Acute promyelocytic leukemia differential diagnosis: Difference between revisions

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{{Acute promyelocytic leukemia}}
{{Acute promyelocytic leukemia}}
{{CMG}}
{{CMG}} {{shyam}}
==Differentiating Acute promyelocytic meukemia from other Diseases==
==Differentiating Acute promyelocytic meukemia from other Diseases==
Acute promyelocytic leukemia can be distinguished from other types of AML based on morphologic examination of a [[bone marrow biopsy]] or aspirate.  Definitive diagnosis requires testing for the ''RARα'' fusion gene. This may be done by [[polymerase chain reaction]] (PCR), [[fluorescent in situ hybridization]] (FISH), or conventional [[cytogenetics]] of peripheral blood or bone marrow.
Acute promyelocytic leukemia can be distinguished from other types of AML based on morphologic examination of a [[bone marrow biopsy]] or aspirate.  Definitive diagnosis requires testing for the ''RARα'' fusion gene. This may be done by [[polymerase chain reaction]] (PCR), [[fluorescent in situ hybridization]] (FISH), or conventional [[cytogenetics]] of peripheral blood or bone marrow.
{| class="wikitable"
!Characteristic
!Causes
!Laboratory abnormalities
!Physical examination
!Therapy
!Other associations
|-
|Acute promyelocytic leukemia
|
* Translocation between chromosomes 15 and 17
* Creation of PML-RAR''alpha''gene product
|
* Low [[white blood cell]] count (typically)
* [[Anemia]]
* [[Neutropenia]]
* [[Thrombocytopenia]]
* Low [[fibrinogen]]
|
* [[Mucosal bleeding]]
* [[Bruising]]
* Infections
* Fatigue
|
* All-''trans'' retinoic acid (ATRA)
* Arsenic trioxide
* [[Cytarabine]]
* [[Anthracycline]]
|
* Presence of Auer rods in promyelocytes
* High risk for early death from hemorrhagic complications
|-
|Acute myeloid leukemia
|
* Chromosomal instability
* Sporadic mutations
|
* [[Schistocytes]] on peripheral blood smear
* Low hemoglobin
* [[Thrombocytopenia]]
* Elevated [[creatinine]]
|
* Bleeding
* Thrombosis
* Pyrexia
* Altered mental status
* Neurologic deficits
* Impaired urine output
|
* Treatment of the underlying cause
* Plasmapheresis if [[thrombotic thrombocytopenia purpura]] is the underlying cause
|
* Can be life-threatening pending the underlying cause
* TTP required immediate treatment
|-
|Paroxysmal cold hemoglobinuria
|
* Production of [[Donath-Landsteiner antibody]], triggered by viral or bacterial infection<ref name="pmid25699184">{{cite journal| author=Akpoguma AO, Carlisle TL, Lentz SR| title=Case report: paroxysmal cold hemoglobinuria presenting during pregnancy. | journal=BMC Hematol | year= 2015 | volume= 15 | issue=  | pages= 3 | pmid=25699184 | doi=10.1186/s12878-015-0023-7 | pmc=4334594 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25699184  }} </ref>
|
* Positive Donath-Landsteiner antibody
* Microscopic hematuria
* Negative Coombs' test for IgG or C3d
* Negative cold agglutinin titer
* Indirect [[hyperbilirubinemia]]
* [[Reticulocytosis]]
* Low [[haptoglobin]]
* Elevated [[LDH]]
|
* [[Hematuria]] in the presence of cold weather
* [[Jaundice]]
|
* Removal of offending agent
* [[Steroids]]
* Alternative [[immunosuppression]]
|
* Associated with syphilis<ref name="pmid25699184">{{cite journal| author=Akpoguma AO, Carlisle TL, Lentz SR| title=Case report: paroxysmal cold hemoglobinuria presenting during pregnancy. | journal=BMC Hematol | year= 2015 | volume= 15 | issue=  | pages= 3 | pmid=25699184 | doi=10.1186/s12878-015-0023-7 | pmc=4334594 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25699184  }} </ref>
