Journal of Postgraduate Medicine
 Open access journal indexed with Index Medicus & ISI's SCI  
Users online: 3163  
Home | Subscribe | Feedback | Login 
About Latest Articles Back-Issues Articlesmenu-bullet Search Instructions Online Submission Subscribe Etcetera Contact
 ::  Similar in PUBMED
 ::  Search Pubmed for
 ::  Search in Google Scholar for
 ::Related articles
 ::  Article in PDF (601 KB)
 ::  Citation Manager
 ::  Access Statistics
 ::  Reader Comments
 ::  Email Alert *
 ::  Add to My List *
* Registration required (free) 

  IN THIS Article
 ::  Abstract
 :: Introduction
 :: Case Report
 :: Discussion
 :: Conclusion
 ::  References
 ::  Article Figures

 Article Access Statistics
    PDF Downloaded35    
    Comments [Add]    
    Cited by others 2    

Recommend this journal


  Table of Contents     
Year : 2018  |  Volume : 64  |  Issue : 1  |  Page : 50-52

Hypereosinophilia: A rare presentation of acute lymphoblastic leukaemia

Department of Medical Oncology, Regional Cancer Centre, Thiruvananthapuram, Kerala, India

Date of Submission15-Nov-2016
Date of Decision23-Jan-2017
Date of Acceptance07-Feb-2017
Date of Web Publication30-Jan-2018

Correspondence Address:
Dr. G Narayanan
Department of Medical Oncology, Regional Cancer Centre, Thiruvananthapuram, Kerala
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jpgm.JPGM_681_16

Rights and Permissions

 :: Abstract 

Acute lymphoblastic leukaemia (ALL) presenting as peripheral blood hypereosinophilia is very rare and the incidence is <1%. The characteristic feature of patients with ALL and hypereosinophilia is the absence of blasts in peripheral blood, and this might lead to misdiagnosis of ALL. It is important for clinicians and pathologists to be aware of this uncommon initial presentation of ALL to avoid delay in diagnosis. We report a 37-year-old man who presented with fever and respiratory symptoms and was found to have hypereosinophilia in peripheral blood. His bone marrow and lymph node biopsies were diagnostic of ALL.

Keywords: Acute lymphoblastic leukaemia, haematologic malignancy, hypereosinophilia

How to cite this article:
Narayanan G, Soman L V, Kumar R. Hypereosinophilia: A rare presentation of acute lymphoblastic leukaemia. J Postgrad Med 2018;64:50-2

How to cite this URL:
Narayanan G, Soman L V, Kumar R. Hypereosinophilia: A rare presentation of acute lymphoblastic leukaemia. J Postgrad Med [serial online] 2018 [cited 2023 Jun 9];64:50-2. Available from:

 :: Introduction Top

Severe eosinophilia defined as eosinophil count more than >5000/μL can occur with allergic disorders, parasitic infections and some malignancies.[1] However, acute lymphoblastic leukaemia (ALL) presenting as peripheral blood hypereosinophilia is very rare and the incidence is <1%.[2] The characteristic feature of patients with ALL and hypereosinophilia is the absence of blasts in peripheral blood, and this might lead to misdiagnosis of ALL. It is important for clinicians and pathologists to be aware of this uncommon initial presentation of ALL to avoid delay in diagnosis. We report a 37-year-old man who presented with hypereosinophilia and was diagnosed as ALL.

 :: Case Report Top

A 37-year-old man presented with breathlessness, intermittent fever, loss of weight and appetite present for 2 months. On examination, he had pallor, bilateral pedal oedema, petechiae and purpura over trunk and extremities, bilateral supraclavicular and left cervical lymphadenopathy and hepatosplenomegaly. There was no neurological symptom or sign. His haemoglobin was 11.5 g/dl; total leucocyte count was 120,500/μL with a differential count of 15% polymorphs, 78% eosinophils and 7% lymphocytes. His absolute eosinophil count was 93,990/μL, and platelet count was 92,000/μL. A peripheral smear examination showed a markedly increased leucocyte count with 70% eosinophils [Figure 1]a. A bone marrow examination showed cellular marrow with sheets of immature cells admixed with eosinophils [Figure 1]b. A lymph node biopsy showed a neoplasm composed of tumour cells in diffuse sheets and focal collection of eosinophils with the Indian file pattern of tumour cells at the periphery [Figure 2]. On immunohistochemistry, the tumour cells were positive for PAX5, CD10, Tdt and CD34, and negative for Bcl6, CD20, CD5, CD7, MPO with an MIBI 40%. He was diagnosed as B lymphoblastic leukaemia. The bone marrow cytogenetic study was normal. A computed tomogram of the chest showed bilateral pleural effusion. He had a normal echocardiogram with the left ventricular ejection fraction of 55% and a normal cerebrospinal fluid study. While awaiting treatment, he developed acute myocardial infarction and expired.
Figure 1: (a) Peripheral smear examination showing marked eosinophilia. (b) Bone marrow smear showing immature cells

