Table of Contents
Definition / general | Clinical features | Prognostic factors | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Molecular / cytogenetics description | Differential diagnosisCite this page: Mihova D. AML with myelodysplasia related changes. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/leukemiaAMLmulti.html. Accessed September 21st, 2021.
Definition / general
- 20%+ blasts in peripheral blood or bone marrow AND (a) prior diagnosis of MDS or MDS/MPN; (b) cytogenetic abnormalities associated with MDS or (c) multilineage dysplasia in > 50% of the cells of at least 2 separate bone marrow lineages
- Excludes patients with (a) prior history of cytotoxic therapy or unrelated disease or (b) cytogenetic abnormalities associated with AML with recurrent genetic abnormalities
- Arises either as de novo AML, from existing myelodysplastic syndrome or from myelodysplastic / myeloproliferative neoplasm
- Includes what was previously called refractory anemia with excess blasts in transformation
- Previously called AML with multilineage dysplasia
- Recommended to include reason for diagnosis, blast count or presence of mutations (NPM1, CEBPA, FLT3)
- Examples: (a) AML-MRC (multilineage dysplasia); (b) AML-MRC (previous MDS or MDS/MPN history); (c) AML-MRC (MDS related cytogenetics and presence of FLT3 mutation)
Clinical features
- Usually presents with severe pancytopenia
- Both children and adults; represent 24 - 35% of all AM
- Children: occurs in 3% with de novo AML, good response to treatment (Int J Hematol 2007;86:358)
- Adults: median age 61 years; higher incidence in AML in older individuals
Prognostic factors
- Poorer prognosis than classic AML, particularly if adverse cytogenetics (Eur J Haematol 2002;68:203), and history of MDS or MDS/MPN (Blood 2010;116:2742), but see Blood 2008;111:1855
- Low blast count less clinically aggressive
Microscopic (histologic) description
- Dysplasia in 50%+ of cells of 2 or more lineages
- Often panmyelosis, usually dysplastic megakaryocyte
- Variably cellular marrow with 20%+ blasts
- Dysgranulopoiesis: hypogranular neutrophils, hyposegmented (Pelger-Huët cells) and bizarrely segmented (as seen in peripheral blood)
- Dyserythropoiesis: megaloblastosis, karyorrhexis, nuclear irregularity, fragmentation, multinucleation, ringed sideroblasts, cytoplasmic vacuoles and PAS+
- Dysmegakaryopoiesis: micromegakaryocytes, normal or large megakaryocytes with nonlobulated or multiple nuclei
Microscopic (histologic) images
Contributed by Daniela Mihova, MD
Molecular / cytogenetics description
- Trisomy 8, abnormalities of #5 or #7 are common
- Also t(3;5)(q25;q34-35) involving MLF1 and NPM (Hum Pathol 2003;34:809)
- Mutations in NPM1, CEBPA, FLT3-ITD, FLT3-D835, N-RAS and MLL-PTD (Blood 2009;113:1906)
- Complex karyotype including 3+ unrelated abnormalities, none of which is included in AML with recurrent genetic abnormalities
- Unbalanced abnormalities: -7/del(7q), -5/del(5q), i(17q)/t(17p), -13/del(13q), del(11q), del(12p)/t(12p), del(9q), idic(X)(q13) (eMedicine: Pathology of Acute Myeloid Leukemia With Myelodysplasia-Related Changes [Accessed 30 March 2018])
- Balanced abnormalities:
- t(11;16)(q23;p13.3) - therapy related myeloid neoplasms should be excluded before diagnosis of AML-MRC
- t(3;21)(q26.2;q22.1) - therapy related myeloid neoplasms should be excluded before diagnosis of AML-MRC
- t(1;3)(p36.3;q21.1)
- t(2;11)(p21;q23) - therapy related myeloid neoplasms should be excluded before diagnosis of AML-MRC
- t(5;12)(q33;p12)
- t(5;7)(q33;q11.2)
- t(5;17)(q33;p13)
- t(5;10)(q33;q21)
- t(3;5)(q25;q34) - young patients; involving MLF1 and NPM (Hum Pathol 2003;34:809)
- Common in MDS but not sufficient for diagnosis of AML-MRC by themselves: +8, del(20q), and loss of Y (in older man)
Differential diagnosis
- Acute erythroid leukemia
- Acute megakaryoblastic leukemia
- AML-M2
- AML-M6a
- AML-NOS
- AML with recurrent genetic abnormalities
- t-AML
