Mastocytosis – A Disease of the Hematopoietic Stem Cell: Problematic Criteria

Abstract

In their review article on systemic mastocytoses, Horny et al. consider the 2001 diagnostic criteria of the World Health Organization (WHO) as the gold standard for diagnosing systemic mastocytosis. In view of today’s insights into mast cell pathology, this significance is no longer justified. The occurrence of the phenomena listed as the primary criterion and two secondary criteria seems to be linked to the simultaneous presence of a point mutation in codon 816 of the amino acid sequence of the tyrosine kinase Kit. Consequently, these criteria are not suitable for determining systemic mastocytosis as a result of other mutations in Kit and in other kinases. Additionally, bone marrow examination may yield negative results even in patients whose disease matches the remaining WHO criteria (1). Besides, the speckled distribution of mast cells in bone marrow can influence the results of the investigation in such a crucial manner that bilateral sampling of several specimens may be necessary to be able to draw a definite conclusion (2), which may raise problems in terms of clinical practice and professional ethics. From an internist’s perspective, a diagnostic approach seems more appropriate in which the pathologically altered mast cell with its pathologically increased mediator release is the main criterion for a diagnosis of systemic mastocytosis. The symptoms of the mast cell mediator syndrome can be reliably detected in a standardized manner with an internationally validated questionnaire (for example, those from the Association Francaise pour les Initiatives de Recherche sur le Mastocyte et les Mastocytoses) (3). When the presence of disorders is excluded in which normal mast cells may be activated, the occurrence of pathological excess production and release of mast cell mediators can only be a manifestation of pathological, uncontrolled, hyperactive mast cells. For this reason, the disorder is appropriately termed as the systemic mast cell hyperactivity syndrome and, in terms of terminology, is a systemic mastocytosis. If the pathologically increased mast cell activity is regarded as main diagnostic criterion, systematic mastocytoses are by no means rare disorders but very likely to be underdiagnosed.