Vestibular tumor

Template:Vestibular tumor Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

Overview

Vestibular tumors are growths that tend to develop underneath the serous tissue of the sublinguinal region. They may be found anywhere between the chin and the larynx (or voicebox) and are not more inclined to one side of the body than the other. They are predominantly present in adolescent females though they are not directly related to any hygienal issues. While surgery is the most often cure, deaths rarely occur due to the existence of vestibular tumors.

Historical Perspective

The first reported case of a vestibular tumor was in 1898 in Lancaster, Pennsylvania. Though there have been stories of growths of the like of vestibular tumors, this was the first medically reported case. At the time, surgery was too dangerous, so Emilia Walfen was forced to live with the tumor, which eventually grew to the size of a Concord grape.

Pathogenesis

Recent studies in NF2 patients led to the identification of the neurofibromin 2 gene, which is located on chromosome 22. The NF2 gene produces merlin, also known as schwannomin, a cell membrane-related protein that acts as a tumor suppressor. Biallelic inactivation of the NF2 gene is found in most sporadic vestibular schwannomas.

Microscopic pathology

• Vestibular schwannomas arise from perineural elements of the Schwann cell.
• They occur with equal frequency on the superior and inferior branches of the vestibular nerve.
• Microscopically, zones of alternately dense and sparse cellularity, called Antoni A and B areas, respectively, are characteristic of vestibular schwannomas.
• Malignant degeneration is extremely rare, with only six cases having been reported.
• Immunohistochemical staining for S100 protein is usually positive in both the benign and the rare malignant forms of this tumor.

Differentiating Vestibular schwannoma from other diseases

The differential diagnosis includes meningioma, facial nerve schwannomas, gliomas, cholesterol cysts, cholesteatomas, hemangiomas, aneurysms, arachnoid cysts, lipomas, and metastatic tumor. For more information click here On the basis of seizure, visual disturbance, and constitutional symptoms, meningioma must be differentiated from oligodendroglioma, astrocytoma, hemangioblastoma, pituitary adenoma, schwannoma, primary CNS lymphoma, medulloblastoma, ependymoma, craniopharyngioma, pinealoma, AV malformation, brain aneurysm, bacterial brain abscess, tuberculosis, toxoplasmosis, hydatid cyst, CNS cryptococcosis, CNS aspergillosis, and brain metastasis.

