Multiple synchronous sites of origin of vestibular schwannomas in neurofibromatosis Type 2

Abstract

Background: Neurofibromatosis Type 2 (NF2) is a dominantly inherited tumour syndrome with a phenotype which includes bilateral vestibular (eighth cranial nerve) schwannomas. Conventional thinking suggests that these tumours originate at a single point along the superior division of the eighth nerve.

Methods: High resolution MRI was performed in children genetically proven to have NF2. The superior vestibular nerve (SVN) and inferior vestibular nerve (IVN) were visualised along their course with points of tumour origin calculated as a percentage relative to the length of the nerve.

Results: Out of 41 patients assessed, 7 patients had no identifiable eighth cranial nerve disease. In 16 patients there was complete filling of the internal auditory meatus by a tumour mass such that its specific neural origin could not be determined. In the remaining 18 cases, 86 discrete separate foci of tumour origin on the SVN or IVN could be identified including 23 tumours on the right SVN, 26 tumours on the right IVN, 18 tumours on the left SVN and 19 tumours on the left IVN.

Discussion: This study, examining the origins of vestibular schwannomas in NF2, refutes their origin as being from a single site on the transition zone of the superior division of the vestibular nerve. We hypothesise a relationship between the number of tumour foci, tumour biology and aggressiveness of disease. The development of targeted drug therapies in addition to bevacizumab are therefore essential to improve prognosis and quality of life in patients with NF2 given the shortcomings of surgery and radiation treatments when dealing with the multifocality of the disease.

Keywords: Cancer: CNS; Cancer: head and neck; Clinical genetics; Diagnostics; Neurology.

Figure 1

T1 spin echo sequences (axial—A and coronal—B), both with fat saturation and contrast administration showing the typical imaging phenotype of a patient with neurofibromatosis Type 2 . There are bilateral vestibular schwannomas that have a component within the internal auditory meatus (dashed arrow) as well as within the cerebellopontine angle (CPA, solid arrows). These components are in continuity and thought to represent one tumour mass. Further discrete disease is seen in the right vestibule (dotted arrow). The coronal sequence again shows the bilateral CPA angle components of the tumours compressing the brainstem (white arrows).

Figure 2

Coronal post contrast gradient echo sequence (A) in a 9-month-old child with failed hearing assessment demonstrates separate nodules of enhancement on the right superior vestibular nerve (SVN) and inferior vestibular nerve (IVN) (solid arrows) and the left (dashed arrows) SVN and IVN. The same sequence in the patient aged 2.5 years (B) shows the right side tumour foci to have grown, and while still being distinct on the nerve roots of origin, they are starting to collide/merge. The left sided appearances are static. By 4.5 years of age, the axial heavily weighted high-resolution T2 of the internal auditory meatus (IAM) (C) shows that there is now a discrete right sided IAM mass (solid arrow). The appearances of the left sided nerve roots in the IAM appear normal on this sequence (dotted arrow). The coronal gradient echo post contrast sequences (D and E) taken at the same age demonstrate once again a static appearance to the tumour foci on the left side (panel D, dashed arrows) while the right sided tumour foci have now coalesced into one tumour mass (panel E, solid arrow).

Figure 3

Graphical comparison of the sites of origin of tumours on the right and left superior vestibular nerve (SVN) (A), right and left inferior vestibular nerve (IVN) (B) and amalgamated results of all tumour sites as a percentage of total number of tumours (C). Tumours grouped and plotted as quartiles along the length of the SVN and IVN within the internal auditory meatus (IAM). A Kolmogorov–Smirnov test was significant for the SVN tumours (p<0.001) but not for the IVN tumours (p=0.11), both as two-sided tests, which indicates a statistical predominance for a tumour position towards the fundus of the IAM on the SVN alone.

Figure 4

Temporal bone histology, H&E stain showing the multicentric origin of schwannomas in the internal auditory canal and labyrinth in a patient with neurofibromatosis Type 2. (A) An axial section of the right temporal bone through the cochlea (C). A large schwannoma is seen in the internal auditory canal (IAC) and a separate schwannoma arising from the saccular macula (SM) within the vestibule medial to the stapes footplate (FP). (B) An axial section through the right temporal bone at the level of the round window (RW). A small intracochlear schwannoma (S) is present within the fluid space of the scalatypmani (ST) and another schwannoma is present at the ampullated end of the posterior semicircular canal (PSCA). An additional, separate schwannoma arises within the descending segment of the facial nerve (FN).