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Year : 2017  |  Volume : 60  |  Issue : 3  |  Page : 445-447
Megakaryocytic blast crisis in chronic myeloid leukemia: A primary presentation

Department of Pathology, Medical College Baroda, SSG Hospital, Vadodara, Gujarat, India

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Date of Web Publication22-Sep-2017

How to cite this article:
Ashar KM, Vaghasiya V, Patel SC. Megakaryocytic blast crisis in chronic myeloid leukemia: A primary presentation. Indian J Pathol Microbiol 2017;60:445-7

How to cite this URL:
Ashar KM, Vaghasiya V, Patel SC. Megakaryocytic blast crisis in chronic myeloid leukemia: A primary presentation. Indian J Pathol Microbiol [serial online] 2017 [cited 2021 Dec 1];60:445-7. Available from: https://www.ijpmonline.org/text.asp?2017/60/3/445/215400


Chronic myeloid leukemia (CML), a classic chronic myeloproliferative disorder, is a clonal stem cell disorder characterized by the acquisition of an oncogenic BCR/ABL fusion protein-a reciprocal translocation (t(9;22) (q34;q11)) and by the proliferation of granulocytic elements at all stages of differentiation. Nearly 10% of patients of CML present in blast phase. Megakaryocytic blast crisis in patients with CML is unusual, constituting <3% of transformed cases.[1]

A 26-year-old male patient presented to our hospital with complaint of low-grade fever and abdominal pain for the past 6 months. There was no history of a cough, anorexia, weight loss, and bleeding from any site. There was no history of any antecedent hematological disorder. On general examination, the patient had pallor, huge splenomegaly. Physical examination was otherwise unremarkable.

Hemogram revealed hemoglobin - 7.2 g/dl, white blood cell (WBC) - 33500/μl, platelet - 2.43 lakh/μl. The peripheral smear showed mild microcytic mild hypochromic red blood cells (RBCs), mild anisopoikilocytosis, few elliptocytes seen with 6 nucleated RBC/100 WBC. The leukocyte differential count was blasts 45%, promyelocyte 1%, myelocyte 3%, metamyelocyte 4%, basophil 8%, eosinophil 5%, band 3%, neutrophil 18%, and lymphocytes 14%. The blasts showed mild to moderate amount of basophilic cytoplasm, round nuclei with the high nucleus-cytoplasm ratio, with fine chromatin, 1–3 nucleoli. Some of the blasts showed cytoplasmic blebs. Platelet count was normal, with some giant platelets and many micromegakaryocytes seen.

Bone marrow aspirate having 46% blasts and 17% basophils and myeloid to the erythroid ratio of 8:1.

Bone marrow biopsy shows striking proliferation of atypical cells showing single to multiple dark hyperchromatic nuclei and moderate to abundant cytoplasm, mimicking megakaryocytic differentiation, distributed diffusely throughout the marrow with few vague clusters of two to many cells. A few focal areas of erythroid precursors are seen, few myeloid precursors seen. Marrow background shows eosinophilic material. Reticulin stain revealed Grade III fibrosis.

Immunohistochemistry showed CD 34 – negative in the blast, CD 117 – negative in the blast, CD 61 – positive in blasts, and megakaryocytes, myeloperoxidase – positive only in the residual myeloid precursor.

A qualitative assay for BCR-ABL translocation was done on peripheral blood leukocyte using reverse transcription-polymerase chain reaction, and hybrid transcript for BCR-ABL was detected in 95% of cells.

A diagnosis of CML is usually straightforward, but when CML presents as a transformed (accelerated or blast-phase) disease, the diagnosis is challenging.

The diagnosis of blast transformation of CML is made by a blast count of >20% in peripheral blood and/or bone marrow, presence of extramedullary blast proliferation or presence of large aggregates of blasts in the marrow. The natural course of transformation from chronic phase to accelerated/blast phase takes 4 years. Blast-phase CML is typically a result of clonal evolution from chronic phase CML and is indicative of an aggressive phase of the disease.[2],[3] The majority of the cases (70%) develop myeloid leukemia.

