进行性转化生发中心样滤泡T细胞淋巴瘤14例临床病理学分析

Progressively transformed germinal center-like follicular T-cell lymphoma:a clinicopathological analysis of 14 cases

目的探讨进行性转化生发中心样滤泡T细胞淋巴瘤(PTGC样FTCL)的临床病理学特征。方法收集首都医科大学附属北京友谊医院病理科2017年1月至2022年1月14例PTGC样FTCL,分析其临床特征、病理形态、免疫表型及EB病毒感染状态。对10例行T细胞受体基因检测,对8例行免疫球蛋白(Ig)基因克隆性检测。结果(1)患者男性10例,女性4例,男女比为5∶2,发病年龄32~70岁,中位年龄61岁,起病时均有淋巴结肿大,按Ann Arbor系统分期,Ⅰ~Ⅱ期7例,Ⅲ~Ⅳ期7例,有B症状者7例,脾肿大者4例,伴皮疹及皮肤瘙痒者2例。10例获得原单位病理报告,3例诊断为小B细胞淋巴瘤,3例诊断为经典霍奇金淋巴瘤,2例诊断为不除外血管免疫母细胞性T细胞淋巴瘤(AITL),1例诊断为EB病毒相关淋巴组织增生性病变,1例诊断为外周T细胞淋巴瘤(PTCL)伴多量B细胞反应。(2)形态学显示由形态成熟的小淋巴细胞构成的深染大结节,结节内可见散在及灶状分布的异型瘤细胞,胞质淡染或透明。2例在深染结节内见增生的生发中心。5例在结节内还见到散在霍奇金(HRS)样大细胞。(3)免疫组织化学染色结果显示构成深染大结节的小淋巴细胞表达CD20、PAX5和IgD,胞质淡染或透明的异型细胞表达CD3(14/14)、CD4(14/14)、PD1(14/14)、ICOS(14/14)、CD10(9/14)、bcl-6(12/14)和CXCL13(10/14);10例(10/14)瘤细胞表达CD30。5例有HRS样大细胞的病例,HRS样大细胞不表达CD3和白细胞共同抗原(LCA),表达CD20(2/5)、PAX5(5/5)、CD30(5/5)、CD15(2/5)、OCT2(5/5)及BOB1(2/5),并见肿瘤性滤泡辅助T细胞包绕HRS样细胞形成花环结构。(4)EB病毒编码的RNA(EBER)原位杂交显示14例中8例见散在较小的B细胞阳性,包括3/5例具有HRS样大细胞的病例,同时显示HRS样细胞阳性。(5)10例病例(包括5例有HRS样大细胞的病例)行T细胞受体基因重排检测均呈单克隆性,8例(包括5例有HRS样大细胞的病例)行Ig基因重排检测均呈多克隆性重排。结论PTGC样FTCL是少见的起源于滤泡辅助T细胞的肿瘤,和AITL的鉴别在于前者形成滤泡结构,缺乏滤泡外的滤泡树突细胞网增生和多形性浸润。该病还需和淋巴细胞丰富的经典霍奇金淋巴瘤及低级别B细胞淋巴瘤鉴别。

Objective To investigate the clinicopathologic features of progressively transformed germinal center-like follicular T-cell lymphoma(PTGC-like FTCL).Methods The clinicopathologic data of 14 PTGC-like FTCL cases that were diagnosed at the Beijing Friendship Hospital Affiliated to the Capital Medical University from January 2017 to January 2022 were retrospectively collected.Clinicopathological features,immunophenotype,and Epstein-Barr virus(EBV)infection status were analyzed in these cases.Polymerase chain reaction(PCR)was performed to detect the clonal gene rearrangements of T cell receptor(TCR)and the immunoglobulin(Ig)in 10 and 8 cases,respectively.Results The male to female ratio was 5∶2.The median age was 61 years(range 32-70 years).All patients had lymphadenopathy at the time of diagnosis.By using the Ann Arbor system staging,seven cases were classified as stageⅠ-Ⅱ,and seven cases as stageⅢ-Ⅳ.Seven cases had B symptoms,four cases had splenomegaly,and two cases had skin rash and pruritus.Previously,three cases were diagnosed as classic Hodgkin′s lymphoma,three cases as small B-cell lymphoma,two cases as atypical lymphoid hyperplasia unable to exclude angioimmunoblastic T-cell lymphoma(AITL),one case as EBV-associated lymphoproliferative disorder,and one case as peripheral T-cell lymphoma(PTCL)associated with the proliferation of B cells.All the 14 cases showed that the large nodules were composed of mature CD20+,IgD+B lymphocytes admixed with small aggregates of neoplastic cells with pale to clear cytoplasm.Moreover,hyperplastic germinal centers(GCs)and Hodgkin/Reed-Sternberg-like(HRS-like)cells were seen within these nodules in two and five cases,respectively.The neoplastic cells expressed CD3(14/14),CD4(14/14),PD1(14/14),ICOS(14/14),CD10(9/14),bcl-6(12/14),CXCL13(10/14),and CD30(10/14).The HRS-like cells in five cases expressed CD20(2/5),PAX5(5/5),CD30(5/5),CD15(2/5),LCA(0/5),OCT2(5/5)and BOB1(2/5).Moreover,neoplastic T cells formed rosettes around HRS-like cells.EBV-encoded RNA(EBER)in situ hybridization showed scattered,small,positive bystander B lymphocytes in 8/14 cases,including 3/5 cases containing HRS-like cells.All tested cases(including five with HRS-like cells)showed monoclonal TCR gene rearrangement and polyclonal Ig gene rearrangement.Conclusions PTGC-like FTCL is a rare tumor originated from T-follicular helper cells.It could be distinguished from angioimmunoblastic T-cell lymphoma by the formation of follicular structure,and lack of follicular dendritic cell proliferation outside the follicles and the polymorphous inflammatory background.In addition,it should be differentiated from lymphocyte-rich classical Hodgkin′s lymphoma and low-grade B cell lymphoma.