Myeloid and Lymphoid Neoplasms with Eosinophilia

  • Joanna M. Chaffin
  • Natasha Marie SavageEmail author
Part of the Atlas of Anatomic Pathology book series (AAP)


Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB, or FGFR1 were first formally accepted as a set of entities in the 2008 edition of the World Health Organization’s Classification of Tumours of Haematopoietic and Lymphoid Tissues. In the 2016 edition, myeloid and lymphoid neoplasms with eosinophilia and t(8;9)(p22;p24.1);PCM1-JAK2 are now recognized as a provisional entity. Collectively, these represent a heterogeneous group of neoplasms in which eosinophilia is typical but not required. Most commonly, patients are men in their 40s or 50s, although they may present across a broad age range. Abnormalities of PDGFRA usually resemble chronic eosinophilic leukemia (CEL). Rarely, patients may display characteristics of acute myeloid leukemia (AML) or T lymphoblastic leukemia/lymphoma (T-ALL), although eosinophilia remains a consistent feature. Additionally, mast cells with abnormal immunophenotype may be increased in bone marrow biopsies, mimicking systemic mastocytosis (SM). Most abnormalities of PDGFRA are the result of a cryptic 4q12 (CHIC2) deletion, necessitating fluorescence in situ hybridization (FISH) analysis or polymerase chain reaction (PCR) for identification (Figs. 16.1, 16.2, 16.3, 16.4, 16.5, 16.6, 16.7, 16.8, 16.9, and 16.10, Table 16.1). Patients with abnormalities of PDGFRB often present with features of chronic myelomonocytic leukemia (CMML) with eosinophilia, but atypical chronic myeloid leukemia (aCML), CEL, and juvenile myelomonocytic leukemia (JMML) phenotypes are also reported (Figs. 16.11, 16.12, 16.13, 16.14, 16.15, and 16.16, Table 16.2). The presentation of abnormalities of FGFR1 is highly variable and partly dependent on the specific gene rearrangement (Figs. 16.17, 16.18, 16.19, and 16.20, Table 16.3). In t(8;13)(p11;q12), lymphadenopathy is common, and a “bilineal lymphoma” phenotype is often seen. In t(8;9)(p11;q33), monocytosis and tonsillar involvement are characteristic. The t(6;8)(q27;p11–12) presents in an older age group with more prominent eosinophilia and erythrocytosis. Unlike abnormalities of PDGFRA, conventional karyotyping can detect most abnormalities associated with PDGFRB and FGFR1. The recognition of these neoplasms is vital, as patients with abnormalities of PDGFRA and PDGFRB are exquisitely sensitive to imatinib. Unfortunately, definitive, effective targeted monotherapy has not yet been discovered for patients with abnormalities of FGFR1, resulting in a poor prognosis. The use of ponatinib in combination with chemotherapy and possible allogeneic transplantation may improve the prognosis, however.


PDGFRA PDGFRB FGFR1 CHIC2 8p11 myeloproliferative syndrome Stem cell leukemia Eosinophilia 


