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Clinical and Molecular Diagnostic Evaluation of Systemic Mastocytosis in the South-Eastern Hungarian Population Between 2001–2013 – A Single Centre Experience

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Pathology & Oncology Research

Abstract

Systemic mastocytosis (SM) is a rare chronic myeloproliferative neoplasm with only limited epidemiologic data published so far. We aimed to analyze the clinical and molecular diagnostic features, and the prognosis and cumulative incidence of SM cases in a cohort of south-eastern Hungarian patients of 13 year follow up. In the period 2001–2013, 35 consecutive SM cases were diagnosed in our regional centre. Immunophenotype, KIT D816V mutation frequency and clinical characteristics, and the prognosis impact of clinical subtypes were tested and compared with published data. Indolent SM (ISM) was diagnosed in 14 patients, SM with an associated clonal hematologic non-mast cell lineage disease (SM-AHNMD) in 15 patients and aggressive SM (ASM) in 6 patients. The KIT D816V mutation was found in 11/14 (78 %) of the ISM cases, in 12/15 (80 %) of the SM-AHNMD cases and in 5/6 (83 %) of the ASM cases. The life expectancy of ISM patients was better, whereas the SM-AHNMD and ASM groups exhibited a reduced median survival. The cumulative incidence for 13 year of the SM was 0.27/10,000. We detected lower 13 year cumulative SM incidence than of published epidemiologic data due to in our analyses involved only those patients who had bone marrow biopsy and histopathologically confirmed SM. This clinical overview clearly showed that the clinical characteristics differ between ISM (UP, anaphylaxis and osteoporosis) and SM-AHNMD/ASM (cytopenia, eosinophilia and splenomegaly).

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References

  1. Brunning RD, McKenna RW, Rosai J, Parkin JL, Risdall R (1983) Systemic mastocytosis. Extracutaneous manifestations. Am J Surg Pathol 7(5):425–438

    Article  CAS  PubMed  Google Scholar 

  2. Stevens EC, Rosenthal NS (2001) Bone marrow mast cell morphologic features and hematopoietic dyspoiesis in systemic mast cell disease. Am J Clin Pathol 116(2):177–182. doi:10.1309/Q2WJ-46CL-YRFT-M5JF

    Article  CAS  PubMed  Google Scholar 

  3. Gotlib J, Pardanani A, Akin C, Reiter A, George T, Hermine O, Kluin-Nelemans H, Hartmann K, Sperr WR, Brockow K, Schwartz LB, Orfao A, Deangelo DJ, Arock M, Sotlar K, Horny HP, Metcalfe DD, Escribano L, Verstovsek S, Tefferi A, Valent P (2013) International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) & European Competence Network on Mastocytosis (ECNM) consensus response criteria in advanced systemic mastocytosis. Blood 121(13):2393–2401. doi:10.1182/blood-2012-09-458521

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Wadleigh M, Tefferi A (2010) Classification and diagnosis of myeloproliferative neoplasms according to the 2008 World Health Organization criteria. Int J Hematol 91(2):174–179. doi:10.1007/s12185-010-0529-5

    Article  PubMed  Google Scholar 

  5. Valent P (2013) Mastocytosis: a paradigmatic example of a rare disease with complex biology and pathology. Am J Cancer Res 3(2):159–172

    PubMed  PubMed Central  Google Scholar 

  6. van Doormaal JJ, Arends S, Brunekreeft KL, van der Wal VB, Sietsma J, van Voorst Vader PC, Oude Elberink JN, Kluin-Nelemans JC, van der Veer E, de Monchy JG (2013) Prevalence of indolent systemic mastocytosis in a Dutch region. J Allergy Clin Immunol 131(5):1429–1431 e1421. doi:10.1016/j.jaci.2012.10.015

    Article  PubMed  Google Scholar 

  7. Cohen SS, Skovbo S, Vestergaard H, Kristensen T, Moller M, Bindslev-Jensen C, Fryzek JP, Broesby-Olsen S (2014) Epidemiology of systemic mastocytosis in Denmark. Br J Haematol. doi:10.1111/bjh.12916

    Google Scholar 

  8. Valent P, Arock M, Bonadonna P, Brockow K, Broesby-Olsen S, Escribano L, Gleixner KV, Grattan C, Hadzijusufovic E, Hagglund H, Hermine O, Horny HP, Kluin-Nelemans HC, Maurer M, Niedoszytko M, Nedoszytko B, Nilsson G, Oude-Elberink HN, Orfao A, Radia D, Reiter A, Siebenhaar F, Sotlar K, Sperr WR, Triggiani M, VanDoormaal JJ, Varkonyi J, Yavuz S, Hartmann K (2012) European Competence Network on Mastocytosis (ECNM): 10-year jubilee, update, and future perspectives. Wien Klin Wochenschr 124(23–24):807–814. doi:10.1007/s00508-012-0293-z

