Soft tissue
Peripheral nerve tumors
Schwannoma

Author: Engy Abdellatif, M.D., Ph.D.
Senior Author: Dia Eldin Kamel, M.D., Ph.D.
Editorial Board Member Review: Michael R. Clay, M.D.
Editor-in-Chief Review: Debra Zynger, M.D.

Revised: 13 September 2018, last major update May 2018

Copyright: (c) 2002-2018, PathologyOutlines.com, Inc.

PubMed Search: Schwannoma[TI] soft tissue free full text[sb]

See also: Ancient, Angiosarcoma, Cellular, Epithelioid, Microcystic / reticular, Pigmented, Plexiform, Psammomatous melanotic

Cite this page: Abdellatif, E. Schwannoma. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/softtissueschwannoma.html. Accessed September 26th, 2018.
Definition / general
  • Benign nerve sheath tumor arising from differentiated Schwann cells
Essential features
  • Biphasic tumor with highly ordered cellular component (Antoni A) that palisades (Verocay bodies) plus myxoid hypocellular component (Antoni B)
  • Usually associated with an identifiable nerve
  • Strong immunoreactivity for S100 (Am J Pathol 1982;106:261)
Terminology
  • Also known as neurilemoma and neurinoma
Epidemiology
  • All ages can be affected
  • Most commonly 20 - 50 years old
  • M = F
  • 90% are sporadic, 3% with neurofibromatosis type 2, 2% with schwannomatosis, 5% with meningiomatosis with or without neurofibromatosis type 2
Sites
  • More frequently on the limbs with a predilection to the upper limbs, followed by the head and neck area, including the oral cavity, orbit and salivary glands
  • Deeply seated tumors are mainly in the posterior mediastinum and retroperitoneum
  • Other areas include posterior spinal roots, bone, gastrointestinal tract, pancreas, liver, thyroid, adrenal glands and lymph nodes
  • Rare sites include penis and vulva (Urol Ann 2017;9:301, World J Surg Oncol 2015;13:139)
Pathophysiology
  • May occur spontaneously
  • Can occur in familial tumor syndromes such as neurofibromatosis type 2 (NF2), schwannomatosis or Carney complex (StatPearls: Carney Complex [Accessed 13 August 2018])
  • Loss of function of the tumor suppressor gene merlin (schwannomin)
    • Direct genetic change involving the NF2 gene on chromosome 22 or secondarily to merlin inactivation
    • Can occur in NF2 and spontaneous schwannomas
    • Can cause other neoplasms including meningioma, mesothelioma, glioma multiforme and carcinomas of breast, colorectum, kidney (clear cell type), liver, prostate and skin
Clinical features
  • Pain and neurological symptoms are uncommon unless the tumor is large
  • Tumor waxes and wanes in size, which may be related to the amount of cystic degeneration it contains (J Lab Physicians 2013;5:60)
Radiology description
  • Well circumscribed masses which displace adjacent structures without direct invasion
  • Cystic and fatty degeneration can be seen
  • Hemorrhage and calcification are less frequent
  • Cystic degeneration or hemorrhage can be seen as areas of heterogeneity in large tumors (Radiographics 2004;24:1477, Radiographics 1999;19:1253)
Prognostic factors
Case reports
Treatment
  • Surgical excision is the treatment of choice with rare recurrence
  • Schwannomas do not infiltrate the parent nerve so they can usually be separated from it
  • Delayed facial nerve palsy can occur after surgical removal of vestibular schwannoma (Neurosurgery 2016;78:251)
Clinical images

Images hosted on PathOut server:

Contributed by Mark R. Wick, M.D.

Skin



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Scalp

Gross description
  • Usually solitary
  • Capsule derived from the epineurium
  • Nerve of origin may be present at the periphery - does not penetrate substance of tumor
  • Dumbbell tumor: in posterior mediastinum, originates from or extends into vertebral canal
  • Small tumors may be difficult to differentiate from neurofibroma due to the fusiform appearance
  • Large tumors have an eccentric position in relation to the nerve
  • Cut section is light tan and glistening and may show yellow patches
  • Large tumors may be cystic
  • Areas of hemorrhage may be seen (Goldblum: Enzinger and Weiss's Soft Tissue Tumors, 6th Edition, 2013)
Gross images

Images hosted on PathOut server:

Contributed by Mark R. Wick, M.D.

