Faculty Profiles - SHIMADA Kazuyuki

Papers - SHIMADA Kazuyuki

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Methotrexate-associated lymphoproliferative disorders of T-cell phenotype: clinicopathological analysis of 28 cases. Open Access

Satou A, Tabata T, Miyoshi H, Kohno K, Suzuki Y, Yamashita D, Shimada K, Kawasaki T, Sato Y, Yoshino T, Ohshima K, Takahara T, Tsuzuki T, Nakamura S

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc Vol. 32 ( 8 ) page： 1135 - 1146 2019.7

Language：English Publisher：Modern Pathology

Methotrexate-associated lymphoproliferative disorders are categorized as “other immunodeficiency-associated lymphoproliferative disorders in the WHO classification. Methotrexate-associated lymphoproliferative disorder is mainly a B-cell lymphoproliferative disorders or Hodgkin lymphoma type, whereas T-cell lymphoproliferative disorders are relatively rare (4–8%). Only a small number of methotrexate-associated T-cell lymphoproliferative disorders have been detailed thus far. Because of the rarity, methotrexate-associated T-cell lymphoproliferative disorder has not been well studied and its clinicopathological characteristics are unknown. A total of 28 cases of methotrexate-associated T-cell lymphoproliferative disorders were retrospectively analyzed. Histologically and immunohistochemically, they were divided into three main types: angioimmunoblastic T-cell lymphoma (n = 19), peripheral T-cell lymphoma, NOS (n = 6), and CD8+ cytotoxic T-cell lymphoma (n = 3). Among the 28 cases, only one CD8+ cytotoxic T-cell lymphoma case was Epstein-Barr virus-positive. The other 27 cases were negative for Epstein-Barr virus on tumor cells, but scattered Epstein-Barr virus-infected B-cells were detected in 24 cases (89%), implying the reactivation of Epstein-Barr virus caused by immunodeficient status of the patients. After the diagnosis of methotrexate-associated T-cell lymphoproliferative disorder, methotrexate was immediately withdrawn in 26 cases. Twenty (77%) cases presented with spontaneous regression. Compared to methotrexate-associated B-cell lymphoproliferative disorder, patients with methotrexate-associated T-cell lymphoproliferative disorder had a significantly higher proportion of males (p = 0.035) and presence of B-symptoms (p = 0.036), and lower proportion of Epstein-Barr virus+ tumor cells (p < 0.001). Although the difference was not significant, the methotrexate-associated T-cell lymphoproliferative disorder also had more frequent spontaneous regression (p = 0.061). In conclusion, methotrexate-associated T-cell lymphoproliferative disorder was divided into three main types: angioimmunoblastic T-cell lymphoma, peripheral T-cell lymphoma, NOS, and CD8+ cytotoxic T-cell lymphoma. Angioimmunoblastic T-cell lymphoma was the most common type. Methotrexate-associated T-cell lymphoproliferative disorder was characterized by a high rate of spontaneous regression after methotrexate cessation. Epstein-Barr virus positivity was relatively rare in methotrexate-associated T-cell lymphoproliferative disorder, significantly less frequent than methotrexate-associated B-cell lymphoproliferative disorder, suggesting different pathogenesis.

DOI： 10.1038/s41379-019-0264-2

Web of Science

Scopus

PubMed

Divergence and heterogeneity of neoplastic PD-L1 expression: Two autopsy case reports of intravascular large B-cell lymphoma. Reviewed

Sakakibara A, Inagaki Y, Imaoka E, Sakai Y, Ito M, Ishikawa E, Shimada S, Shimada K, Suzuki Y, Nakamura S, Satou A, Kohno K

Pathology international Vol. 69 ( 3 ) page： 148 - 154 2019.3

Pyruvate secreted from patient-derived cancer-associated fibroblasts supports survival of primary lymphoma cells Reviewed Open Access

Sakamoto Akihiko, Kunou Shunsuke, Shimada Kazuyuki, Tsunoda Makoto, Aoki Tomohiro, Iriyama Chisako, Tomita Akihiro, Nakamura Shigeo, Hayakawa Fumihiko, Kiyoi Hitoshi

CANCER SCIENCE Vol. 110 ( 1 ) page： 269 - 278 2019.1

Immune evasion-related extranodal large B-cell lymphoma: A report of six patients with neoplastic PD-L1-positive extranodal diffuse large B-cell lymphoma.