  1. 1.
    Cools J, DeAngelo DJ, Gotlib J, Stover EH, Legare RD, Cortes J, et al. A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome. N Engl J Med. 2003;348:1201–14.CrossRefPubMedGoogle Scholar
  2. 2.
    Gotlib J. World Health Organization-defined eosinophilic disorders: 2015 update on diagnosis, risk stratification, and management. Am J Hematol. 2015;90:1078–89.CrossRefGoogle Scholar
  3. 3.
    Bain BJ, Gilliland DG, Horny HP, Vardiman JW. Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1. Pathology and genetics of tumours of haematopoietic and lymphoid tissues. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al., editors. World Health Organization classification of tumours. Lyon: IARC Press; 2008. p. 68–73.Google Scholar
  4. 4.
    Metzgeroth G, Walz C, Score J, Siebert R, Schnittger S, Haferlach C, et al. Recurrent finding of the FIP1L1-PDGFRA fusion gene in eosinophilia-associated acute myeloid leukemia and lymphoblastic T-cell lymphoma. Leukemia. 2007;21:1183–8.CrossRefPubMedGoogle Scholar
  5. 5.
    Chen D, Bachanova V, Ketterling RP, Begna KH, Hanson CA, Viswanatha DS. A case of nonleukemia myeloid sarcoma with FIP1L1-PDGFRA rearrangement: an unusual presentation of a rare disease. Am J Surg Pathol. 2013;37:147–51.CrossRefPubMedGoogle Scholar
  6. 6.
    Savage NM, George TI, Gotlib J. Myeloid neoplasms associated with eosinophilia and rearrangement of PDGFRA, PDGFRB, and FGFR1: a review. Int J Lab Hematol. 2013;35:491–500.CrossRefPubMedGoogle Scholar
  7. 7.
    Pardanani A, Ketterling RP, Brockman SR, Flynn HC, Paternoster SF, Shearer BM, et al. CHIC2 deletion, a surrogate for FIP1L1-PDGFRA fusion, occurs in systemic mastocytosis associated with eosinophilia and predicts response to imatinib mesylate therapy. Blood. 2003;102:3093–6.CrossRefPubMedGoogle Scholar
  8. 8.
    Baxter EJ, Hochhaus A, Bolufer P, Reiter A, Fernandez JM, Senent L, et al. The t(4;22)(9q12;q11) in atypical chronic myeloid leukaemia fuses BCR to PDGFRA. Hum Mol Genet. 2002;11:1391–7.CrossRefPubMedGoogle Scholar
  9. 9.
    Tashiro H, Shirasaki R, Noguchi M, Gotoh M, Kawasugi K, Shirafuji N. Molecular analysis of chronic eosinophilic leukemia with t(4;10) showing good response to imatinib mesylate. Int J Hematol. 2006;83:433–8.CrossRefPubMedGoogle Scholar
  10. 10.
    Legrand F, Renneville A, Macintyre E, Mastrilli S, Ackermann F, Cayuela JM, et al. The spectrum of FIP1L1-PDGFRA-associated chronic eosinophilic leukemia: new insights based on a survey of 44 cases. Medicine (Baltimore). 2013;92:e1–9.CrossRefGoogle Scholar
  11. 11.
    Pardanani A, D’Souza A, Knudson RA, Hanson CA, Ketterling RP, Tefferi A. Long-term follow-up of FIP1L1-PDGFRA-mutated patients with eosinophilia: survival and clinical outcome. Leukemia. 2012;26:2439–41.CrossRefPubMedGoogle Scholar
  12. 12.
    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(512) chromosomal translocation. Cell. 1994;77:307–16.CrossRefPubMedGoogle Scholar
  13. 13.
    Vega F, Medeiros LJ, Bueso-Ramos CE, Arboleda P, Miranda RN. Hematolymphoid neoplasms associated with rearrangements of PDGFRA, PDGFRB, and FGFR1. Am J Clin Pathol. 2015;144:377–92.CrossRefPubMedGoogle Scholar
  14. 14.
    Cheah CY, Burbury K, Apperley JF, Huguet F, Pitini V, Gardembas M, et al. Patients with myeloid malignancies bearing PDGFRB fusion genes achieve durable long-term remissions with imatinib. Blood. 2014;123:3574–7.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Baxter EJ, Kulkarni S, Vizmanos JL, Jaju R, Martinelli G, Testoni N, et al. Novel translocations that disrupt the platelet-derived growth factor receptor beta (PDGFRB) gene in BCR-ABL-negative chronic myeloproliferative disorders. Br J Haematol. 2003;120:251–6.CrossRefPubMedGoogle Scholar
  16. 16.
    Jackson CC, Medeiros LJ, Miranda RN. 8p11 myeloproliferative syndrome: a review. Hum. Pathol. 2010;41:461–76.CrossRefPubMedGoogle Scholar
  17. 17.
    Patnaik MM, Gangat N, Knudson RA, Keefe JG, Hanson CA, Pardanani A, et al. Chromosome 8p11.2 translocations: prevalence, FISH analysis for FGFR1 and MYST3, and clinicopathologic correlates in a consecutive cohort of 13 cases from a single institution. Am J Hematol. 2010;85:238–42.CrossRefPubMedGoogle Scholar
  18. 18.
    Savage NM, Johnson RC, Gotlib J, George TI. Myeloid and lymphoid neoplasms with FGFR1 abnormalities: diagnostic and therapeutic challenges. Am J Hematol. 2013;88:427–30.CrossRefPubMedGoogle Scholar
  19. 19.
    Demiroglu A, Steer EJ, Heath C, Taylor K, Bentley M, Allen SL, et al. The t(8;22) in chronic myeloid leukemia fuses BCR to FGFR1: transforming activity and specific inhibition of FGFR1 fusion proteins. Blood. 2001;98:3778–83.CrossRefPubMedGoogle Scholar
  20. 20.
    Popovici C, Zhang B, Grégoire MJ, Jonveaux P, Lafage-Pochitaloff M, Birnbaum D, et al. The t(6;8)(q27;p11) translocation in a stem cell myeloproliferative disorder fuses a novel gene, FOP, to fibroblast growth factor receptor 1. Blood. 1999;93:1381–9.PubMedGoogle Scholar
  21. 21.
    Vizmanos JL, Hernández R, Vidal MJ, Larráyoz MJ, Odero MD, Marín J, et al. Clinical variability of patients with the t(6;8)(q27;p12) and FGFR1OP-FGFR1 fusion: two further cases. Hematol J. 2004;5:534–7.CrossRefPubMedGoogle Scholar
  22. 22.
    Khodadoust MS, Luo B, Medeiros BC, Johnson RC, Ewalt MD, Schalkwyk AS, et al. Clinical activity of ponatinib in a patient with FGFR1-rearranged mixed-phenotype acute leukemia. Leukemia. 2016;30:947–50.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2018

Authors and Affiliations

  1. 1.Department of PathologyMedical College of Georgia at Augusta UniversityAugustaUSA

Personalised recommendations