* Maternal IgG can cross the placenta and affect the fetus<ref name="pmid25699184">{{cite journal| author=Akpoguma AO, Carlisle TL, Lentz SR| title=Case report: paroxysmal cold hemoglobinuria presenting during pregnancy. | journal=BMC Hematol | year= 2015 | volume= 15 | issue=  | pages= 3 | pmid=25699184 | doi=10.1186/s12878-015-0023-7 | pmc=4334594 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25699184  }} </ref>
|-
|Paroxysmal nocturnal hemoglobinuria
|
* Genetic defect in anchoring proteins for complement factors on [[red blood cells]]
|
* Hemolysis due to loss of complement inhibition on the [[red blood cell]] surface, which in turn is due to defect in CD55 (decay accelerating factor) and CD59
|
* Splenomegaly
* Abdominal tenderness
* Pallor
|
* [[Eculizumab]]
* Immunosuppressive therapy
|
* Associated with [[myelodysplastic syndrome]]
* Associated with mesenteric and portal venous thrombosis
* Risk for progression to [[acute myeloid leukemia]]
|-
|[[Hereditary spherocytosis]]<ref name="pmid24237975">{{cite journal| author=Gallagher PG| title=Abnormalities of the erythrocyte membrane. | journal=Pediatr Clin North Am | year= 2013 | volume= 60 | issue= 6 | pages= 1349-62 | pmid=24237975 | doi=10.1016/j.pcl.2013.09.001 | pmc=4155395 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24237975  }} </ref>
|
* Mutation in ankyrin<ref name="pmid24237975">{{cite journal| author=Gallagher PG| title=Abnormalities of the erythrocyte membrane. | journal=Pediatr Clin North Am | year= 2013 | volume= 60 | issue= 6 | pages= 1349-62 | pmid=24237975 | doi=10.1016/j.pcl.2013.09.001 | pmc=4155395 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24237975  }} </ref>
* Mutation in alpha- or beta-spectrin<ref name="pmid24237975">{{cite journal| author=Gallagher PG| title=Abnormalities of the erythrocyte membrane. | journal=Pediatr Clin North Am | year= 2013 | volume= 60 | issue= 6 | pages= 1349-62 | pmid=24237975 | doi=10.1016/j.pcl.2013.09.001 | pmc=4155395 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24237975  }} </ref>
* Mutation in band 3<ref name="pmid24237975">{{cite journal| author=Gallagher PG| title=Abnormalities of the erythrocyte membrane. | journal=Pediatr Clin North Am | year= 2013 | volume= 60 | issue= 6 | pages= 1349-62 | pmid=24237975 | doi=10.1016/j.pcl.2013.09.001 | pmc=4155395 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24237975  }} </ref>
* Mutation in protein 4.2<ref name="pmid24237975">{{cite journal| author=Gallagher PG| title=Abnormalities of the erythrocyte membrane. | journal=Pediatr Clin North Am | year= 2013 | volume= 60 | issue= 6 | pages= 1349-62 | pmid=24237975 | doi=10.1016/j.pcl.2013.09.001 | pmc=4155395 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24237975  }} </ref>
|
* Positive eosin-5-maleimide binding to [[red blood cells]]<ref name="pmid24237975">{{cite journal| author=Gallagher PG| title=Abnormalities of the erythrocyte membrane. | journal=Pediatr Clin North Am | year= 2013 | volume= 60 | issue= 6 | pages= 1349-62 | pmid=24237975 | doi=10.1016/j.pcl.2013.09.001 | pmc=4155395 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24237975  }} </ref>
