SYSTEMIC MASTOCYTOSIS AND OTHER MAST CELL NEOPLASMS

The mast cell is derived from the multipotent haemopoietic stem cell, and mast cell neoplasms which involve the bone marrow or peripheral blood should therefore be classi®ed with the myeloid leukaemias and myeloproliferative disorders. Neoplasms of mast cells may be acute or chronic. Acute mast cell neoplasms, which can occur either de novo or as a transformation of a chronic mast cell disorder, are designated mast cell leukaemia. Chronic mast cell neoplasms may be localized or generalized. Cutaneous mastocytosis is the commonest localized mast cell neoplasm, although it should be noted that patients with cutaneous mastocytosis often have subclinical involvement of the bone marrow or other organs. It is possible that not all cutaneous mastocytosis is neoplastic in nature. In particular, childhood cases which often remit and never relapse may be reactive. However it is likely that the great majority, if not all, of adult cases with systemic mastocytosis represent a chronic mast cell neoplasm. The evidence for this is: (i) the association with myelodysplastic and myeloproliferative disorders, (ii) the evolution into acute leukaemia, and (iii) the frequent occurrence of clonal cytogenetic and molecular genetic abnormalities. It has been proposed that generalized mastocytosis should be classi®ed as `malignant mastocytosis' when there is no skin involvement and as `systemic mastocytosis' when skin involvement is present (Horny et al, 1989). The basis for these proposals is that skin in®ltration correlates with a better prognosis, probably because mast cells which are more immature or abnormal are less likely to in®ltrate the skin. However, some patients with cutaneous mastocytosis also have generalized disease and even those who appear to have only urticaria pigmentosa may nevertheless have abnormal clones of cells in the bone marrow (Swolin et al, 1987). Furthermore, worse prognosis in generalized mastocytosis correlates not only with the absence of skin disease but also with the presence of myeloproliferative or myelodysplastic features and with a form of the disease characterized by lymphadenopathy and eosinophilia. It therefore seems preferable not to categorize solely on the basis of the presence or absence of cutaneous involvement. In addition, `malignant mastocytosis' does not seem a very appropriate designation for a condition which is sometimes associated with a long survival. The classi®cation of Metcalfe (1991), which is shown in Table I, appears preferable. Since categories II and III do not differ prognostically (Mican et al, 1995) the classi®cation can be further simpli®ed as shown in Table II, cases being assigned to the `aggressive' category when there is an associated haematological disorder or when the clinicopathological features of lymphadenopathic mastocytosis with eosinophilia are present. This proposed simpli®ed classi®cation is similar to the latest recommendations of Horny et al (1998). In addition to mast cell neoplasms in which the mast cell is the only cell showing abnormal proliferation, there are other cases with evident multilineage involvement, suggesting that the mutation responsible may occur in a multipotent stem cell rather than in a committed mast cell precursor. A proportion of patients with systemic mastocytosis have myelodysplastic features and may meet the criteria for any of the FAB categories of myelodysplastic syndrome (MDS) (refractory anaemia, refractory anaemia with ring sideroblasts, refractory anaemia with excess of blasts, refractory anaemia with excess of blasts in transformation and chronic myelomonocytic leukaemia) (Travis et al, 1988b; Horny et al, 1990; Dash et al, 1991; Kluin-Nelemans et al, 1992; Zhang et al, 1994; Valent et al, 1994; Nagata et al, 1995). Other cases show proliferation of lineages other than mast cell (erythroid, granulocytic or megakaryocytic) and meet the criteria for various myeloproliferative disorders. Diagnoses made have included chronic myeloid leukaemia (Horny et al, 1990), polycythaemia rubra vera (Travis et al, 1998b), British Journal of Haematology, 1999, 106, 9±17