Definition/General
Introduction:
MPNST is a malignant tumor of peripheral nerve sheath
Shows Schwann cell or perineurial differentiation
Represents 5-10% of soft tissue sarcomas
FNAC shows atypical spindle cells with variable neural features.
Origin:
Arises from peripheral nerves or nerve sheath cells
Can develop de novo or from neurofibroma
50% associated with NF1
Malignant transformation of neurofibroma (10% in NF1).
Classification:
WHO classification: Malignant nerve sheath tumor
Types: Conventional MPNST
Epithelioid MPNST
MPNST with divergent differentiation
Melanotic MPNST
Perineurioma, malignant.
Epidemiology:
Peak incidence 3rd-6th decades
Equal gender distribution
50% in NF1 patients
Mean age 35 years (NF1)
Mean age 50 years (sporadic).
Clinical Features
Presentation:
Rapidly enlarging mass
Pain (70% of cases)
Neurological deficits
Large size at presentation (>5 cm)
Deep-seated location
Change in pre-existing neurofibroma.
Symptoms:
Severe pain (characteristic)
Paresthesias
Motor weakness
Mass effect
Functional impairment
Constitutional symptoms (advanced).
Risk Factors:
Neurofibromatosis type 1 (8-13% lifetime risk)
Previous radiation (15-20 year latency)
Li-Fraumeni syndrome
Familial schwannomatosis
Pre-existing neurofibroma.
Screening:
Annual surveillance (NF1 patients)
MRI screening
Clinical examination
PET scan (suspicious lesions)
FNAC/Biopsy for diagnosis.
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Gross Description
Appearance:
Large, fusiform mass
Gray-white, firm
Areas of necrosis and hemorrhage
Infiltrative margins
Nerve involvement
Heterogeneous cut surface.
Characteristics:
Poorly circumscribed
Firm to hard
Variable consistency
Necrosis (high-grade)
Hemorrhage
Cystic degeneration.
Size Location:
Extremities (50%)
Trunk (40%)
Head/neck (10%)
Major nerve trunks
Size: Usually >5 cm
Sciatic nerve common.
Multifocality:
Usually solitary
Skip metastases along nerve
Local recurrence common
Distant metastases (lung, bone)
Lymph node involvement rare.
Microscopic Description
Histological Features:
FNAC shows highly atypical spindle cells
Marked nuclear pleomorphism
High mitotic activity
Necrosis
Variable S-100 expression
Loss of schwannian features.
Cellular Characteristics:
Pleomorphic spindle cells
Hyperchromatic nuclei
Prominent nucleoli
Bizarre cells
Multinucleated giant cells
Mitotic figures including atypical.
Architectural Patterns:
Fascicular arrangement
Storiform pattern
Individual cells
Loose cohesion
Necrotic background
Hemorrhagic debris.
Grading Criteria:
High-grade by definition
Nuclear atypia
Mitoses >4/10 HPF
Necrosis
Infiltrative growth
Loss of benign features.
Immunohistochemistry
Positive Markers:
S-100 protein - variable (50-90%)
SOX10 - positive (neural crest)
p75NTR - positive
GFAP - focal positive
Vimentin - positive
CD56 - variable.
Negative Markers:
Neurofilament - negative
EMA - negative (usually)
Cytokeratin - negative (usually)
Desmin - negative
CD34 - negative
Smooth muscle actin - negative.
Diagnostic Utility:
S-100 variable (unlike benign schwannoma)
Loss of S-100 with dedifferentiation
SOX10 more reliable
Ki-67 high (>10%)
p53 overexpression common.
Molecular Subtypes:
Conventional MPNST: S-100+/-, SOX10+
Epithelioid MPNST: Similar profile
With rhabdomyoblastic differentiation: MyoD1+
NF1-associated: Loss of neurofibromin.
Molecular/Genetic
Genetic Mutations:
NF1 mutations (NF1-associated)
TP53 mutations (75%)
CDKN2A deletions (50%)
SUZ12 mutations
EED mutations
Complex karyotype.
Molecular Markers:
NF1/RAS pathway alterations
p53 pathway disruption
PRC2 complex inactivation
H3K27me3 loss
High mutational burden
Chromosomal instability.
Prognostic Significance:
Poor prognosis
5-year survival 20-50%
Size >5 cm: Worse outcome
NF1-associated: Worse prognosis
Epithelioid type: Very aggressive.
Therapeutic Targets:
Wide local excision
Adjuvant radiotherapy
Chemotherapy (limited benefit)
MEK inhibitors (NF1-associated)
Immunotherapy (investigational).
Differential Diagnosis
Similar Entities:
Schwannoma
Neurofibroma
Fibrosarcoma
Leiomyosarcoma
Synovial sarcoma
Spindle cell carcinoma.
Distinguishing Features:
MPNST: S-100+/-, cellular atypia, nerve association
Schwannoma: S-100++ strong, no atypia
Neurofibroma: S-100+ weak, CD34+
Fibrosarcoma: S-100-, herringbone pattern
Leiomyosarcoma: SMA+, desmin+.
Diagnostic Challenges:
Distinguishing from cellular schwannoma
S-100 negative MPNST
Spindle cell carcinoma
Other high-grade sarcomas
Sampling adequacy.
Rare Variants:
Epithelioid MPNST
Glandular MPNST
With rhabdomyosarcomatous differentiation
Melanotic MPNST.
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Specimen Information
Fine needle aspiration from [site], [size] cm mass associated with [nerve]
Clinical History
[age]/[sex] with [duration] history of rapidly enlarging, painful mass at [site]. [NF1 history/previous neurofibroma].
Microscopic Examination
Highly cellular smears showing markedly atypical spindle cells with nuclear pleomorphism, hyperchromatic nuclei, and prominent nucleoli. High mitotic activity noted. [Necrotic background present].
Immunocytochemistry
S-100: [Variable/Focal positive/Negative], SOX10: [result], p53: Overexpressed, Ki-67: High (>20%)
Cytological Diagnosis
Cytological features consistent with MALIGNANT PERIPHERAL NERVE SHEATH TUMOR (MPNST)
Comments
High-grade malignant nerve sheath tumor. Urgent histopathological confirmation recommended. Multidisciplinary sarcoma team evaluation required. Poor prognosis.