• Method:
  • Anticoagulant:
  • Recommendation:
  • Method:
    Cytomorphology
  • Anticoagulant:
    EDTA
  • Recommendation:
    obligatory
  • Method:
    Immunophenotyping
  • Anticoagulant:
    EDTA or Heparin
  • Recommendation:
    obligatory
  • Method:
    Chromosome analysis
  • Anticoagulant:
    Heparin
  • Recommendation:
    obligatory
  • Method:
    FISH
  • Anticoagulant:
    EDTA or Heparin
  • Recommendation:
    facultative
  • Method:
    Molecular genetics
  • Anticoagulant:
    EDTA or Heparin
  • Recommendation:
    obligatory

Mastocytosis is characterized by an accumulation of neoplastic mast cells in one or more organs. It is a heterogeneous disease ranging from skin lesions to aggressive hematological neoplasms.

Classification of Mastocytosis

According to WHO 2017, mastocytosis can be classified into three major categories: Cutaneous mastocytosis, systemic mastocytosis and the rare mast cell sarcoma. Cutaneous and systemic mastocytosis can each be divided into further subgroups. While in cutaneous mastocytosis the mast cells accumulate in the skin, the systemic variant involves at least one extracutaneous organ, with the bone marrow almost always being infiltrated. A mast cell sarcoma is a solid tumor consisting of atypical, malignant mast cells.


WHO classification 2017 of mastocytosis (Swerdlow et al. 2017)

Cutaneous mastocytosis

  • Urticaria pigmentosa/maculopapular cutaneous mastocytosis

  • Diffuse cutaneous mastocytosis

  • Solitary mastocytoma of the skin

Systemic mastocytosis

  • Indolent systemic mastocytosis (ISM)

  • Smouldering systemic mastocytosis (SSM)

  • Systemic mastocytosis with an associated hematological neoplasm (SM-AHN)*

  • Aggressive systemic mastocytosis (ASM)

  • Mast cell leukemia (MZL)

Mast cell sarcoma

*Systemic mastocytosis associated with hematologic neoplasm can cause all known lymphoid and myeloid neoplasms. However, myeloid neoplasms, especially CMML, represent the majority.


Diagnostic criteria of mastocytosis according to WHO 2017:

Cutaneous Mastocytosis

Skin lesions demonstrating the typical findings of urticaria pigmentosa/maculopapular cutaneous mastocytosis, diffuse cutaneous mastocytosis or solitary mastocytoma, and typical histological infiltrates of mast cells in a multifocal or diffuse pattern in an adequate skin biopsy. In addition, features/criteria sufficient to establish the diagnosis of systemic mastocytosis must be absent.

Systemic mastocytosis

The diagnosis of systemic mastocytosis can be made when the major criterion and at least 1 minor criterion are present, or when >3 minor criteria are present..

Major criterion:

Multifocal dense infiltrates of mast cells (> 15 mast cells in aggregates) detected in sections of bone marrow and/or other extracutaneous organ(s)

Minor criteria:

1. In biopsy sections of bone marrow or other extracutaneous organs,

≥ 25% of the mast cells in the infiltrate are spindle-shaped or have atypical morphology or

> 25% of all mast cells in bone marrow aspirate smears are immature or atypical.

2. Detection of an activating point mutation at codon 816 of KIT in bone marrow, blood or another extracutaneous organ

3. Mast cells in bone marrow, blood or other extracutaneous organ express CD25, with or without CD2 in addition to normal mast cell markers

4. Serum total tryptase is persistently >20 ng/mL, unless there is an associated myeloid neoplasm, in which case this parameter is not valid.

Diagnostics of Mastocytosis

Prognosis of Mastocytosis

Cutaneous mastocytosis usually proceeds favourably. It occurs more frequently in childhood. In most cases, the skin lesions regress on their own by adulthood (Valent et al. 2017).

Systemic mastocytosis develops almost exclusively in adulthood. The prognosis depends on the subgroup of patients. ISM is generally favourable and patients in most cases have a normal life expectancy. However, 5-10% of ISM show a progress to advanced systemic mastocytosis and a less favourable prognosis. There are data suggesting that in ISM, in addition to the KIT mutation, additional mutations in the ASXL1, RUNX1 and/or DNMT3A (VAFs ≥30%) genes are associated with shorter progression-free and overall survival (Muñoz-Gonzalez et al. 2019).

The ASM, the MZL and the mast cell sarcoma each have an unfavourable prognosis (Lim et al. 2009, Monnier et al. 2016). In the case of SM-AHN, the associated haematological neoplasm and the associated cyto and/or molecular genetic changes should also be taken into account for the assessment of the prognosis (Naumann et al. 2018, Wang et al. 2013). Classification into risk groups is possible for cytogenetic changes depending on the associated haematological neoplasm. A study by Naumann et al. shows that an unfavourable karyotype is an independent factor with regard to overall survival. In patients with associated MDS a complex karyotype (≥ 3 aberrations) or monosomy 7 is assigned to the unfavourable risk group. However, the favorable risk group includes patients with a normal karyotype, del(5q), trisomy 8, del(1q) or del(12p). In associated AML, patients with a complex karyotype, monosomy 7 or del(5q) are included in the unfavorable risk group (Naumann et al. 2018).

≥90% of patients with systemic mastocytosis have a KIT D816V mutation. Additional mutations are found especially in ASM, SM-AHN and MZL. The most frequently additionally mutated genes are TET2, SRSF2, ASXL1, RUNX1 and CBL, whereby an unfavorable prognosis has been described especially for mutations in the genes SRSF2, ASXL1 and RUNX1 (Jawhar et al. 2016, Schwaab et al. 2013, Naumann et al. 2018). Recently the scoring system MARS (Mutation-Adjusted Risk Score for Advanced Systemic Mastocytosis) was published (Jawhar et al. 2019).

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