Myelodysplastic/Myeloproliferative Neoplasms with Isolated Isochromosome 17q

Definition

Unclassifiable myeldysplastic/myeloproliferative neoplasm (MDS/MPN-U) with isolated isochromosome 17q

Note

This is a newly recognized entity not specifically categorized in the WHO 2008 edition

Diagnostic Criteria

Meets criteria for MDS/MPN-U
- Must have both myelodysplastic and myeloproliferative features
- Must not satisfy criteria for any defined myeloid neoplasm
Demonstrates isochromosome 17q as the sole or primary cytogenetic abnormality
- Molecular pathology evidence of other mutations occasionally seen
Characteristic features
- Pseudo-Pelger-Huet-like neutrophils
- Micromegakaryocytic hyperplasia
- Marrow hypercellularity, fibrosis, and osteosclerosis
- Increased marrow blasts (definitionally <20% in this category)
Short overall survival
- High risk of leukemic transformation

Differential Diagnosis

This is a diagnosis of exclusion
- Isochromosome 17 may be seen as a primary or secondary cytogenetic abnormality in other myeloid neoplasms, which must first be excluded

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