Table 1.

Features of peripheral nerve tumors

Tumor	Cell origin	Gross pathology	Microscopic pathology	IHC marker
Schwannoma	Schwann	Well-circumscribed, encapsulated (epineurium), ovoid, firm, light tan-yellow, may have degenerative changes (cystic, hemorrhagic)	Schwann cells; biphasic architecture (Antoni A/Antoni B); nuclear palisading (Verocay bodies); may have degenerative changes (cystic, hemorrhagic)	S100 protein +++; SOX10 +++; type IV collagen +; CD34 + (subcapsular areas); H3K27me3 intact; NFP + (entrapped axons); GFAP, CK – (peripheral sites); EMA – (+ in capsule); claudin-1, GLUT1 –
Neurofibroma	Schwann, fibroblasts, perineurial cells	Well-circumscribed, unencapsulated, ovoid, grayish-tan, gelatinous to firm	Loose spindle cell proliferation with haphazard arrangement; small hyperchromatic wavy nuclei; myxoid or collagenous (shredded carrot appearance) matrix; mast cells are common multinodular growth pattern (plexiform type); pseudo-Meissner bodies (diffuse and plexiform type); lack of degenerative changes (cystic, hemorrhagic)	S100 protein and SOX10 +++ (in Schwann cells); type IV collagen +; EMA, GLUT1 +++ (perineurial cells); CD34 +++ (fibroblasts); NFP + (entrapped axons)
Granular cell tumor	Schwann	Uninodular unencapsulated subcutaneous/submucosal firm masses; often with overlying epithelial hyperplasia (verrucous appearance); pale yellow-cream cut surface, with finely granular appearance	Irregular borders; monotonous epithelioid/polygonal cells organized as nests, trabeculae, sheets; indistinct cell borders, small, round, central nuclei; abundant, finely granular eosinophilic cytoplasm; perineural growth	S100 protein, SOX10, nestin, inhibin, calretinin +++; CD68, NSE +++; MITF, TFE3 ++; type IV collagen +; SMA, desmin, myogenin, GFAP, HMB45, Melan-A, NFP –
Cellular neurothekeoma	Unclear	Ill-defined borders, multinodular	Spindle and epithelioid cells; micronodular or lobulated architecture; areas of myxoid matrix, not abundant; whorled pattern; multinucleated giant cells (osteoclastic or Touton) may be present; slightly increased mitotic activity	S100 protein, SOX10 –; CD63, NSE, MITF +; HMB45, desmin, keratin –; SMA, p63 +/–
Nerve sheath myxoma	Schwann	Well circumscribed, nodular/multi-nodular; rubbery-firm consistency; white-translucent appearance	Lobular architecture; dense fibrous septa and abundant myxoid matrix; spindle and epithelioid cells, which form cords, networks, syncytial nests, and ring-like structures	S100 protein +++; GFAP, CD57 ++/+++; type IV collagen +; SMA, desmin, CD68, synaptophysin, chromogranin A, HMB45 –; CD34 + in rare fibroblasts; NFP + (entrapped axons); EMA –
Perineurioma	Perineurial	Well circumscribed, nodular, unencapsulated; firm to rubbery; yellow-tan or white cut surface	Growth patterns: fascicular, storiform, whorled, lamellar; spindle cells with bipolar cytoplasmic processes; thin, wavy or tapering/round and pale nuclei; collagenous stroma, focally myxoid	EMA +/+++; claudin-1, GLUT1 +++; CD34 +/–; S100 protein, SOX10, GFAP, SMA, desmin –
MPNST	Schwann	Usually deep, large (>5 cm), fusiform tumors, tan-white, gelatinous/fleshy cut surface; areas of necrosis and hemorrhage	Monomorphic to highly pleomorphic spindle cells, high and conspicuous mitotic activity, geographic necrosis; growth pattern: fascicular, hemangiopericytoma-like, hypercellular and hypocellular areas; myxoid to collagenous stroma; may present heterologous differentiation and/or preexisting benign nerve sheath tumor	S100 – or focally +; SOX10 + patchy/–; type IV collagen +/++; GFAP –/+; EMA – (except MPNST with perineurial differentiation); CD34 +/++; NFP +/+++; loss of nuclear H3K27me3 expression; HMB45, Melan-A –; markers for heterologous elements

CD: Cluster of differentiation; CK: Cytokeratin; EMA: Epithelial membrane antigen; GFAP: Glial fibrillary acidic protein; GLUT1: Glucose transporter 1; H3K27me3: Trimethylation of histone H3 on lysine 27; HMB45: Human melanoma black 45; MITF: Microphthalmia-associated transcription factor; MPNST: Malignant peripheral nerve sheath tumor; NFP: Neurofilament protein; NSE: Neuron-specific enolase; SMA: Smooth muscle actin; SOX10: SRY-box transcription factor 10; TFE3: Transcription factor E3