    Article  PubMed  Google Scholar 

  9. Valent P, Akin C, Escribano L, Fodinger M, Hartmann K, Brockow K, Castells M, Sperr WR, Kluin-Nelemans HC, Hamdy NA, Lortholary O, Robyn J, van Doormaal J, Sotlar K, Hauswirth AW, Arock M, Hermine O, Hellmann A, Triggiani M, Niedoszytko M, Schwartz LB, Orfao A, Horny HP, Metcalfe DD (2007) Standards and standardization in mastocytosis: consensus statements on diagnostics, treatment recommendations and response criteria. Eur J Clin Invest 37(6):435–453. doi:10.1111/j.1365-2362.2007.01807.x

    Article  CAS  PubMed  Google Scholar 

  10. Valent P, Akin C, Arock M, Brockow K, Butterfield JH, Carter MC, Castells M, Escribano L, Hartmann K, Lieberman P, Nedoszytko B, Orfao A, Schwartz LB, Sotlar K, Sperr WR, Triggiani M, Valenta R, Horny HP, Metcalfe DD (2012) Definitions, criteria and global classification of mast cell disorders with special reference to mast cell activation syndromes: a consensus proposal. Int Arch Allergy Immunol 157(3):215–225. doi:10.1159/000328760

    Article  PubMed  PubMed Central  Google Scholar 

  11. Pardanani A (2013) Systemic mastocytosis in adults: 2013 update on diagnosis, risk stratification, and management. Am J Hematol. doi:10.1002/ajh.23459

    Google Scholar 

  12. Garcia-Montero AC, Jara-Acevedo M, Teodosio C, Sanchez ML, Nunez R, Prados A, Aldanondo I, Sanchez L, Dominguez M, Botana LM, Sanchez-Jimenez F, Sotlar K, Almeida J, Escribano L, Orfao A (2006) KIT mutation in mast cells and other bone marrow hematopoietic cell lineages in systemic mast cell disorders: a prospective study of the Spanish Network on Mastocytosis (REMA) in a series of 113 patients. Blood 108(7):2366–2372. doi:10.1182/blood-2006-04-015545

    Article  CAS  PubMed  Google Scholar 

  13. Soucie E, Hanssens K, Mercher T, Georgin-Lavialle S, Damaj G, Livideanu C, Chandesris MO, Acin Y, Letard S, de Sepulveda P, Hermine O, Bernard OA, Dubreuil P (2012) In aggressive forms of mastocytosis, TET2 loss cooperates with c-KITD816V to transform mast cells. Blood 120(24):4846–4849. doi:10.1182/blood-2011-12-397588

    Article  CAS  PubMed  Google Scholar 

  14. Tay CM, Ong CW, Lee VK, Pang B (2013) KIT gene mutation analysis in solid tumours: biology, clincial applications and trends in diagnostic reporting. Pathology 45(2):127–137. doi:10.1097/PAT.0b013e32835c7645

    Article  CAS  PubMed  Google Scholar 

  15. Beghini A, Peterlongo P, Ripamonti CB, Larizza L, Cairoli R, Morra E, Mecucci C (2000) C-kit mutations in core binding factor leukemias. Blood 95(2):726–727

    CAS  PubMed  Google Scholar 

  16. Lim KH, Tefferi A, Lasho TL, Finke C, Patnaik M, Butterfield JH, McClure RF, Li CY, Pardanani A (2009) Systemic mastocytosis in 342 consecutive adults: survival studies and prognostic factors. Blood 113(23):5727–5736. doi:10.1182/blood-2009-02-205237

    Article  CAS  PubMed  Google Scholar 

  17. Pardanani A, Tefferi A (2010) Systemic mastocytosis in adults: a review on prognosis and treatment based on 342 Mayo Clinic patients and current literature. Curr Opin Hematol 17(2):125–132. doi:10.1097/MOH.0b013e3283366c59

    Article  PubMed  Google Scholar 

  18. Verstovsek S (2013) Advanced systemic mastocytosis: the impact of KIT mutations in diagnosis, treatment, and progression. Eur J Haematol 90(2):89–98. doi:10.1111/ejh.12043

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Escribano L, Alvarez-Twose I, Sanchez-Munoz L, Garcia-Montero A, Nunez R, Almeida J, Jara-Acevedo M, Teodosio C, Garcia-Cosio M, Bellas C, Orfao A (2009) Prognosis in adult indolent systemic mastocytosis: a long-term study of the Spanish Network on Mastocytosis in a series of 145 patients. J Allergy Clin Immunol 124(3):514–521. doi:10.1016/j.jaci.2009.05.003

