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Approach to the patient with lymphocytosis or lymphocytopenia

INTRODUCTION

Lymphocytes are a subset of white blood cells (WBC) that form an integral part of the immune system. They facilitate the body's humoral and cellular immunity against foreign proteins and pathogens. An increase in circulating lymphocytes (lymphocytosis) can be seen following infections such as infectious mononucleosis and pertussis, or in lymphoproliferative disorders such as acute and chronic lymphocytic leukemia. A similar array of disorders can cause a decrease in lymphocyte counts (lymphocytopenia), although immunodeficiency states must also be considered, especially in infants and young children.

The various causes of lymphocytosis and lymphocytopenia will be reviewed here. Information on specific malignant conditions associated with abnormal lymphocyte counts (eg, chronic lymphocytic leukemia, large granular lymphocyte leukemia, acute lymphoblastic leukemia) is presented separately.

(See "Pathologic features, diagnosis, and differential diagnosis of chronic lymphocytic leukemia".)

(See "Clinical manifestations, pathologic features, and diagnosis of T cell large granular lymphocyte leukemia".)

(See "Clinical manifestations, pathologic features, and diagnosis of precursor B cell acute lymphoblastic leukemia/lymphoma".)

                                

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Literature review current through: Aug 2014. | This topic last updated: Feb 24, 2014.
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References
Top
  1. Carney D. Peripheral blood lymphocytosis--what is the threshold for further investigation? Leuk Lymphoma 2008; 49:1659.
  2. Andrews JM, Cruser DL, Myers JB, et al. Using peripheral smear review, age and absolute lymphocyte count as predictors of abnormal peripheral blood lymphocytoses diagnosed by flow cytometry. Leuk Lymphoma 2008; 49:1731.
  3. Kanegane H, Yachie A, Miyawaki T, Tosato G. EBV-NK cells interactions and lymphoproliferative disorders. Leuk Lymphoma 1998; 29:491.
  4. Brady KA, Atwater SK, Lowell CA. Flow cytometric detection of CD10 (cALLA) on peripheral blood B lymphocytes of neonates. Br J Haematol 1999; 107:712.
  5. Chantepie SP, Salaün V, Parienti JJ, et al. Hematogones: a new prognostic factor for acute myeloblastic leukemia. Blood 2011; 117:1315.
  6. Sevilla DW, Colovai AI, Emmons FN, et al. Hematogones: a review and update. Leuk Lymphoma 2010; 51:10.
  7. Downey H, McKinlay CA. Acute lymphadenosis compared with acute lymphatic leukemia. Arch Intern Med 1923; 32:82.
  8. Vetsika EK, Callan M. Infectious mononucleosis and Epstein-Barr virus. Expert Rev Mol Med 2004; 6:1.
  9. Balfour HH Jr, Odumade OA, Schmeling DO, et al. Behavioral, virologic, and immunologic factors associated with acquisition and severity of primary Epstein-Barr virus infection in university students. J Infect Dis 2013; 207:80.
  10. Horwitz CA, Henle W, Henle G, et al. Clinical and laboratory evaluation of cytomegalovirus-induced mononucleosis in previously healthy individuals. Report of 82 cases. Medicine (Baltimore) 1986; 65:124.
  11. Steeper TA, Horwitz CA, Hanson M, et al. Heterophil-negative mononucleosis-like illnesses with atypical lymphocytosis in patients undergoing seroconversions to the human immunodeficiency virus. Am J Clin Pathol 1988; 90:169.
  12. Buchanan JG, Goldwater PN, Somerfield SD, Tobias MI. Mononucleosis-like-syndrome associated with acute AIDS retrovirus infection. N Z Med J 1986; 99:405.
  13. Zambello R, Trentin L, Agostini C, et al. Persistent polyclonal lymphocytosis in human immunodeficiency virus-1-infected patients. Blood 1993; 81:3015.
  14. Cooper DA, Gold J, Maclean P, et al. Acute AIDS retrovirus infection. Definition of a clinical illness associated with seroconversion. Lancet 1985; 1:537.
  15. Steeper TA, Horwitz CA, Ablashi DV, et al. The spectrum of clinical and laboratory findings resulting from human herpesvirus-6 (HHV-6) in patients with mononucleosis-like illnesses not resulting from Epstein-Barr virus or cytomegalovirus. Am J Clin Pathol 1990; 93:776.
