Introduction:Acute myeloid leukemia (AML), and acute non-lymphocytic leukemia (ANLL) refer to a groupof marrow based neoplasm that have clinicalsimilarities and distinct morphologic,immunophenotypic, cytogenetic and molecularfeatures. The malignant cell in AML is a blastthat most often shows myeloid or monocyticdifferentiation. In few patients, blasts haveerythroid or megakaryocytic differentiation1.Myeloid lineage is demonstrated by morphology(i.e. Auer rods), cytochemical staining (i.e.MPO, Sudan black, chloroacetate esterase,nonspecific esterase etc.), and orimmunophenotyping (CD markers). The FABClassification identified eight subtypes of AMLbased on morphology and cytochemical stainingwith immunophenotypic data in someinstances. Four types (M0, M1, M2, and M3) arepredominantly granulocytic and differ accordingto the extent of maturation. M4 is bothgranulocytic and monocytic, with at least 20%monocytic cells, whereas M5 is predominantlymonocytic (at least 50% monocytic cells). M6shows primarily erythroid differentiation withdysplastic features including megaloblasticchanges, and M7 is acute megakaryocyticleukemia (AML-M7) identified by the presence

ACUTE MEGAKARYOCYTIC LEUKEMIA (FAB M7)ARA T1, ZAMAN MK2, AFROSE S3, ISLAM MS4, BISWAS AR5, KHAN MA6, RAHMAN MM7

Abstract:Acute megakaryocytic leukemia (AML M7) is a rare type of acute leukemia often presented withmyelofibrosis.This report describes a 65 years old female who presented with progressiveweakness and fatigue. She was diagnosed as a case of de novo AMLM-7 on the basis ofperipheral blood finding, bone marrow examination report and immunophenotyping. She refusedchemotherapy, received only supportive therapy and died after two months of diagnosis.

Key Words: Acute megakaryocytic leukemia, thrombocytosis, immunophenotyping.

J Dhaka Med Coll. 2011; 20(1) : 89-92.

1. Dr.Tasneem Ara, Assistant Professor, Dept. of Hematology, Dhaka Medical College and Hospital, Dhaka.2. Dr. Muhammad Kamruzzaman, Medical Officer, Dept. of Hematology, Dhaka Medical College and Hospital,

Dhaka.3. Dr. Salma Afrose, Associate Professor, Dept. of Hematology, Dhaka Medical College and Hospital, Dhaka..4. Dr. M Sirajul Islam, Assistant Professor, Dept. of Hematology, Dhaka Medical College and Hospital, Dhaka.5. Dr. Akhil Ranjon Biswas, Registrar Dept. of Hematology, Dhaka Medical College and Hospital, Dhaka.6. Dr. Mohiuddin Ahmed Khan, Professor, Dept. of Hematology, Dhaka Medical College and Hospital, Dhaka.7. Dr. M Mizanur Rahman, Registrar, Dept. of Hematology, Dhaka Medical College and Hospital, Dhaka.Correspondence: Dr. Tasneem Ara, Assistant Professor, Department of Hematology, Dhaka Medical College,Dhaka, Bangladesh, E-mail: aratasneem@ymail.com.

of megakaryocytic antigens demonstrated byflow cytometry or immunohistochemistry or thepresence of platelet peroxides or a demarcationmembrane system on ultrastuctural studies byelectron microscopy 2.

Case Report:A 65 years old female attended a district levelhospital with three month history of graduallyincreasing weakness and breathlessness.Complete blood count with peripheral blood filmrevealed severe anaemia, very high ESR andleuco-erythroblastic blood picture with grossthrombocytosis. She was treated conservativelywith three units of whole blood and referred toa specialized haematology centre for properdiagnosis and treatment. But she left hospital,remained clinically stable at home for about 6months. As her symptoms got aggravated shevisited the local hospital and was transferredto our hospital with features of anaemia(gradually increasing weakness, shortness ofbreath on exertion, palpitation). Onexamination marked pallor and bilateral mildankle edema was noted. She had no bonytenderness, lymphadenopathy ororganomegaly. Other systems were normal. Oninvestigation: Complete blood count with

