Patient Presentation 2½ yo boy presented with known NF1 and a right neck mass in 2/09 MRI revealed involvement of the right carotid sheath with collapse of the right internal jugular vein MRI in 8/09 revealed increase in size to include right brachial plexus and into the right lung apex

Types NF1 – von Recklinghausen’s Disease NF2 – central neurofibromatosis NF5 – segmental neurofibromatosis

Central Neurofibromatosis Classically bilateral vestibular schwannomas Meningiomas, neurofibromas, and gliomas now count Chromosome 22 Autosomal Dominant 1:25000 births

Segmental Neurofibromatosis NF5 Café-au-lait spots and neurofibromas, limited to one region (usually dermatomal) of the body ~100 pts. median age of onset is 28 yo Non-inherited

Criteria for NF1 6+ café-au-lait macules 2+ neurofibromas of any type or 1+ plexiform neurofibroma Freckling of the axillae or inguinal area Bilateral optic gliomas 2+ Lisch nodules Bone deformity

Genetics 1:3000 births Autosomal Dominant Chromosome 17q Neurofibromin Penetrance ~100% Expressivity is very variable –Worse when inherited from the mother 50% of cases are new mutations

Quality of Life More impact than asthma Orthopedic manifestations, learning disabilities and at least 2 plexiform neuromas had the most impact. Dermatologic findings had minimal impact.

Sessile Neurofibromas Cutaneous –Surgical incision limited by hypertrophic scar formation in some –Asymptomatic, benign Subcutaneous –Pain and neurological symptoms

Lisch Nodules asymptomatic Pigmented cells, fibroblast-like cells, and mast cells more likely to be present in younger patients than neurofibromas

Neurofibromas Types –Sessile or Pedunculated –Plexiform Neuroma –Elephantiasis Neuromatosa Schwann cellsSchwann cells, fibroblasts, perineural cells, mast cells and axons

Plexiform Neuromas A network of mast cells and fibroblast-like cells that grow along nerves and nerve plexi 17-27% of patients have clinically detectable masses Diffuse tumors that encroach into surrounding tissue are thought to be congenital Give rise to MPNST in 7-13%

Types Nodular Firm, mildly tender nodule along the dosal nerve roots Vertebral disfigurement Neuro deficits Diffuse Hyperpigmentation and hypertrichichosis Hypertrophy of adjacent connective tissue Bone remodeling Systemic symptoms if visceral involvement

Management MRI –Useful in determining potential malignancy –Monitoring of growth

Red Flags Persistent or Nocturnal Pain Rapid increase in Size New neurological deficits Targeted biopsy with FDG PET

Surgical Management Based on symptom management –Neurological symptoms: pain, weakness Sporadic growth rate –Excluding malignancy Recurrence is common –Especially in tumors that are not almost completely removed

Recurrence Factors Head and Neck Neuromas Age <10 yo Incomplete Resection

Experimental Drugs Gleevec Statins Thalidomide 13-cis-retonoic acid Interferon α-2a R11577

Patient Treatment Underwent a excision of the extensive plexiform neurofibroma from the skull base, neck, spine, chest and mediastinum –Involved foramina of C1-C3 –Involvement of aortic arch –Frond-like extensions into muscles of esophagus Removed 12X10 cm of tumor

Post-op Course Extubated on POD #1 –No pneumothorax Hemodynamically stable throughtout Discharged on POD #4

References Evans DG, Baser ME, McGuaghran J et al. Malignant Peripheral Nerve Sheath Tumours in Neurofibromatosis 1. J Med Genet 2002; 39: Ferner R. Neurofibromatosis 1 and neurofibromatosis 2: a twenty first century prespective. Lancet Neurol 2007; 6: Habif. Clinical Dermatology Mosby Needle MN, Cnaan A, Dattilo J et al. Prognostic signs in the clinical management of plexiform neurofibroma: the Children’s Hospital of Philadelphia experience, J Pediatr 1997; 5: Sehgal VN, Srivastava G, Aggarwal AK, Oberai R. Plexiform neurofibromas in neurofibromatosis type 1. Int J of Derm 2009; 48, Wolkenstein P, Rodriguez D, Ferkal S et al. Impact of neurofibromatosis 1 upon quality of life in childhood: a cross- sectional study of 79 cases. British Journal of Dermatology 2009; 160: