Insuasti-Beltran Giovanni, Gale James M, Wilson Carla S, Foucar Kathryn, Czuchlewski David R
From the Department of Hematopathology/Molecular Genetics Pathology, University of Arkansas for Medical Sciences, Little Rock (Dr Insuasti-Beltran); TriCore Reference Laboratories, Albuquerque, New Mexico (Dr Gale); and the Department of Pathology, University of New Mexico, Albuquerque (Drs Wilson, Foucar, and Czuchlewski).
Arch Pathol Lab Med. 2015 Aug;139(8):1035-41. doi: 10.5858/arpa.2014-0322-OA.
Lymphoplasmacytic lymphoma (LPL), marginal zone lymphoma (MZL), and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) are well-defined clinicopathologic entities. However, distinguishing LPL from MZL and from atypical cases of CLL can sometimes be difficult because of overlapping features. Recent studies have identified a recurrent L265P mutation in the MYD88 gene in most cases of LPL. Although this represents a promising diagnostic marker for LPL, the mutation is also reported in rare cases of MZL and CLL (as well as other types of B-cell lymphoma). Detection rates for this mutation have varied depending on the analytic methodology.
To assess the diagnostic utility of MYD88 L265P mutation in diagnosing low-grade B-cell lymphomas.
We developed a novel pyrosequencing assay for the MYD88 L265P mutation and assessed its diagnostic utility in 317 cases of low-grade B-cell lymphoma (45 LPL [14%], 53 MZL [17%], and 219 CLL [69%]). We incorporated formal clinical and pathologic review of selected cases to ensure the most accurate diagnosis and subclassification.
The MYD88 L265P mutation was identified in 43 cases of LPL (96%), including 3 nonimmunoglobulin-M LPL cases. In contrast, the mutation was present in only 2 cases of MZL (4%), and 5 cases of CLL (2%). Thus, pyrosequencing for the MYD88 L265P mutation demonstrates a high clinical sensitivity and specificity to distinguish LPL from MZL and CLL.
This study confirms the strong association of the MYD88 L265P mutation with LPL, as well as the existence of rare cases of small B-cell lymphoma that complicate this association.
淋巴浆细胞淋巴瘤（LPL）、边缘区淋巴瘤（MZL）和慢性淋巴细胞白血病/小淋巴细胞淋巴瘤（CLL）是明确的临床病理实体。然而，由于特征重叠，有时很难将LPL与MZL以及CLL的非典型病例区分开来。最近的研究在大多数LPL病例中发现了MYD88基因中反复出现的L265P突变。尽管这是LPL的一个有前景的诊断标志物，但在罕见的MZL和CLL病例（以及其他类型的B细胞淋巴瘤）中也有该突变的报道。该突变的检测率因分析方法而异。
评估MYD88 L265P突变在诊断低级别B细胞淋巴瘤中的诊断效用。
我们开发了一种针对MYD88 L265P突变的新型焦磷酸测序分析方法，并在317例低级别B细胞淋巴瘤（45例LPL [14%]、53例MZL [17%]和219例CLL [69%]）中评估了其诊断效用。我们纳入了对选定病例的正式临床和病理复查，以确保最准确的诊断和亚分类。
在43例LPL（96%）中发现了MYD88 L265P突变，包括3例非免疫球蛋白M型LPL病例。相比之下，仅2例MZL（4%）和5例CLL（2%）存在该突变。因此，针对MYD88 L265P突变的焦磷酸测序在区分LPL与MZL和CLL方面显示出高临床敏感性和特异性。
本研究证实了MYD88 L265P突变与LPL的强关联，以及存在使这种关联复杂化的罕见小B细胞淋巴瘤病例。