  16. Horwitz CA, Henle W, Henle G, et al. Heterophil-negative infectious mononucleosis and mononucleosis-like illnesses. Laboratory confirmation of 43 cases. Am J Med 1977; 63:947.
  17. Remington JS. Toxoplasmosis in the adult. Bull N Y Acad Med 1974; 50:211.
  18. Ehrlich GD, Han T, Bettigole R, et al. Human T-lymphotropic virus type I-associated benign transient immature T-cell lymphocytosis. Am J Hematol 1988; 27:49.
  19. Shiftan TA, Mendelsohn J. The circulating "atypical" lymphocyte. Hum Pathol 1978; 9:51.
  20. Smith CH. Infectious lymphocytosis. Am J Dis Child 1941; 62:231.
  21. OLSON LC, MILLER G, HANSHAW JB. ACUTE INFECTIOUS LYMPHOCYTOSIS PRESENTING AS A PERTUSSIS-LIKE ILLNESS: ITS ASSOCIATION WITH ADENOVIRUS TYPE 12. Lancet 1964; 1:200.
  22. Cassuto JP, Schneider M, Bourg M, et al. Acute infectious lymphocytosis as a T-cell lymphoproliferative syndrome. Br Med J 1977; 2:1331.
  23. Kubic VL, Kubic PT, Brunning RD. The morphologic and immunophenotypic assessment of the lymphocytosis accompanying Bordetella pertussis infection. Am J Clin Pathol 1991; 95:809.
  24. Heininger U, Stehr K, Schmitt-Grohé S, et al. Clinical characteristics of illness caused by Bordetella parapertussis compared with illness caused by Bordetella pertussis. Pediatr Infect Dis J 1994; 13:306.
  25. Levene I, Wacogne I. Question 3. Is measurement of the lymphocyte count useful in the investigation of suspected pertussis in infants? Arch Dis Child 2011; 96:1203.
  26. Margileth AM. Cat scratch disease. In: Nelson Textbook of Pediatrics, 15th ed, Behrman RE, Kliegman RM, Arvin AM (Eds), WB Saunders, Philadelphia 1996.
  27. Saadatnia G, Golkar M. A review on human toxoplasmosis. Scand J Infect Dis 2012; 44:805.
  28. Rosenbaum GS, Johnson DH, Cunha BA. Atypical lymphocytosis in babesiosis. Clin Infect Dis 1995; 20:203.
  29. Mosqueda J, Olvera-Ramirez A, Aguilar-Tipacamu G, Canto GJ. Current advances in detection and treatment of babesiosis. Curr Med Chem 2012; 19:1504.
  30. Perkins HA, Busch MP. Transfusion-associated infections: 50 years of relentless challenges and remarkable progress. Transfusion 2010; 50:2080.
  31. Pavlos R, Mallal S, Phillips E. HLA and pharmacogenetics of drug hypersensitivity. Pharmacogenomics 2012; 13:1285.
  32. Kano Y, Shiohara T. The variable clinical picture of drug-induced hypersensitivity syndrome/drug rash with eosinophilia and systemic symptoms in relation to the eliciting drug. Immunol Allergy Clin North Am 2009; 29:481.
  33. Teggatz JR, Parkin J, Peterson L. Transient atypical lymphocytosis in patients with emergency medical conditions. Arch Pathol Lab Med 1987; 111:712.
  34. Kho AN, Hui S, Kesterson JG, McDonald CJ. Which observations from the complete blood cell count predict mortality for hospitalized patients? J Hosp Med 2007; 2:5.
  35. Toft P, Tønnesen E, Svendsen P, et al. The redistribution of lymphocytes during adrenaline infusion. An in vivo study with radiolabelled cells. APMIS 1992; 100:593.
  36. Pinkerton PH, McLellan BA, Quantz MC, Robinson JB. Acute lymphocytosis after trauma--early recognition of the high-risk patient? J Trauma 1989; 29:749.
  37. Groom DA, Kunkel LA, Brynes RK, et al. Transient stress lymphocytosis during crisis of sickle cell anemia and emergency trauma and medical conditions. An immunophenotyping study. Arch Pathol Lab Med 1990; 114:570.
  38. Mills PJ, Berry CC, Dimsdale JE, et al. Lymphocyte subset redistribution in response to acute experimental stress: effects of gender, ethnicity, hypertension, and the sympathetic nervous system. Brain Behav Immun 1995; 9:61.
  39. Casassus P, Lortholary P, Komarover H, et al. Cigarette smoking-related persistent polyclonal B lymphocytosis. A premalignant state. Arch Pathol Lab Med 1987; 111:1081.
  40. Delannoy A, Djian D, Wallef G, et al. Cigarette smoking and chronic polyclonal B-cell lymphocytosis. Nouv Rev Fr Hematol 1993; 35:141.
  41. Troussard X, Mossafa H, Valensi F, et al. [Polyclonal lymphocytosis with binucleated lymphocytes. Morphological, immunological, cytogenetic and molecular analysis in 15 cases]. Presse Med 1997; 26:895.
  42. Lesesve JF, Troussard X. Persistent polyclonal B-cell lymphocytosis. Blood 2011; 118:6485.
