Acute lymphoblastic leukemia differential diagnosis: Difference between revisions

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__NOTOC__
__NOTOC__
{{Acute lymphoblastic leukemia}}
[[Image:Home_logo1.png|right|250px|link=https://www.wikidoc.org/index.php/Acute_lymphoblastic_leukemia]]
{{CMG}}; {{AE}} {{CLG}}
{{CMG}}; {{AE}} {{HK}}
== Overview ==
== Overview ==
Acute lymphoblastic leukemia must be differentiated from [[acute myelogenous leukemia]], [[hairy cell leukemia]] and [[malignant lymphoma]].<ref name=ALL>{{cite web | title = National Cancer Institute| url =http://www.cancer.gov/types/leukemia/hp/adult-all-treatment-pdq }}</ref>
Acute lymphoblastic leukemia must be differentiated from other diseases such as [[acute myelogenous leukemia]], [[hairy cell leukemia]] and [[malignant lymphoma]].<ref name=ALL>{{cite web | title = National Cancer Institute| url =http://www.cancer.gov/types/leukemia/hp/adult-all-treatment-pdq }}</ref>


== Differential diagnosis ==
== Differential diagnosis ==
Acute lymphoblastic leukemia must be differentiated from other diseases such as:<ref name=ALL>{{cite web | title = National Cancer Institute| url =http://www.cancer.gov/types/leukemia/hp/adult-all-treatment-pdq }}</ref>
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:
*[[Acute myelogenous leukemia]]
 
