Progression to large B-cell lymphoma in splenic marginal zone lymphoma - Adescription of a series of 12 cases

Splenic marginal zone lymphoma (SMZL) is considered to be an indolent extra nodal B-cell lymphoma. Despite its low aggressivity, histologic progression has been described in sporadic reports, although the frequency, characteri stics, and underlying molecular abnormalities of this phenomenon are largel y unknown. We review here the clinical, morphologic, immunohistochemical, a nd molecular features of a series of 12 SMZL cases that showed progression to large B-cell lymphoma (LBCL). The most frequent location of secondary LB CL was in peripheral lymph node. This occurred between 12 and 85 months aft er diagnosis of SMZL. However, in two cases LBCL was diagnosed at the initi al 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 immunoglobu lin heavy chain gene polymerase chain study revealed the same rearrangement pattern in both primary and secondary tumors, thereby confirming their ide ntity and excluding the possibility of a second malignancy. As is the case with other low-grade lymphoproliferative disorders, SMZL may undergo high-g rade transformation. These 12 cases represent 13% of our series of SMZL wit h adequate follow-up. The incidence of large cell transformation in SMZL se ems to be lower than in follicular lymphoma (25-60%) and mantle cell lympho ma (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 (MIB 1 staining) in initial SMZL specimens of cases wit h LBCL transformation was 28.6%, higher than that of MIB I staining in the overall SMZL series (21.8%), although not statistically significantly so. p 53 or p16(INK4a) inactivation in this series was observed in only one case, in contrast with the situation observed in chronic lymphocytic leukemia, f ollicular lymphoma, and mantle cell lymphoma. It seems that progression in SMZL is mainly independent of p53 or p16(INK4) inactivation. The frequency of the 7q deletion in this series was 3 of 7 (42%). 7q loss may play an alt ernative role in the inactivation of the p53 and p16(INK4a) pathway, thereb y favoring tumoral progression.