Malignant Peripheral Nerve Sheath Tumor
Definition
- A malignant neoplasm arising from or differentiating toward cells intrinsic to the peripheral nerve sheath
- Tumors of the epineurial soft tissue and peripheral nerve vasculature are excluded
Alternate/Historical Names
- Neurogenic Sarcoma
- Neurofibrosarcoma
- Malignant Schwannoma
Diagnostic Criteria
- Minimal criteria to distinguish malignant from benign nerve sheath tumor
- Marked cell crowding
- Generalized nuclear enlargement (3x normal neurofibroma cells)
- Nuclear hyperchromasia
- Mitotic rate over 5/10 hpf
- Identification of a sarcoma as nerve sheath sarcoma requires at least one of the following four criteria
- Arises from a peripheral nerve
- Arises from a pre-existing benign nerve sheath tumor (e.g., neurofibroma)
- In a patient with known NF1 the tumor displays histologic features typical of MPNST
- In a patient without known NF1 the tumor displays histologic features typical of MPNST and evidence of nerve sheath differentiation (S100 staining or ultrastructure)
- Histologic appearance variable but frequently resembles pleomorphic undifferentiated sarcoma (MFH) or fibrosarcoma
- Cells often arranged in sweeping fascicles
- Densely cellular fascicles alternate and interdigitate with myxoid areas
- Creates a “marble-like” effect
- Densely cellular areas may resemble fibrosarcoma
- Some whorled areas suggest tactoid differentiation
- Palisading is very rare and, if present, is often only focal
- Nuclei usually hyperchromatic and wavy, buckled, or comma shaped
- Cytoplasm is usually pale and indistinct
- Cells typically spindled to fusiform
- Rare rounded cells observed
- Other characteristic features include:
- Hyaline bands
- Nodules
- Extensive perineural and intraneural spread
- At least a low level of mitotic activity
- Usually more than 10 per 10 HPF
- Geographic necrosis
- 75% of tumors have geographic necrosis and mitotic activity
- Heterologous elements are present in 10-15% of tumors
- Cartilage and bone are the most common
- S100 staining is variable (50-70%) and usually only focal
- Immunohistochemistry and molecular studies are probably best used in ruling out other lesions (e.g.., synovial sarcoma)
Subtypes
- Malignant Peripheral Nerve Sheath Tumor with Rhabdomyoblastic Differentiation (Malignant Triton Tumor)
- Rhabdomyoblasts scattered throughout an otherwise normal MPNST
- Rhabdomyoblasts are often mature with abundant eosinophilic cytoplasm
- May show cross-striations
- Immunoreactive with Desmin, Myogenin, and MyoD1
- May also show chondroid, osteoid or epithelial differentiation
- Frequently associated with NF1
- Poor prognosis
- Rhabdomyoblasts scattered throughout an otherwise normal MPNST
- Malignant Peripheral Nerve Sheath Tumor with Glands (Glandular MPNST)
- Otherwise normal MPNST with well-differentiated glands
- Cuboidal to columnar cells, usually enteric type
- Mucin may be present
- May contain other heterologous elements
- May be confused histologically with biphasic synovial sarcoma
- Often arises in major nerves
- Strong association with NF1
- Poor prognosis
- Otherwise normal MPNST with well-differentiated glands
- Epithelioid Malignant Peripheral Nerve Sheath Tumor
- Composed primarily of Schwann cells with a polygonal epithelioid appearance
- No association with NF1
- Up to 80% of tumors show strong, diffuse S-100 staining
- Do not express melanoma markers and only rarely express keratins
- Differentiated from metastatic melanomas or carcinomas by their origination in major nerves or a benign nerve sheath tumor
- In cases where this cannot be demonstrated, it may be impossible to make this diagnosis definitively
Clinical
- A distinction is made between WHO grades III and IV based on the presence of necrosis
- Up to 50% of malignant peripheral nerve sheath tumors are associated with neurofibromatosis type 1 (NF 1)
- Lifetime risk of developing a MPNST in NF1 is about 10%
- Most common in adults from 20-50 years old
- Generally poor prognosis
- Approximately 40% locally recur within 1 year
