Kalpadakis Christina, Pangalis Gerassimos A, Vassilakopoulos Theodoros P, Roumelioti Maria, Sachanas Sotirios, Korkolopoulou Penelope, Koulieris Efstathios, Moschogiannis Maria, Yiakoumis Xanthi, Tsirkinidis Pantelis, Pontikoglou Charalampos, Rondoyianni Dimitra, Papadaki Helen A, Panayiotidis Panayiotidis, Angelopoulou Maria K
Department of Haematology, University of Crete, Heraklion, Crete, Greece.
Department of Haematology, Athens Medical Center Psychikon Branch, Athens, Greece.
Hematol Oncol. 2017 Dec;35(4):542-547. doi: 10.1002/hon.2361. Epub 2016 Oct 13.
Clonal B-cell lymphocytosis of marginal zone origin (CBL-MZ) is a recently described entity characterized by the presence of clonal B cells in the blood and/or bone marrow (BM) with morphologic and immunophenotypic features consistent with marginal zone derivation in otherwise healthy individuals. CBL-MZ is commonly associated with paraproteinemia, usually immunoglobulin M (IgM), raising diagnostic difficulties from Waldenstrom macroglobulinemia (WM). The aim of the present study was to determine the presence of MYD-88 L265P mutation in a well-characterized series of CBL-MZ to identify cases that may in fact represent WM. Fifty-three CBL-MZ cases were retrospectively evaluated. MYD-88 L265P mutation was determined by allele-specific polymerase chain reaction in blood and/or BM mononuclear cells. Almost half of the CBL-MZ cases (49%) were associated with paraproteinemia mainly of the IgM type (65%). MYD-88 L265P mutation was identified in 10 cases (19%). These cases may truly represent WM, whereas 43 cases (81%) are still classified as CBL-MZ. Mutated cases were all associated with paraproteinemia compared with 37% of the nonmutated ones (P < .0001). In addition, mutated cases displayed more frequently CD38 and CD25 positivity (P = .002 and P = .005, respectively). Moreover, cases without paraproteinemia presented more frequently with lymphocytosis, irrespective of the presence of the MYD-88 mutation (P = .02). The present study demonstrates that MYD-88 L265P mutation may represent the only sensitive marker for the differentiation of CBL-MZ from probable WM. However, further studies are warranted to better define the biological significance of MYD-88 L265P mutation and to clarify whether the presence of the mutation establishes WM diagnosis or that it can also be present in borderline cases associated with paraproteinemia.
边缘区起源的克隆性B淋巴细胞增多症（CBL-MZ）是一种最近描述的疾病实体，其特征是在血液和/或骨髓（BM）中存在克隆性B细胞，这些细胞在形态学和免疫表型上具有与边缘区来源一致的特征，且患者其他方面健康。CBL-MZ通常与副蛋白血症相关，通常为免疫球蛋白M（IgM），这使得与华氏巨球蛋白血症（WM）的诊断产生困难。本研究的目的是在一系列特征明确的CBL-MZ病例中确定MYD-88 L265P突变的存在，以识别可能实际上代表WM的病例。对53例CBL-MZ病例进行了回顾性评估。通过等位基因特异性聚合酶链反应在血液和/或BM单个核细胞中确定MYD-88 L265P突变。几乎一半的CBL-MZ病例（49%）与主要为IgM型的副蛋白血症相关（65%）。在10例病例（19%）中鉴定出MYD-88 L265P突变。这些病例可能真正代表WM，而43例（81%）仍被归类为CBL-MZ。与未突变病例的37%相比，突变病例均与副蛋白血症相关（P <.0001）。此外，突变病例更频繁地表现为CD38和CD25阳性（分别为P =.002和P =.005）。此外，无论是否存在MYD-88突变，无副蛋白血症的病例更频繁地出现淋巴细胞增多（P =.02）。本研究表明，MYD-88 L265P突变可能是区分CBL-MZ与可能的WM的唯一敏感标志物。然而，有必要进行进一步研究，以更好地确定MYD-88 L265P突变的生物学意义，并阐明该突变的存在是确立WM诊断，还是也可能存在于与副蛋白血症相关的临界病例中。
