Schwannoma
Definition
- A benign nerve sheath tumor that is typically encapsulated and composed entirely of well-differentiated Schwann cells.
Alternate/Historical Names
- Neurilemmoma
- Neurinoma
Diagnostic Features
- Alternating areas of compact spindle cells (Antoni A) and hypocellular less orderly areas (Antoni B) are characteristic
- Nuclear palisading in Antoni A areas is nearly always present
- Verocay bodies are formed by alternating rows of palisading nuclei and intervening nuclei free stroma
- Antoni B areas have myxoid stroma with microcystic or cystic areas
- Both composed of Schwann cells
- Eosinophilic cytoplasm and indistinct cell membranes
- Tapered nuclei (as opposed to blunt ends in smooth muscle)
- May have nuclear pseudoinclusions, but nucleoli are inconspicuous
- Axons are not present within the lesion
- Neurofilament protein-immunoreactive axons are displaced to the periphery
- Nearly always strong diffuse S-100 immunoreactivity
- Usually encapsulated
- Visceral schwannomas and those occurring at mucosal sites (e.g., sinuses) may lack a capsule
- Gastrointestinal schwannomas may represent a distinct lesion and are covered separately
- Usually associated with an identifiable nerve
- Frequently seen stromal features may suggest schwannoma if present
- Hyalinzed blood vessels
- Collections of lipid-laden macrophages
- Hemosiderin
- Lymphoid aggregates
- Mitoses can usually be dismissed in an otherwise typical schwannoma
Subtypes
- Schwannoma with Degenerative Change (Ancient Schwannoma)
- Tumors with marked degenerative atypia
- Schwann cell nuclei are often large, hyperchromatic, and multilobated
- Lack mitotic figures
- Usually show other degenerative changes including cyst formation, calcification, hemorrhage, and hyalinization
- Typically large tumors of long duration
- No clinical significance
- Cellular Schwannoma
- Composed of predominantly or exclusively Antoni A areas without Verocay bodies
- Often deep (mediastinum and retroperitoneum)
- May be mitotically active, but usually <4 mits/10 HPF
- Focal necrosis may be seen in some cases
- Lacks atypia
- Increased rate of recurrence but no malignant behavior
- Melanotic (Pigmented) Schwannoma
- Schwann cells contain melanosomes and are immunoreactive with melanocytic markers (e.g., HMB-45)
- May be grossly pigmented
- Majority are highlighly cellular and contain spindled and epithelioid cells
- Often lack definite capsule, Verocay bodies, and Antoni A and B areas
- Scattered multinucleated cells are common
- Nuclei are often round
- Psammomatous melanotic schwannomas are associated with Carney complex (50%)
- May involve gi tract and heart as well as peripheral nerves
- Higher risk of malignant transformation (10%)
- Plexiform Schwannoma
- Schwannoma with plexiform, often intraneural, growth
- May not be appreciable macroscopically
- Usually superficial
- Often cellular
- Majority Antoni A, infrequent Antoni B
- Associated with NF2 and schwannomatosis syndrome
- Not associated with neurofibromatosis 1
- No behavior difference from usual schwannomas
- Epithelioid Schwannoma
- Consist of predominantly round, epithelioid Schwann cells arranged singly and in clusters
- Schwann cell origin confirmed by strong, diffuse S-100 immunoreactivity
- Antoni A and B areas and Verocay bodies may be absent or only focal
- Often subcutaneous
- Main differential diagnosis is MPNST, small size, sharp circumscription, bland morphology, and low proliferative activity favor epithelioid schwannoma
- No clinical significance
Clinical
- WHO grade 1
- 90% of schwannomas are solitary and sporadic