* Positive osmotic fragility testing<ref name="pmid24237975">{{cite journal| author=Gallagher PG| title=Abnormalities of the erythrocyte membrane. | journal=Pediatr Clin North Am | year= 2013 | volume= 60 | issue= 6 | pages= 1349-62 | pmid=24237975 | doi=10.1016/j.pcl.2013.09.001 | pmc=4155395 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24237975  }} </ref>
* Spherocytes on peripheral blood smear
|
* [[Pallor]]
* [[Jaundice]]
* [[Splenomegaly]]
|
* Removal of offending [[medication]]
* High-dose [[vitamin B6]] (up to 200mg daily)
* Avoidance of [[splenectomy]]
* Symptomatic [[Blood transfusion|transfusion]] support with [[iron]] [[chelation]] as needed
|
* Can be autosomal dominant or recessive
|-
|[[Pernicious anemia]]<ref name="pmid27602354">{{cite journal| author=Chan CQ, Low LL, Lee KH| title=Oral Vitamin B12 Replacement for the Treatment of Pernicious Anemia. | journal=Front Med (Lausanne) | year= 2016 | volume= 3 | issue=  | pages= 38 | pmid=27602354 | doi=10.3389/fmed.2016.00038 | pmc=4993789 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27602354  }} </ref>
|
* Autoimmune gastritis<ref name="pmid27602354">{{cite journal| author=Chan CQ, Low LL, Lee KH| title=Oral Vitamin B12 Replacement for the Treatment of Pernicious Anemia. | journal=Front Med (Lausanne) | year= 2016 | volume= 3 | issue=  | pages= 38 | pmid=27602354 | doi=10.3389/fmed.2016.00038 | pmc=4993789 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27602354  }} </ref>
* Production of anti-intrinsic factor antibodies<ref name="pmid27602354">{{cite journal| author=Chan CQ, Low LL, Lee KH| title=Oral Vitamin B12 Replacement for the Treatment of Pernicious Anemia. | journal=Front Med (Lausanne) | year= 2016 | volume= 3 | issue=  | pages= 38 | pmid=27602354 | doi=10.3389/fmed.2016.00038 | pmc=4993789 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27602354  }} </ref>
* Production of anti-parietal cell antibodies<ref name="pmid27602354">{{cite journal| author=Chan CQ, Low LL, Lee KH| title=Oral Vitamin B12 Replacement for the Treatment of Pernicious Anemia. | journal=Front Med (Lausanne) | year= 2016 | volume= 3 | issue=  | pages= 38 | pmid=27602354 | doi=10.3389/fmed.2016.00038 | pmc=4993789 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27602354  }} </ref>
|
* Low vitamin B12 level
* Presence of anti-intrinsic factor antibodies
* Presence of anti-parietal cell antibodies
|
* Gastrointestinal discomfort
* [[Weakness]]
* [[Tingling]]
* [[Paresthesias]]
|
* Lifelong [[vitamin B12]] therapy (1000mcg daily)<ref name="pmid27602354">{{cite journal| author=Chan CQ, Low LL, Lee KH| title=Oral Vitamin B12 Replacement for the Treatment of Pernicious Anemia. | journal=Front Med (Lausanne) | year= 2016 | volume= 3 | issue=  | pages= 38 | pmid=27602354 | doi=10.3389/fmed.2016.00038 | pmc=4993789 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27602354  }} </ref>
|
* Associated with diabetes, thyroid disease, vitiligo and other autoimmune conditions
|-
|[[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>
|
* Mutations in hematopoietic stem cells and B lymphocytes
|
* Elevated absolute lymphocyte count
* Anemia (Rai stage III) and thrombocytopenia (Rai stage IV)
|
* [[Lymph node enlargement]]
* [[Splenomegaly]] in Rai stage II
* [[Hepatomegaly]] in Rai stage II
* [[Pallor]]
* [[Bleeding]]
|
* Chemotherapy with rituximab
* Ibrutinib
* Venetoclax
|
* Secondary autoimmune hemolytic anemia occurs in 10-25% of patients with CLL
* Treatment with corticosteroids or anti-leukemic therapy will correct the underlying anemia
|}




