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Schwannoma

Authors: Sandra Sanchez, M.D., Ashley Cimino-Mathews, M.D.

Editorial Board Member: Kristen E. Muller, D.O.

Deputy Editor-in-Chief: Gary Tozbikian, M.D.

Last author update: 16 December 2024

Last staff update: 16 December 2024

Copyright: 2024, PathologyOutlines.com, Inc.

PubMed Search: Breast schwannoma

Table of Contents

Cite this page: Sanchez S, Cimino-Mathews A. Schwannoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/breastschwannoma.html. Accessed December 26th, 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

Contributed by Sandra Sanchez, M.D.

Well circumscribed superficial breast mass

Oval hypoechoic mass

Images hosted on other servers:

Oval circumscribed mass

Superficial oval circumscribed mass

Oval circumscribed hypoechoic mass

Heterogeneously enhancing circumscribed mass

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)

Clinical images

Images hosted on other servers:

Firm pedunculated nipple mass

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)

Gross images

Images hosted on other servers:

Solid mass with hemorrhage

Firm encapsulated mass

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

Contributed by Norman Baker, M.A., M.S., Sandra Sanchez, M.D. and Ashley Cimino-Mathews, M.D.

Hypercellular spindle cell lesion

Images hosted on other servers:

Hypocellular myxoid lesion

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
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
- 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)

Microscopic (histologic) images

Contributed by Norman Baker, M.A., M.S., Sandra Sanchez, M.D. and Ashley Cimino-Mathews, M.D.

Nodular and variably cellular

Hypocellular and hypercellular areas

Nuclear palisading (Verocay bodies)

Gaping hyalinized blood vessels

Biopsy of breast schwannoma

Diffuse S100 positivity

Virtual slides

Images hosted on other servers:

Schwannoma from pectoralis minor

Schwannoma from neck

Melanocytic schwannoma

Schwannoma from left elbow

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

Contributed by Norman Baker, M.A., M.S., Sandra Sanchez, M.D. and Ashley Cimino-Mathews, M.D.

Delicate fibrillar cytoplasm

Hypercellular cohesive tissue fragments

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
    - Positive: CD34, ER, smooth muscle markers (variable: SMA, desmin, calponin)
    - Negative: S100, SOX10
- 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
    - Positive: CD34, ER, PR, smooth muscle markers (variable: SMA, desmin, calponin)
    - Negative: S100, SOX10
- 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
    - Positive: CD34 (variable), smooth muscle markers (variable: SMA, desmin, calponin)
    - Negative: S100, SOX10
- 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

Additional references

Semin Diagn Pathol 2017;34:420, Breast J 2018;24:206, WHO Classification of Tumours Editorial Board: Breast Tumours, 5th Edition, 2019

Board review style question #1

An incidental breast lump is noted on screening mammography in an adult woman. Which immunohistochemical stains could be used to support the diagnosis?

ER, PR and HER2
OSCAR and CK903
SOX10 and S100
STAT6 and CD34

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.

Comment Here

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.

Comment Here

Reference: Schwannoma

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