Dx: Nerve Sheath Tumor

KEY FACTS

Terminology Schwannoma: Arises from Schwann cells and displaces axons Neurofibroma (NF): Mixture of Schwann cells and perineural cells that incorporate axons Imaging
Well-defined unilocular radiolucency:Epicenter in symmetrically widened inferior alveolar canal Mandible > maxilla: Usually inferior alveolar nerve

< 1-6 cm reported Anterior lesion may mimic periapical pathology Root divergence may be seen MR will best characterize lesion contents Top Differential Diagnoses
Hemangioma

Perineural tumor spread along CNV3

Simple bone cyst Periapical rarefying osteitis

Pathology Multiple neurofibromas associated with neurofibromatosis type 1 (NF1) Clinical Issues Frequently asymptomatic; pain or paresthesia; delayed eruption of teeth; cortical expansion 2nd-4th decades most common; females > males Slow-growing benign lesion Malignant transformation more common in plexiform NF associated with NF1 Treatment: Surgical enucleation with blunt dissection from involved nerve Neurofibromas more likely to recur because of infiltrative growth Genetic testing if multiple lesions present
TERMINOLOGY

Synonyms Schwannoma: Neurilemmoma, peripheral fibroblastoma, neurinoma Neurofibroma (NF): Neurinoma Definitions Benign perineural tumor arising from cells of neural sheath Schwannoma: Arises from Schwann cells and displaces axons Schwann cells cover myelinated nerves Neurofibroma: Mixture of Schwann cells and perineural cells that incorporate axons Malignant peripheral nerve sheath tumor (MPNST) Most commonly involves major nerve trunks, including brachial plexus
IMAGING

General Features Best diagnostic clue

Well-defined unilocular radiolucency, often as epicenter in symmetrically widened mandibular canal on

panoramic views Concentric expansion of mandibular canal on coronal views Location 25-48% occur in H&N: Tongue most common intraoral site Intraosseous lesions less common than soft tissue lesions: < 1% of all bone tumors Mandible > maxilla Usually associated with inferior alveolar nerve Posterior > anterior Schwannoma reported presenting as periapical lesion in posterior mandible and as unilocular radiolucency in anterior mandible Differentiation from odontogenic pathology may be difficult in these cases Size < 1-6 cm reported Soft tissue lesions can reach larger size Morphology Unilocular with well-defined, often corticated borders Some neurofibromas have been described as poorly defined Radiographic Findings Extraoral plain film Panoramic imaging may show symmetric widening of mandibular canal with localized fusiform expansion Anterior lesion will appear as isolated well-defined unilocular radiolucency and may mimic periapical pathology orodontogenic and nonodontogenic cysts Neurofibromas may be less well defined Neurofibromas may produce flaring of the mandibular foramen: "Blunderbuss" foramen Root divergence may be seen CBCT and bone CT Will show extent of lesion and any expansion Coronal views best to show concentric expansion of mandibular canal MR Findings T1WI Schwannoma: Intermediate signal most common Neurofibroma: Most are homogeneous and isointense to skeletal muscle T2WI: Hyperintense T1WI C+ Schwannoma: Homogeneous enhancement Localized NF: Homogeneous or patchy heterogeneous enhancement; well-circumscribed fusiform mass Imaging Recommendations Best imaging tool: MR will best characterize lesion contents and extent
DIFFERENTIAL DIAGNOSIS

Hemangioma

Expansion of mandibular canal less symmetrical Canal may become curved or serpiginous Perineural Tumor Spread Along CNV3 Spread of malignant lesion through mandibular or mental foramina may cause widening of canal Borders will be less well defined or destroyed May see associated mass in oral cavity adjacent to involved nerve
Simple Bone Cyst

SBCs occur in similar age group Males > females May be difficult to differentiate from solitary neural lesion not in mandibular canal
Periapical Rarefying Osteitis

Inflammatory reaction at apex of pulpally involved tooth Well-defined radiolucency Tooth is nonvital
PATHOLOGY

General Features Etiology: Proliferation of Schwann cells and perineural cells within perineurium causing displacement and compression of surrounding normal nerve tissue Associated abnormalities Multiple neurofibromas associated with neurofibromatosis type 1 (NF1) a.k.a. von Recklinghausen disease Autosomal dominant neurocutaneous disorder with varied expressivity 2 neurofibromas (NF) or 1 plexiform NF (PNF) Caf-au-lait spots Axillary freckling (Crowe sign) Bilateral acoustic schwannomas associated with neurofibromatosis type 2 (NF2) Autosomal dominant disorder associated with chromosome 22 May develop peripheral schwannomas and meningiomas Staging, Grading, & Classification Schwannomas have different origins Soft tissue origin: Acoustic neuroma most common in H&N May involve bone secondarily Arising in nutrient canals: Causes enlargement of canal Arising centrally within bone Neurofibromas Localized: Fusiform mass with nerve running through Diffuse: In soft tissues, see infiltrative growth into subcutaneous fat Plexiform: Highly characteristic of neurofibromatosis; extensive interlacing nerve tissue resembling "tangle of worms" Gross Pathologic & Surgical Features Neurofibroma: Fusiform, firm, gray-white mass intermixed with nerve of origin Schwannoma: Solid lesion more easily separated from associated nerve because of capsule Microscopic Features Schwannoma Encapsulated Typically see palisading organized fusiform cells (Antoni A); less organized (Antoni B) Verocay bodies: Acellular eosinophilic zones
S100 strongly positive

Neurofibroma Nonencapsulated Mixture of Schwann cells, perineural cells, and endoneurial fibroblasts Spindle-shaped Schwann cells with elongated or wavy nuclei S100 positive
CLINICAL ISSUES

Presentation Most common signs/symptoms: Frequently asymptomatic

Other signs/symptoms Pain or paresthesia Patient may report tingling sensation Prevention of eruption of teeth Cortical expansion Demographics Age Neurofibroma: 9-50 years Schwannoma: 10-40 years 2nd-4th decades most common Gender Females:males = 2:1 Literature is contradictory Epidemiology Neurofibroma Frequency of oral peripheral nerve sheath tumors reported as 20-30% Schwannoma Frequency of oral peripheral nerve sheath tumors reported as 16-22% Natural History & Prognosis Malignant transformation more common in PNF associated with NF1 Slow-growing benign lesion Malignant schwannoma rare in CNV Treatment Surgical enucleation with blunt dissection from involved nerve Recurrence uncommon for schwannoma; neurofibromas more likely to recur because of infiltrative growth Genetic testing if multiple lesions present Examine patient for stigmata of NF1
DIAGNOSTIC CHECKLIST

Consider Solitary neurofibroma may represent "forme fruste": 1st or only manifestation of neurofibromatosis Long-term follow-up to monitor for development of other lesions is critical