Peripheral nerve sheath tumours

Peripheral nerve sheath tumours, abbreviated PNSTs, are common in neuropathology and occasionally show-up elsewhere. A very common PNST is the schwannoma.

Classification

A classification:

• Benign:
  • Schwannoma.
  • Neurofibroma.
  • Perineurioma.
  • Traumatic neuroma.
• Malignant:
  • Malignant peripheral nerve sheath tumour (MPNST).

Specific diagnoses

Schwannoma

General

• A common neuropathology tumour that occasionally shows-up elsewhere.
• Tumour of tissue surrounding a nerve.
  • Axons adjacent to the tumour are normal... but may be compressed.
• May be a part of neurofibromatosis type 2.

Microscopic

Features:

• Antoni A:
  • Cellular.
  • 'Fibrillary, polar, elongated'.
• Antoni B:
  • Pauci-cellular.
  • Loose microcystic tissue.
• Verocay bodies - paucinuclear area surrounded by nuclei - diagnostic feature.
• Hyaline thickened blood vessels.
• Thick capsule.
• In the GI tract: classically have a peripheral lymphoid cuff.
• +/-Hemosiderin deposition within tumour.

Notes:

• Tumour does not smear well.
• Antoni A: may look somewhat like scattered matchsticks.

DDx:

• Meningioma.
• Intranodal palisaded myofibroblastoma - if surrounded by a rim of lymphoid tissue, i.e. intranodal.
• Leiomyoma.

Images:

• www:
  • Antoni A (pathguy.com).
  • Antoni A & Antoni B side-by-side (ajnr.org).
  • Cystic schwannoma - several images (upmc.edu).
• WC:
  • Schwannoma - Antoni A & B - intermed. mag. (WC).
  • Scwhannoma - Antoni A & B - very high mag. (WC).
  • Psammomatous melanotic schwannoma - high mag. (WC).
  • Nerve root schwannoma - intermed. mag. (WC).

Schwannoma subtypes

There are four:

1. Conventional schwannoma.
2. Cellular schwannoma.
3. Plexiform schwannoma.
4. Melanotic schwannoma.

Conventional schwannoma

• Most common.

Cellular schwannoma

• May mimic MPNST.

Images:

• Cellular schwannoma (upmc.edu).

Plexiform schwannoma

• May mimic MPNST if cellular - esp. in childhood.

Images:

• Plexiform schwannoma - low mag. (WC).
• Plexiform schwannoma - high mag. (WC).

Melanotic schwannoma

• May be confused with melanoma.
• Psammomatous form (psammomatous melanotic schwannoma) associated with a heritable disorder (Carney complex).

Note:

• Carney complex:
  • Cutaneous lentigines.
  • Myxomas (skin (subcutaneous), subcutanous, heart).
  • Endocrine neoplasms.

Images:

• Psammomatous melanotic schwannoma - several images (upmc.edu).

IHC

Features:

• S-100 +ve.
• Glut1 +ve.
• CD34 +ve.
• Cytokeratins ~70% +ve.^{[citation needed]}
• SOX10 +ve.
  • -ve in synovial sarcoma, rhabdomyosarcoma, chondrosarcoma.
• EMA -ve. (???)
  • Usually +ve (~75% of the time) in meningiomas.

Perineurioma

General

• Benign tumour derived from perineurial cells.

Variant:

• Reticular perineurioma.

Microscopic

Features:

• Perineural epithelioid cells.
  • Abundant pale, fluffy appearing cytoplasm.

Note:

• May be intraneural.

DDx:

• Neuroma.
• Neurofibroma.
• Schwannoma.
  • S100 +ve, EMA -ve.
• Liposarcoma - reticular perineurioma.

Images:

• Perineuroma (conganat.org).

IHC

Features:

• S100 -ve.
• EMA +ve.
• CD34 ~65% +ve.

Traumatic neuroma

General

• Consequence of trauma - diagnosis requires history of trauma.
  • May mimic a cancer recurrence at the site of a surgery.

Microscopic

Features:

• +/-Nerve - that was injured.
• Grouping of disordered nerve fibre bundles in fibrous tissue (collagen) - key feature.
• +/-Myxoid change.
• +/-Axonal swellings (ovoid pink/purple blobs).

DDx:

• Morton neuroma (foot).