Click here to view
Figure 2: Lymph node biopsy showing sheets of tumour cells with focal collection of eosinophils (H and E, ×100)

Click here to view

 :: Discussion Top

The eosinophil counts in a normal adult ranges from 20 to 500/μL; it constitutes 1%–3% of peripheral blood. Eosinophilia is classified as mild (500–1500/μL), moderate (1500–5000/μL) and severe (>5000/μL).[1] Our patient had severe eosinophilia. The haematologic malignancies usually associated with eosinophilia are Hodgkin's lymphoma and myeloproliferative neoplasms where the eosinophilia can be reactive or clonal.

Eosinophilia associated with ALL was first described by Spitzer in 1973.[3] The median age at diagnosis is 14 years; it shows a male preponderance and majority of cases are B-cell origin. Patients usually present with signs and symptoms of organ involvement due to infiltration of organs with eosinophils. The organ systems usually affected are the heart, lungs, skin, central nervous system (CNS), liver and spleen. The common symptoms are cough, shortness of breath, cardiomegaly and lung infiltrates seen in one-third to two-third of patients.[4] Eosinophilia generally precedes the diagnosis of ALL by several months to 2 years, and during this period, the patient may have urticaria rash, and other nonhaematological features of hypereosinophilic syndrome such as cardiomegaly, lung infiltrates and hepatosplenomegaly. Eosinophilia usually resolves on induction, but it returns with relapse of leukaemia. Eosinophilia in these patients is reactive as shown by normal cytogenetics in contrast to the blasts which show abnormal aneuploidy karyotype.[3]

Cytogenetic abnormalities are detected in about more than half the patients with ALL associated with hypereosinophilia.[4] The most common cytogenetic abnormality seen in patients with ALL associated with eosinophilia is t (5;14)(q31;q32) which is otherwise rare in ALL.[2] The eosinophilia is secondary to overproduction of interleukin 3, interleukin 5 and granulocyte stimulating factor by the blasts due to activation of growth factor gene on chromosome 5 when it is translocated adjacent to the immunoglobulin heavy chain gene on chromosome 14.[1],[4] The chromosomal abnormality is usually seen only in leukaemic blasts, and the eosinophils had normal karyotype in 90% of cases supporting the hypothesis that the eosinophilia is reactive. In the 2008 WHO classification of lymphoid neoplasms, this entity is now included as “B lymphoblastic leukaemia/lymphoma with (5;14); IL3-IGH.” The other abnormalities occasionally seen are 45XY, t(7;12) (q22;p13), -9, hyperdiploidy with 5q deletion, or normal karyotype.[5] Our patient had a normal karyotype.

The myeloproliferative neoplasms which are associated with eosinophilia are chronic myeloid leukaemia, acute myeloid leukaemia with inv(16) or t(16;16), chronic eosinophilic leukaemia and myeloid neoplasms with platelet-derived growth factor receptor alpha (PDGFRA), PDGFR beta (PDGFRB) and fibroblast growth factor receptor 1 (FGFR1).[6] These malignancies usually have blasts in the peripheral blood in contrast to ALL with eosinophilia where there is paucity of leukaemia blasts in peripheral blood. In these conditions, there is the formation of fusion genes leading to constitutive stimulation of tyrosine kinase commonly PDGFRA, PDGFRB and FGFR1 which are responsible for eosinophilic proliferation.