*[[Hairy cell leukemia]]
{|
*[[Malignant lymphoma]]
! rowspan="3" align="center" style="background:#4479BA; color: #FFFFFF;" + |Disease
! rowspan="3" align="center" style="background:#4479BA; color: #FFFFFF;" + |Etiology
! colspan="11" align="center" style="background:#4479BA; color: #FFFFFF;" + |Clinical Manifestation
! colspan="3" rowspan="2" align="center" style="background:#4479BA; color: #FFFFFF;" + |Laboratory Findings
! rowspan="3" align="center" style="background:#4479BA; color: #FFFFFF;" + |Gold standard diagnosis
! rowspan="3" align="center" style="background:#4479BA; color: #FFFFFF;" + |Associated findings
|-
! rowspan="2" align="center" style="background:#4479BA; color: #FFFFFF;" + |Demography
! rowspan="2" align="center" style="background:#4479BA; color: #FFFFFF;" + |History
! colspan="4" align="center" style="background:#4479BA; color: #FFFFFF;" + |Symptoms
! colspan="5" align="center" style="background:#4479BA; color: #FFFFFF;" + |Signs
|-
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Constitutional symptoms
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Weight
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Bleeding
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Abdominal Pain
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Vital sign
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Jaundice
! align="center" style="background:#4479BA; color: #FFFFFF;" + |LAP
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Hepatosplenomegaly
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Other
! align="center" style="background:#4479BA; color: #FFFFFF;" + |CBC
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Histopathology
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Other
|-
! align="center" style="background:#DCDCDC;" + |[[Acute myelogenous leukemia]]<ref name="pmid30410824">{{cite journal |vauthors=Saif A, Kazmi SFA, Naseem R, Shah H, Butt MO |title=Acute Myeloid Leukemia: Is That All There Is? |journal=Cureus |volume=10 |issue=8 |pages=e3198 |date=August 2018 |pmid=30410824 |doi=10.7759/cureus.3198 |url=}}</ref><ref name="pmid23526416">{{cite journal |vauthors=Estey EH |title=Acute myeloid leukemia: 2013 update on risk-stratification and management |journal=Am. J. Hematol. |volume=88 |issue=4 |pages=318–27 |date=April 2013 |pmid=23526416 |doi=10.1002/ajh.23404 |url=}}</ref>
| align="left" style="background:#F5F5F5;" + |
* Clonal proliferation of malignant myeloid blast cells in the marrow
* Genetic abnormalities t(8;21), inv(16), and t(15;17)
| align="left" style="background:#F5F5F5;" + |
* The most common type of acute leukemia in adults
* Median age of 63 years old
* More in [[congenital]] disorders such as  [[Down syndrome]], [[Bloom syndrome]]
| align="left" style="background:#F5F5F5;" + |
* [[Smoking]], previous [[chemotherapy]] or [[radiation therapy]], [[myelodysplastic syndrome]], and exposure to the chemical [[benzene]]
| align="left" style="background:#F5F5F5;" + |
* [[Fatigue]]
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | –
| align="left" style="background:#F5F5F5;" + |
* [[Fever]]
| align="center" style="background:#F5F5F5;" + | –
| align="center" style="background:#F5F5F5;" + |Rare
| align="center" style="background:#F5F5F5;" + |Mild and asymptomatic
| align="left" style="background:#F5F5F5;" + |
* Bone [[tenderness]]
* [[Dyspnea]]
* Leukemia cutis
* Swelling of the [[Gingiva|gums]]
* Chloroma
| align="left" style="background:#F5F5F5;" + |
* [[Anemia]]
* [[Thrombocytopenia]]
* [[Leukocytosis]] or [[leukopenia]]
| align="left" style="background:#F5F5F5;" + |
* Leukemic blasts
* Positive [[Auer rod|Auer rods]]
| align="center" style="background:#F5F5F5;" + |NA
| align="left" style="background:#F5F5F5;" + |
* [[Flow cytometry]] > 20% blasts of [[myeloid]] lineage
| align="left" style="background:#F5F5F5;" + |
* Persistent or frequent [[infections]]
* Fatal within weeks or months if left untreated
|-
! align="center" style="background:#DCDCDC;" + |[[Acute lymphoblastic leukemia]]<ref name="pmid30302234">{{cite journal |vauthors=Sawalha Y, Advani AS |title=Management of older adults with acute lymphoblastic leukemia: challenges & current approaches |journal=Int J Hematol Oncol |volume=7 |issue=1 |pages=IJH02 |date=March 2018 |pmid=30302234 |pmc=6176956 |doi=10.2217/ijh-2017-0023 |url=}}</ref><ref name="pmid23841506">{{cite journal |vauthors=Portell CA, Advani AS |title=Novel targeted therapies in acute lymphoblastic leukemia |journal=Leuk. Lymphoma |volume=55 |issue=4 |pages=737–48 |date=April 2014 |pmid=23841506 |doi=10.3109/10428194.2013.823493 |url=}}</ref>
| align="left" style="background:#F5F5F5;" + |
* Arrest of  [[lymphoblasts]]
* Chromosomal translocations: t(9;22) , t(12;21), t(5;14), t(1;19)
| align="left" style="background:#F5F5F5;" + |
* The most common form of cancer in children
*Peak 2-5 years of age
*Boys > girls
| align="left" style="background:#F5F5F5;" + |
