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

Pardanani, Animesh; Chen, Dong; Abdelrahman, Ramy A.; Reichard, Kaaren K.; Zblewski, Darci; Wood, Adam; McClure, Rebecca F.; Butterfield, Joseph H.; Hanson, Curtis A.; Tefferi, Ayalew

doi:10.1038/leu.2013.227

Cited by 27 publications

(15 citation statements)

References 14 publications

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“…Another potential contributor in this regard is the proportion of patients enrolled via allergy clinics where there is a higher index of suspicion for underlying SM. The aforementioned observations are also consistent with detection of low-burden clonal mast cells in symptomatic patients in specific clinical contexts (e.g., "idiopathic anaphylaxis") [15,16], where some patients are found to satisfy only 1 or 2 minor SM diagnostic criteria, with this entity being termed "monoclonal mast cell activation syndrome" or "subdiagnostic SM" [17,18]. The highest proportion of patients without mast cell aggregates (60%) in the study by Pieri et al belonged to the ISM subgroup without skin involvement (ISM-).…”

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confidence: 73%

Systemic mastocytosis: evolving lessons from large patient registry datasets

Pardanani

2016

American J Hematol

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Systemic mastocytosis (SM) is a clinically heterogeneous and relatively infrequent chronic myeloproliferative neoplasm [1]. In the Danish nationwide cohort study, the incidence and prevalence rates were 0.89 per 100,000 inhabitants per year and 9.59 per 100,000 inhabitants, respectively, for the period between 1997 and 2010 [2]. Similarly, in the Groningen region, The Netherlands, prevalence of indolent SM (ISM) was estimated at 13 per 100,000 inhabitants, albeit with a roughly five-to sixfold increase in cases from 1998 to 2010, the latter likely relating to a recent increased awareness of SM combined with advances in diagnostic testing and expertise in specialized centers for this disease [3]. The increasing number of cases diagnosed with SM at least partly reflects the development of standardized diagnostic, classification and treatment-response criteria by international collaborative organizations such as the World Health Organization (WHO) and European Competence Network on Mastocytosis (ECNM) [4][5][6]. Prior to these larger-scale projects, most SM related data emerged from single center or single country registry studies, which despite their inherent limitations helped establish the early foundational principles of SM evaluation and treatment [7][8][9][10][11][12][13]. The article by Pieri et al. in the current issue of the American Journal of Hematology represents a large study of SM patients from 10 Italian centers with dedicated mastocytosis programs participating in the Italian Registry of Mastocytosis [14].There are two aspects of special note related to the study by Pieri et al. First, it represents the largest study of SM patients diagnosed by WHO 2008 criteria ever published [5]. Second, patients in this study were diagnosed relatively recently, with 75% being diagnosed between the years 2009 and 2014. The latter aspect ensured the use of relatively state-of-the-art diagnostic testing in the current study, which is not the case in older studies wherein a significant subset of patients was diagnosed prior to the development of such tests. A downside, however, of the recency bias in the article by Pieri et al. is the short patient follow up which limits the conclusions one might draw regarding clinical outcomes in SM patients.There are several additional observations that flow from the above two points: first, while the study by Pieri et al. includes 460 patients, as compared with the erstwhile largest study of 342 patients from the Mayo Clinic group [8], it is unclear whether either study is generalizable to the SM patient at large. While both were multidisciplinary studies, the former is predominantly a study of ISM patients (89% of all cases), likely reflecting a bias toward patient enrollment via dermatology and/or allergy clinics (73% had allergy/anaphylaxis symptoms). In contrast, the study by Lim et al. exhibited a hematology bias with 46% and 40% presenting with ISM and SM with associated clonal non-mast cell lineage disease (SM-AHNMD), respectively. This has to be taken into account when ex...

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confidence: 73%

Systemic mastocytosis: evolving lessons from large patient registry datasets

Pardanani

2016

American J Hematol

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“…As the primary feature of MCAD is inappropriate MCA (39,52,53), treatment invariably involves trigger identification/avoidance plus control of MC mediator production/action (Supplementary Figure 1).…”

Section: Treatmentmentioning

confidence: 99%

Often seen, rarely recognized: mast cell activation disease – a guide to diagnosis and therapeutic options

et al. 2016

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Mast cell (MC) disease has long been thought to be just the rare disease of mastocytosis (in various forms, principally cutaneous and systemic), with aberrant MC mediator release at symptomatic levels due to neoplastic MC proliferation. Recent discoveries now show a new view is in order, with mastocytosis capping a metaphorical iceberg now called "MC activation disease" (MCAD, i.e. disease principally manifesting inappropriate MC activation), with the bulk of the iceberg being the recently recognized "MC activation syndrome" (MCAS), featuring inappropriate MC activation to symptomatic levels with little to no inappropriate MC proliferation. Given increasing appreciation of a great menagerie of mutations in MC regulatory elements in mastocytosis and MCAS, the great heterogeneity of MCAD's clinical presentation is unsurprising. Most MCAD patients present with decades of chronic multisystem polymorbidity generally of an inflammatory ± allergic theme. Preliminary epidemiologic investigation suggests MCAD, while often misrecognized, may be substantially prevalent, making it increasingly important that practitioners of all stripes learn how to recognize its more common forms such as MCAS. We review the diagnostically challenging presentation of MCAD (with an emphasis on MCAS) and current thoughts regarding its biology, epidemiology, natural history, diagnostic evaluation, and treatment.

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“…A total of 10 patients with the provisional diagnosis of "mastocytosis in the skin" (MIS), in which full assessment of SM criteria has not been performed [5], were also included in the study. A single patient diagnosed with monoclonal mast cell activation syndrome (MMAS) based on proposed criteria was also included in the study, because this entity has been proposed to represent sub-diagnostic SM [15,16]. All patients were >18 years of age.…”

Section: Methodsmentioning

confidence: 99%

Sensitive KIT D816V mutation analysis of blood as a diagnostic test in mastocytosis

et al. 2014

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The recent progress in sensitive KIT D816V mutation analysis suggests that mutation analysis of peripheral blood (PB) represents a promising diagnostic test in mastocytosis. However, there is a need for systematic assessment of the analytical sensitivity and specificity of the approach in order to establish its value in clinical use. We therefore evaluated sensitive KIT D816V mutation analysis of PB as a diagnostic test in an entire case-series of adults with mastocytosis. We demonstrate for the first time that by using a sufficiently sensitive KIT D816V mutation analysis, it is possible to detect the mutation in PB in nearly all adult mastocytosis patients. The mutation was detected in PB in 78 of 83 systemic mastocytosis (94%) and 3 of 4 cutaneous mastocytosis patients (75%). The test was 100% specific as determined by analysis of clinically relevant control patients who all tested negative. Mutation analysis of PB was significantly more sensitive than serum tryptase >20 ng/mL. Of 27 patients with low tryptase, 26 tested mutation positive (96%). The test is furthermore readily available and we consider the results to serve as a foundation of experimental evidence to support the inclusion of the test in diagnostic algorithms and clinical practice in mastocytosis.

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

Cited by 27 publications

References 14 publications

Systemic mastocytosis: evolving lessons from large patient registry datasets

Systemic mastocytosis: evolving lessons from large patient registry datasets

Often seen, rarely recognized: mast cell activation disease – a guide to diagnosis and therapeutic options

Sensitive KIT D816V mutation analysis of blood as a diagnostic test in mastocytosis

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