Systemic mast cell disease (SMCD)

2000-06-01   Lidia Larizza  , Lidia Larizza  

1.Medical Genetics, San Paolo School of Medicine, University of Milan Via A. di Rudini, 8, 20142 Milano, Italy

Clinics and Pathology

Phenotype stem cell origin

mast cell

Etiology

involvement of KIT/SCF has been demonstrated in a few cases, but the diversity of the clinical pattern has not yet been elucidated;increased soluble SCF has been reported in the skin of patient with indolent mastocytosis; c-KIT mutations have been identified in patients with all forms of sporadic mastocytosis.

Clinics

  • indolent mastocytosis involves the skin, bone marrow and gastrointestinal tract; clinical features range from a single cutaneous nodule to multiple pigmented macules resulting from increased epidermal melanin and papules (urticaria pigmentosa) or diffuse cutaneous involvement; bullae, vescicles and abnormal telangiectasia may be seen; gastrointestinal involvement leads to symptoms such as nausea, vomiting and abdominal pain.
  • in mastocytosis with an associated hematological disorder the urticaria pigmentosa symptoms are accompanied by a variety of haematological findings due to mast cell infiltrates to bone marrow, spleen, liver and lymph nodes.
  • mast cell leukemia is characterized by proliferation and infiltration of immature mast cells in bone marrow, peripheral blood and various extramedullary tissues.
  • aggressive mastocytosis is characterized by aggressive involvement of several haematopoietic organs

    • Pathology

    accumulation of mast cells in various organs and release of mast cell mediators which are responsible for the different clinical signs

    Prognosis

    highly dependent on the form being severe, often fatal, in all types with the exception of the indolent form

    Definition

    {"GENE_NAME":"<CC: TXT: KIT ID: 127 > (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog)","ID":"127","LOCATION":"4q12","DNA_RNA_DESCRIPTION":"21 exons","PROTEIN_DESCRIPTION":"transmembrane SCF\/MGF receptor with tyrosine kinase activity; binding of ligand (SCF) induces receptor dimerization, autophosphorylation and signal transduction via molecules containing SH2- domains","SOMATIC_MUTATIONS":"(<A HREF=\"..\/Genes\/Images\/kit1.gif\">see diagram<\/A>) Gly560Val, Asp816Val, Asp816Tyr, Asp820Gly <LI> Asp816Val in peripheral blood lymphocytes (mastocytosis with an associated hematological disorder: AHD) <LI> Asp816Val in skin and spleen mast cells from patients with aggressive mastocytosis <LI> Asp816Tyr in blasts from a patient with AML-M2 with mast cell involvement <LI> Asp820 Gly in blasts from a patient with aggressive SMCD <LI> Asp816Val and Gly560Val have been found in a human mast cell leukemia cell line (HMC1)","NOTE All":"mutations with the exception of Gly560Val cluster to c-kit exon 17. Direct or indirect evidence has been provided that mutations affecting codon 816 promote ligand-independent autophosphorylation of the mutant receptor","GENE_NAME1":"<CC: TXT: KITLG ID: 142 > (KIT ligand)","ID2":"142","LOCATION3":"12q21.32","DNA_RNA_DESCRIPTION4":"9 exons","PROTEIN_DESCRIPTION5":"<LI> soluble SCF : 248 aminoacids containing a proteolytic cleavage site encoded by exon 6 sequences, which is processed, giving rise to an active form (soluble) of 165 aminoacids; membrane-bound SCF : 220 aminoacids, results from alternative splicing of exon 6 <BR><LI> Note: increased soluble SCF has been detected in the skin of patients with indolent mastocytosis; SCF-specific transcripts are detected by in situ RT-PCR in mast cell infiltrates in papulae from mastocytosis patients"}

    Article Bibliography

    Pubmed IDLast YearTitleAuthors
    97147031998In vivo differentiation of mast cells from acute myeloid leukemia blasts carrying a novel activating ligand-independent C-kit mutation.Beghini A et al
    76918851993Identification of mutations in the coding sequence of the proto-oncogene c-kit in a human mast cell leukemia cell line causing ligand-independent activation of c-kit product.Furitsu T et al
    76822881993Altered metabolism of mast-cell growth factor (c-kit ligand) in cutaneous mastocytosis.Longley BJ Jr et al
    85897241996Somatic c-KIT activating mutation in urticaria pigmentosa and aggressive mastocytosis: establishment of clonality in a human mast cell neoplasm.Longley BJ et al
    74798401995Identification of a point mutation in the catalytic domain of the protooncogene c-kit in peripheral blood mononuclear cells of patients who have mastocytosis with an associated hematologic disorder.Nagata H et al
    90290281997A new c-kit mutation in a case of aggressive mast cell disease.Pignon JM et al
    158789762005Bcl10 can promote survival of antigen-stimulated B lymphocytes.Tian MT et al

    Summary

    Note

    mastocytosis is a heterogeneous clinical entity which is classified into four categories:
    1- indolent mastocytosis (the most common form),
    2- mastocytosis with an associated hematologic disorder,
    3- mast cell leukemia and
    4- aggressive mastocytosis

    Citation

    Lidia Larizza ; Lidia Larizza

    Systemic mast cell disease (SMCD)

    Atlas Genet Cytogenet Oncol Haematol. 2000-06-01

    Online version: http://atlasgeneticsoncology.org/haematological/2064/systemic-mast-cell-disease-(smcd)

    Historical Card

    1998-09-01 Systemic mast cell disease (SMCD) by  Alessandro Beghini,Lidia Larizza 

    Medical Genetics, San Paolo School of Medicine, University of Milan Via A. di Rudini, 8, 20142 Milano, Italy