Characterization of Chronic Lymphocytic Leukemia with Mantle-Like Phenotype
Prashanti Reddy, Bashar Dabbas, Hong Drum, Thomas Kocher, Jesalyin Taylor, Maggie Gama, Yin Xu. Genoptix Medical Laboratory, Carlsbad, CA
Background: Chronic lymphocytic leukemia is essentially diagnosed by flow cytometry (FC) based on its typical CD5/CD23 positive and FMC-7 negative phenotype. However, a small subset of CLLs express FMC-7 and lack CD23, showing a classic phenotype for mantle cell lymphoma (MCL). While lacking cytogenetic evidence of t(11;14) may support the diagnosis of CLL, rare cases of t(11;14)-negative MCL have been reported. We have studied the morphology of blood and bone marrow (BM) in a cohort of CLLs with mantle-like phenotype and compared molecular genetic features with typical CLL phenotype.
Design: CLLs with complete cytogenetics/FISH and IgVH studies were retrieved over a 2-year period. 48 cases were identified with mantle-like phenotype by FC, 42 of which had available PB/BM for morphologic evaluation. There were 1562 cases with typical CLL phenotype. The parameters compared include CD38, ZAP-70 and surface light chain intensity by FC, cytogenetic abnormalities, and IgVH status.
Results: All cases with mantle-like phenotype were negative for t(11;14) by FISH and karyotyping. Among 42 cases with morphologic studies, 19 had PB and 23 BM specimens. Eighteen (43%) cases exhibited atypical morphology with slightly irregular nuclei and more abundant cytoplasm. Only 2 cases showed greater than 10% prolymphocytes. Twelve cases showed nodular and interstitial pattern of marrow involvement and 10 showed diffuse involvement. One paratrabecular and one intrasinusoidal distribution were seen. All were negative for bcl-1 by IHC staining and showed a higher light chain intensity (73% vs. 47%; p=0.0003). Thirty five (73%) cases with mantle-like phenotype harbored chromosome abnormalities, with a higher percentage of deletion 17 (31%; p<0.0001) and complex cytogenetic abnormalities (15%; p=0.0093) than typical CLL phenotype (9% and 5% respectively). Trisomy 12 was more common in mantle-like phenotype (29% vs. 14%; p=0.004). Deletion 13q was more common in typical CLL phenotype (59% vs. 35%; p=0.0016). IgVH hypermutation was more frequent in mantle-like phenotype (71% vs. 51%; p=0.011). No difference was observed for CD38 and ZAP 70.
Conclusions: CLL with mantle-like phenotype is morphologically atypical but shows similar BM infiltration patterns to typical CLL. Bcl-1 is negative in mantle-like phenotype by IHC staining, a useful marker for cases lacking cytogenetic studies. While mantle-like phenotype frequently harbored 13q- and trisomy 12, it correlated more with 17p deletion, complex cytogenetic and IgVH hypermutation. Our findings suggest that CLL with mantle-like phenotype is related to, but biologically distinct from, typical CLL.
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 262, Tuesday Afternoon