Schwannoma pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:  ; Maneesha Nandimandalam, M.B.B.S.[2]

Overview

Schwannomas may arise sporadically or in association with Neurofibromatosis type 2 as a result of mutations involving merlin protein. Loss of function of a tumor suppressor gene called merlin gene is noted commonly. Schwannomas are composed of spindle cells which demonstrate two growth patterns Antoni type A and Antoni type B. Antoni type A pattern in which elongated cells are densely packed and arranged in fascicles. Palisades are sometimes seen, when prominent these form verocay bodies. Antoni type B pattern cells are less compact and are prone to cystic degeneration. Schwannoma variants include ancient schwannoma, cellular schwannoma, melanotic schwannoma, plexiform schwannoma. Immunohistochemistry positive for S100, collagen IV, CD34, neurofilament protein, podoplanin, calretinin, Sox10. Associated conditions include neurofibromatosis type 2, schwannomatosis, carney's complex.

Pathophysiology

Pathogenesis

• Unilateral schwannomas are usually sporadic.
• Bilateral schwannomas are associated with Neurofibromatosis type 2.

• Neoplastic proliferation of schwann cell differentiation leading to tumor cells growing diffusely within and along the nerves affecting the neural elements.
• Those associated with Neurofibromatosis type 2 are due to deletion of NF2 locus (22q12.2) which encodes a tumor suppressor protein, merlin (schwannomin).
• Loss of merlin expression affects the cell cycle and mitogenic signal pathways.

Genetics

• Loss of function of a tumor suppressor gene called merlin gene, either by:

1. Direct genetic change involving the NF2 gene on chromosome 22
2. Secondarily to merlin inactivation
   

Associated Conditions

• Neurofibromatosis type 2 (NF2)
• Schwannomatosis
• Carney's complex

Gross and Microscopic Pathology

Microscopic appearance

• Conventional schwannomas are composed of spindle cells which demonstrate two growth patterns: Antoni type A and Antoni type B.
• Antoni type A pattern: elongated cells are densely packed and arranged in fascicles. Palisades are sometimes seen; when prominent these form Verocay bodies.
• Antoni type B pattern cells are less compact and are prone to cystic degeneration.

Microscopic images of the ancient schwannoma: spindle cells arranged in short fascicles with focal vague Verocay bodies (haematoxylin and eosin [H&E] stain, 100x magnification) (top left), schwannoma with focal collection of haemosiderin laden macrophages (H&E stain, 100x magnification) (top right), cholesterol clefts in ancient schwannoma (H&E stain, 100x magnification) (bottom left) and spindle cells immunoreactive for S100 protein (nuclear positivity) (indirect immunoperoxidase staining, 100x magnification) (bottom right),Sayed SI, Rane P, Deshmukh A, et al. Ancient schwannoma of the parapharynx causing dysphagia: a rare entity. Ann R Coll Surg Engl. 2012;94(7):e217–e220. doi:10.1308/003588412X13373405385737,https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3954264/

Variants

Schwannoma variants include:

• ancient schwannoma
• cellular schwannoma
  • predominantly composed of Antoni A tissue
  • no Verocay bodies
  • most commonly found in a paravertebral location, or trigeminal nerves (CN V)
• melanotic schwannoma: dense melanin pigment
• plexiform schwannoma
  • usually arise from skin or subcutaneous tissues
  • usually diagnosed at birth or childhood
  • usually sporadic, but rarely associated with NF2
  • should not be confused with plexiform neurofibromas
    • associated with NF1
    • may undergo malignant change

Immunohistochemistry

Positive for :

• S100
• Collagen IV
• CD34
• Neurofilament protein
• Podoplanin
• Calretinin
• Sox10

Negative for:

• EMA