Comparison of karyotyping, TCL1 fluorescence in situ hybridisation and TCL1 immunohistochemistry in T cell prolymphocytic leukaemia.

AIMS: T cell prolymphocytic leukaemia (T-PLL) is defined as an aggressive T cell leukaemia composed of small to medium-sized lymphocytes with a mature T cell immunophenotype. Most of these cases are known to be associated with inv(14q11q32)/t(14;14)(q11;q32) or rarely t(X;14)(q28;q11). However, T-PLL can show variations in clinical presentation, morphology or immunophenotype that can make a diagnosis of T-PLL challenging. We aim to explore the value of ancillary testing in the diagnosis of T-PLL.

METHODS: With this large cohort of 69 patients with T-PLL, we compared the diagnostic utility of conventional cytogenetics, TCL1 rearrangement by fluorescence in situ hybridisation (FISH) and TCL1 expression by immunohistochemistry (IHC).

RESULTS: Conventional karyotyping was performed in all 69 patients and was abnormal in 44 (65%), showing 14q32 abnormalities in 31 (43%) and t(X;14) ( MTCP ) in 2 (3%). TCL1 rearrangement was assessed by FISH in 26 cases and was positive in 23 (85%). All cases with 14q32 abnormalities shown by karyotype were positive for TCL1 rearrangement by FISH, whereas 12/15 (80%) cases without 14q32 abnormalities were also positive. TCL1 overexpression by IHC was detected in 51/64 (81%), including 40/42 (95%) cases with TCL1 /14q32 rearrangement, and 3 cases without, showing a concordance of 89%. TCL1 IHC was negative in both cases with t(X;14)(q28;q11).

CONCLUSIONS: Our study shows that TCL1 by IHC is a convenient test, positive in >80% T-PLL. Conventional cytogenetics is insensitive in the detection of 14q32/ TCL1 rearrangements but provides more complete information of the chromosomal landscape of T-PLL. FISH for TCL1 rearrangement is very valuable in diagnostic challenging cases.