Indian Journal of Pathology and Microbiology
Home About us Instructions Submission Subscribe Advertise Contact e-Alerts Ahead Of Print Login 
Users Online: 3212
Print this page  Email this page Bookmark this page Small font sizeDefault font sizeIncrease font size

  Table of Contents    
Year : 2011  |  Volume : 54  |  Issue : 3  |  Page : 647-648
Morphological characteristics of leukemic blasts in acute leukemia in a patient of Down syndrome following transient abnormal myelopoiesis

1 Department of Pathology, Lady Hardinge Medical College and Associated Hospitals, New Delhi, India
2 Department of Pediatrics, Lady Hardinge Medical College and Associated Hospitals, New Delhi, India

Click here for correspondence address and email

Date of Web Publication20-Sep-2011

How to cite this article:
Sharma S, Pujani M, Pujani M, Chandra J. Morphological characteristics of leukemic blasts in acute leukemia in a patient of Down syndrome following transient abnormal myelopoiesis. Indian J Pathol Microbiol 2011;54:647-8

How to cite this URL:
Sharma S, Pujani M, Pujani M, Chandra J. Morphological characteristics of leukemic blasts in acute leukemia in a patient of Down syndrome following transient abnormal myelopoiesis. Indian J Pathol Microbiol [serial online] 2011 [cited 2020 Nov 23];54:647-8. Available from: https://www.ijpmonline.org/text.asp?2011/54/3/647/85133


Children with Down syndrome have a 10- to 100- fold increased risk of developing leukemia. [1] Myeloid leukemias related to Down syndrome have been assigned a separate category in the recent World Health Organization classification of hemopoietic and lymphoid tumors-2008, which includes transient abnormal myelopoiesis (TAM) and myeloid leukemia associated with Down syndrome. [2] Here, we highlight the morphological features of blasts in a case of a 2-year-old child with Down syndrome who presented initially as TAM and progressed to acute myeloid leukemia 3 years after the initial diagnosis.

A 2-year-old male child with Down syndrome presented in 2006 with complaints of an episode of generalized tonic clonic seizure, fever, vomiting, loose stools and epistaxis for 2 days. On examination, there was no lymphadenopathy or hepatosplenomegaly. Features suggestive of Down syndrome were seen. Hematological findings revealed hemoglobin (Hb) 5.1 g/dl, total leucocyte count (TLC) 7,100/ ml, platelet count 60,000/ ml, peripheral smear-shift to left with 5% blasts. Bone marrow aspiration (BMA) smears were diluted; however, showed 8% blasts. Bone marrow biopsy (BMB) showed increased and dysplastic megakaryocytes and scattered blasts with grade 3 fibrosis on reticulin stain. Blasts were myeloperoxidase (MPO) negative, Sudan Black B (SBB) negative but Periodic acid Schiff (PAS) positive. CD 61 was positive in blasts. However, flow cytometry could not be performed. A diagnosis of TAM was made. The patient was treated with antibiotics and antiepileptics and discharged after 3 weeks. Since then, he was on regular follow-up and had persistent thrombocytopenia, with variable number of blasts (2-10%) in the peripheral smear. He presented in 2009 with generalized lymphadenopathy and moderate hepatosplenomegaly. Hematological findings revealed Hb 5.1 g/dl, TLC 8,200/ml, platelet count 8000/ ml, peripheral smear-shift to left with 8% blasts. BMA smears showed presence of 25% blasts, which were two- to four-times the size of small lymphocyte with a high nucleocytoplasmic ratio, scant to moderate amount of cytoplasm with coarse basophilic granules and blebbing. Nuclei were round to oval, few showing indentation with fine to slightly condensed chromatin and 0-3 nucleoli [Figure 1]. Bone marrow biopsy and cytochemistry revealed similar features. Blasts were CD33, CD13, CD117, CD34, HLADR-positive, CD3, CD10, CD19, CD14 and CD11C-negative. CD61 on bone marrow biopsy was negative. A diagnosis of myeloid leukemia associated with Down syndrome, possibly acute megakaryoblastic leukemia (AMKL), was suggested. The patient expired 3 days after admission.
Figure 1: Bone marrow aspirate smear showing a large leukemic blast with characteristic cytoplasmic blebbing, coarse granules and moderately condensed chromatin (Wright stain, ×1000)

