymphoma masquerading as follicular gastritis 933 EN Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takehiro Tanaka Department of Pathology, Okayama University Hospital Kenji Nishida Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiromitsu Kanzaki Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiji Kawano Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshiro Kawahara Department of Endoscopy, Okayama University Hospital Tadashi Yoshino Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Okada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences In this report, we describe two cases of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) of the stomach, which presented with multiple small, whitish nodules in the gastric body. The endoscopic appearance was similar to that of lymphoid follicular hyperplasia found in follicular gastritis or nodular gastritis. Both patients were positive for Helicobacter pylori, and the eradication treatment resulted in complete remission of the lymphoma. However, recurrence was noted in one patient. These cases indicate that, although infrequent, gastric MALT lymphoma can show a nodular appearance resembling that of follicular gastritis. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 03858146 46 6 2019 Methotrexate-associated lymphoproliferative disorder with multiple pulmonary nodules and bilateral cervical lymphadenopathy 927 933 EN Seiichiro Makihara Department of Otolaryngology-Head & Neck Surgery, Kagawa Rosai Hospital Shin Kariya Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mai Noujima-Harada Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Nobuya Ohara Department of Pathology, Kagawa Rosai Hospital Tomoyuki Naito Department of Otolaryngology-Head & Neck Surgery, Kagawa Rosai Hospital Junya Matsumoto Department of Otolaryngology-Head & Neck Surgery, Kagawa Rosai Hospital Yohei Noda Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mitsuhiro Okano Department of Otolaryngology, International University of Health and Welfare School of Medicine Tadashi Yoshino Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Kazunori Nishizaki Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences As has been well recognized, methotrexate (MTX) leads to a state of immunosuppression and can provide a basis for the development of lymphoproliferative disorders (LPDs). MTX-associated LPDs can affect nodal sites as well as extranodal sites, though the manifestation of an LPD in the form of multiple pulmonary nodules is rare. Here, we report two cases of MTX-associated LPD with multiple bilateral pulmonary nodules, which was a finding suggestive of lung cancer, and bilateral cervical lymphadenopathy. After withdrawal of MTX, the multiple bilateral pulmonary nodules and bilateral cervical lymphadenopathy disappeared without chemotherapy in both cases. From these results, patients with pulmonary nodules and cervical lymphadenopathy should be examined for head and neck malignant tumors. Also, physicians should carefully check the administration of MTX. In patients with an MTX-associated LPD, we need to make an early diagnosis and consider discontinuing the administration of MTX as soon as possible. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 119 1 2012 Synthetic retinoid Am80 ameliorates chronic graft-versus-host disease by down-regulating Th1 and Th17. 285 295 EN Hisakazu Nishimori Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takanori Teshima Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Haruko Sugiyama Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Koichiro Kobayashi Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yoshiko Yamasuji Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Sachiyo Kadohisa Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hidetaka Uryu Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kengo Takeuchi Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takehiro Tanaka Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tadashi Yoshino Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yoichiro Iwakura Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Mitsune Tanimoto Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Chronic GVHD (cGVHD) is a main cause of late death and morbidity after allogeneic hematopoietic cell transplantation, but its pathogenesis remains unclear. We investigated the roles of Th subsets in cGVHD with the use of a well-defined mouse model of cGVHD. In this model, development of cGVHD was associated with up-regulated Th1, Th2, and Th17 responses. Th1 and Th2 responses were up-regulated early after BM transplantation, followed by a subsequent up-regulation of Th17 cells. Significantly greater numbers of Th17 cells were infiltrated in the lung and liver from allogeneic recipients than those from syngeneic recipients. We then evaluated the roles of Th1 and Th17 in cGVHD with the use of IFN-γ-deficient and IL-17-deficient mice as donors. Infusion of IFN-γ(-/-) or IL-17(-/-) T cells attenuated cGVHD in the skin and salivary glands. Am80, a potent synthetic retinoid, regulated both Th1 and Th17 responses as well as TGF-β expression in the skin, resulting in an attenuation of cutaneous cGVHD. These results suggest that Th1 and Th17 contribute to the development of cGVHD and that targeting Th1 and Th17 may therefore represent a promising therapeutic strategy for preventing and treating cGVHD. No potential conflict of interest relevant to this article was reported.

BioMed Central Acta Medica Okayama 1746-1596 8 2013 De novo CD5-positive diffuse large B-cell lymphomas show high specificity for cyclin D2 expression 81 EN Takuro Igawa Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuharu Sato Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuyoshi Takata Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Noriko Iwaki Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takehiro Tanaka Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naoko Asano Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshinobu Maeda Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yorihisa Orita Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naoya Nakamura Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shigeo Nakamura Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tadashi Yoshino Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 　D cyclins positively regulate the cell cycle and mediate the pathogenesis of some lymphomas. Cyclin D1 overexpression is the hallmark of mantle cell lymphoma, whereas cyclins D2 and D3 are reportedly not as specific to certain lymphomas as cyclin D1. In this study, cyclin D2 was found to be overexpressed in 98% of de novo CD5-positive diffuse large B-cell lymphomas (DLBCLs) (50/51) and in 28% of CD5-negative DLBCLs (14/51). A statistically significant difference was observed between these two groups (p<0.0001). In contrast, no statistical difference was found in the cyclin D3 expression between CD5-positive (18/51) and CD5-negative (24/51) DLBCLs (p=0.23). Based on these findings, cyclin D2 is therefore considered to be closely associated with de novo CD5-positive DLBCLs. This insight may be useful for overcoming the inferior survival of this aggressive lymphoma. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 71 2 2017 Diagnostic Value of Dual-time-point F-18 FDG PET/CT and Chest CT for the Prediction of Thymic Epithelial Neoplasms 105 112 EN Takayoshi Shinya Department of Radiology, Okayama University Hospital Takashi Tanaka Department of Radiology, Okayama University Hospital Junichi Soh Department General Thoracic Surgery, Okayama University Hospital Toshi Matsushita Department of Radiology, Okayama University Hospital Shuhei Sato Department of Radiology, Okayama University Hospital Shinichi Toyooka Department General Thoracic Surgery, Okayama University Hospital Tadashi Yoshino Department of Pathology, Okayama University Hospital Shinichiro Miyoshi Department General Thoracic Surgery, Okayama University Hospital Susumu Kanazawa Department of Radiology, Okayama University Hospital Original Article 10.18926/AMO/54978 We retrospectively assessed the dual-time-point (DTP) F-18 FDG PET/CT findings of thymic epithelial neoplasms (TENs) and investigated the diagnostic capacity of PET/CT compared to that of CT for predicting carcinoma. We calculated the ratio of the standardized uptake value of the tumor and that of the aortic arch (T/M ratio) for both the 90-min early scan and the 2-h delayed scan in 56 TEN patients. We used a multivariate logistic regression (MLR) analysis to estimate the CT features of carcinoma. We compared the diagnostic capacities of PET/CT and chest CT using receiver operating characteristic (ROC) analyses. The ROC curve revealed that the appropriate cut-off T/M ratio value for the highest accuracy was 2.39 with 75.0% accuracy. The area under the curve (AUC) was 0.855. The statistical analyses for DTP scans of 35 TEN patients demonstrated 74.3% accuracy and 0.838 AUC for the early scan versus 82.9% and 0.825 for the delayed scan. The MLR analysis indicated that mediastinal fat infiltration was a predictor of carcinoma. The ROC curve obtained for the model yielded an AUC of 0.853. Delayed scanning could improve the diagnostic capacity for carcinoma. The T/M ratio and mediastinal fat infiltration are predictive of carcinoma with moderate diagnostic accuracy. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 70 6 2016 Two Relapsed Stage III Childhood Anaplastic Large Cell Lymphoma Patients with NPM-ALK Fusion in Bone Marrow from Initial Diagnosis 503 506 EN Yui Kanazawa Department of aPediatrics, Okayama University Hospital Yuka Yamashita Clinical Research Center, Nagoya Medical Center Mitsuhiro Fujiwara Department of Pediatrics, Kurashiki Central Hospital Michiko Muraoka Department of aPediatrics, Okayama University Hospital Kana Washio Department of aPediatrics, Okayama University Hospital Kiichiro Kanamitsu Department of aPediatrics, Okayama University Hospital Hisashi Ishida Department of aPediatrics, Okayama University Hospital Takae Nakano Department of aPediatrics, Okayama University Hospital Miho Yamada Clinical Research Center, Nagoya Medical Center Keizo Horibe Clinical Research Center, Nagoya Medical Center Takehiro Tanaka Department of Pathology, Okayama University Hospital Tadashi Yoshino Department of Pathology, Okayama University Hospital Akira Shimada Department of aPediatrics, Okayama University Hospital Case Report 10.18926/AMO/54815 Childhood anaplastic large cell lymphoma (ALCL) accounts for approx. 