Vestibular Schwannoma And Neurofibroma

Neurilemomas, also known as schwannomas and neurinomas, arise from the Schwann cells of the myelin sheath of the peripheral nerves. When occurring close to the eighth cranial nerve, they are also called vestibular schwannomas or acoustic neuromas. These tumors account for approximately 6% of CNS neoplasms in adults. They may be sporadic or associated with NF2, with bilateral vestibular schwannomas being pathognomonic of this disease. The majority of sporadic vestibular schwannomas are unilateral and occur in the fourth and fifth decades of life. Those arising in patients with NF2 tend to occur in the second or third decades. These tumors grow slowly in a well-circumscribed, expansile fashion, displacing adjacent nerves rather than invading them. The majority arise from cranial nerve VIII in the medial internal auditory canal. Less commonly, they may arise from other cranial nerves, the trigeminal nerve being the most common alternate site.
Growth in the internal auditory canal gives rise to vestibular and hearing abnormalities in up to 95% of patients. A progressive unilateral sensorineural hearing loss is characteristic. Expansion into the cerebellopontine angle may lead to trigeminal symptoms, and a unilateral absent corneal reflex is an early sign of trigeminal involvement. Large tumors may impinge on the cerebellum and brainstem, leading to ataxia and long tract signs as well as involvement of cranial nerves IX, X, XI, and XII.
Pure tone and speech audiometry are the most useful screening tests. Selective loss of speech discrimination in excess of pure tone loss is particularly suggestive of vestibular schwannoma. Brainstem auditory evoked responses typically demonstrate a slowing of conduction, and electronystagmography may detect a decrease in caloric response on the ipsilateral side. Thin-slice Gd-enhanced MRI through the cerebellopontine angle is the imaging modality of choice for suspected vestibular schwannoma. Thin-slice, contrast-enhanced, high-resolution CT scan is an acceptable alternative when MRI is not obtainable. An intensely enhancing lesion close to the internal auditory canal is highly suggestive of this diagnosis. Patients with suspected neurofibromatosis should have complete imaging of the craniospinal axis to document other neurilemomas, neurofibromas, and meningiomas that may be present.
Neurofibromas differ from neurilemomas in their cellular composition and growth pattern. Although neurofibromas also arise from peripheral nerves, they are most commonly multiple and associated with NF1. Neurofibromas expand rather than displace the nerve of origin. Histologically, neurofibromas are composed of a hypertrophied mass of fibroblasts and Schwann cells through which run normal neurons. Symptoms are caused primarily through compression of the involved or adjacent nerves.
Treatment
Treatment should offer a high chance of local control as well as preservation of cranial nerve function. Observation alone may be appropriate in patients willing to undergo regular clinical and imaging follow-up and may allow treatment to be deferred for some time. The mainstay of treatment has been microsurgical resection. Retrosigmoid (suboccipital) middle fossa and translabyrinthine approaches offer the possibility of hearing preservation but are associated with higher incidences of seventh nerve damage and postoperative complications. The translabyrinthine approach is associated with low operative morbidity and mortality but sacrifices hearing. At centers with expertise in microsurgical resection, total or near-total resection rates of 90% are routinely obtained with a surgical mortality rate of <2%. Anatomic preservation of the facial nerve may be achieved in 90% of patients and functional preservation in more than two-thirds. Preservation of useful hearing is reported in 30% to 50%. In patients in whom a near-total or total resection is achieved, the tumor recurrence rate is <10%. In patients in whom a subtotal resection is achieved, tumor recurrence may occur in one-third to one-half. Adjuvant radiotherapy may reduce the rate of recurrence to that of complete resection.
At the University of Californiaโ€“San Francisco, the percentage of tumors that are totally resected has increased from 50% to over 80% in the past three decades (262). Only 2/63 patients who had total resection recurred. Patients who underwent near-total resection (defined as removal of 90% to 99% of the tumor, as judged by the surgeon at the time of operation) had a recurrence rate of only 7% compared with 46% (6/13) in patients who underwent subtotal resection (<90% of the tumor resected), with an actuarial recurrence rate of 59% at
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15 years. Patients who received postoperative irradiation after subtotal resection had an actuarial recurrence rate of only 6% at 15 years (p = .01). Three patients treated with radiotherapy after biopsy alone were without disease progression at 7 to 14 years after therapy. All recurrences were in the tumor bed.
