Malignant Peripheral Nerve Sheath Tumor



Malignant Peripheral Nerve Sheath Tumor


David R. Lucas, MD

Cyril Fisher, MD, DSc, FRCPath





Key Facts


Terminology



  • Sarcoma arising from a nerve or benign nerve sheath tumor or showing nerve sheath cellular differentiation


Etiology/Pathogenesis



  • 50% associated with NF1


  • 10% associated with radiation


Clinical Issues



  • Mostly adults (20-50 years)


  • Most (70%) arise in major nerve trunks


  • Local recurrence: > 40%


  • Metastasis: 30-60%


  • 5-year survival: 15-34%


Microscopic Pathology



  • Mostly high-grade sarcomas


  • Spindle cell MPNST (80%)



    • Long fascicles of closely spaced hyperchromatic spindle cells


    • Small round blue cells


    • Pleomorphic cells


    • Extensive necrosis with perivascular preservation


  • Epithelioid MPNST (5%)


  • Heterologous differentiation (15%)


Ancillary Tests



  • S100: 50-60%


Top Differential Diagnoses



  • Synovial sarcoma


  • Cellular schwannoma


  • Atypical neurofibroma


  • Malignant melanoma






MPNSTs often arise from a major nerve trunk, such as this sciatic nerve tumor forming a fusiform, lobulated, intraneural mass image. MPNSTs can extend along the nerve to form satellite nodules image.






Microscopically, MPNSTs are highly variable in appearance and degree of differentiation. Well-differentiated tumors have spindle cells with tapered and wavy nuclei and indistinct cytoplasm, as shown.


TERMINOLOGY


Abbreviations



  • Malignant peripheral nerve sheath tumor (MPNST)


Synonyms



  • Neurofibrosarcoma, malignant schwannoma, neurogenic sarcoma


Definitions



  • Sarcoma arising from a nerve or benign nerve sheath tumor or showing nerve sheath cellular differentiation



    • Diagnostic criteria



      • Arises from a 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


ETIOLOGY/PATHOGENESIS


Genetic Predisposition



  • 50% associated with neurofibromatosis type 1 (NF1)



    • Lifetime incidence: 2-16%


  • 40% sporadic


Environmental Exposure



  • 10% associated with radiation


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


CLINICAL ISSUES


Epidemiology



  • Incidence



    • Rare: 5-10% of soft tissue sarcomas


  • Age



    • Mostly adults (20-50 years)



      • Wide age range: 10-70 years


      • Average age in NF1: 30 years


      • Average age in sporadic MPNST: 40 years


  • Gender



    • Women and men roughly equal


Site



  • Common sites: Thigh, buttock, trunk, upper arm, retroperitoneum, head and neck



    • Mostly deep-seated


    • Central body axis more common in NF1


  • Most (70%) arise in major nerve trunks



    • Sciatic nerve most common


    • Brachial plexus, sacral plexus, paraspinal nerves


Presentation



  • Painful mass


  • Neurological deficit in some


Treatment



  • Surgical approaches



    • Wide excision/resection


    • Amputation


  • Adjuvant therapy



    • Radiation


  • Drugs



    • Generally poor response to chemotherapy


Prognosis



  • Poor



    • Local recurrence: > 40%


    • Metastasis: 30-60%



      • Lungs, bone, pleura most common



    • > 60% die of disease


    • 5-year survival: 15-34%


    • NF1 patients have worse overall prognosis



      • Probably due to higher incidence of large, central axis tumors


IMAGE FINDINGS


General Features



  • Morphology



    • Large heterogeneous mass


    • Fusiform mass within major nerve trunk


MACROSCOPIC FEATURES


General Features



  • Similar to other soft tissue sarcomas



    • Pseudoencapsulated


    • Gray-tan


    • Firm to fleshy


    • Necrosis and hemorrhage common


  • Fusiform or eccentric mass when arising in major nerve trunk


  • Coexisting neurofibroma in some



    • Solitary or plexiform


Size



  • Most > 5 cm


  • Sometimes very massive


MICROSCOPIC PATHOLOGY


Histologic Features



  • Wide spectrum of cytoarchitectural patterns



    • Mostly high-grade sarcomas



      • High mitotic rate and necrosis


      • Only around 15% are low grade


    • Nerve sheath differentiation



      • Nuclear palisading uncommon (15%), usually focal


      • Tactoid differentiation with whorling or Wagner-Meissner-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


      • Schwannoma, ganglioneuroma, ganglioneuroblastoma, or pheochromocytoma; very rare


    • Diffuse sarcomatous proliferation with no evidence of nerve or nerve sheath origin


  • Spindle cell MPNST (80%)



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


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


    • Storiform arrays


    • Small round blue cells


    • Pleomorphic cells



      • Multinucleated giant cells


    • Extensive necrosis with perivascular preservation


    • Hemangiopericytoma-like vascular pattern in some


  • Epithelioid MPNST (5%)



    • 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%)



    • Osseous and osteosarcomatous


    • Chondroid and chondrosarcomatous


    • Rhabdomyosarcomatous (Triton tumor)


    • Angiosarcomatous


    • Glandular


    • Neuroepithelial (rosettes)



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


ANCILLARY TESTS


Immunohistochemistry



  • S100 protein(+) in about 60%, usually focal


  • Nestin(+) in 50-80%


Cytogenetics



  • Complex structural and numeric chromosomal abnormalities



    • Frequent loss of NF1 at 17q11


    • Frequent loss of P53 at 17q13


DIFFERENTIAL DIAGNOSIS


Monophasic or Poorly Differentiated Synovial Sarcoma



  • Nuclei have softer, less coarse chromatin


  • Usually has lower mitotic rate


  • TLE1(+)



    • MPNST rarely (2%) positive


  • Usually cytokeratin(+) and EMA(+)



    • MPNST usually negative


  • Usually S100(-)


  • t(X:18) by cytogenetics


  • SYT break apart by FISH


  • SSX-SYT fusion by RT-PCR


Cellular Schwannoma



  • Usually located in retroperitoneum, pelvis, posterior mediastinum


  • Exclusively Antoni A areas; often lacks Verocay bodies


  • Necrosis and mitotic figures present


  • Can erode/destroy bone


  • Lacks malignant cytological atypia


  • Strong, diffuse S100 staining



    • MPNST usually has only focal staining


Atypical Neurofibroma



  • Large, hyperchromatic spindle cells


  • Degenerated (smudged) chromatin


  • Low miotic rate


  • Usually retains cytoarchitectural features of neurofibroma



    • Edematous fibrillary or myxoid matrix with collagen bundles (“shredded carrots” pattern)


Malignant Melanoma

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Jul 9, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Malignant Peripheral Nerve Sheath Tumor

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