10–30 of cases of non-Hodgkin lymphoma, and the ALCL99 study reported 60–75 disease-free survival; however, a relatively high relapse rate was observed (25–30 ). We report 2 patients with Stage III ALCL who relapsed 6–18 months after the end of ALCL99 chemotherapy. A retrospective molecular analysis identified the nucleophosmin (NPM)-anaplastic lymphoma kinase (ALK) fusion gene in the first diagnostic bone marrow samples taken from both patients. However, antibodies against the ALK protein appeared to be relatively low in the serum of both patients (×100 and ×750). An increase in chemotherapy intensity may be beneficial if Stage III ALCL patients are shown to be NPM-ALK chimera-positive in the first diagnostic bone marrow sample. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 128 3 2016 集学的治療により長期生存が得られた食道神経内分泌癌の2 例 207 212 EN Tatsuhiro Gotoda Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine， Dentistry and Pharmaceutical Sciences Seiji Kawano Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine， Dentistry and Pharmaceutical Sciences Yoshiyasu Kono Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine， Dentistry and Pharmaceutical Sciences Kou Miura Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine， Dentistry and Pharmaceutical Sciences Hiromitsu Kanzaki Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine， Dentistry and Pharmaceutical Sciences Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine， Dentistry and Pharmaceutical Sciences Yoshiro Kawahara Department of Endoscopy, Okayama University Hospital Takehiro Tanaka Department of Pathology, , Okayama University Graduate School of Medicine， Dentistry and Pharmaceutical Sciences Tadashi Yoshino Department of Pathology, , Okayama University Graduate School of Medicine， Dentistry and Pharmaceutical Sciences Yasuhiro Shirakawad Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine， Dentistry and Pharmaceutical Sciences Masahiro Tabata Department of Hematology and Oncology, Okayama University Graduate School of Medicine， Dentistry and Pharmaceutical Sciences Mitsune Tanimoto Department of Hematology and Oncology, Okayama University Graduate School of Medicine， Dentistry and Pharmaceutical Sciences Hiroyuki Okada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine， Dentistry and Pharmaceutical Sciences 　Esophageal neuroendocrine carcinoma （ECC） is rare and has a poor prognosis when presenting with vascular invasion and distant metastasis from an early stage. Multidisciplinary therapy with surgery, chemotherapy, and radiation therapy may prolong survival in patients with advanced ECC, but there is as yet no standard therapy for advanced ECC. We treated two patients who have achieved long-term survival （＞ 4 years） who underwent multidisciplinary therapy, including chemotherapy, for ECC. Our experience with these two cases suggests that multidisciplinary therapy, including chemotherapy, may be effective for treating ECC at an advanced stage. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 128 2 2016 拡大内視鏡検査にて形態変化を観察しえた十二指腸濾胞性リンパ腫の1例 111 116 EN Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuyoshi Takata Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiji Kawano Department of Endoscopy, Okayama University Hospital Yoshiro Kawahara Department of Endoscopy, Okayama University Hospital Tadashi Yoshino Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Okada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 　A 63-year-old Japanese woman was diagnosed with duodenal follicular lymphoma. The initial esophagogastroduodenoscopic examination with magnifying observation revealed opaque white spots and enlarged whitish villi. Nine months later, esophagogastroduodenoscopy showed that the size of the lymphoma lesion decreased, and only opaque white spots were visible. The histological analysis of biopsy samples obtained during the initial endoscopy examination showed both neoplastic follicles and an inter-follicular infiltration of lymphoma cells, whereas the biopsy samples obtained at the endoscopy performed 9 months later showed only neoplastic follicle formation. These results suggest that the magnifying endoscopic features may reflect the underlying pathological mechanisms : enlarged whitish villi are probably due to lymphoma cell infiltration in the inter-follicular area, and opaque white spots are probably caused by neoplastic follicle formation. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 127 3 2015 Rituximab併用CHOP療法が奏効した肝原発びまん性大細胞型Ｂ細胞リンパ腫の１例 209 212 EN Hiroshi Okada Soichiro Fujii Kentaro Watanabe Terunobu Shigematu Katsuhiro Miyashita Morihiro Okazaki Haruhiko Kobashi Motohiro Yokoyama Tadashi Yoshino 　A 78-year-old Japanese man was referred to our hospital after experiencing black feces. No abnormal finding was detected in the endoscopic examination of his stomach and large intestines. Computed tomography (CT) of the abdomen revealed a tumor lesion in the right lobe of the liver. A needle biopsy of the tumor under ultrasound guidance was performed. A pathological examination of the biopsy specimen showed a diffuse proliferation of lymphoma cells, which was compatible with diffuse large B-cell lymphoma (DLBCL). F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)-CT demonstrated increased FDG uptake only in the liver tumor. We made the diagnosis of primary DLBCL of the liver. After six cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP), the patient achieved complete remission and has maintained remission for 2 years since the diagnosis. The R-CHOP regimen might be effective therapy for primary DLBCL of the liver. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 69 5 2015 Primary Duodenal Follicular Lymphoma Treated With Rituximab Monotherapy and Followed-up for 15 Years 301 306 EN Anna Seki Masaya Iwamuro Masao Yoshioka Nobuharu Fujii Hiroyuki Okada Soichiro Nose Katsuyoshi Takata Tadashi Yoshino Kazuhide Yamamoto Case Report 10.18926/AMO/53676 A 41-year-old woman was diagnosed with duodenal follicular lymphoma. She had no other lesions and was assigned to a "watch and wait" policy. Swelling of the inguinal lymph nodes appeared 45 months later, and rituximab monotherapy resulted in complete remission. However, follicular lymphoma recurred in the stomach, rectum and mesenteric and external iliac lymph nodes 81 months after the therapy. The patient received rituximab monotherapy again and has remained in complete remission in the fifteenth year after the initial diagnosis. This case suggests the usefulness of rituximab monotherapy in the long-term management of intestinal follicular lymphoma. No potential conflict of interest relevant to this article was reported.

Nature Publishing Group Acta Medica Okayama 2045-2322 5 2015 A subset of ocular adnexal marginal zone lymphomas may arise in association with IgG4-related disease 13539 EN Ohno Kyotaro Sato Yasuharu Ohshima Koh-ichi Takata Katsuyoshi Miyata-Takata Tomoko Takeuchi Mai Gion Yuka Tachibana Tomoyasu Orita Yorihisa Ito Toshihiro H. Swerdlow Steven Yoshino Tadashi We previously suggested a relationship between ocular immunoglobulin (Ig)G4-related disease (IgG4-RD) and marginal zone lymphomas (MZLs). However, the cytokine background associated with these disorders and whether it differs between ocular adnexal MZLs with (IgG4-associated MZL) and without (IgG4-negative MZL) numerous IgG4+ plasma cells are unknown. In this study, we identified the mRNA expression pattern of Th2 and regulatory T-cell (Treg) cytokines in IgG4-RD and in IgG4-associated MZL and IgG4-negative MZL using real-time polymerase chain reaction analysis. Ocular IgG4-RD and IgG4-associated MZL exhibited significantly higher expression ratios of interleukin (IL)-4/β-actin, IL-10/β-actin, IL-13/β-actin, transforming growth factor (TGF) β1/β-actin, and FOXP3/β-actin than did IgG4-negative MZL (p < 0.05). This finding further supports our prior observations that a significant subset of ocular MZLs arises in the setting of IgG4-RD. Furthermore, the presence of a different inflammatory background in IgG4-negative MZLs suggests that IgG4-associated MZLs may have a different pathogenesis. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 69 1 2015 Magnified Endoscopic Features of Duodenal Follicular Lymphoma and Other Whitish Lesions 37 44 EN Masaya Iwamuro Hiroyuki Okada Katsuyoshi Takata Yoshinari Kawai Seiji Kawano Junichiro Nasu Yoshiro Kawahara Takehiro Tanaka Tadashi Yoshino Kazuhide Yamamoto Original Article 10.18926/AMO/53120 The sensitivity and specificity of magnified endoscopic features for differentiating follicular lymphoma from other diseases with duodenal whitish lesions have never been investigated. Here we compared the magnified endoscopic features of duodenal follicular lymphoma with those of other whitish lesions. We retrospectively reviewed the cases of patients with follicular lymphoma (n＝9), lymphangiectasia (n＝7), adenoma (n＝10), duodenitis (n＝4), erosion (n＝1), lymphangioma (n＝1), and hyperplastic polyp (n＝1). The magnified features of the nine follicular lymphomas included enlarged villi (n＝8), dilated microvessels (n＝5), and opaque white spots of various sizes (n＝9). The lymphangiectasias showed enlarged villi, dilated microvessels, and white spots, but the sizes of the white spots were relatively homogeneous and their margin was clear. Observation of the adenoma and duodenitis revealed only whitish villi. Although the lymphangioma was indistinguishable from the follicular lymphomas by magnified features, it was easily diagnosed based on the macroscopic morphology. In conclusion, magnified endoscopic features, in combination with macroscopic features, are useful for differentiating follicular lymphomas from other duodenal diseases presenting whitish lesions. