Faculty Profiles - SATO Yasuharu

Papers - SATO Yasuharu

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Young adult patients with squamous cell carcinoma of the tongue strongly express p16 without human papillomavirus infection Reviewed

Tomoyasu Tachibana, Yorihisa Orita, Yuka Gion, Kentaro Miki, Kana Ikegami, Hidenori Marunaka, Takuma Makino, Yusuke Akagi, Naoki Akisada, Munechika Tsumura, Toshihiro Ito, Tadashi Yoshino, Kazunori Nishizaki, Yasuharu Sato

Acta Oto-Laryngologica 139 ( 1 ) 80 - 84 2019.1

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

Background: Long-term smoking and drinking are known to contribute to the onset of tongue cancer (TC). However, the increasing incidence of TC in younger adults has been suggested to be associated with other factors. Objectives: The present study investigated the relationship between TC and human papillomavirus (HPV) infection. Material and methods: Clinical records and surgically resected specimens from 86 patients (<40-years-old, n = 12; ≥40-years-old, n = 74) with TC were analyzed. Strong nuclear and cytoplasmic p16 staining was considered positive. HPV DNA (high-risk subtypes: 16, 18, 31, 33, 35, 52b, and 58; low-risk subtypes: 6 and 11) was detected using consensus primer-mediated polymerase chain reaction. Results: Strong p16 expression was observed in 10 (11.6%) patients. HPV DNA was detected in 9 (10.5%) patients (high-risk subtypes, n = 2; low-risk subtypes, n = 7). Strong p16 expression was observed more frequently among younger adults than among older adults (33.3% vs. 8.1%; p =.045). p16 staining did not correlate with the detection of HPV DNA (correlation coefficient, 0.113; p =.300). Conclusions and significance: In TC, p16 expression was not associated with HPV infection, suggesting that it may be caused by a different mechanism.

DOI： 10.1080/00016489.2018.1541506

Factors that prolong the duration of recovery in acute rhinosinusitis with orbital complications. Reviewed International journal

Tomoyasu Tachibana, Shin Kariya, Yorihisa Orita, Michihiro Nakada, Takuma Makino, Takenori Haruna, Yuko Matsuyama, Yasutoshi Komatsubara, Yuto Naoi, Yasuharu Sato, Kazunori Nishizaki

Acta oto-laryngologica 139 ( 1 ) 52 - 56 2019

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Regarding prognostic factors of acute rhinosinusitis (ARS) with orbital complications, there are few studies including adult cases. OBJECTIVES: The present study aims to delineate prognostic factors of ARS with orbital complications. MATERIAL AND METHODS: We conducted a retrospective analysis of medical records of 21 patients (6 pediatric and 15 adult patients) with ARS with orbital complications. The duration of recovery was defined as the time from initial diagnosis to complete resolution of local findings and all symptoms. Orbital complications due to postoperative cysts or mycosis were excluded. RESULTS: Twenty-one patients comprised 11 males and 10 females. Chandler's classification showed group I in 4, group II in 8, and group III in 9. None of six pediatric patients required any surgical intervention, whereas five adult patients (23.8%) underwent surgical intervention. The average period of recovery was 8.1 days. In univariate analysis, the duration of recovery was significantly longer among adult cases (p < .01) and cases with Chandler's groups II-III (p = .019). In multivariate analysis, adult patients had a significantly longer duration of recovery than pediatric patients (p = .027). CONCLUSION AND SIGNIFICANCE: The present study suggested that ARS with orbital complications may have prolonged clinical course in adults.

DOI： 10.1080/00016489.2018.1539516

Frequent structural variations involving programmed death ligands in Epstein-Barr virus-associated lymphomas. Reviewed International journal

Keisuke Kataoka, Hiroaki Miyoshi, Seiji Sakata, Akito Dobashi, Lucile Couronné, Yasunori Kogure, Yasuharu Sato, Kenji Nishida, Yuka Gion, Yuichi Shiraishi, Hiroko Tanaka, Kenichi Chiba, Yosaku Watatani, Nobuyuki Kakiuchi, Yusuke Shiozawa, Tetsuichi Yoshizato, Kenichi Yoshida, Hideki Makishima, Masashi Sanada, Masahiro Onozawa, Takanori Teshima, Yumiko Yoshiki, Tadao Ishida, Kenshi Suzuki, Kazuyuki Shimada, Akihiro Tomita, Motohiro Kato, Yasunori Ota, Koji Izutsu, Ayako Demachi-Okamura, Yoshiki Akatsuka, Satoru Miyano, Tadashi Yoshino, Philippe Gaulard, Olivier Hermine, Kengo Takeuchi, Koichi Ohshima, Seishi Ogawa

