Kezlarian Brie, Alhyari Mohammad, Venkataraman Girish, Karner Kristin, Inamdar Kedar V, Menon Madhu P
Departments of Pathology and Laboratory Medicine.
Hematology and Oncology, Henry Ford Hospital, Detroit, MI.
Appl Immunohistochem Mol Morphol. 2019 Mar;27(3):180-184. doi: 10.1097/PAI.0000000000000581.
Classic Hodgkin lymphoma (CHL) and nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) are clinically distinct entities, with different prognostic and treatment implications. In addition, several large B-cell lymphomas and some T-cell lymphomas can mimic CHL. Differentiating these entities from CHL is crucial for ensuring appropriate therapy. GATA3 is a T-cell transcription factor involved in T-cell maturation and has been previously shown to be overexpressed in CHL cells via gene expression profiling. We investigated the utility of GATA3 immunostain in differentiating CHL from NLPHL and other mimicking entities.
We accrued 17 NLPHLs, 49 CHLs [23 nodular sclerosis (NS), 3 syncytial variants, 3 lymphocyte rich and 13 mixed cellularity types], 4 primary mediastinal large B-cell lymphomas (PMBLs), 2 Epstein-Barr virus (EBV) positive diffuse large B-cell lymphomas (DLBCLs) (EBV+LBCLs), 2 T-cell/histiocyte-rich large B-cell lymphomas (TCHRBCLs), 1 gray zone lymphoma, and 2 tissue microarrays consisting of 72 DLBCLs. One slide from each was stained with GATA3 and percent positive tumor cells and intensity of nuclear expression was semiquantitatively graded independently by 2 board certified hematopathologists.
GATA3 was positive in 80% of CHLs. Both percent positivity and intensity of staining varied greatly. Syncytial variant of NS subtype showed the highest positivity rate (3/3; 100%), followed by NS (20/23; 87%), mixed cellularity (9/13; 70%), and lymphocyte rich (2/3; 67%). GATA3 was negative in all NLPHLs, EBV+LBCLs, TCRBCLs, and DLBCLs stained. The single gray zone lymphoma and 3/4 PMBLs were positive.
Nuclear expression of GATA3 can be used to delineate CHL from NLPHL. GATA3 positivity effectively excludes NLPHL with 100% negative predictive value. However, as 20% of CHL can be negative for GATA3, CHL cannot be ruled out with negative GATA3. Additional findings include GATA3 positivity among PMBLs, whereas all 72 DLBCLs were negative for GATA3. This finding further highlights similarities between CHL and PMBL.
经典型霍奇金淋巴瘤（CHL）和结节性淋巴细胞为主型霍奇金淋巴瘤（NLPHL）是临床不同的实体，具有不同的预后和治疗意义。此外，一些大B细胞淋巴瘤和某些T细胞淋巴瘤可模仿CHL。将这些实体与CHL区分开来对于确保适当治疗至关重要。GATA3是一种参与T细胞成熟的T细胞转录因子，先前通过基因表达谱分析已证实在CHL细胞中过表达。我们研究了GATA3免疫染色在区分CHL与NLPHL及其他模仿实体中的效用。
我们收集了17例NLPHL、49例CHL[23例结节硬化型（NS）、3例合体细胞变异型、3例富于淋巴细胞型和13例混合细胞型]、4例原发性纵隔大B细胞淋巴瘤（PMBL）、2例 Epstein-Barr病毒（EBV）阳性弥漫大B细胞淋巴瘤（DLBCL）（EBV+LBCL）、2例T细胞/组织细胞丰富的大B细胞淋巴瘤（TCHRBCL）、1例灰色地带淋巴瘤以及2个由72例DLBCL组成的组织芯片。每例样本的一张玻片用GATA3染色，2名经过委员会认证的血液病理学家独立对阳性肿瘤细胞百分比和核表达强度进行半定量分级。
80%的CHL中GATA3呈阳性。阳性百分比和染色强度差异很大。NS亚型的合体细胞变异型显示出最高的阳性率（3/3；100%），其次是NS（20/23；87%）、混合细胞型（9/13；70%）和富于淋巴细胞型（2/3；67%）。所有染色的NLPHL以及EBV+LBCL、TCRBCL和DLBCL中GATA3均为阴性。单个灰色地带淋巴瘤和3/4的PMBL呈阳性。
GATA3的核表达可用于区分CHL与NLPHL。GATA3阳性可有效排除NLPHL，阴性预测值为100%。然而，由于20%的CHL中GATA3可能为阴性，GATA3阴性不能排除CHL。其他发现包括PMBL中GATA3阳性，而所有72例DLBCL中GATA3均为阴性。这一发现进一步凸显了CHL与PMBL之间的相似性。
