Journal of Clinical and Experimental Hematopathology

It is widely accepted that the tumor microenvironment plays an important role in the progression of lymphoid malignancies. Interaction between the tumor and its surrounding immune cells is considered a potential therapeutic target. For example, anti-programmed cell death 1 (PD-1) antibody stimulates the surrounding exhausted immune cells to release PD-1/PD-L1, thereby leading to the regression of PD-L1-positive tumors. Recently, biological phenomena, such as trogocytosis and exosome-mediated transport were demonstrated to be involved in establishing and maintaining the tumor microenvironment. We found that trogocytosis-mediated PD-L1/L2 transfer from tumor cells to monocytes/macrophages is involved in immune dysfunction in classic Hodgkin lymphoma. Exosomes derived from Epstein-Barr virus (EBV)-associated lymphoma cells induce lymphoma tumorigenesis by transferring the EBV-coding microRNAs from the infected cells to macrophages. In this review, we summarized these biological phenomena based on our findings.

Masaharu Kawashima

Hiroshi Higuchi

Ai Kotani

Significance of trogocytosis and exosome-mediated transport in establishing and maintaining the tumor microenvironment in lymphoid malignancies

淋巴系统恶性肿瘤中吞噬作用和外泌体介导的转运在建立和维持肿瘤微环境中的重要性

Ayumi Numata

Rika Sakai

Kae Kawachi

Yasufumi Ishiyama

Yukako Hattori

Hirotaka Takasaki

Tomoyuki Yokose

Naoya Nakamura

Hideaki Nakajima

Clinicopathological and genetic analyses of thyroid large B-cell lymphoma in a Japanese population

日本人群中甲状腺大B细胞淋巴瘤的临床病理学和遗传学分析

Asami Nishikori

Midori Filiz Nishimura

Shuta Tomida

Ryota Chijimatsu

Himawari Ueta

You Cheng Lai

Yuri Kawahara

Yudai Takeda

Sayaka Ochi

Tomoka Haratake

Daisuke Ennishi

Shuji Momose

Yasuharu Sato

Transcriptome analysis of the cytokine storm-related genes among the subtypes of idiopathic multicentric Castleman disease

原发性多中心Castleman病亚型间细胞因子风暴相关基因的转录组分析

Acute promyelocytic leukemia (APL) is a medical emergency. The diagnosis of APL requires morphological examination, cytochemistry, immunophenotyping, and reverse transcriptase polymerase chain reaction (RT-PCR) for PML::RARA or its variants. However, due to the rapid development of complications, diagnosis often relies on morphology and cytochemistry for early treatment. Herein, we describe a 72-year-old gentleman who presented with pancytopenia diagnosed as acute promyelocytic leukemia with an unusual morphology. The bone marrow smear showed 80% myelocyte-like cells with prominent granules and maturation arrest, with an occasional neutrophil. On careful re-examination of the peripheral smear and bone marrow, an occasional poorly preserved cell with a bundle of Auer rods was identified. Cytochemistry for MPO was strongly positive in abnormal promyelocytes and flow cytometry showed positivity for MPO, CD13, CD33, and CD117 and was negative for CD34 and HLA-DR. Cytogenetics showed a complex karyotype of 45,XY, -14, t(15;17)(q24;21)t(14;21)(q11.2;p13)[10]/ 45, XY, idem, add(5)(q35)[5]/ 45,X,-Y[5]. RT-PCR for PML-RARA was positive for the bcr-3 transcript and FISH was positive for t(15;17) (q24;q21). The take home point from our case is to look for the presence of cells with bundle of Auer rods whenever there is pancytopenia with the presence of myelocyte-like cells with prominent granulations.

Narasimhapriyan Kannan

Jasmita Dass

Ganesh Kumar Viswanathan

Preeti Khokhar

Mukul Aggarwal

Acute promyelocytic leukemia masquerading as myeloid maturation arrest- A Case report