Leukemia 33 ( 7 ) 1687 - 1699 2019

Language：English Publishing type：Research paper (scientific journal)

Viral infection induces potent cellular immunity and activated intracellular signaling, which may dictate the driver events involved in immune escape and clonal selection of virus-associated cancers, including Epstein-Barr virus (EBV)-positive lymphomas. Here, we thoroughly interrogated PD-L1/PD-L2-involving somatic aberrations in 384 samples from various lymphoma subtypes using high-throughput sequencing, particularly focusing on virus-associated lymphomas. A high frequency of PD-L1/PD-L2-involving genetic aberrations was observed in EBV-positive lymphomas [33 (22%) of 148 cases], including extranodal NK/T-cell lymphoma (ENKTL, 23%), aggressive NK-cell leukemia (57%), systemic EBV-positive T-cell lymphoproliferative disorder (17%) as well as EBV-positive diffuse large B-cell lymphoma (DLBCL, 19%) and peripheral T-cell lymphoma-not otherwise specified (15%). Predominantly causing a truncation of the 3'-untranslated region, these alterations represented the most prevalent somatic lesions in ENKTL. By contrast, the frequency was much lower in EBV-negative lymphomas regardless of histology type [12 (5%) of 236 cases]. Besides PD-L1/PD-L2 alterations, EBV-positive DLBCL exhibited a genetic profile distinct from EBV-negative one, characterized by frequent TET2 and DNMT3A mutations and the paucity of CD79B, MYD88, CDKN2A, and FAS alterations. Our findings illustrate unique genetic features of EBV-associated lymphomas, also suggesting a potential role of detecting PD-L1/PD-L2-involving lesions for these lymphomas to be effectively targeted by immune checkpoint blockade.

DOI： 10.1038/s41375-019-0380-5

A Long-term Survival after Surgical Treatment for Atypical Aortic Coarctation Complicating Takayasu Arteritis with Inactive Disease at the Diagnosis: An Appropriately Treated Autopsy Case. Reviewed

Yoshida M, Zoshima T, Hara S, Mizushima I, Fujii H, Yamada K, Sato Y, Harada K, Kawano M

Intern Med. 58 ( 15 ) 2241 - 2246 2019

Expression of T-cell receptor signalling pathway components in extranodal NK/T-cell lymphoma

Tomoko Miyata-Takata, Shih-Sung Chuang, Katsuyoshi Takata, Tomohiro Toji, Yoshinobu Maeda, Yasuharu Sato, Tadashi Yoshino

Histopathology 73 ( 6 ) 1030 - 1038 2018.12

Language：English Publishing type：Research paper (scientific journal) Publisher：Blackwell Publishing Ltd

Aims: Although the neoplastic cells of extranodal natural killer (NK)/T-cell lymphoma (ENKTL) usually do not express T-cell antigens, the T-cell receptor (TCR) gene might be rearranged and TCR protein expressed. The aim is to elucidate the expression of the downstream TCR pathway components and their importance in ENKTL. Methods and results: We used formalin-fixed paraffin-embedded tissues from 91 ENKTL samples to immunohistochemically characterise the expression of TCR pathway components. The following proteins were variably expressed: ZAP70 (94%
83/88), GRAP2/GADS (68%
60/88), DOK2 (42%
38/90), LCK (35%
31/88), and ITK (10%
9/90). When these tumours were classified as being of T lineage (16%), NK lineage (45%), or indeterminate lineage (38%), the GRAP2/GADS expression rate was higher in T lineage tumours (versus NK, P = 0.0073
versus indeterminate, P = 0.00082). GRAP2/GADS-positive NK lineage tumours more frequently expressed DOK2 (P = 0.0073), and were more often confined to the nasal areas (P = 0.014). Furthermore, when these tumours were immunophenotypically classified into a T signature (42%) or NK signature (58%), the expression rates of GRAP2/GADS and ITK were higher in T signature tumours (P = 0.00074 and P = 0.067, respectively), whereas that of LCK was higher in NK-signature tumours (P = 0.10). Conclusions: Although some ENTKL cases were polyclonal for TCR rearrangement and others lacked TCR expression, we speculate that the TCR pathway might be functioning in ENKTLs. A T signature versus a NK signature might be better for delineating the physiology of ENKTL than cellular lineage. Furthermore, ITK may represent a potential therapeutic target for patients with ITK-expressing tumours.

