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Year : 2012  |  Volume : 55  |  Issue : 2  |  Page : 274-276
Refractory cytopenia of the childhood


Department of Pediatric Oncology, Department of Hematology, Apollo Hospitals, Sarita Vihar, Delhi Mathura Road, New Delhi, India

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Date of Web Publication3-Jul-2012
 

How to cite this article:
Chowdhry M, Makroo R N, Srivastava P, Mishra M. Refractory cytopenia of the childhood. Indian J Pathol Microbiol 2012;55:274-6

How to cite this URL:
Chowdhry M, Makroo R N, Srivastava P, Mishra M. Refractory cytopenia of the childhood. Indian J Pathol Microbiol [serial online] 2012 [cited 2014 Apr 24];55:274-6. Available from: http://www.ijpmonline.org/text.asp?2012/55/2/274/97916


Sir

Myelodysplastic syndrome (MDS) is uncommon in children accounting for less than 5% of all hematological neoplasms in children less than 14 years of age. [1] Childhood MDS is now formally recognized in the World Health Organization (WHO) classification, and includes a provisional entity, refractory cytopenia of childhood (RCC), which is characterized by persistent cytopenias and fewer than 5% blasts in a usually hypocellular marrow. Loss of chromosome 7 material, either as complete loss of one chromosome-monosomy 7 (-7) - or as deletion of the long arm (7q-), is the most common cytogenetic abnormality seen in approximately 30% of the cases. We report a case of RCC in an 18-year-old male.

An 18-year-old male patient was referred with progressive anemia since two months, hemoglobin of 7.3 gm/dl and a total leukocyte count of 3,100/cumm. On clinical examination, he had marked pallor, dysmorphic facies, low set ears, and short stature. Around 10-15 Caf'e au Lait spots [Figure 1], each measuring 0.5 cm or more were seen over the trunk and upper arm. The left little finger had a sessile nodule. No nail dystrophy, abnormal dentition, or congenital stigmata signs were found. There was no hepatosplenomegaly. The hematological findings revealed pancytopenia. Bone marrow (BM) aspirates and biopsy showed marked erythroid hyperplasia with suppressed myelopoeisis. [Figure 2], [Figure 3] Erythroid dysplasia, multinuclearity, nuclear budding, and inter nuclear bridging were prominent. Myeloblasts formed 3-4% of non-erythroid cells. Blasts were positive for CD34. Dysmegakaryopoiesis and micromegakaryocytes were conspicuous. A negative HAM's test ruled out the possibility of congenital dyserythropoietic anemia. A small clone of PNH positive cells was observed on immunoflowcytometry. Based on the above findings, a diagnosis of RCC was suggested and a cytogenetic study was advised. Karyotyping was performed on Bone Marrow aspirates, following the standard G-banding procedure. Chromosomes were identified and arranged in accordance with ISCN (2005). Modal karyotype showed the following result: 45, XY,-7 [Figure 4] i.e. Chromosomal analyses revealed a male karyotype with monosomy 7 at the level of banding resolution (ISCN) 400. Fluorescence in situ hybridization (FISH), performed with LSI D7S486 SO/ CEP7 SG dual color DNA probe that hybridizes to band 7q 31 and to the centromere. In a normal cell, the expected pattern of hybridized probe is the appearance of two orange, two green signals. However, on our analysis, only one green and one orange signal was observed which confirmed the Monosomy 7. [Figure 5]. Chromosome breakage study was also done to rule out Fanconi Anemia and no significant increase in breaks was observed in Mitomycin C induced culture of patients as compared to control sample.
Figure 1: Cafe au Lait spots

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Figure 2: BM aspiration: Showing erythroid dysplasia

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Figure 3: BM biopsy: Showing myeloblasts

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Figure 4: Modal karyotype: 45, XY,-7

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Figure 5: FISH analysis revealed one green and one red signal signifying monosomy 7

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MDS is a clonal hematopoietic stem cell disorder characterized by ineffective hematopoiesis, peripheral cytopenias, and dysplastic changes in the bone marrow. [4] Childhood MDS is different from adult MDS in several important ways. Hypocellularity and pancytopenia are much more common in childhood than in adult MDS. A variety of non-hematological disorders such as viral infections nutritional deficiencies and metabolic disorders can give rise to secondary myelodysplasia in children, thereby mimicking RCC. The differential diagnosis of aplastic anemia, congenital dyserythropoietic anemia, and PNH has to be carefully ruled out. Interestingly, a small clone of PNH positive cells was observed in our case. The finding of a PNH positive clone in absence of hemolysis and thrombosis have been previously observed by other workers in childhood MDS. [1] A careful clinical history and examination helps to distinguish inherited bone marrow failures such as Shwachman-Diamond syndrome, Fanconi anemia or pancytopenia with radioulnar synostosis which may show overlapping morphological features with RCC. Fanconis anemia was ruled out by carrying a Mitomycin C induced chromo­some breakage study.

Karyotyping is the most important factor for progression to advanced MDS. [1] Presence of Monosomy 7 or partial loss of 7 q is a common cytogenetic abnormality in these patients and is associated with poor prognosis. [4],[1] Morphology may not help to distinguish between cases with or without monosomy 7. However, a few authors like Hasle H have observed that unlike what has been found in adults, monosomy 7 is not a poor prognostic factor in childhood MDS. [3]

To conclude, the present case throws light upon the diagnostic dilemmas associated with childhood MDS as well as emphasis on the need for intensive work-up required in such condition. The importance of cytogenetics in childhood MDS not only aids in the diagnosis but also help on better prognostication of the said entity.


   Acknowledgment Top


We acknowledge the contribution of Dr Amita Mahajan, DR Sangeeta Rawat, Dr Rashmi Thakur of our institute.[6]

 
   References Top

1.Baumann I, Niemeyer CM, Bennett JM, Shannon K. Childhood myelodysplastic syndrome. In: Swerdlow S, Campo E, Harris NL, editors. International Agency for Research on Cancer. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissue. Geneva, Switzerland: World Health Organization; 2008. p. 104-7.  Back to cited text no. 1
    
2.Steensma DP. The changing classification of myelodysplastic syndromes: What's in a name? Hematology Am Soc Hematol Educ Program 2009:645-55.  Back to cited text no. 2
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3.Hasle H. Significance of Monosomy 7 in Myeloid Leukemias in Children. Pediatr Pathol Mol Med 2000;19:235-50.  Back to cited text no. 3
    
4.Aktas D, Tuncbilek E. Myelodysplastic syndrome associated with monosomy 7 in childhood: A retrospective study. Cancer Genet Cytogenet 2006;171:72-5.  Back to cited text no. 4
[PUBMED]  [FULLTEXT]  
5.Theos A, Korf BR. Pathophysiology of Neurofibromatosis Type 1. Ann Intern Med 2006;144:842-9.  Back to cited text no. 5
    
6.Moustacchi E. Fanconi Anemias. Orphanet encyclopedia. October 2003. Available from: http://www.orpha.net/data/patho/GB/uk-FA.pdf. [Last accessed on 2012 Jan 06].  Back to cited text no. 6
    

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Correspondence Address:
M Chowdhry
Associate Consultant, Transplant Immunology, Molecular Biology and Transfusion Medicine, Apollo Hospitals, Sarita Vihar, Delhi Mathura Road, New delhi-110076
India
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DOI: 10.4103/0377-4929.97916

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