The distinctive cytological features of T‐cell prolymphocytic leukemia
Authors: Vishal Jayakar, Kan Cheung, Eva Yebra‐Fernandez, Barbara J. Bain
Journal: American Journal of Hematology (2017)

The first patient was a 64-year-old man, referred for investigation of asymptomatic lymphocytosis. He had no palpable lymphadenopathy or hepatosplenomegaly and no rash. His presenting full blood count (FBC) showed: white cell count (WBC) 15.6 × 109/L, hemoglobin concentration (Hb) 161 g/L, platelet count 165 × 109/L, and lymphocyte count 10.2 × 109/L. Other than a marginally elevated lactate dehydrogenase of 285 iu/L, biochemical tests were normal. His blood film showed mature lymphocytes with hyperchromatic irregular nuclei, indistinct nucleoli, and scanty basophilic cytoplasm forming blebs (Figure 1, left). In addition, there were abnormal lymphoid cells, which were larger with a lesser degree of chromatin condensation and with a more evident nucleolus (Figure 1, right). A presumptive diagnosis of T-cell prolymphocytic leukemia (T-PLL) was made on the basis of the cytological features. This was confirmed by immunophenotyping and cytogenetic analysis. Immunophenotyping of peripheral blood (PB) and bone marrow cells demonstrated an abnormal population of T lymphocytes expressing CD2, CD3, CD4, CD5, and strong CD7 with homogeneous co-expression of CD52. They were negative for CD8 and CD25. The karyotype was 46,XY,+8,-11,inv(14)(q11q32),add(15)(p13)[4]/46,idem,?t(2;15)(q21;q2?6)[1]/44,idem,add(2)(q37),-5,-8,-12,add(14)(q32),+19[2]/46,XY[4] (Figure 2). Peripheral blood (PB) film, case 1 Karyogram, case 1 The second patient, a 72-year-old woman, also had asymptomatic lymphocytosis with no hepatosplenomegaly, lymphadenopathy, or rash. Biochemical tests were normal. Her FBC showed: WBC 5.9 × 109/L, Hb 143 g/L, platelet count 333 × 109/L, and lymphocytes 4.9 × 109/L. Cytological features (Figure 3) were similar to those of the first patient but more subtle, again leading to a provisional diagnosis of T-PLL. PB immunophenotyping showed that most of the lymphocytes were T cells expressing CD2, CD4, and CD5 with stronger expression of CD3 and CD7 and homogeneous expression of CD26, CD28, and CD52. They were negative for CD8, CD11c, and CD25. The karyotype was 46,XX,inv(14)(q11.2q32)[2]/46,idem,add(12)(p1?)[12]/46,idem,add(12)(p1?),t(1;11)(p1;p1)[1]/46,idem,add(22)(q13)[2]/46,XX[3] (Figure 4). PB film, case 2 Karyogram, case 2 In both patients, fluorescence in situ hybridization confirmed the inv(14) and showed that the TRA/TRD locus was rearranged. Serology for human T-cell lymphotropic virus 1 was negative in both. The cytological features of T-PLL differ from those of B-PLL. The nucleus is more often hyperchromatic with the nucleolus being smaller and not so readily detected. The cytoplasm in many of the cells is scanty and basophilic and forms blebs. These features are sufficiently distinctive to strongly suggest this diagnosis. The diagnosis is supported by the detection of strong CD7 expression, this being unusual in other disorders of mature T lymphocytes but typical of T-PLL. Immunophenotyping also serves to demonstrate CD52 expression, which is clinically relevant since alemtuzumab may be used in therapy. In patients with appropriate cytological and immunophenotypic features, the diagnosis is confirmed by the demonstration of a karyotypic abnormality with a 14q32 breakpoint, particularly inv(14)(q11.2q32.1) (as in the current patients) or t(14;14)(q11.2;q32.1); the genes involved are TCL1A and TCL1B at 14q32.1 and the TRA/TRD locus at 14q11.2. A minority of patients (about 15%) with T-PLL are, like our patients, asymptomatic at diagnosis. This indolent phase can persist for a variable length of time, sometimes several years.1 However, progression is inevitable and may be very rapid when it occurs. Nothing to report.