急性早幼粒细胞白血病伪装成粒细胞成熟停滞——一例报告

TAFRO syndrome is a rare systemic inflammatory disease characterized by thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly. We encountered a case of calreticulin mutation-positive essential thrombocythemia (ET) with TAFRO syndrome-like features, followed by a rapid fatal course. The patient had been on anagrelide therapy for approximately three years for management of ET; however, she suddenly stopped going for follow-up and discontinued the medicine for a year. She presented with fever and hypotension, suggestive of septic shock, and was transferred to our hospital. The platelet count at the time of admission to another hospital was 50 × 104 / μL; however, it decreased to 25 × 104 / μL upon transfer to our hospital and further decreased to 5 × 104 / μL on the day of her death. In addition, the patient showed remarkable systemic edema and progression of organomegaly. Her condition suddenly worsened and led to her death on the 7th day of hospitalization. Postmortem, serum and pleural effusion interleukin (IL)-6 and vascular endothelial growth factor (VEGF) levels were significantly increased. Consequently, a diagnosis of TAFRO syndrome, since she met the diagnostic criteria for clinical findings and had high cytokine concentrations. Dysregulation of cytokine networks has also been reported in ET. Therefore, concurrent ET and TAFRO syndrome may have further triggered cytokine storms and contributed to the aggravation of the disease on development of TAFRO syndrome. To the best of our knowledge, this is the first report of complications seen in a patient with TAFRO syndrome due to ET.

Hiroko Iizuka-Honma

Haruko Takizawa

Hideaki Nitta

Toru Mitsumori

Masaaki Noguchi

Development of rapidly fatal TAFRO syndrome-like features in a patient with essential thrombocythemia

原发性血小板增多症患者出现快速致命的TAFRO综合征样特征的发展

Kikuchi-Fujimoto disease (KFD), also known as histiocytic necrotizing lymphadenitis, is a rare condition characterized by benign localized lymphadenopathy and clinical symptoms such as fever, sore throat, odynophagia, and leukopenia. Though the etiology of KFD is unknown, this condition is similar to viral infection, including increased infiltration of activated plasmacytoid dendritic cells. KFD exhibits three histological phases that reflect its progression status: proliferative, necrotic, and xanthomatous lesions. The expression loss of pan T-cell markers, such as CD2, CD5, and CD7, of infiltrating T-cells is observed in KFD cases, complicating the distinction from T-cell lymphoma. However, reports on the loss of their expression in KFD have been limited. Furthermore, the precise population of the T-cell subset in KFD is still unclear. Here, we focused on surface markers and transcription factors for T-cell differentiation and analyzed them immunohistochemically in 46 KFD cases. We observed diminished CD5 expression of CD8-positive (CD5dim CD8+) T-cells in the proliferative lesion of KFD cases. Furthermore, these CD5dim CD8+ T-cells expressed T-BET, a master regulator of type 1 helper T-cells. The upregulation of T-BET and downregulation of CD5 in CD8+ T-cells causes dysregulated activation and proliferation of CD8+ T-cells, potentially contributing to the unique histopathological features of KFD. Recognizing the frequent infiltration of T-BET-positive CD5dim CD8+ T-cells in KFD is important for distinguishing it from mature T-cell lymphoma. Our findings suggest that the immune response in KFD shares similarities with viral infections and highlight the importance of characterizing T-BET-positive CD5dim CD8+ T-cell populations for understanding KFD pathogenesis.

Takahisa Yamashita

Hiroki Imada

Natsuko Takayanagi

Chiaki Murakami

Marino Nagata

Keisuke Sawada

Mami Yamazaki

Tomomi Shimizu

Yukina Kikuchi

Wataru Yamamoto

Morihiro Higashi

The significance of T-BET-positive CD8 T-cells with diminished CD5 expression in Kikuchi-Fujimoto disease

T-BET阳性CD8 T细胞CD5表达降低在Kikuchi-Fujimoto病中的意义

Alemtuzumab is recommended as first-line and second-line therapies for T-cell prolymphocytic leukemia (T-PLL). This study retrospectively evaluated the efficacy and safety of alemtuzumab in nine Japanese patients with T-PLL at five participating institutions who were treated between January 2015 and August 2023. The median age at first administration of alemtuzumab was 72 years (range, 39 to 78). Two patients were treatment naïve, and seven had been treated with a median of one (range, 1 to 3) prior systemic therapy. Six patients were refractory to their most recent therapy. Three patients completed 12 weeks of treatment. The overall response rate and the complete response (CR) rate were 78% and 11%, respectively. Among the six patients who achieved a partial response, two achieved clinical CR but did not undergo bone marrow examination. One patient also achieved clinical CR but did not undergo CT or bone marrow examination for response evaluation. The median progression-free survival time was 8.1 months (95% confidence interval, 0.9 to 18.6). Three patients received readministration of alemtuzumab monotherapy after disease progression. There were no treatment-related deaths. The grade 3 or 4 nonhematologic adverse events included infusion reaction (grade 3, n = 2), cytomegalovirus reactivation (grade 3, n = 2), and pulmonary edema (grade 3, n = 1). One patient experienced Epstein‒Barr virus-positive diffuse large B-cell lymphoma 15 months after the last dose of alemtuzumab. These results confirm that the efficacy and safety of alemtuzumab monotherapy in Japanese patients are comparable to those previously reported.

