Abstract
Composite lymphoma (CL) involving B-cell lymphoma and T-cell lymphoma is extremely rare. Herein, we report three such cases using immunohistochemistry, flow cytometry, and the next-generation sequencing (NGS) to identify the pathological and molecular characteristics of CL. In the first case, the patient was admitted to hospital for generalized pruritic maculopapular rash over the whole body. An excisional biopsy of the skin lesions showed T-cell lymphoma. At the same time, the staging bone marrow (BM) biopsy revealed a diffuse large B-cell lymphoma (DLBCL). After R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) therapies, the patient produced a good response with substantial dissipation of the rashes and relief of skin. The other two patients were admitted to hospital due to lymphadenopathy and were diagnosed with DLBCL and follicular lymphoma (FL) after core needle biopsy of lymph nodes, BM biopsy, BM aspiration, and flow cytometry. Following R-CHOP and R-COP (rituximab, cyclophosphamide, vincristine, and prednisone) therapies, they achieved complete remission unconfirmed (CRu) and complete remission (CR). However, one or two years later, they suffered a relapse of lymphadenopathy. The shocking fact was that re-biopsy of lymphadenopathy revealed peripheral T-cell lymphoma (PTCL) and angioimmunoblastic T-cell lymphoma (AITL). NGS findings identified DNA methyltransferase 3a (DNMT3a), isocitrate dehydrogenase 2 (IDH2), Ras homolog gene family, member A (RHOA), splicing factor 3B subunit 1 (SF3B1), and tumor protein p53 (TP53) mutations. After immunochemotherapy, these patients achieved CRu and CR again. Nevertheless, they suffered a second relapse of T-cell lymphoma. Finally, they died due to progression of disease. We found that the occurrence of CL is associated with Epstein-Barr virus infection and DNMT3a, IDH2, and TP53 mutations, and the prognosis of the disease is closely related to the T-cell lymphoma components.
摘要
复合性B细胞和T细胞淋巴瘤发病率很低. 为了研究复合性淋巴瘤的临床、 病理和分子学特征, 本文报道了三例复合性B细胞和T细胞淋巴瘤患者, 并通过免疫组化、 流式细胞术和二代测序检测分析患者的病理和分子学特征. 第一例患者通过皮肤活检、 骨髓活检和流式细胞术明确诊断为皮肤T细胞淋巴瘤和骨髓弥漫大B细胞淋巴瘤. 另外两例患者通过淋巴结粗针穿刺活检和骨髓活检明确诊断为B细胞淋巴瘤, 但疾病复发后再次经过病理活检明确诊断为T细胞淋巴瘤, 同时二代测序检测发现了DNA甲基转移酶3a(DNMT3a)和肿瘤蛋白p53(TP53)等基因突变. 在此基础上, 本文回顾了复合性淋巴瘤的相关文献, 并总结了复合性B细胞和T细胞淋巴瘤的临床、 病理和分子特征. 我们发现复合性淋巴瘤的发病和EB病毒感染, 以及DNMT3a、 异柠檬酸脱氢酶2(IDH2)和TP53突变等相关, 同时该疾病的预后与侵袭性更高的T细胞淋巴瘤成分密切相关.
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The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
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Acknowledgments
This work was supported by the Zhejiang Medical Health Science and Technology Project (No. 2021KY166) and the Natural Science Foundation of Zhejiang Province (No. LQ23H080003), China.
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Xueli JIN and Yun LIANG performed the clinical data collection, and wrote and edited the manuscript. Hui LIU and Fengbo HUANG performed the pathological data collection. Jing LI and Boxiao CHEN performed the data collection of PET/CT. Xibin XIAO, Xianggui YUAN, and Panpan CHEN contributed to the study design, writing and editing of the manuscript. All authors have read and approved the final manuscript, and therefore, have full access to all the data in the study and take responsibility for the integrity and security of the data.
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Xueli JIN, Hui LIU, Jing Li, Xibin XIAO, Xianggui YUAN, Panpan CHEN, Boxiao CHEN, Yun LIANG, and Fengbo HUANG declare that they have no conflict of interest.
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2013. The study was approved by the ethical committee of the Second Affiliated Hospital, School of Medicine, Zhejiang University (No. 2023 (0227)). Informed consent was obtained from all patients for being included in the study. Additional informed consent was obtained from all patients for whom identifying information is included in this article.
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Jin, X., Liu, H., Li, J. et al. Composite B-cell and T-cell lymphomas: clinical, pathological, and molecular features of three cases and literature review. J. Zhejiang Univ. Sci. B 24, 711–722 (2023). https://doi.org/10.1631/jzus.B2300181
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DOI: https://doi.org/10.1631/jzus.B2300181