Superficial Malignant Peripheral Nerve Sheath Tumor

Superficial Malignant Peripheral Nerve Sheath Tumor

David R. Lucas, MD

MPNST can rarely present as a primary skin tumor, such as this scalp tumor excised from a 90-year-old woman. Superficial MPNST typically occurs in mid-to-deep dermis or as a subcutaneous primary.

Unless one sees continuity with a cutaneous nerve or adjacent neurofibroma, immunohistochemistry is required for diagnosis. Often negative or patchy, diffuse S100 staining is present in this case.



  • Malignant peripheral nerve sheath tumor (MPNST)


  • Neurofibrosarcoma, “malignant schwannoma” (older terms)


  • Superficial sarcoma arising from cutaneous nerve or benign nerve sheath tumor, or showing nerve sheath differentiation

    • Diagnostic criteria

      • Arises from nerve or benign nerve sheath tumor

      • Or shows histological evidence of nerve sheath differentiation in a NF1 patient

      • Or shows histological plus immunohistochemical or ultrastructural evidence of nerve sheath differentiation in non-NF1 patient


Genetic Predisposition

  • 40% associated with neurofibromatosis type 1 (NF1)

    • Lifetime incidence: 2-16%

Molecular Pathogenesis

  • NF1 caused by germline mutation of NF1 tumor suppressor gene

    • Somatic loss of 2nd NF1 allele required for tumorigenesis

  • Malignant transformation in both NF1-associated and sporadic MPNST often involves INK4A and P53 and their downstream pathways



  • Incidence

    • MPNST accounts for 5-10% of soft tissue sarcomas

      • Superficial MPNST very rare

  • Age

    • Mostly adults (20-50 years)

      • Average: 40 years

      • Wide range: 4-79 years

  • Gender

    • Women and men roughly equal


  • Head and neck (60%), trunk, upper and lower extremities

  • Dermis &/or subcutis

    • Mid- or deep dermis in most cases

    • May invade deeper structures


  • Painful or painless mass


  • Surgical approaches

    • Wide excision/resection

  • Adjuvant therapy

    • Radiation

  • Drugs

    • Generally MPNST shows poor response to chemotherapy


  • Local recurrence: 60%

  • Metastasis: 25%

    • Lung, lymph node, bone

  • 30% die of disease

    • Average survival: 3.3 years


General Features

  • Morphology

    • Cutaneous nodule

    • Superficial soft tissue mass


General Features

  • Epidermal alterations absent

  • Coexisting neurofibroma in some cases


  • Average: 3 cm (range: 2-16 cm)


Histologic Features

  • Wide spectrum of cytoarchitectural patterns

    • Mostly intermediate or high-grade sarcomas

      • High mitotic rate and necrosis

      • Only around 15% are low grade

    • Nerve sheath differentiation

      • Nuclear palisading uncommon, usually focal

      • Tactoid differentiation with whorling or Wagner-Meissner body-like features

    • Intraneural tumors

      • Plexiform architecture

      • Microscopic extension within nerve fascicle

    • Tumors arising from preexisting benign nerve sheath tumor

      • Neurofibroma most common, transitional areas, usually in NF1 patients

    • Diffuse infiltrative sarcomatous proliferation without evidence of nerve or nerve sheath tumor origin

  • Spindle cell MPNST (most common pattern)

    • Long fascicles of uniform, closely spaced, hyperchromatic spindle cells

    • Alternating cellular fascicles and hypocellular areas (“tapestry” or “marbled” pattern)

    • Myxoid matrix, focal

    • Storiform arrays

    • Wavy nuclei with tapered ends

    • Small round blue cells

    • Pleomorphic cells

      • Multinucleated giant cells

    • Extensive necrosis with perivascular preservation

  • Epithelioid MPNST

    • Multinodular architecture

    • Cords and clusters in some

    • Large epithelioid cells

      • Abundant eosinophilic cytoplasm

      • Large vesicular nuclei with macronucleoli

      • Clear cytoplasm in some

    • Often mixed with spindle cells

  • Heterologous differentiation (15% of MPNSTs)

    • Osseous and osteosarcomatous

    • Chondroid and chondrosarcomatous

    • Rhabdomyosarcomatous (Triton tumor)

    • Angiosarcomatous

    • Glandular

Cytologic Features

  • Spindle cells

    • Ill-defined cytoplasm

    • Hyperchromatic nucleus with dispersed coarse chromatin

    • Tapered and wavy nuclei in well-differentiated tumors

    • Very brisk mitotic activity in high-grade tumors

  • Epithelioid cells

    • Abundant eosinophilic or clear cytoplasm

    • Vesicular nucleus with prominent inclusion-like nucleolus



  • S100 protein (+) in about 60% of cases (more often in well-differentiated and epithelioid MPNST), usually focal

Jul 8, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Superficial Malignant Peripheral Nerve Sheath Tumor

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