Motoko Yamaguchi

Noriko Fukuhara

Jun Takizawa

Kenji Ishitsuka

Akihiko Yokohama

Kana Miyazaki

Yuma Nato

Satoshi Ichikawa

Masaki Mitobe

Kodai Shima

Yuri Miyazawa

Koji Izutsu

Ritsuro Suzuki

Hirokazu Nagai

Alemtuzumab monotherapy for T-cell prolymphocytic leukemia: an observational study in Japan

阿仑单抗单药治疗T细胞幼淋巴细胞白血病：日本的一项观察性研究

In diagnosing TAFRO syndrome, lymph node histology often may not be evaluated due to inapparent lymphadenopathy. In this study, we analyzed the differences in the pathophysiology of TAFRO syndrome with or without lymphadenopathy. We used an anonymous questionnaire to survey 70 hematologists at 50 hospitals in the Kanto Koshinetsu area of Japan from February to April 2020. We received 31 responses and collected 26 cases with TAFRO syndrome. Compared to cases with or without lymph node biopsy, clinical features and laboratory test findings in both groups were not significantly different, except for stronger renal insufficiency found in those without biopsy. It was also revealed that clinical features and laboratory test findings had no significant differences between the cases with and without lymphadenopathy. However, renal insufficiency was more pronounced in those without lymphadenopathy. There were no significant differences in pathophysiology between cases with or without lymphadenopathy in the group that did not undergo lymph node biopsy. In the treatment strategies, no significant differences were found dependent on lymphadenopathy. This study shows that lymphadenopathy in TAFRO syndrome may be secondary to inflammation and unrelated to the underlying disease.

Takayoshi Uchiyama

Aki Yokoyama

Yuzu Kuroda

Sadao Aoki

Comparison of pathophysiological differences in TAFRO syndrome with or without lymphadenopathy

TAFRO综合征有无淋巴结肿大时病理生理差异的比较

短名	J Clin Exp Hematopathol
Journal Impact	0.89
国际分区	HEMATOLOGY(Q4)

ISSN	1346-4280, 1880-9952
h-index	34

涉及主题	医学生物内科学免疫学病理遗传学淋巴瘤化学外科生物化学抗体癌症研究化疗细胞生物学基因疾病胃肠病学免疫系统
出版信息	出版商: Nihon Rinpa Monaikei Gakkai，出版周期: ，期刊类型: journal，开源期刊: 否
基本数据	创刊年份: 2019，原创研究文献占比: 74.42%，自引率:11.10%， Gold OA占比: 99.04%
平均审稿周期	网友分享经验：11 Weeks

Journal of Clinical and Experimental Hematopathology

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Significance of trogocytosis and exosome-mediated transport in establishing and maintaining the tumor microenvironment in lymphoid malignancies

Clinicopathological and genetic analyses of thyroid large B-cell lymphoma in a Japanese population

Transcriptome analysis of the cytokine storm-related genes among the subtypes of idiopathic multicentric Castleman disease

Acute promyelocytic leukemia masquerading as myeloid maturation arrest- A Case report

Development of rapidly fatal TAFRO syndrome-like features in a patient with essential thrombocythemia

Clinicopathological and genetic analyses of thyroid large B-cell lymphoma in a Japanese population

Transcriptome analysis of the cytokine storm-related genes among the subtypes of idiopathic multicentric Castleman disease

The significance of T-BET-positive CD8 T-cells with diminished CD5 expression in Kikuchi-Fujimoto disease

Alemtuzumab monotherapy for T-cell prolymphocytic leukemia: an observational study in Japan

Comparison of pathophysiological differences in TAFRO syndrome with or without lymphadenopathy