Chronic lymphocytic leukemia differential diagnosis: Difference between revisions

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{{Chronic lymphocytic leukemia}}
[[Image:Home_logo1.png|right|250px|link=https://www.wikidoc.org/index.php/Chronic_lymphocytic_leukemia]]
{{CMG}} {{AE}}{{HL}} {{HK}}
{{CMG}} {{AE}}{{HL}} {{HK}}
==Overview==
==Overview==
* Chronic lymphocytic leukemia must be differentiated from other diseases that cause [[weight loss]],  [[night sweats]], [[hepatosplenomegaly]], and palpable [[lymph node]]s, such as [[hairy cell leukaemia]], [[Prolymphocytic leukemia|prolymphocytic leukaemia]], [[follicular lymphoma]], and [[mantle cell lymphoma]].<ref name="H">Hoffbrand V, Moss P. Essential Haematology. John Wiley & Sons; 2011</ref>
Chronic lymphocytic leukemia must be differentiated from other diseases that cause [[weight loss]],  [[night sweats]], [[hepatosplenomegaly]], and palpable [[lymph node]]s, such as [[hairy cell leukaemia]], [[Prolymphocytic leukemia|prolymphocytic leukaemia]], [[follicular lymphoma]], and [[mantle cell lymphoma]].


==Differenting Chronic lymphocytic leukemia from other Diseases==
==Differenting Chronic lymphocytic leukemia from other Diseases==
===Differentials based on Biomarkers===
Chronic lymphocytic leukemia must be differentiated from other diseases that cause [[weight loss]],  [[night sweats]], [[hepatosplenomegaly]], and palpable [[lymph node]]s, such as [[hairy cell leukaemia]], [[Prolymphocytic leukemia|prolymphocytic leukaemia]], [[follicular lymphoma]], and [[mantle cell lymphoma]].
* Chronic lymphocytic leukemia must be differentiated from other diseases that cause [[weight loss]],  [[night sweats]], [[hepatosplenomegaly]], and palpable [[lymph node]]s, such as [[hairy cell leukaemia]], prolymphocytic leukaemia, [[follicular lymphoma]], and [[mantle cell lymphoma]].
* Based on the expression of cell surface markers, the table below differentiates chronic lymphocytic leukemia from other diseases that cause similar clinical presentations:<ref name="H">Hoffbrand V, Moss P. Essential Haematology. John Wiley & Sons; 2011</ref>
<br>
{| style="border: 0px; font-size: 90%; margin: 3px; width: 1000px"
| valign="top" |
|+
! style="background: #4479BA; width: 600px;" | {{fontcolor|#FFF|'''Differential Diagnosis'''}}
! style="background: #4479BA; width: 300px;" | {{fontcolor|#FFF|'''Surface Immunoglobulin'''}}
! style="background: #4479BA; width: 300px;" | {{fontcolor|#FFF|'''CD5'''}}
! style="background: #4479BA; width: 400px;" | {{fontcolor|#FFF|'''CD22/FMC7'''}}
! style="background: #4479BA; width: 300px;" | {{fontcolor|#FFF|'''CD23'''}}
! style="background: #4479BA; width: 300px;" | {{fontcolor|#FFF|'''CD79b'''}}
! style="background: #4479BA; width: 300px;" | {{fontcolor|#FFF|'''CD103'''}}
 
|-
 
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
'''Chronic lymphocytic leukemia'''
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |
'''Weakly positive'''
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |
'''Positive'''
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |
'''Negative'''
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |
'''Positive'''
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |
'''Negative'''
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |
'''Positive/Negative'''
 
|-
 
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
'''[[Prolymphocytic leukemia]]'''
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |
'''Strongly positive'''
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |
'''Negative'''
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |
'''Positive'''
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |
'''Negative'''
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |
'''Positive'''
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |
'''Negative'''
 
|-
 
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
'''[[Hairy cell leukemia]]'''
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |
'''Strongly positive'''
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |
'''Negative'''
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |
'''Positive'''
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |
'''Negative'''
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |
'''Positive/Negative'''
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |
'''Positive'''
 
|-
 
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
'''[[Mantle cell lymphoma]]'''
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |
'''Positive'''
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |
'''Positive'''
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |
'''Strongly positive'''
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |
'''Negative'''
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |
'''Strongly positive'''
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |
'''Negative'''
 
|-
 
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
'''[[Follicular lymphoma]]'''
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |
'''Strongly positive'''
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |
'''Negative'''
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |
'''Positive'''
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |
'''Negative'''
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |
'''Strongly positive'''
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |
'''Negative'''
|}
<br>
* Chronic lymphocytic leukemia must also be differentiated from other causes of fever, hepatosplenomegaly, and lymph node swelling such as:
:* [[Splenic marginal zone lymphoma]]
:* Nodal marginal zone [[lymphoma]]
:* [[Lymphoplasmacytic lymphoma]]
:* [[Sézary syndrome]]
:* Smoldering [[adult T cell leukemia]]
 
===Other Differentials===
The following table differentiates chronic lymphocytic 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:
 