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 0046-8177 45 7 2014 Low-grade B-cell lymphoma presenting primarily in the bone marrow 1379 1387 EN Kayoko Iwatani Katsuyoshi Takata Yasuharu Sato Tomoko Miyata-Takata Noriko Iwaki Wei Cui Seiko Sawada-Kitamura Hiroshi Sonobe Maiko Tamura Katsuhiko Saito Katsuya Miyatani Rie Yamasaki Ichiro Yamadori Nobuharu Fujii Yasushi Terasaki Yoshinobu Maeda Mitsune Tanimoto Naoya Nakamura Tadashi Yoshino Cases of low-grade B-cell lymphoma presenting primarily in the bone marrow are rare, and its clinicopathology remains unclear. We retrospectively examined patients with low-grade B-cell lymphoma presenting primarily in the bone marrow. Fourteen patients met the inclusion criteria, including 5 with lymphoplasmacytic lymphoma (LPL), 3 with chronic lymphocytic leukemia/small lymphocytic lymphoma, 2 with follicular lymphoma (FL), and 4 with low-grade B-cell lymphoma not otherwise specified (LGBCL-NOS). The median age was 69.5 years (range, 42-89 years), and a slight male predominance was noted (9 men and 5 women, 1.8: 1). Immunohistochemically, all cases were positive for CD20. One case was positive for CD138. Both cases of FL were positive for CD10 and B-cell lymphoma 2 (BCL-2), and immunoglobulin heavy locus (IgH)/B-cell lymphoma 2 rearrangement was observed by fluorescence in situ hybridization. The myeloid differentiation primary response gene (88) leucine to proline mutation was observed in 3 of 5 LPL, 1 of 2 FL, and 2 of 4 LGBCL-NOS patients. Paraproteinemia was observed in 10 patients; IgM and IgG paraproteinemia were observed in 6 and 3 patients, respectively. In this patient series, 3 patients had died at a median follow-up of 36.5 months; the cause of death of 1 LPL patient was malignant lymphoma itself. Thus, low-grade B-cell lymphoma presenting primarily in the bone marrow has various subtypes, and approximately one-third of the patients had LGBCL-NOS. The immunophenotypic features and myeloid differentiation primary response gene (88) leucine to proline mutation data of LGBCL-NOS suggested that some cases present with characteristics similar to those of LPL or marginal zone lymphoma. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 1618-1247 100 2 2012 Histological and immunohistochemical features of gingival enlargement in a patient with AML 254 257 EN Norihiro Sonoi Yoshihiko Soga Hiroshi Maeda Koichi Ichimura Tadashi Yoshino Kazutoshi Aoyama Nobuharu Fujii Yoshinobu Maeda Mitsune Tanimoto Richard Logan Judith Raber-Durlacher Shogo Takashiba Here, we discuss the pathophysiology of leukemia-associated gingival enlargement based on a case of acute myelomonocytic leukemia (AML-M4) with typical gingival enlargement. Uniquely, this patient was well enough to allow full periodontal examination and incisional gingival biopsy to be performed both before and after chemotherapy. The patient was a 39-year-old Japanese woman with AML-M4 showing gingival enlargement. Histological and immunohistochemical features of gingiva and bacterial counts in the periodontal pockets were examined before and after chemotherapy. The results were as follows: (1) infiltration of myelomonocytic blasts in enlarged gingiva; (2) resolution of gingival enlargement with complete remission of AML by anticancer chemotherapy; and (3) the numbers of bacteria in the periodontal pockets were not high and were not altered before or after chemotherapy. In patients with AML-M4, remarkable mucosal enlargement is not generally observed in the body except in the gingiva. We hypothesized that antigens derived from periodontal bacteria, even if they are not present in large numbers, could act as chemoattractants for myelomonocytic leukemic cells. No potential conflict of interest relevant to this article was reported.

Public Library Science Acta Medica Okayama 1932-6203 8 2 2013 A20 (TNFAIP3) Deletion in Epstein-Barr Virus-Associated Lymphoproliferative Disorders/Lymphomas EN Midori Ando Yasuharu Sato Katsuyoshi Takata Junko Nomoto Shigeo Nakamura Koichi Ohshima Tamotsu Takeuchi Yorihisa Orita Yukio Kobayashi Tadashi Yoshino A negative regulator of the nuclear factor (NF)-kappa B pathway, A20 (TNFAIP3), is inactivated in several types of lymphomas; particularly in diffuse large B-cell lymphoma (DLBCL), classical Hodgkin's lymphoma, and extranodal marginal zone lymphoma of the mucosa-associated lymphoid tissue. These findings suggest that the NF-kappa B activation is related to A20 inactivation. Recently, A20 inactivation has also been observed in Epstein-Barr virus (EBV)-related lymphomas; however, this occurrence has not been well investigated. Moreover, NF-kappa B is a key molecule in activated B-cell-like (ABC)-type DLBCL; EBV-associated DLBCL is of the ABC type. Therefore, we focused on A20 deletions in EBV-associated lymphoproliferative disorders/lymphomas. Using fluorescent in situ hybridization analysis, A20 deletions were identified in 4 of 13 samples from patients with pyothorax-associated lymphoma (PAL) (31%), 3 of 20 samples from nasal-type NK/T cell lymphomas (NKTLs) (15%), 1 of 8 samples of EBV-positive DLBCL of the elderly (DLBCL-e) (13%), but not in any of the 11 samples from individuals with methotrexate-related lymphoproliferative disorder (MTX-LPD) (0%). Among the samples with A20 deletions, EBV latent membrane protein 1 (LMP-1) expression was detected in all 4 of the PAL samples with A20 deletions and in the DLBCL-e sample with an A20 deletion, but not in any of the 3 NKTL samples. This finding indicated that A20 deletions were not directly related to the EBV latency pattern of lymphomas, although such deletions might be related to the diagnostic category. Immunohistologically, the A20 protein was absent in 2 (15%) of the13 PAL samples, 1 (9%) of 11 MTX-LPD samples, and in none of the 20 NKTL (0%) or 8 DLBCL-e samples. In conclusion, A20 deletion and/or dysfunctional expression are frequently associated with PALs, and A20 abnormalities may be related to the pathogenesis of PAL. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 0945-6317 463 5 2013 In aggressive variants of non-Hodgkin lymphomas, Ezh2 is strongly expressed and polycomb repressive complex PRC1.4 dominates over PRC1.2 697 711 EN Lamia Abd Al Kader Takashi Oka Katsuyoshi Takata Xu Sun Hiaki Sato Ichiro Murakami Tomohiro Toji Akihiro Manabe Hiroshi Kimura Tadashi Yoshino D Polycomb group (PcG) proteins are important for the regulation of hematopoiesis by regulating chromatin compaction and silencing genes related to differentiation and cell cycle. Overexpression of enhancer of zeste homologue 2 (Ezh2) and Bmi-1/PCGF4 has been implicated in solid organ cancers, while Mel-18/PCGF2 has been reported as a tumor suppressor. Detailed expression profiles of PcG proteins and their diagnostic significance in malignant lymphomas are still unknown. In this study, we analyzed the expression levels of Ezh2, Bmi-1, Mel-18, and Ki67 in 197 Hodgkin's and non-Hodgkin's lymphoma patient samples and in lymphoma cell lines using immunohistochemistry, fluorescent immunocytochemistry, and Western blotting. Immunohistochemical staining showed that Ezh2 expression was significantly increased in aggressive compared to indolent subtypes of B cell neoplasms (P = 0.000-0.030), while no significant differences in Bmi-1 expression were found between these subtypes. Compared to the normal counterpart, T cell lymphomas showed significant overexpression of Bmi-1 (P = 0.011) and Ezh2 (P = 0.000). The Ki67 labeling index showed a positive correlation with Ezh2 expression in B cell lymphomas (correlation coefficient (Co) = 0.983, P = 0.000) and T/NK cell lymphomas (Co = 0.629, P = 0.000). Fluorescent immunohistochemical staining showed coexpression of Ezh2 and Ki67 in the same tumor cells, indicating that Ezh2 expression correlates with cell proliferation. Both B and T/NK cell neoplasms showed low expression of Mel-18 and high expression of both Bmi-1 and Ezh2. In conclusion, in aggressive lymphoma variants, Ezh2 is strongly expressed and polycomb repressive complex PRC1.4 dominates over PRC1.2. Coexpression of Bmi-1 and Ezh2 is a characteristic of aggressive lymphomas. Ezh2 correlates with the proliferation and aggressive nature of non-Hodgkin's lymphomas. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 0046-8177 44 9 2013 Distinct morphologic, phenotypic, and clinical-course characteristics of indolent peripheral T-cell lymphoma 1927 1936 EN Eiko Hayashi Katsuyoshi Takata Yasuharu Sato Yukie Tashiro Yoshiro Tachiyama Seiko Sawada-Kitamura Yasushi Hiramatsu Shun Sugiguchi Soichiro Nose Mitsuyoshi Hirokawa Midori Ando Lamia Abd Mader Yoshinobu Maeda Mitsune Tanimoto Tadashi Yoshino Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) consists of a heterogeneous group of lymphomas. Patients. generally show an aggressive clinical course and very poor outcome. Although the 2008 World Health Organization classification of PTCL-NOS includes 3 variants, low-grade lymphoma is not Included. Of 277 PTCL-NOS cases recorded in our consultation files, we examined the clinicopathologic characteristics of 10 patients with T-cell lymphomas composed of small-sized cells with slight nuclear atypia. Eight patients showed extranodal involvement (5 patients, spleen; 3 patients, thyroid), and 5 patients were at clinical stage I or II. Histologically, all samples presented diffuse infiltrate of small lymphoid cells, with few mitotic figures. Immunohistologically, all samples were positive for CD3, and CD:20 Was detected in 5 samples. All samples showed a low Ki-67 labeling index (mean, 1.05%), and 7 samples were positive for central memory T-cell markers. Clonal T-cell receptor gamma chain and/or alpha-beta chain gene rearrangements were detected in all 10 patients. Five patients received chemotherapy, whereas for 3 patients, treatment consisted only of observation following surgical resection of the spleen or thyroid. Nine patients were alive at a median follow-up time of 19.5 months, whereas 1 patient died of an unrelated disease. The present study strongly indicates that T-cell lymphoma with small-sized lymphoma cells and a low Ki-67 labeling index is a distinct variant. Recognition of this novel lymphoma subtype, which should not be defined merely as PTCL-NOS, should be seriously considered. No potential conflict of interest relevant to this article was reported.