In our patient, blast count in peripheral blood was 45%. The clinical and morphologic features that prompted us to consider an uncommon evolution from a myeloproliferative neoplasm were massive splenomegaly and peripheral basophilia. In addition, many micromegakaryocytes were seen on peripheral smear but with a normal platelet count.[4],[5] Confirmation of megakaryocytic lineage is by demonstration of megakaryocyte-platelet lineage-specific markers, namely, CD41, CD42b, CD61, CD62, and Factor VIII.[6] In our patient, CD61 was positive [Figure 1] and [Figure 2].
Figure 1: (a) Peripheral blood smear showing blast cells with basophils and an eosinophil. Blast cells are large with abundant cytoplasm, large nucleus, open chromatin, 2–4 prominent nucleoli (Giemsa, ×100). (b) Peripheral blood smear showing blast cells with cytoplasmic blebs. (c) Bone marrow aspirate showing large blast with irregular nuclear contour, and a micromegakaryocyte (Giemsa, ×100). (d) Bone marrow aspirate showing cluster of micromegakaryocytes and platelet clumping

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Figure 2: (a) Bone marrow biopsy showing increased cellularity, atypical large cells, having abundant cytoplasm and large hyperchromayic nucleus (H and E, ×400). (b) IHC stained slide with CD61 antibody showing cytoplasmic positivity in blast as well as megakaryocyte (×400). (c) Reticulin stain shows grade III fibrosis (×400). (d) IHC slide stained with anti-myeloperoxidase antibody showing positivity in residual myeloid precursors (×400)

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Leukoerythroblastic reaction in the peripheral blood along with >20% blasts and marrow fibrosis with atypical megakaryocytes and megakaryoblasts, includes the differential diagnosis of acute megakaryoblastic leukemia, acute panmyelosis with myelofibrosis, and transformed primary myelofibrosis, CML with blast crisis.

Clinicopathological features that help to reach the diagnosis of CML with blast crisis are as follows [Table 1].[2],[3],[4]
Table 1: Differential diagnosis of chronic myeloid leukemia with blast crisis based on clinic-pathological parameters

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Hence, patient with massive splenomegaly with peripheral smear showing more than 20% blasts, basophilia should be worked for cytogenetics/fluorescence in situ hybridization to rule out CML with blast crisis.

CML with blast crisis carries significantly poor prognosis; however, it needs to be differentiated from other conditions that come under differential diagnosis as there are therapeutic implications. In CML blast crisis, the initial use of imatinib followed by combination chemotherapy may improve the outcome and may even convert the blastic crisis of CML into the chronic, stable phase.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Pagano L, Pulsoni A, Vignetti M, Mele L, Fianchi L, Petti MC, et al. Acute megakaryoblastic leukemia: Experience of GIMEMA trials. Leukemia 2002;16:1622-6.  Back to cited text no. 1
Soupir CP, Vergilio JA, Dal Cin P, Muzikansky A, Kantarjian H, Jones D, et al. Philadelphia chromosome-positive acute myeloid leukemia: A rare aggressive leukemia with clinicopathologic features distinct from chronic myeloid leukemia in myeloid blast crisis. Am J Clin Pathol 2007;127:642-50.  Back to cited text no. 2
Pullarkat ST, Vardiman JW, Slovak ML, Rao DS, Rao NP, Bedell V, et al. Megakaryocytic blast crisis as a presenting manifestation of chronic myeloid leukemia. Leuk Res 2008;32:1770-5.  Back to cited text no. 3
Pelloso LA, Baiocchi OC, Chauffaille ML, Yamamoto M, Hungria VT, Bordin JO. Megakaryocytic blast crisis as a first presentation of chronic myeloid leukemia. Eur J Haematol 2002;69:58-61.  Back to cited text no. 4
Al-Shehri A, Al-Seraihy A, Owaidah TM, Belgaumi AF. Megakaryocytic blast crisis at presentation in a pediatric patient with chronic myeloid leukemia. Hematol Oncol Stem Cell Ther 2010;3:42-6.  Back to cited text no. 5
Swerdlow SH, Campo E, Harris NL. WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC Press; 2008.  Back to cited text no. 6

Correspondence Address:
Komal Mahendra Ashar
“Isha Vasyam,” Street No. 19, Kailash Baugh, Gondal, Rajkot - 360 311, Gujarat
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/IJPM.IJPM_841_16

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  [Figure 1], [Figure 2]

  [Table 1]

This article has been cited by
1 Megakaryocytic blast crisis in chronic myeloid leukiemia: An uncommon presentation in a common neoplasm
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[Pubmed] | [DOI]


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