{| class="wikitable"
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Characteristic
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Causes
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Laboratory abnormalities
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Physical examination
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Therapy
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Other associations
|-
|[[Acute myeloid leukemia|'''Acute myeloid leukemia''']]
|
* [[Chromosomal]] instability
* Sporadic [[mutations]]
* Prior exposure to [[benzene]]
* Prior exposure to alkylating agents
* Prior exposure to [[Topoisomerase II|topoisomerase II inhibitors]]
* [[Germline]] ''[[RUNX1]]'' [[mutation]]
|
* [[Anemia]]
* [[Thrombocytopenia]]
* [[Neutropenia]]
* Elevated [[LDH]]
* Elevated [[uric acid]]
* Elevated [[phosphorus]]
* Elevated [[potassium]]
* Low [[calcium]]
* Greater than 20% [[myeloblasts]] on [[bone marrow]] aspirate<ref name="pmid27895058">{{cite journal| author=Döhner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Büchner T et al.| title=Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. | journal=Blood | year= 2017 | volume= 129 | issue= 4 | pages= 424-447 | pmid=27895058 | doi=10.1182/blood-2016-08-733196 | pmc=5291965 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27895058  }} </ref>
|
* [[Pyrexia]]
* Evidence of [[infection]]
* [[Pallor]]
* [[Mucosal]] [[bleeding]] (less common than in [[acute promyelocytic leukemia]])
* [[Bruising]] (less common than in [[acute promyelocytic leukemia]])
|
* [[Cytarabine]]
* [[Anthracycline]]
* [[Enasidenib]]
* [[Liposomal]] [[daunorubicin]] plus [[cytarabine]]
* [[Gemtuzumab ozogamicin|Gemtuzumab ozogamycin]]
* [[Midostaurin]]
* [[Enasidenib]]
* Ivosidenib
* [[Stem cell transplant]]
|
* Variable [[prognosis]] based on [[cytogenetic]] and molecular profile
* Five new [[Food and Drug Administration|FDA]]-approved therapies became available in 2017-2018
|-
|[[Acute promyelocytic leukemia|'''Acute promyelocytic leukemia''']]
|
* Prior exposure to alkylating agents
* Prior exposure to [[topoisomerase II]] inhibitors
* [[Chromosomal translocation|Translocation]] between [[Chromosome 15 (human)|chromosomes 15]] and [[Chromosome 17 (human)|17]]
* Creation of PML-RAR''alpha'' [[gene]] product
* Differentiation block in [[myeloid cells]]
|
* Low [[white blood cell]] count (typically)
* [[Anemia]]
* [[Neutropenia]]
* [[Thrombocytopenia]]
* Low [[fibrinogen]]
* Elevated prothrombin time (PT)
* Elevated partial thromboplastin time (PTT)
|
* [[Mucosal bleeding]]
* [[Petechiae]]
* [[Ecchymoses]]
* Evidence of [[infection]]
* [[Pallor]]
* [[Thrombosis]]
|
* [[All-trans retinoic acid|All-''trans'' retinoic acid]] (ATRA)
* Arsenic trioxide
* [[Cytarabine]]
* [[Anthracycline]]
|
* Presence of [[Auer rods]] in promyelocytes
* High risk for early death from [[hemorrhagic]] complications<ref name="pmid21993679">{{cite journal| author=McClellan JS, Kohrt HE, Coutre S, Gotlib JR, Majeti R, Alizadeh AA et al.| title=Treatment advances have not improved the early death rate in acute promyelocytic leukemia. | journal=Haematologica | year= 2012 | volume= 97 | issue= 1 | pages= 133-6 | pmid=21993679 | doi=10.3324/haematol.2011.046490 | pmc=3248942 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21993679  }} </ref>
|-
|[[Acute lymphoblastic leukemia|'''Acute lymphoblastic leukemia''']]
|
* [[Chromosomal]] instability
* Sporadic [[mutations]]
|
* [[Anemia]]
* [[Thrombocytopenia]]
* [[Neutropenia]]
* Elevated [[LDH]]
* Elevated [[uric acid]]
* Elevated [[phosphorus]]
* Elevated [[potassium]]
* Low [[calcium]]
* Greater than 20% [[lymphoblasts]] on [[bone marrow]] aspirate
|
* [[Neurological|Neurologic]] deficits
* [[Pallor]]
* [[Lymphadenopathy]]
|
* HyperCVAD ([[cyclophosphamide]], [[vincristine]], [[doxorubicin]], [[dexamethasone]])<ref name="pmid28665419">{{cite journal| author=Terwilliger T, Abdul-Hay M| title=Acute lymphoblastic leukemia: a comprehensive review and 2017 update. | journal=Blood Cancer J | year= 2017 | volume= 7 | issue= 6 | pages= e577 | pmid=28665419 | doi=10.1038/bcj.2017.53 | pmc=5520400 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28665419  }} </ref>
* R-HyperCVAD (inclusion of [[rituximab]])
* Peg-asparaginase
* [[Intrathecal]] [[methotrexate]]
* [[Intrathecal]] [[cytarabine]]
