T-cell chronic lymphocytic leukemia or small-cell variant of T-cell prolymphocytic leukemia: a historical perspective and search for consensus

Eur J Haematol. 2015 Sep;95(3):199-210. doi: 10.1111/ejh.12560. Epub 2015 Apr 24.


There is a rich history behind the extinct entity 'T-cell chronic lymphocytic leukemia (T-CLL)' and the now-established replacement, small-cell variant of T-cell prolymphocytic leukemia (T-PLL-sv). Herein, we review the history of the events, observations, and discussions that led to this replacement. We also provide a systematic analysis of all previously reported cases of T-PLL-sv as well as our four new additional cases. Despite the higher frequency of a normal karyotype and perhaps an overrepresented CD4(-) CD8(-) immunophenotype among these patients (compared to T-PLL in general) as well as bland morphology (that makes them superficially appear more similar to B-CLL), we argue that the current World Health Organization (WHO)-based classification as T-PLL-sv is adequate and should continue for the time being. Morphologically, T-PLL-sv represents approximately one-fifth of all T-PLL cases. However, morphology alone does not determine the clinical course and should not be the basis for clinical decision making and prognostication. We propose a clonal evolution model in which mature T-cell leukemias classified in the past as T-CLL are perhaps T-PLL diagnosed early in the course of the disease. Future research using next-generation sequencing, comparative genomic hybridization, and molecular array studies, including serial analyses of individual cases over time, is needed to better identify this rarely diagnosed, inherently controversial form of T-cell leukemia.

Keywords: World Health Organization; chronic lymphocytic leukemia; nucleolus; prolymphocytic leukemia; small-cell variant.

Publication types

  • Review

MeSH terms

  • Animals
  • Clonal Evolution
  • Humans
  • Immunophenotyping
  • Leukemia, Lymphocytic, Chronic, B-Cell / diagnosis*
  • Leukemia, Lymphocytic, Chronic, B-Cell / etiology
  • Leukemia, Lymphocytic, Chronic, B-Cell / metabolism
  • Leukemia, Prolymphocytic, T-Cell / diagnosis*
  • Leukemia, Prolymphocytic, T-Cell / etiology
  • Leukemia, Prolymphocytic, T-Cell / metabolism
  • Research