Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Diagnosis | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Clinical images | Gross description | Gross images | Frozen section description | Frozen section images | Microscopic (histologic) description | Microscopic (histologic) images | Virtual slides | Cytology description | Cytology images | Positive stains | Negative stains | Molecular / cytogenetics description | Videos | Sample pathology report | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Sanchez S, Cimino-Mathews A. Schwannoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/breastschwannoma.html. Accessed December 4th, 2024.
Definition / general
- Breast schwannomas are uncommon benign peripheral nerve sheath tumors composed of Schwann cells
- Breast schwannomas resemble those of other anatomic sites but they pose a diagnostic pitfall with other breast spindle cell tumors
Essential features
- Majority present clinically as a superficial palpable breast mass but may be detected on screening mammography
- May be excised if symptomatic and not known to recur
- Histology similar to other anatomic sites: bland spindle cells with wavy nuclei, nuclear palisading (Verocay bodies), variably hypercellular (Antoni A) and hypocellular (Antoni B) areas, myxoid stroma, hyalinized vessels and cystic degeneration (variable)
- Immunophenotype similar to other anatomic sites: diffuse and strong labeling for S100 and SOX10
- Notable diagnostic pitfalls in the breast: myofibroblastoma, particularly the palisaded variant and fascicular pseudoangiomatous stromal hyperplasia (PASH)
Terminology
- Not recommended: neurilemmoma
ICD coding
- ICD-O: 9560/0 - schwannoma, NOS
- ICD-11: 2F30.Y & XH98Z3 - other specified benign neoplasm of breast & schwannoma, NOS
Epidemiology
- Adults
- M = F
- May be seen in neurofibromatosis type 2, schwannomatosis and Carney complex (StatPearls: Vestibular Schwannoma [Accessed 31 October 2024])
Sites
- Breast (2.6%): may involve dermis, subcutaneous tissue or breast parenchyma (Case Rep Med 2011;2011:930841)
- Axilla (5%) (Int J Surg Case Rep 2018:52:49)
- Flexor surfaces of upper and lower extremities
- Head and trunk
Pathophysiology
- Pathophysiology is similar across anatomic locations; no aspects unique to the breast
- Hypothesis
- Genetic mutations or sporadic changes lead to loss of merlin
- Loss of merlin causes overexpression of membrane proteins (growth factor expression)
- Leads to tumorigenesis with decreased cell cycle arrest (Brain Pathol 2014;24:205)
- Hypothesis
- Genetic mutations cause peripheral nerves to be vulnerable to stress and injury
- Causes unregulated Schwann cell proliferation
- Leads to tumorigenesis (Oncogene 2020;39:5421)
Etiology
- 90% of schwannomas in the breast and other anatomic sites occur sporadically
- Remainder of schwannomas are associated with genetic mutations (loss of heterozygosity [LOH] at chromosome 22q, DGCR8, NF2, LZTR1, SMARCB1 or PRKAR1a) (GeneReviews: LZTR1 and SMARCB1 Related Schwannomatosis [Accessed 1 November 2024], Am J Med Genet A 2023;191:2467, Brain Pathol 2014;24:205)
- Inactivation of the NF2 gene, encoding protein NF2 (merlin, schannomin), accounts for over half of schwannomas (Genes Chromosomes Cancer 1996;17:45)
- Presence of multiple schwannomas may suggest a syndrome such as schwannomatosis or neurofibromatosis type 2
Diagnosis
- Majority present as palpable, mobile and nontender mass (Radiol Case Rep 2016;11:129)
- May involve dermis, subcutaneous tissue, breast parenchyma or axilla
- May be incidentally detected on screening mammography
- Breast Imaging Reporting and Data System (BI-RADS) often reports schwannomas as 4A
- Diagnosed on follow up biopsy or resection (Medicine (Baltimore) 2021;100:e27903, StatPearls: Mammography BI RADS Grading [Accessed 31 October 2024])
- WHO 2019 criteria: peripheral nerve sheath tumor - schwannoma, NOS
Radiology description
- Mammogram: well circumscribed, hyperdense nodule (Surg Today 2005;35:238, Tumori 2007;93:308)
- Ultrasound: round / oval, well circumscribed, homogenous, hypoechoic nodule with parallel orientation
- Magnetic resonance imaging (MRI) T1: low signal, isointense
- MRI T2: heterogeneous hyperintense signal (Medicine (Baltimore) 2021;100:e27903, Radiol Case Rep 2021;16:2154)
Radiology images
Prognostic factors
- Benign tumor with favorable prognosis
- No evidence of recurrence after excision (Medicine (Baltimore) 2021;100:e27903, Ann Diagn Pathol 2021;54:151773)
Case reports
- 37 year old woman with a painless lump in the right breast (Asian J Surg 2023;46:1395)
- 60 year old man with a 6 year history of a breast lump (Int J Surg Case Rep 2022;99:107667)
- 60 year old woman with breast pain (Medicine (Baltimore) 2021;100:e27903)
- 79 year old woman with a new lump detected on mammography (Radiol Case Rep 2021;16:2154)
Treatment
- Expectant management if stable and asymptomatic
- Surgical excision if growing or symptomatic (Medicine (Baltimore) 2021;100:e27903)
