Background and Aims

The risk of malignancy in Primary Immunodeficiency patients is high, especially with Ataxia-Telangiectasia (AT) – 30% develop malignancies, and T-cell leukaemia is frequent.

We intend to highlight the need for awareness concerning the risk of malignancy in AT, with emphasis on the importance of surveillance.

Methods

Case-Report:

26-year-old male, diagnosed at the age of 3 with AT, presenting a homozygous mutation of the ATM gene on exon-28. He has been under surveillance ever since, with regular immunological workup including immunoglobulin levels and evaluation of lymphocyte subpopulations.

Since 2013, a population of CD8+/CD4+dim T-lymphocytes was detected by flow-cytometry (9% of T-lymphocytes), remaining relatively steady until 2019, when a considerable increase was found (20,5%). In result, T-cells were characterized in more detail.

Results

There was no lymphocytosis nor cytopenias. TCRα/β+CD8+ T-cells (which represented 73% of peripheral blood T-cells, and from which 23% were CD4+dim) were increased in number (1145/mm³), had an immunophenotype indistinguishable from that typically found in T-cell Prolymphocytic Leukaemia (T-PLL) and strongly expressed the oncoprotein TCL-1, which is usually related with cytogenetic changes typical of T-PLL. Therefore, genetic (TCR gene rearrangements) and cytogenetic studies were requested and bone marrow evaluation was suggested.

Conclusions

In patients with AT, T-PLL can be preceded by a clonal (pre-leukemic) T-cell expansion.

It is imperative that clinicians are aware of the enhanced risk of malignancy in AT, namely T-PLL, so that proper surveillance and timely diagnosis are possible, allowing for a better treatment planning, so critical in these patients.