Paroxysmal nocturnal hemoglobinuria-myelodysplastic syndrome associated with marked thrombocytosis and acquired clonal cytogenetic abnormality of t(3;12)(q28;q15)

Abstract

Th e frequency of simultaneous paroxysmal nocturnal hemoglobinuria (PNH) clones in patients with myelodysplastic syndrome (MDS) ranges from 12.8 to 15.5% [1]. Th e clinical signifi cance of PNH-type cells in MDS is controversial. One study reports that the presence of an increased number of PNH-type cells was predictive of a good response to immunosuppressive therapy and a favorable prognosis among patients with marrow failure [2]. However, another study reports that patients with MDS of worse prognosis more strongly expressed the PNH clone compared to patients with refractive anemia (RA) and refractory anemia with ringed sideroblasts (RARS), who had a better prognosis [1]. Marrow failure, especially MDS, occasionally shows thrombocytosis due to an overlap of myeloproliferative neoplasms (MPNs) and association with some MDS subtypes. Classically, thrombocytosis has been associated with the MDS subtypes RARS and 5q Ϫ syndrome. Here, we report an extremely rare and interesting case of PNH-MDS associated with marked thrombocytosis and clonal chromosomal abnormality.A 51-year-old man suff ered from fever and pleural eff usion with left chest pain, which persisted for 1 month despite antimicrobial treatment. Th e patient was a heavy alcohol drinker and smoker. Physical examination revealed anemic conjunctiva, crackles in the left lung and splenomegaly. At admission, the following hematologic features were found: hemoglobin 8.3 g/dL, hematocrit 25.9%, mean corpuscular volume 103.8 fL, leukocyte count 10 300/ μ L with 2.6% basophils, 10.8% monocytes, and a platelet count of 532 000/ μ L. Serum levels of vitamin B12 and folate were in the normal ranges. Serum iron (16 μ g/dL) and total iron binding capacity (166 μ g/dL) levels were decreased, and the ferritin level (496.4 ng/dL) was elevated. Th e coagulation profi le showed a slightly prolonged prothrombin time (16.5 s, international normalized ratio 1.50, 46.9%), prolonged activated partial thromboplastin time (51.6 s), and elevated levels of D-dimer (0.74 mg/L), fi brin degradation product (10.0 μ g/mL) and fi brinogen (474.3 mg/dL). Th e C-reactive protein level (1.98 mg/dL) and lactate dehydrogenase (LDH) activity (1545 U/L) were also elevated. Laboratory parameters for evaluating hemolysis were in the normal ranges: total bilirubin 0.66 mg/dL, direct bilirubin 0.22 mg/ dL, haptoglobin 63.7 mg/dL, no abnormal urine analysis and negative for occult blood. Computed tomography scans of the chest showed empyema with pleural eff usion in the left hemithorax. Examination of pleural fl uid revealed a bloody color and leukocytes 1382/ μ L (96% lymphocytes), protein 5.0 g/dL (serum protein 6.5 mg/dL), albumin 2.9 g/dL (serum albumin 3.6 mg/dL), LDH activity 1457 U/L (serum LDH 1545 U/L), adenosine deaminase 59.8 IU/L and glucose 86 mg/dL (serum glucose 99 mg/dL). Screening for tuberculosis using the QuantiFERON assay was positive. Th erefore, tuberculosis pleurisy was suspected and the patient was treated for tuberculosis. Peripheral blood smears revealed moderate macrocytic...