DOI： 10.1111/his.13728

Computed Tomography Findings for Diagnosing Follicular Thyroid Neoplasms. Reviewed

Takuma Makino, Yorihisa Orita, Tomoyasu Tachibana, Hidenori Marunaka, Kentaro Miki, Naoki Akisada, Yusuke Akagi, Yoshiyuki Usui, Yasuharu Sato, Tadashi Yoshino, Kazunori Nishizaki

Acta medica Okayama 72 ( 6 ) 577 - 581 2018.12

Language：English Publishing type：Research paper (scientific journal)

Since no diagnostic method has been established to distinguish follicular thyroid carcinoma (FTC) from follicular thyroid adenoma (FTA), surgery has been the only way to reach a diagnosis of follicular neoplasm. Here we investigated the computed tomography (CT) features of follicular neoplasms, toward the goal of being able to identify specific CT features allowing the preoperative differentiation of FTC from FTA. We retrospectively analyzed the cases of 205 patients who underwent preoperative CT of the neck and were histopathologically diagnosed with FTC (n=31) or FTA (n=174) after surgery between January 2002 and June 2016 at several hospitals in Japan. In each of these 205 cases, non-enhanced and contrast-enhanced CT images were obtained, and we analyzed the CT features. On univariate analysis, inhomogeneous features of tumor lesions on contrast-enhanced CT were more frequently observed in FTC than in FTA (p=0.0032). A multivariate analysis identified inhomogeneous features of tumor lesions on contrast-enhanced CT images as an independent variable indicative of FTC (p=0.0023). CT thus offers diagnostic assistance in distinguishing FTC from FTA.

DOI： 10.18926/AMO/56375

Recent progress in follicular lymphoma in Japan and characteristics of the duodenal type

Tadashi Yoshino, Katsuyoshi Takata, Takehiro Tanaka, Yasuharu Sato, Akira Tari, Hiroyuki Okada

PATHOLOGY INTERNATIONAL 68 ( 12 ) 665 - 676 2018.12

Language：English Publisher：WILEY

The incidence of lymphoma has rapidly increased over the last 40 years in Japan, following a trend that is very similar to that of breast cancer. In particular, the relative frequency of follicular lymphoma (FL) has reached that in Western countries. Given its indolence, a "watch-and-wait" approach is often applied to FL patients. We have shown that FL is often detected in the second portion of the duodenum and has a distinct follicular dendritic cell distribution and heavy chain variable usage similar to mucosa-associated lymphoid tissue (MALT) lymphoma. Although the t(14;18)(q32;q21) frequency is the same as in the nodal subtype of FL, there are also ongoing mutations, immunopositivity for cluster of differentiation 10 and B-cell lymphoma (BCL)6, and overexpression of BCL2. Gene expression profiling has shown that it is more similar to gastric MALT lymphoma than to nodal FL. Duodenal-type FL lacks the activation-induced cytidine deaminase (AID) expression observed in nodal ones, although this may be compensated for by BTB domain and CNC homolog 2. Based on these findings, duodenal-type FL has been included in the Revised 4th edition of the World Health Organization classification published in late 2017.

DOI： 10.1111/pin.12733

The efficacy and safety of anti-interleukin-6 receptor monoclonal blockade in a renal transplant patient with Castleman disease: early post-transplant outcome. Reviewed International journal

Masatoshi Matsunami, Yoshifumi Ubara, Keiichi Sumida, Yoichi Oshima, Masahiko Oguro, Kazuya Kinoshita, Kiho Tanaka, Yuki Nakamura, Keiichi Kinowaki, Kenichi Ohashi, Takeshi Fujii, Takuro Igawa, Yasuharu Sato, Yasuo Ishii

