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Malignant Peripheral Nerve Sheath Tumor, MPNST

DEFINITION AND PATHOGENESIS

  • (Malignant peripheral nerve sheath tumor, MPNST, neurofibrosarcoma, malignant schwannoma, neurofibrosarcoma, neurogenic sarcoma)
  • Malignant nerve sheath tumor of Schwann or perineural cells or fibroblasts of the nerve sheath
  • Criteria for dx:
    • Tumor arrises from a peripheral nerve, OR
    • Tumor arises from a preexisting neurofibroma or neurilemmoma, OR
    • Tumor has hsitologic features that reflect Schwann cell differentiation
      • Dense and hypodense fascicles ("marble-like" pattern)
      • Spindled cells with irregular nuclei
      • Immunohistochemisty stains (or EM) consistent with Schwann cell differentiation

IMPORTANCE

  • About 50% occur with neurofibromatosis (~ 4% of those patients develop malignant lesions)
    • Lifetime risk of MPNST in NF1 reported to be 10-30%
    • MPNST may be multiple
  • Originates in radiated fields reportedly 2-29% of the time

CLINICAL FEATURES

  • Age range 16-76
  • Up to 11% may be XRT related
  • Most pts between 20-50 (lower end of the spectrum with NF1)
  • M>F (M=F in some studies) due to M predominance in NF
  • Enlarging masses (1.5-32cm, mean 9.5cm), usually painful or tender on palpation, ± sensory or motor findings
    • Sudden enlargement of a pre-existing mass in NF1
  • Have caused sxs similar to CTS, and cubital tunnel syndrome (1st thoracic nerve root)
  • Size not always predictive of malignancy
  • Enlargement of preexisting mass, superficial or deep
  • Extremities (45%), trunk (34%), head/neck (19%)
  • Unusual location

RADIOLOGIC FEATURES

  • MRI may reveal area of inhomogeneity within the lesion
  • PET/CT

GROSS PATHOLOGY

  • Large mass within a nerve, typically > 5cm and between anatomical compartments

HISTOLOGIC/MOLECULAR FEATURES

  • May be arising within a preexisting neurofibroma
  • Wavy, comma shaped nuclei, parallel orientation (nuclear palisading) <10%
  • Hyperplastic perivascular changes
  • Dense fascicles of cells alternating with myxoid areas
  • 94% high grade
  • Hyaline nodules = rosettes
  • Mature islands of (heterologous) cartilage, bone, skeletal muscle
  • Cytology
  • EM
    • Branching cytoplasmic processes from the cell body with microtubules, neurofilaments
  • Immunohistochemistry
    • Focally + S-100 in 50-90%
    • Vimentin +
    • Cytokeratins -
    • HMB-45 -
    • p53 protein expression in 21%
  • Molecular
    • TP53 mutations in 24% (36% were from NF1 pts)

DIFFERENTIAL CLINICOPATHOLOGIC DIAGNOSIS

  • Neurofibroma
  • Schwannoma (neurilemoma) with mitoses
    • Ancient schwannoma
  • Fibrosarcoma
  • Pleomorphic undifferentiated sarcoma (previously known as MFH)
  • Monophasic synovial sarcoma
  • Leiomyosarcoma
  • Angiosarcoma arising in a preexisitng neurofibroma

DISEASE COURSE AND TREATMENT

  • Wide excision ± chemotherapy/XRT
  • Proximal perineural spread may occur
  • Metastases to lung, liver, subcutaneous tissue, and bone
    • Unusual metastases
  • Long term survival ~ 50% (early detection and complete resection important)
  • LR 22%
  • 5- and 100-year disease-specific survival 60% and 45%
  • Poor prognostic factors
    • ? 5 cm size
    • LR
    • High tumor grade
    • Truncal location

SPECIAL CONSIDERATIONS

  • MALIGNANT TRITON TUMOR

    • (Malignant schwannoma with rhabdomyoblastic differentiation)
    • 67% occur in NF
    • Similar clinically to malignant schwannoma
    • Scattered rhabdomyoblasts within an otherwise typical malignant schwannoma
  • GLANDULAR MALIGNANT SCHWANNOMA

    • Rare, with cuboidal or columnar glands producing epithelial mucins
    • Well-differentiated glands scattered throughout a MPNST
    • Usually associated with NF1
    • Median age 30 yrs
  • MALIGNANT EPITHELIOID SCHWANNOMA

    • ? of malignant schwannomas, with the appearance of non-pigmented melanoma
  • CUTANEOUS MPNST

    • 78% LR (intraneural extension proximally and distally)
    • "Preservation of function" compromises resection
    • Pain an ominous sign
    • Hematogenous and lymphatic metastases have been reported
  • PLEXIFORM MPNST OF INFANCY AND EARLY CHILDHOOD

    • Incomplete resection with residual disease reported
    • LN and abdominal metastases have been reported in a newborn with a fungating foot lesion
      • Death reported at 6 mos of age
  • ANIMAL MODEL

    • MPNST induced by transplacental injection of ethylnitrosourea
    • MPNST induced by administration of methylcholanthrene

REFERENCES

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