Lymphocytosis (lymphocytes > 4 G/L in adults)
BioMG follows French guidelines. Adapt it to the guidelines and the tests available where you practise.
Lymphocytosis in adults: first tests and recheck
Laboratory tests
- FBC with blood film
- ASTif needednon-French guidelineRecent fever, sore throat, fatigue or jaundice suggesting a viral infection (mononucleosis, hepatitis): the Lothian pathway combines liver function tests and viral serology in primary care [2].
- ALTif needednon-French guidelineRecent fever, sore throat, fatigue or jaundice suggesting a viral infection (mononucleosis, hepatitis): the Lothian pathway combines liver function tests and viral serology in primary care [2].
- GGTif needednon-French guidelineRecent fever, sore throat, fatigue or jaundice suggesting a viral infection (mononucleosis, hepatitis): the Lothian pathway combines liver function tests and viral serology in primary care [2].
- Alkaline phosphataseif needednon-French guidelineRecent fever, sore throat, fatigue or jaundice suggesting a viral infection (mononucleosis, hepatitis): the Lothian pathway combines liver function tests and viral serology in primary care [2].
- Monospot test or EBV serology (if mononucleosis-like syndrome or febrile sore throat)if needednon-French guidelineSore throat, fever, cervical lymphadenopathy or mononucleosis-like syndrome reported on the blood film: look for primary EBV infection [2].
- CMV IgG and IgM serology (if mononucleosis-like syndrome without EBV)if neededMononucleosis-like syndrome or prolonged fever with a negative mononucleosis spot test: look for recent CMV infection [2] (covered by the French laboratory fee schedule (NABM) when recent infection is suspected [3]).
- HIV serology (if risk factor or mononucleosis-like syndrome)if needednon-French guidelineAt-risk exposure, mononucleosis-like syndrome or unexplained fever: primary HIV infection may cause lymphocytosis; the Lothian pathway includes HIV in the viral serology [2].
- Hepatitis B serology (HBsAg, anti-HBc)if needednon-French guidelineCytolysis on the liver function tests or at-risk exposure: the Lothian pathway includes hepatitis B and C in the viral serology [2].
- Hepatitis C serologyif needednon-French guidelineCytolysis on the liver function tests or at-risk exposure: the Lothian pathway includes hepatitis B and C in the viral serology [2].
- Pertussis PCR on nasopharyngeal sample (paroxysmal cough, infant or contact)if needednon-French guidelineParoxysmal cough or contact with a case, especially in young infants, in whom pertussis is accompanied by leucocytosis [4]: see also the page “Whooping cough (suspected)”.
In 3 months
- FBC with blood film (repeat)
Persistent lymphocytosis (> 3 months) without reactive cause
Laboratory tests
- FBC with blood film
- Blood lymphocyte immunophenotyping (search for a monoclonal B population)
- Refer to a haematology consultation, non-urgently, to confirm the diagnosis (enclose previous FBCs).
Do not order
- Bone marrow aspirate, bone marrow biopsy or lymph node biopsy to establish the diagnosis of CLL: unnecessary when the full blood count and the Matutes score are characteristic [6].
- CT scan, PET-CT, cytogenetics or molecular biology in an asymptomatic stage A or B patient: none is to be performed [6].
Stage A CLL or monoclonal B lymphocytosis: monitoring in the community
Every 6 to 12 months (depending on progression)
- FBC with blood film
- Reticulocyte count
- Haptoglobinif neededOnset of anaemia: look for autoimmune haemolytic anaemia, a complication of CLL [6].
- Bilirubinif neededOnset of anaemia: look for autoimmune haemolytic anaemia, a complication of CLL [6].
- LDHif neededOnset of anaemia: look for autoimmune haemolytic anaemia, a complication of CLL [6].
- Direct Coombs testif neededOnset of anaemia: look for autoimmune haemolytic anaemia, a complication of CLL [6].
- Serum protein electrophoresis (if infections)if neededInfectious complication: look for hypogammaglobulinaemia [6].
Do not order
Warning signs: urgent advice
- Hyperlymphocytosis with general symptoms, lymphadenopathy or splenomegaly (adult); unexplained petechiae or hepatosplenomegaly (child); infant with whooping cough and hyperleucocytosis: urgent specialist opinion.
Sources (14)
- Ryan CE, Ahn IE, Sekar A, et al. State of the art biology, progression, and clinical management of monoclonal B-cell lymphocytosis (MBL): consensus report from the Intercepting Blood Cancers Workshop Committee. Blood Cancer J. 2025;15(1):148.
- NHS Lothian. RefHelp : Lymphocytosis (haematology referral guideline), version du 24 juillet 2026.
- Assurance maladie. Nomenclature des actes de biologie médicale (NABM), version 105 : actes 1103 (phénotypage des cellules anormales), 1104 (hémogramme) et 1260 (cytomégalovirus, IgG et IgM).
- Carbonetti NH. Pertussis leukocytosis: mechanisms, clinical relevance and treatment. Pathog Dis. 2016;74(7):ftw087.
- Warny M, Helby J, Nordestgaard BG, Birgens H, Bojesen SE. Lymphopenia and risk of infection and infection-related death in 98,344 individuals from a prospective Danish population-based study. PLoS Med. 2018;15(11):e1002685.
- Institut national du cancer. Leucémie lymphoïde chronique : du diagnostic au suivi. Collection Outils pour la pratique des médecins généralistes. Boulogne-Billancourt : INCa ; 2023 (expertise adoptée par décision n° 2023-16 du 05/06/2023).
- Régent A, Kluger N, Bérezné A, Lassoued K, Mouthon L. Démarche diagnostique devant une lymphopénie : quand penser à la lymphopénie CD4 idiopathique ? Rev Med Interne. 2012;33(11):628-634.
- Humber and North Yorkshire Policy and Pathway Repository (York). Lymphocytosis pathway. York and Scarborough Teaching Hospitals, équipe d'hématologie ; créé le 18 juin 2025, modifié le 16 septembre 2025 (révision prévue le 31 mars 2027).
- Riley LK, Rupert J. Evaluation of Patients with Leukocytosis. Am Fam Physician. 2015;92(11):1004-1011.
- Haute Autorité de santé, Institut national du cancer. Actes et prestations — ALD n° 30 « Leucémie lymphoïde chronique ». Octobre 2012.
- Wendtner CM, Al-Sawaf O, Binder M, Dreger P, et al. Chronische Lymphatische Leukämie (CLL). Leitlinie Onkopedia (DGHO), octobre 2026.
- Kreuzer KA, Brüggemann M, Egle A, Gregor M, et al. Monoklonale B-Zell Lymphozytose. Leitlinie Onkopedia (DGHO), août 2024.
- National Institute for Health and Care Excellence. Suspected cancer: recognition and referral (NG12). Mise à jour du 15 avril 2026 : recommandations 1.10.2 et 1.10.3.
- Labe P, Meunier A, Leroux P, et al. Variability in the Diagnostic Criteria for Severe Pertussis: A Systematic Review. JAMA Netw Open. 2026;9(7):e2622211.