Abstract：
Objective: To investigate the clinicopathological features and molecular genetics of diffuse large B-cell lymphomas (DLBCL) with concurrent or secondary to nodal T-follicular helper cell lymphoma, angioimmunoblastic-type (nTFHL-AI). Methods: The clinicopathological features and molecular genetics of DLBCL associated with nTFHL-AI diagnosed between January 2015 and October 2022 at the First Affiliated Hospital of Zhengzhou University were analyzed using histology, immunohistochemistry, PCR, EBV-encoded RNA in situ hybridization and fluorescence in situ hybridization (FISH). Clinical information was collected and analyzed. Results: A total of 6 cases including 3 nTFHL-AI with secondary DLBCL and 3 composite lymphomas were reviewed. There were 4 male and 2 female patients, whose ages ranged from 40 to 74 years (median 57 years). All patients presented with nodal lesions at an advanced Ann Arbor stage Ⅲ/Ⅳ (6/6). Bone marrow involvement was detected in 4 patients. All cases showed typical histologic and immunophenotypic characteristics of nTFHL-AI. Among them, 5 cases of DLBCL with concurrent nTFHL-AI exhibited numerous large atypical lymphoid cells and the tumor cells were CD20 and CD79α positive. The only case of DLBCL secondary to nTFHL-AI showed plasma cell differentiation and reduced expression of CD20. All of cases were activated B-cell (ABC)/non-germinal center B-cell (non-GCB) subtype. Three of the 6 cases were EBV positive with>100 positive cells/high power field, meeting the diagnostic criteria of EBV+DLBCL. The expression of MYC and CD30 protein in the DLBCL region was higher than that in the nTFHL-AI region (n=5). C-MYC, bcl-6 and bcl-2 translocations were not detected in the 4 cases that were subject to FISH. Four of the 6 patients received chemotherapy after diagnosis. For the DLBCL cases of nTFHL-AI with secondary DLBCL, the interval was between 2-20 months. During the follow-up period ranging from 3-29 months, 3 of the 6 patients died of the disease. Conclusions: DLBCL associated with nTFHL-AI is very rare. The expansion of EBV-infected B cells in nTFHL-AI may progress to secondary EBV+DLBCL. However, EBV-negative cases have also been reported, suggesting possible other mechanisms. The up-regulation of MYC expression in these cases suggests a possible role in B-cell lymphomagenesis. Clinicians should be aware that another biopsy is still necessary to rule out concurrent or secondary DLBCL when nodal and extranodal lesions are noted after nTFHL-AI treatment.
