title: Progression to large B-cell lymphoma in splenic marginal zone lymphoma: a description of a series of 12 cases.
abstract: 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.
authors.affiliation: Molecular Pathology Program, Fundación Centro Nacional de Investigaciones Oncológicas Carlos III-CNIO, Madrid, Spain.
authors.forename: F I
authors.initials: FI
authors.lastname: Camacho
authors.forename: M
authors.initials: M
authors.lastname: Mollejo
authors.forename: M S
authors.initials: MS
authors.lastname: Mateo
authors.forename: P
authors.initials: P
authors.lastname: Algara
authors.forename: C
authors.initials: C
authors.lastname: Navas
authors.forename: J M
authors.initials: JM
authors.lastname: Hernández
authors.forename: C
authors.initials: C
authors.lastname: Santoja
authors.forename: F
authors.initials: F
authors.lastname: Solé
authors.forename: M
authors.initials: M
authors.lastname: Sánchez-Beato
authors.forename: M A
authors.initials: MA
authors.lastname: Piris
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D034961:Antigens, Nuclear; D014408:Biomarkers, Tumor / Q000032:analysis; D002872:Chromosome Deletion; D002897:Chromosomes, Human, Pair 7; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis / Q000235:genetics; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D016393:Lymphoma, B-Cell / Q000737:chemistry / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000737:chemistry / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000032:analysis; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics; D051560:Proto-Oncogene Proteins c-bcl-6; D013160:Splenic Neoplasms / Q000737:chemistry / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D015996:Survival Rate; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics
chemical_list: D034961:Antigens, Nuclear; D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53