Final Diagnosis -- Myelodysplastic syndromes




Although usually resulting in chronic anemia, myelodysplasia can occasionally present with an isolated decrease in other lineages. In the case presented, the apparent defect manifested as an isolated thrombocytopenia with cytogenetic and morphologic abnormalities.

Myelodysplastic syndromes (MDS) are heterogeneous hematological malignancies, characterized by ineffective hematopoiesis of one or more cell lines and the potential for progression to acute leukemia. A diagnosis of MDS is generally correlated clinically with refractory anemia. Although other cytopenias are also commonly seen in MDS, isolated thrombocytopenia is rare, with an incidence estimated at 1- 4% (1). By morphologic review, the marrow did not show the usual features of MDS, and CBC data indicated no anemia. On morphology alone, the findings in this case are somewhat subtle, with increased megakaryocytes, loose clustering of megakaryocytes and morphologically abnormal forms, including hypolobate and hyperchromatic forms, some of them small in size. These findings superficially mimic those that can be seen in immune mediated thrombocytopenia. No abnormal blast population or increased blast percentage was identified by either direct morphologic counts or by flow cytometry evaluation.

Cytogenetic evaluation did reveal a clonal deletion involving chromosome 20q. This finding is most frequently seen in MDS, in addition to acute myeloid leukemia and chronic myeloproliferative disorders. As the sole abnormality in patients with myelodysplastic or myeloproliferative disorders, the 20q deletion is associated with a relatively good prognosis (2).

The overall clinical, karyotypic, and morphologic features of this case are consistent with the previously reported, albeit not well defined, "refractory thrombocytopenia" (RT). The term has been proposed as a counterpart of refractory anemia, to describe MDS cases with isolated thrombocytopenia (1). In the present World Health Organization classification of myeloid neoplasms (3, 4), cases of RT are included under the category of "Myelodysplasia, unclassified (MDS-U)", which comprises unusual MDS cases that do not fit within other well-defined categories.

Very few series of RT cases have been reported. A recent study by Sashida et al. (5) examined a cohort of 146 patients with MDS and found 13 cases with isolated thrombocytopenia (8.9 %), in which the spectrum of changes is remarkably similar to the case described above. These patients were predominantly men (10:3) and appeared to have a favorable prognosis. Leukemic transformation was rare (1/13), although in light of previous studies, this is somewhat controversial (1). One patient (1/13) progressed to myelofibrosis. Cytogenetic studies revealed del20q (3 cases) as one of the more commonly recurring cytogenetic abnormalities, in addition to t(1;7)(q10;p10) (2 cases) and normal karyotypes. The most prominent morphologic feature was the presence of micromegakaryocytes (5/13). Of note, 7/13 patients had an increased number of megakaryocytes in the marrow. Dysplastic changes of the erythroid series were detectable in some patients. Hypogranulated neutrophils were present, but no pseudo - Pelger-Huet forms were noted. The authors state that "most patients survived for more than 2 years". Menke et al. (1) reported a 45% 5-year survival.

Misdiagnosis as immune thrombocytopenic purpura (ITP) is possible in the context of megakaryocytic hyperplasia without identified features of dysplasia and without documented clonal cytogenetics. In order to establish the correct diagnosis, a careful assessment of potential dysplastic features, as well as cytogenetic studies, should be performed at presentation. Of course, other secondary causes of thrombocytopenia must be excluded as well. Some patients with RT show megakaryocytic hyperplasia with normal karyotype of bone marrow, which indicates the possibility of an intermediate category of RT. It is also possible that RT per se represents a "borderline" category between chronic ITP and MDS. Interestingly, a DNA microarray study of bone marrow mononuclear cells from a patient with RT revealed the MDS-like differential expression of a number of genes, but also alterations in gene expression patterns that were distinct from those observed in other MDS patients (6).

Although rare, an atypical myelodysplasia can present with isolated thrombocytopenia. This is often accompanied by dysplastic morphologic changes. However, in the absence of proven clonality by cytogenetics or other molecular studies, a definitive diagnosis of myelodysplasia is often difficult to establish. Secondary etiologies of thrombocytopenia must also be carefully excluded.


  1. Menke, D.M., Otero, G.C., Cockerill, K.J., Jenkins, R.B., Noel, P. and Pierr, R.V. (1992) Refractory thrombocytopenia: a myelodysplastic syndrome that may mimic immune thrombocytopenic purpura, Am. J. Clin. Pathol. 98, 502-510.
  2. Brezinova, J., Zemanova, Z., Ransdorfova, S., Sindelarova, L., Siskova, M., Neuwirtova, R., Cermak, J. and Michalova, K. (2005) Prognostic significance of del(20q) in patients with hematological malignancies, Cancer Genet. Cytogenet. 160, 188-192.
  3. Vardiman, J.W, Harris, N.L. and Brunning, R.D. (2002) World Health Organization (WHO) classification of myeloid neoplasms, Blood. 100, 2292-2302.
  4. Jaffe ES, Harris NL, Stein H, Vardiman JW. Pathology and Genetics of Tumours of Haematopoietic and lymphoid tissues. IARC Press, Lyon, France, 2001.
  5. Sashida, G., Takaku, T.I., Shoji, N., Nishimaki, J., Ito, Y., Miyazawa, K., Kimura, Y., Ohyashiki, J.H. and Ohyashiki K. (2003) Clinico-hematologic features of myelodysplastic syndrome presenting as isolated thrombocytopenia: an entity with a relatively favorable prognosis, Leuk. Lymphoma 44, 653-658.
  6. Qian, J., Xue, Y., Pan, J., Cen, J., Wang, W. and Chen, Z. (2005) Refractory thrombocytopenia, an unusual myelodysplastic syndrome with an initial presentation mimicking idiopathic thrombocytopenic purpura, Int. J. Hematol. 81, 142-147.

Contributed by Mihaela Avramut, MD, PhD and Raymond E. Felgar, MD, PhD

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