Refractory Anemia with Ring Sideroblasts Associated with Marked Thrombocytosis (RARS-T)
Definition
- Provisional entity exhibiting features of both RARS and Essential Thrombocythemia
Note
- In at least some patients this represents acquisition of a prothrombocythemic JAK2 mutation in a background of RARS
Diagnostic Criteria
- Must satisfy diagnostic features of RARS
- Refractory anemia - Hemoglobin <10 mg/dL
- Dysplasia involving erythroid lineage (see below for criteria for dysplasia)
- Must involve ≥10% of erythroids
- Ring sideroblasts (see definition below)
- Must involve ≥15% of total erythroid precursors
- Sustained platelet elevation ≥450 x 103/μL
- Bone marrow biopsy with megakaryocytic hyperplasia
- Large to giant mature megakaryocytes
- Abundant cytoplasm
- Deeply lobulated nuclei (staghorn-like)
- Not hyperchromatic and clustered (as in cellular phase primary myelofibrosis)
- Not monolobated or multinucleated (as in MDS)
- Large to giant mature megakaryocytes
- JAK2V617F (present in about 60%)
- MPL W515K/L mutation less frequent
- <5% blasts in the marrow
Morphologic features of erythroid dysplasia
- Dyserythropoeisis
- Dimorphic red blood cells (RBC)
- Mixture of normal or macrocytic RBC and hypochromic microcytic RBC
- High RDW
- Basophilic stippling (Pappenheimer bodies)
- Bone marrow erythroid lineage abnormalties
- Ring sideroblasts
- ≥5 iron granules encircling ≥1/3 of the nucleus
- Must involve ≥15% of erythroids to make the diagnosis of RARS
- Usually either many or none
- Erythroid hyperplasia
- Megaloblastoid / megaloblastic changes
- Dyssynchronous maturation of nucleus and cytoplasm of erythroid precursors
- Nucleus lags behind cytoplasm
- Dyssynchronous maturation of nucleus and cytoplasm of erythroid precursors
- Megaloblastoid / megaloblastic changes
- Cytoplasmic vacuoles
- Also seen in copper deficiency
- Nuclear changes
- Multinuclearity
- Nuclear budding, hyperlobulation and satellite nuclei
- Internuclear bridging
- Ring sideroblasts
- Often increased iron in histiocytes
- Due to lysis of defective erythrocytes
- Dimorphic red blood cells (RBC)
Differential Diagnosis
- Exclude non-neoplastic causes of ring sideroblasts
- Drug/toxin to include alcohol, isoniazid, lead, benzene
- Zinc excess/copper deficiency
- Congenital sideroblastic anemia
- If chemotherapy or radiation therapy related, should be reported as "therapy-related myeloid neoplasm"
Clinical
- Optimal management of this rare and poorly characterized patient subgroup is not yet established
Dita Gratzinger MD PhD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342
Original posting: 10/23/11
