Mastocytosis: 2016 updated WHO classification and novel emerging treatment concepts

Abstract

Over the past few years, substantial advances have been made in understanding the pathogenesis, evolution, and complexity of mast cell neoplasms. New diagnostic and prognostic parameters and novel therapeutic targets with demonstrable clinical impact have been identified. Several of these new markers, molecular targets, and therapeutic approaches have been validated and translated into clinical practice. At the same time, the classification of mastocytosis and related diagnostic criteria have been refined and updated by the consensus group and the World Health Organization (WHO). As a result, more specific therapies tailored toward prognostic subgroups of patients have been developed. Emerging treatment concepts use drugs directed against KIT and other relevant targets in neoplastic mast cells and will hopefully receive recognition by health authorities in the near future. This article provides an overview of recent developments in the field, with emphasis on the updated WHO classification, refined criteria, additional prognostic parameters, and novel therapeutic approaches. Based on these emerging concepts, the prognosis, quality of life, and survival of patients with advanced mastocytosis are expected to improve in the coming years.

Figure 1.

Markers and targets expressed on neoplastic stem cells and mast cells in patients with SM. Neoplastic stem cells propagate the malignancy through their self-renewal capacity and ability to undergo asymmetrical cell division, resulting in daughter cells that are committed to differentiate into neoplastic mast cells (arrows). In common with normal stem cells, neoplastic stem cells in SM display CD34 and KIT as well as CD133. In addition, these cells usually express the cell-surface targets CD33, CD44, and CD52; however, they do not express CD2, CD25, or CD30. Some of the markers used to define stem cells or mast cells, such as KIT, also serve as molecular targets of therapy. Neoplastic mast cells themselves usually display CD2, CD25, and CD30 in an aberrant manner together with KIT, but lack CD34. In addition, neoplastic mast cells in SM express a number of potential therapeutic cell-surface targets, including CD30, CD33, CD52, or CD123.