Morphologic Features in Small Lymphocytic Lymphoma Are Predominantly Not Predictive of Underlying Prognostic FISH or Immunophenotypic Markers
C Garcia, K Hunt, H Kang, J Gale, MA Vasef, K Reichard. U. of Pittsburgh, Pittsburgh, PA; U. of New Mexico, Albuquerque, NM; Tricore Reference Lab, Albuquerque, NM
Background: Common recurring genetic abnormalities with prognostic relevance are detected by FISH in 80% of SLL/CLL cases. The presence of ZAP-70 and an unmutated immunoglobulin heavy chain gene variable region (IgVH) each also independently predicts an overall worse survival. Given the heterogeneity in outcome, we evaluated SLL lymph nodes for morphologic clues that may predict a more or less favorable genetic or immunophenotypic profile. Thus, the pathologist could devise a directed approach to performing these ancillary studies.
Design: We identified 41 cases of conventional SLL diagnosed by a hematopathologist. Cases with atypical morphology or those with a component of transformation were excluded. H&E sections were evaluated for three morphologic features: expanded proliferation centers (EPC) comprising >35% of surface area, >10 large cells per 40X hpf outside of proliferation centers (LC) and marked nuclear contour irregularities (NCI) in tumor small and large cells (KR, CG). ZAP-70 IHC, FISH for del13q14, +12, del11q22 (ATM), del17p (p53) and IgVH mutational status (MS) were performed on paraffin sections and interpreted in a blinded fashion (KR, CG, KH, JG). Statistical analysis was performed using R and Stata.
Results: FISH, ZAP-70 and IgVH MS were determined in 100%, 100% and 65% of cases, respectively. 27/41 cases (66%) had FISH abnormalities with the following frequencies: del 13q14 (63%) (sole abnormality in 55%), del 11q (30%), +12 (26%) and del 17p (4%). There was no association between FISH markers and EPC or LC. There was however an association between NCI in small cells and the presence of del 11q (p=0.0055), while NCI in large cells predicts against finding del 13q (p=0.0013). No significant association was found between morphology and ZAP-70+. ZAP-70+ however did correlate with a less favorable FISH abnormality (p=0.04), and lacks the favorable del 13q14 (p=0.006). 13/14 ZAP-70+ cases were IgVH unmutated (p=0.001).
Conclusions: Nuclear contour irregularities in SLL may signal the presence of an underlying adverse FISH abnormality (del 11q). However, given that SLL morphology does not substantially predict FISH, ZAP-70 or IgVH mutational status, performance of these specialized tests should be directed by clinical parameters as needed.
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 113, Tuesday Morning