Suzuki Y, Sakakibara A, Shimada K, Shimada S, Ishikawa E, Nakamura S, Kato S, Takahara T, Asano N, Satou A, Kohno K

Pathology international Vol. 69 ( 1 ) page： 13 - 20 2019.1

Language：English Publisher：Pathology International

We identified six patients with Epstein-Barr virus (EBV)-negative extranodal diffuse large B-cell lymphoma (DLBCL) and immunohistochemical expression of PD-L1 on their tumor cells by examining 283 DLBCL cases with the PD-L1 SP142 clone between 2015 and 2017. They consisted of two men and four women with a median age of 71 years, and were examined in an autopsy (n = 1) and biopsies from the adrenal gland (n = 2), skin (n = 1), pelvic cavity (n = 1), and kidney (n = 1). All showed a monomorphic population of large transformed B-cells leading to diagnoses of DLBCL with two intravascular large B-cell lymphoma (IVLBCL) and one de novo CD5+ type and were featured by an invariable immunephenotype: CD3-, CD20+, BCL-2+, and MUM1+. In addition, CD5 and CD10 were each detected in one case. All cases expressed PD-L1 on >10% to >90% of tumor cells, which was confirmed with two other PD-L1 antibodies (E1J2J and 28-8). Three untreated patients had a rapid, lethal clinical course within 7 months after diagnosis; while, the remaining three achieved complete remission after treatment and were alive at the last follow-up. We suggest immune evasion-related extranodal large B-cell lymphoma should be recognized beyond the currently identified entities of IVLBCL and de novo CD5+ DLBCL.

DOI： 10.1111/pin.12742

Web of Science

Scopus

PubMed

Clinicopathological analysis of primary intestinal diffuse large B-cell lymphoma: Prognostic evaluation of CD5, PD-L1, and Epstein-Barr virus on tumor cells Open Access

Ishikawa Eri, Kato Seiichi, Shimada Kazuyuki, Tanaka Tsutomu, Suzuki Yuka, Satou Akira, Kohno Kei, Sakakibara Ayako, Yamamura Takeshi, Nakamura Masanao, Miyahara Ryoji, Goto Hidemi, Nakamura Shigeo, Hirooka Yoshiki

CANCER MEDICINE Vol. 7 ( 12 ) page： 6051 - 6063 2018.12

Biology and management of primary effusion lymphoma. Invited Reviewed Open Access

Shimada K, Hayakawa F, Kiyoi H

Blood Vol. 132 ( 18 ) page： 1879 - 1888 2018.11

Outcomes after R-CHOP in patients with newly diagnosed advanced follicular lymphoma: a 10-year follow-up analysis of the JCOG0203 trial

Watanabe T., Tobinai K., Wakabayashi M., Morishima Y., Kobayashi H., Kinoshita T., Suzuki T., Yamaguchi M., Ando K., Ogura M., Taniwaki M., Uike N., Yoshino T., Nawano S., Terauchi T., Hotta T., Nagai H., Tsukasaki K., Kurosawa M., Yamagishi K., Kobayashi N., Minauchi K., Harigae H., Fukuhara N., Takahashi N., Kameoka Y., Matsuda S., Saitoh Y., Tsukamoto N., Yokohama A., Kubota N., Minami Y., Yamauchi N., Kumagai K., Tsujimura H., Izutsu K., Maruyama D., Takayama N., Ohyashiki K., Akahane D., Shimoyama T., Shimada T., Kamiyama Y., Dobashi N., Wasada I., Sano F., Takimoto M., Chou T., Ishiguro T., Masaki Y., Yamauchi T., Ono T., Yamamoto K., Kato H., Tokunaga T., Shimada K., Ushijima Y., Iida S., Kusumoto S., Uchida T., Hanamura I., Kanasugi J., Kagami Y., Hiraga J., Miyazaki K., Utsumi T., Kuroda J., Kobayashi T., Matsumura I., Rai S., Murayama T., Gomyo H., Sunami K., Makita M., Ichinohe T., Fukushima N., Yoshida I., Yakushijin Y., Asai H., Suehiro Y., Choi I., Takamatsu Y., Sasaki H., Yamasaki S., Tsukada J., Morimoto H., Kimura S., Yokoo M., Yoshida S., Moriuchi Y., Miyazaki Y., Imaizumi Y., Jo T., Nosaka K., Tatetsu H., Hidaka M., Harada N., Ohtsuka E., Ishitsuka K., Yoshimitsu M.

