Plexiform neurofibromas in NF1

Abstract

Neurofibromatosis type 1 (NF1) is one of the most common neurogenetic diseases affecting adults and children. Neurofibromas are one of the most common of the protean manifestations of NF1. Plexiform neurofibromas, which will frequently cause cosmetic abnormalities, pain, and neurologic deficits, are composed of "neoplastic" Schwann cells accompanied by other participating cellular and noncellular components. There is increasing evidence that loss of NF1 expression in neoplastic Schwann cells is associated with elevated levels of activated RAS, supporting the notion that the NF1 gene product, neurofibromin, acts as a growth regulator by inhibiting ras growth-promoting activity. In addition, there is increasing evidence that other cooperating events, which may be under cytokine modulation, are important for neurofibroma development and growth. Treatment of plexiform neurofibromas has been empiric, with surgery being the primary option for those with progressive lesions causing a major degree of morbidity. The efficacy of alternative treatment approaches, including the use of antihistamines, maturation agents, and antiangiogenic drugs, has been questionable. More recently, biologic-based therapeutic approaches, using drugs that target the molecular genetic underpinnings of plexiform neurofibromas or cytokines believed important in tumor growth, have been initiated. Evaluation of such trials is hindered by the unpredictable natural history of plexiform neurofibromas and difficulties in determining objective response in tumors that are notoriously large and irregular in shape. Innovative neuroimaging techniques and the incorporation of quality-of-life scales may be helpful in evaluation of therapeutic interventions. The ability to design more rational therapies for NF1-associated neurofibromas is heavily predicated on an improved understanding of the molecular and cellular biology of the cells involved in neurofibroma formation and growth.

Neurofibromatosis 1

“…Several chemotherapy trials have been conducted to treat plexiform neurofibromas, including antihistamines, maturation agents, and antiangiogenesis drugs. 48 A randomised placebo-controlled trial is in progress to assess an oral farnesyltransferase inhibitor and the antifibrotic agent pirfenidone is being evaluated in adults with progressive plexiform and spinal neurofibromas. 48 MPNST Clinicians and patients need to be alert to the symptoms of malignant change in a neurofibroma and prompt referral to a specialist NF/sarcoma unit should be ensured.…”

“…48 A randomised placebo-controlled trial is in progress to assess an oral farnesyltransferase inhibitor and the antifibrotic agent pirfenidone is being evaluated in adults with progressive plexiform and spinal neurofibromas. 48 MPNST Clinicians and patients need to be alert to the symptoms of malignant change in a neurofibroma and prompt referral to a specialist NF/sarcoma unit should be ensured. 9 The use of 18 fluorodeoxyglucose positron emission tomography facilitates early diagnosis of MPNST.…”

Neurofibroma of the cervical part of the vagus nerve: A case report

“…There are only ten reported cases of such lesions found in literature [2]. Majority of neoplasms of vagus nerve are schwannomas [4,5].…”

“…Patients present with a painless neck lump with no significant disability. Some case studies have documented dysphagia and cough with percussion of the mass [4]. The most common age range is 20-40 years with no sex predisposition [7].…”

Phase II trial of pegylated interferon alfa-2b in young patients with neurofibromatosis type 1 and unresectable plexiform neurofibromas

“…15 A study evaluating short acting interferon alpha-2a in patients with PN showed a high rate of prolonged radiographic stability by standard imaging as well as clinical improvement in approximately 20%. 16 The pegylated form of interferon (PI) has a significantly prolonged plasma half-life, allowing protracted activity and less frequent administration. A phase I study of PI in pediatric patients with unresectable PN showed both clinical and imaging responses by volumetric MRI analysis and established the recommended phase II dose of 1.0 mcg/kg/wk given by subcutaneous injection.…”