Schwannoma
Definition
A benign nerve sheath tumor that is typically encapsulated and composed entirely of well-differentiated Schwann cells.
Alternate/Historical Names
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
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 Stain
Neurofibroma
Schwannoma
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
Neurofibroma
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
Solitary Circumscribed (Palisaded Encapsulated) Neuroma
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 Traumatic Neuroma
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
MPNST
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)
MPNST
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
Cellular Schwannoma
Meningioma
Associated with nerve
Associated with dura
Enlarges spinal foramen
Rarely enlarges foramen
Only occasional, vague whorls
Whorls more numerous and well-formed
Rare psammoma bodies (only in melanotic)
Frequent psammoma bodies
Strong S-100 immunoreactivity
Infrequent, patchy S-100 staining
Infrequent EMA immunoreactivity
Cytoplasmic EMA immunoreactivity
Plexiform Neurofibroma
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
Original posting : 9/2/15
