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  Table of Contents    
LETTER TO EDITOR  
Year : 2015  |  Volume : 58  |  Issue : 2  |  Page : 254-255
8p11 myeloproliferative syndrome: A case report of this rare clinical entity


1 Department of Hematology, SGPGI, Lucknow, Uttar Pradesh, India
2 Department of Pathology, RGCIRC, New Delhi, India
3 Department of Pathology, RMLIMS, Lucknow, Uttar Pradesh, India
4 Department of Pathology, Max Hospital, New Delhi, India

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Date of Web Publication17-Apr-2015
 

How to cite this article:
Rahman K, Kamboj M, Qayoom S, Khurana A. 8p11 myeloproliferative syndrome: A case report of this rare clinical entity. Indian J Pathol Microbiol 2015;58:254-5

How to cite this URL:
Rahman K, Kamboj M, Qayoom S, Khurana A. 8p11 myeloproliferative syndrome: A case report of this rare clinical entity. Indian J Pathol Microbiol [serial online] 2015 [cited 2019 Dec 12];58:254-5. Available from: http://www.ijpmonline.org/text.asp?2015/58/2/254/155345


Editor,

The 8p11 myeloproliferative syndrome (EMS) is a relatively rare condition characterized by a BCR-ABL negative myeloproliferative disease and an aggressive lymphoma usually T lymphoblastic lymphoma. The myeloproliferative component usually transforms into myeloblastic phase (acute myeloid leukemia [AML]), typically within 1-2 years of diagnosis, which is aggressive and resistant to conventional chemotherapy. The characteristic genetic abnormality is a translocation involving fibroblast growth-factor receptor 1 (FGFR1) at location 8p11. [1]

A 57-year-old female presented with complaints of breathlessness on exertion, and progressively increasing lymphadenopathy of cervical and inguinal region. She had a palpable splenomegaly, 3-4 cm below the costal margin. Peripheral blood examination showed a leukocytosis with shift to left without basophilia. A qualitative test for BCR-ABL fusion transcript was negative. Excision biopsy from the cervical lymph node showed diffuse infiltration by medium-sized atypical lymphoid cells which on immunostaining were positive for CD2, CD3, CD5 (weak), TdT, and CD1a; while negative for CD20 and myeloperoxidase stain (MPO), suggesting a diagnosis of T lymphoblastic lymphoma. Few eosinophils were noted in the background [Figure 1]. Bone marrow aspirate and biopsy showed a hypercellular marrow with myeloid hyperplasia and eosinophilia. She was started on UK acute lymphoblastic leukemia protocol based chemotherapy. After 15 months of initial presentation, she complained of weakness and body ache. Investigations showed a progressive increase in leukocyte count with 21% circulating blasts. Immunophenotyping by flow cytometry showed these blasts to be positive for CD34, CD13, CD33, CD117 (dim), CD11c, CD4 (dim), and human leukocyte antigen-DR; while negative for other B and T cell markers suggesting a diagnosis of an AML. Bone marrow examination done subsequently showed hypercellular marrow with 64% blasts which were negative for MPO [Figure 2]. Cytogenetic analysis showed a 47,XX karyotype with t (8;13) (p11.2;q12), and +12. The patient was started on 3 + 7 induction chemotherapy for acute leukemia, however, showed no response and succumbed to the disease within 2 months.
Figure 1: (a) Lymph node biopsy shows a monotonous population of medium-sized atypical lymphoid cell proliferation (b) which on immunohistochemistry is positive for CD3, (c) CD2 (d) and TdT. (e) Bone marrow aspiration smears were particulate and hypercellular. (f) Higher power examination showed myeloid proliferation with shift to left and eosinophilia. Mild dyspoiesis in myeloid cells in the form of abnormal condensation of chromatin is also appreciated ([a] H and E, ×40, [b-d] Immunohistochemical stain, ×40, [e] May grunwald Giemsa ×2, [f] ×40)


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Figure 2: After the transformation to acute myeloid leukemia. Bone marrow aspirate was particulate and hypercellular, higher power examination showed proliferation of blasts (~60%), these blasts were negative for myeloperoxidase (MPO inset). (May Grunwald giemsa ×2 [left upper], ×40 [right upper)]; MPO [inset]) Lower panel showing the scatter plot of the peripheral blood sample for immunophenotyping. The cells in dim CD45 low side scatter-blast region, show positivity for CD34, CD13, CD33, CD11c, CD4, CD117 (dim and partly), and human leukocyte antigen-DR. A small proportion (~3%) of these blasts is positive for cytoplasmic MPO. These were negative for other B and T cell markers


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Although "8p11 EMS" is the most common name, this entity is designated as myeloid and lymphoid neoplasm with FGFR1 abnormalities as per current World Health Organisation 2008 classification. [2] Genetically, the disease is defined by the fusion of FGFR1 gene (8p11) with partner genes as a consequence of chromosomal translocations. The fusion gene is formed from 3' part of FGFR1 and 5' part of the other gene. Till date, about 12 partner genes have been identified. [3] These are ZNF198/ZMYM2 (13q12), FGFR1OP (6q27), CEP110 (9q33), BCR (22q11), NUP98 (11p15), HERVK (19q13), FGFR10P2 (12p11),TRIM24(7q34), MYO18A(17q23), CPSF6 (12q15), LRRF1P1(2q37), and TPR (1q25). [3] Translocation t(8;13)(p11;q12) ZMYM2-FGFR1 is the most common translocation and has been found in more than 50% cases of EMS. Whatever be the partner gene, the fusion protein causes constitutive and ligand-independent activation of FGFR1 kinase activity leading to activation of several effector pathways including STAT1 and STAT5, PI3K, PLC-g, and MAP-kinase. This culminates in unregulated cell proliferation and neoplastic transformation of hematopoietic cells.

The clinical course is aggressive with a high rate of progression to AML resistant to conventional therapy. Additional cytogenetic abnormalities are noted at the time of transformation which includes trisomy of chromosome 8, 9, 12, or 19 and deletions of chromosome 7 or its either arms and derivative chromosome 9. [4] Similarly, trisomy 12 was noted in the present case.

Transplant is the only successful treatment option with the median survival time for patients who received transplantation after transformation being 24 months as compared to 12 months for patients without transplant. [4] However, FGFR1 tyrosine kinase inhibitors can serve as promising targeted therapeutic agent.

 
   References Top

1.
Xiao S, Nalabolu SR, Aster JC, Ma J, Abruzzo L, Jaffe ES, et al. FGFR1 is fused with a novel zinc-finger gene, ZNF198, in the t (8;13) leukaemia/lymphoma syndrome. Nat Genet 1998;18:84-7.  Back to cited text no. 1
    
2.
Bain BJ, Gilliland DG, Horny HP, Vardiman JW. Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al., editors. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon: IARC; 2008. p. 67-74.  Back to cited text no. 2
    
3.
Trimaldi J, Carballido EM, Bowers JW, Anguiano AL, Zhang ZJ, Shah BD, et al. B-lymphoblastic leukemia/lymphoma associated with t (8;13)(p11;q12)/ZMYM2 (ZNF198)-FGFR1: Rare case and review of the literature. Acta Haematol 2013;130:127-34.  Back to cited text no. 3
    
4.
Jackson CC, Medeiros LJ, Miranda RN 8p11 myeloproliferative syndrome: A review. Hum Pathol 2010;41:461-76.  Back to cited text no. 4
    

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Correspondence Address:
Dr. Khaliqur Rahman
Department of Hematology, SGPGI, Raebareily Road, Lucknow - 226 014, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0377-4929.155345

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