Click here to view

TAM resolves spontaneously over a period of several weeks to 3 months. In 20-30% of the affected cases, nonremitting AMKL frequently develops in 1-3 years. [2] In the study conducted by Children's cancer group studies 2861 and 2891, AML-M7 subtype was found in 62% of the cases in Down syndrome children as compared with only 6% in children without Down syndrome. [3]

Athale et al. [4] in their study of 41 cases of AMKL over a 14-year period observed that blast cells in bone marrow showed surface blebbing in all cases, which was prominent in 86% of them. On immunophenotyping, leukemic cells of 33 patients expressed at least one platelet-associated antigen (CD36, CD41a, CD61, vWF, cytoplasmic factor VIII). There are various reports suggesting that CD61 and vWF staining is affected by fixation and decalcification procedures such that it can be falsely negative and should be supplemented with CD42/factor VIII staining. [5] In the present case, CD61 was positive only in blasts at the TAM stage (on bone marrow imprint smears) but not in the leukemic stage, where it was applied on bone marrow biopsy sections, and this could be because of loss of antigen during processing.

Leukemic blasts of transient leukemia in Down syndrome harbor somatic mutations of GATA1, an essential transcription factor of megakaryocytic differentiation, along with trisomy 21/ mosaicism. [6] The same mutation is observed in blasts from TAM as well as those from AMKL. [7]

Thus, to conclude, in the present case, the typical morphology of the blasts, i.e. variable size, surface blebbing, coarse MPO- negative granules, variably clumped chromatin with round to oval nuclei,still suggest a megakaryocytic lineage in spite of negative CD61 staining on biopsy. However, in such cases, GATA1 mutation analysis should be performed for confirmation.

   Acknowledgments Top

Dr. Richa Chauhan, Dr. Varinder Singh

   References Top

1.Massey GV. Transient leukemia in new borns with down syndrome. Pediatr Blood Cancer 2005;44:29-32.  Back to cited text no. 1
2.Baumann I, Niemeyer CM, Brunning RD, Arber DA, Porwit A. Myeloid proliferations related to Down syndrome. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al., editors. WHO Classification of Haematopoietic and Lymphoid Tissues. Lyon: IARC; 2008. p. 142-4.  Back to cited text no. 2
3.Lange BJ, Kobrinsky N, Barnard DR, Arthur DC, Buckley JD, Howells WB, et al. Distinctive demography, biology and outcome of Acute Myeloid Leukemia and Myelodyplastic syndrome in children with Down Syndrome: Children's Cancer Group Studies 2861 and 2891. Blood 1998;91:608-15.  Back to cited text no. 3
4.Athale UH, Razzouk BI, Raimondi SC, Tong X, Behm FG, Head DR, et al. Biology and outcome of childhood acute megakaryoblastic leukemia: A single institution's experience. Blood 2001;97:3727-32.  Back to cited text no. 4
5.John KC. Hematopoietic disorders in Down Syndrome. Int J Clin Exp Pathol 2008;1:287-95.  Back to cited text no. 5
6.Cabelof DC, Patel HV, Chen Q, van Remmen H, Matherly LH, Ge Y, et al. Mutational spectrum at GATA1 provides insights into mutagenesis and leukemogenesis in Down syndrome. Blood 2009;114:2753-63.  Back to cited text no. 6
7.Hitzler JK. Acute megakaryoblastic leukemia in Down syndrome. Pediatr Blood Cancer 2007;49:1066-9.  Back to cited text no. 7

Correspondence Address:
Meenu Pujani
Department of Pathology, Lady Hardinge Medical College and Associated Hospitals, New Delhi - 110 001
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.85133

Rights and Permissions


  [Figure 1]


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
    Email Alert *
    Add to My List *
* Registration required (free)  

    Article Figures

 Article Access Statistics
    PDF Downloaded89    
    Comments [Add]    

Recommend this journal