• Users Online: 654
  • Print this page
  • Email this page


 
 
Table of Contents
CASE REPORT
Year : 2017  |  Volume : 4  |  Issue : 1  |  Page : 7-10

Eosinophilia with PDGFRB gene rearrangement and isolated del 5q; an extremely rare presentation of myeloid neoplasm


Department of Hematology, Cytogenetics and Molecular Medicine, National Institute of Blood Disease & BMT, Karachi, Pakistan

Date of Web Publication6-Jul-2017

Correspondence Address:
Nida Anwar
St 2/A Block 17 Gulshan-e- Iqbal KDA Scheme 24, Karachi
Pakistan
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.5530/ami.2017.4.2

Get Permissions

  Abstract 

Introduction: Myeloproliferative neoplasms with PDGFRA, PDGFRB and FGFR1 rearrangements are reported to be very rare entities. Myeloid neoplasms with PDGFRB rearrangement have prominent eosinophilia, neutrophilia or monocytosis and presence of t (5;12)(q31~q33;p12-13) or variant translocation.
Case Report: We report a 55 years old female patient who presented with eosinophilia along with predominant eosinophil precursors on bone marrow and concomitant isolated del (5q) and PDGFRB gene rearrangement which is an infrequent and rare finding.
Conclusion: isolated acquired deletion of the long arm of chromosome 5 (del 5q) also known as 5q- syndrome, is a distinct hematologic disorder reported to be primary myelodys plastic syndrome which is found in females of middle age and usually presents with macrocytic anemia, oval macrocytes, with white blood cell counts normal or reduced, platelet counts normal or elevated and bone marrow exhibitery throid hypoplasia with megakaryocytes showing hypolobated nuclei

Keywords: Del 5q, Eosinophilia, PDGFRB rearrangement


How to cite this article:
Anwar N, Nadeem M, Shan S, Shamsi T. Eosinophilia with PDGFRB gene rearrangement and isolated del 5q; an extremely rare presentation of myeloid neoplasm. Acta Med Int 2017;4:7-10

How to cite this URL:
Anwar N, Nadeem M, Shan S, Shamsi T. Eosinophilia with PDGFRB gene rearrangement and isolated del 5q; an extremely rare presentation of myeloid neoplasm. Acta Med Int [serial online] 2017 [cited 2017 Sep 20];4:7-10. Available from: http://www.actamedicainternational.com/text.asp?2017/4/1/7/209825


  Introduction Top


Myeloproliferative neoplasms with PDG- FRA, PDGFRB and FGFR1 rearrangements are rare entities with reported incidence of <1/100,000.[1]Golub and Gilliland in 1994 first described the ETV6-PDGFRB fusion genes in patients with chronic myelomonocytic leukemia with eosinophilia andt(5;12).[2] Since then, a number of fusion partners for PDGFRB have been described, however most of them being onlycasereports.[3] The diagnostic criteria for a myeloproliferative neoplasm with PDGFRB rearrangement include prominenteosinophilia, havingmonocytosis or neutrophilia and presence of t(5;12)(q31~q33;p12-13) or variant translocations.4 It frequently presents with peripheral blood monocytosis mimicking chronic myelomonocytic leukemia with concomitant eosinophilia.[3],[4] On cytogenetic analysist (5;12)(q31~q33;p12-13) or variant translocations are found.3On the other hand in 1974 Berghe and colleagues reported a distinct hematologic disorder i.e. isolated acquired deletion of the long arm of chromosome 5 del(5q) which found in middle aged females having macrocytic anemia and erythroid hypoplasia with non-lobulated megakaryocyte nuclei on bone marrow.[5],[6],[7] Subsequently Boult wood and Wains coat proposed the definition of the 5q- syndrome as primary myelodysplastic syndrome (MDS) with del(5q) as the sole cytogenetic abnormality without excess of blasts and having low risk of transformation to acute leukemia.[8]