In patients with a medical contraindication to surgery, treatment with external beam irradiation alone is an option. A dose of 50 to 55 Gy in 25 to 30 fractions over 5 to 6 weeks is recommended. Maire et al. (139) evaluated 24 patients with stage III and IV cerebellopontine angle schwannomas treated with external irradiation; seven had phacomatosis. Indications for radiotherapy were poor general condition or old age contraindicating surgery in 14 cases, hearing preservation in bilateral neurinomas after contralateral tumor removal in five cases, partial resection or high risk of recurrence after subsequent surgery for relapse in four cases, and nonsurgical relapse in two cases. Mean doses were 51 Gy in fractions of 1.8 Gy. With median follow-up of 60 months, there was an 88% tumor control rate with no injuries to the cranial nerve V or VIII.
Radiosurgery may be an alternative to microsurgical resection. The well-circumscribed nature of these tumors, coupled with their typical intense enhancement on MRI, facilitates their localization and treatment using stereotactic techniques. The progression-free survival rate with radiosurgery is nearly 90% at 20 years. Radiosurgical treatment with higher doses yielded high rates of tumor growth arrest (>80%) and tumor shrinkage in up to two thirds of patients, although facial or trigeminal neuropathy develops in nearly one third of patients as long as 2 years after therapy. The volume of the lesion is a significant risk factor for complications involving cranial nerve V, VII, or VIII. Temporary enlargement may occur up to 2 years following radiosurgery (155).
Noren (163) reviewed the results of 669 patients with vestibular schwannoma treated with Gamma Knife radiosurgery between 1969 and 1997. Long-term growth control was achieved in 95%. Facial weakness and/or numbness occurred in approximately one third of patients during the 1970s but in <2% in the 1990s. Hearing was preserved in 65% to 70% of patients, although tinnitus was rarely changed by treatment. With dose reduction to 12 to 13 Gy, high rates of tumor control and cranial nerve preservation may be achieved. Flickinger et al. (71) reported the results of 313 patients treated with radiosurgery to median dose of 13 Gy. The actuarial 6-year tumor control rate was 98.6%. The actuarial 6-year rates for preservation of seventh nerve function, normal fifth nerve function, unchanged hearing level, and useful hearing were 100%, 95.6%, 70.3%, and 78.6%, respectively.
Radiosurgery provides similar local control with less morbidity than surgery for small (<3 cm) unilateral tumors. In a series from the University of Pittsburgh, radiosurgery was found to have improved preservation of facial function (p <.05) and hearing (p <.03) with decreased associated morbidity (p <.01) when compared to surgical resection (182). Postoperative functional outcomes and patient satisfaction were greater after radiosurgery, although this did not reach statistical significance. Return to independent functioning occurred earlier (p <.001), and hospital stay was shorter (p <.001) after radiosurgery, suggesting that radiosurgery may be an equally effective and less costly management strategy than surgical resection for small tumors.
FSRT has been shown to give local control rates of 91% to 97% with similar effects on cranial nerves V and VII (2,144,221,234). However, in one series FSRT resulted in 2.5-fold greater preservation of hearing compared to radiosurgery (2).
For neurofibromas, treatment is usually complete resection of compressive lesions with expectant observation of any asymptomatic synchronous lesions. Treatment of neurofibromas is associated with a high rate of local control (>90%) when complete excision is possible. For subtotally excised lesions, adjuvant radiotherapy (50 to 55 Gy) may decrease the risk of local recurrence.
Evidence-Based Treatment Summary
Small nonprogressive tumors can be observed.
Surgical resection is generally considered the standard of care for symptomatic lesions.
Radiosurgery produces outcomes equivalent to surgery, although these modalities have not been prospectively compared.
Fractionated stereotactic radiotherapy is being increasingly employed, with institutional reports suggesting a lower incidence of cranial neuropathies than radiosurgery, but this has not been prospectively validated.