Although the distinction of classical Hodgkin lymphoma from nodular lymphocyte predominant Hodgkin lymphoma using morphology and immunostains is straightforward in most instances, occasional cases pose diagnostic challenge. We sought to determine the utility of the novel YE361 STAT6 rabbit monoclonal antibody in Hodgkin lymphoma and diagnostically challenging B- and T-cell non-Hodgkin lymphoma entities with Hodgkin-like features. Cases from seven institutions included: 57 classical Hodgkin lymphomas (31% EBV+), 34 nodular lymphocyte predominant Hodgkin lymphomas, 34 mimicking B- and T-cell non-Hodgkin lymphomas, and 7 reactive lymphoproliferations. After review of histology, STAT6YE361 immunostaining was performed. The intensity and spatial localization of immunopositivity was assessed in neoplastic cells. Additional FISH for programmed death ligand-1 (PD-L1) was performed in one patient in paired treatment-naive and relapse biopsy tissues. Two STAT6YE361 immunopositive cases were examined by whole-exome sequencing after flow sorting to assess mutations in STAT6 pathway genes. Most classical Hodgkin lymphomas showed nuclear staining for STAT6YE361 [46/57 cases (80%)] on Hodgkin cells. Staining was exclusively nuclear in a minority [12/46 (26%)], while dual nuclear and cytoplasmic localization was more common [34/46 (74%)]. In contrast, all nodular lymphocyte predominant Hodgkin lymphomas [0/34 (0%)] were negative for nuclear STAT6YE361 staining on the lymphocyte predominant cells. Within B- and T-cell non-Hodgkin lymphomas, nuclear STAT6YE361 was seen in: B-cell lymphoma unclassifiable with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma, and in primary mediastinal large B-cell lymphoma. Strong PD-L1 gene amplification was noted in the paired cHL and relapse B-cell lymphoma unclassifiable with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma, although STAT6YE361 was negative in both biopsies. Whole-exome sequencing identified mutations in B2M, XPO1, and ITPKB as well CISHP213L (in the STAT pathway) in one classical Hodgkin lymphoma patient positive for nuclear STAT6YE361 although no underlying STAT6 mutations were observed in either sample examined. STAT6YE361 nuclear staining has 100% positive predictive value and 85.7% negative predictive value in confirming or excluding classical Hodgkin lymphoma diagnosis in the distinction from nodular lymphocyte predominant Hodgkin lymphoma and other benign and malignant entities.

中文翻译：

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STAT6YE361 表达在经典霍奇金淋巴瘤和相关实体中的诊断效用。

虽然在大多数情况下，使用形态学和免疫染色可以直接区分经典霍奇金淋巴瘤与结节性淋巴细胞为主的霍奇金淋巴瘤，但偶尔也会对诊断提出挑战。我们试图确定新型 YE361 STAT6 兔单克隆抗体在霍奇金淋巴瘤和具有霍奇金样特征的具有诊断挑战性的 B 细胞和 T 细胞非霍奇金淋巴瘤实体中的效用。来自七个机构的病例包括：57 例经典霍奇金淋巴瘤（31% EBV+）、34 例结节性淋巴细胞为主的霍奇金淋巴瘤、34 例模拟 B 细胞和 T 细胞非霍奇金淋巴瘤以及 7 例反应性淋巴组织增生。在检查组织学后，进行 STAT6YE361 免疫染色。在肿瘤细胞中评估了免疫阳性的强度和空间定位。程序性死亡配体 1 (PD-L1) 的额外 FISH 在配对的初治和复发活检组织中对一名患者进行。两个 STAT6YE361 免疫阳性病例在流式分选后通过全外显子组测序进行检查，以评估 STAT6 通路基因中的突变。大多数经典霍奇金淋巴瘤在霍奇金细胞上显示出 STAT6YE361 [46/57 例 (80%)] 的核染色。少数染色完全是核染色 [12/46 (26%)]，而双核和细胞质定位更为常见 [34/46 (74%)]。相反，所有结节性淋巴细胞为主的霍奇金淋巴瘤 [0/34 (0%)] 对淋巴细胞为主的细胞核 STAT6YE361 染色呈阴性。在 B 细胞和 T 细胞非霍奇金淋巴瘤中，核 STAT6YE361 见于：无法分类的 B 细胞淋巴瘤，其特征介于弥漫性大 B 细胞淋巴瘤和经典霍奇金淋巴瘤之间，以及原发性纵隔大 B 细胞淋巴瘤。在成对的 cHL 和无法分类的复发 B 细胞淋巴瘤中发现强 PD-L1 基因扩增，其特征介于弥漫性大 B 细胞淋巴瘤和经典霍奇金淋巴瘤之间，尽管 STAT6YE361 在两次活检中均为阴性。全外显子组测序在一名核 STAT6YE361 阳性经典霍奇金淋巴瘤患者中鉴定出 B2M、XPO1 和 ITPKB 以及 CISHP213L（在 STAT 通路中）的突变，尽管在所检查的任一样本中均未观察到潜在的 STAT6 突变。STAT6YE361 核染色具有 100% 的阳性预测值和 85。