The Lancet Haematology Vol. 5 ( 11 ) page： e520 - e531 2018.11

Language：Japanese Publisher：The Lancet Haematology

Background: Standard treatment for untreated advanced-stage follicular lymphoma is rituximab plus chemotherapy. The incidence of histological transformation of follicular lymphoma has been reported only in heterogeneously treated populations and rarely with long-term follow-up. Additionally, the incidence of secondary malignancies after treatment, without high-dose therapy for follicular lymphoma, is largely unknown. The aim of our study was to assess progression-free survival, overall survival, incidence of secondary malignancies, and incidence of histological transformation in a 10-year follow-up analysis of the JCOG0203 trial. Methods: In the phase 2–3 randomised JCOG0203 trial, previously untreated patients with stage III or IV indolent B-cell lymphoma, including grades 1–3 follicular lymphoma, from 44 hospital centres in Japan, were randomly assigned (1:1) by use of a minimisation method to receive six cycles of R-CHOP (rituximab [375 mg/m2], given on day 1, plus cyclophosphamide [750 mg/m2], doxorubicin [50 mg/m2], vincristine [1·4 mg/m2, capped at 2·0 mg] given intravenously on day 3, and oral prednisone [100 mg once daily on days 3–7]) every 3 weeks (R-CHOP-21) or every 2 weeks (enabled by mandatory granulocyte-colony stimulating factor administration once daily for 6 days, starting on day 8; R-CHOP-14) without rituximab maintenance. Age, bulky disease (nodal or extranodal mass ≥10 cm in diameter on CT), and institution were used as adjustment factors. Investigators enrolled participants, and assignment to trial groups was done with a computer-assisted randomisation allocation sequence that took place centrally at the Japan Clinical Oncology Group Data Center, without the intervention of investigators. Interventions were not masked for patients or investigators. Data were collected 10 years after enrolment of the last patient. The primary endpoint of the phase 3 part of the study was progression-free survival, and the primary endpoint of the phase 2 part of the study was the proportion of patients who achieved a complete response. Accrual was 4·5 years, and follow-up was 3 years after registration was closed. Data were updated on the cutoff date of Feb 28, 2017. Intention-to-treat analyses (ie, progression-free survival, overall survival, and incidence of secondary malignancies) were predefined, to be done at 10 years after the last patient was enrolled. An additional analysis of the incidence of histological transformation was defined 15 years after the protocol, on May 8, 2017, in a supplementary analysis plan, and assessed at 10 years after the last patient was enrolled. Follow-up is ongoing. This trial is registered with ClinicalTrials.gov, number NCT00147121. Findings: Between Sept 1, 2002, and Feb 28, 2007, 300 patients were enrolled, and 149 (50%) were assigned to the R-CHOP-21 group and 151 (50%) were assigned to the R-CHOP-14 group. After eligibility was assessed, one patient was excluded from the R-CHOP-21 group. 10-year progression-free survival was not different between groups (R-CHOP-21 33%, 95% CI 25–41; R-CHOP-14 39%, 31–47; hazard ratio 0·89, 95% CI 0·67–1·17). In 248 patients with grade 1–3a follicular lymphoma, progression-free survival was 39% (33–45) at 8 years and 36% (30–42) at 10 years. The cumulative incidence of histological transformation was 3·2% (95% CI 1·5–6·0) at 5 years, 8·5% (5·4–12·4) at 8 years, and 9·3% (6·1–13·4) at 10 years after enrolment. At 10 years, the cumulative incidence of secondary malignancies was 8·1% (5·1–12·0) and the cumulative incidence of haematological secondary malignancies was 2·9% (1·3–5·5). Interpretation: R-CHOP is a viable option for first-line treatment in patients with newly diagnosed advanced follicular lymphoma. Clinicians choosing a first-line treatment for patients with follicular lymphoma should be cautious of secondary malignancies caused by immunochemotherapy and severe complications of infectious diseases in the long-term follow-up—both of which could lead to death. Funding: National Cancer Center and Ministry of Health, Labour and Welfare of Japan.