* History of [[cancer]]
* History of drug exposure
| align="left" style="background:#F5F5F5;" + |
* Generalized weakness and [[Fatigue (physical)|fatigue]]
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | –
| align="left" style="background:#F5F5F5;" + |
* [[Fever]]
| align="center" style="background:#F5F5F5;" + | –
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="left" style="background:#F5F5F5;" + |
* Musculoskeletal pain
* [[Dyspnea]]
* [[Pallor]]
* [[Papilledema]]
* [[Meningism|Nuchal rigidity]]
* [[Cranial nerve palsy]]
* [[Testicle|Testicular]] enlargement
* [[Mediastinal mass]]
| align="left" style="background:#F5F5F5;" + |
* [[Anemia]]
* [[Thrombocytopenia]] 
* Normal or slightly increased [[White blood cells|WBC]] counts 
| align="left" style="background:#F5F5F5;" + |
* [[Lymphoblast|Lymphoblasts]]
* Atypical cells
| align="center" style="background:#F5F5F5;" + |NA
| align="left" style="background:#F5F5F5;" + |
* [[Bone marrow examination|Bone marrow biopsy]]
| align="left" style="background:#F5F5F5;" + |
* [[CNS]] involvement
|-
! align="center" style="background:#DCDCDC;" + |[[Chronic myelogenous leukemia]]<ref name="pmid25814082">{{cite journal |vauthors=Saußele S, Silver RT |title=Management of chronic myeloid leukemia in blast crisis |journal=Ann. Hematol. |volume=94 Suppl 2 |issue= |pages=S159–65 |date=April 2015 |pmid=25814082 |doi=10.1007/s00277-015-2324-0 |url=}}</ref><ref name="pmid30285354">{{cite journal |vauthors=Eden RE, Coviello JM |title= |journal= |volume= |issue= |pages= |date= |pmid=30285354 |doi= |url=}}</ref>
| align="left" style="background:#F5F5F5;" + |
* Dysregulated production and uncontrolled proliferation of mature and maturing [[Granulocyte|granulocytes]]
* [[BCR/ABL|BCR-ABL1]] fusion gene
* [[Dominance relationship|Autosomal dominant]] mutation
| align="left" style="background:#F5F5F5;" + |
* Median age 50 years old
| align="center" style="background:#F5F5F5;" + |
| align="left" style="background:#F5F5F5;" + |
* Generalized [[Muscle weakness|weakness]] and [[Fatigue (physical)|fatigue]]
* [[Satiety|Early satiety]]
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Abdominal fullness
| align="left" style="background:#F5F5F5;" + |
* Normal
| align="center" style="background:#F5F5F5;" + | –
| align="center" style="background:#F5F5F5;" + | –
| align="center" style="background:#F5F5F5;" + | +
| align="left" style="background:#F5F5F5;" + |
*Asymptomatic
*[[Blast crisis]] resembling acute leukemia
*Excessive [[Perspiration|sweating]]
* [[Papilledema]]
* [[Tenderness]] over the lower [[sternum]]
| align="left" style="background:#F5F5F5;" + |
* [[Anemia]]
* [[White blood cells|WBC]] > 100,000/microL
* Absolute [[basophilia]] and [[eosinophilia]]
* [[Platelet|Plt]] > 600,000 to 700,000/microL
| align="left" style="background:#F5F5F5;" + |
* All cells of the neutrophilic series, from [[Myeloblast|myeloblasts]] to mature [[Neutrophil|neutrophils]]
* [[Myelocyte]] bulge
| align="left" style="background:#F5F5F5;" + |
* Low [[leukocyte alkaline phosphatase]]
* High [[uric acid]]
| align="left" style="background:#F5F5F5;" + |
* [[Bone marrow examination|Bone marrow biopsy]]
| align="left" style="background:#F5F5F5;" + |
* Acute [[Gout|gouty arthritis]]
* Venous obstruction
|-
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Disease
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Etiology
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Demography
! align="center" style="background:#4479BA; color: #FFFFFF;" + |History
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Constitutional symptoms
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Weight
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Bleeding
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Abdominal Pain
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Vital sign
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Jaundice
! align="center" style="background:#4479BA; color: #FFFFFF;" + |LAP
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Hepatosplenomegaly
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Other
! align="center" style="background:#4479BA; color: #FFFFFF;" + |CBC
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Histopathology
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Other
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Gold standard diagnosis
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Associated findings
|-
! align="center" style="background:#DCDCDC;" + |'''Chronic lymphocytic leukemia'''<ref name="pmid266906142">{{cite journal |vauthors=Rai KR, Jain P |title=Chronic lymphocytic leukemia (CLL)-Then and now |journal=Am. J. Hematol. |volume=91 |issue=3 |pages=330–40 |date=March 2016 |pmid=26690614 |doi=10.1002/ajh.24282 |url=}}</ref>
| align="left" style="background:#F5F5F5;" + |
* Progressive accumulation of monoclonal [[B cell|B lymphocytes]]
