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.