Schwannoma

Microscopic (histologic) description
  • Biphasic: compact hypercellular Antoni A areas and myxoid hypocellular Antoni B areas (may be absent in small tumors)
  • Nuclear palisading around fibrillary process (Verocay bodies) is often seen in cellular areas
  • Large, irregularly spaced vessels are most prominent in Antoni B areas
  • Cells are narrow, elongated and wavy with tapered ends interspersed with collagen fibers
  • Tumor cells have ill defined cytoplasm, dense chromatin
  • Often displays degenerative nuclear atypia (ancient change)
  • Rare mitotic figures
  • Blood vessels may show gaping tortuous lumina having thickened hyalinized walls; may have thrombi
  • Dilated vessels surrounded by or invested by hemorrhage can be seen
  • May have foamy macrophages
  • Lymphoid aggregates
  • Amianthoid fibers or collagenous spherules: large nodular masses of collagen with radiating edges
  • No axons except where nerve is attached
  • Malignant transformation can show malignant epithelioid cells and may rarely show divergent differentiation as angiosarcoma-like areas

  • Variants include:
    • Ancient schwannoma: degenerative change such as hyalinization
    • Plexiform schwannoma: must differentiate from conventional schwannomas, which can be resected with minimal damage to nerve fascicles; however, plexiform schwannomas involve multiple fascicles, requiring complete resection to prevent recurrence
    • Cellular schwannoma: common location is the paravertebral region; hypercellular areas composed entirely of Antoni A tissue and devoid of Verocay bodies; pseudoglandular elements can be noted
    • Epithelioid schwannoma: moderate amount of cytoplasm in Schwann cells
    • Microcystic / reticular variant (Am J Surg Pathol 2008;32:1080):
      • Has a preference for the GI tract and rarely in subcutaneous soft tissue
      • Formed of strands of bland spindle cells in a myxoid background, with various proportions of microcystic structures
      • No alternating Antoni A, Antoni B areas or Verocay bodies
    • Melanotic (pigmented) schwannoma:
      • Contains pigmented cells with melanosomes that express melanocytic markers
      • Usually arises around the spinal nerve roots
      • May show sheets of adipose-like cells and psammoma bodies
      • Large, vesicular nuclei with macronucleoli, high mitotic activity and necrosis portend worse prognosis
      • Positive for S100, HMB45, MelanA
      • GFAP and neurofilament protein are sometimes positive
      • Loss of PRKAR1A expression may indicate a causal relationship to Carney complex
Microscopic (histologic) images

Images hosted on PathOut server:

Contributed by Dia Eldin Kamel, M.D., Ph.D.

Schwannoma from right lateral border of tongue

S100+

Desmin-

SMA-


Left gluteus maximus schwannoma (H&E)

Ancient changes

S100+


Schwannoma from the dorsum of the left hand (H&E)

Plexiform schwannoma from the periosteum of the left tibia (H&E)

Virtual slides

Images hosted on other servers:

Schwannoma:

13 year old girl with cystic index finger lesion

45 year old man with thigh lump: H&E, S100

53 year old man with chest wall lump

77 year old woman with small tumor in stomach wall


Ancient schwannoma:

55 year old man with retroperitoneal tumor

Cytology description
  • Aggregates of spindled cells with indistinct cytoplasm and elongated nuclei with blunt pointed ends (World J Gastroenterol 2011;17:3459)
  • Ancient changes can show nuclear pleomorphism and occasionally nuclear inclusions
Cytology images

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Fine needle aspirate biopsy

Cell block



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Cellular schwannoma

Positive stains
Negative stains
Electron microscopy description
  • Basal lamina consisting of electron dense material coats the surface of Schwann cells (Cancer 1981;48:1381, Acta Cytol 1983;27:441)
  • Elongated cells with continuous basal lamina, thin cytoplasmic processes, aggregates of intracytoplasmic microfibrils, peculiar intracytoplasmic lamellar bodies, extracellular long spacing collagen
  • Basal lamina is fragmented in Antoni B areas, suggesting that these areas are degenerated Antoni A areas
  • Contains lipid
  • Has characteristic Luse bodies (collagen fibers with abnormally long spacing exceeding 100 nm between electron-dense bands)
Electron microscopy images