  43. Cornet E, Lesesve JF, Mossafa H, et al. Long-term follow-up of 111 patients with persistent polyclonal B-cell lymphocytosis with binucleated lymphocytes. Leukemia 2009; 23:419.
  44. Delage R, Roy J, Jacques L, Darveau A. All patients with persistent polyclonal B cell lymphocytosis present Bcl-2/Ig gene rearrangements. Leuk Lymphoma 1998; 31:567.
  45. Dasanu CA, Codreanu I. Persistent polyclonal B-cell lymphocytosis in chronic smokers: more than meets the eye. Conn Med 2012; 76:69.
  46. Loembé MM, Lamoureux J, Deslauriers N, et al. Lack of CD40-dependent B-cell proliferation in B lymphocytes isolated from patients with persistent polyclonal B-cell lymphocytosis. Br J Haematol 2001; 113:699.
  47. Himmelmann A, Gautschi O, Nawrath M, et al. Persistent polyclonal B-cell lymphocytosis is an expansion of functional IgD(+)CD27(+) memory B cells. Br J Haematol 2001; 114:400.
  48. Salcedo I, Campos-Caro A, Sampalo A, et al. Persistent polyclonal B lymphocytosis: an expansion of cells showing IgVH gene mutations and phenotypic features of normal lymphocytes from the CD27+ marginal zone B-cell compartment. Br J Haematol 2002; 116:662.
  49. Delage R, Jacques L, Massinga-Loembe M, et al. Persistent polyclonal B-cell lymphocytosis: further evidence for a genetic disorder associated with B-cell abnormalities. Br J Haematol 2001; 114:666.
  50. Juneja S, Januszewicz E, Wolf M, Cooper I. Post-splenectomy lymphocytosis. Clin Lab Haematol 1995; 17:335.
  51. Garcia-Suarez J, Prieto A, Reyes E, et al. Persistent lymphocytosis of natural killer cells in autoimmune thrombocytopenic purpura (ATP) patients after splenectomy. Br J Haematol 1995; 89:653.
  52. Kelemen E, Gergely P, Lehoczky D, et al. Permanent large granular lymphocytosis in the blood of splenectomized individuals without concomitant increase of in vitro natural killer cell cytotoxicity. Clin Exp Immunol 1986; 63:696.
  53. Barton AD. T-cell lymphocytosis associated with lymphocyte-rich thymoma. Cancer 1997; 80:1409.
  54. Cranney A, Markman S, Lach B, Karsh J. Polymyositis in a patient with thymoma and T cell lymphocytosis. J Rheumatol 1997; 24:1413.
  55. Doll DC, Landreneau RJ, List AF. Malignant thymoma associated with peripheral T-cell lymphocytosis. Med Pediatr Oncol 1991; 19:496.
  56. Lishner M, Ravid M, Shapira J, et al. Delta-T-lymphocytosis in a patient with thymoma. Cancer 1994; 74:2924.
  57. Snow AL, Xiao W, Stinson JR, et al. Congenital B cell lymphocytosis explained by novel germline CARD11 mutations. J Exp Med 2012; 209:2247.
  58. Darte JM, McClure PD, Saunders EF, et al. Congenital lymphoid hyperplasia with persistent hyperlymphocytosis. N Engl J Med 1971; 284:431.
  59. Shim YK, Rachel JM, Ghia P, et al. Monoclonal B-cell lymphocytosis in healthy blood donors: an unexpectedly common finding. Blood 2014; 123:1319.
  60. Matos DM, Falcão RP. Monoclonal B-cell lymphocytosis: a brief review for general clinicians. Sao Paulo Med J 2011; 129:171.
  61. Mowery YM, Lanasa MC. Clinical aspects of monoclonal B-cell lymphocytosis. Cancer Control 2012; 19:8.
  62. Macintyre EA, Linch DC. Lymphocytosis: is it leukaemia and when to treat. Postgrad Med J 1988; 64:42.
  63. Berz D, Freeman NJ. Extreme hyperlymphocytosis. J Clin Oncol 2008; 26:674.
  64. Sivakumaran M, Richards S. Immunological abnormalities of chronic large granular lymphocytosis. Clin Lab Haematol 1997; 19:57.
  65. Kaito K, Otsubo H, Ogasawara Y, et al. Severe aplastic anemia associated with chronic natural killer cell lymphocytosis. Int J Hematol 2000; 72:463.
  66. Loughran TP Jr. Clonal diseases of large granular lymphocytes. Blood 1993; 82:1.
  67. Bockorny B, Dasanu CA. Autoimmune manifestations in large granular lymphocyte leukemia. Clin Lymphoma Myeloma Leuk 2012; 12:400.
  68. Pontikoglou C, Kalpadakis C, Papadaki HA. Pathophysiologic mechanisms and management of neutropenia associated with large granular lymphocytic leukemia. Expert Rev Hematol 2011; 4:317.
  69. Liu X, Loughran TP Jr. The spectrum of large granular lymphocyte leukemia and Felty's syndrome. Curr Opin Hematol 2011; 18:254.
  70. Castelino DJ, McNair P, Kay TW. Lymphocytopenia in a hospital population--what does it signify? Aust N Z J Med 1997; 27:170.