Pathology of vestibular schwannoma

Pathology of vestibular schwannoma

Acknowledegement: Dr Louis de Jager and Dr Kathy Taylor from Pathcare for images and review

Macroscopic view of a vestibular schwannoma

A vestibular schwannoma, also known as an acoustic neuroma, is a benign tumour that typically arises from the Schwann cells of the vestibular portion of the eighth cranial nerve (1). From a macroscopic perspective, a vestibular schwannoma appears as a well-defined, round or oval-shaped mass near the internal auditory canal(2). The tumour usually presents as a white to pinkish, firm mass ranging from a few millimetres to several centimetres in diameter.

 

Vestibular schwannoma/ acoustic neuroma

On the surface of the tumour, there may be areas of cystic degeneration or haemorrhage, giving it a variegated appearance. In larger tumours, compression of surrounding structures such as the brainstem, cerebellum, and cranial nerves may be seen. Additionally, some vestibular schwannomas may have a characteristic ” mushroom” appearance on imaging studies, with the tumour tapering to a point as it extends towards the internal auditory canal (3).

Mushroom appearance of vestibular schwannoma on MRI

Microscopic view of a vestibular schwannoma

Nils Ragnar Eugène Antoni, a Swedish neurologist and researcher working in the Royal Neurologic Clinic of Stockholm in 1920 under the supervision of the neuropathologist Frithiof Lennmalm, described two distinct patterns of cellular architecture in peripheral nerve sheath tumours, later known as Schwannomas (4). Antoni went on to become a professor of neurology at the Karolinska Institute in Stockholm.

Under the microscope, a vestibular schwannoma typically has two distinct regions: Antoni A and Antoni B.

Antoni A

Antoni A areas are histological patterns commonly found in vestibular schwannomas and benign vestibular nerve tumours (5). These areas are characterised by highly cellular zones with compactly arranged Schwann cells and densely packed collagen fibres. These areas are often associated with rapid tumour growth and increased cell proliferation (more aggressive growth).  They may also contain Verocay bodies, unique structures formed by elongated Schwann cell nuclei arranged in parallel rows within a background of eosinophilic cytoplasm.

Cellular Antoni A area demonstrating Verocay bodies (circle) and palisading of nuclei (arrow)

Antoni B

On the other hand, the Antoni B area is composed of loose, disorganised tissue with a more myxoid appearance. This region often contains many hyalinised blood vessels and stroma, imparting a softer consistency.  Antoni B areas may indicate a less aggressive or non-growing tumour. It may also relate to vestibular weakness (6).

The presence of Antoni B areas in vestibular schwannomas is also associated with decreased cellularity, degeneration, and cyst formation within the tumour.

Less cellular, Antoni B areas

SOX10 immunohistochemical stain of a vestibular schwannoma

SOX10 is a protein (transcription factor) expressed by Schwann cells. In the case of vestibular schwannoma, the SOX10 immunohistochemical stain is used to help differentiate Schwann cells from other cell types (7).

SOX10 is involved in developing and maintaining Schwann cells, which are the cells responsible for forming the myelin sheath around nerves. The tumour primarily comprises Schwann cells in vestibular schwannoma, making the SOX10 stain a valuable tool in confirming the diagnosis. By highlighting the presence of SOX10 protein in the tumour cells, pathologists can accurately identify the tumour as a vestibular schwannoma.

In the following picture, the brown colour is due to SOX10 nuclear staining.

SOX10 immunohistochemical stain. Diffuse nucleur staining of neoplastic cells

“Ancient” change in a vestibular schwannoma

Over time, microscopic “ancient” change of vestibular schwannoma can occur where the tumour becomes more fibrous and less cellular. This can lead to the formation of areas of calcification, cystic degeneration, and hyalinisation within the tumour (8,9,10)).  Individual larger, atypical cells (due to degenerative change) are also frequently observed. Additionally, the tumour may also show signs of chronic inflammation and scarring. These changes can impact the overall appearance and composition of the vestibular schwannoma, making it appear less cellular compared to a “younger” tumour.

Large cell with a hyperchromatic, atypical nucleus, indicative of “ancient” change

References

1. Brodhun M, Stahn V, Harder A. Pathogenese und Molekularpathologie des Vestibularisschwannoms [Pathogenesis and molecular pathology of vestibular schwannoma]. HNO. 2017 May;65(5):362-372. German. doi: 10.1007/s00106-016-0201-3. PMID: 27421984.

2. Hilton DA, Hanemann CO. Schwannomas and their pathogenesis. Brain Pathol. 2014 Apr;24(3):205-20. doi: 10.1111/bpa.12125. Epub 2014 Feb 25. PMID: 24450866; PMCID: PMC8029073.

3. Gaillard F, Mahmoud Q, Bell D, et al. Vestibular schwannoma. Reference article, Radiopaedia.org (Accessed on 10 Jul 2024) https://doi.org/10.53347/rID-839

4. Hannan CJ, Lewis D, O’Leary C, Donofrio CA, Evans DG, Stapleton E, Freeman SR, Lloyd SK, Rutherford SA, Hammerbeck-Ward C, Brough D, Allan SM, Coope D, King AT, Pathmanaban ON. Beyond Antoni: A Surgeon’s Guide to the Vestibular Schwannoma Microenvironment. J Neurol Surg B Skull Base. 2020 Sep 10;83(1):1-10. doi: 10.1055/s-0040-1716688. PMID: 35155063; PMCID: PMC8824628.

5. Nager GT. Acoustic neurinomas. Acta Otolaryngol. 1985 Mar-Apr;99(3-4):245-61. doi: 10.3109/00016488509108905. PMID: 3874515.

6. Stipkovits EM, Graamans K, Jansen GH, Velthof MA. Acoustic neuroma: predominance of Antoni type B cells in tumors of patients with vestibular paresis. Otol Neurotol. 2001 Mar;22(2):215-7. doi: 10.1097/00129492-200103000-00017. PMID: 11300272.

7. Doddrell RD, Dun XP, Shivane A, Feltri ML, Wrabetz L, Wegner M, Sock E, Hanemann CO, Parkinson DB. Loss of SOX10 function contributes to the phenotype of human Merlin-null schwannoma cells. Brain. 2013 Feb;136(Pt 2):549-63. doi: 10.1093/brain/aws353. PMID: 23413263; PMCID: PMC3572932.

8. Zhang Y, Yu J, Qu L, Li Y. Calcification of vestibular schwannoma: a case report and literature review. World J Surg Oncol. 2012 Oct 2;10:207. doi: 10.1186/1477-7819-10-207. PMID: 23031739; PMCID: PMC3499265.

9. Mehrotra N, Behari S, Pal L, Banerji D, Sahu RN, Jain VK. Giant vestibular schwannomas: focusing on the differences between the solid and the cystic variants. Br J Neurosurg. 2008 Aug;22(4):550-6. doi: 10.1080/02688690802159031. PMID: 18803080.

10. Takeuchi Y, Arakawa Y, Yokoo H, Mikami Y, Terada Y, Yoshida K, Miyamoto S, Haga H. Intra-cerebellar schwannoma with various degenerative changes: a case report and a systematic review. BMC Neurol. 2022 Feb 24;22(1):66. doi: 10.1186/s12883-022-02596-3. PMID: 35209854; PMCID: PMC8867888.