Surgical Pathology Criteria



General Diagnostic Criteria



Differential Diagnosis




S-100 and Sox10

Moderate positivity

Strong, diffuse positivity



Scattered cells in Antoni B areas

Neurofilament (and Bielshowsky)

Stains entrapped axons within lesion

Stains peripherally located axons of parent nerve

Factor XIIIa


Negative to focal


Negative to focal



Variable, weak

Variable, moderate




Uniphasic, Low to moderate cellularity

Biphasic (cellular Antoni A & hypocellular Antoni B), some hypercellularity



Random pattern, only rare palisading, no well formed Verocay bodies

Palisading and Verocay bodies

Nerve often not identified

Nerve often identifiable

If nerve identified: incorporates nerve, axons often present in lesion

Eccentric to nerve, axons generally absent within lesion

Seldom cystic

Occasionally cystic

NF1-associated; Not NF2

Not NF1-associated; Occasionally NF2


Plexiform Neurofibroma

Plexiform Schwannoma

Cells separated by collagen bundles

Infrequent extracellular collagen

Hypocellular with abundant mucinous matrix

Infrequent hypocellular Antoni B areas (majority entirely hypercellular Antoni A)

Associated with NF1

Associated with NF2



Palisaded Encapsulated Neuroma

Can occur anywhere

90% of lesions affect the face

Frequently multiple

Usually solitary

Hypocellular lesion

Moderately cellular lesion

No peripheral perineurial capsule

Delicate EMA peripheral positivity

Can be GFAP positive

GFAP negative

Frequent mast cells

Rare mast cells

Contain neural fibroblasts and fibrillary collagen

Predominantly composed of Schwann cells

May be associated with neurofibromatosis

No known familial association

Both contain axons throughout


Traumatic Neuroma

No history of prior trauma or surgery

History of trauma or surgery

Random proliferation of Schwann cells and axons

Numerous well formed small nerve twigs

Widespread soft tissue infiltration

Limited soft tissue infiltration

Contains scattered admixed axons

Contains axons in abundant haphazardly arranged nerves


Cutaneous Neurofibroma

Neurotized Melanocytic Nevus

Lacks nevoid cells

Superficial classic nevoid melanocytes

More diffuse growth pattern

Congenital and nested growth patterns

Scant cytoplasm

More abundant cytoplasm

Tends to displace adnexa

Tends to surround adnexa

Immunohistochemistry has been reported to be useful. Neurofibromas should stain with Factor 13a and not MelanA while nevi stain conversely. However, in our experience this has limited utility. Both are S100 positive.


Cutaneous Myxoma (Superficial Angiomyxoma)

Wavy cells with buckled nuclei

Spindled to stellate cells with oval nuclei

Usually smaller (<2cm)

Generally larger (between 1 and 5 cm)

S100 positive

Rarely express S100

Associated with NF-1

Associated with Carney Complex

No epitheliaal component Frequent entrapped epithelium
Both may express CD34


Nerve Sheath Myxoma

Usually has at least areas of typical neurofibroma

Markedly hypocellular with abundant mucopolysaccharides

Lacks distinct lobulation

Lobulated architecture

Features of specific differentiation (e.g., pseudomeissnerian bodies) occasionally may be present


Both are S100 positive

Neurofibroma with Degenerative Atypia (“Ancient Change”)

Malignant Peripheral Nerve Sheath Tumor

Localized cells with large, pleomorphic nuclei, cytoplasmic nuclear inclusions, smudgy chromatin, and inconspicuous nucleoli

Generalized atypia

Absent or very low mitotic activity

Increased mitotic activity

Low to moderate cellularity

Diffuse hypercellularity

S100 positive 100%

S100 variably positive, about 30%


Diffuse Neurofibroma

Dermatofibrosarcoma protuberans (DFSP)

Less cellular

More cellular

Lack uniform storiform pattern

Distinct storiform pattern

S100 immunoreactive, CD34 stains only a subset of spindled cells

Strong CD34 immunoreactivity,
S100 negative

Diffuse process

Usually forms a mass



Spindle Cell Lipoma

Variable location

Deep soft tissue posterior neck


Delicate encapsulation

Generally lack fat

Most cases contain fat

May show degenerative atypia

Lacks degenerative atypia, may see floret cell formation

S100 immunoreactive, CD34 stains only a subset of spindled cells

Strong CD34 immunoreactivity,
S100 stains only fat cells


  • Goldblum, J.R., Folpe, A. L., Weiss, S.W., Enzinger and Weiss's Soft Tissue Tumors. 6th ed 2014. Philadelphia, PA: Mosby Elsevier.
  • Scheithauer BW, Woodruff JM, Erlandson RA. Tumors of the Peripheral Nervous System, Atlas of Tumor Pathology, AFIP Third Series, Fascicle 24, 1999.
  • 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
  • Chen Y, Klonowski PW, Lind AC, Lu D. Differentiating neurotized melanocytic nevi from neurofibromas using Melan-A (MART-1) immunohistochemical stain. Arch Pathol Lab Med. 2012 Jul;136(7):810-5.


    Kurt Schaberg MD
    Donald Born MD
    Robert V Rouse MD
    Department of Pathology
    Stanford University School of Medicine
    Stanford CA 94305-5342

    Original posting : 9/2/15

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