Diseases	Clinical manifestations					Para-clinical findings			Gold standard	Additional findings
	Symptoms				Physical examination
						Lab Findings	MRI	Immunohistopathology
	Head- ache	Seizure	Visual disturbance	Constitutional	Focal neurological deficit
Adult primary brain tumors
Meningioma	+	+/−	+/−	−	+	−	Well circumscribed Extra-axial mass Dural attachment CSF vascular cleft sign Sunburst appearance of the vessels	Arachnoid origin Psammoma bodies Whorled spindle cell pattern	Biopsy	Highest incidence is between 40 and 50 years of age. Most of the time, focal neurological deficit and epileptic seizure are the presenting signs. May be associated with NF-2
Glioblastoma multiforme	+	+/−	+/−	−	+	−	Supratentorial Irregular ring-nodular enhancing lesions Central necrosis Surrounding vasogenic edema Cross corpus callosum (butterfly glioma)	Astrocyte origin Pleomorphic cell Pseudopalisading appearance GFAP + Necrosis + Hemorrhage + Vascular prolifration +	Biopsy	Highest incidence in fifth and sixth decades of life Most of the time, focal neurological deficit is the presenting sign.
Oligodendroglioma	+	+	+/−	−	+	−	Almost always in cerebral hemisphers (frontal lobes) Hypointense on T1 Hyperintense on T2 Calcification Chicken wire capillary pattern	Oligodendrocyte origin Calcification + Fried egg cell appearance	Biopsy	Highest incidence is between 40 and 50 years of age. Most of the time, epileptic seizure is the presenting sign.
Hemangioblastoma	+	+/−	+/−	−	+	−	Infratentorial Cystic lesion with a solid enhancing mural nodule	Blood vessel origin Capillaries with thin walls	Biopsy	Might secret erythropoietin and cause polycythemia May be associated with von hippel-lindau syndrome
Pituitary adenoma	−	−	+ Bitemporal hemianopia	−	−	Endocrine abnormalities as a result of functional adenomas or pressure effect of non-functional adenomas	Isointense to normal pituitary gland in T1	Endocrine cell hyperplasia	Biopsy	It is associated with MEN1 disease. Initialy presents with upper bitemporal quadrantanopsia followed by bitemporal hemianopsia (pressure on optic chiasma from below)
Schwannoma	−	−	−	−	+	−	Split-fat sign Fascicular sign Often have areas of hemosiderin	Schwann cell origin S100+	Biopsy	It causes hearing loss and tinnitus May be associated with NF-2 (bilateral schwannomas)
Primary CNS lymphoma	+	+/−	+/−	−	+	−	Usually deep in the white matter Single mass with ring enhancement	B cell origin Similar to non hodgkin lymphoma (diffuse large B cell)	Biopsy	Usually in young immunocompromised patients (HIV) or old immunocompetent person.
Childhood primary brain tumors
Pilocytic astrocytoma	+	+/−	+/−	−	+	−	Infratentorial Solid and cystic component Mostly in posterior fossa Usually in cerebellar hemisphers and vermis	Glial cell origin Solid and cystic component GFAP +	Biopsy	Most of the time, cerebellar dysfunction is the presenting signs.
Medulloblastoma	+	+/−	+/−	−	+	−	Infratentorial Mostly in cerebellum Non communicating hydrocephalus	Neuroectoderm origin Homer wright rosettes	Biopsy	Drop metastasis (metastasis through CSF)
Ependymoma	+	+/−	+/−	−	+	−	Infratentorial Usually found in 4th ventricle Mixed cystic/solid lesion Hydrocephalus	Ependymal cell origin Perivascular pseudorosette	Biopsy	Causes an unusually persistent, continuous headache in children.
Craniopharyngioma	+	+/−	+ Bitemporal hemianopia	−	+	Hypopituitarism as a result of pressure effect on pituitary gland	Calcification Lobulated contour Motor-oil like fluid within tumor	Ectodermal origin (Rathkes pouch) Calcification +	Biopsy	Initialy presents with lower bitemporal quadrantanopsia followed by bitemporal hemianopsia (pressure on optic chiasma from above)
Pinealoma	+	+/−	+/−	−	+ vertical gaze palsy	B-hCG rise leads to precocious puberty in males	Hydrocephalus (compression of cerebral aqueduct)	Similar to testicular seminoma	Biopsy	May cause prinaud syndrome (vertical gaze palsy, pupillary light-near dissociation, lid retraction and convergence-retraction nystagmus
Vascular
AV malformation	+	+	+/−	−	+/−	−	Supratentorial: ~85% Flow voids on T2 weighted images	We do not perform biopsy for AVM	Angiography	We may see bag of worms appearance in CT angiography
Brain aneurysm	+	+/−	+/−	−	+/−	−	In magnetic resonance angiography, we may see aneurysm mostly in anterior circulation (~85%)	We do not perform biopsy for brain aneurysm	MRA and CTA	It is associated with autosomal dominant polycystic kidney disease, Ehlers-Danlos syndrome, pseudoxanthoma elasticum and Bicuspid aortic valve (Angiography is reserved for patients who have negative MRA and CTA)
Infectious
Bacterial brain abscess	+	+/−	+/−	+	+	Leukocytosis Elevated ESR Blood culture may be positive for underlying organism	Central hypodense signal and surrounding ring-enhancement in T1 Central hyperintense area surrounded by a well-defined hypointense capsule with surrounding edema in T2	We do not perform biopsy for brain abscess	History/ imaging	The most common causes of brain abscess are Streptococcus and Staphylococcus.
Tuberculosis	+	+/−	+/−	+	+	Positive acid-fast bacilli (AFB) smear in CSF specimen Positive CSF nucleic acid amplification testing Hyponatremia (inappropriate secretion of antidiuretic hormone) Mild anemia Leukocytosis	Hydrocephalus combined with marked basilar meningeal enhancement	We do not perform biopsy for brain tuberculosis	Lab data/ Imaging	It is associated with HIV infection
Toxoplasmosis	+	+/−	+/−	−	+	Normal CSF	Multifocal masses with ring enhancement Mostly in basal ganglia, thalami, and corticomedullary junction.	We do not perform biopsy for brain toxoplasmosis	History/ imaging	It is associated with HIV infection
Hydatid cyst	+	+/−	+/−	+/−	+	Positive serology (Antibody detection for E. granulosus)	Honeycomb appearance Necrotic area	We do not perform biopsy for hydatid cysts	Imaging	Brain, eye, and splenic cysts may not produce detectable amount of antibodies
CNS cryptococcosis	+	+/−	+/−	+	+	Positive CSF antigen testing (coccidioidomycosis) CSF lymphocytic pleocytosis Elevated CSF proteins and lactate Low CSF glucose	Dilated perivascular spaces Basal ganglia pseudocysts Soap bubble brain lesions (cryptococcus neoformans)	We may see numerous acutely branching septate hyphae	Lab data/ Imaging	It is the most common brain fungal infection It is associated with HIV, immunosuppressive therapies, and organ transplants In may happen in immunocompetent patients undergoing invasive procedures ( neurosurgery) or exposed to contaminated devices or drugs Since brain biopsies are highly invasive and may may cause neurological deficits, we diagnose CNS fungal infections based on laboratory and imaging findings
CNS aspergillosis	+	+/−	+/−	+	+	Positive galactomannan antigen testing (aspergillosis) CSF lymphocytic pleocytosis Elevated CSF proteins and lactate Low CSF glucose	Multiple abscesses Ring enhancement Peripheral low signal intensity on T2	We may see numerous acutely branching septate hyphae	Lab data/ Imaging	It is associated with HIV, immunosuppressive therapies, and organ transplants In may happen in immunocompetent patients undergoing invasive procedures ( neurosurgery) or exposed to contaminated devices or drugs Since brain biopsies are highly invasive and may may cause neurological deficits, we diagnose CNS fungal infections based on laboratory and imaging findings
Other
Brain metastasis	+	+/−	+/−	+	+	−	Multiple lesions Vasogenic edema	Based on the primary cancer type we may have different immunohistopathology findings.	History/ imaging	Most common primary tumors that metastasis to brain: Lung cancer Renal cell carcinoma Breast cancer Melanoma Gastrointestinal tract If there is any uncertainty about etiology, biopsy should be performed

