Camacho F I, Mollejo M, Mateo M S, Algara P, Navas C, Hernández J M, Santoja C, Solé F, Sánchez-Beato M, Piris M A
Molecular Pathology Program, Fundación Centro Nacional de Investigaciones Oncológicas Carlos III-CNIO, Madrid, Spain.
Am J Surg Pathol. 2001 Oct;25(10):1268-76. doi: 10.1097/00000478-200110000-00007.
Splenic marginal zone lymphoma (SMZL) is considered to be an indolent extranodal B-cell lymphoma. Despite its low aggressivity, histologic progression has been described in sporadic reports, although the frequency, characteristics, and underlying molecular abnormalities of this phenomenon are largely unknown. We review here the clinical, morphologic, immunohistochemical, and molecular features of a series of 12 SMZL cases that showed progression to large B-cell lymphoma (LBCL). The most frequent location of secondary LBCL was in peripheral lymph node. This occurred between 12 and 85 months after diagnosis of SMZL. However, in two cases LBCL was diagnosed at the initial stage of the disease (one spleen tumoral nodule and one hilar lymph node). The histologic and immunophenotypic features of these cases were similar to those of transformed LBCL at other sites. In four cases the immunoglobulin heavy chain gene polymerase chain study revealed the same rearrangement pattern in both primary and secondary tumors, thereby confirming their identity and excluding the possibility of a second malignancy. As is the case with other low-grade lymphoproliferative disorders, SMZL may undergo high-grade transformation. These 12 cases represent 13% of our series of SMZL with adequate follow-up. The incidence of large cell transformation in SMZL seems to be lower than in follicular lymphoma (25-60%) and mantle cell lymphoma (11-39%), although it is similar to the frequency of transformation in B-chronic lymphocytic lymphoma/small lymphocytic lymphoma (1-10%). The mean proliferative index (MIB1 staining) in initial SMZL specimens of cases with LBCL transformation was 28.6%, higher than that of MIB1 staining in the overall SMZL series (21.8%), although not statistically significantly so. p53 or p16INK4a inactivation in this series was observed in only one case, in contrast with the situation observed in chronic lymphocytic leukemia, follicular lymphoma, and mantle cell lymphoma. It seems that progression in SMZL is mainly independent of p53 or p16INK4a inactivation. The frequency of the 7q deletion in this series was 3 of 7 (42%). 7q loss may play an alternative role in the inactivation of the p53 and p16INK4a pathway, thereby favoring tumoral progression.
脾边缘区淋巴瘤（SMZL）被认为是一种惰性结外B细胞淋巴瘤。尽管其侵袭性较低，但散在报道中已描述了组织学进展情况，不过这种现象的频率、特征及潜在分子异常在很大程度上尚不清楚。我们在此回顾了12例进展为大B细胞淋巴瘤（LBCL）的SMZL病例的临床、形态学、免疫组化及分子特征。继发性LBCL最常见的部位是外周淋巴结。这发生在SMZL诊断后的12至85个月之间。然而，有2例LBCL在疾病初始阶段被诊断出来（一个脾脏肿瘤结节和一个肺门淋巴结）。这些病例的组织学和免疫表型特征与其他部位转化型LBCL的特征相似。在4例病例中，免疫球蛋白重链基因聚合酶链反应研究显示原发性和继发性肿瘤中存在相同的重排模式，从而证实了它们的一致性并排除了第二种恶性肿瘤的可能性。与其他低度淋巴增殖性疾病一样，SMZL可能会发生高级别转化。这12例病例占我们有充分随访的SMZL系列的13%。SMZL中发生大细胞转化的发生率似乎低于滤泡性淋巴瘤（25 - 60%）和套细胞淋巴瘤（11 - 39%），尽管它与B细胞慢性淋巴细胞白血病/小淋巴细胞淋巴瘤的转化频率（1 - 10%）相似。LBCL转化病例的初始SMZL标本中的平均增殖指数（MIB1染色）为28.6%，高于整个SMZL系列中MIB1染色的平均增殖指数（21.8%），尽管差异无统计学意义。在该系列中仅1例观察到p53或p16INK4a失活，这与慢性淋巴细胞白血病、滤泡性淋巴瘤和套细胞淋巴瘤中观察到的情况不同。似乎SMZL的进展主要与p53或p16INK4a失活无关。该系列中7号染色体长臂缺失的频率为7例中的3例（42%）。7号染色体长臂缺失可能在p53和p16INK4a途径失活中发挥替代作用，从而促进肿瘤进展。
