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

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:

• Schwannoma.
• Dermatofibrosarcoma protuberans (DFSP) - S-100 -ve, CD34 +ve.
• Ganglioneuroma.

Images:

• WC:
  • Neurofibroma - low mag. (WC).
  • Neurofibroma - high mag. (WC).
  • Neurofibroma - high mag. (WC).
• www:
  • Plexiform neurofibroma (rsna.org).
  • Plexiform neurofibroma (rsna.org).
• Plexiform neurofibroma - several images (upmc.edu).

IHC

Features:

• S100 +ve.
• CD34 +ve.
• Glut1 +ve.
• EMA +ve/-ve.

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FOURTH TOE, LEFT, EXCISION:
- NEUROFIBROMA.

Micro

The sections show skin with poorly circumscribed groups of bland dermal spindle cells with wavy nuclei and pale-eosinophilic cytoplasm. Mast cells are seen scattered throughout the lesion. There is no nuclear atypia. Mitotic activity is not appreciated.

The overlying epidermis matures to the surface.

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.