BMC nephrology 19 ( 1 ) 263 - 263 2018.10

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Multicentric Castleman disease (MCD) is an uncommon lymphoproliferative disease characterized by systemic inflammatory reactions associated with the dysregulated production of interleukin-6 (IL-6). In patients with MCD, renal involvement is uncommon, with only one report published regarding kidney transplantation (KTx) to treat end-stage renal disease (ESRD) secondary to MCD. Recent clinical observations have shown that IL-6 production is implicated in allograft rejection, while IL-6 receptor blockade (with tocilizumab [TCZ]) reduces alloantibody generation and thereby improves graft survival; however, the efficacy and safety of TCZ in MCD patients undergoing KTx is still unknown. CASE PRESENTATION: Herein, we describe the case of a 50-year-old man with MCD who received living-donor KTx for ESRD. Post-operative immunosuppression consisted of a triple-drug regimen (tacrolimus, mycophenolate mofetil and methylprednisolone) with TCZ that was administered intravenously every 2 weeks. At 17 months post-transplantation, the patient remains asymptomatic, and the allograft pathology has shown no evidence of rejection and no development of de novo donor-specific antibody (DSA). CONCLUSIONS: To our knowledge, this is the second reported case of an MCD patient with ESRD who underwent successful KTx. TCZ safely supported the patient during the perioperative period, and this drug may be useful for blocking the generation of donor-specific antibodies and reducing the risk of rejection episodes. KTx in combination with TCZ is thus considered a viable treatment option for ESRD due to MCD.

DOI： 10.1186/s12882-018-1065-4

Serum soluble interleukin-2 receptor as a biomarker in immunoglobulin G4-related disease Reviewed

Tomohiro Handa, Shoko Matsui, Hajime Yoshifuji, Yuzo Kodama, Hiroshi Yamamoto, Seijiro Minamoto, Yuko Waseda, Yasuharu Sato, Keishi Kubo, Tsuneyo Mimori, Tsutomu Chiba, Toyohiro Hirai, Michiaki Mishima

Modern Rheumatology 28 ( 5 ) 838 - 844 2018.9

Publishing type：Research paper (scientific journal)

© 2017, © 2017 Japan College of Rheumatology. Objectives: Serum soluble interleukin-2 (IL-2) receptor (sIL-2R) might reflect disease activity in immunoglobulin G4-related disease (IgG4-RD). We aimed to elucidate the clinical significance of blood markers, including sIL-2R, in patients with IgG4-RD. Methods: We enrolled 59 patients with IgG4-RD and investigated the association between blood markers (white blood cells, C-reactive protein, sIL-2R, IgG, IgG4, IgE, total hemolytic complement), and clinical indices. Results: At baseline, serum sIL-2R (Rs = 0.532, p <.001) and IgG4 (Rs = 0.545, p <.001) levels showed significant correlation to the number of organs involved. During follow-up period (median, 70 months; range, 7–195 months), 40 patients were treated with corticosteroids. Receiver operating characteristic (ROC) analysis showed that baseline sIL-2R levels most accurately predicted patients requiring glucocorticoid treatment (area under the ROC curve, 0.807). Among the 46 patients who improved, sIL-2R and IgG4 levels decreased in 42 and 41 patients, respectively. Among them, serum sIL-2R levels decreased to a normal range in 42 patients (91%), whereas IgG4 levels normalized in 19 (41%). Conclusion: The serum sIL-2R level is a potential biomarker for IgG4-RD that may reflect the number of involved organs and may predict patients requiring glucocorticoid treatment.

DOI： 10.1080/14397595.2017.1416739

Gastrointestinal manifestation of immunoglobulin G4-related disease: clarification through a multicenter survey Reviewed

Kenji Notohara, Terumi Kamisawa, Kazushige Uchida, Yoh Zen, Mitsuhiro Kawano, Satomi Kasashima, Yasuharu Sato, Masahiro Shiokawa, Takeshi Uehara, Hajime Yoshifuji, Hiroko Hayashi, Koichi Inoue, Keisuke Iwasaki, Hiroo Kawano, Hiroyuki Matsubayashi, Yukitoshi Moritani, Katsuhiko Murakawa, Yoshio Oka, Masatoshi Tateno, Kazuichi Okazaki, Tsutomu Chiba

Journal of Gastroenterology 53 ( 7 ) 845 - 853 2018.7

Language：English Publishing type：Research paper (scientific journal) Publisher：Springer Tokyo

