Case Presentation
A 59-year old gentleman of Malay ethnicity who had no past medical history, presented to the department of hematology with fever, lethargy, headache, skin bruising, anorexia, and loss of weight for the past 3 weeks. He also complained of gingival bleeding which occurred spontaneously. He had no significant family history. He was a non-smoker and a teetotaler. He had no history of consuming recreational drugs. He works as a construction worker. He is married with 5 children, whom are all healthy.
Physical examination revealed an alert and medium-built gentleman. His Eastern Cooperative Oncology group (ECOG) performance status was 0 (fully active). He had no dysmorphic features. He was pale with a blood pressure was 110/60 and pulse rate of 96 beats per minute. He had noticeable cutaneous bruising on the lower limbs. The cardiovascular and respiratory systems were unremarkable on examination. There was no palpable lymphadenopathy or organomegaly.
The complete blood count (CBC) which was analysed by an automated haematologic analyser (Sysmex, XE-5000, Vienna, Austria) showed severe peripheral pancytopenia; haemoglobin of 6.5 g/dL, total white blood cell count of 1.5 x 109/L and a platelet count of 21 x 109/L. He had an elevated lactate dehydrogenase (LDH) of 550 U/L. His serology screen was negative for viral hepatitis and Human Immunodeficiency Virus (HIV). The peripheral blood film which was stained with Wright-Giemsa revealed red blood cell anisopoikilocytosis, nucleated red blood cells, numerous mononuclear cells and giant platelets. The chest radiograph did not show any mediastinal widening. The bone marrow aspiration which was stained with May-Grunwald-Giemsa (Figure 1A) showed hypercellular particles for age and trilineage dysplasia with 52% megakaryoblasts. The megakaryoblasts were described as agranular, medium-to-large cells with round nucleus, basophilic cytoplasm with cytoplasmic blebs and pseudopods. Erythropoiesis and granulopoiesis were suppressed. Bone marrow trephine biopsy (Figure 1B) showed topographical dysplasia, marrow fibrosis and infiltration by clusters of megakaryoblasts. The tumour cells (Figure 1C-E) stained positive for CD33, CD34 and CD61. They were negative for MPO. The immunohistochemical stains used in this specimen originated from Dako Artisan Link, Denmark. Immunophenotyping of the bone marrow sample by 8-colour flow cytometer (BD FACSCanto II) showed 55% cluster of blasts expressing CD13, CD33, CD34, CD36, CD41 and CD61 and were negative for cMPO and HLA DR. Silver impregnation stain of the trephine biopsy (Figure 1F) showed increased reticulin fibrosis (World Health Organisation 2016 grading system for bone marrow fibrosis: Grade 2). Cytogenetic studies using Giemsa banding technique revealed -7q and trisomy 8 abnormalities.
He was diagnosed as transformation of myelodysplastic syndrome to acute megakaryoblastic leukemia. He was induced with standard combination chemotherapy consisting of daunorubicin (60mg/m2), an anthracycline for three days, and continuous infusion of cytarabine (100mg/m2), an antimetabolite for seven days. However, he was refractory to induction chemotherapy. He was re-induced with FLAG chemotherapy (fludarabine 30mg/m2 and high dose cytarabine 2g/m2 once daily for 5 days), in which he failed to respond. He succumbed to his illness at 7 months of diagnosis.