Difference between revisions of "Myelodysplastic syndromes"

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'''Myelodysplastic syndromes''' can be thought of a pre-leukemia/pre-lymphoma.   
'''Myelodysplastic syndromes''', abbreviated '''MDS''', can be thought of a pre-leukemia/pre-lymphoma.   


They should not be confused with ''[[myeloproliferative neoplasms]]''.
They should not be confused with ''[[myeloproliferative neoplasms]]''.


==See also==
=Overview=
==Lab findings==
*+/-[[Anemia]].
*+/-Neutropenia.
*+/-Thrombocytopenia.
 
Notes:
*MDS is usu. an incidental finding, i.e. it is asymptomatic.
 
==Associations==
Syndromes associated with MDS:<ref name=dg21mar20011>D. Good. 21 March 2011.</ref>
*Fanconi syndrome.
*Diamond-blackfan syndrome.
*Shwachman-diamond syndrome.
 
==Diagnostic criteria==
All of the following:<ref name=dg21mar20011>D. Good. 21 March 2011.</ref>
#At least 6 months + persistent.
#Dysplasia.
#*Cytologic:
#**Need >=10% abnormal.
#*Cytogenetic.
#All other causes excluded.
#Blast percentage <20%.
#*If >=20% = [[leukemia]].
#*Criteria blast percentage:
#**Bone marrow: 500 nucleated cells - includes erythroblasts, plasma cells; excludes megakaryocytes.
#**Peripheral blood: 200 leukocytes.
 
===Required clinical information===
*CBC - usu. macrocytic anemia.
*Rx - may be Rx effect.
*Peripheral blood film.
*Clinical history (symptoms/presentation/PMHx).
 
===Laboratory work-up===
*[[H&E stain]].
*Giemsa/Wright stain.
*Iron stain.
*Gomori silver stain.
 
===DDx of MDS===
#Nutritional deficiency.
#*Vitamin B12.
#*Folate.
#Toxic exposures.
#*Rx.
#**G-CSF.
#*Biologic agents.
#*Heavy metals.
#*Chemotherapy.
#Infections.
#*Parovirus B19.
#Other.
#*Paroxysmal nocturnal hemoglobinuria (PNH).<ref>URL: [http://emedicine.medscape.com/article/207468-overview http://emedicine.medscape.com/article/207468-overview]. Accessed on: 29 May 2011.</ref> (???)
#*Congenital hematopoietic disorder.
#**Congenital dyserythropoietic anemia.
 
=Bone marrow specimens=
==Normal==
*Age (years) ~ percentage of fat.
**Example 80 years old has ~ 80% fat in marrow space.
 
Erythroblasts:
*Typically away from bone.
 
Megakaryocytes:
#Alone - not in clusters.
#Not close to bone.
 
Myeloid cells:
*Adjacent to bone.
 
=Histologic features=
*[[Auer rods]] - '''used to be''' diagnostic of MDS regardless of blast count.
 
==Dyserythropoiesis==
*Abnormal [[RBC]] formation.
 
===Histology===
====Nuclear====
Features:<ref name=dg21mar20011>D. Good. 21 March 2011.</ref>
*Nuclear budding.
*Intranuclear bridging (nuclei fail to separate post-division).
*Multinucleation.
*Megablastoid change.
**May be hard to see.
*Karyorrhexis (nuclear fragmentation).
 
====Cytoplasmic====
Features:<ref name=dg21mar20011>D. Good. 21 March 2011.</ref>
*Ring sideroblasts.
**Rim of RBC has ring of iron.
*Vacuolization.
 
==Dysgranulopoiesis==
*Abnormal granulocyte formation.
 
===Histology===
Features:<ref name=dg21mar20011>D. Good. 21 March 2011.</ref>
*Nuclear hypolobation (pseudo Pelger-Huët).
*Hypersegmentation.
**May be seen in vitamin B12 deficiency, Rx.
*Cytoplasmic hypogranulation.
*Pseudo-Chediak-Higashi granules.
*Small size.
 
==Dysmegakaryocytopoiesis==
*Abnormal megakaryocyte formation.
 
===Histology===
Features:<ref name=dg21mar20011>D. Good. 21 March 2011.</ref>
*Micromegakaryoctes with hypolobated nuclei.
*Non-lobated nuclei of any size.
*Multiple widely separated nuclear lobes.
 
Image:
*[http://www.atlasbloodcells.es/ficha.php?codigo=410&codigo2=499&indice=410 Dysmegakaryocytopoiesis (atlasbloodcells.es)].
 