Background: Several reports on immunoglobulin (Ig)G4-related disease (IgG4-RD) with gastrointestinal involvement (IgG4-related gastrointestinal disease
IgG4-GID) have been published, although this entity has not been fully established clinicopathologically. Thus, we carried out a multicenter survey. Methods: Patients with possible IgG4-GID who underwent resection were collected. Histologic slides were reevaluated, and eight cases with diffuse lymphoplasmacytic infiltration but without numerous neutrophils, granulations or epithelioid granulomas were further analyzed. Results: Overall, the IgG4 counts (87–345/high-power field) and IgG4/IgG-positive ratio were high (44–115%). The demographic findings included advanced age among the patients (55–80 years) and male preponderance (six cases). Six lesions (five gastric, one esophageal), consisting of lymphoplasmacytic infiltration with neural involvement in the muscularis propria and/or bottom-heavy plasmacytosis in the gastric mucosa, were histologically regarded as highly suggestive of IgG4-RD. Storiform fibrosis and obliterative phlebitis were found in two cases, and the former gave rise to a 7-cm-sized inflammatory pseudotumor (IPT) in one case. Ulceration and carcinoma co-existed in three and two lesions, respectively. All the patients had other organ involvement (OOI), and serum IgG4 levels were markedly elevated (four of five patients). The remaining two cases with gastric IPTs featuring reactive nodular fibrous pseudotumor or nodular lymphoid hyperplasia were regarded as possible cases of IgG4-RD because of the histologic findings and lack of OOI. Conclusions: IgG4-GID is found in the setting of IgG4-RD, often with ulceration or cancer. Characteristic histologic findings are observed in the muscularis propria and gastric mucosa. Cases with IPT may be heterogeneous, and there may be mimickers of IgG4-GID.

DOI： 10.1007/s00535-017-1420-4

Overexpression of folate receptor alpha is an independent prognostic factor for outcomes of pancreatic cancer patients Reviewed

Shizuma Omote, Katsuyoshi Takata, Takehiro Tanaka, Tomoko Miyata-Takata, Yoshiyuki Ayada, Mai Noujima-Harada, Rika Omote, Tetsuya Tabata, Yasuharu Sato, Tatsuya Toyokawa, Hironari Kato, Takahito Yagi, Hiroyuki Okada, Tadashi Yoshino

Medical Molecular Morphology 51 ( 4 ) 1 - 7 2018.6

Language：English Publishing type：Research paper (scientific journal) Publisher：Springer Tokyo

Pancreatic cancer has a poor prognosis
hence, novel prognostic markers and effective therapeutic targets should be identified. We aimed to evaluate folate receptor alpha (FR-α) expression in pancreatic cancer and examine its association with clinicopathological features. We utilized tissue samples from 100 primary pancreatic cancer patients who underwent surgery. FR-α was expressed in 37 of 100 cases (37%). The FR-α-positive group (median, 18.8 months) had a significantly poorer prognosis than the FR-α-negative group [median 21.3 months
HR 1.89 (1.12–3.12)
P = 0.017]. These groups were not significantly different regarding progression-free survival (P = 0.196). Furthermore, other serum tumor markers including CA19-9 (mean, 186 vs. 822 U/ml
P = 0.001), Dupan-2 (286 vs. 1133 U/ml
P = 0.000), and Span-1 (69.7 vs. 171.9 U/ml
P = 0.006) were significantly downregulated in the FR-α-positive group. CA19-9 was another prognostic factor, in addition to FR-α, and patient prognosis showed clear stratification curves with the expression of these two molecules. Along with CA19-9, FR-α expression was an independent prognostic factor for the overall survival. FR-α and CA19-9 helped predict patient prognosis based on stratification curves.

DOI： 10.1007/s00795-018-0197-8

Prognostic factors and importance of recognition of adult croup Reviewed

Tomoyasu Tachibana, Yorihisa Orita, Takuma Makino, Yasutoshi Komatsubara, Yuko Matsuyama, Yuto Naoi, Michihiro Nakada, Yasuharu Sato, Kazunori Nishizaki

Acta Oto-Laryngologica 138 ( 6 ) 579 - 583 2018.6

Language：English Publishing type：Research paper (scientific journal) Publisher：Taylor and Francis Ltd

Objectives: Croup, or laryngotracheobronchitis, is a common disease in childhood. On the other hand, to our knowledge, there are only 14 cases in six English literatures describing adult croup (AC). The clinical features of AC have not been well known. Methods: We conducted a retrospective analysis of medical records of 18 patients with AC during the period from 2008 to 2016. Results: None of the 18 patients required an urgent airway intervention. Univariate analysis indicated that the duration of symptoms was significantly longer in patients with cough (p &lt
.01) and younger patients (age &lt
60, p =.037). The duration of subglottic edema was significantly longer in female (p =.035), patients with high levels of CRP (≥1 mg/dL, p =.049), and patients with cough symptom (p =.035). Conclusions: Female, young age (&lt
60 years), the symptom of cough, and high levels of CRP should be recognized as signs of prolonged AC. It is important to confirm the diagnosis of AC by laryngoscopic examination, which also help to avoid airway intervention.

