Perineurioma
Definition
- A tumour composed entirely of neoplastic perineurial cells. Tumors may be intraneural or within the soft tissue
- See separate description of Gastrointestinal Tract Perineurioma
Alternate/Historical Names
- Localized hypertrophic neuropathy
Diagnostic Features
- Spindle cell proliferation
- Characteristic long, thin, delicate, bipolar cytoplasmic processes
- Pale, eosinophilic cytoplasm
- Wavy or tapering nuclei
- finely distributed chromatin
- By definition, immunohistochemical staining positive for EMA and S100 negative
- Immunophenotype matches normal perineurial cells
- EMA staining varies from focal, weak to strong, diffuse
- Highlights delicate bipolar cytoplasmic processes
- May require procedure variation to increase sensitivity for EMA
- Examples of ultrastructurally diagnosed EMA-negative perineuriomas exist
- Often express Claudin-1, and GLUT.
- May express CD34 and actins
- Perivascular whorls
- Mitotic activity may be present
- 0-13/30 high-power (40x with 10x oculars) fields (mean of 1)
- 65% of tumors having none
- May have degenerative atypia
- Changes include nuclear pleomorphism, hyperchromasia, cytoplasmic-nuclear inclusions
- Most common in long-standing tumors
- As a rule, necrosis is absent
Subtypes
- Intraneural Perineurioma
- Neoplastic perineurial cells proliferating throughout the endoneurium
- Form repetitive concentric layers around nerve fibers forming characteristic pseudo-onion bulbs
- Pseudo-onion bulbs best appreciated on cross-section
- Due to organized architecture, may be mistaken for reparative or reactive process
- Produce segmental, tubular enlargement of the affected nerve
- Residual S100-positive nerve fibers are surrounded by EMA-positive perineurial cells
- WHO grade I
- Do not undergo malignant transformation
- Frequently present with muscle weakness with or without obvious atrophy
- sensory disturbances are rare
- Most common in peripheral nerves of extremities in young adults
- Most common in upper extremity
- Extraneural (Soft Tissue) Perineurioma
- Not grossly associated with a nerve
- Solitary, generally small (usually <10 cm)
- Well-circumscribed, but not encapsulated
- Varying growth patterns
- Storiform most common
- Can also show lamellar, whorled, pacinian, or fascicular patterns
- Often collagenous stoma
- Up to 20% contain at least focal myxoid stroma
- Present with non-specific mass effect
- More common in superficial soft tissue of trunk and extremities particularly the hands
- Sclerosing Perineurioma
- Extraneural (soft tissue) perineurioma variant
- Plump spindled and epithelioid tumor cells in a hyalinized stroma
- Prominent thin-walled vessels
- Perivascular and lace-like arrangement tumor cells around vessels
- Described occurring mainly in the fingers of young males
- Reticular Perineurioma
- Extraneural (soft tissue) perineurioma variant
- Prominent degenerative myxoid changes
- May form pseudocystic spaces
- Tumor cells show lace-like, reticular pattern
- Malignant Perineurioma (Perineurial MPNST)
- Features of malignant perineuriomas
- Hypercellularity
- Nuclear atypia
- Hyperchromasia
- High mitotic rate
- Infiltrative growth
- Necrosis
- The presence of necrosis upgrades from WHO grade 2 to 3
- Arise exclusively from Extraneural (soft tissue) perineuriomas
- Very uncommon
- Less likely to metastasize than conventional MPNSTs
- Gastrointestinal Perineurioma
Clinical
- Benign, rarely recur
- Surgical resection with negative margins is usually curative
- Sporadic tumors
- Rare cases reported in patients with NF1 or NF2
Differential Diagnosis
- Intraneural Neurofibroma/Schwannoma
- Neurofibroma
- Intraneural MPNST
- Neural lipofibroma
- Pacinian Neuroma
- Low-grade fibromyxoid sarcoma
- Ectopic Meningioma
- Desmoid fibromatosis
- Smooth Muscle tumor
- Solitary fibrous tumor
- Superficial acral myxoma
- Dermatofibroma
- Dermatofibrosarcoma protuberans
|
Extraneural Perineurioma |
|
S100 negative |
Express S100 |
May have collagenous stroma |
“Shredded Carrot” collagen bundles |
Both may express CD34 and EMA as neurofibromas have a perineurial component
Intraneural Perineurioma |
|
Uniform cylindrical shape |
Fusiform or eccentric mass |
Pseudo-onion bulb formation |
Absent |
Expresses EMA |