Although our patient presented with severe eosinophilia, he did not have any organ involvement as shown by normal electrocardiogram, echocardiogram, absence of CNS involvement and skin rash. However, he died due to acute myocardial infarction before we could start specific treatment. Eosinophils secrete eosinophil granulated proteins which are responsible for the cardiotoxic effects manifesting as acute pericarditis, myocarditis or endocarditis, formation of thrombi adjacent to the injured myocardium and subsequent fibrosis leading to restrictive heart failure.[7] A 61-year-old man who presented with features of eosinophilic toxicity including myocardial infarction, eosinophilic pneumonia and urticaria subsequently was diagnosed to have B ALL.[8] Two patients with eosinophilia associated with ALL also developed myocardial infarction, respiratory failure and cerebrovascular accident as severe complications of eosinophilia.[9]

The prognosis of patients with ALL associated with hypereosinophilia is poor with a median survival of 7.5 months.[10] In a review of ALL associated with hypereosinophila, 26% deaths were eosinophilia related.[4] Since anthracyclines are an important component of chemotherapy for ALL, eosinophilic infiltration of the heart and lungs could compromise the treatment.

 :: Conclusion Top

Hypereosinophilia in the peripheral blood can mask the diagnosis of ALL in this rare entity of ALL associated with hypereosinophilia. Since there is the absence of blasts in the peripheral blood, there may be a delay in diagnosis. Hence, clinicians and pathologists should be aware of this rare disease for early diagnosis and treatment.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

 :: References Top

Rothenberg ME. Eosinophilia. N Engl J Med 1998;338:1592-600.  Back to cited text no. 1
Grimaldi JC, Meeker TC. The t(5;14) chromosomal translocation in a case of acute lymphocytic leukemia joins the interleukin-3 gene to the immunoglobulin heavy chain gene. Blood 1989;73:2081-5.  Back to cited text no. 2
Spitzer G, Garson OM. Lymphoblastic leukemia with marked eosinophilia: A report of two cases. Blood 1973;42:377-84.  Back to cited text no. 3
Sutton R, Lonergan M, Tapp H, Venn NC, Haber M, Norris MD, et al. Two cases of hypereosinophilia and high-risk acute lymphoblastic leukemia. Leukemia 2008;22:1463-5.  Back to cited text no. 4
Bhatti FA, Hussain I, Ali MZ. Adult B lymphoblastic leukaemia/lymphoma with hypodiploidy (-9) and a novel chromosomal translocation t(7;12)(q22;p13) presenting with severe eosinophilia – Case report and review of literature. J Hematol Oncol 2009;2:26.  Back to cited text no. 5
Albano F, Anelli L, Zagaria A, Coccaro N, Tota G, Impera L, et al. Acute myeloid leukemia with t(16;16) (p13;q22) showing a new CBFB-MYH11 fusion transcript associated with an atypical leukemic blasts morphology. Hum Pathol 2014;45:643-7.  Back to cited text no. 6
deMello DE, Liapis H, Jureidini S, Nouri S, Kephart GM, Gleich GJ. Cardiac localization of eosinophil-granule major basic protein in acute necrotizing myocarditis. N Engl J Med 1990;323:1542-5.  Back to cited text no. 7
Song G, Liu H, Sun F, Gu L, Wang S. Acute lymphocytic leukemia with eosinophilia: A case report and review of the literature. Aging Clin Exp Res 2012;24:555-8.  Back to cited text no. 8
Wilson F, Tefferi A. Acute lymphocytic leukemia with eosinophilia: Two case reports and a literature review. Leuk Lymphoma 2005;46:1045-50.  Back to cited text no. 9
Rezamand A, Ghorashi Z, Ghorashi S, Nezami N. Eosinophilic presentation of acute lymphoblastic leukemia. Am J Case Rep 2013;14:143-6.  Back to cited text no. 10


  [Figure 1], [Figure 2]

This article has been cited by
1 High-risk B-cell acute lymphoblastic leukaemia presenting with hypereosinophilia and acquiring a novel PAX5 fusion on relapse
Barbara J. McClure, Susan L. Heatley, Jacqueline Rehn, James Breen, Rosemary Sutton, Timothy P. Hughes, Ram Suppiah, Tamas Revesz, Michael Osborn, Daniel White, David T. Yeung, Deborah L. White
British Journal of Haematology. 2020; 191(2): 301
[Pubmed] | [DOI]
2 Hyperoeosinophilia at diagnosis in adolescent acute lymphoblastic leukaemia/lymphoma: A case report and review of the literature
Dilshad Jahan, Mainul Haque
Advances in Human Biology. 2020; 10(1): 29
[Pubmed] | [DOI]


Print this article  Email this article
Online since 12th February '04
2004 - Journal of Postgraduate Medicine
Official Publication of the Staff Society of the Seth GS Medical College and KEM Hospital, Mumbai, India
Published by Wolters Kluwer - Medknow