Vestibular Schwannoma/Acoustic Neuroma

Updated by Sarah McAvoy

BACKGROUND

What is the cell of origin for vestibular schwannomas and acoustic neuromas (ANs)?

The Schwann cell of the myelin sheath is the cell of origin for ANs.

Which CN do ANs affect?

ANs affect CN VIII. Most affect the vestibular portion of the nerve.

In which anatomic region do ANs arise?

Most ANs are found in the cerebellopontine angle (CPA).

What are the most common presenting symptoms, incidence, and what cranial nerves (CNs) are they associated with?

Hearing loss (95% of pts) and tinnitus (63%) → CN VIII; cochlear nerve unsteadiness/veering/tilting (61%) → CN VIII; vestibular nerve, facial paresthesia, or pain (17%) → CN V; facial paresis (6%) → CN VII (Matthies C and Samii M, Neurosurg 1997).

What is the median age at diagnosis?

50 yrs

Most people with symptomatic ANs will present between what ages?

Most symptomatic pts are 30–50 yo.

What proportion of ANs are sporadic?

The majority (90%) are sporadic as well as unilateral.

What % of ANs are bilat, and with what genetic abnormality are they associated?

10% are bilateral and associated with NF-2, the tumor suppressor gene on chromosome 22.

What protein is abnl in NF-2 pts?

Merlin or schwannomin (involved in actin cytoskeleton organization)

What is the name of the anatomic layer of CN VIII that gives rise to most ANs?

The Obersteiner-Redlich zone (the junction between the central and peripheral myelin) gives rise to most ANs.

Subclinical ANs are present in what % of the general population?

Up to 1% (autopsy series) of the general population harbor subclinical ANs.

ANs account for what % of intracranial tumors?

5%–8% of intracranial tumors are ANs. Overall incidence is ∼1/100,000 person-years.

Apart from NF-2, what are 2 other risk factors that predispose to the development of ANs?

Loud noise exposure (ORR 13) and parathyroid adenoma (ORR 3.4), childhood exposure to low-dose radiation (RR per Gy 1.14).

What are the Antoni A and Antoni B areas on histopathology?

Antoni A and B are zones of dense and sparse cellularity, respectively.

For what do ANs stain on immunohistochemistry?

Most ANs stain for S100.

How do bilat ANs fare after Tx when compared to unilat ANs?

Bilat ANs have similar failure rates to unilat lesions if treated adequately.

WORKUP/STAGING

What tests are performed on physical exam for pts with CPA lesions?

Rinne test (mastoid bone, air conduction > bone conduction) and Weber test (occiput, vibratory sound louder on good side) to confirm sensorineural hearing loss; also need to check for other CN deficits (CN VII, hypesthesia, corneal twitching)

What CN is being tested when a pt is asked to tighten the ant neck muscles?

CN VII (innervates platysma muscle) can often be affected with large AN lesions.

Why are pts with CPA lesions often asked to march in place with their eyes closed on physical exam?

When the vestibular nerve is affected, pts will often veer to the side of the lesion.

What is the best initial screening test for ANs, and what does it usually show?

Audiometry (asymmetric sensorineural loss, more prominent at ↑ frequencies) is the best screening tool for ANs.

What is the avg growth rate per yr for ANs?

~1 mm/yr. Growth rates range from 0.5–2.5 mm/yr (slow-growing lesions) to ≥2.5 mm/yr (fast-growing lesions).

What % of ANs are stable (shrink/do not grow)?

~20%–40% of ANs are considered stable.

Is the size of the tumor at presentation predictive of the tumor’s growth rate?

No. Tumor size is generally not predictive of the tumor’s growth rate.

Does AN tumor size correlate with hearing loss?

Usually not. The location of the tumor (i.e., intracanalicular vs. not intracanalicular) is more predictive. Pts with tumor growth rate ≤2.5 mm/yr have higher hearing preservation than those with higher tumor growth (Sughrue ME et al., J Neurosurg 2010)

What do brainstem auditory evoked potentials typically show in pts with ANs?

A delay of conduction time on the affected side is seen with auditory evoked potentials.

What imaging study is typically performed for ANs?

Thin-slice (1–1.5 mm) MRI with gadolinium. MRI can detect tumors as small as 1–2 mm in diameter. If NF is suspected, neuraxis MRI is performed. If pt cannot undergo MRI, high-resolution CT scan +/– contrast is the alternative.

To what is the “ice cream cone” appearance of ANs on MRI due?

This AN appearance is due to enhancing lesions in the canal (cone) and CPA (ice cream).

TREATMENT/PROGNOSIS

What options are available for AN pts?

