PT  - JOURNAL ARTICLE
AU  - Konstantinos Liapis
AU  - Nikolaos J Tsagarakis
AU  - Fotis Panitsas
AU  - Anna Taparkou
AU  - Ioannis Liapis
AU  - Christophoros Roubakis
AU  - Dimitris Tsokanas
AU  - Paraskevi Vasileiou
AU  - Eirini Grigoriou
AU  - Georgios Kakiopoulos
AU  - Katerina Psarra
AU  - Evangelia Farmaki
AU  - George Paterakis
TI  - Causes of double-negative T-cell lymphocytosis in children and adults
AID  - 10.1136/jclinpath-2019-206255
DP  - 2020 Jul 01
TA  - Journal of Clinical Pathology
PG  - 431--438
VI  - 73
IP  - 7
4099  - http://jcp.bmj.com/content/73/7/431.short
4100  - http://jcp.bmj.com/content/73/7/431.full
SO  - J Clin Pathol2020 Jul 01; 73
AB  - 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.