Plexiform neurofibromas in NF1: Toward biologic-based therapy

The Children's Hospital of Philadelphia, Filadelfia, Pennsylvania, United States
Neurology (Impact Factor: 8.29). 06/2002; 58(10):1461-70. DOI: 10.1212/WNL.58.10.1461
Source: PubMed


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.

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    • "Thus, it may be difficult to justify resection of a small plexiform neurofibroma in a child with a plexiform neurofibroma on the assumption that the tumor might grow at some time in the future. Therefore, surgical resection of PNs is usually reserved for markedly symptomatic lesions that compromise function [15] [16]. "
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    ABSTRACT: Plexiform neurofibromas are benign tumors of the peripheral nerve. Diagnosis may be challenging, if they present mimicking other peripheral nerve pathologies. We report the case of a patient who had severe foot pain, which progressively hampered her walking ability, erroneously attributed to recurrent Morton's neuroma. Diagnosis of plexiform neurofibroma of her right medial plantar nerve was made 15 years after the appearance of symptoms. Pain and function recovered after radical neurotomy of the medial plantar nerve. A correct diagnosis is an essential starting point in the treatment of neurofibromas and a misdiagnosis may lead to an inappropriate treatment.
    Full-text · Article · Sep 2014 · The Foot
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    • "About 10% of PNFs undergo transformation into a malignant peripheral nerve sheath tumor (MPNST).[20] The formation of malignant tumor from neurofibroma is associated with the loss of expression of the cyclin-dependent kinase inhibitor 2A (CDKN2A) or TP53 gene in nonmyelinating schwann cells that also exhibit biallelic inactivation of the NF-I gene.[21] "
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    ABSTRACT: Plexiform neurofibromas (PNFs) are one of the most common and debilitating complications of neurofibromatosis type I (NF-I). They account for substantial morbidity, disfigurement, functional impairment and are life threatening. PNFs can also be subjected to transformation into malignant peripheral nerve sheath tumor (MPNST). This complication is refractory to treat due to paucity of effective therapies for malignant soft tissue sarcomas in general and also the delay in diagnosis from a preexisting tumor. We report a case of PNF of face involving oral cavity with literature review.
    Full-text · Article · Apr 2014 · Journal of Oral and Maxillofacial Pathology
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    • "Solitary plexiform neurofibroma could be a clinical manifestation of segmental NF resulting from mosaicism of NF-1 [15]. Although genetic testing for some of the mutations of the NF-1 gene is available, there is no evidence that such testing is helpful in diagnosing NF-1 in patients with isolated plexiform neurofibroma [14]. Immunohistochemically, the tumour is positive for anti-S 100 protein. "
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    ABSTRACT: Plexiform neurofibroma is more commonly seen in the orbit, neck, back, and inguinal region. It is extremely rare in the submandibular gland. These lesions rarely transform into malignancy but are locally infiltrative and can lead to haemorrhage. Therefore, plexiform neurofibroma should always be considered during differential diagnosis while excising a submandibular gland mass. We present here a case of plexiform neurofibroma in the submandibular gland and diffuse neurofibroma in the floor of the mouth in a 27-year-old female, not associated with neurofibromatosis-1.
    Full-text · Article · May 2013 · ecancermedicalscience
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