Acute lymphoblastic leukemia differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Syed Hassan A. Kazmi BSc, MD [2]


Acute lymphoblastic leukemia must be differentiated from other diseases such as acute myelogenous leukemia, hairy cell leukemia and malignant lymphoma.[1]

Differential diagnosis

The following table differentiates acute lymphoblastic leukemia from other leukemias that may present with similar clinical features such as fever, fatigue, weight loss, recurrent infections and elevated leukocyte counts. The following are the differentials:

Disease Etiology Clinical Manifestation Laboratory Findings Gold standard diagnosis Associated findings
Demography History Symptoms Signs
Constitutional symptoms Weight Bleeding Abdominal Pain Vital sign Jaundice LAP Hepatosplenomegaly Other CBC Histopathology Other
Acute myelogenous leukemia[2][3]
  • Clonal proliferation of malignant myeloid blast cells in the marrow
  • Genetic abnormalities t(8;21), inv(16), and t(15;17)
+ Rare Mild and asymptomatic NA
  • Persistent or frequent infections
  • Fatal within weeks or months if left untreated
Acute lymphoblastic leukemia[4][5]
  • Arrest of lymphoblasts
  • Chromosomal translocations: t(9;22) , t(12;21), t(5;14), t(1;19)
  • The most common form of cancer in children
  • Peak 2-5 years of age
  • Boys > girls
  • History of cancer
  • History of drug exposure
+ + + NA
  • CNS involvement
Chronic myelogenous leukemia[6][7]
  • Median age 50 years old
+ Abdominal fullness
  • Normal
Disease Etiology Demography History Constitutional symptoms Weight Bleeding Abdominal Pain Vital sign Jaundice LAP Hepatosplenomegaly Other CBC Histopathology Other Gold standard diagnosis Associated findings
Chronic lymphocytic leukemia[8]
  • The most common leukemia in adults in western countries
  • M > F
  • Median age 70 years old
+ + +

The most common abnormal finding

Hairy cell leukemia[9][10]
  • Accumulation of small mature B cell lymphoid cells with abundant cytoplasm and "hairy" projections
  • BRAF mutation
  • Uncommon
  • Median age 50 to 55 years old
  • M >> F
  • More common in Caucasians than Blacks
+ Abdominal fullness
  • Normal
± +


Large granular lymphocytic leukemia[11][12]
  • Clonal proliferation of cytotoxic T cells
  • Dysregulation of apoptosis through abnormalities in the Fas/Fas ligand pathway
  • Rare
  • Median age 60 years
  • M = F
  • Autoimmune diseases
  • Lymphoproliferative disorders
± +
  • Mostly asymptomatic
  • Modest lymphocytosis
  • Neutropenia
  • Anemia
  • Thrombocytopenia
  • Large lymphocytes with a condensed round or oval nucleus, abundant pale basophilic cytoplasm, and small azurophilic granules
  • Multiple serological abnormalities including rheumatoid factor, antinuclear antibody, antiplatelet antibodies, antineutrophil antibodies, positive direct Coombs test, hyper- or hypogammaglobulinemia, monoclonal gammopathies, and elevated β2-microglobulin
  • Biopsy and flow cytometry + T-cell receptor gene rearrangement studies
  • Recurrent bacterial infection
Chronic neutrophilic leukemia[13]
  • Mature granulocytic proliferation in the blood and marrow
  • Point mutations in the CSF3R gene
  • Very rare
  • M = F
  • Multiple myeloma

