Similar articles

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.

三例复合性B细胞和T细胞淋巴瘤患者的临床、病理和分子学特征的分析及文献回顾

[1]AmaraK, ZiadiS, HachanaM, et al., 2010. DNA methyltransferase DNMT3b protein overexpression as a prognostic factor in patients with diffuse large B-cell lymphomas. Cancer Sci, 101(7):1722-1730.

[2]BalaguéO, MartínezA, ColomoL, et al., 2007. Epstein-Barr virus negative clonal plasma cell proliferations and lymphomas in peripheral T-cell lymphomas: a phenomenon with distinctive clinicopathologic features. Am J Surg Pathol, 31(9):1310-1322.

[3]ChunSM, SungCO, JeonH, et al., 2018. Next-generation sequencing using S1 nuclease for poor-quality formalin-fixed, paraffin-embedded tumor specimens. J Mol Diagn, 20(6):802-811.

[4]ClearyML, SklarJ, 1984. Lymphoproliferative disorders in cardiac transplant recipients are multiclonal lymphomas. Lancet, 324(8401):489-493.

[5]CouronnéL, BastardC, BernardOA, 2012. TET2 and DNMT3A mutations in human T-cell lymphoma. N Engl J Med, 366(1):95-96.

[6]CusterR, 1954. Pitfalls in the diagnosis of lymphoma and leukemia from the pathologist’s point of view. Proceeding of the Second National Cancer Conference. American Cancer Society, New York, p.554-557.

[7]HuE, WeissLM, WarnkeR, et al., 1987. Non-Hodgkin’s lymphoma containing both B and T cell clones. Blood, 70(1):287-292.

[8]KämmererU, KappM, GasselAM, et al., 2001. A new rapid immunohistochemical staining technique using the EnVision antibody complex. J Histochem Cytochem, 49(5):623-630.

[9]KimH, HendricksonMR, DorfmanRF, 1977. Composite lymphoma. Cancer, 40(3):959-976. https://doi.‍org/10.1002/1097-0142(197709)40:‍3<959::‍aid-cncr2820400302>3.0.co;2-3

[10]KüppersR, DührsenU, HansmannML, 2014. Pathogenesis, diagnosis, and treatment of composite lymphomas. Lancet Oncol, 15(10):e435-e446.

[11]LuoC, YuT, YoungKH, et al., 2022. HDAC inhibitor chidamide synergizes with venetoclax to inhibit the growth of diffuse large B-cell lymphoma via down-regulation of MYC, BCL2, and TP53 expression. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 23(8):666-681.

[12]OdejideO, WeigertO, LaneAA, et al., 2014. A targeted mutational landscape of angioimmunoblastic T-cell lymphoma. Blood, 123(9):1293-1296.

[13]OnaindiaA, Santiago-QuispeN, Iglesias-MartinezE, et al., 2021. Molecular update and evolving classification of large B-cell lymphoma. Cancers, 13(13):3352.

[14]RappaportH, WinterWJ, HicksEB, 1956. Follicular lymphoma. A re-evaluation of its position in the scheme of malignant lymphoma based on a survey of 253 cases. Cancer, 9(4):792-821.

[15]SuefujiN, NiinoD, ArakawaF, et al., 2012. Clinicopathological analysis of a composite lymphoma containing both T- and B-cell lymphomas. Pathol Int, 62(10):690-698.

[16]TanakaJ, SuP, LuedkeC, et al., 2018. Composite lymphoma of follicular B-cell and peripheral T-cell types with distinct zone distribution in a 75-year-old male patient: a case study. Hum Pathol, 76:110-116.

[17]ThirumalaS, EspositoM, FuchsA, 2000. An unusual variant of composite lymphoma: a short case report and review of the literature. Arch Pathol Lab Med, 124(9):‍1376-1378.

[18]TrimechM, LetourneauA, MissiagliaE, et al., 2021. Angioimmunoblastic T-cell lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma: a novel form of composite lymphoma potentially mimicking Richter syndrome. Am J Surg Pathol, 45(6):773-786.

[19]WangED, PapavassiliouP, WangAR, et al., 2014. Composite lymphoid neoplasm of B-cell and T-cell origins: a pathologic study of 14 cases. Hum Pathol, 45(4):768-784.

[20]WhitlingNA, ShanesmithRP, JacobL, et al., 2013. Composite lymphoma of mycosis fungoides and cutaneous small B-cell lymphoma in a 73-year-old male patient. Hum Pathol, 44(4):670-675.

[21]WolfeJA, BorowitzMJ, 1984. Composite lymphoma: a unique case with two immunologically distinct B-cell neoplasms. Am J Clin Pathol, 81(4):526-529.

[22]XieCQ, LiX, ZengH, et al., 2020. Molecular insights into pathogenesis and targeted therapy of peripheral T cell lymphoma. Exp Hematol Oncol, 9:30.

[23]XuY, McKennaRW, HoangMP, et al., 2002. Composite angioimmunoblastic T-cell lymphoma and diffuse large B-cell lymphoma: a case report and review of the literature. Am J Clin Pathol, 118(6):848-854.

[24]ZettlA, LeeSS, RüdigerT, et al., 2002. Epstein-Barr virus-associated B-cell lymphoproliferative disorders in angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma, unspecified. Am J Clin Pathol, 117(3):368-379.

[25]ZhangB, ZhangYY, LiQ, et al., 2022. Case report: chronic lymphocytic leukemia/small lymphocytic lymphoma and monomorphic epitheliotropic intestinal T-cell lymphoma: a composite lymphoma. Pathol Oncol Res, 28:1610653.