Neurofibroma differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sara Mohsin, M.D.[2] Shanshan Cen, M.D. [3]

Overview

Neurofibroma must be differentiated from schwannoma, dermatofibrosarcoma protuberans (DFSP), ganglioneuroma, and melanocytic nevus.

Differential Diagnosis

Neurofibroma must be differentiated from:

• Schwannoma
• Dermatofibrosarcoma protuberans (DFSP)
• Ganglioneuroma
• Melanocytic nevus
• Myxoid liposarcoma
• Solitary circumscribed neuroma (palisaded encapsulated neuroma)
• Traumatic neuroma
• Neurotized nevus
• Superficial angiomyxoma
• Nerve sheath myxoma
• Malignant peripheral nerve sheath tumor (MPNST): has marked atypia and increased mitotic activity, may have necrosis
• Spindle cell lipoma
• Leiomyoma: has cigar-shaped nuclei, S100 negative, positive for smooth muscle actin and desmin
• Inflammatory myofibroblastic tumor: reactive spindle cells in inflammatory background

Differentiating neurofibroma from other diseases

Disease entity	Etiology (Genetic or other)	Histopathological findings	Immunohistochemical staining	Benign/Malignant	Risk factors	Common site of involvement	Clinical manifestations	Other associated features
Neurofibroma		Uniphasic, low to moderate cellularity Non-encapsulated Random pattern, only rare palisading No well formed verocy bodies Cells separated by collagen bundles Hypocellular with abundant mucinous matrix No peripheral perineural capsule Frequent mast cells Contains neural fibroblasts and fibrillary collagen Random proliferation of Schwann cells and scattered admixed axons No nevoid cells No epithelial component Diffuse growth pattern Scant cytoplasm Wavy cells with buckled nuclei Pseudomeissnerian bodies representing specific differentiation may be present Lacks storiform pattern Neurofibroma with degenerative atypia ("ancient change") has following microscopic features: Localized cells with large pleomorphic nuclei, cytoplasmic nuclear inclusions, smudgy chromatin, and inconspicuous nuclei Absent or very low mitotic activity Low to moderate cellularity	Positive for: S100 Sox10 Neurofilament (and Bielshowsky) GFAP CD34 Factor XIIIa Calretinin (focal)		NF-1 associated	Can occur anywhere		Nerve often not identified, incorporates nerve, axons often present in lesion Seldom cystic Frequently multiple Widespread soft tissue infiltration Tends to displace adnexa <2cm in diameter Lacks distinct lobulation Lacks fat
Schwannoma		Encapsulated Biphasic (majority entirely hypercellular Antoni A & hypocellular Antoni B) Palisading Verocay bodies Infrequent extracellular collagen	Positive for: S-100 Sox10 CD34 Neurofilament (and Bielshowsky) Factor XIIIa (focal) Calretinin GFAP		NF-2 associated			Nerve often identifiable Eccentric to nerve, axons generally absent within lesion Occasionally cystic
Palisaded encapsulated neuroma
Traumatic neuroma
Neurotized Melanocytic Nevus
Cutaneous Myxoma (Superficial angiomyxoma)
Nerve sheath myxoma
Malignant peripheral nerve sheath tumor
Dermatofibrosarcoma protuberans (DFSP)
Spindle cell lipoma

References

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