Images:

• Traumatic neuroma (nih.gov).
• Traumatic neuroma - several images (upmc.edu).
• Traumatic neuroma (sarcomaimages.com).
• Traumatic neuroma (nih.gov).

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SOFT TISSUE LESION, RIGHT WRIST, EXCISION:
- TRAUMATIC NEUROMA.
- BENIGN FIBROADIPOSE TISSUE.

Micro

The sections show disordered nerve fibre bundles in fibrous tissue.

Palisaded encapsulated neuroma

• Abbreviated PEN.
• AKA palisaded and encapsulated neuroma.

General

• Flesh-colour papule - classically on the face.
• Isolated finding - not associated with a systemic disease or malignancy.
• Superficial skin.

Microscopic

Features:

• Encapsulated dermal spindle cell lesion.
  • Fasciular arrangement.
  • Neural-type spindle cells:
    1. Not vacuolated.
    2. Nuclei have pointy ends.
• Intralesional clefts.
  • Useful to differentiate from schwannoma.

DDx:

• Schwannoma:
  • No intralesional clefts.
  • More variability in the cellularity.
  • May be deep.

Other considerations:

• Leiomyoma - cytoplasm not vacuolated, nuclei more elliptical.

Images:

• PEN (cdlib.org).

IHC

Features:

• S100 +ve.
• EMA +ve (capsule of lesion).

Neurofibroma

This section includes plexiform neurofibroma.

General

• May be a part of neurofibromatosis 1 (NF1).
• A painful skin lesion.
• Composed of Schwann cells, axons, fibrous material.

Classification:

1. Localized - sporatic.
2. Diffuse - usually poorly defined, young adults and children; sporatic.
3. Plexiform - associated with NF1.

Gross/radiologic

Gross features (plexiform NF):

• "Bag of worms" appearance.

Radiologic:

• Fusiform mass.

Microscopic

Features:

• Spindle cells with wavy nuclei without pleomorphism - key feature.
  • Often described as "shredded carrots".
• May be arranged in fascicles and intermixed with collagen.
  • Often no pattern is apparent.
• Moderate increase of cellularity vis-a-vis normal dermis.
• May be poorly or well-circumscribed.
• +/-Plexiform growth pattern - "bag of worms".
  • Multiple well-circumscribed nests.
• Mast cells - one has to look for them at high power.
  • Very useful for confirming the low power suspicion.

DDx:

• Plexiform neurofibroma.
• Schwannoma.
• Dermatofibrosarcoma protuberans (DFSP) - S-100 -ve.
• Ganglioneuroma.
• Neurotized melanocytic nevus - melanocyte nests make the diagnosis, otherwise immunostains are needed to differentiate.
  • Usually have more mast cells than neurofibromas.

Images

• 

  Neurofibroma - low mag. (WC)

• 

  Neurofibroma - intermed. mag. (WC)

• 

  Neurofibroma - high mag. (WC)

www:

• Plexiform neurofibroma (rsna.org).
• Plexiform neurofibroma (rsna.org).
• Plexiform neurofibroma - several images (upmc.edu).
• Neurofibroma - S-100 (eyewiki.aao.org).

IHC

Features:

• S100 +ve -- wavy pattern.
• CD34 +ve.
• Glut1 +ve.
• EMA +ve/-ve.
• NF +ve/-ve.
• MART-1 -ve.
  • Positive in neurotized melanocytic nevi.

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FOURTH TOE, LEFT, EXCISION:
- NEUROFIBROMA.

Micro

The sections show skin with a lesion composed of irregular-shaped groups of bland dermal spindle cells with wavy nuclei and pale-eosinophilic cytoplasm. Mast cells are seen scattered throughout the lesion. Thick collagen separates the clusters of the spindle cells. There is no nuclear atypia. Mitotic activity is not appreciated. No melanocytic nests are identified.

The overlying epidermis matures to the surface.

Alternate

The sections show skin with an unencapsulated dermal spindle cell lesion with navy nuclei that have a likeness to shredded carrots. Occasional mast cells are present within the lesion. There is no nuclear atypia. Mitotic activity is not appreciated. No melanocytic nests are identified.

Neurothekeoma

• AKA myxoma of the nerve sheath, AKA nerve sheath myxoma.

General

• Rare.
• Female > male.