ABBREVIATIONS

CNS=Central nervous system, AV=Arteriovenous, CSF=Cerebrospinal fluid, NF-2=Neurofibromatosis type 2, MEN-1=Multiple endocrine neoplasia, GFAP=Glial fibrillary acidic protein, HIV=Human immunodeficiency virus, BhCG=Human chorionic gonadotropin, ESR=Erythrocyte sedimentation rate, AFB=Acid fast bacilli, MRA=Magnetic resonance angiography, CTA=CT angiography

Risk Factors

Common risk factors for the development of vestibular schwaomas include:

• Childhood exposure to low-dose radiation for benign conditions of the head and neck
• Radiofrequency radiation from the use of mobile phones
• Noise exposure

Epidemiology and Demographics

Incidence

• The overall incidence of vestibular schwannomas is approximately 1 per 100,000 person-years in the United States.
• Bilateral vestibular schwannomas are primarily observed in patients with neurofibromatosis type 2 (NF2).
• The tumors are unilateral in more than 90 percent of cases, affecting the right and left sides with equal frequency.

Age

• The median age at diagnosis is approximately 50 years.

Gender

• Vestibular schwannomas occur equally in both genders.

Natural History, Complications, and Prognosis

Vestibular schwanama pose a major health impediment if left untreated as they might cause pressure on adjacent posterior fossa structures such as cerebellum or brainstem and result in ataxia Brainstem compression, cerebellar tonsil herniation, hydrocephalus, and death can occur in untreated cases. Common complication include seizures and paralysis difficulty swallowing due to the pressure on the tongue or pharynx. The functions of the lower cranial nerves can also become impaired, leading to dysarthria, dysphagia, aspiration, and hoarseness.

Diagnosis

History and Symptoms

• Symptoms associated with vestibular schwannoma can be due to cranial nerve involvement, cerebellar compression, or tumor progression. Clinical manifestations in this series included the following:

Never involvement	Incidence	Symtpoms
Cochlear nerve	95 percent	Hearing loss Tinnitus
Vestibular nerve	61 percent	Unsteadiness while walking Brief tilting or veering
Trigeminal nerve	17 percent	Facial numbness (paresthesia), hypesthesia, and pain.
Facial nerve	6 percent	Facial paresis Taste disturbances (due to nervus intermedius impairment). Xerophthalmia Paroxysmal lacrimation Xerostomia
Tumor progression		Pressure on adjacent posterior fossa structures such as cerebellum or brainstem and result in ataxia Brainstem compression, cerebellar tonsil herniation, hydrocephalus, and death can occur in untreated cases

Physical Examination

• Hearing tests are typically abnormal due to involvement of the acoustic nerve.
  • The Weber and Rinne tests may be useful in suggesting asymmetric sensorineural hearing impairment.