Revision as of 05:24, 6 May 2018

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Shyam Patel [2]

Differentiating Acute promyelocytic meukemia from other Diseases

Acute promyelocytic leukemia can be distinguished from other types of AML based on morphologic examination of a bone marrow biopsy or aspirate. Definitive diagnosis requires testing for the RARα fusion gene. This may be done by polymerase chain reaction (PCR), fluorescent in situ hybridization (FISH), or conventional cytogenetics of peripheral blood or bone marrow.


Characteristic Causes Laboratory abnormalities Physical examination Therapy Other associations
Acute promyelocytic leukemia
  • Translocation between chromosomes 15 and 17
  • Creation of PML-RARalphagene product
  • Presence of Auer rods in promyelocytes
  • High risk for early death from hemorrhagic complications
Acute myeloid leukemia
  • Chromosomal instability
  • Sporadic mutations
  • Bleeding
  • Thrombosis
  • Pyrexia
  • Altered mental status
  • Neurologic deficits
  • Impaired urine output
  • Can be life-threatening pending the underlying cause
  • TTP required immediate treatment
Paroxysmal cold hemoglobinuria
  • Associated with syphilis[1]
  • Maternal IgG can cross the placenta and affect the fetus[1]
Paroxysmal nocturnal hemoglobinuria
  • Genetic defect in anchoring proteins for complement factors on red blood cells
  • Hemolysis due to loss of complement inhibition on the red blood cell surface, which in turn is due to defect in CD55 (decay accelerating factor) and CD59
  • Splenomegaly
  • Abdominal tenderness
  • Pallor
Hereditary spherocytosis[2]
  • Mutation in ankyrin[2]
  • Mutation in alpha- or beta-spectrin[2]
  • Mutation in band 3[2]
  • Mutation in protein 4.2[2]
  • Positive eosin-5-maleimide binding to red blood cells[2]
  • Positive osmotic fragility testing[2]
  • Spherocytes on peripheral blood smear
  • Can be autosomal dominant or recessive
Pernicious anemia[3]
  • Autoimmune gastritis[3]
  • Production of anti-intrinsic factor antibodies[3]
  • Production of anti-parietal cell antibodies[3]
  • Low vitamin B12 level
  • Presence of anti-intrinsic factor antibodies
  • Presence of anti-parietal cell antibodies
  • Associated with diabetes, thyroid disease, vitiligo and other autoimmune conditions
Chronic lymphocytic leukemia[4]
  • Mutations in hematopoietic stem cells and B lymphocytes
  • Elevated absolute lymphocyte count
  • Anemia (Rai stage III) and thrombocytopenia (Rai stage IV)
  • Chemotherapy with rituximab
  • Ibrutinib
  • Venetoclax
  • Secondary autoimmune hemolytic anemia occurs in 10-25% of patients with CLL
  • Treatment with corticosteroids or anti-leukemic therapy will correct the underlying anemia


References

  1. ↑ 1.0 1.1 1.2 Akpoguma AO, Carlisle TL, Lentz SR (2015). "Case report: paroxysmal cold hemoglobinuria presenting during pregnancy". BMC Hematol. 15: 3. doi:10.1186/s12878-015-0023-7. PMC 4334594. PMID 25699184.
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 Gallagher PG (2013). "Abnormalities of the erythrocyte membrane". Pediatr Clin North Am. 60 (6): 1349–62. doi:10.1016/j.pcl.2013.09.001. PMC 4155395. PMID 24237975.
  3. ↑ 3.0 3.1 3.2 3.3 3.4 Chan CQ, Low LL, Lee KH (2016). "Oral Vitamin B12 Replacement for the Treatment of Pernicious Anemia". Front Med (Lausanne). 3: 38. doi:10.3389/fmed.2016.00038. PMC 4993789. PMID 27602354.
  4. ↑ Kipps TJ, Stevenson FK, Wu CJ, Croce CM, Packham G, Wierda WG; et al. (2017). "Chronic lymphocytic leukaemia". Nat Rev Dis Primers. 3: 16096. doi:10.1038/nrdp.2016.96. PMC 5336551. PMID 28102226.

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