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
- 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
- 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
- MRI may reveal area of inhomogeneity within the lesion
- Large mass within a nerve, typically > 5cm and between anatomical compartments
- 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
- Branching cytoplasmic processes from the cell body with microtubules, neurofilaments
- Focally + S-100 in 50-90%
- Vimentin +
- Cytokeratins -
- HMB-45 -
- p53 protein expression in 21%
- TP53 mutations in 24% (36% were from NF1 pts)
DIFFERENTIAL CLINICOPATHOLOGIC DIAGNOSIS
- Schwannoma (neurilemoma) with mitoses
- Pleomorphic undifferentiated sarcoma (previously known as MFH)
- Monophasic synovial sarcoma
- 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
- 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
- High tumor grade
- Truncal location
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
- 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
- MPNST induced by transplacental injection of ethylnitrosourea
- MPNST induced by administration of methylcholanthrene
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