| align="left" style="background:#F5F5F5;" + |
* The most common leukemia in adults in western countries
* M > F
* Median age 70 years old
| align="left" style="background:#F5F5F5;" + |
* Positive family history
* Exposure to [[Herbicide|herbicides]] or [[Insecticide|insecticides]]
| align="left" style="background:#F5F5F5;" + |
* Generalized [[weakness]]
* [[Anorexia]]
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="left" style="background:#F5F5F5;" + |
* [[Fever]]
| align="center" style="background:#F5F5F5;" + | –
| align="center" style="background:#F5F5F5;" + | +
The most common abnormal finding
| align="center" style="background:#F5F5F5;" + | +
| align="left" style="background:#F5F5F5;" + |
* [[Skin lesion|Skin lesions]] (leukemia cutis)
* [[Sleep hyperhidrosis|Night sweats]]
* [[Muscle wasting]]
| align="left" style="background:#F5F5F5;" + |
* [[Anemia]]
* [[Thrombocytopenia]]
* Absolute [[lymphocytosis]] >5000 cells/μl
* [[Neutropenia]]
| align="left" style="background:#F5F5F5;" + |
* Presence of smudge cells
* Monoclonality of [[Light chain|kappa]] and [[Lambda (anatomy)|lambda]] producing [[B cell|B cells]]
* Express [[CD19]], [[CD20]], [[CD23]], and [[CD5]] on the [[cell]] surface
| align="left" style="background:#F5F5F5;" + |
* Positive direct antiglobulin (Coombs) test
* [[Hypogammaglobulinemia]]
* Elevated levels of serum [[lactate dehydrogenase]] and [[beta-2 microglobulin]]
| align="left" style="background:#F5F5F5;" + |
* [[Flow cytometry]] of the [[Venous blood|peripheral blood]]
| align="left" style="background:#F5F5F5;" + |
* Extranodal involvement of [[skin]], [[kidney]], [[lung]], [[Spinal cord|spine]]
* [[Membranoproliferative glomerulonephritis]]
* [[Autoimmune hemolytic anemia]]
|-
! align="center" style="background:#DCDCDC;" + |[[Hairy cell leukemia]]<ref name="pmid29110361">{{cite journal |vauthors=Troussard X, Cornet E |title=Hairy cell leukemia 2018: Update on diagnosis, risk-stratification, and treatment |journal=Am. J. Hematol. |volume=92 |issue=12 |pages=1382–1390 |date=December 2017 |pmid=29110361 |pmc=5698705 |doi=10.1002/ajh.24936 |url=}}</ref><ref name="pmid29118233">{{cite journal |vauthors=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 |title=Hairy Cell Leukemia, Version 2.2018, NCCN Clinical Practice Guidelines in Oncology |journal=J Natl Compr Canc Netw |volume=15 |issue=11 |pages=1414–1427 |date=November 2017 |pmid=29118233 |doi=10.6004/jnccn.2017.0165 |url=}}</ref>
| align="left" style="background:#F5F5F5;" + |
* Accumulation of small mature [[B cell]] lymphoid cells with abundant [[cytoplasm]] and "hairy" projections
* [[BRAF]] mutation
| align="left" style="background:#F5F5F5;" + |
* Uncommon
* Median age 50 to 55 years old
* M >> F
* More common in Caucasians than Blacks
| align="left" style="background:#F5F5F5;" + |
* Exposures to [[ionizing radiation]], [[Pesticide|pesticides]], and farming
| align="left" style="background:#F5F5F5;" + |
* [[Muscle weakness|Weakness]] and [[fatigue]]
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Abdominal fullness
| align="left" style="background:#F5F5F5;" + |
* Normal
| align="center" style="background:#F5F5F5;" + | –
| align="center" style="background:#F5F5F5;" + |±
| align="center" style="background:#F5F5F5;" + | +
[[Splenomegaly]]
| align="left" style="background:#F5F5F5;" + |
* Asymptomatic
* Spontaneous [[splenic rupture]]
* [[Rash|Skin rash]]
* [[Ascites]]
* [[Pleural effusion]]
| align="left" style="background:#F5F5F5;" + |
* [[Cytopenia]]
* [[Leukocytosis]] in 10 to 20 percent
| align="left" style="background:#F5F5F5;" + |
* [[Pancytopenia]] with [[monocytopenia]] and circulating tumor cells characteristic of HCL
* Dry [[bone marrow]]
| align="left" style="background:#F5F5F5;" + |
* [[Azotemia]]
* Abnormal [[liver function tests]]
* [[Hypergammaglobulinemia]]
| align="left" style="background:#F5F5F5;" + |
* Analysis of [[Venous blood|peripheral blood]] + [[immunophenotyping]] by [[flow cytometry]]
| align="left" style="background:#F5F5F5;" + |
* [[Vasculitis]]
|-
! align="center" style="background:#DCDCDC;" + |Large granular lymphocytic leukemia<ref name="pmid28128670">{{cite journal |vauthors=Matutes E |title=Large granular lymphocytic leukemia. Current diagnostic and therapeutic approaches and novel treatment options |journal=Expert Rev Hematol |volume=10 |issue=3 |pages=251–258 |date=March 2017 |pmid=28128670 |doi=10.1080/17474086.2017.1284585 |url=}}</ref><ref name="pmid28717070">{{cite journal |vauthors=Oshimi K |title=Clinical Features, Pathogenesis, and Treatment of Large Granular Lymphocyte Leukemias |journal=Intern. Med. |volume=56 |issue=14 |pages=1759–1769 |date=2017 |pmid=28717070 |pmc=5548667 |doi=10.2169/internalmedicine.56.8881 |url=}}</ref>​
| align="center" style="background:#F5F5F5;" + |
* Clonal proliferation of cytotoxic T cells
* Dysregulation of apoptosis through abnormalities in the Fas/Fas ligand pathway