DOI： 10.1016/S2352-3026(18)30155-8

Scopus

Reappraisal of nodal Epstein-Barr Virus-negative cytotoxic T-cell lymphoma: Identification of indolent CD5(+) diseases Reviewed Open Access

Yamashita Daisuke, Shimada Kazuyuki, Takata Katsuyoshi, Miyata-Takata Tomoko, Kohno Kei, Satou Akira, Sakakibara Ayako, Nakamura Shigeo, Asano Naoko, Kato Seiichi

CANCER SCIENCE Vol. 109 ( 8 ) page： 2599 - 2610 2018.8

A prognostic model, including the EBV status of tumor cells, for primary gastric diffuse large B-cell lymphoma in the rituximab era Reviewed Open Access

Ishikawa Eri, Tanaka Tsutomu, Shimada Kazuyuki, Kohno Kei, Satou Akira, EladI Ahmed E., Sakakibara Ayako, Furukawa Kazuhiro, Funasaka Kohei, Miyahara Ryoji, Nakamura Masanao, Goto Hidemi, Nakamura Shigeo, Kato Seiichi, Hirooka Yoshiki

CANCER MEDICINE Vol. 7 ( 7 ) page： 3510 - 3520 2018.7

Early disease progression in patients with localized natural killer/T-cell lymphoma treated with concurrent chemoradiotherapy Reviewed Open Access

Yamaguchi Motoko, Suzuki Ritsuro, Kim Seok Jin, Ko Young Hyeh, Oguchi Masahiko, Asano Naoko, Miyazaki Kana, Terui Yasuhiko, Kubota Nobuko, Maeda Takeshi, Kobayashi Yukio, Amaki Jun, Soejima Toshinori, Saito Bungo, Shimoda Emiko, Fukuhara Noriko, Tsukamoto Norifumi, Shimada Kazuyuki, Choi Ilseung, Utsumi Takahiko, Ejima Yasuo, Kim Won Seog, Katayama Naoyuki

CANCER SCIENCE Vol. 109 ( 6 ) page： 2056 - 2062 2018.6

Bortezomib plus dexamethasone vs thalidomide plus dexamethasone for relapsed or refractory multiple myeloma Reviewed Open Access

Iida Shinsuke, Wakabayashi Masashi, Tsukasaki Kunihiro, Miyamoto Kenichi, Maruyama Dai, Yamamoto Kazuhito, Takatsuka Yoshifusa, Kusumoto Shigeru, Kuroda Junya, Ando Kiyoshi, Kikukawa Yoshitaka, Masaki Yasufumi, Kobayashi Miki, Hanamura Ichiro, Asai Hiroaki, Nagai Hirokazu, Shimada Kazuyuki, Tsukamoto Norifumi, Inoue Yoshiko, Tobinai Kensei

CANCER SCIENCE Vol. 109 ( 5 ) page： 1552 - 1561 2018.5

Phase I study of cord blood transplantation with intrabone marrow injection of mesenchymal stem cells: A clinical study protocol Reviewed Open Access