Microscopic

Features:

• Superficial dermal lesion:
  • Usu. lobulated or micronodular architecture - key feature.
    • +/-Focal sheeting.
  • Spindle/epithelioid morphology with pale eosinophilic cytoplasm - key feature.
  • +/-Inflammation around lesion.
  • +/-Surrounded by collagen.

Notes:

• No atypia.
• Mitoses rare/none.
• Often poorly circumscribed.

Subtypes:

• Cellular.
• Myxoid.
• Intermediate.

DDx:

• Dermatofibroma.
• Angiomatoid fibrous histiocytoma -- have cystic blood filled spaces, inflammation.

Images:

• Neurothekeoma (WP).
• Neurothekeoma - several images (upmc.edu).

IHC

Features:

• NKI/C3 (AKA NKI-C3) +ve.
• NSE +/-ve.

Others:

• Vimentin +ve.
• CD10 +ve.
• Microphthalmia transcription factor +ve.
• PGP9.5 +ve.

Exclusionary:

• S100 -ve.
  • Exclude other peripheral nerve sheath tumours. (???)

Malignant peripheral nerve sheath tumour

• AKA neurofibrosarcoma.
• Commonly abbreviated MPNST.

General

• Malignant - as the name implies.
• Usu. assoc. with a peripheral nerve.^{[citation needed]}
• May be seen in the context of neurofibromatosis type 1.

Microscopic

Features:

• Cellular.
• Nuclear atypia.
• Mitoses.
• +/-Herring bone pattern.

Notes:

• May be diagnosed in a poorly diff. tumour if patient has NF1.

DDx:

• Cellular schwannoma.
• Plexiform schwannoma.
• Malignant triton tumour.

DDx of herring bone:

• MPNST.
• Synovial sarcoma.
• Fibrosarcoma.

Images:

• MPNST - intermed. mag. (WC).
• MPNST - high mag. (WC).
• MPNST - several images (upmc.edu).
• MPNST - case 2 - several images (upmc.edu).

Grading

• Can be graded histologically, and this is prognostic.

Sarcoma grading system - based on:

• Tumour differentiation.
• Mitotic rate.
• Necrosis.

IHC

Features:

• S-100 +ve ~ 30% of tumours.
• SOX10 +ve ~ 50% of tumours.

Others:

• p53.
• p16.
• p27.
• MIB1.

Malignant triton tumour

• Abbreviated MTT.
• AKA malignant peripheral nerve sheath tumor with rhabdomyosarcomatous differentiation.

General

• Rare.
• Considered to be a variant of MPNST.
• Prognosis worse that conventional MPNST.
  • Five year survival ~14%.
• Diagnosis may require clinical information, i.e. individual has a history of neurofibromatosis type 1 (NF1).

Note:

• A handful of benign triton tumours are reported; these are considered neuromuscular hamartomas.

Microscopic

Features - Woodruff criteria - all three required:

1. (a) Tumour arise from a peripheral nerve or (b) individual has NF1 or (c) lesion a metastasis arising in the context of (a) or (b).
2. Schwann cell tumour characteristics.
3. Rhabdomyoblasts.
   • Eccentric nucleus.
   • Moderate amount of eosinophilic cytoplasm.
   • +/-Cross-striations.

DDx:

• Malignant peripheral nerve sheath tumour.
• Adult fibrosarcoma.
• Synovial sarcoma.
• Rhabdomyosarcoma.
• Carcinosarcoma.

IHC

Features:

• S100 +ve/-ve -- usu. focal if positive.
• Leu-7 +ve/-ve.
• Myelin basic protein +ve/-ve.

Rhabdomyoblastic differentiation:

• Desmin.
• Actin.
• Myogenin.

EM

• +/-Sarcomeres.

Morton neuroma

General

• Benign foot condition.
• Uncommon.
• Usu. interdigital nerves.

Etiology:

• Indirect nerve trauma.

Clinical:

• Foot pain.

Microscopic

Features:

• Extensive fibrosis around and within the nerve.
• Digital artery:
  • +/-Thrombosis.
  • +/-Arterial thickening.

DDx:

• Traumatic neuroma.

Images:

• Morton neuroma (tumorlibrary.com).
• Perineural fibrosis (els-cdn.com).

See also

• Neuropathology.
• Gastrointestinal pathology.