  Case Report Top


A 55 year old female presented with history of cough for 01 week duration and increased frequency of micturition for 5 days. Her physical examination was unremarkable. On systemic examination chest was clear, abdomen was soft, non tender and there was no visceromegaly or lymphadenopathy. Complete blood counts showed hemoglobin 142 g/L, white cell count 51×109/L, and platelet count 251×109/L. Peripheral blood film revealed normocytic normochromic blood picture, leukocytosis and absolute eosinophilia with 90% eosinophils [Figure 1]. Bone marrow examination showed suppressed erythropoiesis and myelopoiesis and predominant population of eosinophil and precursors. Megakaryocytes were adequate, majority exhibiting dysplastic features like multinucleation [Figure 2]. Renal and liver function tests were normal, urinalysis revealed 8-10WBC/HPF. X-Ray chest was unremarkable, serum Ig E levels were within normal range, echocardiography was normal, stool for ova and cyst was negative. Cytogenetic analysis was performed on overnight, 24-hrs un-stimulated and 72-hrs stimulated bone marrow cultures using standard procedures. The GTG (G-bands via trypsin using Giemsa) banding technique was applied, karyotypes were described according to the International System for Human Cytogenetic Nomenclature (ISCN) 2013, karyogram were made using Meta system. Out of 20 meta- phases analyzed, 06 cells(30%) showed del(5q33) whereas 14 cells(70%) showed 46 number of chromosomes with normal female karyotype {46,XX,del(5q33)(06)/46, XX(14)} [Figure 3]. For molecular cytogenetics fresh slides were used for FISH analysis using XL 5q31/5q33 locus-specific probe to see deletion in long arm of chromosome 5. Total 25 inter-phase nuclei were analyzed out of which 12 cells showed normal signal pattern whereas 13 cells showed evidence of del 5q31.2/5q33 locus [Figure 4]. Using a LSI BCR/ABL dual color dual fusion translocation probe (metasystem), a total of 100 interphases + metaphases were analyzed, using a fluorescence Nikon Eclipse Ci microscope equipped with appropriate filters. Image capturing and processing were carried out using Cytovison imaging system (Leica, Richmond, USA). Total 326 inter-phase nuclei were analyzed out of which 120 cells (37%) showed evidence of PDGFR-B gene rearrangement whereas 206 cells (63%) showed normal signal pattern [Figure 5]. FISH results were negative for detection of FIP1L1/CHIC2/ PDGFRA 4q12, and BCR-ABL ([Figure 6]a and 6b. Treatment was started with prednisolone at a dose of 0.5 mg/kg/day for 15 days after which her blood counts revealed hemoglobin 149 g/L, white cell count 12×109/L, and platelet count 381 × 109/L with 36 % eosinophils. She was also treated for her urinary tract infection. She is now given Imatinib 200 mg/ day. Patient is stable and on regular follow up.
Figure 1: Peripheral Blood Film

Click here to view
Figure 2: Bone Marrow Trephine Biopsy

Click here to view
Figure 3: Bone Marrow Cytogenetics (Out of 20 metaphases analyzed, 06 cells(30%) showed del(5q33) where as 14 cells(70%) showed 46 number of chromosomes with normal female karyotype {46,XX,del(5q33)(06)/46,XX(14)})

Click here to view
Figure 4: FISH Analysis for del 5q (Total 25 inter-phase nuclei were analyzed out of which 12 cells showed normal signal pattern whereas 13 cells showed evidence of del 5q31.2/5q33 locus)

Click here to view
Figure 5: FISH Analysis for PDGFRB gene rearrangement (Total 326 inter-phase nuclei were analyzed out of which 120 cells (37%) showed evidence of PDGFR-B gene rearrangement whereas 206 cells (63%) showed normal signal pattern)

Click here to view
Figure 6

Click here to view



  Discussion Top


In our patient, the presence of concomitant del (5q) and PDGFRB gene rearrangement is an infrequent and rare finding. There was no peripheral blood monocytosis or basophilia and neither increase in bone marrow mast cells. The patient presented with preserved platelet counts and she did not have anemia though bone marrow megakaryocytes showed dysplastic features like multi nucleation, only few megakaryocytes were exhibiting monolobation. There was absence of splenomegaly. On cytogenetic analysis unlike translocations involving chromosome 5, isolated deletion 5q was seen. Isolated del (5q) is feature of MDS category of 5q- syndrome. In literature isolated del (5q) abnormality with concomitant JAK2 V617F mutation has been reported earlier,[9] but to best of our knowledge no case has been reported so far with concomitant PDGFRB gene rearrangement and isolated del (5q). Since 5q- alone has good prognosis, it is quite likely that she had it before she developed eosinophilia and 5q- was discovered accidently. However, since this has not been reported earlier we present this unusual combination of molecular abnormalities. If this 5q- has any prognostic advantage to this PDGFRB positive case is unclear and warrants more studies.


