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Clonal mast cell disease not meeting WHO criteria for diagnosis of mastocytosis: clinicopathologic features and comparison with indolent mastocytosis

Leukemia volume 27, pages 2091–2094 (2013)Cite this article

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Mastocytosis results from a clonal proliferation of morphological and immunophenotypically abnormal mast cells.1, 2, 3, 4 Extracutaneous involvement is commonly seen in adults, and the diagnosis of systemic mastocytosis (SM) is established as per World Health Organization (WHO) criteria.5 Patients are frequently referred with episodic symptoms of ‘mast cell activation’ (MCA), wherein an underlying allergic or autoimmune disorder cannot be identified.6, 7 In the absence of cutaneous involvement by mastocytosis, the next step typically is to determine whether SM is present. Increasingly, during such testing, patients who do not satisfy full diagnostic criteria for SM are identified; the major criterion (compact infiltrates of ⩾15 mast cells) is not met; instead, only one or two minor criteria are met. Previous reports have implicated such patients in the context of idiopathic anaphylaxis or anaphylaxis following Hymenoptera sting,8, 9, 10 however, the full spectrum of clinical presentation is currently not understood. Given the paucity of data regarding these patients, variously described as having monoclonal MCA syndrome (MMCAS) or pre-diagnostic indolent SM (ISM),11, 12, 13 we sought to describe their clinicopathologic characteristics, and to compare them with ISM cases, or those with MCA symptoms without clonal mast cells.

This study was approved by the Mayo Clinic Institutional Review Board and adhered to the tenets of the Declaration of Helsinki. We retrospectively studied consecutive patients who were referred to our institution for evaluation for SM. Every patient had symptoms attributed by the referring physician as being related to mast cell degranulation. The diagnostic assessment included a bone marrow biopsy with tryptase immunostaining and mast cell immunophenotyping for CD25/CD2 expression by flow cytometry and/or immunohistochemistry. Bone marrow histology was reviewed by two experienced hematopathologists (DC and CAH) with careful assessment for mast cell cytologic atypia (for example, spindling or hypogranularity), presence or absence of mast cell aggregates (⩾15 mast cells) and pattern of mast cell infiltration (that is, compact clusters versus singly distributed/interstitial). KITD816V analysis was performed using a sensitive (0.01%) allele-specific PCR assay.7, 14 The diagnosis and classification of SM was as per WHO criteria.5 After a full review of clinicopathological characteristics, three groups were identified: ‘sub-diagnostic SM’ (that is, those meeting 1–2 minor criteria for SM only), ISM (that is, those meeting WHO diagnostic criteria for SM) and those with MCA symptoms without clonal mast cells. In the group with sub-diagnostic SM, those with cutaneous mast cell infiltration (for example, urticaria pigmentosa) were excluded. Similarly, patients with non-ISM were also excluded from the study. All statistical analyses considered clinical and laboratory parameters obtained at time of referral. Differences in the distribution of continuous variables between categories were analyzed by either Mann–Whitney or Kruskal–Wallis tests. Patient groups with nominal variables were compared by χ2 test. P-values <0.05 were considered significant. The Stat View statistical package (SAS Institute, Cary, NC, USA) was used for all calculations.

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References

  1. Pardanani A . Systemic mastocytosis in adults: 2012 Update on diagnosis, risk stratification, and management. Am J Hematol 2012; 87: 401–411.

    Article  PubMed  Google Scholar 

  2. Elliott MA, Pardanani A, Li CY, Tefferi A . Immunophenotypic normalization of aberrant mast cells accompanies histological remission in imatinib-treated patients with eosinophilia-associated mastocytosis. Leukemia 2004; 18: 1027–1029.

    Article  CAS  PubMed  Google Scholar 

  3. Tefferi A . Novel mutations and their functional and clinical relevance in myeloproliferative neoplasms: JAK2, MPL, TET2, ASXL1, CBL, IDH and IKZF1. Leukemia 2010; 24: 1128–1138.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Lasho T, Tefferi A, Pardanani A . Inhibition of JAK-STAT signaling by TG101348: a novel mechanism for inhibition of KITD816V-dependent growth in mast cell leukemia cells. Leukemia 2010; 24: 1378–1380.

    Article  CAS  PubMed  Google Scholar 

  5. Horny HP, Metcalfe DD, Bennett JM, Bain BJ, Akin C, Escribano L et al. Mastocytosis. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al (eds). WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues 4th edn International Agency for Research and Cancer (IARC): Lyon, 2008; pp 54–63.