=IHC=
Typical [[IHC]] in work-up of MDS:
*CD34 - (myeloid) progenitor/precursor cells.
*CD117 - (myeloid) progenitor/precursor cells, [[mast cell]]s.
*Tryptase - mast cells, immature basophils.
**Uncommonly done.
*CD61 - megakaryocytes.
*CD42b - megakaryocytes.
*CD20 - B cells.
*CD3 - T cells.
*Glycophorin A - erythroid cells.
*Glycophorin C - erythroid cells.
 
Notes:
*Other markers:
**Factor VIII.
**vWF.
*Blasts - the gold standard: histomorphology.
**Most blasts are CD34 +ve.
***[[Flow cytometry]] not useful (yet) for MDS -- as CD34 +ve != blast; may change with more multiplexing.
**CD117 marks some blasts that are CD34 -ve.
 
=[[Cytogenetics]]=
*Important in the Dx and prognostication of MDS; however, only ~50% have a cytogenetic abnormality based on karyotyping.
 
Common changes:
#Isolated del(5q).
#Isolated del(17p).
#*Assoc. with pseudo-Pelger-Huet. (???)
#Monosomy 7.
#Monosomy 8.
 
There is a scoring system for cytogenetic abnormalities ''International Prognostic Scoring System'',<ref name=pmid21594886>{{Cite journal  | last1 = Garcia-Manero | first1 = G. | title = Myelodysplastic syndromes: 2011 update on diagnosis, risk-stratification, and management. | journal = Am J Hematol | volume = 86 | issue = 6 | pages = 490-8 | month = Jun | year = 2011 | doi = 10.1002/ajh.22047 | PMID = 21594886 }}
</ref> abbreviated ''IPSS'':
*Higher score = worse outcome.
 
=WHO classification (2008)=
*Refractory cytopenia with unilineage dysplasia (RCUD).
*#Anemia.
*#Neutropenia
*#Thrombocytopenia.
*Refractory anemia with ringed sideroblasts (RARS).
*Refractory cytopenia with multilineage dysplasia (RCMD).<ref name=pmid8558932>{{Cite journal  | last1 = Rosati | first1 = S. | last2 = Mick | first2 = R. | last3 = Xu | first3 = F. | last4 = Stonys | first4 = E. | last5 = Le Beau | first5 = MM. | last6 = Larson | first6 = R. | last7 = Vardiman | first7 = JW. | title = Refractory cytopenia with multilineage dysplasia: further characterization of an 'unclassifiable' myelodysplastic syndrome. | journal = Leukemia | volume = 10 | issue = 1 | pages = 20-6 | month = Jan | year = 1996 | doi =  | PMID = 8558932 }}</ref>
*Refractory anemia with excess blasts (RAEB).
**RAEB-1.
**RAEB-2: Auer rods ''or'' >= 10% blasts. 
*MDS with isolated del(5q).
*MDS unclassifiable.
 
=See also=
*[[Haematopathology]].
*[[Haematopathology]].
*[[Myeloproliferative neoplasms]].
*[[Myeloproliferative neoplasms]].
*[[Leukemia]].
=References=
{{Reflist|1}}


[[Category:Haematopathology]]
[[Category:Haematopathology]]

Latest revision as of 15:42, 18 February 2016

Myelodysplastic syndromes, abbreviated MDS, can be thought of a pre-leukemia/pre-lymphoma.

They should not be confused with myeloproliferative neoplasms.

Overview

Lab findings

  • +/-Anemia.
  • +/-Neutropenia.
  • +/-Thrombocytopenia.

Notes:

  • MDS is usu. an incidental finding, i.e. it is asymptomatic.

Associations

Syndromes associated with MDS:[1]

  • Fanconi syndrome.
  • Diamond-blackfan syndrome.
  • Shwachman-diamond syndrome.

Diagnostic criteria

All of the following:[1]

  1. At least 6 months + persistent.
  2. Dysplasia.
    • Cytologic:
      • Need >=10% abnormal.
    • Cytogenetic.
  3. All other causes excluded.
  4. Blast percentage <20%.
    • If >=20% = leukemia.
    • Criteria blast percentage:
      • Bone marrow: 500 nucleated cells - includes erythroblasts, plasma cells; excludes megakaryocytes.
      • Peripheral blood: 200 leukocytes.

Required clinical information

  • CBC - usu. macrocytic anemia.
  • Rx - may be Rx effect.
  • Peripheral blood film.
  • Clinical history (symptoms/presentation/PMHx).

Laboratory work-up

  • H&E stain.
  • Giemsa/Wright stain.
  • Iron stain.
  • Gomori silver stain.