DOI： 10.1080/00016489.2017.1422140

Neck metastasis in patients with T1-2 supraglottic cancer Reviewed

Tomoyasu Tachibana, Yorihisa Orita, Hidenori Marunaka, Sei-ichiro Makihara, Misato Hirai, Yuka Gion, Kana Ikegami, Kentaro Miki, Takuma Makino, Yasuyuki Noyama, Yasutoshi Komatsubara, Miyuki Kimura, Tadashi Yoshino, Kazunori Nishizaki, Yasuharu Sato

Auris Nasus Larynx 45 ( 3 ) 540 - 545 2018.6

Language：English Publishing type：Research paper (scientific journal) Publisher：Elsevier Ireland Ltd

Objectives: Unlike glottic cancer, supraglottic cancer often presents with neck metastases. This different might be attributable to the location of the primary lesion. This study aimed to clarify the relationships between the sublocation of T1-2 supraglottic cancer, human papillomavirus (HPV) infection, neck metastasis, and prognosis of supraglottic cancer. Methods: This retrospective clinical study investigated 55 Japanese patients with T1-2 supraglottic cancer treated between 1994 and 2015. Results: Of 55 patients with T1-2 supraglottic cancer, neck metastasis was present at initial diagnosis in 14 patients (25.5%). Presence of neck metastasis was the only factor associated with worse prognosis of T1-2 supraglottic cancer (p = 0.004). In multivariate analysis, age &lt
70 years (p = 0.033) and sublocation of the primary lesion in the superior epilaryngeal portion (p = 0.017) were significantly associated with presence of neck metastasis in multivariate analysis. Twelve (27.9%) of 43 patients showed positive results for human papillomavirus infection. However, human papillomavirus infection was not associated with prognosis, presence of neck metastasis, or primary lesion sublocation in T1-2 supraglottic cancer. Conclusion: Relatively young patients with supraglottic cancer at the superior epilaryngeal portion are more likely to show neck metastasis. Human papillomavirus infection was not associated with frequency of neck metastasis.

DOI： 10.1016/j.anl.2017.06.002

Diffuse large B-cell lymphoma of the lacrimal sac arising from a patient with IgG4-related disease Reviewed

Hidenori Marunaka, Yorihisa Orita, Tomoyasu Tachibana, Kentaro Miki, Takuma Makino, Tadashi Yoshino, Kazunori Nishizaki, Yasuharu Sato

Modern Rheumatology 28 ( 3 ) 559 - 563 2018.5

Authorship：Last author Language：English Publishing type：Research paper (scientific journal) Publisher：Taylor and Francis Ltd

A rare case of diffuse large B-cell lymphoma (DLBCL) possibly induced by IgG4-related disease is described. A 78-year-old woman was presented with a mass of the right lacrimal sac that extended to the inferior nasal meatus through the nasolacrimal duct. Pathological diagnosis was DLBCL with diffuse distribution of IgG4 + cells in the background of this lesion. The chronic inflammatory state of IgG4-related disease could have caused the development of DLBCL.

DOI： 10.3109/14397595.2015.1131353

Gastrointestinal follicular lymphoma: Current knowledge and future challenges Invited Reviewed

Katsuyoshi Takata, Tomoko Miyata-Takata, Yasuharu Sato, Masaya Iwamuro, Hiroyuki Okada, Akira Tari, Tadashi Yoshino

Pathology International 68 ( 1 ) 1 - 6 2018.1

Language：English Publishing type：Research paper (scientific journal) Publisher：Blackwell Publishing

The gastrointestinal (GI) tract is the most commonly involved site of extranodal follicular lymphoma (FL). GI-FL shows very indolent clinical behavior and localized at GI tract without any progression or transformation compared to nodal FL. The most frequently involved site of the GI tract was the duodenum followed by the jejunum and ileum, and only 15% of FL arising in the second part of the duodenum were localized there without scattered very small daughter lesions in other GI tract examined by double-balloon endoscopy. The typical macroscopic appearance of GI-FL was multiple white nodules. Microscopically, neoplastic cells were small- to medium-sized lymphoid cells and formed neoplastic follicles. Most of the cases (&gt
95%) were histologically Grade 1 to 2 (low grade). Several pathological and molecular characteristics were seen in GI-FL (especially duodenal FL) compared with nodal FL: immunoglobulin heavy chain deviation to VH4 and VH5
memory B-cell immunophenotype
and molecular features shared by mucosa-associated lymphoid tissue lymphoma. Considering the pathological and molecular uniqueness of this disease, GI-FL should be separately managed from nodal FL.