• Neurologic examination may reveal other cranial nerve deficits
  • A decreased or absent ipsilateral corneal reflex and facial twitching or hypesthesia may occur as cranial nerves V and VII become affected.
  • Romberg, Hall-Pike, and other common office balance tests are typically normal.

CT

Findings of vestibular schwanoma on CT include:

• Erosion and widening of the internal acoustic canal.
• The density of these tumors on non-contrast imaging is variable, and often they are hard to see, especially on account of beam hardening and streak artefact from the adjacent petrous temporal bone.

• Contrast enhancement is present but can be underwhelming, especially in larger lesions with cystic components.

MRI

MRI findings of vestibular schwanoma include:

MRI findings of Vestibular Schwanoma
T1	Slightly hypointense to the adjacent brain. Isointense to the adjacent brain May contain hypointense cystic areas
T2	Heterogeneously hyperintense to adjacent brain Fluid intensity cystic areas May have associated peritumoral arachnoid cysts
T1 C+ (Gd)	Contrast enhancement is intense however, heterogeneous in larger tumors

Other Diagnostic Studies

Audiometry

• Audiometry is the best initial screening laboratory test for the diagnosis of vestibular schwannoma.
• Pure tone and speech audiometry should be performed in an acoustically shielded area.
• Test results typically show an asymmetric sensorineural hearing loss, usually more prominent in the higher frequencies.
• Hearing loss does not necessarily correlate with tumor size.
• The speech discrimination score is usually markedly reduced in the affected ear and out of proportion to the measured hearing loss.
• Common audiometry tests that are of current practice include:
  • Acoustic reflex testing,
  • Impedance audiometry
  • Bekesy audiometry.
  • Brainstem-evoked response audiometry (AER/ABR).

Vestibular testing

• Vestibular testing has limited utility as a screening test for the diagnosis of vestibular schwannoma because of the accuracy of evoked response audiometry.
• When testing is performed, a decreased or absent caloric response on the affected side may be seen. When the tumor is small, though, a normal response is often seen.

Treatment

Treatment options for patients with a vestibular schwannoma include surgery and radiation therapy.

Surgery

Surgery generally results in satisfactory long-term control of vestibular schwannomas. There are three standard operative approaches.

Surgery
Retromastoid suboccipital (retrosigmoid)	The suboccipital approach can be used for any size tumor with or without attempted hearing preservation.
Translabyrinthine	The translabyrinthine approach has been recommended for acoustic tumors larger than 3 cm and for smaller tumors when hearing preservation is not an issue.
Middle fossa	The middle fossa approach is suitable for small (<1.5 cm) tumors when hearing preservation is a goal.

Radiation therapy

Radiation therapy for patients with vestibular schwannoma include stereotactic radiosurgery (SRS), stereotactic radiotherapy (SRT), and proton beam therapy, as well as conventional fractionated radiation therapy.

Radiation therapy
Stereotactic radiosurgery	SRS is a technique that utilizes multiple convergent beams to deliver a high single dose of radiation to a radiographically discrete treatment volume, thereby minimizing injury to adjacent structures. This can be accomplished with either the gamma knife or a linear accelerator. Radiosurgery is a viable treatment option for selected patients with smaller tumors (<3 cm) or for enlarging tumors in patients who are not candidates for surgery
Stereotactic radiotherapy	Fractionated SRT utilizes focused doses of radiation given over a series of treatment sessions. The intent is to reduce radiation injury to critical neural structures while preserving tumor control.
Proton beam therapy	Proton beam therapy may provide maximal local tumor control while minimizing cranial nerve injuries. The physical characteristics of the beam result in the majority of the energy being deposited at the end of a linear track (the Bragg peak), with the dose falling rapidly to zero beyond the Bragg peak. Thus, the use of proton beam therapy permits the delivery of high doses of radiation therapy to the target volume while limiting the "scatter" dose received by surrounding tissues.