  Conflict of Interest Top


Nil



 
  References Top

1.
Gotlib J, Cools J. Five years since the discovery of FIP1L1- PDGFRA: what we have learned about the fusion and other molecularly defined eosinophils. Leukemia 2008;22(11):1999- 2010. http://dx.doi.org/10.1038/leu.2008.287 PMid:18843283  Back to cited text no. 1
    
2.
Golub TR, Barker GF, Lovett M, Gilliland DG. Fusion of PDGF receptor beta to a novel ets-like gene, tel, in chronic myelomonocytic leukemia with t (5; 12) chromosomal translocation. Cell 1994;77(2):307-16. http://dx.doi.org/10.1016/0092- 8674(94)90322-0.  Back to cited text no. 2
    
3.
Savage N, George TI, Gotlib J. Myeloid neoplasms associated with eosinophilia and rearrangement of PDGFRA, PDGFRB, and FGFR1: a review. Int J Lab Hematol. 2013 Oct 1;35(5):491-500. http://dx.doi.org/10.1111/ijlh.12057 ; PMid:23489324.  Back to cited text no. 3
    
4.
Dunphy HC. Myeloid and Lymphoid Neoplasms with Eosinophilia and Abnormalities of PDGFRA, PDGFRB or FGFR1. Current Cancer Therap Rev. 2012 Feb 1;8(1):44-51.  Back to cited text no. 4
    
5.
Cazzola M. Myelodysplastic syndrome with isolated 5q deletion (5q-syndrome). A clonal stem cell disorder characterized by defective ribosome biogenesis. Haematologica 2008 Jul 1;93(7):967-72. http://dx.doi.org/10.3324/haematol.13377 ; PMid:18591621.  Back to cited text no. 5
    
6.
Jädersten M. Pathophysiology and treatment of the myelodysplastic syndrome with isolated 5q deletion. Haematologica. 2010 Mar 1;95(3):348-51 http://dx.doi.org/10.3324/haematol.2009.019141; PMid:20207839 PMCid:PMC2833060.  Back to cited text no. 6
    
7.
Gokalp-Yasar D, Liu JM. Lenalidomide, p53 and del (5q) Myelodysplastic Syndrome: Ribosome Stress Relief. Int Blood Res & Rev;1(1):14-21.  Back to cited text no. 7
    
8.
Boultwood J, Fidler C, Strickson AJ, Watkins F, Gama S, Kearney L, Tosi S, Kasprzyk A, Cheng JF, Jaju RJ, Wainscoat JS. Narrowing and genomic annotation of the commonly deleted region of the 5q- syndrome. Blood. 2002 Jun 15;99(12):4638-41. http://dx.doi.org/10.1182/blood.V99.12.4638 ; PMid:12036901.  Back to cited text no. 8
    
9.
Musto P, Simeon V, Guariglia R, Bianchino G, Grieco V, Nozza F, et al., Myelodysplastic disorders carrying both isolated del (5q) and JAK2V617F mutation: concise review, with focus on lenalidomide therapy. Onco Targets and therapy. 2014;7:1043. PMid:24966686 PMCid:PMC4063862.  Back to cited text no. 9
    

 
  Authors Top





Nida Anwar graduated from Liaquat University of Medical and Health Sciences (LUMHS) Pakistan. She is Gold Medalist throughout M.B.B.S. She did her Post Graduation training in Hematology from National Institute of Blood Diseases and Bone Marrow Transplant (NIBD). She is a fellow of College of Physicians and Surgeons Pakistan and currently working as Consultant Hematologist at NIBD. Her main areas of research are Transfusion Medicine and Myelodysplastic Syndromes.








Mohammad Nadeem graduated from Army Medical College Rawalpindi Pakistan. He is a fellow of College of Physicians and Surgeons Pakistan since 1999 and has served as Consultant Hematologist at various CMHs of country. He also worked as Head of Pathology Department and Consultant Hematologist in military hospital Najran KSA from 2000-2003. Presently he is working at National Institute of Blood Disease and Bone Marrow Transplantation, as “Head of Department of Pathology, Molecular, Cytogenetic and Blood Transfusion Services” and Consultant Hematologist








Saira Shan is Cytogeneticist working at National institute of Blood Diseases and Bone Marrow Transplant Karachi Pakistan (NIBD). She has 10 years of experience in Diagnostic Prognostic/Research Cytogenetics & FISH on Peripheral Blood, Bonemarrow, Amniotic Fluids, and CVS. She is a position holder and did her masters in Science (M.Sc.) from Baqai Medical University Pakistan in 2004 and then trained at Clinical Laboratory Aga Khan University Karachi,Pakistan.








Tahir S Shamsi graduated from Dow Medical College Karachi Pakistan. He was trained in UK during 1990-1994 in Internal Medicine, Hematology and Bone Marrow Transplantation. He is member and fellow of Royal College of Pathologists, UK. He is currently Medical Director of National Institute of Blood Diseases and Bone Marrow Transplantation, Karachi and Director Stem Cell Research. He is approved supervisor for PhD and FCPS Hematology






    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]



 

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

 
  In this article
Abstract
Introduction
Case Report
Discussion
Conflict of Interest
References
Authors
Article Figures

 Article Access Statistics
    Viewed79    
    Printed4    
    Emailed0    
    PDF Downloaded21    
    Comments [Add]    

Recommend this journal