Causes of double-negative T-cell lymphocytosis in children and adults.
AIMS
The causes and diagnosis of 'double-negative' (CD3+CD4-CD8-) T-cell lymphocytosis are not well studied. We aimed to define the causes of double-negative T-cell lymphocytosis in children and adults, and to identify simple clinical and laboratory features that would help to differentiate between the underlying conditions.


METHODS
We collected clinical and laboratory data on 10 children and 30 adults with significantly increased peripheral-blood double-negative T-cells (>10% of total lymphocytes). We identified conditions associated with double-negative T-lymphocytosis with flow cytometry, peripheral-blood morphology and T-cell receptor-gene rearrangement studies. Patients were assigned to diagnostic categories on the basis of these test results.


RESULTS AND CONCLUSIONS
The causes of double-negative T-cell lymphocytosis in children were autoimmune lymphoproliferative syndrome (ALPS) and reactive γ/δ Τ-lymphocytosis. T-cell large granular lymphocyte (T-LGL) leukaemia, reactive γ/δ T-lymphocytosis and hepatosplenic T-cell lymphoma (HSTL) were the the most common disorders underlying double-negative T-cell lymphocytosis in adults. Less common causes included hypereosinophilic syndrome, peripheral T-cell lymphoma, ALPS and monoclonal, double-negative T-lymphocytosis of uncertain significance. CD5/CD7/Vδ2 expression and absolute double-negative lymphocyte count (<1.8×109/L) were useful discriminators for distinguishing patients with reactive γ/δ T-lymphocytosis from those with γ/δ lymphoproliferative disorders. Differentiating between γ/δ T-LGL and HSTL can be difficult. Expression of CD57 and cellular morphology (pale cytoplasm with distinct granules) would support a diagnosis of γ/δ T-LGL.
['Liapis|Konstantinos|K|http://orcid.org/0000-0003-1165-9639', 'Tsagarakis|Nikolaos J|NJ|', 'Panitsas|Fotis|F|', 'Taparkou|Anna|A|', 'Liapis|Ioannis|I|', 'Roubakis|Christophoros|C|', 'Tsokanas|Dimitris|D|', 'Vasileiou|Paraskevi|P|', 'Grigoriou|Eirini|E|', 'Kakiopoulos|Georgios|G|', 'Psarra|Katerina|K|', 'Farmaki|Evangelia|E|', 'Paterakis|George|G|']
D000293:Adolescent D000328:Adult D000368:Aged D000369:Aged, 80 and over D056735:Autoimmune Lymphoproliferative Syndrome D015704:CD4 Antigens D018959:CD57 Antigens D016827:CD8 Antigens D002648:Child D002675:Child, Preschool D005260:Female D006115:Greece D006801:Humans D054066:Leukemia, Large Granular Lymphocytic D018655:Lymphocyte Count D008218:Lymphocytosis D008232:Lymphoproliferative Disorders D008297:Male D008875:Middle Aged D012189:Retrospective Studies D055815:Young Adult
flow cytometry morphology haemato-oncology haematology haematopathology