Mast-Cell Stabilization to Decrease Neurofibroma Growth

Abstract

Based on (1) the large numbers of mast cells present in neurofibromas, (2) the possibility that these mast cells contribute directly to neurofibroma growth, and (3) the ability of ketotifen therapy to stabilize (ie, block) mast-cell secretion, treatment with ketotifen was started in a patient with severe neurofibromatosis (NF) in August 1983. Subsequently, ten additional patients with one or more symptomatic neurofibromas were treated with comparable doses of ketotifen, 2 to 4 mg/d, orally administered for 30 to 43 months. This represents a total of 389 patient-months or 32.4 patient-years. All of these patients showed an unequivocal decrease in neurofibroma-associated pruritus and/or pain and tenderness; a consistent, but less-uniform, decrease in the rate of neurofibroma growth; and an unexpected improvement in overall sense of well-being, productivity, and general performance. It appears likely that mast-cell secretions do contribute to the growth and associated symptoms of neurofibromas, and that mast-cell blockers, such as ketotifen therapy, can retard this growth.

It takes two to tango: mast cell and Schwann cell interactions in neurofibromas

“…Thus, the development of medical treatment targeted to mast cell function may be a rational approach to decreasing neurofibroma formation in NF1. In a pilot study, Riccardi used ketotifen as a stabilizer of mast cells to demonstrate less small-vessel bleeding in surgical excisions of neurofibromas (23). He followed up this study with a controlled multiphase trial of ketotifen in 27 patients, assessing pain and itching associated with neurofibromas, and showed a response (24) that was reviewed as encouraging, but not definitely beneficial (25).…”

Characterization of Mast Cells Residing in Cutaneous Neurofibromas

“…Cutaneous mast cell suspension, which efficient ly responds to nonimmunologic secretory stimuli, was ob tained by enzymatic dispersion of neurofibromas. These mast cells may provide a new approach to the elucidation of the etiological roles of mast cells in the development of neurofibromas in neurofibromatosis [4] and an experimen tal source of human connective tissue mast cells for the in vestigation of mast cell-mediated cutaneous inflammation.…”

Solitary Sclerotic Neurofibroma of the Skin

“…It is known that large numbers of mast cells are present in neurofibroma. 8 We found some mast cells in close contact with tumor cells and abundant collagen synthesis. Sanguinetti et al 9 have ultrastructurally described the close contact between mast cells and tumor cells in neurofibroma.…”