Public Library Science Acta Medica Okayama 1932-6203 8 2 2013 Clinicopathologic Analysis of Localized Nasal/Paranasal Diffuse Large B-Cell Lymphoma EN Hiroko Toda Yasuharu Sato Katsuyoshi Takata Yorihisa Orita Naoko Asano Tadashi Yoshino Diffuse large B-cell lymphoma (DLBCL) comprises 2 molecularly distinct subgroups of non-germinal center B-cell-like (non-GCB) and germinal center B-cell-like (GCB) DLBCLs, with the former showing relatively poor prognosis. In the present study, we analyzed the clinicopathological features of 39 patients with localized nasal/paranasal DLBCL. Immunohistochemistry-based subclassification revealed that 11 patients (28%) were of the GCB-type according to Hans' algorithm and 11 (28%) were of the GCB-type according to Choi's algorithm. According to both Hans' and Choi's algorithms, the non-GCB type was predominant. Nevertheless, prognosis was good. Overall survival did not differ significantly between the GCB and non-GCB subgroups (Hans' algorithm: p = 0.57, Choi's algorithm: p = 0.99). Furthermore, the prognosis of localized nasal/paranasal DLBCL was better than that of other localized extranodal DLBCLs. The prognosis of extranodal DLBCL is usually considered poorer than that of nodal DLBCL. However, in our study, no difference was noted between patients with localized nasal/paranasal DLBCL and patients with localized nodal DLBCL. In conclusion, although the non-GCB subtype is thought to show poor prognosis, in our study, the prognosis for localized nasal/paranasal DLBCL patients was good irrespective of subclassification. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 67 4 2013 Large Ulceration of the Oropharynx Induced by Methotrexate-Associated Lymphoproliferative Disorders 265 269 EN Hiroyuki Hanakawa Yorihisa Orita Yasuharu Sato Kinya Uno Kazunori Nishizaki Tadashi Yoshino Case Report 10.18926/AMO/51072 We present a case of a 67-year-old Japanese man with a serious oropharyngeal ulceration that at first seemed to be destructive malignant lymphoma or oropharyngeal carcinoma. We suspected methotrexate (MTX)-associated lymphoproliferative disorder (LPD) induced by MTX treatment for rheumatoid arthritis (RA). About 3 weeks after simple discontinuation of MTX, complete regression of the disease was observed, confirming our diagnosis. No potential conflict of interest relevant to this article was reported.

Wiley-Blackwell Acta Medica Okayama 0902-4441 90 2 2013 Morphologic, flow cytometric, functional, and molecular analyses of S100B positive lymphocytes, unique cytotoxic lymphocytes containing S100B protein 99 110 EN Yukari Miki Yuka Gion Yuriko Mukae Atsushi Hayashi Hiaki Sato Tadashi Yoshino Kiyoshi Takahashi Little is known about the S100B+ lymphocytes, which are unique human peripheral blood lymphocytes (PBL) containing the S100B protein. It has recently been shown that S100B is released from various types of S100B+ cells and exhibits varied cytokine-like activities. In this study, we precisely characterized the S100B+ lymphocytes of healthy adults with respect to the proportion in the whole PBL, immunophenotypes, function, and their S100B mRNA expression and also evaluated their S100B-releasing activity upon stimulation. S100B+ lymphocytes were detected in all individuals examined, and the proportion of S100B+ lymphocytes in the whole PBL ranged from 0.42% to 16.15% (mean, 4.21%). In addition, two subtypes of S100B+ lymphocytes, a CTL subtype (CD3+ CD8+ CD16-) and a NK subtype (CD3- CD8- CD16+), were detected. The majority of the CTL subtype of S100B+ lymphocytes expressed the alpha beta-T-cell receptor. Surprisingly, S100B mRNA was detected not only in S100B+ lymphocytes, but also in every S100B- lymphocytes, although the expression levels of S100B mRNA in S100B- lymphocytes were much lower than those of S100B+ lymphocytes. The CTL subtype of S100B+ lymphocytes exhibited blastic morphological changes, proliferated and released S100B upon stimulation with phytohemagglutinin. The NK subtype of S100B+ lymphocytes exhibited morphological NK activity when cocultivated with NK-sensitive target, K-562 cells. Thus, the CTL subtype of S100B+ lymphocytes exhibit the biological characteristics of T cells, while the NK subtype of S100B+ lymphocytes exhibit the characteristics of NK cells. These results suggest that S100B+ lymphocytes are a particular subtype of cytotoxic lymphocytes that play a unique role in antitumor immunity. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 125 2 2013 十二指腸濾胞性リンパ腫はAIDの発現を欠くがBACH2の発現を有しmemoryB細胞としての性質を有する 103 107 EN Katsuyoshi Takata Yasuharu Sato Naoya Nakamura Mami Tokunaka Yukari Miki Yara Yukie Kikuti Kazuhiko Igarashi Etsuro Ito Hideo Harigae Seiichi Kato Eiko Hayashi Takashi Oka Yoshinobu Hoshii Akira Tari Hiroyuki Okada ABD Alkader Lamia Mohamado Yoshinobu Maeda Mitsune Tanimoto Tomohiro Kinoshita Tadashi Yoshino No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 125 2 2013 外傷性脳傷害に対する抗HMGB-1抗体治療 97 102 EN Yu Okuma Keyue Liu Hidenori Wake Jun Haruma Tadashi Yoshino Aiji Ohtsuka Hideo Takahashi Shuji Mori Masahiro Nishibori Isao Date No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 46 6 1992 Detection of oncogene rearrangements in human non-Hodgkin's lymphomas. 407 415 EN Eisaku Kondo Tadashi Yoshino Tadaatsu Akagi Kazuhiko Hayashi Kiyoshi Takahashi Article 10.18926/AMO/32636 <p>Southern blot hybridization was used to detect the rearrangement and amplification of five proto-oncogenes (bcl-2, bcl-1, c-myc, c-myb and c-Ha-ras) and one tumor suppressor gene (RB-1) in 55 Japanese patients with non-Hodgkin's lymphoma; 16 with T-cell lymphomas and 39 with B-cell lymphomas (7 follicular and 32 diffuse lymphomas). Genetic abnormalities of the proto-oncogenes were detected in 7 of the 55 (13%). Genetic abnormalities of bcl-2 plus other genes were detected in 5 of 7 cases of follicular lymphoma (71%), rearrangements of bcl-2 and c-myc, rearrangement of bcl-2 and amplification of c-myb. Genetic abnormalities were observed in only three cases of diffuse lymphoma. In each of 3 cases of B-cell lymphoma, one of the genes, blc-2 mbr, bcl-2 mcr and c-myc, was rearranged respectively. The incidence of genetic abnormalities in diffuse lymphomas (6.3%) was lower than that in follicular lymphomas. None of diffuse lymphomas had double oncogene abnormality. No abnormalities were found in RB-1, bcl-1, and Ha-ras. These findings suggest that follicular lymphomas are associated with some abnormalities of oncogenes not restricted to bcl-2 that facilitate growth which may be associated with their clinical features.</p> No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 46 4 1992 Establishment and characterization of a cell line, KaMi, from human lung large cell carcinoma. 257 264 EN Hiroshi Takata Tadashi Yoshino Yoshihiko Hoshida Ikuko Takata Tadaatsu Akagi Article 10.18926/AMO/32620 <p>A cell line of human lung large cell carcinoma (LCC) was established directly from the metastatic skin tumor tissue. The clinical course of the patient who carried this carcinoma was peculiar; generalized lymphadenopathy, histologically resembling Hodgkin's disease, was found as the first clinical symptom. The lung tumor was not discovered until the time of autopsy. This cell line (KaMi) grew adherent to culture vessels with the population doubling time of 20.6h, formed colonies in soft agars with efficiency of 22.6%, and formed tumors in athymic nude mice. The authenticity of KaMi was confirmed by chromosomal analysis and isoenzyme patterns. KaMi cells bore a strong resemblance to the original tumor cells which were composed of small spindle cells, large polygonal cells, and multinucleated giant cells. Immunohistochemically, KaMi cells showed a weak tendency to differentiate to squamous cells, and these immunohistochemical reactivities were almost compatible to those of the original tumor cells, but ultrastructurally, KaMi cells were more immature than the original ones. Treatment with several reagents could not augment a differentiation of KaMi cells. Cytokeratin profiles showed a tendency of squamous cell differentiation. KaMi cells may aid in elucidating the pathogenesis and biology of LCC and its relationship to other lung tumors. </p> No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 54 5 2000 Characterization of epstein-barr virus-infected mantle cell lymphoma lines. 