Cytogenetic Analysis of Marginal Zone Lymphoma Reveals Shared and Distinct Aberrations among Different Subtypes
M Levin, V Murty, B Alobeid, G Bhagat. Columbia University, NY, NY
Background: Marginal Zone Lymphomas (MZLs) are subdivided into three distinct categories: nodal (NMZL), extranodal (EMZL), and splenic (SMZL) according to the WHO classification, which share similar histologic and phenotypic features, but differ with regard to genetic alterations. To gain further insights into the relationship between these subtypes, we retrospectively reviewed cytogenetic data of all MZLs evaluated at our institute over a 10-year period.
Design: G-band karyotypes of all MZLs submitted for cytogenetic analysis were examined. In addition, FISH with a panel of probes for CEP3, CEP18, MALT1 and IgH was performed. Morphology was assessed using H&E stained sections and phenotype was determined by flow cytometry and immunohistochemical staining. Cases were categorized according to the current WHO classification.
Results: Forty-five of 55 MZLs (from 53 patients) had informative karyotypes (10 normal and 35 abnormal). These MZL subtypes comprised 10 NMZL (M:F-1:1.5 median age 72; range 50-84), 24 EMZL (M:F-1:1.3 median age 66; range 36-83) and 11 SMZL (M:F-1:1.8 median age 73; range 55-97); seven(20%) had complex and 28(80%) had simple karyotypes. Structural abnormalities were noted in 7 cases, numerical in 19, and a combination of both in 9 cases. Multiple related (n=4) and unrelated (n=1) clones were identified at diagnosis in 11% of MZL, the former representing clonal evolution. Overall, the most common aberrations were those of: chromosome (chr) 3(n=16,36%), including trisomy 3 (n=13,29%), in 3(30%) NMZL, 7(29%) EMZL, and 6(55%) SMZL; chr 1 (n=12,27%) in 3(30%) NMZL, 5(21%) EMZL, and 4(36%) SMZL; chr X (n=7,16%) in 3(30%) NMZL and 4(17%) EMZL, and IgH rearrangements (n=7,16%) in 1(10%) NMZL, 3(13%) EMZL, and 3(27%) SMZL. However, variability in the chr regions and loci involved was noted in some cases. The IgH partner loci included 3q12, 6p21.1, 8q24, 9p13, and 17p11.2. BCL6 rearrangements were noted in 2 cases. Recurrent deletions at 7q22-31 and 14q21-2 were only seen in 3 and 2 cases of SMZL, respectively. FISH analysis in 41 cases identified additional aberrations in 4 MZL with normal and 3 with abnormal karyotypes. MALT1 translocations were restricted to EMZL (n=5, 21%).
Conclusions: We observed both shared and distinct karyotypic aberrations amongst MZL subtypes. Trisomy 3 and chr 1 abnormalities were the most common and a novel IgH partner locus was identified (17p11.2). Multiple clones were not infrequent in our series of MZLs. FISH analysis aids in correct classification by identifying subtype associated chromosomal aberrations.
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 187, Monday Morning