The most common clinical finding

  • Pruritus
  • Gout
  • Peripheral blood neutrophilia (> 25 x 109/L) with myeloid precursors (promyelocytes, myelocytes, metamyelocytes)
  • Toxic granulation in the neutrophils
  • Nuclear hypersegmentation
  • Increased myeloid:erythroid ratio > 20:1
  • WHO diagnostic criteria include leukocytosis of ≥ 25 x 109/L
  • More than 80% neutrophils,
  • Less than 10% circulating neutrophil precursors with blasts
  • Poor prognosis
  • Absence of the Philadelphia chromosome or a BCR/ABL fusion gene
Disease Etiology Demography History Constitutional symptoms Weight Bleeding Abdominal Pain Vital sign Jaundice LAP Hepatosplenomegaly Other CBC Histopathology Other Gold standard diagnosis Associated findings


  1. "National Cancer Institute".
  2. Saif A, Kazmi S, Naseem R, Shah H, Butt MO (August 2018). "Acute Myeloid Leukemia: Is That All There Is?". Cureus. 10 (8): e3198. doi:10.7759/cureus.3198. PMID 30410824. Vancouver style error: initials (help)
  3. Estey EH (April 2013). "Acute myeloid leukemia: 2013 update on risk-stratification and management". Am. J. Hematol. 88 (4): 318–27. doi:10.1002/ajh.23404. PMID 23526416.
  4. Sawalha Y, Advani AS (March 2018). "Management of older adults with acute lymphoblastic leukemia: challenges & current approaches". Int J Hematol Oncol. 7 (1): IJH02. doi:10.2217/ijh-2017-0023. PMC 6176956. PMID 30302234.
  5. Portell CA, Advani AS (April 2014). "Novel targeted therapies in acute lymphoblastic leukemia". Leuk. Lymphoma. 55 (4): 737–48. doi:10.3109/10428194.2013.823493. PMID 23841506.
  6. Saußele S, Silver RT (April 2015). "Management of chronic myeloid leukemia in blast crisis". Ann. Hematol. 94 Suppl 2: S159–65. doi:10.1007/s00277-015-2324-0. PMID 25814082.
  7. Eden RE, Coviello JM. PMID 30285354. Missing or empty |title= (help)
  8. Rai KR, Jain P (March 2016). "Chronic lymphocytic leukemia (CLL)-Then and now". Am. J. Hematol. 91 (3): 330–40. doi:10.1002/ajh.24282. PMID 26690614.
  9. Troussard X, Cornet E (December 2017). "Hairy cell leukemia 2018: Update on diagnosis, risk-stratification, and treatment". Am. J. Hematol. 92 (12): 1382–1390. doi:10.1002/ajh.24936. PMC 5698705. PMID 29110361.
  10. Wierda WG, Byrd JC, Abramson JS, Bhat S, Bociek G, Brander D, Brown J, Chanan-Khan A, Coutre SE, Davis RS, Fletcher CD, Hill B, Kahl BS, Kamdar M, Kaplan LD, Khan N, Kipps TJ, Lancet J, Ma S, Malek S, Mosse C, Shadman M, Siddiqi T, Stephens D, Wagner N, Zelenetz AD, Dwyer MA, Sundar H (November 2017). "Hairy Cell Leukemia, Version 2.2018, NCCN Clinical Practice Guidelines in Oncology". J Natl Compr Canc Netw. 15 (11): 1414–1427. doi:10.6004/jnccn.2017.0165. PMID 29118233.
  11. Matutes E (March 2017). "Large granular lymphocytic leukemia. Current diagnostic and therapeutic approaches and novel treatment options". Expert Rev Hematol. 10 (3): 251–258. doi:10.1080/17474086.2017.1284585. PMID 28128670.
  12. Oshimi K (2017). "Clinical Features, Pathogenesis, and Treatment of Large Granular Lymphocyte Leukemias". Intern. Med. 56 (14): 1759–1769. doi:10.2169/internalmedicine.56.8881. PMC 5548667. PMID 28717070.
  13. Elliott MA, Tefferi A (August 2018). "Chronic neutrophilic leukemia: 2018 update on diagnosis, molecular genetics and management". Am. J. Hematol. 93 (4): 578–587. doi:10.1002/ajh.24983. PMID 29512199.

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