Observation, surgery, or RT

When is observation appropriate for ANs?

Observation is appropriate with small tumors (<2 cm) or no/slow growth without Sx progression. 43% with growth, 51% stable, and 6% regressed without treatment. (Smouha EE et al., Laryngoscope 2005)

What follow-up is required for AN pts opting for observation?

Audiometry and MRI scans q6–12mo

What are the 4 surgical approaches available for ANs, and what are the prominent disadvantages/advantages of each?

Retromastoid: may not be able to achieve GTR/good facial nerve preservation, good hearing preservation, can be used for any size tumor

Middle cranial fossa: GTR, facial nerve preservation moderate-hearing preservation better, good for small <1.5-cm tumors

Translabyrinthine: sacrifices hearing/good facial nerve preservation, recommended if tumor >3 cm

Retrolabyrinthine: sacrifices hearing

When is surgery the preferred Tx option for ANs?

Surgery is preferred for large (>4 cm) symptomatic tumors or recurrence/progression after RT.

What are the recurrence rates after GTR for ANs?

<1% (Samii M et al., J Neurosurg 2001; Guerin C et al., Ann Acad Med Singapore 1999; Gormley WB et al., Neurosurgery 1997)

What are the overall facial nerve and hearing preservation rates after surgery for ANs?

After surgery for ANs, there is an 80%–90% facial nerve preservation rate and a 50% hearing preservation rate.

What are the overall facial nerve and hearing preservation rates after RT for ANs?

With SRS: facial nerve preservation rate >95%, hearing preservation 70%–90%

With fractionated RT (FSR): ~95% facial nerve preservation rate and ~55%–65% hearing preservation rate

What are the long-term LC rates after RT for ANs?

Long-term LC after RT for ANs is 90%–97%. (Lunsford LD et al., J Neurosurg 2005; Combs SE et al., IJROBP 2006; Litre F et al., Radiother Oncol 2013; Hasegawa T et al., J Neurosurg 2013; Maniakas A et al., Otol Neurotol 2012)

What are some commonly employed doses when SRS/Gamma Knife (GK) SRS is used for ANs?

12–13 Gy to 50% IDL is a commonly employed SRS regimen for ANs.

What has the dose trend been for the Tx of ANs with SRS?

The dose was lowered from 16 Gy to 12–13 Gy. Pittsburgh and Japanese data showed similar LC rates but less facial weakness and hearing loss with lower doses.

What doses are used with FSR?

50–55 Gy (in 25–30 fx at 1.8 Gy/fx) if larger (>2–3 cm) lesions Alternative approach: 25 Gy (5 Gy ×5 fx) with smaller lesions

What are the hearing preservation rates with FSR?

This is controversial, but hearing preservation rates are thought to be slightly better with FSR than with SRS or surgery (94% in Combs SE et al., IJROBP 2005; 81% in Andrews DW et al., IJROBP 2001). Other studies suggest outcomes are equivalent if SRS dose <13 Gy (Combs SW et al., IJROBP 2011)

What recent data suggest better hearing preservation and similar LC rates with lower-dose FSR therapy?

Thomas Jefferson data: a lower dose of 46.8 Gy (vs. 50.4 Gy) had 100% LC at 5 yrs with a better hearing preservation rate. (Andrews DW et al., IJROBP 2009)

What other RT modalities have been successfully employed in AN?

CyberKnife (Chang SD et al., J Neurosurg 2005) and protons (Weber DC et al., Neurosurg 2003; Vernimmen FJ, Radiother Oncol 2009): worse hearing preservation (not used with tumors >2 cm and if pt can hear well)

What important AN studies prospectively compared surgery to SRS? What did they show?

Mayo Clinic data: <3-cm tumors, same tumor control rates but worse pt QOL after surgery. (Pollock BE et al., J Neurosurg 2006)

French data: largest prospective study. GK pts had better function overall. (Regis J et al., Neurochirurgie 2002)

Meta-analysis: included 16 studies showed SRS better long-term hearing preservation (70% vs. 50%) but no difference in tumor outcome. (Maniakas A and Saliba I, Otol Neurotol 2012)

What AN study prospectively evaluated SRS vs. FSR?

Dutch data: dentate pts rcvd FSR (20–25 Gy in 5 fx) and edentate SRS (10–12.5 Gy), with similar LC and functional outcomes. (Meijer OW et al., IJROBP 2003)

What agent has recently been shown to be effective in NF-2 pts with refractory ANs?

Bevacizumab (Avastin) was recently shown to be effective in NF-2 pts with refractory ANs. (Plotkin SR et al., NEJM 2009)