* [[Blinatumomab]] (bispecific [[T cell]] engager)
* [[Inotuzumab ozogamicin|Inotuzumab]] ozogamycin (anti-CD22 antibody)
* [[Tisagenlecleucel]] (chimeric antigen receptor T (CAR-T) cell therapy)
* [[Stem cell transplant]]
|
* Sanctuary sites include the [[central nervous system]] ([[CNS]]) and [[testes]]<ref name="pmid23523389">{{cite journal| author=Inaba H, Greaves M, Mullighan CG| title=Acute lymphoblastic leukaemia. | journal=Lancet | year= 2013 | volume= 381 | issue= 9881 | pages= 1943-55 | pmid=23523389 | doi=10.1016/S0140-6736(12)62187-4 | pmc=3816716 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23523389  }} </ref>
|-
|[[Chronic myelogenous leukemia|'''Chronic myeloid leukemia''']]
|
* [[Translocation]] between [[Chromosome 9 (human)|chromosomes 9]] and [[Chromosome 22|22]]
* Creation of [[Bcr-abl|BCR-Abl]] [[gene]] product
|
* Elevated [[white blood cell]] count
* Presence of [[white blood cell]] precursors at various stages of maturation
* Presence of excess metamyelocytes, [[basophils]], [[eosinophils]], and [[band cells]]
|
* [[Splenomegaly]]
* [[Abdominal tenderness]]
* [[Pallor]]
* Evidence of [[infection]]
|
* [[Imatinib]]
* [[Nilotinib]]
* [[Dasatinib]]
* [[Bosutinib]]
* [[Ponatinib]]
* [[Omacetaxine]]<ref name="pmid24516334">{{cite journal| author=Chen Y, Li S| title=Omacetaxine mepesuccinate in the treatment of intractable chronic myeloid leukemia. | journal=Onco Targets Ther | year= 2014 | volume= 7 | issue=  | pages= 177-86 | pmid=24516334 | doi=10.2147/OTT.S41786 | pmc=3916637 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24516334  }} </ref>
|
* High response rate to [[tyrosine kinase inhibitors]]
* Risk for development of T315I [[kinase]] domain [[mutation]]
* Typically does not require [[stem cell transplant]]
* Three phases include chronic, accelerated, and blast phase
|-
|-
|[[Chronic lymphocytic leukemia|'''Chronic lymphocytic leukemia''']]<ref name="pmid28102226">{{cite journal| author=Kipps TJ, Stevenson FK, Wu CJ, Croce CM, Packham G, Wierda WG et al.| title=Chronic lymphocytic leukaemia. | journal=Nat Rev Dis Primers | year= 2017 | volume= 3 | issue=  | pages= 16096 | pmid=28102226 | doi=10.1038/nrdp.2016.96 | pmc=5336551 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28102226  }} </ref>
|
* Chromosomal instability
* Sporadic [[mutations]]
* [[Infections]]
|
* Elevated absolute [[lymphocyte]] count (in all stages)
* Presence of >5000 clonal [[B cells]] per microliter in peripheral blood
* Anemia (in Rai stage III)
* [[Thrombocytopenia]] (in Rai stage IV)
|
* [[Lymph node enlargement]] in Rai stage I
* [[Splenomegaly]] in Rai stage II
* [[Hepatomegaly]] in Rai stage II
* [[Pallor]]
* [[Bleeding]]
|
* Fludarabine
* Cyclophosphamide
* Rituximab
* Obinutuzumab<ref name="pmid28182141">{{cite journal| author=Al-Sawaf O, Fischer K, Engelke A, Pflug N, Hallek M, Goede V| title=Obinutuzumab in chronic lymphocytic leukemia: design, development and place in therapy. | journal=Drug Des Devel Ther | year= 2017 | volume= 11 | issue=  | pages= 295-304 | pmid=28182141 | doi=10.2147/DDDT.S104869 | pmc=5279834 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28182141  }} </ref>
* Ofatumumab
* Ibrutinib
* Venetoclax
|
* Associated with [[autoimmune hemolytic anemia]], which occurs in 10-25% of patients with CLL
* Associated with [[immune thrombocytopenia purpura]]
* Associated with [[pure red cell aplasia]]
* Treatment with corticosteroids or anti-leukemic therapy will correct the autoimmune complications of CLL
|}


==References==
==References==
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Latest revision as of 20:33, 27 February 2019

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Haytham Allaham, M.D. [2] Syed Hassan A. Kazmi BSc, MD [3]

Overview

Chronic lymphocytic leukemia must be differentiated from other diseases that cause weight loss, night sweats, hepatosplenomegaly, and palpable lymph nodes, such as hairy cell leukaemia, prolymphocytic leukaemia, follicular lymphoma, and mantle cell lymphoma.

Differenting Chronic lymphocytic leukemia from other Diseases

Chronic lymphocytic leukemia must be differentiated from other diseases that cause weight loss, night sweats, hepatosplenomegaly, and palpable lymph nodes, such as hairy cell leukaemia, prolymphocytic leukaemia, follicular lymphoma, and mantle cell lymphoma.

References