Refining Diagnostic Subtypes of Peripheral T-cell Lymphoma Using a Multiparameter Approach.

IF 7.1 1区 医学 Q1 PATHOLOGY
Catalina Amador, Dennis D Weisenburger, Ana Gomez, Alyssa Bouska, Ahmad Alshomrani, Sunandini Sharma, Rauf Shah, Timothy C Greiner, Francisco Vega, Andreas Rosenwald, German Ott, Andrew L Feldman, Elaine S Jaffe, Neval Ozkaya, Sarah L Ondrejka, James R Cook, Philipp W Raess, Kerry J Savage, Graham W Slack, Joo Y Song, David W Scott, Elias Campo, Lisa M Rimsza, Joseph D Khoury, Louis M Staudt, Wing C Chan, Javeed Iqbal
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引用次数: 0

Abstract

Peripheral T-cell lymphoma (PTCL) is a heterogeneous category, and many cases are unclassifiable and designated as PTCL-not otherwise specified (PTCL-NOS). Gene expression profiling (GEP) has delineated two prognostic subtypes within PTCL-NOS, PTCL-TBX21, and PTCL-GATA3, characterized by distinctive transcriptomes and a different prognosis. To further evaluate the pathologic features of these subgroups, 101 PTCL cases that did not meet specific criteria for well-defined T-cell lymphoma entities underwent detailed pathologic, immunophenotypic (including TFH biomarkers) and GEP analyses, separating them into PTCL-NOS (n=63) and PTCL-TFH (a.k.a. nodal PTCL-TFH, NOS, and TFH lymphoma, NOS) (n=38). PTCL-NOS cases were further categorized into PTCL-GATA3 (n=22; 34%) and PTCL-TBX21 (n=41; 66%), and a significant association (p < 0.02) with overall survival (OS) was reaffirmed. Histopathological assessment showed PTCL-GATA3 cases were characterized by monotonous medium-sized or large transformed cells with a minimal tumor microenvironment (TME) compared to PTCL-TBX21 cases, which consisted of pleomorphic cells in a polymorphous TME (p < 0.05). GEP analysis validated these TME distinctions. Immunophenotypic analysis showed that PTCL-GATA3 cases were predominantly CD4+CD8- and associated with significantly higher LEF1, MYC, and CD30 expression (p < 0.05). PTCL-TBX21 displayed a more diverse biomarker profile with two subgroups: one expressing cytotoxic antigens and enriched in CD8+CD4- or CD8-CD4- phenotype, and another lacking cytotoxic markers but showing a CD4+CD8- phenotype with increased ICOS expression, but devoid of other TFH markers. The PTCL-TFH cases correlated with an angioimmunoblastic T-cell lymphoma (AITL) gene signature, had more EBER-positive cells than the PTCL-GATA3 and PTCL-TBX21 cases, and a subset had some morphologic features of AITL (p < 0.01). This study highlights the unique morphologic and phenotypic variations within the newly-identified PTCL subtypes and should enable more precise diagnosis and tailored therapeutic strategies in the future.

利用多参数方法完善外周 T 细胞淋巴瘤的诊断亚型
外周T细胞淋巴瘤(PTCL)是一个异质性的类别,许多病例无法分类,被称为未另作规定的PTCL(PTCL-NOS)。基因表达谱分析(GEP)已在 PTCL-NOS 中划分出两种预后亚型,即 PTCL-TBX21 和 PTCL-GATA3,它们具有不同的转录组和不同的预后。为进一步评估这些亚群的病理特征,对101例不符合明确定义的T细胞淋巴瘤实体特定标准的PTCL病例进行了详细的病理、免疫表型(包括TFH生物标记物)和GEP分析,将其分为PTCL-NOS(n=63)和PTCL-TFH(又称结节性PTCL-TFH,NOS和TFH淋巴瘤,NOS)(n=38)。PTCL-NOS病例被进一步分为PTCL-GATA3(22例,占34%)和PTCL-TBX21(41例,占66%),并再次证实其与总生存率(OS)有显著关联(P<0.02)。组织病理学评估显示,与PTCL-TBX21病例相比,PTCL-GATA3病例以单形中型或大型转化细胞为特征,肿瘤微环境(TME)极小,而PTCL-TBX21病例则由多形TME中的多形性细胞组成(P<0.05)。GEP 分析验证了这些 TME 区分。免疫表型分析表明,PTCL-GATA3 病例主要为 CD4+CD8-,LEF1、MYC 和 CD30 表达明显较高(p < 0.05)。PTCL-TBX21 的生物标志物特征更为多样,有两个亚群:一个亚群表达细胞毒性抗原,富含 CD8+CD4- 或 CD8-CD4- 表型;另一个亚群缺乏细胞毒性标志物,但显示 CD4+CD8- 表型,ICOS 表达增加,但没有其他 TFH 标志物。PTCL-TFH病例与血管免疫母细胞性T细胞淋巴瘤(AITL)基因特征相关,与PTCL-GATA3和PTCL-TBX21病例相比,有更多的EBER阳性细胞,而且一部分病例具有AITL的某些形态特征(P<0.01)。这项研究强调了新发现的PTCL亚型中独特的形态学和表型变异,有助于今后更精确地诊断和制定有针对性的治疗策略。
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来源期刊
Modern Pathology
Modern Pathology 医学-病理学
CiteScore
14.30
自引率
2.70%
发文量
174
审稿时长
18 days
期刊介绍: Modern Pathology, an international journal under the ownership of The United States & Canadian Academy of Pathology (USCAP), serves as an authoritative platform for publishing top-tier clinical and translational research studies in pathology. Original manuscripts are the primary focus of Modern Pathology, complemented by impactful editorials, reviews, and practice guidelines covering all facets of precision diagnostics in human pathology. The journal's scope includes advancements in molecular diagnostics and genomic classifications of diseases, breakthroughs in immune-oncology, computational science, applied bioinformatics, and digital pathology.
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