EMA Negative (except in areas of glandular differentiation) |
S100 Negative |
May express focal or weak S100 |
Mitoses may be present in both lesions
Intraneural Perineurioma |
Nveural Fibrolipoma |
Purely perineural proliferation |
Mature adipose tissue and fibrous tissue proliferation |
Both may show pseudo-onion bulb formation and express EMA and CD34
Intraneural Perineurioma |
Pacinian Neuroma |
Neoplastic, not associated with trauma |
Hyperplastic/hypertrophic, frequently associated with prior trauma |
Non-painful |
Often painful |
Segmental enlargement of nerve |
Enlarged or multiple pacinian corpuscles |
Varied locations, may occur on hands |
Most commonly on hands, especially fingers |
Both may contain concentric onion-like proliferations. In both, perineural cells stain with EMA and residual nerve fibers stain with S100
Extraneural Perineurioma |
|
Monosomy chromosome 22 |
Characteristic FUS-CREB3L2 translocation (chromosomes 7 and 16) |
MUC 4 Negative |
Express MUC4 |
Well-circumscribed |
Grossly-circumscribed, but microscopically infiltrative |
Alternating pattern not prominent |
Alternating fibrous and myxoid areas |
Myxoid areas infrequent |
Myxoid areas definitional |
Express EMA (definitional) |
Occasional, focal, weak EMA |
Collagen rosettes absent |
Occasional giant collagen rosettes |
Both may express Claudin-1
Extraneural Perineurioma |
Ectopic Meningioma |
Well-circumscribed |
Infiltrative growth |
Long, thin, spindled cells |
Syncytial epithelioid cells |
Varied architecture, may form whorls |
Whorled architecture |
Psammoma bodies absent |
Frequent Psammoma bodies |
Intranuclear inclusions absent |
Frequent intranuclear pseudoinclusions |
Both express EMA and Claudin-1
Extraneural Perineurioma |
|
Well-circumscribed |
Ill-defined, invasive growth |
Variable architecture |
Broad, sweeping fascicles |
Nuclear Beta-catenin absent |
Nuclear Beta-catenin staining often |
Infrequently express actins |
Express smooth muscle actin and muscle-specific actin |
Extraneural Perineurioma |
|
Wavy or tapering nuclei |
Blunt-ended nuclei |
Characteristic long, thin, delicate, bipolar cytoplasmic processes |
Abundant eosinophilic cytoplasm |
Negative for actins and desmin |
Express actins and desmin |
Variable architecture |
Perpendicular intersecting fascicles |
Extraneural Perineurioma |
|
Staghorn vessels absent |
Prominent vascular pattern with staghorn vessels |
Variable patterns |
“Patternless” pattern (alternating and varying cellularity and pattern) |
Express EMA |
Variable EMA expression |
No characteristic gene fusion |
NAB2-STAT6 gene fusion |
STAT6 negative |
Express STAT6 |
May express CD34 |
Diffuse CD34 expression |
Extraneural Perineurioma |
|
Usually on extremities or trunk, infrequently periungual |
Most common on hands or feet and often periungual |
Express EMA |
May express EMA (~50%) |
May express CD34 |
Express CD34 |
Express Claudin-1 |
Claudin-1 Negative |
Extraneural Perineurioma |
Dermatofibroma |
No epidermal induction |
Hyperplastic epidermis |
Long, thin, spindled cells |
Plump, spindled and histiocytoid cells |
EMA positive |
EMA may be focal or weak |
Well-circumscribed |
Infiltrative growth |
Extraneural Perineurioma |
|
May express CD34 |
Strong, diffuse CD34 expression |
Express EMA |
EMA focal or weak |
May have storiform architecture |
Characteristic storiform architecture |
Usually centered in subcutaneous tissue and well-circumscribed |
Centered in dermis often invading subcutaneous tissue |
No characteristic gene fusion |
Characteristic COL1A-PDGFB fusion |
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 B.W., Woodruff J.M., Erlandson R.A. Tumors of the Peripheral Nervous System, Atlas of Tumor Pathology, AFIP Third Series, Fascicle 24, 1999.
- Macarenco R.S., Ellinger F., Oliveira A.M. Perineurioma: a distinctive and underrecognized peripheral nerve sheath neoplasm. Arch Pathol Lab Med. 2007 Apr;131(4):625-36.
- Fisher, C. et al. Diagnostic pathology: Soft tissue tumors. Amsirsys, 2011.
- Fletcher, C.D.M. et al. WHO Classification of Tumours of Soft Tissue and Bone. IARC, Lyon, 2013.
- 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
Kurt Schaberg MD
Donald Born MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342
Original posting :1/15/16