193 200 EN Zaishun Jin Norihiro Teramoto Tadashi Yoshino Kenzo Takada Takashi Oka Kazuhiko Hayashi Tadaatsu Akagi Article 10.18926/AMO/32293 <p>It has been reported that Epstein-Barr virus (EBV) resides in resting B cells in vivo. However, an ideal in vitro system for studying EBV latent infection in vivo has not yet been established. In this study, a mantle cell lymphoma line, SP53, was successfully infected with a recombinant EBV containing a neomycin-resistant gene. The EBV-carrying SP53 cells were obtained by selection using G418. They expressed EBER-1, EBNAs, and LMP1; this expression pattern of the EBV genes was similar to that in a lymphoblastoid cell line (LCL). However, proliferation assay showed that the EBV-carrying SP53 cells have a doubling time of 73 h, compared with 57 h of SP53 cells. Transplantation of 10(8) SP53 cells to nude mice formed tumors in 4 of 10 mice inoculated, but the EBV-carrying SP53 cells did not. Unexpectedly, EBV infection reduced the proliferation and tumorigenicity of SP53 cells. However, the EBV-carrying SP53 cells showed higher resistance to apoptosis induced by serum starvation than did the SP53 cells. The inhibition of proliferation and the resistance to apoptosis induced in SP53 cells by EBV infection indicate that this cell line might to some extent provide a model of in vivo EBV reservoir cells.</p> No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 45 3 1991 A monoclonal antibody (OPT1) to T cells which is available for paraffin-embedded materials. 147 154 EN Hiroshi Mukuzono Tadashi Yoshino Tadaatsu Akagi Article 10.18926/AMO/32209 <p>A monoclonal antibody (MAb), OPT1, reactive with T cells in formalin-fixed, paraffin-embedded tissue sections, has been identified through immunization with activated T cells from peripheral blood lymphocytes (PBL). The antibody is an IgG1 antibody as demonstrated by the Ouchterlony technique. By cytofluorometric analysis, almost all CD3+ lymphocytes and only a few CD20+ lymphocytes of peripheral blood expressed the OPT1 antigen. Nonhematolymphoid cell lines were negative for OPT1 by the immunoperoxidase staining using acetone-fixed cell lines. On the contrary, peripheral T cells, cells of two T cell lines out of four and a part of the cells of one B cell line out of two were positive for OPT1. The immunoperoxidase staining of paraffin-embedded tissue sections revealed that most of lymphocytes in T cell areas of lymph nodes expressed OPT1 antigen. Some lymphocytes in both cortex and medulla of the thymus and erythroid precursors of the bone marrow were OPT1+. In the malignant lymphoma series, approximately 90% of T cell lymphomas and 6% of B cell lymphomas reacted with OPT1. None of the Reed-Sternberg cells nor Hodgkin cells in Hodgkin's disease were positive. Consequently, OPT1 may be useful for the diagnosis and study of malignant lymphomas and other related lesions.&#60;/P&#62;</p> No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 45 2 1991 Effect of a long-acting somatostatin analogue (SMS 201-995) on a growth hormone and thyroid stimulating hormone-producing pituitary tumor. 107 115 EN Ryoto Hirasawa Hozo Hashimoto Shinya Makino Shuso Suemaru Toshihiro Takao Zensuke Ota Yoshihiko Hoshida Tadashi Yoshino Tadaatsu Akagi Article 10.18926/AMO/32184 <p>A 46-year-old woman with acromegaly and hyperthyroidism due to a pituitary adenoma. She had high serum thyroid-stimulating hormone (TSH) levels and very high serum growth hormone (GH) levels. Transsphenoidal removal of the tumor, post-operative irradiation, frontal craniotomy for removal of residual tumor and large-dose bromocriptine therapy were carried out consecutively. After therapy, serum GH levels gradually decreased, but not to the normal range, and serum TSH levels remained at inappropriately normal levels. Using immunoperoxidase techniques, GH-, TSH- and follicle-stimulating hormone (FSH)-containing cells were demonstrated in the adenoma. A long-acting somatostatin analogue (SMS 201-995, 600 micrograms/day) suppressed the serum GH level to the normal range with a concomitant suppression of TSH. Furthermore, the paradoxical serum GH responses to TRH and LH-RH were slightly improved. No important subjective side-effects were noted. Therefore, SMS 201-995 appeared to be a very effective drug in this patient with a GH- and TSH-producing pituitary tumor.&#60;/P&#62;</p> No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 58 2 2004 Induction and prevention of virus-associated malignant lymphoma by serial transmission of EBV-related virus from cynomolgus by blood transfusion in rabbits. 67 74 EN Tirtha Raj Koirala Kazuhiko Hayashi Zaishun Jin Sachiyo Onoda Takehiro Tanaka Wakako Oda Koichi Ichimura Nobuya Ohara Takashi Oka Masao Yamada Tadashi Yoshino Okayama University Article 10.18926/AMO/32097 <p>Epstein-Barr virus (EBV)-related herpesvirus (Si-IIA-EBV) was serially transmitted for 3 passages from rabbit to rabbit of the opposite sex by blood transfusion, which subsequently induced virus-associated rabbit lymphomas. The virus could be transmitted by transfusion with 15-20 ml of whole blood (7/7) or irradiated blood (1/6) from the EBV-related virus-infected rabbits, but there was no transmission with transfusion of cell-free plasma (0/6) from the infected rabbits. Passive anti-EBV-VCA IgG (x 20 approximately x 10) titers decreased during the first 1-2 weeks in the transfused rabbits. The virus-transmitted rabbits showed a gradual increase in antibody titers ranging from peak titers of x 640 to x 2560 after 3 weeks of transfusion. The recipient origin of malignant lymphoma that developed in the first rabbit transfused by infected blood was confirmed by chromosomal analysis. This rabbit model thus shows that EBV-related herpesvirus is serially transmissible by blood transfusion and that transmission can not be completely prevented by irradiation of blood, but removal of blood cells is the best way to prevent transmission of EBV-related virus. Therefore, this animal model provides a convenient in vivo system for studies of the prevention and therapy of transfusion-related transmission of EBV and EBV-associated lymphoproliferative diseases in immunocompromised human beings.</p> No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 58 4 2004 Expression and intracellular localization of FKHRL1 in mammary gland neoplasms. 197 205 EN Gui-Shan Jin Eisaku Kondo Takayoshi Miyake Masao Shibata Takako Takashima Yi-Xuan Liu Kazuhiko Hayashi Tadaatsu Akagi Tadashi Yoshino Article 10.18926/AMO/32088 <p>FKHRL1 (FOXO3a), a member of the Forkhead family of genes, has been considered to be involved in the development of breast tumors; however, the in vivo expression and activation status of FKHRL1 in breast tumors still remains unclear. We immunohistochemically demonstrated the expression and intracellular localization of FKHRL1 in human breast tumors by the novel anti-FKHRL1 antibody which is available for formalin-fixed paraffin-embedded specimens. In a total of 51 cases of benign tumors, FKHRL1 was diffusely expressed in all cases, and its intracellular localization was revealed to be cytoplasmic (inactive form) in 94% of cases of intraductal papillomas (16/17) and 91% cases of fibroadenomas (31/34), with a similar pattern to normal glandular epithelium. In invasive ductal carcinomas, 83% of the cases (93/112) diffusely expressed FKHRL1; however, unlike benign tumors, 71% of the cases (66/93) showed the nuclear-targeted, active form of FKHRL1. Moreover, activated FKHRL1 was predominantly observed in scirrhous (29/36, 81% of the cases) and papillotubular (30/38, 79% of the cases) subtypes, compared to the solid-tubular subtype (7/19, 37% of the cases). Furthermore, the cases with nuclear-targeted FKHRL1 showed a tendency to have lymph nodal metastasis with statistical significance (P < 0.0001). Thus, the activation of FKHRL1 seems to be recognized as one of the specific features of invasive ductal carcinoma of the breast.