Indian Journal of Pathology and Microbiology

CASE REPORT
Year
: 2022  |  Volume : 65  |  Issue : 3  |  Page : 699--701

”TAM”ing of the shrew-challenges in the diagnosis of Neonatal leukemia with Down's syndrome -A case report with literature review


Srijanaki Manohar, Niveditha Jayakumar 
 Department of Pathology, Government Sivagangai Medical College, Sivagangai, Tamil Nadu, India

Correspondence Address:
Srijanaki Manohar
Department of Pathology, Government Sivagangai Medical College, Sivagangai, Tamil Nadu
India

Abstract

The latest WHO (2017) classification describes the hematological abnormalities of Down's syndrome as a separate entity under 'Myeloid proliferations associated with Down's syndrome'. It includes Transient Abnormal Myelopoiesis and Myeloid leukemia of Down's syndrome. Here we report a case of a 3 days old neonate with Down's syndrome, presenting with a leukemic blood picture. The baby had icterus, fever and hepatosplenomagaly. Peripheral blood showed megakaryoblasts and giant platelets. A diagnosis of transient abnormal myelopoiesis was made by confirming with karyotyping and immunophenotyping. We attempt to address all the diagnostic challenges faced by a clinician and pathologist same, upon encountering such a case,by following an algorithmic approach. The mandatory need for follow up and cytogenetic studies in identifying high risk cases that will become myeloid leukemia of Down's syndrome are stressed. Our case also throws light upon the significance of identification of GATA1 mutation in diagnosing and prognostication of such cases.



How to cite this article:
Manohar S, Jayakumar N. ”TAM”ing of the shrew-challenges in the diagnosis of Neonatal leukemia with Down's syndrome -A case report with literature review.Indian J Pathol Microbiol 2022;65:699-701


How to cite this URL:
Manohar S, Jayakumar N. ”TAM”ing of the shrew-challenges in the diagnosis of Neonatal leukemia with Down's syndrome -A case report with literature review. Indian J Pathol Microbiol [serial online] 2022 [cited 2022 Oct 7 ];65:699-701
Available from: https://www.ijpmonline.org/text.asp?2022/65/3/699/351616


Full Text



 Introduction



Acute myeloid leukemia (AML) is a marrow based neoplasm with distinct morphological, immunophenotypical, cytogenetic and molecular features. The WHO (revised 2017) classification has categorized AML based on recurrent genetic abnormalities, gene mutations, therapy based abnormalities, myelodysplasia related changes, myeloid proliferations associated with Down's syndrome (DS) and NOS (not otherwise specified).[1] Transient abnormal myelopoiesis (TAM), is a disorder clinically, morphologically indistinguishable from AML seen in Down's syndrome. In this case report, we present a case of a three day old newborn with Down's syndrome who presented with respiratory distress and went on to be diagnosed as transient abnormal myelopoiesis (TAM). We discuss the diagnostic challenges that are encountered in newborns presenting with a leukemic blood picture in a resource limited setting.

 Case Report



A term male newborn was referred to our NICU with complaints of respiratory distress. The baby was a product of non-consanguineous marriage of a 25 year old mother, delivered through a normal vaginal delivery. Upon arrival, the baby was alert, pink, normothermic and weighing 2.3 kg. Physical examination revealed presence of syndromic facies (low set ears, flattened nasal bridge and mongoloid slant of eyes) which was later confirmed by karyotyping. On day 3, the baby developed respiratory distress, icterus, fever and mild hepatosplenomagaly. The blood count showed hyperleukocytosis (125.2 × 1000 cells per mm3), hemoglobin 17.7 gm% and platelet count (270.0 × 1000 cells per mm3). Peripheral smear showed a shift to left in WBCs with presence of 30% blasts, nucleated RBCs and giant platelets. Blasts were large with round nuclei, 1-2 nucleoli, basophilic and occasionally granulated cytoplasm [Figure 1]. The possibilities of both myeloid leukemia and TAM, associated with Down's syndrome were considered. Bone marrow examination was deferred upon the deteriorating condition of the baby. Immunophenotyping of peripheral blood revealed 32% blasts with markers positive for CD117, cCD 41a, cCD 61, CD 11c, CD13, CD33, CD 34 (precursor markers), CD36, CD71(subset), MPO (subset) along with aberrant expression of CD7 [Figure 2]. Karyotyping depicted trisomy 21 confirming the Down's phenotype. The baby was referred to a higher Hemato oncology tertiary center and in spite of our best efforts was unfortunately lost to follow up.{Figure 1}{Figure 2}

