Soft tissue
Peripheral nerve
Malignant
Malignant peripheral nerve sheath tumor (MPNST)

Resident / Fellow Advisory Board: Farres Obeidin, M.D.
Editorial Board Member: Borislav A. Alexiev, M.D.
Erica Kao, M.D.
Jose G. Mantilla, M.D.

Topic Completed: 20 January 2021

Minor changes: 20 January 2021

Copyright: 2002-2021, PathologyOutlines.com, Inc.

PubMed Search: Malignant peripheral nerve sheath tumor [title] free full text [SB] review

Erica Kao, M.D.
Jose G. Mantilla, M.D.
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Cite this page: Kao E, Mantilla JG. Malignant peripheral nerve sheath tumor (MPNST). PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/softtissuempnst.html. Accessed April 16th, 2021.
Definition / general
  • Malignant neoplasm arising from peripheral nerve
  • May arise from a preexisting nerve sheath tumor in neurofibromatosis type 1 (NF1) or in the setting of prior radiation therapy
  • In the absence of association with NF1 or radiation, diagnosis is challenging and based on histologic and immunohistochemical features suggesting Schwannian differentiation (Am J Surg Pathol 2016;40:896)

  • Variants:
Essential features
  • Sarcoma with peripheral nerve sheath differentiation with typically aggressive behavior
  • Can occur in the following settings:
  • Morphology: marbling at low magnification (alternating areas of hypocellularity and hypercellularity) with perivascular accentuation, uniform cytologic features
  • Heterologous differentiation in 10 - 15% of cases
  • Rhabdomyoblastic differentiation associated with adverse clinical behavior (Eur J Surg Oncol 2013;39:46)
  • SOX10 and S100 IHC only seen in 50% of cases
Terminology
  • Malignant peripheral nerve sheath tumor (MPNST)
  • Obsolete: neurofibrosarcoma, malignant schwannoma, neurogenic sarcoma
ICD coding
  • ICD-O: 9540/3 - malignant peripheral nerve sheath tumor
  • ICD-11:
    • 2B5E & XH2XP8 - malignant nerve sheath tumor of peripheral nerves or autonomic nervous system, primary site, malignant peripheral nerve sheath tumor
    • 2B5E & XH4V81 - malignant nerve sheath tumor of peripheral nerves or autonomic nervous system, primary site, malignant peripheral nerve sheath tumor, epithelioid
    • 2B5E & XH2VV8 - malignant nerve sheath tumor of peripheral nerves or autonomic nervous system, primary site, malignant peripheral nerve sheath tumor with rhabdomyoblastic differentiation
Epidemiology
Sites
  • Can arise in virtually any anatomic location
  • Most common sites are the trunk and extremities, followed by head and neck (Am J Surg Pathol 2016;40:896)
Pathophysiology
  • Germline mutations in NF1 predispose to the development of peripheral nerve sheath neoplasms in patients with type 1 neurofibromatosis (Acta Neuropathol 2012;123:349)
  • In the setting of NF1, lesions often arise from plexiform neurofibroma (Acta Neuropathol 2012;123:349)
    • Transformation process is accompanied by progressive genomic changes involving NF1, CDKN2A / CDKN2B and PRC2 (Hum Pathol 2017;67:1)
    • Radiation therapy predisposes to the development of secondary sarcomas through repeated DNA damage and defective repair
Etiology
Clinical features
  • No sex predilection
  • Patients with NF1 are typically younger than their sporadic and radiation associated counterparts (J Med Genet 2002;39:311)
Diagnosis
  • Histologic evaluation is necessary but not always specific and requires correlation with clinical and radiologic findings
  • Helpful features include close association with peripheral nerves and history of NF1 or precursor lesions
Radiology description
Radiology images

Contributed by Jose G. Mantilla, M.D.

Forearm lesion T1

Forearm lesion T2

Cerebellopontine angle mass coronal view

Cerebellopontine angle mass sagittal view

Prognostic factors
Case reports
Treatment
Gross description
  • Fusiform to globoid, pseudoencapsulated tumor often with gross evidence of necrosis
    • If the tumor is arising from a nerve, an attached medium or large nerve is evident
Gross images

Contributed by Jose G. Mantilla, M.D.