Images hosted on PathOut server:

Various images



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Cellular schwannoma

Molecular / cytogenetics description
  • May occur spontaneously
  • Can occur in familial tumor syndromes such as neurofibromatosis type 2 (NF2), schwannomatosis or Carney complex
  • Can be caused by loss of function of the tumor suppressor gene, merlin (schwannomin)
  • Merlin acts as a tumor suppressor gene; overexpression can hinder cell proliferation and the changes induced by oncogenes; its downregulation leads to neoplastic transformation
  • Mutations affecting SMARCB1 have a role in the pathogenesis of a small subset of spinal schwannomas and biallelic inactivation of SMARCB1 may cooperate with deficiency of NF2 function (J Neurooncol 2018;137:33)
Videos

Benign soft tissue tumors lecture

Schwannoma (neurilemmoma)

Differential diagnosis
  • Leiomyoma and leiomyosarcoma:
    • May show palisading and extensive degenerative changes in the form of hyalinization, calcification, myxoid changes and ancient nuclear atypia
    • Cells are elongated with eosinophilic or occasional fibrillar cytoplasm with distinct cell membranes
    • S100-
    • SMA+ and desmin+
    • Ultrastructurally evidence of leiomyogenic differentiation
  • Malignant melanoma:
    • Lamin and collagen type IV are positive in melanotic schwannoma, can be used to differentiate between melanotic schwannoma and malignant melanoma
    • HMB45 and MelanA are positive in melanoma and negative in schwannoma
  • Malignant melanoma with neural differentiation (neurotized melanoma) (Am J Dermatopathol 2014;36:e5):
    • Preference for the head and neck area
    • Often amelanotic
    • Biphasic consisting of malignant melanoma and mature appearing neural component
    • MelanA is positive in the melanoma component and negative in the neural component
  • Malignant peripheral nerve sheath tumor (MPNST):
    • Infiltrative growth
    • Hypercellular, pleomorphic nuclei and high mitotic activity
    • Areas of geographic necrosis can show divergent differentiation
    • Patchy S100 or negative
  • Neurofibroma:
    • Usually lacks capsule, formed of spindle cells, shredded carrot collagen and mast cells
    • Hypocellular, myxoid areas without hypercellular areas
    • Weaker S100, focal calretinin, stronger CD34, factor XIIIa+
    • See table below
  • Pleomorphic hyalinizing angiectatic tumor (PHAT) (J Clin Diagn Res 2017;11:ED15):
    • Nonencapsulated with infiltrative border
    • Large ectatic vascular spaces with perivascular hyalinization
    • Fibrin in and around vessels
    • Negative for S100 and CD31, positive for CD34
  • Solitary circumscribed neuroma (palisaded encapsulated neuroma):
    • Encapsulated dermal or subcutaneous tumor which may be seen with club-like extension in the subcutaneous tissue
    • May show nuclear palisading
    • Silver stains show the axons traversing the Schwann cells; however, they are near the capsule in schwannomas
    • Peripheral delicate EMA positivity

Schwannoma Neurofibroma
Epidemiology Age 20 - 50, M = F Age 20 - 40, M = F
May occur in younger age
Etiology Sporadic but may occur in NF2 > NF1 Sporadic, some in NF1
Macroscopic Encapsulated Usually lacks capsule
Microscopic Antoni A and Antoni B
Alternating hypercellular and hypocellular areas 
Spindle cells, shredded carrot collagen, mast cells
Hypocellular, myxoid areas without hypercellular areas 
Plexiform variant Less common More common
Immunohistochemistry S100: almost diffuse
Calretinin: stronger
CD34: scattered
Factor XIIIa: negative / focal
S100: weaker
Calretinin: focal
CD34: stronger
Factor XIIIa: stronger
Malignant transformation  Extremely rare Rare but can occur in 2 - 3% of NF1 patients
Board review question #1
Which of the following immunohistochemical stains best differentiates schwannoma from neurofibroma?

  1. Calretinin
  2. CK5 / 6
  3. MNF116
  4. p63
  5. S100
Board review answer #1
E. S100 shows strong and almost diffuse positivity with schwannoma in contrast to neurofibroma, which variably expresses the antigen due to the presence of other cell populations.