 Discussion



Acute myeloid leukemia (AML) is a heterogeneous disorder of clonal expansion of myeloid blasts in peripheral blood and bone marrow. In children less than 5 years with Down's syndrome, increased incidence of AML (about 150 fold) is observed of which 70% accounts for acute megakaryoblastic leukemia.[1] The identification of cases of myeloid leukemia associated with Down's syndrome is of utmost importance as they are more responsive to chemotherapy and carry a favorable prognosis.[2]

About 10% of neonates with Down's syndrome present with Transient abnormal myelopoiesis (TAM), a disorder clinically, morphologically indistinguishable from AML.[3],[4] TAM invariably presents at 3-7 days and mostly before 2 months.[5],[6] The clinical presentation ranges from commonly jaundice, respiratory distress, hepatosplenomagaly which were seen in our case, to rare complications of skin rash, cardiopulmonary failure and hepatic fibrosis.[7] The blood picture may show thrombocytopenia with marked leukocytosis as in our case. The percentage of blasts observed in peripheral blood is greater than bone marrow.

The megakaryoblasts observed in both TAM and myeloid leukemia associated with Down's syndrome are similar with basophilic cytoplasm, coarse basophilic granules, cytoplasmic blebbing and vacuolation. The flow cytometry in our case showed positivity for CD117, cCD 41a, cCD 61, CD 11c, CD13, CD33, CD 34 suggesting the blasts to be of megakaryoblastic lineage. Karandikar et al.[8] states that the expression of CD 11c and CD 13 along with HLA-DR negativity, as seen in our case, is predominantly seen in myeloid leukemia associated with Down's syndrome. This clue can help in delineating difficult cases of myeloid leukemia from TAM, when the age of presentation of both overlaps. In our case of TAM we would like to suggest that there is a high probability of it to turn out into myeloid leukemia associated with Down's syndrome based on the blast count and immunophenotyping result. Hence a mandatory follow up and further molecular analysis is essential in this newborn.

In case of a suggestive diagnosis of TAM, GATA1 mutational analysis of peripheral blood is strongly recommended as it is pathognomonic of TAM. GATA1 is a transcription factor, required for normal development of erythroid and megakaryocytic cells that is mutated in TAM and myeloid leukemia associated with Down's syndrome.[9] All GATA1 mutation positive cases can be followed up for every 90 days to monitor development of myeloid leukemia associated with Down's syndrome. The presence of leukemic picture in a newborn with Down's syndrome is not essentially synonymous with AML-FAB M7 or acute megakaryoblastic leukemia.

The following differential diagnoses can be considered in this regard:

Congenital leukemia (AML of any subtype), that can be coexistent with Down's syndrome.[10]Transient abnormal myelopoiesis (TAM) that can progress to myeloid leukemia associated with Down's syndrome.AML with t (1, 22) showing an acute megakaryoblastic leukemia that can present congenitally albeit rarely as is trisomy 21.[11]

The most challenging part of diagnosis is fixing a threshold level of blasts, when mutational studies are unavailable. Most of the newborns with DS have circulating blasts.[12] The Oxford Imperial Down Syndrome Cohort (OIDSC) Study has stated the criterion of blasts >10% and a GATA1 mutation is a must for the diagnosis of TAM.[13],[14]

 Conclusion



Our case of Transient abnormal myelopoiesis has provided us with an experience to diagnose future similar cases with a diligent mind, by identifying and following up high risk cases of TAM that will invariably become myeloid leukemia associated with Down's syndrome. Also, when presented with a case of Down's syndrome newborn with AML, we suggest an algorithmic approach. Firstly, karyotyping must confirm the Down's phenotype in order not to miss any normal mosaics. Secondly, immunophenotyping of peripheral blood can help us identify myeloid lineage and accurate blast percentage. Finally, if possible, a genetic study to identify GATA1 mutation will seal the diagnosis of TAM and myeloid leukemia of Down's syndrome.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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