</p> No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 63 3 2009 Infusion of Hypertonic Saline into the Lung Parenchyma during Radiofrequency Ablation of the Lungs with Multitined Expandable Electrodes:Results Using a Porcine Model 137 144 EN Tatsuhiko Iishi Takao Hiraki Hidefumi Mimura Hideo Gobara Taichi Kurose Hiroyasu Fujiwara Jun Sakurai Hiroyuki Yanai Tadashi Yoshino Susumu Kanazawa Original Article 10.18926/AMO/31848 <p>The present study was performed to clarify the effect of hypertonic saline infusion into the lung parenchyma on radiofrequency ablation (RFA) of the lungs. A total of 20 ablation zones were created in 3 pigs. The ablation zones were divided into 3 groups. Group 1 (n6) consisted of ablation zones created by applying smaller radiofrequency (RF) power without saline infusion;group 2 (n5) zones were created by applying greater RF power without saline infusion;and group 3 (n9) zones were created by applying greater RF power with saline infusion. The techniques of saline infusion included administration of hypertonic saline 1ml before RFA, followed by continuous administration at a rate of 1ml/min during the first 2min after the initiation of RFA. The ablation parameters and coagulation necrosis volumes were compared among the groups. Group 3 had a tendency toward smaller mean impedance than group 1 (p0.059) and group 2 (p0.053). Group 3 showed significantly longer RF application time than group 2 (p0.004) and significantly greater maximum RF power than group 1 (p0.001) and group 2 (p0.004). Group 3 showed significantly larger coagulation necrosis volume (mean, 1,421mm3) than group 2 (mean, 858mm3, p0.039) and had a tendency toward larger necrosis volume than group 1 (mean, 878mm3, p0.077). Although this small study had limited statistical power, hypertonic saline infusion during RFA appeared to enlarge coagulation necrosis of the lung parenchyma.</p> No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 63 2 2009 Expression of thyroglobulin on follicular dendritic cells of thyroid mucosa-associated lymphoid tissue (MALT) lymphoma 71 78 EN Mitsuru Munemasa Tadashi Yoshino Keita Kobayashi Takayoshi Miyake Sumie Takase Sakugawa Tomohiko Mannami Katsuji Shinagawa Mitsune Tanimoto Tadaatsu Akagi Original Article 10.18926/AMO/31834 <p>Reportedly, thyroid mucosa-associated lymphoid tissue (MALT) lymphoma is closely associated with Hashimoto's thyroiditis. However, it remains unknown which antigen is closely associated with thyroid MALT lymphoma. We examined whether B cell response to thyroglobulin (Tg), which is a common thyroid-specific autoantigen, is related etiologically to the pathogenesis of thyroid MALT lymphoma. Expression of human Tg antigens and Cluster of differentiation (CD) 35 was examined immunohistochemically in 15 cases of thyroid MALT lymphoma using paraffin-embedded, formalin-fixed tissue specimens. In all cases of thyroid MALT lymphoma, human Tg was detected immunohistochemically in the follicular epithelial cells and follicular dendritic cells (FDCs). These FDCs were positive by double immunostaining for anti-human Tg rabbit polyclonal antibody (Ab) and for CD35. Results showed that the Tg, a thyroid autoantigen, had immunostained the germinal center of the thyroid MALT lymphoma. The Tg was present in the FDCs, as revealed by the staining pattern of the germinal center;this fact was confirmed by double immunostaining of anti-human Tg mouse monoclonal Ab and anti-CD35 mouse monoclonal Ab. The results of our study suggest that Tg is an autoantigen that is recognized by thyroid MALT lymphoma cells.</p> No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 41 1 1987 Metaplastic bone formation in a hyperplastic polyp of the stomach: a case report. 43 46 EN Yuji Ohtsuki Yoshifumi Danbara Isao Takeda Kiyoshi Takahashi Kazuhiko Hayashi Hiroshi Sonobe Tadashi Yoshino Tadaatsu Akagi Article 10.18926/AMO/31765 <p>Metaplastic bony tissue along with hyperplastic mucosal epithelium showing no atypism was detected in biopsy materials from a Yamada type I gastric polyp. The tissue was metaplastic woven bone associated with calcification. Histogenesis of the bone formation is as yet unknown. This is the first reported case of the presence of metaplastic bone accompanied by hyperplastic gastric mucosa so far.</p> No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 53 1 1999 Hydrocortisone Sodium Succinate Suppressed Production of Interleukin-10 by Human Peripheral Blood Mononuclear Cells: Clinical Significance 55 59 EN Hideo Kohka Hiromi Iwagaki Tadashi Yoshino Kenta Kobashi Shinnya Saito Hiroshi Isozaki Norihisa Takakura Noriaki Tanaka Article 10.18926/AMO/31646 <p>Corticoids are well known for their immunosuppressive properties. Interleukin-10 (IL-10) is an intrinsic antiinflammatory peptide in immune diseases, originally identified as cytokine synthesis inhibitory factor. We examined the effect of hydrocortisone sodium succinate (HSS) on the production of IL-10 by human peripheral blood mononuclear cells (PBMCs). PBMCs from healthy volunteers and cancer-burden patients were preincubated separately with or without HSS for 1 h, then stimulated with 5 microg/ml lipopolysaccharide (LPS). Production of IL-10 by human PBMCs was detected with LPS stimulation and its production was higher in cancer-burden patients than in normal volunteers, although this was not statistically significant. HSS suppressed production of IL-10 by LPS-stimulated PBMCs in a dose-dependent manner both in normal volunteers and in cancer-burden patients. These results indicate that, in addition to their antiinflammatory properties, corticoids act to restore the immunosuppressive states even in cancer-burden states</p> No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 47 1 1993 Distribution of Lectin Receptors in the Human Hyperplastic Tonsil: Histochemical and Flow Cytometric Analyses 13 19 EN Ashit Baran Sarker Tadaatsu Akagi Tadashi Yoshino Kotaro Fujiwara Soichiro Nose Article 10.18926/AMO/31606 <p>The distribution of lectin receptors in the human tonsil was studied using 16 biotinylated lectins. The avidin-biotin-peroxidase complex (ABC) method was used on frozen and paraffin-embedded tissue sections. Cell suspensions were also analysed by dual flow cytometry using respective fluorescein isothiocyanate-conjugated lectins and phycoerythrin-labeled anti-CD3 and anti-human immunoglobulin. Frozen sections fixed with acetone and paraffin-embedded materials fixed in three solutions were compared for lectin affinity; ethanol-fixed sections gave best results followed by frozen and buffered formalin-fixed ones, then nonbuffered formalin. Con-A, RCA-1, LcH, WGA, MPA, PHA, PSA, PNA, SJA and GSA-1 reacted with all tissue components of the tonsil in immunohistochemical studies, but binding intensity was fixative dependent. Binding of Lotus and BPA to lymphocytes was limited to germinal center lymphocytes. Other tissue components were also reactive but staining intensity was weaker in Lotus compared with BPA. SBA and DBA did not react with lymphocytes, but reacted with macrophages/histiocytes, vascular endothelia, and epithelial cells. LBA and LPA were constantly negative with all tissue components irrespective of fixatives. Flow cytometric analyses showed that all but three (DBA, LBA and LPA) partially or totally stained lymphocyte surfaces. Lotus receptors were expressed exclusively on B-lymphocytes.</p> No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 47 3 1993 Expression of a lymphocyte adhesion molecule (CD44) in malignant lymphomas: relevance to primary site, histological subtype and clinical stage. 215 222 EN Kotaro Fujiwara Tadashi Yoshino Kenji Miyake Nobuya Ohara Tadaatsu Akagi Article 10.18926/AMO/31588 <p>Lymphocyte adhesion molecules defined by anti-CD44 antibody (Hermes-3) may be involved in lymphocyte binding to high endothelial venules at sites where lymphocytes exist the blood. CD44 expression was immunohistochemically examined in 167 well characterized cases of malignant lymphomas (MLs). None of 12 nodal follicular lymphomas (FLs) were CD44+, whereas 3 of 4 extranodal ones showed distinct CD44 expression. In contrast to nodal FLs, 28 of the 38 (74%) nodal diffuse B-cell lymphomas were CD44+ (p < 0.0001). T-cell lymphomas showed a significantly higher expression of CD44 antigen than diffuse B-cell lymphomas in the nodal cases (p < 0.04), but not in the extranodal ones. In nodal diffuse lymphomas, 3 of 5 stage I lymphomas (60%) were CD44+ in contrast to 53 of 63 stage II-IV lymphomas (84%), but the difference was not statistically significant. Of 14 Hodgkin's diseases, 9 cases were CD44+ with no significant correlation with clinical stage. The data of flow cytometric analysis confirmed the results of immunohistochemical analysis. In conclusion, CD44 expression is relevant to primary sites of distinctive MLs originating in the mucosal regions (MALToma) and some histological subtypes, but the relation with clinical stage was not defined. Some other adhesion molecules or different mechanisms must also be taken into account concerning the genesis and the expansion of MLs.