Expanded and highly active proliferation centers identify a histological subtype of chronic lymphocytic leukemia ("accelerated" chronic lymphocytic leukemia) with aggressive clinical behavior.
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.
Giné
Eva
E
Department of Hematology, Hospital Clínic Villarroel n masculine 170, 08036-Barcelona, Spain.
Martinez
Antoni
A
Villamor
Neus
N
López-Guillermo
Armando
A
Camos
Mireia
M
Martinez
Daniel
D
Esteve
Jordi
J
Calvo
Xavier
X
Muntañola
Ana
A
Abrisqueta
Pau
P
Rozman
Maria
M
Rozman
Ciril
C
Bosch
Francesc
F
Campo
Elias
E
Montserrat
Emili
E
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
D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human