Clinicopathologic Analysis of 18 Cases with Refractory Anemia with Ringed Sideroblasts and Thrombocytosis
I Gurevich, R Luthra, LJ Medeiros, P Lin. The University of Texas MD Anderson Cancer Center, Houston, TX
Background: The provisional MDS/MPD-U entity refractory anemia with ringed sideroblasts(RS) and thrombocytosis (RARS-T) in the WHO classification is reported to be associated with a platelet count of > 600x109/L, frequent JAK2 V617F mutation and megakaryocytic hyperplasia morphologically resembling essential thrombocytosis. Recent studies show that RARS with thrombocytosis or RARS with JAK2 V617F are not necessarily RARS-T, suggesting that clinicopathological correlation is required for the diagnosis of this entity. The aim of this study is to evaluate the morphological features of cases presenting with RARS and thrombocytosis to better characterize RARS-T.
Design: Cases of RARS (>15% RS) and thrombocytosis (>500x109/L) were identified from our clinical database. CBC and the bone marrow aspirate and biopsy were reviewed. JAK2 and MPL mutations were analyzed by pyrosequencing in cases with available DNA. Cases with inv(3) or 5q- were excluded.
Results: 18 patients were identified, 10 male and 8 female, age range from 40 to 83 (median 63). 13 patients had a platelet count >600x109/L. Only 2 patients presented with a mildly elevated WBC count (12.7-12.9x109/L), all other patients had a normal WBC count. The JAK2 mutation was identified in 10 of 15 cases analyzed with the mutant alleles ranging from 18-55%. MPL was germline in all 9 cases tested. 8 of 10 patients in the JAK2 mutated group had a platelet count >600x109 /L, and 2 had platelet counts of 550 and 580x109/L, respectively. There was a morphologic spectrum of atypical megakaryocytes among different cases ranging from large forms, as in essential thrombocytosis, to pleomorphic forms as in chronic myelofibrosis, as well as non-specific forms associated with variable degree of fibrosis. 3 cases that had a platelet count ranging from 529-568x109/L and were negative for JAK2 mutation; these cases were not considered to be diagnostic of RARS-T despite ringed sideroblasts and thrombocytosis.
Conclusions: RARS-T with JAK2 mutation is more likely to display morphologic features of a myeloproliferative disease with a platelet count > 600x109/L. However, occasional cases may present with a platelet count <600x109/L. There is a spectrum of megakaryocytic morphology. MPL mutation is infrequent.
Wednesday, March 11, 2009 1:00 PM
Poster Session VI # 198, Wednesday Afternoon