Gross description
- Gross appearance is similar across anatomic locations; none unique to the breast
- Tan or yellow cut surface
- Well demarcated from adjacent breast stroma
- May show hemorrhage or cystic change
- Plexiform variant of schwannoma has multinodular architecture (Brain Pathol 2014;24:205, Ann Diagn Pathol 2021;54:151773)
Frozen section description
- Features on frozen section are similar across anatomic locations; none unique to the breast
- Bland spindle cell proliferation (J Pathol Transl Med 2023;57:278)
- Varying degrees of cellularity
- Wavy, elongated nuclei with tapering ends
- Anisonucleosis
- Variably collagenous stroma
- May contain hemosiderin deposition (Cytopathology 2022;33:196)
- Frozen artifact is often prominent and includes (Adesina: Atlas of Pediatric Brain Tumors, 2nd Edition, 2016)
- Cytoplasmic vacuolization
- Gaps between collagen
Frozen section images
Microscopic (histologic) description
- Microscopic features similar across anatomic locations; none unique to the breast
- Well circumscribed or encapsulated
- Bland spindle cell proliferation
- Wavy, elongated nuclei with tapering ends
- Parallel nuclear palisading (Verocay bodies)
- Anisonucleosis
- Variably cellular and collagenous stroma
- Antoni A regions
- Hypercellular area with spindle cells
- Parallel nuclear palisading (Verocay bodies)
- Antoni B regions
- Hypocellular area with spindle cells
- Myxoid stroma
- Antoni A regions
- Hyalinized vessels with thrombi
- May contain areas of hemorrhage or hemosiderin deposition
- Variants
- Ancient schwannoma
- Degenerative atypia
- Cystic degeneration
- Hemorrhage
- Calcifications
- Stromal hyalinization
- Frequent histiocytes and macrophages
- Cellular schwannoma
- Predominantly Antoni A pattern
- < 10% of total tumor Antoni B area
- Fascicular growth pattern
- Foamy histiocyte aggregates
- Lymphoid aggregates
- Increased mitotic activity (usually < 4 - 5 mitoses/10 high power fields [HPFs])
- Coagulative necrosis (up to 10% of cases)
- Infiltrative margins
- Plexiform schwannoma
- Intraneural nodular pattern
- Predominantly Antoni A pattern
- Absent to rare mitosis
- Less well circumscribed
- Capsule may be absent
- Associated with NF2 related schwannomatosis
- Epithelioid cell schwannoma
- Epithelioid cells
- Abundant eosinophilic cytoplasm
- Nuclear pseudoinclusions
- Prominent nucleoli
- Fibromyxoid stroma
- Can have nuclear atypia
- Epithelioid cells
- Reticular schwannoma
- Abundant myxoid change
- Microcysts
- Rare variant
- Other rare features
- Neuroblastoma-like schwannoma
- Pseudoglandular structures
- Lipoblastic differentiation (Acta Neuropathol 2012;123:295, StatPearls: Vestibular Schwannoma [Accessed 31 October 2024], Diagnostics (Basel) 2022;12:1463)
- Ancient schwannoma
Microscopic (histologic) images
Virtual slides
Cytology description
- Fine needle aspiration (FNA) of breast masses is performed worldwide but less often in the United States
- Cytologic features similar to those of other anatomic sites; none unique to the breast
- Antoni A
- Cohesive fascicles with variable cellularity
- Dense fibrillary matrix
- Verocay bodies
- Antoni B
- Short spindle / wavy cells
- Myxoid background
- Microcysts
- Limitation
- FNA for schwannomas has low diagnostic sensitivity (0 - 40%)
- Often unsatisfactory specimens on FNA (Head Neck 2018;40:2695)
Cytology images
Positive stains
- S100 (strong and diffuse)
- SOX10 (strong and diffuse)
- May display weak, variable CD34
- Calretinin, CD56, CD68, podoplanin
- Collagen / type IV, laminin
- Reference: Adv Anat Pathol 2024;31:411
Negative stains
- Cytokeratins (rare labeling) (Mod Pathol 2006;19:115)
- EMA (capsule / perineurium only)
- CD34 (uncommon weak, variable labeling)
- SMA, desmin, calponin
- ER, PR and HER2
Molecular / cytogenetics description
- Similar to those in other anatomic sites; none unique to the breast
- Loss of heterozygosity of chromosome 22q
- Nontruncating (missense) and truncating (frameshift or nonsense) mutations leading to DGCR8, NF2, LZTR1 and SMARCB1 related schwannomatosis
- PRKAR1a mutation in Carney complex
- References: GeneReviews: LZTR1 and SMARCB1 Related Schwannomatosis [Accessed 1 November 2024], GeneReviews: NF2 Related Schwannomatosis [Accessed 1 November 2024], Am J Med Genet A 2023;191:2467, Brain Pathol 2014;24:205
Videos
Nerve: schwannoma microscopy (talking slide) - Pathweb Teacher
Tip-44; breast schwannoma - Al Hussaini Virtual Lab
Schwannoma (explained in 5 minutes) Verocay bodies Antoni A & B USMLE nerve sheath tumor pathology by Dr. Gardner
Schwannoma: 5 minute pathology pearls by Dr. Gardner
Sample pathology report
- Right breast, mass, ultrasound guided core biopsy:
- Schwannoma involving breast parenchyma (see comment)
- Comment: Immunohistochemical stains show the bland spindle cell proliferation to be diffusely positive for S100 and SOX10, while negative for CD34 and AE1 / AE3, supporting the above diagnosis.