- Transformation to a malignant peripheral nerve sheath tumor is extremely rare
- May compress or erode nearby structures including bone
- Neurofibromatosis type 2 (NF2) is an autosomal dominant disease characterized by bilateral vestibular schwannomas
- May include plexiform schwannomas
- Other CNS tumors often occur including: schwannomas of other cranial nerves, meningiomas, ependymomas, and gliomas
- Schwannomatosis presents with multiple schwannomas involving skin or soft tissue
- Often painful
- May be sporadic or inherited
- May include plexiform schwannomas
Differential Diagnosis
- Neurofibroma
- Solitary Circumscribed (Palisaded Encapsulated) Neuroma
- Traumatic Neuroma
- MPNST
- Leiomyoma/Leiomyosarcoma
- Meningioma
- Plexiform neurofibroma
- Metastatic melanoma
- Pigmented neurofibroma
Immunohistochemical |
||
S-100 and Sox10 |
Moderate positivity |
Strong, diffuse positivity |
CD34 |
Moderate |
Scattered cells in Antoni B areas |
Neurofilament (and Bielshowsky) |
Stains entrapped axons within lesion |
Stains peripherally located axons of parent nerve |
Factor XIIIa |
Moderate |
Negative to focal |
Calretinin |
Negative to focal |
Moderate |
GFAP |
Variable, weak |
Variable, moderate |
- Only the neurofilament and Bielshowsky stains are very helpful
- S100 and SOX10 stain classic lesions with different intensities because of their differing cellularities
- They are not very helpful for distinguishing problematic examples of these two lesions
Schwannoma |
|
Uniphasic, Low to moderate cellularity |
Biphasic (cellular Antoni A & hypocellular Antoni B), some hypercellularity |
Non-encapsulated |
Encapsulated |
Random pattern, only rare palisading, no well formed Verocay bodies |
Palisading and Verocay bodies |
Nerve often not identified |
Nerve often identifiable |
If nerve identified: incorporates nerve, axons often present in lesion |
Eccentric to nerve, axons generally absent within lesion |
Seldom cystic |
Occasionally cystic |
NF1-associated; Not NF2 |
Not NF1-associated; Occasionally NF2 |
Schwannoma |
|
Can occur anywhere |
90% of lesions affect the face |
Uncommon in the dermis |
Common in the dermis |
Completely surrounded by perineurial capsule |
Peripheral delicate EMA positivity, indistinct capsule |
Can be GFAP positive |
GFAP negative |
Axons, when present, are typically peripheral / subcapsular |
Axons throughout the lesion |
Feature Antoni A and Antoni B areas |
Absent |
Palisading with frequent Verocay bodies |
Indistinct palisading, no well formed Verocay bodies |
| Schwannoma | |
No history of prior trauma or surgery |
History of trauma or surgery |
Random proliferation of Schwann cells and axons |
Numerous well formed small nerve twigs |
Circumscribed/encapsulated |
Ill-defined |
Antoni A, Antoni B areas, palisading and Verocay bodies |
Absent |
Contain rare axons (predominantly subcapsular) |
Contain abundant haphazardly arranged axons |
Conventional Schwannoma |
Cellular Schwannoma |
|
Biphasic, Antoni A and B areas |
Uniform, Hypercellular (Majority Antoni A) |
Hypercellular |
Small nuclei |
Small nuclei |
Nuclei typically 3x normal size |
Variable chromatin |
May show hyperchromasia |
Pronounced hyperchromasia |
Verocay bodies, hyalinized vessels, lipid laden histocytes, lymphoid infiltrates |
Hyalinized vessels, lipid-laden histiocytes, lymphocytic infiltrates |
All absent |
Mitoses usually rare |
Few mitoses (usu. <4/10 HPF) |
Very mitotically active (usu. >10/10 HPF) |
Strong, diffuse S-100 immunoreactivity |
Strong, diffuse S-100 immunoreactivity |
S100 neg to weak, patchy |
Rare necrosis |
Poorly demarcated rare foci of necrosis without palisading |