- Approximately 50% develop metastases within 1 year
- Poorer prognosis is associated with large size and lack of S-100 protein expression
Differential Diagnosis
- Schwannoma
- Cellular schwannoma
- Neurofibroma
- Synovial sarcoma
- Fibrosarcoma
- Leiyomyosarcoma
- Desmoplastic melanoma
MPNST |
||
Biphasic, Antoni A and B areas |
Uniform, Hypercellular (Majority Antoni A) |
Hypercellular |
Variable chromatin |
May show hyperchromasia |
Pronounced hyperchromasia |
Small nuclei |
Small nuclei |
Enlarged nuclei (3x normal) |
Verocay bodies, hyalinized vessels, lipid laden histocytes, lymphoid infiltrates |
Hyalinized vessels, lipid-laden histiocytes, lymphocytic infiltrates |
All absent |
Mitoses usually rare |
Few mitoses (usu. <4/10 HPF) |
Very mitotically active (usu. >10/10 HPF) |
Strong, diffuse S100 immunoreactivity |
Strong, diffuse S100 immunoreactivity |
Weak, patchy S100 immunoreactivity |
Rare necrosis |
Poorly demarcated rare foci of necrosis without palisading |
Geographic necrosis |
Globoid, encapsulated |
Globoid, encapsulated |
Fusiform to globoid with infiltration |
Rare divergent differentiation |
Rare divergent differentiation |
Occasional divergent differentiation (e.g., rhabdomyosarcoma in malignant triton tumor) |
MPNST |
|
Occasional bizarre, hyperchromatic cells, other cells cytologically benign |
Uniform, cytologically malignant features |
Normal cellularity |
Marked cell crowding |
Low mitotic activity |
High mitotic activity |
S100 positive |
S100 variably positive |
MPNST |
|
Localized cells with large, pleomorphic nuclei, cytoplasmic nuclear inclusions, smudgy chromatin, and inconspicuous nucleoli |
Generalized atypia |
No or very low mitotic activity |
Increased mitotic activity |
Low to moderate cellularity |
Diffuse hypercellularity |
S100 positive |
S100 variably positive |
MPNST |
|
May be S100 positive |
S100 negative |
More variable architecture |
Uniform fascicular pattern |
Generally more pleomorphic |
Uniform, symmetric fusiform cells resembling fibroblasts |
May arise from a nerve or neurofibroma |
No relation to a nerve or neurofibroma |
May arise in NF1 |
Not related to NF1 |
No consistent translocations |
t(12;15) usually present in infantile fibrosarcoma |
MPNST |
|
No consistent translocations |
t(X;18;p11;q11) translocation |
Prominent vessels uncommon |
Hemangiopericytoma-like vessels |
Hyperchromatic, wavy or buckled nuclei |
Plump, stubby nuclei |
Diffuse atypia |
No more than mild pleomorphism |
Glands rare but may be seen |
Glands in biphasic synovial sarcoma |
Keratin negative spindle cells |
Spindled cells may be keratin positive |
Calcifications uncommon |
Calcifications common |
| TLE1 ipox 5% | TLE1 ipox 97% |
MPNST |
|
Wavy nuclei |
Nuclei with blunt ends |
Light, indistinct cytoplasm |
Eosinophilic cytoplasm with juxtanuclear vacuoles |
May be S-100 immunoreactive |
S-100 negative, Smooth muscle markers positive |
May be associated with nerve or neurofibroma |
Not associated with nerve or neurofibroma |
MPNST |
Desmoplastic Melanoma |
May arise in existing nerve or neurofibroma |
Fibrosing dermal lesion typically of head and neck |
No association with atypical junctional melanocytes |
Often associated junctional component of atypical melanocytes |
No associated lymphoid infiltrate |
Often lymphoid infiltrate |
Variable, weak S-100 expression |
Strong S-100 immunoreactivity |
Light, indistinct cytoplasm |
Amphophilic cytoplasm |
Bibliography
- Goldblum, J.R., Folpe, A. L., Weiss, S.W., Enzinger and Weiss's Soft Tissue Tumors. 6th ed 2014. Philadelphia, PA: Mosby Elsevier.
- Scheithauer BW, Woodruff JM, Erlandson RA. Tumors of the Peripheral Nervous System, Atlas of Tumor Pathology, AFIP Third Series, Fascicle 24, 1999.
- Louis, D.N., Ohgaki, H., Wiestler, O.D., Cavenee, W.K. eds. WHO Classification of Tumours of the Central Nervous System, Fourth Edition. IARC Press: Lyon 2004
Kurt Schaberg MD
Donald Born MD
Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342
Original posting : 9/2/15
