Table 1. Major characteristics of the various categories of mastocytosis, and distribution of KIT mutations along these categories.

Categories of disease and their major characteristics	Relative frequency	Prognosis	Type and frequency of KIT mutations/presence of additional genetic lesions
Pediatric mastocytosis Disease frequently limited to the skin Resolves at adolescence in most cases	++	Usually very good	25% KIT WT{Bodemer, 2010 #96} 35% KIT D816V (D816I or D816Y){Bodemer, 2010 #96} 40% ECD KIT mutations{Bodemer, 2010 #96}
Indolent Systemic Mastocytosis (ISM) Mostly chronic and stable evolution over decades Symptoms are mostly related to mediators released by MCs Progression into a more aggressive disease is very rare	++	Very good to good	> 80 % KIT D816V{Bibi, 2014 #5} A few patients are KIT WT or may present non codon 816 KIT mutations{Garcia-Montero, 2006 #1665;Orfao, 2007 #129;Bibi, 2014 #5} The presence of the KIT D816V mutation in non-MC lineages appears to be a predictor for risk of progression{Escribano, 2009 #419;Teodosio, 2012 #66}
Smoldering Systemic Mastocytosis Stable evolution over years or decades Presence of a high MC burden in the BM Presence of borderline begin symptoms (B-findings)* Some patients may progress to more aggressive disease	+	Relatively good	> 80 % KIT D816V{Arock, 2010 #80} Additional genetic non-KIT lesions may be acquired during the evolution if the patient progresses to a more aggressive disease{Bibi, 2014 #5}
Aggressive Systemic Mastocytosis (ASM) Presence of clinical signs related to organ dysfunction linked to MC infiltration (C-findings)** Can transform into MCL	+/−	Poor	> 70% KIT D816V{Arock, 2010 #80} A few patients may present non codon 816 KIT mutations{Arock, 2010 #80} Additional genetic non-KIT lesions can be found {Bibi, 2014 #5}
Systemic mastocytosis with an Associated Hematological non MC disease (SM-AHNMD) SM part can be indolent or aggressive AHNMD component is mostly a myeloid neoplasm	+	Depending on the type of SM and on the prognosis of the AHNMD	> 80% KIT D816V{Arock, 2010 #80} The AHNMD may present its own recurrent genetic lesion (BCR/ABL, JAK2 V617F,…){Hussein, 2011 #239},{Wang, 2013 #39} Additional genetic non-KIT lesions can be found (see{Bibi, 2014 #5})
Mast Cell Leukemia (MCL) >20% of atypical MCs in the BM smears Presence of C-findings	+/−	Very poor	KIT D816V mutant is less frequent than in ISM{Georgin-Lavialle, 2013 #44} KIT mutations in ECD or JMD or no KIT mutations are frequent{Joris, 2012 #1464;Georgin-Lavialle, 2012 #63;Georgin-Lavialle, 2013 #44}
Mast Cell Sarcoma (MCS) Presence of very atypical malignant MCs in a solitary mass Progress to MCL in a short time period	+/−−	Very poor	No KIT D816V mutation described to date Other non codon 816 KIT mutations can be found{Ryan, 2013 #45;Kim, 2013 #42;Georgin-Lavialle, 2013 #301}
Familial mastocytosis Reported in more than 50 families since the mid-1880s. Mostly indolent pediatric CM	+/−	Usually very good	Rare somatic KIT D816V mutations described in a few adult-onset SM.{Bodemer, 2010 #96;Broesby-Olsen, 2012 #56;Zanotti, 2013 #43} Most cases without KIT mutations or with uncommon germline mutations (i.e., K509I, A533D, R634W, N822I, M835K, S849I or deletion of amino-acids 419 or 559-560).{Zhang, 2006 #161;Wasag, 2011 #71;Hoffmann, 2008 #497;Wohrl, 2013 #1465;Pollard, 2014 #1674}

^*B-findings: hypercellular BM, dysplasia, organomegaly without organ failure, and high serum tryptase levels.

^**C-findings: organ dysfunction, such as cytopenia (ANC<1×10⁹/L, Hb<10 g/dL, or platelets<100×10⁹/l), hepatomegaly with impaired liver function, palpable splenomegaly with signs of hypersplenism, malabsorption with significant hypoalbuminemia, significant weight loss >10% over the last 6months and/or large osteolyses.

AHNMD: Associated clonal hematologic non-mast cell lineage diseases; ASM: aggressive systemic mastocytosis; BM: bone marrow; CM: cutaneous mastocytosis; ECD: extracellular domain; ISM: indolent systemic mastocytosis; MCL: mast cell leukemia; MCS: mast cell sarcoma; MCs: mast cells; WT: wild type.

++: frequent; +: relatively frequent; +/−: rare; +/−− extremely rare.