Mastocytosis and Mast Cells

Abstract

Mastocytosis is defined by abnormal accumulations of mast cells in various tissue sites. The clinical features of this multifaceted disorder originate from mast cell infiltration leading to local and systemic effects induced by numerous pharmacological mediators. As mastocytosis is an unusual disorder and presents a multiplicity of symptoms, it is an often overlooked consideration in a differential diagnosis that includes not only chronic diarrhoea, urticaria, syncope and peptic ulceration but also various haematological neoplasms. Diagnosis of mastocytosis can be confirmed only by the pathologist who should use a combined immunohistochemical and molecular approach. Recognition and subtyping of its rare, life‐threatening high‐grade disease variants including aggressive systemic mastocytosis and mast cell leukaemia is based on the thorough investigation of tissue samples (usually bone marrow) but also smear preparations of blood and bone marrow.

Key Concepts

  • Mastocytosis is an unusual haematopoietic disorder derived from transformed bone marrow progenitor cells.
  • Clinically and histologically, mastocytosis presents an extremely broad spectrum of subvariants ranging from a benign, sometimes even regressive, cutaneous disease to the progressively fatal mast cell leukaemia.
  • Mastocytosis is a histological diagnosis established by the pathologist and cannot be confirmed by clinical findings alone.
  • Most patients with systemic mastocytosis carry the activating point mutation KIT‐D816V.
  • The presence of KIT‐D816V enables targeting therapy using some of the recently developed tyrosine kinase inhibitors.
  • Although stated in the recent WHO classification system on haematopoietic neoplasms, mastocytosis should not be grouped among myeloproliferative neoplasms.
  • Mastocytosis rather should be considered as a distinct group of disorders among haematological tumours/neoplasms.
  • Mastocytosis must be separated from a variety of reactive (mast cell activation syndrome) and neoplastic (basophilic and myelomastocytic leukaemias) disease states.
  • In more than 80% of patients with advanced systemic mastocytosis (aggressive and leukaemic SM and SM‐AHNMD) mutations other than KIT‐D816V are detected.

Keywords: mast cell; mast cell leukaemia; mastocytosis; SM‐AHNMD; systemic mastocytosis; tryptase; KIT‐D816V

Figure 1. Indolent systemic mastocytosis. A focal compact infiltrate of medium‐sized, hypogranulated, exclusively round mast cells dominates the picture. At first glance, the lesion resembles a ‘granuloma’. The definitive diagnosis of mastocytosis should be made after immunostaining with antibodies against tryptase, CD117 and CD25. Conventional staining alone does not allow a diagnosis of mastocytosis to be established, as prominent spindling of mast cells is missing. However, the notion of an aberrant immunophenotype with coexpression of CD25, CD117 and tryptase (not depicted) enables the diagnosis of systemic mastocytosis on the basis of morphology alone.
Figure 2. The picture shows a diffuse–compact infiltration of the distorted, extremely hypercellular bone marrow by atypical round mast cells. Normal blood cell precursors and fat cells are strongly reduced. Note the unusual proliferation of dilated sinus‐like structures. As the bone marrow smear contained abundant atypical mast cells (not depicted), the criteria for diagnosis of mast cell leukaemia were fulfilled.
Figure 3. Diagnosis of mastocytosis can only be achieved when appropriate immunostaining is applied. Neoplastic cells show strong cytoplasmic‐granular expression of tryptase, indicating that they belong to the mast cell lineage. Anti‐tryptase (ABC method).
Figure 4. Mast cells exhibit abnormal expression of CD25. This represents an atypical immunophenotype that is almost exclusively encountered in neoplastic states of mastocytosis. Anti‐CD25 (ABC method).
Figure 5. Intestinal mastocytosis. Colonic mucosa shows a band‐like subepithelial infiltrate of round CD117‐expressing mast cells, thus enabling diagnosis of mastocytosis. Immunostainings with antibodies against tryptase, CD117 and CD25 are crucial in every case to confirm a diagnosis of mastocytosis. Anti‐tryptase (ABC method).
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Further Reading

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Horny, Hans‐Peter, Sotlar, Karl, Reiter, Andreas, and Valent, Peter(Sep 2015) Mastocytosis and Mast Cells. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0002175.pub3]