Gross findings


Frozen section description
  • In high grade tumors, overt features of malignancy are readily identified, including nuclear pleomorphism, brisk mitotic activity and areas of geographic necrosis
  • Diagnosis of low grade lesions is difficult in frozen sections
  • In NF1, mitotic activity, increased cellularity and nuclear atypia within a neurofibroma raise concern for MPNST
Microscopic (histologic) description
  • Low power: marbled appearance due to alternating hypocellular and hypercellular areas with perivascular accentuation
  • Uniform spindle cells with hyperchromatic, thin, wavy, or focally buckled nuclei
  • May have uniform cellularity with fibrosarcoma-like fascicular growth, raising the differential diagnosis of synovial sarcoma
  • Can have foci of myxoid stroma and hyalinization
  • Epithelioid morphology can be present
  • Precursor lesion, such as neurofibroma, may be identifiable
  • Nuclear palisading is uncommon
  • Heterologous differentiation may include chondrosarcomatous, osteosarcomatous and rhabdomyosarcomatous components (malignant triton tumor)
  • Glandular elements are exceedingly rare (Int J Surg Pathol 2017;25:310)
  • Proposed nomenclature for the spectrum of NF1 associated nerve sheath tumors:
    • Atypical neurofibromatous neoplasm of uncertain biologic potential (ANNUBP):
      • At least 2 of the following features: cytologic atypia, loss of neurofibroma architecture, hypercellularity, > 1/50 HPF and < 3/10 HPF
    • MPNST, low grade: features of ANNUBP but with mitotic index of 3 - 9/10 HPF and no necrosis
    • MPNST, high grade: MPNST with at least 10 mits/10 HPF or 3 - 9 mits/10 HPF combined with necrosis (Hum Pathol 2017;67:1)
Microscopic (histologic) images

Contributed by Jose G. Mantilla, M.D.

Marbling

Fascicular growth

Rhabdomyo-
sarcomatous elements

Epithelioid type, low power

Epithelioid type, higher power

Virtual slides

Images hosted on other servers:

Marbling, hyperchromatic nuclei

Perivascular accentuation

Cytology description
  • Highly cellular smears of uniform spindled cells singly and in clusters (Cancer Cytopathol 2012;120:334)
  • Cytomorphologic overlap with other sarcomas is significant
Cytology images

Contributed by Jose G. Mantilla, M.D.

Uniform spindle cells

Positive stains
Negative stains
Molecular / cytogenetics description
Sample pathology report
  • Right hand mass, excision (consult case):
    • Spindle cell sarcoma, consistent with malignant peripheral nerve sheath tumor (see comment)
    • Tumor size: 3.8 cm in greatest dimension, per outside report
    • Inked tissue edges involved by sarcoma
    • Comment: Histologic sections contain a dermal based neoplasm with a plexiform architectural pattern. It is composed of variably pleomorphic spindle cells forming fascicles and storiform structures with a marbling pattern. Mitotic activity is present in up to 7/10 high power fields and no necrosis is identified. The periphery of the lesion is relatively hypocellular with a single area composed of cytologically bland spindle cells, which morphologically resembles neurofibroma (slide A3). This portion of the lesion shows immunoreactivity for S100 and CD34. The remainder of the lesion is has focal S100 reactivity. Negative stains include EMA, CK AE1 / AE3, desmin, SMA, MART1, MUC4, CD56, neurofilament and ER. Overall, the findings are consistent with malignant peripheral nerve sheath tumor.
Differential diagnosis
Board review style question #1

    Which of the following is true about malignant peripheral nerve sheath tumors?

  1. Characteristic histology is of a marbled appearance at low power with alternating hypocellular and hypercellular areas
  2. Glandular elements are never seen in this entity, which can help distinguish it from synovial sarcoma
  3. Lesion always has diffuse and strong S100 positivity due to its nerve sheath origin
  4. Most of these tumors are radiation associated as opposed to arising de novo or in a preexisting neurofibroma
Board review style answer #1
A. Characteristic histology is of a marbled appearance at low power with alternating hypocellular and hypercellular areas

Comment Here

Reference: MPNST
Board review style question #2
    Which of the following is true about the immunophenotypic and molecular characteristics of MPNST?

  1. Loss of expression of H3K27me3 has been described in high grade appearing tumors
  2. All cases have some degree of SOX10 expression
  3. Germline mutations have no influence on the development of MPNST
  4. MPNST is defined by recurrent cytogenetic alterations
Board review style answer #2
A. Loss of expression of H3K27me3 has been described in high grade appearing tumors

Comment Here

Reference: MPNST
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