目的： 探讨淋巴结滤泡辅助T细胞淋巴瘤，血管免疫母细胞型（nodal T-follicular helper cell lymphoma，angioimmunoblastic-type，nTFHL-AI）继发/合并弥漫大B细胞淋巴瘤（DLBCL）的临床病理学及分子遗传学特征、治疗及预后。 方法： 收集郑州大学第一附属医院病理科2015年1月至2022年10月经病理确诊为nTFHL-AI后继发或合并DLBCL病例，应用HE染色、免疫组织化学、EB病毒编码RNA（EBER）原位杂交、聚合酶链反应（PCR）技术及荧光原位杂交（FISH）分析其组织病理学特点及分子遗传学特征，并收集临床随访资料。 结果： （1）收集到3例nTFHL-AI继发DLBCL和3例nTFHL-AI合并DLBCL共6例，男性4例，女性2例，年龄范围40~74岁，中位年龄57岁。病变部位均位于淋巴结。其中4例可见骨髓累及（4/6），Ann Arbor分期均为Ⅲ/Ⅳ期（6/6）。（2）6例nTFHL-AI（其中3例为复合型淋巴瘤中的nTFHL-AI区域）均表现为典型nTFHL-AI组织学形态及免疫表型特点；6例DLBCL（其中3例为复合型淋巴瘤中DLBCL区域）形态及免疫表型特点如下：5例DLBCL形态为弥漫成片异型大细胞，均弥漫强表达B细胞标志物CD20和CD79α，另1例继发DLBCL形态为大细胞伴明显浆细胞分化且CD20表达减弱，这6例DLBCL免疫表型均提示为活化B细胞起源，6例中3例为肿瘤细胞EB病毒弥漫阳性（热点区>100个/HPF），符合EB病毒阳性DLBCL诊断标准。与nTFHL-AI区域相比，DLBCL区域CD30和MYC阳性表达率上调（n=5）。6例中4例行FISH检测均未发现C-MYC、bcl-6和bcl-2基因断裂。（3）6例患者中4例确诊后接受化疗，2例对症治疗。3例nTFHL-AI继发DLBCL病例中，2次肿瘤发生间隔时间为2~20个月。随访时间3~29个月，6例中3例死于本病。 结论： nTFHL-AI继发/合并DLBCL非常少见。nTFHL-AI中EB病毒感染B细胞增生与继发EB病毒阳性DLBCL有关，但仍存在EB病毒阴性病例，提示其他可能的发病机制。nTFHL-AI相关的DLBCL中MYC表达上调提示其在B细胞淋巴瘤转化中可能发挥一定作用。临床需注意，nTFHL-AI患者治疗后若继发结内或结外病变，仍有活检的必要除外nTFHL-AI复发或继发DLBCL可能性。.
目的： 探讨淋巴结滤泡辅助T细胞淋巴瘤，血管免疫母细胞型（nodal T-follicular helper cell lymphoma，angioimmunoblastic-type，nTFHL-AI）继发/合并弥漫大B细胞淋巴瘤（DLBCL）的临床病理学及分子遗传学特征、治疗及预后。 方法： 收集郑州大学第一附属医院病理科2015年1月至2022年10月经病理确诊为nTFHL-AI后继发或合并DLBCL病例，应用HE染色、免疫组织化学、EB病毒编码RNA（EBER）原位杂交、聚合酶链反应（PCR）技术及荧光原位杂交（FISH）分析其组织病理学特点及分子遗传学特征，并收集临床随访资料。 结果： （1）收集到3例nTFHL-AI继发DLBCL和3例nTFHL-AI合并DLBCL共6例，男性4例，女性2例，年龄范围40~74岁，中位年龄57岁。病变部位均位于淋巴结。其中4例可见骨髓累及（4/6），Ann Arbor分期均为Ⅲ/Ⅳ期（6/6）。（2）6例nTFHL-AI（其中3例为复合型淋巴瘤中的nTFHL-AI区域）均表现为典型nTFHL-AI组织学形态及免疫表型特点；6例DLBCL（其中3例为复合型淋巴瘤中DLBCL区域）形态及免疫表型特点如下：5例DLBCL形态为弥漫成片异型大细胞，均弥漫强表达B细胞标志物CD20和CD79α，另1例继发DLBCL形态为大细胞伴明显浆细胞分化且CD20表达减弱，这6例DLBCL免疫表型均提示为活化B细胞起源，6例中3例为肿瘤细胞EB病毒弥漫阳性（热点区>100个/HPF），符合EB病毒阳性DLBCL诊断标准。与nTFHL-AI区域相比，DLBCL区域CD30和MYC阳性表达率上调（n=5）。6例中4例行FISH检测均未发现C-MYC、bcl-6和bcl-2基因断裂。（3）6例患者中4例确诊后接受化疗，2例对症治疗。3例nTFHL-AI继发DLBCL病例中，2次肿瘤发生间隔时间为2~20个月。随访时间3~29个月，6例中3例死于本病。 结论： nTFHL-AI继发/合并DLBCL非常少见。nTFHL-AI中EB病毒感染B细胞增生与继发EB病毒阳性DLBCL有关，但仍存在EB病毒阴性病例，提示其他可能的发病机制。nTFHL-AI相关的DLBCL中MYC表达上调提示其在B细胞淋巴瘤转化中可能发挥一定作用。临床需注意，nTFHL-AI患者治疗后若继发结内或结外病变，仍有活检的必要除外nTFHL-AI复发或继发DLBCL可能性。.
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