DDx of MDS

  1. Nutritional deficiency.
    • Vitamin B12.
    • Folate.
  2. Toxic exposures.
    • Rx.
      • G-CSF.
    • Biologic agents.
    • Heavy metals.
    • Chemotherapy.
  3. Infections.
    • Parovirus B19.
  4. Other.
    • Paroxysmal nocturnal hemoglobinuria (PNH).[2] (???)
    • Congenital hematopoietic disorder.
      • Congenital dyserythropoietic anemia.

Bone marrow specimens

Normal

  • Age (years) ~ percentage of fat.
    • Example 80 years old has ~ 80% fat in marrow space.

Erythroblasts:

  • Typically away from bone.

Megakaryocytes:

  1. Alone - not in clusters.
  2. Not close to bone.

Myeloid cells:

  • Adjacent to bone.

Histologic features

  • Auer rods - used to be diagnostic of MDS regardless of blast count.

Dyserythropoiesis

  • Abnormal RBC formation.

Histology

Nuclear

Features:[1]

  • Nuclear budding.
  • Intranuclear bridging (nuclei fail to separate post-division).
  • Multinucleation.
  • Megablastoid change.
    • May be hard to see.
  • Karyorrhexis (nuclear fragmentation).

Cytoplasmic

Features:[1]

  • Ring sideroblasts.
    • Rim of RBC has ring of iron.
  • Vacuolization.

Dysgranulopoiesis

  • Abnormal granulocyte formation.

Histology

Features:[1]

  • Nuclear hypolobation (pseudo Pelger-Huët).
  • Hypersegmentation.
    • May be seen in vitamin B12 deficiency, Rx.
  • Cytoplasmic hypogranulation.
  • Pseudo-Chediak-Higashi granules.
  • Small size.

Dysmegakaryocytopoiesis

  • Abnormal megakaryocyte formation.

Histology

Features:[1]

  • Micromegakaryoctes with hypolobated nuclei.
  • Non-lobated nuclei of any size.
  • Multiple widely separated nuclear lobes.

Image:

IHC

Typical IHC in work-up of MDS:

  • CD34 - (myeloid) progenitor/precursor cells.
  • CD117 - (myeloid) progenitor/precursor cells, mast cells.
  • Tryptase - mast cells, immature basophils.
    • Uncommonly done.
  • CD61 - megakaryocytes.
  • CD42b - megakaryocytes.
  • CD20 - B cells.
  • CD3 - T cells.
  • Glycophorin A - erythroid cells.
  • Glycophorin C - erythroid cells.

Notes:

  • Other markers:
    • Factor VIII.
    • vWF.
  • Blasts - the gold standard: histomorphology.
    • Most blasts are CD34 +ve.
      • Flow cytometry not useful (yet) for MDS -- as CD34 +ve != blast; may change with more multiplexing.
    • CD117 marks some blasts that are CD34 -ve.

Cytogenetics

  • Important in the Dx and prognostication of MDS; however, only ~50% have a cytogenetic abnormality based on karyotyping.

Common changes:

  1. Isolated del(5q).
  2. Isolated del(17p).
    • Assoc. with pseudo-Pelger-Huet. (???)
  3. Monosomy 7.
  4. Monosomy 8.

There is a scoring system for cytogenetic abnormalities International Prognostic Scoring System,[3] abbreviated IPSS:

  • Higher score = worse outcome.

WHO classification (2008)

  • Refractory cytopenia with unilineage dysplasia (RCUD).
    1. Anemia.
    2. Neutropenia
    3. Thrombocytopenia.
  • Refractory anemia with ringed sideroblasts (RARS).
  • Refractory cytopenia with multilineage dysplasia (RCMD).[4]
  • Refractory anemia with excess blasts (RAEB).
    • RAEB-1.
    • RAEB-2: Auer rods or >= 10% blasts.
  • MDS with isolated del(5q).
  • MDS unclassifiable.

See also

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 D. Good. 21 March 2011.
  2. ↑ URL: http://emedicine.medscape.com/article/207468-overview. Accessed on: 29 May 2011.
  3. ↑ Garcia-Manero, G. (Jun 2011). "Myelodysplastic syndromes: 2011 update on diagnosis, risk-stratification, and management.". Am J Hematol 86 (6): 490-8. doi:10.1002/ajh.22047. PMID 21594886.
  4. ↑ Rosati, S.; Mick, R.; Xu, F.; Stonys, E.; Le Beau, MM.; Larson, R.; Vardiman, JW. (Jan 1996). "Refractory cytopenia with multilineage dysplasia: further characterization of an 'unclassifiable' myelodysplastic syndrome.". Leukemia 10 (1): 20-6. PMID 8558932.
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