title: Expanded and highly active proliferation centers identify a histological subtype of chronic lymphocytic leukemia ("accelerated" chronic lymphocytic leukemia) with aggressive clinical behavior.
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.
  
  
  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.
authors.affiliation: Department of Hematology, Hospital Clínic Villarroel n masculine 170, 08036-Barcelona, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Giné
authors.forename: Antoni
authors.initials: A
authors.lastname: Martinez
authors.forename: Neus
authors.initials: N
authors.lastname: Villamor
authors.forename: Armando
authors.initials: A
authors.lastname: López-Guillermo
authors.forename: Mireia
authors.initials: M
authors.lastname: Camos
authors.forename: Daniel
authors.initials: D
authors.lastname: Martinez
authors.forename: Jordi
authors.initials: J
authors.lastname: Esteve
authors.forename: Xavier
authors.initials: X
authors.lastname: Calvo
authors.forename: Ana
authors.initials: A
authors.lastname: Muntañola
authors.forename: Pau
authors.initials: P
authors.lastname: Abrisqueta
authors.forename: Maria
authors.initials: M
authors.lastname: Rozman
authors.forename: Ciril
authors.initials: C
authors.lastname: Rozman
authors.forename: Francesc
authors.initials: F
authors.lastname: Bosch
authors.forename: Elias
authors.initials: E
authors.lastname: Campo
authors.forename: Emili
authors.initials: E
authors.lastname: Montserrat
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000473:pathology*; D008198:Lymph Nodes / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D055815:Young Adult; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000032:analysis
chemical_list: D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human