From the Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
Arch Pathol Lab Med. 2020 May;144(5):602-611. doi: 10.5858/arpa.2019-0007-OA. Epub 2019 Sep 26.
CONTEXT.—: Angioimmunoblastic T-cell lymphomas originate from T follicular helper cells and express respective markers (BCL6, CD10, CXCL13, ICOS, and PD-1). Although commonly present, bone marrow involvement by angioimmunoblastic T-cell lymphoma can be diagnostically challenging. Additionally, only little is known about the distribution of T follicular helper cells in healthy and reactively changed bone marrows or in samples affected by other lymphomas.
OBJECTIVE.—: To establish a diagnostic approach to reliably identify bone marrow infiltration of angioimmunoblastic T-cell lymphoma.
DESIGN.—: We analyzed the morphologic infiltration pattern and the expression of T follicular helper-cell markers in 42 matched paired lymph node and bone marrow samples and applied comparative clonality testing. Furthermore, we studied the expression of BCL6 and PD-1 in a control cohort of healthy, reactively changed, and otherwise affected bone marrows.
RESULTS.—: We identified 3 different bone marrow infiltration patterns correlating with overall survival (interstitial/micronodular infiltration with or without eosinophilia and diffuse infiltration with eosinophilia). The matched pairs showed a consistent (co)expression of PD-1 and BCL6 with a generally weaker expression in the bone marrow than in the lymph nodes. Comparative clonality testing was helpful in only a minority of cases. Infiltrates of the most important differential diagnoses contained either PD-1- or BCL6-positive tumor-infiltrating cells, but no coexpressing cells.
CONCLUSIONS.—: Bone marrow infiltration by angioimmunoblastic T-cell lymphoma displays 3 different patterns that correlate with prognosis. BCL6 and PD-1 can be reliably used to identify lymphoma infiltrates and to help rule out several differential diagnoses. Comparative clonality testing rarely provides additional value and cannot replace morphologic and phenotypic analyses.
血管免疫母细胞性 T 细胞淋巴瘤起源于滤泡辅助 T 细胞，并表达相应的标志物（BCL6、CD10、CXCL13、ICOS 和 PD-1）。尽管常见，但血管免疫母细胞性 T 细胞淋巴瘤骨髓累及的诊断具有挑战性。此外，对于滤泡辅助 T 细胞在健康和反应性骨髓中的分布，或在受其他淋巴瘤影响的样本中的分布，人们知之甚少。
建立一种可靠的方法，以识别血管免疫母细胞性 T 细胞淋巴瘤骨髓浸润。
我们分析了 42 对配对的淋巴结和骨髓样本的形态学浸润模式和滤泡辅助 T 细胞标志物的表达，并应用了比较克隆性检测。此外，我们还研究了 BCL6 和 PD-1 在健康、反应性改变和其他受影响骨髓的对照队列中的表达。
我们发现 3 种不同的骨髓浸润模式与总生存相关（伴有或不伴有嗜酸性粒细胞增多的间质/微结节状浸润和伴有嗜酸性粒细胞增多的弥漫性浸润）。配对样本显示 PD-1 和 BCL6 的一致（共）表达，与淋巴结相比，骨髓中的表达通常较弱。比较克隆性检测在少数情况下有帮助。最重要的鉴别诊断的浸润物含有 PD-1 阳性或 BCL6 阳性的肿瘤浸润细胞，但没有共表达的细胞。
血管免疫母细胞性 T 细胞淋巴瘤骨髓浸润有 3 种不同的模式，与预后相关。BCL6 和 PD-1 可用于可靠地识别淋巴瘤浸润，并有助于排除几种鉴别诊断。比较克隆性检测很少提供额外的价值，不能替代形态学和表型分析。
