Proliferation Centers in Bone Marrows Involved by Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL): A Clinicopathologic Analysis.
Jason C Chang, Alexandra M Harrington, Horatiu Olteanu, Steven H Kroft. Medical College of Wisconsin, Milwaukee
Background: Nodular collections of prolymphocytes (PLs) and paraimmunoblasts, known as proliferation centers (PCs), are a characteristic finding in lymph nodes involved by CLL/SLL, and are known to represent the mitotically active compartment of the neoplastic clone. Clinicopathologic analyses of PCs in lymph nodes have been published, and the presence and extent of PCs are not currently felt to be related to clinical course. In contrast, PCs are generally considered to be uncommon in bone marrow (BM), and detailed clinicopathologic analyses of BM PCs have not previously been reported.
Design: BMs obtained from 2006-10 with >5% CLL/SLL involvement and adequate tissue were retrieved, resulting in 88 cases from 45 patients (7 diagnostic, 81 f/u). BM PCs were graded as: 0--absent; 1--present, but small and ill-defined; 2--distinct; 3--extensive; 4--diffuse increase in prolymphocytes without discrete PC formation. BM PCs were correlated with other morphologic, immunophenotypic (IP), FISH [+12, del(13q), del11q, del(17p), IgH translocation], and laboratory features. 1° and 2° patterns of BM infiltration were assessed, and the degree of involvement was semi-quantitatively estimated. When possible, peripheral blood (PB) lymphocyte morphology was assessed; increased PLs or atypical lymphocyte cytology was defined as >10% PLs or >10% cleaved/irregular cells, respectively.
Results: PCs were present in 69 BMs (78%), and were distinct/prominent (grades 2-4) in 50 (57%), with the latter more commonly found in f/u BMs (p=0.04). PCs tended to be perivascular or parasinusoidal in distribution. Distinct/prominent PCs were associated with a nodular BM pattern (p=0.03), lower platelet count (p=0.02), and absence of trisomy 12 (p=0.01), but did not correlate with other BM infiltration patterns, increased PB PLs, atypical PB cytology, degree of BM involvement, other FISH abnormalities, or IP features. Increased PB PLs were associated with an increased degree of BM infiltration (p=0.001), higher serum LDH (p<0.001), and trisomy 12 (p<0.001), but not with distinct/prominent PCs in BM (p=0.24).
Conclusions: Our results show that PCs in CLL/SLL BMs are more common than previously described. However, they are more often seen in f/u than diagnostic BMs, and thus our results are likely skewed based on a referral bias toward advanced/aggressive CLL/SLL. While prominent PCs were associated with a nodular infiltration pattern, thrombocytopenia, and lack of trisomy 12, they surprisingly were not associated with increased PB PLs or atypical PB cytology.
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 164, Wednesday Morning