Chronic myeloid neoplasms
MDS / MPN
Myelodysplastic / myeloproliferative neoplasm with ring sideroblasts and thrombocytosis


Topic Completed: 14 March 2019

Revised: 14 March 2019

Copyright: 2019, PathologyOutlines.com, Inc.

PubMed Search: Myelodysplastic / myeloproliferative neoplasm with ring sideroblasts and thrombocytosis
Page views in 2019 to date: 49
Cite this page: Tsang P. Myelodysplastic / myeloproliferative neoplasm with ring sideroblasts and thrombocytosis. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/myeloproliferativemdsmpnrst.html. Accessed March 19th, 2019.
Definition / general
  • Clonal myeloid disorder with mixed myelodysplastic and myeloproliferative features
  • Ring sideroblasts ≥ 15% of erythroblasts (Cancer Biol Med 2016;13:360)
  • Persistent thrombocytosis ≥ 450 x 109/L (Blood Cancer J 2018;8:15)
  • No increase in blast count, < 1% in blood and < 5% in bone marrow (Blood Cancer J 2018;8:15)
  • Lacking BCR-ABL1, isolated del(5q), t(3;3)(q21.3;q26.2) and inv(3)(q21.3;q26.2) (Cancer Biol Med 2016;13:360)
  • No previous history of myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN), except for MDS with ring sideroblasts
  • New distinct entity in 2016 WHO classification; related to 2008 WHO provisional entity, refractory anemia with ring sideroblasts associated with marked thrombocytosis (RARS-T) (Blood Cancer J 2018;8:15, Haematologica 2015;100:1117)
Essential features
  • Mixed myelodysplastic and myeloproliferative features with ring sideroblasts (≥ 15% of marrow erythroblasts), persistent thrombocytosis (≥ 450 x 109/L), anemia and normal blast count (Blood Cancer J 2018;8:15)
  • Strong association with SF3B1 mutation, often in conjunction with JAK2 V617F mutation but not required for diagnosis (Haematologica 2015;100:1117)
Terminology
  • Myelodysplastic and myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS / MPN-RS-T)
  • Previously, refractory anemia with ring sideroblasts associated with marked thrombocytosis (RARS-T)
ICD coding
Epidemiology
Sites
  • Myeloid cells primarily in bone marrow and blood
  • Splenomegaly 40%
  • Occasional hepatomegaly
Pathophysiology
  • Probable multistep genetic and epigenetic changes, leading to signaling deregulation, impaired DNA damage response and other cellular abnormalities (Int J Hematol 2015;101:229)
Etiology
  • Unclear
Clinical features
Diagnosis
Laboratory
  • Macrocytic or normocytic anemia
  • Thrombocytosis, ≥ 450 x 109/L
  • White blood cell (WBC) absolute and differential counts usually normal but mild leukocytosis can occur
Prognostic factors
Case reports
Treatment
Microscopic (histologic) description
  • Hypercellularity of bone marrow with < 5% blasts
  • Erythroid hyperplasia with dyserythropoiesis, including megaloblastic change, common in marrow
  • Ring sideroblasts ≥ 15% of normoblasts on iron stain (Blood Cancer J 2018;8:15)
  • Multilineage dysplasia possible
  • Atypical megakaryocytic hyperplasia and cluster formation with large, hyperlobated megakaryocytes, reminiscent of BCR-ABL negative MPN (Haematologica 2015;100:1117)
  • Marrow fibrosis can occur
Microscopic (histologic) images

Contributed by Patricia Tsang, M.D., M.B.A.

Hypercellular marrow

Megakaryocyte proliferation

Iron stain with ring sideroblast

Peripheral smear description
  • Normocytic to macrocytic, normochromic red blood cells
  • Thrombocytosis, sometimes with large, giant or atypical platelets
  • No or rare blasts, < 1% (Blood Cancer J 2018;8:15)
Peripheral smear images

Contributed by Patricia Tsang, M.D., M.B.A.

Dyserythropoiesis

Normoblast with megaloblastic change

Thrombocytosis

Positive stains
  • Iron stain on aspirate smear shows ring sideroblasts
  • Immunostains generally not needed for diagnosis
Flow cytometry description
  • No increase in blasts detected
  • Aberrant CD56 on myeloid cells sometimes seen
Molecular / cytogenetics description
Sample pathology report
  • Bone marrow biopsy and aspirate smears, left posterior iliac crest:
    • Myelodysplastic / myeloproliferative neoplasm with ring sideroblasts and thrombocytosis, formerly refractory anemia with ring sideroblasts and thrombocytosis
  • Cytogenetics, next generation sequencing for myeloid disorders, reticulin and trichrome stains are pending for further evaluation
  • Peripheral blood smear:
    • Macrocytic anemia with occasional teardrop RBCs
    • Mild neutrophilia and marked thrombocytosis with some giant platelets

  • Microscopic description:
    • The peripheral blood smear shows leukocytosis with mild neutrophilia (8,400/mcL) and no circulating blasts. Anisopoikilocytosis with macrocytic RBCs and occasional teardrop cells are seen. Platelet count is elevated (610,000/mcL).
    • The bone marrow aspirate (dry tap) is aspicular and hypocellular with evidence of maturing granulopoiesis and erythropoiesis. Some of the normoblasts show megaloblastic change and nuclear lobation, consistent with dyserythropoietic changes. The iron stain on aspirate reveals adequate storage iron. Ring sideroblasts constitute about 35% of the erythroid precursors.
    • The bone marrow biopsy is hypercellular (about 80%) with trilineage hyperplasia. There is focal crush cell artifact, suggestive of marrow fibrosis. Myeloid:erythroid ratio appears unremarkable. No increase in myeloblasts is seen histologically. Proliferation of atypical megakaryocytes with cluster formation is present. Megakaryocytes are characteristically enlarged and hyperlobated. No abnormal lymphoid or plasma cell infiltrate is noted.
Differential diagnosis
Board review question #1
Myelodysplastic / myeloproliferative neoplasm with ring sideroblasts and thrombocytosis is most frequently associated with alterations of which pair of genes?

  1. ABL1 and CALR
  2. ASXL1 and KRAS
  3. SETBP1 and TP53
  4. SF3B1 and JAK2
  5. TET2 and FLT3
Board review answer #1
D. SF3B1 and JAK2 are the two most frequently altered genes in myelodysplastic / myeloproliferative neoplasm with ring sideroblasts and thrombocytosis

Comment Here
Board review question #2
Which of the following features is characteristic of myelodysplastic / myeloproliferative neoplasm with ring sideroblasts and thrombocytosis?



  1. Blasts < 1% in the blood and < 5% in the bone marrow
  2. Circulating ring sideroblasts > 15% in the peripheral blood
  3. Deletion 5q or monosomy 5
  4. Persistent monocytosis with no secondary etiology
  5. Proliferation of hypolobated megakaryocytes in the bone marrow
Board review answer #2
A. Blasts < 1% in the blood and < 5% in the bone marrow. No increase in blasts is seen in the blood or bone marrow in myelodysplastic / myeloproliferative neoplasm with ring sideroblasts and thrombocytosis.

Comment Here
Back to top