Soft tissue
Peripheral nerve tumors
Schwannoma
Copyright: 2002-2019, PathologyOutlines.com, Inc.
PubMed Search: Schwannoma[TI] soft tissue free full text[sb]
See also: Ancient, Cellular, Microcystic / reticular, Pigmented, Plexiform
Peripheral nerve tumors
Schwannoma
Editorial Board Member: Michael R. Clay, M.D.
Editor-in-Chief: Debra Zynger, M.D.
Topic Completed: 1 May 2018
Minor changes: 8 December 2019
Copyright: 2002-2019, PathologyOutlines.com, Inc.
PubMed Search: Schwannoma[TI] soft tissue free full text[sb]
See also: Ancient, Cellular, Microcystic / reticular, Pigmented, Plexiform
Table of Contents
Definition / general | Essential features | Terminology | Epidemiology | Sites | Pathophysiology | Clinical features | Radiology description | Prognostic factors | Case reports | Treatment | Clinical images | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Virtual slides | Cytology description | Cytology images | Positive stains | Negative stains | Electron microscopy description | Electron microscopy images | Molecular / cytogenetics description | Videos | Differential diagnosis | Additional references | Board review style question #1 | Board review answer #1Cite this page: Abdellatif E. Schwannoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/softtissueschwannoma.html. Accessed May 30th, 2020.
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
- Slow growing tumor that very rarely undergoes malignant transformation (Am J Surg Pathol 2001;25:13)
- Malignant transformation:
- Extremely rare
- Sudden progressive increase in size is a concerning feature
- Occurs even without neurofibromatosis; tumors usually have epithelioid features and often areas of benign schwannoma (Am J Surg Pathol 2001;25:13)
- Higher risk in melanotic (pigmented) schwannoma
- Transforms to malignant peripheral nerve sheath tumor (MPNST), angiosarcoma or epithelioid malignant change (EMC)
- Most common sites are limb, limb girdles, head / neck
Case reports
- 12 year old boy with painless subconjunctival mass in the left eye (Indian J Ophthalmol 2015;63:620)
- 36 year old man with melanotic schwannoma of the L5 root (Neuroradiol J 2016;29:219)
- 56 year old woman with a large lytic lesion in her lower femur (J Med Case Rep 2017;11:147)
- 56 year old man with lower back pain and hematuria (World J Surg Oncol 2016;14:29)
- 58 year old woman with painless palpable vulvar mass (Case Rep Dermatol 2018;10:41)
- 61 year old woman with mass in right mandible (Medicine (Baltimore) 2015;94:e1974)
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
Images hosted on other servers:
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
Images hosted on PathOut server:
Fine needle aspirate biopsy
Cell block
Images hosted on other servers:
Cellular schwannoma
Positive stains
- S100 (strong and diffuse staining)
- Calretinin, CD56, SOX10, podoplanin
- Weak CD34
- EMA (capsule) highlights the perineural fibroblasts
- Other stains include laminin, type IV collagen, vimentin, CD68
Negative stains
- Keratin (cytokeratin) immunoreactivity may be seen in some cellular schwannomas, which may represent cross reactivity with GFAP (Acta Neuropathol 2012;123:295)
- Neurofilament (rare staining)
- Desmin, SMA
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
Images hosted on other servers:
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):
- 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 |
Additional references
Board review style question #1
Which of the following immunohistochemical stains best differentiates schwannoma from neurofibroma?
- Calretinin
- CK5 / 6
- MNF116
- p63
- 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.
