Advances in the understanding and management of T-cell prolymphocytic leukemia

Abstract

T-prolymphocytic leukemia (T-PLL) is a rare T-cell neoplasm with an aggressive clinical course. Leukemic T-cells exhibit a post-thymic T-cell phenotype (Tdt^-, CD1a^-, CD5⁺, CD2⁺ and CD7⁺) and are generally CD4⁺/CD8^-, but CD4⁺/CD8⁺ or CD8⁺/CD4^- T-PLL have also been reported. The hallmark of T-PLL is the rearrangement of chromosome 14 involving genes for the subunits of the T-cell receptor (TCR) complex, leading to overexpression of the proto-oncogene TCL1. In addition, molecular analysis shows that T-PLL exhibits substantial mutational activation of the IL2RG-JAK1-JAK3-, STAT5B axis. T-PLL patients have a poor prognosis, due to a poor response to conventional chemotherapy. Monoclonal antibody therapy with antiCD52-alemtuzumab has considerably improved outcomes, but the responses to treatment are transient; hence, patients who achieve a response to therapy are considered for stem cell transplantation (SCT). This combined approach has extended the median survival to four years or more. Nevertheless, new approaches using well-tolerated therapies that target growth and survival signals are needed for most patients unable to receive intensive chemotherapy.

Keywords: T-cell prolymphocytic leukemia; cytogenetic; molecular biology; morphology; treatment.

Figure 1. Small cells containing distinct nucleoli, irregular nuclei, and slightly basophilic cytoplasm (classical form) (MGG, X 100)

Figure 2. Small cell with inconspicuous nucleoli and a regular nucleus indistinguishable from CLL cells

Two larger cells with distinct nucleoli, round-oval nuclei, and basophilic cytoplasm (MGG, X 100).

Figure 3

Small cell with fine chromatin, cytoplasmic extensions, inconspicuous nucleoli, and basophilic cytoplasm (A). Small cell with distinct nucleoli and folded (wrinkled) nucleus (B): Sezary aspect (MGG, X 100).

Figure 4. Small and medium-sized cells containing distinct nucleoli and very irregular nuclei (flower-like appearance): ATLL aspect (MGG, X 100)

Figure 5. Small cells containing distinct nucleoli, basophilic cytoplasm, and irregular nuclei, barely distinguishable from CLL cells, except for the presence of characteristic cytoplasmic extensions (Blebs) (MGG, X 100)

Figure 6. Dermal infiltration with perivascular and periadnexal involvement without epidermotropism (HES, X 5)

Figure 7. Dermal infiltration by medium-sized cells with irregular immature nuclei (HES, X 40)

Figure 8. Diffuse lymph node infiltrate with paracortical expansion

Persistence of two residual lymphoid follicles (HES,X 5).

Figure 9. Lymph node infiltrate by medium-sized cells with irregular nuclei (HES, X 40)