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
Intraneural Perineurioma
Intraneural Neurofibroma /Schwannoma
S100 negative
Express S100
Pseudo-onion bulb formation
Absent
Closely encircle nerve fibers
Nerve fibers scattered (neurofibroma) or at periphery (schwannoma)
Extraneural Perineurioma
Neurofibroma
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
Intraneural MPNST
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
Low-grade Fibromyxoid Sarcoma
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
Desmoid Fibromatosis
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
Smooth Muscle Tumors
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
Solitary Fibrous Tuvmor
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
Superficial Acral Fibromyxoma
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
DFSP
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
Original posting :1/15/16
