Martinez Daniel, Navarro Alba, Martinez-Trillos Alejandra, Molina-Urra Ricardo, Gonzalez-Farre Blanca, Salaverria Itziar, Nadeu Ferran, Enjuanes Anna, Clot Guillem, Costa Dolors, Carrio Ana, Villamor Neus, Colomer Dolors, Martinez Antonio, Bens Susanne, Siebert Reiner, Wotherspoon Andrew, Beà Sílvia, Matutes Estella, Campo Elias
*Hospital Clinic, Hematopathology Unit†Department of Anatomic Pathology, Universitat de Barcelona‡Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain§Pathology and Cytopathology Department, Hospital Base Puerto Montt, Puerto Montt, Chile∥Institute of Human Genetics, Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany¶Royal Marsden Hospital, London, UK.
Am J Surg Pathol. 2016 Feb;40(2):192-201. doi: 10.1097/PAS.0000000000000523.
Splenic diffuse red pulp small B-cell lymphoma (SDRPL) is considered an indolent neoplasm and its pathogenesis is not well known. We investigated the molecular characteristics of 19 SDRPL patients, 5 of them with progressive disease. IGHV genes were mutated in 9/13 (69%). Cytogenetic and molecular studies identified complex karyotypes in 2 cases, and IGH rearrangements in 3, with PAX5 and potentially TCL1 as partners in each one of them. Copy number arrays showed aberrations in 69% of the tumors, including recurrent losses of 10q23, 14q31-q32, and 17p13 in 3, and 9p21 in 2 cases. Deletion of 7q31.3-q32.3 was present in only 1 case and no trisomies 3 or 18 were detected. NOTCH1 and MAP2K1 were mutated in 2 cases each, whereas BRAF, TP53, and SF3B1 were mutated each in single cases. No mutations were found in NOTCH2 or MYD88. Four of the 5 patients with aggressive disease had mutations in NOTCH1 (2 cases), TP53 (1 case), and MAP2K1 (1 case). The progression-free survival of patients with mutated genes was significantly shorter than in the unmutated (P=0.011). These findings show that SDRPL share some mutated genes but not chromosomal alterations, with other splenic lymphomas, that may confer a more aggressive behavior.
脾弥漫性红髓小B细胞淋巴瘤（SDRPL）被认为是一种惰性肿瘤，其发病机制尚不清楚。我们研究了19例SDRPL患者的分子特征，其中5例为疾病进展患者。13例中有9例（69%）的IGHV基因发生突变。细胞遗传学和分子研究在2例中鉴定出复杂核型，3例中发现IGH重排，其中每例的伙伴基因分别为PAX5和可能的TCL1。拷贝数阵列显示69%的肿瘤存在畸变，包括3例中10q23、14q31 - q32和17p13的反复缺失，以及2例中9p21的缺失。仅1例存在7q31.3 - q32.3缺失，未检测到三体3或18。NOTCH1和MAP2K1各有2例发生突变，而BRAF、TP53和SF3B1各有1例发生突变。NOTCH2或MYD88未发现突变。5例侵袭性疾病患者中有4例在NOTCH1（2例）、TP53（1例）和MAP2K1（1例）发生突变。基因发生突变的患者无进展生存期明显短于未发生突变的患者（P = 0.011）。这些发现表明，SDRPL与其他脾淋巴瘤有一些共同的突变基因，但染色体改变不同，这些突变基因可能导致更具侵袭性的行为。
