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Causes of double-negative T-cell lymphocytosis in children and adults
  1. Konstantinos Liapis1,
  2. Nikolaos J Tsagarakis2,
  3. Fotis Panitsas3,
  4. Anna Taparkou4,
  5. Ioannis Liapis5,
  6. Christophoros Roubakis6,
  7. Dimitris Tsokanas1,
  8. Paraskevi Vasileiou7,
  9. Eirini Grigoriou8,
  10. Georgios Kakiopoulos9,
  11. Katerina Psarra8,
  12. Evangelia Farmaki4,
  13. George Paterakis2
  1. 1 Department of Clinical Haematology, Peripheral General Hospital Athens Giorgos Gennimatas, Athens, Greece
  2. 2 Department of Immunology, Peripheral General Hospital Athens Giorgos Gennimatas, Athens, Greece
  3. 3 Department of Haematology, General University Hospital of Larisa, Larissa, Thessaly, Greece
  4. 4 Paediatric Immunology and Rheumatology Referral Center, First Department of Paediatrics, Aristotle University of Thessaloniki, Thessaloniki, Greece
  5. 5 Department of Haematology, University Hospital of Crete, Heraklion, Greece
  6. 6 Department of Haematology, Metaxa Cancer Hospital of Piraeus, Piraeus, Greece
  7. 7 Department of Flow Cytometry, Flowdiagnosis Diagnostic Center, Athens, Greece
  8. 8 Flow Cytometry Laboratory, Department of Immunology and Histocompatibility, Evangelismos Athens General Hospital, Athens, Greece
  9. 9 Department of Pathology, Peripheral General Hospital Athens Giorgos Gennimatas, Athens, Greece
  1. Correspondence to Dr Konstantinos Liapis, Department of Clinical Haematology, Peripheral General Hospital Athens Giorgos Gennimatas, Athens, Greece; kosliapis{at}


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.

  • haematology
  • haemato-oncology
  • haematopathology
  • flow cytometry
  • morphology

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  • Handling editor Stephen R A Jolles.

  • Contributors KL conceived the idea for this study, collected and analysed data, reviewed blood smears and wrote the manuscript. NJT contributed to the concept of the study and collected the data. FP collected and analysed data. AT, CR, PV and EG collected the data. IL and DT collected the data and reviewed the literature. KP and EF reviewed flow cytometry data. GK provided expert histopathology review. GP contributed to the concept of the study and reviewed blood smears and flow cytometry data. All authors contributed to the writing of the manuscript. All authors reviewed and approved the final version of the manuscript.

  • Disclaimer This manuscript contains original material that has not been published or submitted previously to another journal. All authors agree to the submission of this manuscript to the Journal of Clinical Pathology.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval All clinical samples and data were collected for routine patient care. This retrospective study was done in accordance with the ethical standards of the institutional research committees of Georgios Gennimatas Hospital and Evangelismos Hospital.

  • Provenance and peer review Not commissioned; externally peer reviewed.