| align="center" style="background:#F5F5F5;" + |
* Rare
* Median age 60 years
* M = F
| align="center" style="background:#F5F5F5;" + |
* Autoimmune diseases
* Lymphoproliferative disorders
| align="center" style="background:#F5F5F5;" + |
* [[Muscle weakness|Weakness]] and [[fatigue]]
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |–
| align="center" style="background:#F5F5F5;" + |–
| align="center" style="background:#F5F5F5;" + |
* [[Fever]]
| align="center" style="background:#F5F5F5;" + |–
| align="center" style="background:#F5F5F5;" + |±
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |
* Mostly asymptomatic
| align="center" style="background:#F5F5F5;" + |
* Modest lymphocytosis
* Neutropenia
* Anemia
* Thrombocytopenia
| align="center" style="background:#F5F5F5;" + |
* Large lymphocytes with a condensed round or oval nucleus, abundant pale basophilic cytoplasm, and small azurophilic granules
| align="center" style="background:#F5F5F5;" + |
* 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
| align="center" style="background:#F5F5F5;" + |
* Biopsy and flow cytometry + T-cell receptor gene rearrangement studies
| align="center" style="background:#F5F5F5;" + |
* Recurrent bacterial infection
|-
! align="center" style="background:#DCDCDC;" + |[[Chronic neutrophilic leukemia]]<ref name="pmid29512199">{{cite journal |vauthors=Elliott MA, Tefferi A |title=Chronic neutrophilic leukemia: 2018 update on diagnosis, molecular genetics and management |journal=Am. J. Hematol. |volume=93 |issue=4 |pages=578–587 |date=August 2018 |pmid=29512199 |doi=10.1002/ajh.24983 |url=}}</ref>
| align="center" style="background:#F5F5F5;" + |
* Mature granulocytic proliferation in the blood and marrow
* Point mutations in the CSF3R gene
| align="center" style="background:#F5F5F5;" + |
* Very rare
* M = F
| align="center" style="background:#F5F5F5;" + |
* Multiple myeloma
| align="center" style="background:#F5F5F5;" + |
* [[Muscle weakness|Weakness]] and [[fatigue]]
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |–
| align="center" style="background:#F5F5F5;" + |–
| align="center" style="background:#F5F5F5;" + |
* [[Fever]]
| align="center" style="background:#F5F5F5;" + |–
| align="center" style="background:#F5F5F5;" + |–
| align="center" style="background:#F5F5F5;" + | +
The most common clinical finding
| align="center" style="background:#F5F5F5;" + |
* Pruritus
* Gout
| align="center" style="background:#F5F5F5;" + |
* Peripheral blood neutrophilia (> 25 x 10<sup>9</sup>/L) with myeloid precursors (promyelocytes, myelocytes, metamyelocytes)
| align="center" style="background:#F5F5F5;" + |
* Toxic granulation in the [[Neutrophil|neutrophils]]
* Nuclear hypersegmentation
* Increased myeloid:erythroid ratio > 20:1
| align="center" style="background:#F5F5F5;" + |
* Elevated [[leukocyte alkaline phosphatase]]
| align="center" style="background:#F5F5F5;" + |
* WHO diagnostic criteria include leukocytosis of ≥ 25 x 109/L
* More than 80% neutrophils,
* Less than 10% circulating neutrophil precursors with blasts
| align="center" style="background:#F5F5F5;" + |
* Poor prognosis
* Absence of the Philadelphia chromosome or a BCR/ABL fusion gene
|-
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Disease
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Etiology
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Demography
! align="center" style="background:#4479BA; color: #FFFFFF;" + |History
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Constitutional symptoms
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Weight
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Bleeding
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Abdominal Pain
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Vital sign
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Jaundice
! align="center" style="background:#4479BA; color: #FFFFFF;" + |LAP
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Hepatosplenomegaly
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Other
! align="center" style="background:#4479BA; color: #FFFFFF;" + |CBC
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Histopathology
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Other
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Gold standard diagnosis
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Associated findings
|-
|}


==References==
==References==
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[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Hematology]]
[[Category:Immunology]]

Latest revision as of 20:32, 27 February 2019

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

Overview

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
± +

Splenomegaly

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

References

  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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