The two cases seen in the present study demonstrate the immunophenotypic heterogeneity in T-PLL as in case #1 the neoplastic T-cells were CD8 positive while in case#2 the neoplastic T-cells were CD4 positive. In fact, T-PLL can also be double positive for CD4/CD8 or double negative for CD4/CD8. Furthermore, although the expression of CD52 is consistently expressed in T-PLL, and therefore this leukemia is a prime target for campath (aletuzumab) therapy, this feature is not unique to T-PLL as other T-cell lymphoma/leukemias as well as non-neoplastic T-cells are often positive for CD52.
From a morphologic stand-point, the two cases were also quite different with case #1 showing a more mature small lymphocytic appearance with inconspicuous nucleoli whereas case#2 showed larger lymphocytes with prominently placed central nucleolus (prolymphocytes). In fact, it is recognized that a subset of T-PLL cases will have a small lymphocytic appearance and these cases are often referred to as the small cell variant of T-PLL [2, 5]. Finally, the clinical scenarios were quite different in both cases with case#1 having a more indolent presentation whereas case#2 had a more typical aggressive presentation.
Complex karyotypes with structural abnormalities [1–8, 10–13] including 14q11.2 rearrangements as seen in our cases is observed in 80% of T-PLL cases. These abnormalities include inv(14)(q11.2q32) or the t(14;14)(q11;q32) . Rarely, the t(X;14)(q28;q11) or t(Y;14)(q12;q11) . The 14q32.1 region is very important because it is the locus of the TCL1 gene and any rearrangement at this locus is sufficient to activate TCL1 gene expression through juxtaposition of TCRA sequences [4, 12]. TCR stimulation leads to rapid recruitment of TCL1, AKT and tyrosine kinases to membrane associated activation complexes . However, TCL1 can also be activated by hypomethylation or loss of methylation on one allele of the TCL1 promoter region [7, 12]. Supporting this is the fact that the TCL-1 oncoprotein has been found to be expressed in approximately 70% of T-PLL cases . A study, using SNP-array and gene expression array technologies, 734 genes were found to be directly linked to inv(14), which were differentially expressed and involved in leukemia, cell cycle regulation, apoptosis and DNA repair .
Chromosome 8 anomalies as seen in our case are also common in T-PLL. Maljaei et al.  and Olivera et al.  suggest in their study the synergistic effect as a result of the increased expression of the MYC gene (8q24) due to an i(8q) and a deleterious loss of TSG on 8p such as MTUS1 when 8p is deleted in the pathogenesis of T-PLL.
Other findings in T-PLL that may be overlooked by conventional cytogenetics are anomalies of 11q  like in case 1 and abnormalities of chromosome 22 like in case 2. Both abnormalities were also confirmed by CGH  and SNP-array studies . The minimal deleted regions on chromosome 22 include the genes SMARCB1 (which encodes the SWI/SNF related proteins which might be involved in chromatin remodeling, chromosomal stability, and checkpoint control) and CHECK, which seem to be inactivated by biallelic mutation during T-PLL progression. This supports the hypothesis that there might be additional tumor suppressor genes (TSG) on chromosome 22 spanning from the centromere to the 22q12.1 region .
CGH studies  suggests that there are multiple additional chromosomal abnormalities involved in T-PLL that were previously under recognized by conventional karyotype and FISH analysis including gain of genetic material in many different chromosomal regions including 5p (62%), and 14q (37%), 6p and 21 (both 25%) and loss of genetic material on 13q (37%), 6q, 7q, 16q, 17p, and 17q (25%).
Durig et al.  using SNP-based array technique also found deletions in 6p, 8p, 11p, 11q, 12p, 13q and gains in 4q, 5p, 6p and 8q and 14q. Nowak et al.  found homozygous deletions on chromosomes 14 and 7 in the T-cell receptor loci, 12p, 5p; heterozygous deletions involving 13q, 17p and 17q and abnormalities involving 5q, 6p, 12p, 13q and 17p.
In conclusion, with the textbook cytogenetic abnormalities revealed in both of these cases that are highly associated with T-PLL we were able to come to a correct diagnosis. Of special note case#2 was initially incorrectly diagnosed as T-lymphoblastic leukemia highlighting that these cases can be diagnostic challenging. Morphologic evaluation, clinical data and techniques with higher resolution such as CGH and SNP-based genomic mapping will elucidate common deletions and gains of chromosomal material unique to T-PLL. Further studies using gene expression profiling techniques are needed to better understand and open more avenues for treatment targets of this disease.