Geographic necrosis |
Globoid, encapsulated |
Globoid, encapsulated |
Fusiform to globoid with infiltration |
Rare divergent differentiation |
Rare divergent differentiation |
Occasional divergent differentiation (e.g., rhabdomyosarcoma in malignant triton tumor) |
Schwannoma with Degenerative Change (Ancient Schwannoma) |
|
Occasional bizarre, hyperchromatic cells, other cells cytologically benign |
Uniform, cytologically malignant features |
Normal cellularity |
Marked cell crowding |
Low mitotic activity |
High mitotic activity |
Cellular Schwannoma |
Leiomyoma / Leiomyosarcoma |
Fibrous capsule |
Unencapsulated |
Associated with nerve |
No association with nerves |
Tapered nuclei |
Nuclei with blunt ends |
S100 immunoreactive; Smooth muscle actin negative |
Smooth muscle actin immunoreactive; S100 negative |
Plexiform Schwannoma |
|
Cells separated by collagen bundles |
Infrequent extracellular collagen |
Hypocellular with abundant mucinous matrix |
Infrequent hypocellular Antoni B areas (majority entirely hypercellular Antoni A) |
Associated with NF1 |
Associated with NF2 |
Melanotic (pigmented) Schwannoma |
Metastatic Melanoma |
Low-grade cytology |
Frequently cytologically malignant |
Occasional psammoma bodies |
No psammoma bodies |
Frequent dendritic-shaped cells |
Rare-dendritic shaped cells |
Melanotic (pigmented) Schwannoma |
Pigmented Neurofibroma |
Localized |
Usually diffuse |
Macroscopic pigmentation |
Microscopic pigmentation |
May contain psammoma bodies |
No psammoma bodies |
Round nuclei with delicate chromatin and central nucleolus |
Small, elongate nuclei |
Bibliography
- Goldblum, J.R., Folpe, A. L., Weiss, S.W., Enzinger and Weiss's Soft Tissue Tumors. 6th ed 2014. Philadelphia, PA: Mosby Elsevier.
- Scheithauer BW, Woodruff JM, Erlandson RA. Tumors of the Peripheral Nervous System, Atlas of Tumor Pathology, AFIP Third Series, Fascicle 24, 1999.
- Louis, D.N., Ohgaki, H., Wiestler, O.D., Cavenee, W.K. eds. WHO Classification of Tumours of the Central Nervous System, Fourth Edition. IARC Press: Lyon 2004
- Kindblom LG, Meis-Kindblom JM, Havel G, Busch C. Benign epithelioid schwannoma. Am J Surg Pathol. 1998 Jun;22(6):762-70.
- Fine SW, McClain SA, Li M. Immunohistochemical staining for calretinin is useful for differentiating schwannomas from neurofibromas. Am J Clin Pathol. 2004 Oct;122(4):552-9.
- Hirose T, Tani T, Shimada T, Ishizawa K, Shimada S, Sano T. Immunohistochemical demonstration of EMA/Glut1-positive perineurial cells and CD34-positive fibroblastic cells in peripheral nerve sheath tumors. Mod Pathol. 2003 Apr;16(4):293-8.
- Gray MH, Smoller BR, McNutt NS, Hsu A. Immunohistochemical demonstration of factor XIIIa expression in neurofibromas. A practical means of differentiating these tumors from neurotized melanocytic nevi and schwannomas. Arch Dermatol. 1990 Apr;126(4):472-6.
- Kawahara E, Oda Y, Ooi A, Katsuda S, Nakanishi I, Umeda S. Expression of glial fibrillary acidic protein (GFAP) in peripheral nerve sheath tumors. A comparative study of immunoreactivity of GFAP, vimentin, S-100 protein, and neurofilament in 38 schwannomas and 18 neurofibromas. Am J Surg Pathol. 1988 Feb;12(2):115-20.
- Nonaka D, Chiriboga L, Rubin BP. Sox10: a pan-schwannian and melanocytic marker. Am J Surg Pathol. 2008 Sep;32(9):1291-8.
- Agaimy A, Buslei R, Coras R, Rubin BP, Mentzel T. Comparative study of soft tissue perineurioma and meningioma using a five-marker immunohistochemical panel. Histopathology. 2014 Jul;65(1):60-70.
Kurt Schaberg MD
Donald Born MD
Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342
Original posting : 9/2/15