    Article  PubMed  Google Scholar 

  20. Ustun C, DeRemer DL, Akin C (2011) Tyrosine kinase inhibitors in the treatment of systemic mastocytosis. Leuk Res 35(9):1143–1152. doi:10.1016/j.leukres.2011.05.006

    Article  CAS  PubMed  Google Scholar 

  21. Akin C, Fumo G, Yavuz AS, Lipsky PE, Neckers L, Metcalfe DD (2004) A novel form of mastocytosis associated with a transmembrane c-kit mutation and response to imatinib. Blood 103(8):3222–3225. doi:10.1182/blood-2003-11-3816

    Article  CAS  PubMed  Google Scholar 

  22. Hungarian Central Statistical Office-Population census (2011). Regional data-Bács-Kiskun county http://www.ksh.hu/nepszamlalas/tables_regional_03; Regional data- Békés county http://www.ksh.hu/nepszamlalas/tables_regional_04; Regional data - Csongrád county http://www.ksh.hu/nepszamlalas/tables_regional_06

  23. Valent P, Sperr WR, Akin C (2010) How I treat patients with advanced systemic mastocytosis. Blood 116(26):5812–5817. doi:10.1182/blood-2010-08-292144

    Article  CAS  PubMed  Google Scholar 

  24. Lim KH, Pardanani A, Butterfield JH, Li CY, Tefferi A (2009) Cytoreductive therapy in 108 adults with systemic mastocytosis: Outcome analysis and response prediction during treatment with interferon-alpha, hydroxyurea, imatinib mesylate or 2-chlorodeoxyadenosine. Am J Hematol 84(12):790–794. doi:10.1002/ajh.21561

    Article  CAS  PubMed  Google Scholar 

  25. Pardanani A (2013) How I treat patients with indolent and smoldering mastocytosis (rare conditions but difficult to manage). Blood 121(16):3085–3094. doi:10.1182/blood-2013-01-453183

    Article  CAS  PubMed  Google Scholar 

  26. Valent P (1996) Biology, classification and treatment of human mastocytosis. Wien Klin Wochenschr 108(13):385–397

    CAS  PubMed  Google Scholar 

  27. Escribano L, Akin C, Castells M, Orfao A, Metcalfe DD (2002) Mastocytosis: current concepts in diagnosis and treatment. Ann Hematol 81(12):677–690. doi:10.1007/s00277-002-0575-z

    Article  CAS  PubMed  Google Scholar 

  28. Valent P, Akin C, Sperr WR, Horny HP, Arock M, Lechner K, Bennett JM, Metcalfe DD (2003) Diagnosis and treatment of systemic mastocytosis: state of the art. Br J Haematol 122(5):695–717

    Article  PubMed  Google Scholar 

  29. Schumacher JA, Elenitoba-Johnson KS, Lim MS (2008) Detection of the c-kit D816V mutation in systemic mastocytosis by allele-specific PCR. J Clin Pathol 61(1):109–114. doi:10.1136/jcp.2007.047928

    Article  CAS  PubMed  Google Scholar 

  30. Akin C (2005) Clonality and molecular pathogenesis of mastocytosis. Acta Haematol 114(1):61–69. doi:10.1159/000085563

    Article  CAS  PubMed  Google Scholar 

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Acknowledgment

The authors would like to acknowledge Balázs Kotosz PhD for his help with statistical analysis and Professor Zoltán Vokó MD. PhD. DSc for epidemiological supervision.

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Authors and Affiliations

  1. 2nd Department of Medicine and Cardiology Centre, Medical Faculty, Albert Szent-Györgyi Clinical Centre, University of Szeged, Szeged, Hungary

    Imelda Marton & Zita Borbényi

  2. Laboratory of Tumour Pathology and Molecular Diagnostics, Szeged, Hungary

    László Krenács, Enikő Bagdi & Annamária Bakos

  3. 1st Department of Internal Medicine, Semmelweis University, Budapest, Hungary

    Judit Demeter

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  1. Imelda Marton
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Correspondence to Imelda Marton.

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Marton, I., Krenács, L., Bagdi, E. et al. Clinical and Molecular Diagnostic Evaluation of Systemic Mastocytosis in the South-Eastern Hungarian Population Between 2001–2013 – A Single Centre Experience. Pathol. Oncol. Res. 22, 293–299 (2016). https://doi.org/10.1007/s12253-015-9948-1

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