    Google Scholar 

  6. Pardanani A, Finke C, Abdelrahman RA, Lasho TL, Hanson CA, Tefferi A . Increased circulating IL-2Ralpha (CD25) predicts poor outcome in both indolent and aggressive forms of mastocytosis: a comprehensive cytokine-phenotype study. Leukemia 2013; 27: 1430–1433.

    Article  CAS  PubMed  Google Scholar 

  7. Lim KH, Tefferi A, Lasho TL, Finke C, Patnaik M, Butterfield JH et al. Systemic mastocytosis in 342 consecutive adults: survival studies and prognostic factors. Blood 2009; 113: 5727–5736.

    Article  CAS  PubMed  Google Scholar 

  8. Akin C, Scott LM, Kocabas CN, Kushnir-Sukhov N, Brittain E, Noel P et al. Demonstration of an aberrant mast-cell population with clonal markers in a subset of patients with "idiopathic" anaphylaxis. Blood 2007; 110: 2331–2333.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Bonadonna P, Perbellini O, Passalacqua G, Caruso B, Colarossi S, Dal Fior D et al. Clonal mast cell disorders in patients with systemic reactions to Hymenoptera stings and increased serum tryptase levels. J Allergy Clin Immunol 2009; 123: 680–686.

    Article  CAS  PubMed  Google Scholar 

  10. Alvarez-Twose I, Gonzalez de Olano D, Sanchez-Munoz L, Matito A, Esteban-Lopez MI, Vega A et al. Clinical, biological, and molecular characteristics of clonal mast cell disorders presenting with systemic mast cell activation symptoms. J Allergy Clin Immunol 2010; 125: e2.

    Article  Google Scholar 

  11. Akin C, Valent P, Metcalfe DD . Mast cell activation syndrome: proposed diagnostic criteria. J Allergy Clin Immunol 2010; 126: e4.

    Article  Google Scholar 

  12. Pardanani A . How I treat patients with indolent and smoldering mastocytosis (rare conditions but difficult to manage). Blood 2013; 121: 3085–3094.

    Article  CAS  PubMed  Google Scholar 

  13. Valent P, Akin C, Arock M, Brockow K, Butterfield JH, Carter MC et al. Definitions, criteria and global classification of mast cell disorders with special reference to mast cell activation syndromes: a consensus proposal. Int Arch Allergy Immunol 2012; 157: 215–225.

    Article  PubMed  Google Scholar 

  14. Tefferi A, Levine RL, Lim KH, Abdel-Wahab O, Lasho TL, Patel J et al. Frequent TET2 mutations in systemic mastocytosis: clinical, KITD816V and FIP1L1-PDGFRA correlates. Leukemia 2009; 23: 900–904.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Sanchez-Munoz L, Alvarez-Twose I, Garcia-Montero AC, Teodosio C, Jara-Acevedo M, Pedreira CE et al. Evaluation of the WHO criteria for the classification of patients with mastocytosis. Mod Pathol 2011; 24: 1157–1168.

    Article  PubMed  Google Scholar 

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Author notes

  1. A Pardanani and D Chen: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Hematology and Department of Medicine, Mayo Clinic, Rochester, MN, USA

    A Pardanani, R A Abdelrahman, D Zblewski & A Tefferi

  2. Division of Hematopathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA

    D Chen, K K Reichard, A J Wood, R F McClure & C A Hanson

  3. Division of Allergy, Department of Medicine, Mayo Clinic, Rochester, MN, USA

    J H Butterfield

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  1. A Pardanani
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Correspondence to A Pardanani.

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The authors declare no conflict of interest.

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Author contributions

AP, DC and AT designed the study, contributed patients, analyzed the data and wrote the paper. RAA abstracted data from the clinical records. DZ, JHB, KKR and RFM contributed patients to the study. DC and CAH reviewed all the bone marrow slides. KKR, RFM, and AJW provided additional review of bone marrow slides. RFM performed molecular analysis for KITD816V mutation.

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Pardanani, A., Chen, D., Abdelrahman, R. et al. Clonal mast cell disease not meeting WHO criteria for diagnosis of mastocytosis: clinicopathologic features and comparison with indolent mastocytosis. Leukemia 27, 2091–2094 (2013). https://doi.org/10.1038/leu.2013.227

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