</p> No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 48 3 1994 Endoscopical Segmental Piecemeal Tumorectomy for Nodular Elevation of Colorectal Tumor: Applicability and Patient's Quality of Life 169 171 EN Norifumi Ariki Hiromi Iwagaki Tadashi Yoshino Yasuyuki Nonaka Shigeatsu Fujiki Jose Antonio Perdomo Akio Hizuta Jun Tomoda Noriaki Tanaka Takao Tsuji Kunzo Orita Article 10.18926/AMO/31124 <p>Endoscopical segmental piecemeal tumorectomy (ESPT) for nodular elevation of colorectal tumor is advantageous in terms of minimizing both surgical invasion and postoperative burden to the patients. Nodular elevation of colorectal tumors is said to occur when the body of the tumor is adenomatous and the surface of the focal cancer grows more horizontally into the lumen than vertically. We report here four cases of nodular elevation of colorectal tumors which were each treated by different surgical procedures.</p> No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 48 2 1994 Partial Purification and Chraracterization of Dendritic Cell Differentiation Factor 67 72 EN Katsuya Miyatani Kiyoshi Takahashi Hiroyuki Yanai Tadashi Yoshino Tadaatsu Akagi Article 10.18926/AMO/31108 <p>Previously, we reported that interleukin-2 (IL-2)-stimulated helper T cells produced an unknown soluble factor which induced dendritic cell-like differentiation in primary cultures of monocytic leukemia cells and we referred to this factor as dendritic cell differentiation factor (DCDF). In this study, we attempted to purify and characterize DCDF and investigated its biological effect on normal human monocytes. Gel filtration chromatography indicated that the molecular weight of DCDF is approximately 30-35 kDa. Chromatofocusing indicated that the isoelectric point of DCDF is approximately 5.0. DCDF, partially purified by subsequent gel filtration, chromatofocusing, and hydrophobic chromatography, significantly enhanced the HLA-DR expression of normal human monocytes and a human monocytic leukemia cell line, THP-1. This biological activity was not neutralized by any known antibodies to human cytokines. DCDF significantly amplified the T-cell stimulatory activity of monocytes in the allogeneic mixed leukocyte reaction (MLR). Moreover, DCDF significantly enhanced IL-1 beta and IL-6 production by monocytes in a dose-dependent manner. These results suggest that DCDF is a novel human cytokine which stimulates the accessory cell function of monocytes.</p> No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 48 4 1994 Application of polymerase chain reaction (PCR) to the microscopically identified cells on the slides: evaluation of specificity and sensitivity of single cell PCR. 189 193 EN Norihiro Teramoto Yuji Tonoyama Tadaatsu Akagi Ashit Baran Sarker Tadashi Yoshino Ichiro Yamadori Kiyoshi Takahashi Article 10.18926/AMO/31091 <p>The sensitivity and specificity of single cell polymerase chain reaction (PCR) were studied. Its high sensitivity enabled detection of a single-copy gene, such as human T-lymphotropic virus type I genome in paraffin sections. The rate of obtaining positive signals with this method was affected by the number of copies of the gene in the target cell. Specificity was satisfactory if the procedure was properly and carefully followed. Since the single cell PCR is a time-consuming method which requires skill and experience to pick up the target cells accurately, the applicability of this method is limited. It works best when it is used to analyze a single or a few copy genes in histologically identified cells.</p> No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 43 3 1989 Immortalization of rat spleen and thymus T cells by human T-cell leukemia virus type I. 143 151 EN Tadaatsu Akagi Hiroshi Takata Tadashi Yoshino Norihiro Teramoto Shoki Yano Takashi Oka Article 10.18926/AMO/30886 <p>Co-cultivation of thymus and spleen cells of Fisher and Lewis rats with lethally irradiated MT-2 cells harboring human T-cell leukemia virus type I (HTLV-I) resulted in the establishment of lymphoid cell lines, FIRT-1, FIRS-1, LERT-1, and LERS-1, respectively. Cells of these cell lines had rat T-cell characters as demonstrated by the positive reaction to monoclonal antibodies (MAbs) to rat T cell antigens (Thy 1 and pan T). They lacked surface immunoglobulins and strongly expressed rat interleukin-2 receptor antigen (Tac) and Ia antigen. Karyotypic analysis revealed that they had the normal rat karyotype in early cultures, but showed marked aneuploidy after long cultivation. None of them expressed HTLV gag proteins (p19 and p24) or virus particles, but they contained HTLV-I proviral DNA monoclonally and weakly expressed pX gene products (p40x). They were not transplantable into syngeneic newborn rats.</p> No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 43 4 1989 Ontogeny of S-100 protein-positive histiocytes and lymphocytes in the human fetal lymphoreticular system. 203 210 EN Tadaatsu Akagi Soichiro Nose Kiyoshi Takahashi Tadashi Yoshino Yasushi Horie Makoto Motoi Hiroshi Sonobe Hideaki Enzan Article 10.18926/AMO/30854 <p>In the human lymphoreticular system, the alpha and beta subunits of S-100 protein are found in ordinary monocyte-macrophages and non-phagocytic histiocytes such as Langerhans cells and interdigitating reticulum cells, respectively. The beta subunit is also present in some CD8+ T cells. In the present study, we investigated the ontogeny of these histiocytes and lymphocytes in humans. Yolk sacs and 4 to 21-week fetuses were examined immunohistochemically for the presence of S-100 protein subunits using antisera monospecific to each subunit. S-100 alpha + macrophages were present in the yolk sacs and the hepatic sinusoids of the 4th week embryos prior to bone marrow hematopoiesis. These macrophages later appeared in other lymphoid organs when anlagen of these organs were formed. No S-100 beta + cells were found in the yolk sacs. S-100 beta+ histiocytes were first detected in the hepatic sinusoids of the 5th week embryo, and after the 8th week of gestation, they were distributed in other lymphoid organs. S-100 beta+ lymphocytes were not found in the liver. They were first detected in the thymus at the 12th week of gestation, and were subsequently distributed in other lymphoid organs. These results suggest that S-100 beta+ lymphocytes and histiocytes may belong to different cell lineages, and the former may not be the precursor of the latter.</p> No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 51 4 1997 Analysis of the genome of an Epstein-Barr-virus (EBV)-related herpesvirus in a cynomolgus monkey cell line (Si-IIA) 207 212 EN Hideo Ino Kazuhiko Hayashi Hiroyuki Yanai Norihiro Teramoto Tirtha Raj Koirala Hong-Li Chen Takashi Oka Tadashi Yoshino Kiyoshi Takahashi Tadaastu Akagi Article 10.18926/AMO/30764 <p>A simian cell line, Si-IIA, harboring Epstein-Barr-virus (EBV) -related herpesvirus (Si-IIA-EBV), produces malignant lymphoma in rabbits when administered by intravenous inoculation. In this study, we analyzed the Si-IIA-EBV genome and compared it with human EBV and herpesvirus macaca fascicularis 1 (HVMF 1 ), which is associated with B-cell lymphoma developing in SIV-infected immunosuppressed monkeys. DNA from Si-IIA-EBV was amplified by the polymerase chain reaction using three different primer pairs complementary to human EBV (B95-8) DNA; two of the primer pairs covered part of the long internal repeat 1 region (IR 1) and the third covered part of the BRRF 1 region. Direct sequencing of the three PCR products revealed that Si-IIA-EBV DNA had about 82% nucleotide homology to the human EBV DNA in all three regions and 92.4% homology to HVMF1 in the IR1 region. The blotting pattern by Southern blot analysis was different between Si-IIA-EBV and human EBV.