peripheral blood revealed hemoglobin 5 g/dl,leucocyte count 29 ×10 9/Lwith a differentialcount of - 30% segmented neutrophils, 20 %lymphocytes, 03% eosinophils and 47% blastand platelet count of 1200×109/L.Peripheralblood smear examination showed normocyticnormochromic red blood cells including fewnucleated red blood cells, white blood cellsshowed left, shift with significant number ofundifferentiated blast suggestive of acuteleukemia. Platelets were markedly increasedwith platelet anisocytosis including many giantplatelets (Figure-1). Bone marrow aspirationwas difficult; blood tap was obtained withsufficient cells in marrow blood smear. Thecells were medium to large sized blast havingbasophilic agranular cytoplasm densechromatin, 1-3 nucleoli including few cellsshowing cytoplasmic blebs (Figure - 2).

Immunophenotype: T-cell markers: CD3, CD5,CD7 were negative,B cell markers: CD19, CD22were negative, myeloid associated markers:CD13, CD33 and platelet associated markersCD42a, CD61 were positive (Figure-3), CD14,CD15, CD117, MPO were negative, othermarkers: CD45, CD34, HLA-DR are positive,CD10 was negative. The biochemical parametersincluding electrolytes, uric acid, creatinine,bilirubin, liver enzymes were normal. SerumLDH was slightly raised. The diagnosis wasconfirmed as AML-M7 as the blasts were positivefor CD42 and CD61 (megakaryocyte specificantigen) along with myeloid markers CD13 andCD33. Other investigation reports were normalincluding skeletal survey for bony lytic lesions.We explained treatment options but our patientrefused chemotherapy and died two months afterdiagnosis.

Fig.-3: Immunophenotyping shows strong positivity for CD42a (left panel) and CD61 (right panel).

Fig.-1: Peripheral blood film shows blasts and agiant platelet

Fig.-2: Bone marrow smear shows plentyundifferentiated blast

J Dhaka Med Coll. Vol. 20, No. 1. April, 2011

90

Discussion:The incidence of acute leukemia isapproximately 2.3 per 100000 people peryear.AML M-7 is a rare subtype of leukemiaand represents 1.2% of cases of adult leukemia,compared to 3-10% of childhood leukemia 3.Acute megakaryocytic leukaemia is a form ofleukaemia where a majority of the blasts aremagakaryoblastic. It is classified under M-7 inthe French-American-British classification.There is bimodal age distribution, with onepeak in the infancy another in the elderly 4

.Our patient was a sixty five years elderlyfemale. Clinical features are not different fromother type of AML but organomegaly is notedinfrequently in adults. In our patient symptomsof anemia that is progressive weakness andmild ankle edema were only symptoms.Cytopenias are usually present but 30% ofpatients have platelet counts >100000/uL asin our case who had very high platelet count(1200x109/L). Osteosclerotic and osteolyticlesions have been described in few casereports 5, 6, 7. The diagnosis depends on theexpression of at least one platelet antigen(CD41, CD42b, CD61 or factor V111 relatedantigen) on the leukemic cells 8, 9. In ourpatient Immunophenotyping of peripheral bloodrevealed blast cells were positive for CD41 andCD 61.The bone marrow may be difficult toaspirate, and more than two third of patientshave significant fibrosis 10. In or case; repeatedattempts at aspiration were unsuccessful,finally blood tap was obtained and diagnosis wasmade from the cell trail. Unfortunately we couldnot perform trephine biopsy including reticulinstain to find out the evidence of fibrosis. AMLM 7 may present as de novo leukemia,secondary leukemia after chemotherapy, ortransformed myeloproliferative disorders andmyelodysplastic syndromes11. Our reportdescribes a de novo presentation of AML M7with thrombocytosis. Although nonspecific,cytogenetic abnormalities are more frequent(>90%) in AMLM-7 than in other subtypes of

AML 8. Cytogenetic analysis was not carriedout in our case. The prognosis of adult AML M-7 is usually poor when compared to other AMLtypes. The complete remission (CR) rate foradult AMLM-7 is 43 to 50% and median disease

free survival is only 6 to 10 months 3. An ECOGseries reported an inferior disease free survivalin M7 AML compared to non M7 AML, and foundM7 AML to be an independent adverseprognostic factor for DFS 3.However completeremission and long term survival are commonin children with AML M7 specially in childrenwith Down syndrome 12, 13. Because of the poorprognosis of adult AMLM-7 early allogenic SCTshould be considered. Interestingly our patientremained alive and clinically stable for severalmonths with symptomatic treatment despitepoor prognosis of AML-M7.

