A Case Report of An Unusual Case of Myelodysplatic Syndrome in a 26 year old Female

A 25 y/o African American female was referred to hematology clinic for abnormal lab values (Hemoglobin 8 g/dL, White cell count 2.7 k/uL, Platelets 86 K/uL, Mean corpuscular volume 106, and retic count 3.55) of several years for which she had not been thoroughly investigated. The patient reported she was always anemic since childhood. She had no new symptoms or abnormal bleeding except for fatigue and feeling weak. Peripheral blood review showed moderate anisopoikilocytosis. Few macrocytes, schistocytes, teardrop cells, ovalocytes and schistocytes, and polychromasia were seen. Leukocytes were markedly decreased. Small mature-appearing lymphocytes represent the predominant circulating cell type. Rare hyposegmented neutrophils were noted. No blasts were seen. Platelets were markedly decreased. Iron studies including Ferritin were all within normal, EPO level 282. Hemoglobin electrophoresis revealed a hereditary persistence of HgF (HgF=8.9%) with HbA0 of 89.5 L % (normal 97 – 99%) and Hb A2 1.6 % (normal 1 – 3%). Genetic test for thalassemia revealed: b- globulin negative and a-globulin deletion - consistent with Alfa thalassemia carrier state. Since the degree of anemia was disproportionate to alpha thalassemia carrier state, BM biopsy was obtained: morphological exam showed hypocellular bone marrow for age with an average similarity of 30–40%. There was a preponderance of erythroid precursors seen in clusters. No excessive blastic activity was present. Megakaryocytes appeared to be normal in number with a few showing mono/hypolobated nuclei. Bony trabeculae were unremarkable. Flow cytometry revealed no abnormalities. On cytogenetics, the following abnormal karyotype was found: 46,XX,add(5)(p15),add(6)(p21.3)[17]/46,XX,der(10)(1;10)(q21;p15)[3]. Thus, two abnormal and different clones with atypical aberrations were detected. One clone (85% of metaphases) exhibited additional material at 5p and 6p and the other clone (15%) showed a derivative chromosome composed of the two long arms of chromosome 1 and 10, with net gain of 1q and loss of 10p. No normal metaphases were detected. Peripheral blood flowcytometry for PNH was negative. The etiology of the patient’s pancytopenia was not immediately apparent from the examination of the bone marrow specimen. Differential diagnoses that were considered included effects of drugs/toxins, or medications, or infectious process, but none was identified. However, the karyotypic abnormality strongly argues for the diagnosis of a clonal hematological malignancy, in particular a myelodysplastic syndrome. The cytogenetic abnormalities, although atypical, are indicative of a neoplasm involving the bone marrow. Gain of 1q has been observed mainly in myeloid malignancies and multiple myeloma. Presence of two different clones and absence of normal metaphases is usually indicative of unfavorable prognosis. BM evaluation was repeated about 2 months from the initial evaluation, it confirmed initial findings including the cytogenetic findings. The patient has been managed conservatively; she is being evaluated for Hematopoeitic Stem Cell Transplantation. She had required red cells transfusion only once for symptomatic treatment of fatigue and dyspnea.

Conclusion: This case documents the rare diagnosis of myelodsyplastic syndrome (hypoplastic) in a young patient. MDS seems to be the likely diagnosis based on the clonal evidence that has been confirmed on two occasions in this case; of particular interest is the multiclonal process that exists in this patient.