DOI： 10.1111/pin.12621

Expression of T-cell Receptor Signaling Pathway Components in Extranodal NK/T-cell Lymphoma Reviewed

Tomoko Takata, Katsuyoshi Takata, Shih-Sung Chuang, Yasuharu Sato, Tadashi Yoshino

LABORATORY INVESTIGATION 98 559 - 559 2018

Factors in glucocorticoid regimens associated with treatment response and relapses of IgG4-related disease: a multicentre study. Reviewed International journal

Mirei Shirakashi, Hajime Yoshifuji, Yuzo Kodama, Tsutomu Chiba, Motohisa Yamamoto, Hiroki Takahashi, Kazushige Uchida, Kazuichi Okazaki, Tetsuya Ito, Shigeyuki Kawa, Kazunori Yamada, Mitsuhiro Kawano, Shintaro Hirata, Yoshiya Tanaka, Masafumi Moriyama, Seiji Nakamura, Terumi Kamisawa, Shoko Matsui, Hiroto Tsuboi, Takayuki Sumida, Motoko Shibata, Hiroshi Goto, Yasuharu Sato, Tadashi Yoshino, Tsuneyo Mimori

Scientific reports 8 ( 1 ) 10262 - 10262 2018

Language：English Publishing type：Research paper (scientific journal)

Glucocorticoids (GC) are effective for treating IgG4-related disease (IgG4-RD); however, relapse is often observed. We conducted a retrospective multicentre study to investigate risk factors in GC regimens associated with relapses of IgG4-RD. Data on 166 patients with definitive IgG4-RD diagnosis were collected from 12 institutions. Comprehensive surveillance of clinical backgrounds and GC regimens as well as multivariate analysis of factors associated with treatment responses and relapses was performed. To determine the initial maximal GC dose, the patients were stratified into three groups depending on the initial prednisolone (PSL) dosage: <0.39, 0.4-0.69 and >0.7 mg/kg/day. The multivariate analysis extracted the disease duration and reduction speed of initial GC dose. Patients treated with initial GC <0.39 or >0.7 mg/kg/day of PSL showed higher relapse rates than those treated with 0.4-0.69 mg/kg/day. The relapse rates were significantly higher in patients with fast reduction of the initial dose (>0.4 mg/day) than in patients with slow reduction (<0.4 mg/day). To avoid relapse, 0.4-0.69 mg/kg/day of initial PSL with slow reduction speed (<0.4 mg/day) is needed in the early treatment of IgG4-RD.

DOI： 10.1038/s41598-018-28405-x.

Mast Cells Exhibiting Strong Cytoplasmic Staining for IgE and High Affinity IgE Receptor are Increased in IgG4-Related Disease. Reviewed International journal

Kenji Nishida, Yuka Gion, Mai Takeuchi, Takehiro Tanaka, Tatsuki R Kataoka, Tadashi Yoshino, Yasuharu Sato

Scientific reports 8 ( 1 ) 4656 - 4656 2018

Authorship：Last author,　Corresponding author Language：English Publishing type：Research paper (scientific journal)

Immunoglobulin G4 (IgG4)-related disease is characterized by elevated serum IgG4 levels and increased numbers of IgG4-positive cells. However, its pathogenesis is not fully understood. We previously suggested that mast cells may play an important role in IgG4-related disease. In this study, we confirmed the characteristics of mast cells in IgG4-related lymphadenopathy by using immunohistochemistry and dual immunofluorescence. We analyzed 23 cases of IgG4-related lymphadenopathy and compared them with 23 cases of non-specific lymphoid hyperplasia. The majority of patients with IgG4-related lymphadenopathy had cervical lesions with involvement of other organs. Immunohistologically, mast cells with strong cytoplasmic staining for immunoglobulin E and high affinity immunoglobulin E receptor were significantly increased in IgG4-related lymphadenopathy as compared to those in non-specific lymphoid hyperplasia (mean: 3.83 ± 3.99 cells per high power field and 7.14 ± 8.21 cells per high power field, respectively; P = 0.007 and P = 0.011). In addition, dual immunofluorescence assay showed that immunoglobulin E and high affinity immunoglobulin E receptor staining exhibited a cytoplasmic granular pattern in IgG4-related lymphadenopathy, suggesting internalization of the antibodies and receptors. Our findings showed that mast cell activation might be involved in the pathogenesis of IgG4-related disease.