Conclusion:The morphologic diagnosis of AML M-7 can bedifficult and confused with L2 subtype of ALL orwith AML M1. Cytoplasmic blebs suggestive ofmegakaryocytic differentiation may be presenton the blasts. As AML-M7 represents aproliferation predominantly of megakaryoblastsit can be diagnosed by immunophenotypingdemonstrating the expression of one or moreplatelet specific antigen along with myeloidmarkers. We conclude that acutemegakaryocytic leukemia should be consideredin the differential diagnosis of undifferentiatedacute leukemia with high platelet count.

References:1. Maria R. Baer. Jhon P. Green et al. Acute Myeloid

Leukemia in Adult; Wintrobe, s ClinicalHematology; 12th, 2009: p.79; 1883, 1849, 1852,1858.

2. Werdlow SH, Campoo E, Harris NL,Jaffe ES,PileriSA, Setin H, et.al., editors. WHOclassification of tumors of haemopoietic andlymphoid tissues. 4th Edition. Lyon:JARKPress;2008.

3. Talman MS, NeubergD,Cotelingam JD,etal. Acutemegakaryocytic leukaemia:The Eastern CoperativeOncology Group experience. Blood 2000:65:5-13

4. Peterson BA,Levine EG. Uncommon subtypes ofacute nonlymphocytic leukemia: clinical featuresand management of FABM5, M6, and M7.SeminOncol 1987; 14: 425-434.

5. Moody A, Simpson E, Shaw D, Florid radiologicalappearance of megakaryoblastic leukaemia an aidto diagnosis. Pediatr Radiology 1989;486-488.

6. Muler JH, ValdezR,Hayes C,Kaminiski MS. Acutemegakaryocytic leukaemia presenting ashypercalcemia with skeletal lytic lesion.Eur JHematol 2002;68: 392-396.

Acute Megakaryocytic Leukemia (FAB M7) T Ara et al

91

7. Kumar S,Mow B,Kaufman S. Hypercalcemiacomplicating leukemic transformation ofagnogenic myeloid metaplasia.M ayo clinic Proc1999;74:1233-1237.

8. Khalidi HS, Medeiros LJ, Chang KL, et al. Theimmunophenotype of adult acute myeloid leukemia:high frequency of lymphoid antigen expressionand comparison of immunophenotype, French-American-British classification, and karyotypicabnormalities. Am J Clin Pathol 1998; 109:211–220.

9. Bene MC, Castoldi G, Knapp W, et al. Proposalsfor the immunological classification of acuteleukemias. European Group for the ImmunologicalCharacterization of Leukemias (EGIL). Leukemia1995;9:1783–1786

10. Medical Research Council Leukaemia Committee.The relation between morphology and otherfeatures of acute myeloid leukemia, and theirprognostic significance. Br J Haematol 1975;31:165–180.

11. Cheson BD, Bennett JM, Kopecky KJ et al. Revisedrecommendations of the International WorkingGroup for Diagnosis, Standardization of ResponseCriteria, Treatment Outcomes, and ReportingStandards for Therapeutic Trials in Acute MyeloidLeukemia. J Clin Oncol 2003; 21:4642–4649.

12. Hitzler, JK2007 Acute megakaryoblastic leukaemiain Down syndrome. Paeditric blood and cancer49(7 suppl: 1066-9).

13. Hama A,Yagasaki H,Takahashi Y, et. al. Acutemegakaryoblastic leukemia in children: acomparison of AMKL with or without Downsyndrome 2008; Br. J. Haematol.140(5): 552-61.

J Dhaka Med Coll. Vol. 20, No. 1. April, 2011

92