血管免疫母细胞性T细胞淋巴瘤模式Ⅰ型临床病理学特征

Clinicopathological features of angioimmunoblastic T-cell lymphoma patternⅠ

目的探讨血管免疫母细胞性T细胞淋巴瘤(angioimmunoblastic T-cell lymphoma,AITL)模式Ⅰ型的临床病理学特征。方法回顾性收集2019年1月至2021年10月首都医科大学附属北京友谊医院及北京陆道培医院共11例AITL模式Ⅰ型病例的临床病理资料,检测肿瘤细胞的免疫表型、EB病毒感染状态和T细胞受体(TCR)克隆性,分析患者的临床病理特征。结果(1)11例AITL模式Ⅰ型病例中,男性6例,女性5例,男女比例为1.2∶1.0,中位年龄为59岁(范围47~78岁)。有B症状者7例。11例起病时均有全身多处淋巴结肿大。按Ann Arbor系统分期,Ⅰ~Ⅱ期占2/11,Ⅲ~Ⅳ期占9/11。肝或(和)脾肿大者占2/11,有皮疹及皮肤瘙痒者占3/11,出现胸水者占2/11。初始诊断中,有6例诊断为反应性增生,1例诊断为EB病毒相关淋巴组织增生性病变,4例诊断为淋巴组织增生,不除外淋巴瘤。(2)形态学特点为所有病例均表现为副皮质区多量增生活跃的淋巴滤泡,滤泡内生发中心明显。7例生发中心外套细胞层不完整或呈"虫蚀"状,界限不清,4例套细胞层完全消失。滤泡存在薄层胞质透亮或淡染的非典型淋巴细胞围绕,其中有2例透明细胞位于生发中心与残留菲薄的套细胞层之间,呈现环状生长模式。细胞体积中等,细胞核型略不规则,染色质略粗,未见明显核仁。(3)免疫表型:11例CD21染色显示滤泡树突细胞(follicular dendritic cell,FDC)网主要局限于滤泡内,4例见FDC网轻微扩张,周围呈毛刺样。生发中心周围环绕的非典型细胞表达CD3(11/11)、CD4(11/11)、PD1(11/11)、CXCL13(6/11)、ICOS(10/11)和CD10(7/11)。PD1染色表现为强的生发中心周围分布模式,滤泡间区高内皮静脉周围散在少量阳性细胞簇。CXCL13、ICOS和CD10染色均表现出类似的分布模式。(4)EB病毒编码的RNA(EBER)原位杂交检测显示11例滤泡间区散在分布EBER阳性的B淋巴细胞(5~20个/HPF)。11例T细胞受体基因重排均呈单克隆性。结论血管免疫母细胞性T细胞淋巴瘤模式Ⅰ型容易漏诊,临床出现全身淋巴结肿大、伴系统性症状(皮疹、发热等),组织形态及免疫表型上出现特征性肿瘤细胞分布,综合分子检测结果,方能做出正确的诊断。

Objective To investigate the clinicopathological features of angioimmunoblastic T-cell lymphoma patternⅠ(AITL PatternⅠ).Methods The clinicopathological data of 11 AITL PatternⅠcases that were diagnosed at the Beijing Friendship Hospital Affiliated to Capital Medical University(10 cases)and Beijing Lu Daopei Hospital(1 cases)from January 2019 to October 2021 were retrospectively collected.Immunophenotype,Epstein-Barr virus infection status and T cell receptor(TCR)clonality of the tumor cells were tested,and clinicopathological features of cases were analyzed.Results Among the 11 AITL PatternⅠcases,the male to female ratio was 1.2∶1.0.The median age was 59 years(range 47-78 years).Seven cases had B symptoms,while eleven cases presented with systemic lymphadenopathy.According to Ann Arbor system staging,two cases were classified as stageⅠ-Ⅱ,and 9 cases as stageⅢ-Ⅳ.Hepatosplenomegaly was present in two cases(2/11),three cases(3/11)had skin rash and pruritus,and two cases(2/11)had pleural effusion.Previously,6 cases(6/11)were diagnosed as reactive hyperplasia,1 case(1/11)as EBV-associated lymphoproliferative disorder,and 4 cases(4/11)as hyperplasia of lymphoid tissue,which was unable to exclude lymphoma.Histologically,all the 11 cases showed hyperplastic follicles in the paracortical regions with well-formed germinal centers.The hyperplastic follicles showed ill-defined borders and attenuated mantle zones in 7 cases.Mantle zones completely disappeared in 4 cases.The follicles were surrounded by a thin layer of atypical lymphocytes with bright or faintly stained cytoplasm.In 2 cases,the clear cells were located between the germinal centers and the thin residual mantle cell layers,showing a circular growth pattern.The cells were medium in size,with irregular karyotype,coarse chromatin and indistinct nucleoli.Immunohistochemically,CD21 staining showed that the meshworks of follicular dendritic cells(FDC)were mainly confined to the follicles.There was a subtle expansion of the meshworks of FDC in 4 cases with ill-defined borders.The atypical cells surrounding the follicles expressed CD3(11/11),CD4(11/11),PD-1(11/11),CXCL13(6/11),ICOS(10/11)and CD10(7/11).PD-1 staining showed a strong perifollicular pattern,and a small number of positive cells were scattered around the high endothelial veins in the interfollicular region.CXCL13,ICOS and CD10 showed similar distribution patterns.EBV-encoded small RNA probe(EBER)in situ hybridization showed that EBER positive B lymphocytes were scattered in the interfollicular region(5-20/HPF)in all cases.T cell receptor gene rearrangement was monoclonal in all cases.Conclusions Diagnosing AITL PatternⅠmay be challenging and requires comprehensive analysis of clinical manifestations,histological morphology,immunophenotype and gene rearrangement results.