Overview
Mastocytosis, which exists in several forms, was the first recognised mast cell activation disorder (MCAD) and can affect both adults and children.1 While symptoms and some aspects of pathology differ depending on the type, mastocytosis is broadly caused by the abnormal growth (excessive proliferation) and buildup of mast cells in the skin or internal organs, such as the liver, spleen and bone marrow.2,3,4 This abnormal growth is called a neoplasm, a term that means an uncontrolled increase in cells.5,6
Although sometimes considered a blood cancer, most mastocytosis is indolent, meaning it is slow to progress or often remains stable over time, and is managed very differently from common cancers. Many children with cutaneous mastocytosis experience resolution or meaningful improvement by adolescence, without an impact on life expectancy.
While advanced forms have different prognoses and may affect life expectancy, they are uncommon, accounting for approximately 5 per cent of systemic mastocytosis cases, most adults with mastocytosis have a life expectancy close to that of the general population.7,8,9
Variants of mastocytosis
The World Health Organization (WHO) classifies mastocytosis into three categories:10,11,12
SM is further divided into variants based on severity and specific organ involvement.12,13
Further information on these categories is outlined below:
Cutaneous Mastocytosis (CM)
CM affects the skin without systemic organ involvement.14 CM affects the skin in the absence of systemic organ involvement. It is most commonly seen in children and typically resolves by adolescence, although rare adult presentations do occur.15 In adults, maculopapular cutaneous mastocytosis is the predominant form, while other variants are uncommon.15
The variants of CM are:
Cutaneous Local Mastocytoma
Can present as a solitary lesion (solitary mastocytoma) or multiple lesions (multiple mastocytomas). Characterised by one or more hyperpigmented macules, plaques or nodules resulting from an abnormal accumulation of mast cells in the skin. It is typically benign, often appearing in infancy or early childhood.16
Maculopapular Cutaneous Mastocytosis (MPCM)
Formerly known as urticaria pigmentosa, is the most common form of cutaneous mastocytosis.17 It is characterised by brownish spots (known as macules or papules) on the skin due to an abnormal accumulation of mast cells.17 This subtype now covers diagnoses of telangiectasia macularis eruptiva perstans (TMEP).18,19
Diffuse Cutaneous Mastocytosis (DCM)
Involves widespread redness or inflammation of the skin, varying degrees of blistering, and a thickened texture that often looks like “orange peel”, also known as peau d’orange, a recognised medical term for this appearance. It results from a significant build-up of mast cells in the skin. Two sub-variants of DCM exist: one which involves extensive blistering (bullous DCM), and one which presents with yellow-orange raised skin patches, similar to xanthogranuloma-type lesions and only limited blistering (pseudoxanthomatous DCM).20
Non-Advanced Systemic Mastocytosis (Non-AdvSM)
Non-advanced forms of systemic mastocytosis involve mast cell infiltration in the bone marrow and/or other organs but do not cause significant organ dysfunction.2 Subtypes include:
Indolent Systemic Mastocytosis (ISM)
The most common form of systemic mastocytosis, typically involving multiple organ systems, such as the bone marrow, skin and gastrointestinal tract.21 It is generally characterised by a low bone marrow mast cell burden, typical life expectancy and has a low risk of progression to advanced forms of mastocytosis.22,23
Bone Marrow Mastocytosis (BMM)
A rare subvariant of indolent systemic mastocytosis (ISM) that fulfills the criteria of SM and shows the involvement of the bone marrow but no skin lesions, a low burden of neoplastic mast cells and often normal or near-normal serum tryptase levels.24 BMM has a low risk of progression to advanced systemic mastocytosis. While studies focusing solely on BMM are limited, broader research on ISM supports the consideration of a normal life expectancy.22,23
Smouldering Systemic Mastocytosis (SSM)
Characterised by a higher mast cell burden than ISM and an increased risk of progression to forms of Advanced Systemic Mastocytosis (AdvSM).25 While SSM carries a higher risk of progression to AdvSM than ISM, if cases do not progress, life expectancy is generally favourable.22,23
Advanced Systemic Mastocytosis (AdvSM)
Advanced forms of systemic mastocytosis involve significant organ dysfunction and have a higher risk of progression.26 These include:
Aggressive Systemic Mastocytosis (ASM)
Marked by extensive mast cell infiltration across multiple tissues, significant organ dysfunction beyond the skin (extracutaneous) and the need for intensive treatment, but without evidence of mast cell leukemia or another haematologic neoplasm.27
Systemic Mastocytosis with Associated Haematological Neoplasm (SM-AHN)
Occurs alongside another blood disorder.28 The prognosis depends on disease severity.29,30 The prognosis for SM-AHN depends on both the severity of the associated blood disorder and whether the mastocytosis is milder (indolent) or aggressive.29,30
Mast Cell Leukemia (MCL)
The rarest and most severe form of mastocytosis, characterised by high mast cell counts in the blood and bone marrow, often with a poor prognosis and classified as acute or chronic depending on if mast cell infiltration is present in organ dysfunction. MCL subtypes are further defined based on whether mast cells circulate in the bloodstream (leukaemic) or remain confined to the bone marrow and are not found in the blood (aleukaemic).31,79
Further categorisation of mastocytosis
Combined MCAD
In some patients, mastocytosis occurs with other conditions that increase mast cell activation, most often allergies or hypersensitivity disorders, such as Hymenoptera venom allergy (HVA), an allergy to bee or wasp venom.
These cases, sometimes referred to as combined MCAD in recent medical literature, involve a clonal MCAD such as mastocytosis coexisting with a secondary cause of mast cell activation (MCA).4 For example, patients with both mastocytosis and HVA have a higher risk of severe anaphylaxis and may need additional specialised treatment. Identifying and managing combined MCAD improves patient safety by addressing both the clonal disorder and secondary factors that may worsen MCA.8,32,33
Hereditary alpha tryptasemia (HαT)-associated MCAD
HαT is an inherited trait caused by extra copies of the TPSAB1 gene, leading to increased α-tryptase production and higher baseline tryptase levels in the blood. Many individuals with HαT have no symptoms (asymptomatic) and are unaware that they carry the trait.
Although some studies show HαT is more common in patients with systemic mastocytosis, other studies conflict with these findings, and consistent differences in symptoms, severity, or anaphylaxis risk between those with and without HαT have not been widely observed. Therefore, the clinical significance of HαT may differ among individuals.32,33,34,35,36
Patients with mastocytosis and HαT may be described as having HαT-associated MCAD. This is a proposed descriptive classification that does not replace a mastocytosis diagnosis, but may help specialists interpret basal serum tryptase and guide monitoring and treatment decisions for some patients.
Read more information on HαT testing. or management strategies.
Disclaimer
Last updated: 27 August 2026
Please note that this information is provided for general educational purposes only and does not replace medical advice, nor should it be used in place of consultation with a qualified health professional. While care has been taken to reflect current information based on reputable scientific source material at the time of writing, and TAMS will continue to update information periodically, omissions or inconsistencies may occur as scientific knowledge evolves.