Goto Tatsunori, Murata Makoto, Terakura Seitaro, Nishida Tetsuya, Adachi Yoshiya, Ushijima Yoko, Shimada Kazuyuki, Ishikawa Yuichi, Hayakawa Fumihiko, Nishio Nobuhiro, Nishiwaki Satoshi, Hirakawa Akihiro, Kato Katsuyoshi, Takahashi Yoshiyuki, Kiyoi Hitoshi

MEDICINE Vol. 97 ( 17 ) page： e0449 2018.4

Autopsy case report of intravascular large B-cell lymphoma with neoplastic PD-L1 expression Reviewed

Sakakibara Ayako, Inagaki Yuichiro, Imaoka Eiki, Ishikawa Eri, Shimada Satoko, Shimada Kazuyuki, Suzuki Yuka, Nakamura Shigeo, Satou Akira, Kohno Kei

JOURNAL OF CLINICAL AND EXPERIMENTAL HEMATOPATHOLOGY Vol. 58 ( 1 ) page： 32 - 35 2018.3

Altered EZH2 splicing and expression is associated with impaired histone H3 lysine 27 tri-Methylation in myelodysplastic syndrome Reviewed

Shirahata-Adachi Mizuho, Iriyama Chisako, Tomita Akihiro, Suzuki Yasuhiro, Shimada Kazuyuki, Kiyoi Hitoshi

LEUKEMIA RESEARCH Vol. 63 page： 90 - 97 2017.12

YM155 induces apoptosis through proteasome-dependent degradation of MCL-1 in primary effusion lymphoma. Reviewed

Kojima Y, Hayakawa F*, Morishita T, Sugimoto K, Minamikawa Y, Iwase M, Yamamoto H, Hirano D, Imoto N, Shimada K, Okada S, Kiyoi H.

Pharmacol Res Vol. 120 page： 242 - 251 2017.6

Emetine elicits apoptosis of intractable B-cell lymphoma cells with MYC rearrangement through inhibition of glycolytic metabolism Reviewed Open Access

Aoki Tomohiro, Shimada Kazuyuki, Sakamoto Akihiko, Sugimoto Keiki, Morishita Takanobu, Kojima Yuki, Shimada Satoko, Kato Seiichi, Iriyama Chisako, Kuno Shunsuke, Harada Yasuhiko, Tomita Akihiro, Hayakawa Fumihiko, Kiyoi Hitoshi

ONCOTARGET Vol. 8 ( 8 ) page： 13085 - 13098 2017.2

Malignant lymphoma with cardiac involvement. Reviewed

Terakura S, Onji M, Iriyama C, Goto T, Ushijima Y, Shimada K, Ishikawa Y, Nishida T, Hayakawa F, Murata M, Kiyoi H.

Rinsho Ketsueki Vol. 58 ( 3 ) page： 239 - 242 2017

Molecular pathogenesis and treatment strategy in diffuse large B-cell lymphoma. Invited Reviewed

Shimada K

[Rinsho ketsueki] The Japanese journal of clinical hematology Vol. 58 ( 10 ) page： 2033 - 2042 2017

SPIB is a novel prognostic factor in diffuse large B-cell lymphoma that mediates apoptosis via the PI3K-AKT pathway. Reviewed

Takagi, Yusuke; Shimada, Kazuyuki; Shimada, Satoko; Sakamoto, Akihiko; Naoe, Tomoki; Nakamura, Shigeo; Hayakawa, Fumihiko; Tomita, Akihiro; Kiyoi, Hitoshi

Cancer science Vol. 107 ( 9 ) page： 1270-80 2016.9

Development and analysis of patient-derived xenograft mouse models in intravascular large B-cell lymphoma. Reviewed

Shimada, K; Shimada, S; Sugimoto, K; Nakatochi, M; Suguro, M; Hirakawa, A; Hocking, T D; Takeuchi, I; Tokunaga, T; Takagi, Y; Sakamoto, A; Aoki, T; Naoe, T; Nakamura, S; Hayakawa, F; Seto, M; Tomita, A; Kiyoi, H

Leukemia Vol. 30 ( 7 ) page： 1568-79 2016.7

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Papers - SHIMADA Kazuyuki