DOI： 10.1038/s41598-018-23043-9.

Laryngeal squamous cell papilloma is highly associated with human papillomavirus Reviewed

Yorihisa Orita, Yuka Gion, Tomoyasu Tachibana, Kana Ikegami, Hidenori Marunaka, Seiichiro Makihara, Yasuhiko Yamashita, Kentaro Miki, Takuma Makino, Naoki Akisada, Yusuke Akagi, Miyuki Kimura, Tadashi Yoshino, Kazunori Nishizaki, Yasuharu Sato

Japanese Journal of Clinical Oncology 48 ( 4 ) 350 - 355 2018

Publishing type：Research paper (scientific journal)

Objective: To delineate the association between characteristics of adult-onset laryngeal squamous cell papilloma and human papillomavirus (HPV) infection. Methods: Clinical records and paraffin-embedded specimens of 77 papilloma patients who had been treated between 1998 and 2014 were collected. Of the 77 cases, 34 were identified in the larynx, 28 in the oral cavity and 15 in the oropharynx. Specimens were investigated by polymerase chain reaction (PCR) to detect HPV 6, 11, 16, 18, 31, 33, 35, 52b and 58, and immunohistochemical (IHC) staining for anti-p16 antibody. Results: In 21 cases (61.8%) with laryngeal squamous cell papilloma, various types of HPV were detected: 14 cases (41.2%) were positive of high-risk HPV, 18 (52.9%) were positive of low-risk HPV and 11 (32.4%) were positive of both high-risk HPV and low-risk HPV. Younger patients (<60 years) showed a higher rate of HPV infection than older patients. Among the 34 cases with laryngeal papilloma, no malignant transformation was observed during the study period. With IHC staining, positive expression of p16 was observed in 20 cases (58.8%). HPV infection and p16-expression were associated with the pathological finding of koilocytosis. Only four cases (14.3%) showed HPV-positivity in the oral cavity, and none of the 15 oropharyngeal cases were positive for HPV, and none of the oral cavity and oropharyngeal cases showed koilocytosis. Results of HPV-PCR and p16-IHC staining were significantly correlated each other. Conclusions: HPV infection is frequently associated with laryngeal squamous cell papilloma, and koilocytosis is a characteristic pathological finding. To the best of our knowledge, this is the first report which have described infections with multiple HPV types in laryngeal papilloma. INK4a

DOI： 10.1093/jjco/hyy009.

A20 (TNFAIP3) Alterations in Primary Intestinal Diffuse Large B-cell Lymphoma Reviewed

Masayoshi Fujii, Katsuyoshi Takata, Shih-Sung Chuang, Tomoko Miyata-Takata, Midori Ando, Yasuharu Sato, Tadashi Yoshino

ACTA MEDICA OKAYAMA 72 ( 1 ) 23 - 30 2018

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

The gastrointestinal (GI) tract is the most frequently involved site of extranodal non-Hodgkin lymphomas, and diffuse large B-cell lymphoma (DLBCL) is the most common subtype occurring in the GI tract. TNFAIP3 (A20) genetic alterations were reported to be involved in DLBCL's pathogenesis and a portion of GI-DLBCL cases harbor this alteration. However, the frequency and clinicopathological relations focusing on small and large intestinal DLBCL are unclear. Here, we examined A20 deletion and protein expression and analyzed the clinicopathological features of 52 cases of primary intestinal DLBCL. The most frequently involved site was the ileocecal region (75%), followed by small bowel (13.5%) and large intestine. Immunohistochemically, the ileocecal cases expressed BCL6 (p=0.027) and MUM1 (p=0.0001) significantly more frequently than the small intestinal cases. Six of 47 cases (13%) had A20 heterozygous deletion, whereas all 6 heterozygously deleted cases had detectable A20 protein expression. In summary, A20 abnormality was less prevalent among intestinal DLBCLs with some discordancy between gene deletion and protein expression. Although the A20 alteration status did not affect any clinicopathological characteristics in this series, further studies exploring alterations of A20 and other NF-kappa B components in primary intestinal DLBCL are needed.

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