Expanded and highly active proliferation centers identify a histological subtype of chronic lymphocytic leukemia ("accelerated" chronic lymphocytic leukemia) with aggressive clinical behavior
Open Access
- 26 April 2010
- journal article
- Published by Ferrata Storti Foundation (Haematologica) in Haematologica
- Vol. 95 (9), 1526-1533
- https://doi.org/10.3324/haematol.2010.022277
Abstract
Background The concept of “accelerated” chronic lymphocytic leukemia is frequently used by both pathologists and clinicians. However, neither histological criteria to define this form of chronic lymphocytic leukemia nor its clinical correlates and prognostic impact have been formally defined in large series of patients. Design and Methods Tissue biopsies from 100 patients with chronic lymphocytic leukemia were analyzed for the size of proliferation centers and their proliferation rate as assessed by mitosis count and Ki-67 immunostaining. Histological patterns were correlated with main clinico-biological features and outcome. Results A suspicion of disease transformation was the main reason for carrying out tissue biopsy, which was performed at a median time of 14 months (range, 0 to 204 months) after the diagnosis of chronic lymphocytic leukemia. The biopsy showed histological transformation to diffuse large B-cell lymphoma in 22 cases. In the remaining 78 patients, the presence of expanded proliferation centers (broader than a 20x field) and high proliferation rate (either >2.4 mitoses/proliferation center or Ki-67 >40%/proliferation center) predicted a poor outcome and were selected to define a highly proliferative group. Thus, 23 patients with either expanded proliferation centers or high proliferation rate were considered as having “accelerated” chronic lymphocytic leukemia. These patients displayed particular features, including higher serum lactate dehydrogenase levels and more frequently elevated ZAP-70 than “non-accelerated” cases. The median survival from biopsy of patients with “non-accelerated” chronic lymphocytic leukemia, “accelerated” chronic lymphocytic leukemia and transformation to diffuse large B-cell leukemia was 76, 34, and 4.3 months, respectively (P<0.001). Conclusions The presence of expanded and/or highly active proliferation centers identifies a group of patients with “accelerated” chronic lymphocytic leukemia characterized by an aggressive clinical behavior.Keywords
This publication has 29 references indexed in Scilit:
- ZAP-70 Expression as a Surrogate for Immunoglobulin-Variable-Region Mutations in Chronic Lymphocytic LeukemiaThe New England Journal of Medicine, 2003
- Genetic Imbalances in Progressed B-Cell Chronic Lymphocytic Leukemia and Transformed Large-Cell Lymphoma (Richter's Syndrome)The American Journal of Pathology, 2002
- Multiple cell cycle regulator alterations in Richter's transformation of chronic lymphocytic leukemiaLeukemia, 2002
- B-cell chronic lymphocytic leukemia cells express a surface membrane phenotype of activated, antigen-experienced B lymphocytesBlood, 2002
- Immunophenotype Does Not Correlate With Lymph Node Histology in Chronic Lymphocytic Leukemia/Small Lymphocytic LymphomaThe American Journal of Surgical Pathology, 2002
- Survivin is expressed on CD40 stimulation and interfaces proliferation and apoptosis in B-cell chronic lymphocytic leukemiaBlood, 2001
- Genomic Aberrations and Survival in Chronic Lymphocytic LeukemiaThe New England Journal of Medicine, 2000
- Lymphocytic lymphoma/B-chronic lymphocytic leukaemia – An immunohistopathological study of peripheral B lymphocyte neoplasiaBritish Journal of Cancer, 1984
- The lymph node in chronic lymphocytic leukemiaCancer, 1978
- Conservatism of the approximation sigma (O-E)2-E in the logrank test for survival data or tumor incidence data.1973