Acute megakaryoblastic leukemia (AMKL) is a rare subtype of acute myeloid leukemia. Although known as a distinct entity for a very long time, because of lack of distinct clinical features and morphological criteria, it is difficult to diagnose this variant correctly. We herein present the clinical, morphological, cytochemical, and immunocytochemical features of five cases of AMKL. Certain morphological features such as presence of abnormal platelet count, giant platelets, and cytoplasmic blebbing in blasts were found to be important pointers towards the diagnosis. However, none of the features were found to be consistent and thus morphological diagnosis has to be confirmed by cytochemistry and immunocytochemistry.
Acute megakaryoblastic leukemia (AMKL) is a rare entity and accounts for 3–5% of all acute myeloid
leukemia [
All acute megakaryoblastic leukemias diagnosed in the Department of Pathology of Lady Hardinge Medical College, New Delhi, in the period 1997 to 2007, were included in the study. A total of five cases were retrieved. The clinical history and other details were taken from the case files.
Wright's stained peripheral smears and bone marrow aspirate (BMA) smears were examined. Bone marrow biopsy was available in only one case.
Cytochemistry, including myeloperoxidase (MPO), Sudan black B (SBB), periodic acid Schiff (PAS), and nonspecific esterase (NSE), was available in all the cases.
Immunophenotyping
was done in 4 out of 5 cases. In 3/4 cases, immunocytochemistry was done by APAAP
technique using DAKO antibodies (Figure
Clinical and haematological profiles of our 5 cases are summarized in
Tables
Clinical features and hematological parameters.
Features | Case I | Case II | Case III | Case IV | Case V |
---|---|---|---|---|---|
Age/sex | 6 years/M | 20 years/F | 1.5 years/M | 2 years/M | 22 years/M |
C/F | Pallor, easy bruisability | Pallor, dyspnea, gum bleeds, malena, hematemesis | Fever, petechiae | Fever, epistaxis, seizures | Fever |
Down's syndrome | — | — | — | + | — |
Hepatomegaly | + | — | + | — | + |
Splenomegaly | + | — | + | — | + |
Lymphadenopathy | — | — | + | — | — |
Hb (g/dL) | 10.7 | 4.9 | 4.8 | 5.1 | 9.4 |
WBC ( | 40 | 30 | 17.5 | 7.1 | 7.9 |
Plt count ( | 30 | 480 | 14 | 60 | 203 |
Morphology, cytochemistry and immunocytochemistry.
Case I | Case II | Case III | Case IV | Case V | ||
---|---|---|---|---|---|---|
Morphology | ||||||
Peripheral smear | * | |||||
Normocytic Normochromic | Present | Present | Present | Present | Present with tear drop cells | |
*Blasts (%) | 18% | 40% | 4% | 5% | 25% | |
*Blast morphology | ||||||
(i) agranular blue cytoplasm with cytoplasmic blebbing | Present | Present | Present | Present (some blasts were granular) | Present | |
(ii) Giant platelets | Present | Absent | Absent | Absent | Present | |
(iii) Platelet budding | Present | Present | Absent | Absent | Present | |
Bone marrow aspiration/biopsy | *Hypercellular marrow showing megakaryoblasts, micromegakaryocytes, promegakaryocytes (full range of differentiation) | Present with clustering mimicking metastasis | Present | Present | Diluted BMA & Biopsy showed blasts with clustering and increased reticulin fibres | Present |
*Blast (%) | 25% | 45% | 56% | 25% (biopsy) | 28% | |
Cytochemistry | ||||||
PAS | Positive | Positive | Negative | Positive | Positive | |
NSE | Positive, fluoride resistant | Positive, fluoride resistant | Positive, fluoride resistant | Positive, fluoride resistant | Positive, fluoride resistant | |
MPO/SBB | Negative | Negative | Negative | Negative | Negative | |
Immunocytochemistry | ||||||
Lymphoid markers (CD5, 7,19, 20) | Negative | Negative | Negative | Negative | Negative | |
Myeloid markers (CD13,33) | Negative | Negative | Negative | Negative | Equivocal | |
CD61 (Gp Illa) | Positive | Positive | Positive | Positive | ND |
Most of the cases were males (M:F = 4:1). Out of the 5 cases, two were adults while the other three were in the pediatric age group (1.5 years to 6 years).
Four out of the five cases had an acute onset illness and presented with symptoms of marrow infiltration while the fifth patient had a long history of 3 years duration which is described separately.
One patient out of these 4 cases had features
suggestive of Down's syndrome (Case IV). Hepatosplenomegaly and lymphadenopathy
were observed in two and one patient, respectively (Table
All the four cases were anemic. Leucocytosis was noted in 3 while one case showed thrombocytosis (Case II). Giant platelets were present in Case I only.
Peripheral
blood blast count was in the range of 4% to 40%. The blasts were large, 3-4
times the size of a small mature lymphocyte with moderate to abundant agranular
basophilic cytoplasm. The nuclei were round to oval with fine to stippled chromatin
& 1-2 prominent nucleoli. Few blasts in all the cases showed cytoplasmic
blebbing (Figure
Megakaryoblast with cytoplasmic blebbing (1000X).
Megakaryoblast with platelet budding (1000X).
CD61 positivity in blast (200X).
Bone marrow aspirate smears were cellular in three out of four cases showing blasts ranging from 25% to 56% of all nucleated cells with morphology similar to that seen in the peripheral blood along with presence of micromegakaryocytes and promegakaryocytes. In one of the cases, blasts showed clustering mimicking metastases (Case I). In the fourth case (Case IV), repeated attempts of BMA yielded diluted marrow. Bone marrow biopsy in this case showed blasts with clustering and increased reticulin fibers (Grade III).
The fifth case (Case V) had a long duration illness and presented with weakness and abdominal distension for 3 years.
This
patient had massive splenomegaly, 7 cm below costal margin and mild
hepatomegaly. The patient was anemic with a normal total leukocyte count and
platelet count. Peripheral smear showed a leukoerythroblastic blood picture
with presence of tear drop cells and 25% blasts. Bone marrow aspirate revealed
28% blasts. These blasts had morphology and cytochemical findings similar to those
of the other cases (Table
AMKL is a rare leukemia, accounting for 7–10% of childhood
AML [
It is difficult to diagnose this variant solely on the basis of morphology. However,
there are features like clustering of blasts, presence of cytoplasmic blebbing,
and platelet budding which may be useful in clinching the diagnosis [
Thrombocytosis
was present in one patient who was a 22-year-old female while the other adult
patient had a normal platelet count. All the three pediatric patients were
thrombocytopenic. This observation is similar to that seen in other studies [
AMKL is a rare leukemia. It is important to correctly diagnose this variant in view of its prognostic implications. Although immunophenotyping is the gold standard, it is not available in all the centers. Careful search for features like cytoplasmic blebbing, platelet budding, bone marrow fibrosis, clustering of blasts, and cytochemical positivity for nonspecific esterase which is fluoride resistant can help in correctly diagnosing a significant number of AMKL.