</p> No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 50 3 1996 Regulation of Interleukin-2 Receptor y Chain mRNA Expression in Human Monocytic Cell Line THP-1 145 150 EN Hiroyuki Yanai Tadashi Yoshino Kiyoshi Takahashi Yoshifumi Ninomiya Tadaatsu Akagi Article 10.18926/AMO/30509 <p>Circulating hepatitis C virus (HCV) particles can be fractionated by means of differential flotation centrifugation. It is reported that in the bottom fraction HCV is in the form immune complexes, whereas in the top, it is free of antibodies. We evaluated the significance of circulating complex and free HCV in chronic hepatitis C, and assessed the relationship in terms of the response to interferon (IFN) therapy. We examined sera before, just after, and 1 year after administering IFN to 18 patients with chronic hepatitis C, 10 of whom responded (group CR), and 8 did not (group NR). The amounts of virus were similar between both groups before therapy. After differential flotation centrifugation with 1.063 g/ml of NaCl, the top and bottom fractions were assayed for HCV RNA. Before therapy, HCV RNA was detected in the top fraction in 1 of 10 in group CR, and in 6 of 8 in group NR (P &#60; 0.05, chi-square test). HCV RNA was positive in the bottom fraction of all samples. In a follow-up study of group NR, HCV RNA was detected in the top fraction in 3 of 8 just after IFN therapy, and in 7 of 8 after 1 year. This study suggests that the presence of HCV in the top fraction can predict a poor response to IFN therapy.</p> No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 50 5 1996 Variable expression of Epstein-Barr virus latent membrane protein I in Reed-Sternberg cells of Hodgkin's disease. 267 270 EN Norihito Teramoto liu Cao Nobuhiro Kawasaki Yuji Tonoyama Ashit Baran Sarker Tadashi Yoshino Kiyoshi Takahashi Tadaatsu Akagi Article 10.18926/AMO/30493 <p>&#60;P&#62;Reed-Sternberg cells (RS cells) of Hodgkin's disease (HD) are frequently infected with Epstein-Barr virus (EBV) and express EBV-encoded nonpolyadenylated RNA transcripts (EBER)-1. EBV latency has been classified into three distinct forms: Latency I, expressing only one of the latent proteins, EBV nuclear antigen (EBNA)-1, latency II, coexpressing EBNA-1 and LMPs, and latency III, expressing all latent viral proteins. RS cells express LMP-1 in addition to EBNA-1 and are considered to be EBV latency II frequently encountered in nasopharyngeal carcinoma. We examined 13 cases of EBV-infected HD by combined EBER-1 in situ hybridization and immunostaining for LMP-1. All of the RS cells expressed EBER-1, but a substantial number of EBER-1+ RS, cells were negative for LMP-1. The percentage of LMP-1+ RS cells out of EBER-1+ RS cells varied from 7% to 100% (average 69%). In this study, we showed that all EBV-infected RS cells were not restricted to latency II, and some belonged to latency I.&#60;/P&#62;</p> No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 50 2 1996 Detection of Epstein-Barr virus RNA and related antigens in non-neoplastic lymphoid lesions. 89 96 EN Yuji Tonoyama Norihiro Teramoto Ashit Baran Sarker Tadashi Yoshino Kazuhiko Hayashi Kiyoshi Takahashi Tadaatsu Akagi Article 10.18926/AMO/30484 <p>To elucidate the latent state and reactivation of Epstein-Barr virus (EBV) in non-neoplastic lymphoid lesions, we investigated 144 non-neoplastic lymphoid lesions by in situ hybridization (ISH) to detect the expression of EBV-encoded small RNAs (EBER)-1 and BCRF-1 and by immunostaining for latent membrane protein (LMP)-1 and ZEBRA. ISH for EBER-1 detected EBER-1-positive cells (EPC) in 31 of the 144 examined lesions (22%). EPC were detected in 4 of 49 cases of nonspecific lymphoid hyperplasia, in 16 of 20 abscess-forming granulomatous lymphadenitis (AFGL), 5 of 25 Kikuchi's disease, and in 3 of 3 infectious mononucleosis. LMP-1 was expressed in 6 of 124 non-neoplastic lymphoid lesions (4.8%). LMP-1-positive cells were observed in 6 of the 31 EBER-1-positive cases (19%). EPC were detected significantly more frequently in LMP-1- and ZEBRA-positive specimens than in the LMP-1- and ZEBRA-negative specimens. BCRF-1 was expressed in 4 of 11 cases examined: 2 of 3 AFGL, 1 of 2 Kikuchi's disease, and in the 1 case of atypical lymphoid hyperplasia. This study suggests that Epstein-Barr virus is prevalent and can be reactivated in the lymph nodes effaced by destructive inflammation, such as AFGL. Such inflammation may provide a local milieu that is conducive for EBV to enter the lytic cycle.</p> No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 44 5 1990 Primary non-Hodgkin's lymphoma of the rectum: a case report. 279 282 EN Luis Fernando Moreira Hiromi Iwagaki Kazuhiko Watanabe Tadashi Yoshino Sadanori Fuchimoto Kunzo Orita Article 10.18926/AMO/30452 <p>A rare gastrointestinal tract neoplasm, primary non-Hodgkin's B-cell lymphoma in a 39-year-old, asymptomatic woman is described. The tumor was originally localized in the rectum without evidence of any other lymphoma-involved organ and treated by curative surgical procedure associated with postoperative chemotherapy.</p> No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 44 5 1990 Comparison of monoclonal antibodies reactive with lymphocyte subsets in routinely fixed paraffin-embedded material: flow cytometric analyses, immunoperoxidase staining and influence of fixatives. 243 250 EN Tadashi Yoshino Yoshihiko Hoshida Ichiro Murakami Kiyoshi Takahashi Tadaatsu Akagi Article 10.18926/AMO/30447 <p>We have attempted to clarify the characteristics of monoclonal antibodies (MAbs) detecting lymphocyte subsets in fixed materials. We examined by means of flow cytometric technique influences of fixatives and reactivity with malignant lymphomas (MLs). Specific markers for T-cells were UCHL1 and OPD4, which reacted especially with helper/inducer T-cells. MT1 recognized almost all of T-cells from peripheral blood and tonsils, but reacted with a part of B-MLs. As for B-cell markers, L26 was the most reliable marker for B-MLs. L26 and MB1 antigens could not be detected on living cells flow cytometrically. LN1 reacted with a part of T-cells as well as B-cells, but fluorescent intensity of the former was apparently stronger than that of the latter. Although LN2 antigen was located mainly in the cytoplasm close to the nuclear membrane immunohistochemically, it could be detected on living cells flow cytometrically. LN2 positive cells belonged to B-cells in peripheral blood and tonsils. When fixed for relatively short time, B5 and buffered formalin were better for examining MAbs than non-buffered formalin and ethanol.</p> No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 38 2 1984 Immunohistochemical demonstration of lysozyme in normal, reactive and neoplastic cells of the mononuclear phagocyte system. 125 133 EN Makoto Motoi Tadashi Yoshino Kenji Kawabata Ikuko Ikehara Shozo Ohsumi Katsuo Ogawa Article 10.18926/AMO/30333 <p>Using the peroxidase antiperoxidase (PAP) method, lysozyme (LZM) was shown to exist in normal, reactive and neoplastic cells belonging to the mononuclear phagocyte system (MPS), but was not detected in histiocytosis X cells. Immunostaining for cytoplasmic LZM by the PAP method is useful for identification of mononuclear phagocytes and for diagnosis of the diseases in which these cells participate.</p> No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 122 1 2010 IgG4 関連疾患 77 79 EN Yasuharu Sato Tadashi Yoshino No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 120 3 2008 ラット中脳動脈閉塞・再灌流モデルにおける抗 HMGB1 単クローン抗体の治療効果 271 277 EN Keyue Liu Shuji Mori Hideo Takahashi Yasuko Tomono Hidenori Wake Toru Kanke Yasuharu Sato Norihito Hiraga Naoto Adachi Tadashi Yoshino Masahiro Nishibori No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 113 1 2001 胃 MALTリンパ腫：基礎 87 91 EN No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 00301558 119 3 2008 エピジェネティクス 323 325 EN Katsuyoshi Takata Tadashi Yoshino No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 00301558 119 2 2007 非小細胞肺癌における癌・精巣抗原XAGE-1の発現と免疫応答の解析 127 129 EN Kazuhiko Nakagawa Yuji Noguchi Hideo Okumura Shuichiro Sato Motoyuki Tanaka Michihide Shimono Ali Mohamed Ali Eldib Motoi Aoe Toshiro Ono Akiko Uenaka Nobuya Ohara Tadashi Yoshino Kazuki Yamashita Tsukasa Tsunoda Nobuyoshi Shimizu Eiichi Nakayama No potential conflict of interest relevant to this article was reported.