Spada Francesca, Rosenwald Andreas, Klapper Wolfram, Feller Alfred C, Fend Falko, Ott German, Fürstberger Axel, Barth Thomas F E, Möller Peter
Institute of Pathology, Ulm University, Ulm, Germany.
Institute of Pathology, Julius-Maximilians-Universität Würzburg, Würzburg, Germany.
Am J Clin Pathol. 2025 Feb 12;163(2):277-289. doi: 10.1093/ajcp/aqae120.
Primary nodal marginal B-cell lymphoma (NMZL) is rare and histologically very variable. Its large-cell presentation is difficult to distinguish from nodal diffuse large B-cell lymphoma (nDLBCL) due to the absence of specific markers for nodal marginal zone lymphomas in general.
Using a comprehensive cohort of NMZLs and a control cohort of nDLBCLs, we conducted a methylome analysis on subgroups of both.
The methylomes were strikingly different between the cohorts but unexpectedly homogeneous within the NMZL cohort. This allowed us to describe the morphologic spectrum of NMZL in all its value ranges. The considerable overlap in growth pattern and cytology of NMZL with nDLBCL was explored morphometrically, leading to an operational tool for separating both by a simple measurement of cell size and nuclear size. This was integrated in a hierarchical approach, including a scoring system for the parameter growth pattern, follicular colonization, follicular dendritic network, IgD expression, and Ki-67 rate, and led to a proposal for a classifier that we present here.
This methylome-based study extends the morphological spectrum of NMZL towards large cell morphology and offers a conventional way to distinguish it from nDLBCL.
原发性淋巴结边缘区B细胞淋巴瘤（NMZL）较为罕见，组织学表现差异很大。由于一般缺乏淋巴结边缘区淋巴瘤的特异性标志物，其大细胞表现型难以与淋巴结弥漫性大B细胞淋巴瘤（nDLBCL）相区分。
我们使用一组全面的NMZL病例以及一组nDLBCL对照病例，对两组的亚组进行了甲基化组分析。
两组之间的甲基化组存在显著差异，但NMZL组内出人意料地具有同质性。这使我们能够描述NMZL在其所有值范围内的形态学谱。通过形态计量学方法探究了NMZL与nDLBCL在生长模式和细胞学方面的相当大的重叠，从而形成了一种通过简单测量细胞大小和核大小来区分两者的实用工具。这被整合到一种分层方法中，包括针对参数生长模式、滤泡定植、滤泡树突状网络、IgD表达和Ki-67率的评分系统，并得出了我们在此提出的一种分类器方案。
这项基于甲基化组的研究将NMZL的形态学谱扩展至大细胞形态，并提供了一种将其与nDLBCL区分开来的常规方法。
