Unclassifiable Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPN-U)

Definition

Myeloid neoplasm with both dysplastic and myeloproliferative features, which does not show specific disease-defining cytogenetic abnormalities and does not now or on previous biopsies satisfy criteria of a defined myeloid neoplasm

Diagnostic Criteria

Myelodysplastic and myeloproliferative features are BOTH REQUIRED
- Presence of dysplastic features sufficient for an MDS diagnosis
- Prominent myeloproliferative features
  - e.g. prominent thrombocytosis with megakaryocytic proliferation, prominent leukocytosis, etc
Must not satisfy criteria for any defined myeloid neoplasm
- Peripheral blood and bone marrow blasts <20%
- No evidence of disease-defining cytogenetic abnormalities
  - e.g. BCR/ABL1 translocations, isolated 5q minus, inv(3q21q26) or t(3;3)(q21;q26), acute myeloid leukemia-defining abnormalities inv(16), t(8;21)
No prior history of a defined myeloid neoplasm
No recent cytotoxic or growth factor therapy which may obscure diagnostic features
Includes new and provisional entities (see individual descriptions):
- Refractory anemia with ring sideroblasts associated with marked thrombocytosis (RARS-T, provisional category in WHO 2008)
- MDS/MPN with isolated isochromosome 17q (new, not specifically categorized in WHO 2008)

Dita Gratzinger MD PhD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342

Original posting: 11/6/11

Myelodysplasia is defined by morphologic features of abnormal cellular maturation in at least one bone marrow lineage

Not all features are applicable to all disorders
Dyserythropoeisis
- Peripheral blood erythrocyte abnormalities
  - Normocytic, normochromic anemia
  - Macrocytosis
  - Dimorphic red blood cells (RBC)
    - Mixture of normal RBC and hypochromic microcytic RBC
      - Often seen in Sideroblastic Anemia (RARS)
  - Basophilic stippling
  - Poikilocytosis
    - Varying shapes, frequently macro-ovalocytes
- Bone marrow erythroid lineage abnormalties
  - Erythroid hyperplasia or hypoplasia
    - Megaloblastoid / megaloblastic changes
      - Dyssynchronous maturation of nucleus and cytoplasm of erythroid precursors
        
        Nucleus lags behind cytoplasm
  - Ring sideroblasts
    - ≥5 iron granules encircling ≥1/3 of the nucleus
    - Usually either many or none
  - Cytoplasmic vacuoles
    - Also seen in copper deficiency
  - Nuclear changes
    - Multinuclearity
    - Nuclear budding, hyperlobulation and satellite nuclei
    - Internuclear bridging
Dysgranulopoiesis
- Peripheral blood and/or bone marrow findings (easier seen in peripheral blood)
  - Hypogranularity
    - Pale cytoplasm almost indistinguishable from background on slide
  - Nuclear hypolobation or irregular hypersegmentation (>5 lobes)
    - Pseudo Pelger-Huet anomaly
      - Two equal size nuclear lobes connected by a thin strand of chromatin
  - Infrequent findings
    - Abnormal cytoplasmic granules (pseudo Chediak-Higashi granules)
      - Giant grey to red granules
    - Dohle bodies
      - Small blue cytoplasmic inclusions
      - Often found at periphery of cell
    - Auer rods
      - Rod-like structures formed by fusion of primary granules
      - May be found in blasts or maturing granulocytes
Dysmegakaryopoiesis
- Peripheral blood platelet abnormalities
  - Giant
    - Larger than a red blood cell
  - Bizarre
    - Irregular shapes and protrusions
  - Hypogranularity
    - Compare to normal platelets with purple granules
- Bone marrow megakaryocyte abnormalities
  - Micromegakaryocytes
    - Smaller than a promyelocyte
  - Nuclear hypolobation
    - Prominent in 5q- syndrome
    - A single lobe is typically seen in a small megakaryocyte
  - Multinucleation
    - Distinct nuclei without a connecting strand of chromatin
  - Cytoplasmic hypogranularity

Classification / Lists

WHO 2008 Classification of Myeloid Neoplasms

Myeloproliferative Neoplasms (MPN)

Chronic myeloid leukemia, BCR-ABL1 pos
Chronic neutrophilic leukemia
Chronic eosinophilic leukemia NOS
- (see also Idiopathic hypereosinophilic syndrome)
Polycythemia vera
Essential thrombocythemia
Primary myelofibrosis
Mastocytosis
Myeloproliferative neoplasm unclassifiable

Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1

Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPN)

Myelodysplastic Syndromes (MDS)

Refractory cytopenia with unilineage dysplasia (RCUD)
Refractory cytopenia with multilineage dysplasia (RCMD)
Refractory anemia with ring sideroblasts (RARS)
Refractory anemia with excess blasts (RAEB)
MDS associated with isolated del(5q)
Childhood myelodysplastic syndrome
- Refractory cytopenia of childhood
MDS unclassifiable
Additional features that may be superimposed on above classification:
- MDS with fibrosis
- MDS, hypocellular

Therapy Related Myeloid Neoplasms

Bibliography

Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, World Health Organization Classification of Tumours 2008
Hall J, Foucar K, Diagnosing myelodysplastic/myeloproliferative neoplasms: laboratory testing strategies to exclude other disorders, International Journal of Laboratory Hematology, 2010, 32
Orazi A, Germing U. (2008) The myelodysplastic/myeloproliferative neoplasms: myeloproliferative diseases with dysplastic features. Leukemia, 22, 1308–1319.
Kanagal-Shamanna R et al, Myeloid neoplasms with isolated isochromosome 17q represent a clinicopathologic entity associated with myelodysplastic/ myeloproliferative features, a high risk of leukemic transformation, and wild-type TP53. Cancer. 2011 Oct 28. doi: 10.1002/cncr.26537. [Epub ahead of print]

Printed from Surgical Pathology Criteria: http://surgpathcriteria.stanford.edu/


© 2010 Stanford University School of Medicine

Unclassifiable Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPN-U)