Differential diagnosis
- Similar differential diagnosis as in other anatomic sites
- Additional differential diagnoses particularly relevant in the breast
- Myofibroblastoma, palisaded variant (Hum Pathol 2013;44:1941, Breast J 2017;23:354):
- Spindle cells with nuclear palisading resembling Verocay bodies
- May contain gaping, hyalinized blood vessels, hypocellular and hypercellular areas, cystic degeneration and myxoid stroma
- Differentiating features, if present
- Admixed adipocytes
- Brightly eosinophilic, keloidal-like collagen bundles
- Differentiating immunohistochemistry
- Pseudoangiomatous stromal hyperplasia (PASH):
- Spindle cells with tapering ends and occasionally wavy nuclei
- Fascicular PASH is cellular with nuclear palisading
- Differentiating features
- Forms slit-like spaces mimicking vascular spaces
- Appears infiltrative due to involvement of intralobular and extralobular stroma
- Differentiating immunohistochemistry
- Fibroepithelial neoplasm (fibroadenoma and phyllodes tumor):
- May contain stromal fascicular PASH-like pattern with nuclear palisading
- Differentiating features, if present
- Benign epithelial component with intracanalicular, pericanalicular or leaf-like architecture
- Infiltrative growth
- Differentiating immunohistochemistry
- Fibromatosis-like metaplastic carcinoma:
- Spindle cells with only mild to moderate cytologic atypia
- Differentiating features, if present
- Widely infiltrative
- Brightly eosinophilic keloidal-like collagen
- Associated low grade adenosquamous carcinoma
- Differentiating immunohistochemistry
- Positive: cytokeratins (variable: AE1 / AE3, 34 beta E12, OSCAR), p63
- Negative: S100, SOX10
- Myofibroblastoma, palisaded variant (Hum Pathol 2013;44:1941, Breast J 2017;23:354):
Additional references
Board review style question #1
Board review style answer #1
C. SOX10 and S100. Schwannomas stain diffusely positive for SOX10 and S100. Answer A is incorrect because schwannomas are negative for breast markers (ER, PR and HER2). Answer D is incorrect because STAT6 and CD34 are positive in solitary fibrous tumors. Answer B is incorrect because OSCAR and CK903 are positive in fibromatosis-like metaplastic carcinoma.
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Reference: Schwannoma
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Reference: Schwannoma
Board review style question #2
A breast mass is identified in an adult woman on a routine mammogram and subsequently biopsied using ultrasound guidance. Histologic sections demonstrate a hypercellular bland spindle cell neoplasm with hyalinized vessels. Immunohistochemistry shows the lesion to be diffusely and strongly positive for SOX10 and S100, focally positive for CD34 and negative for AE1 / AE3. What is the correct diagnosis?
- Neurofibroma
- Schwannoma
- Solitary fibrous tumor
- Spindle cell (metaplastic) carcinoma
Board review style answer #2
B. Schwannoma. Classic features of schwannoma include hyalinized vessels, Verocay bodies and Antoni A and Antoni B areas. It is diffusely positive for SOX10 and S100 protein. Answer A is incorrect because neurofibroma is patchy for SOX10 and S100. Answer D is incorrect because spindle cell (metaplastic) carcinoma has marked cytologic atypia and frequent mitosis. Answer C is incorrect because solitary fibrous tumor has staghorn blood vessels and is positive for CD34.
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Reference: Schwannoma
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Reference: Schwannoma