• 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 haematologic neoplasms. Based on the current guidelines and the current state of research, different diagnostic recommendations emerge. We have summarized the most important information about classification and diagnostic methods at the MLL. In addition, we have compiled further literature and links on prognosis and therapy in mastocytosis, so that you can inform yourself in more detail.

Mastocytosis: Classification and staging

According to WHO, mastocytosis can be classified into three major categories (Tab. 1). Cutaneous and systemic mastocytosis can each be further divided into subgroups. While in cutaneous mastocytosis the mast cells accumulate in the skin, the systemic variant involves at least one extracutaneous organ, almost always infiltrating the bone marrow. The very rare mast cell sarcoma is a solid tumor consisting of atypical malignant mast cells.

Tab. 1: WHO classification of mastocytosis (Swerdlow et al. 2017, Khoury et al. 2022)

Cutaneous mastocytosis

  • Urticaria pigmentosa/maculopapular cutaneous mastocytosis
  • Diffuse cutaneous mastocytosis
  • Cutaneous mastocytoma

Systemic mastocytosis

  • Indolent systemic mastocytosis (ISM)
  • Bone marrow mastocytosis (BMM)
  • Smoldering systemic mastocytosis (SSM)
  • Systemic mastocytosis with an associated hematologic neoplasm (SM-AHN)*
  • Aggressive systemic mastocytosis (ASM)
  • Mast cell leukemia (MZL)

Mast cell sarkoma

 

* In systemic mastocytosis associated with an associated hematologic neoplasm, all known lymphoid and myeloid neoplasms can occur. However, myeloid neoplasms, especially CMML, represent the majority.


Tab. 2: Diagnostic criteria according to WHO 2017 (Swerdlow et al. 2017, Valent et al. 2021)

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. Detection of atypical spindle-shaped mast cells (≥25% of all mast cells): histologically in BM or other extracutaneous organs or cytologically in BM smear

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

3. Mast cells in bone marrow, peripheral blood, or another extracutaneous organ express CD2, CD25, or CD30*

4. Serum tryptase >20 ng/mL (in the case of an unrelated myeloid neoplasm, an elevated tryptase does not count as an SM criterion. In the case of a known hereditary HαT, correction based on the number of additional α-tryptase gene copies is recommended*)

*Update of the diagnostic criteria according to Valent et al. 2021

Fig. 1: Diagnostic criteria for subtypes of systemic mastocytosis (Swerdlow et al. 2017, Khoury et al. 2022)

Mastocytosis: Diagnostic methods and their relevance

Mastocytosis: Prognosis and Therapy

Cutaneous mastocytosis usually has a favorable course. 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 associated subgroup. ISM usually has a favorable course and patients have a normal life expectancy in most cases; however, 5-10% of ISM show progression to advanced systemic mastocytosis and an associated less favorable prognosis. There are data suggesting that in ISM, in addition to the KIT mutation, additional mutations in the ASXL1, RUNX1, and/or DNMT3A genes (VAFs ≥30%) are associated with shorter progression-free and overall survival (Muñoz-González et al. 2019).

ASM, MZL, and mast cell sarcoma show an unfavorable prognosis (Lim et al. 2009, Monnier et al. 2016). ASM, MZL, and SM-ANH are also grouped together as advanced systemic mastocytosis because of their generally unfavorable prognosis. For SM-AHN, the associated haematologic neoplasm and the associated cytogenetic and/or molecular genetic alterations should also be considered to assess prognosis (Wang et al. 2013, Naumann et al. 2018). For cytogenetic alterations, classification into risk groups is possible depending on the associated haematologic neoplasm (Naumann et al. 2018).

Several prognostic scores have been published in recent years for both ISM and advanced SM individually and for SM as a whole: The International Prognostic Scoring System for Mastocytosis (IPSM) is based on simple clinical variables such as age, blood count changes, serum tryptase, and alkaline phosphatase (Sperr et al. 2019). The Mutation-Adjusted Risk Score for Advanced Systemic Mastocytosis (MARS) includes mutations in SRSF2, ASXL1, and RUNX1 in addition to age and blood count changes (Jawhar et al. 2019). The Global Prognostic Score (GPS) for SM similarly integrates additional mutations in the SRSF2, ASXL1, RUNX1, and DNMT3A genes with blood count alterations and serum biomarkers (Muñoz-González et al. 2021).

The therapeutic options strongly depend on the progress of the disease and comorbidities and should be considered individually. An overview of therapy algorithms is among others given in (Pardanani 2021) and in the Onkopedia guideline systemic mastocytosis 2020.

Status: July 2022

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