Mastocytosis and Mast Cells

Hans‐Peter Horny, Institute of Pathology, Ansbach, Germany

Published online: March 2010

DOI: 10.1002/9780470015902.a0002175.pub2

Mastocytosis is defined by abnormal accumulation of mast cells in various sites in the body. The clinical features of this chronic, multifaceted disorder originate from mast cell infiltration leading to systemic and local effects induced by numerous pharmacological mediators. Since 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 asthma, chronic diarrhoea, urticaria, syncope, peptic ulceration but also various haematological neoplasms. Diagnosis of mastocytosis can be confirmed only by the pathologist using a combined immunohistochemical and molecular approach. Recognition and subtyping of its rare, life-threatening high-grade disease variant (i.e. mast cell leukaemia) includes not only the investigation of tissue samples (usually bone marrow) but also the blood and bone marrow smears.

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 KITD816V in the c-kit proto-oncogene.
  • The presence of KITD816V not only explains pathophysiological disease characteristics but also enables targeting therapy using the recently developed tyrosine kinase inhibitors.
  • Although stated in the recent WHO classification book on haematopoietic neoplasms, mastocytosis should not be grouped among myeloproliferative neoplasms.
  • Mastocytosis should be considered as a separate group of disorders among haematological neoplasms.
  • Mastocytosis must be separated from a variety of reactive (i.e. mast cell hyperplasia) and neoplastic (i.e. basophilic leukaemia) states.

Keywords: mast cell; mast cell leukaemia; mastocytosis; SM-AHNMD; mystemic mastocytosis; tryptase

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, since 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. Since 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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Article Title: Mastocytosis and Mast Cells
 
How to Cite close
Horny, Hans‐Peter(Mar 2010) Mastocytosis and Mast Cells. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0002175.pub2]