Definition/General
Introduction:
Leiomyosarcoma is a malignant smooth muscle tumor
It represents 10-20% of soft tissue sarcomas
Shows smooth muscle differentiation with malignant features
FNAC demonstrates atypical spindle cells with smooth muscle phenotype.
Origin:
Arises from smooth muscle cells in soft tissues
Can develop from blood vessel walls
De novo development most common
Deep soft tissues, retroperitoneum, and extremities
Does not arise from leiomyomas.
Classification:
WHO classification: Malignant smooth muscle tumor
Subtypes include: Conventional leiomyosarcoma
Epithelioid leiomyosarcoma
Myxoid leiomyosarcoma
Inflammatory leiomyosarcoma.
Epidemiology:
Peak incidence in 5th-7th decades
Female predominance (1.5:1)
Accounts for 5-10% of adult soft tissue sarcomas
Deep soft tissues more common than superficial
Retroperitoneal location in 15-20%.
Clinical Features
Presentation:
Enlarging mass (most common)
Painless initially
Large size at presentation (>5 cm)
Firm to hard consistency
Deep-seated location
Rapid growth in high-grade tumors.
Symptoms:
Initially asymptomatic
Pain in advanced cases
Mass effect symptoms
Functional impairment
Weight loss (advanced disease)
Systemic symptoms (metastatic disease).
Risk Factors:
Previous radiation exposure (5-10 year latency)
Li-Fraumeni syndrome
Hereditary retinoblastoma
Neurofibromatosis type 1
Previous chemotherapy
Genetic predisposition.
Screening:
Imaging studies for soft tissue masses
MRI for local extension
CT chest for metastases
FNAC/Biopsy for diagnosis
Multidisciplinary evaluation
Genetic counseling if syndrome suspected.
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Gross Description
Appearance:
Large, fleshy mass
Multinodular or lobulated
Gray-white to tan cut surface
Areas of necrosis and hemorrhage
Firm consistency
Poorly circumscribed margins.
Characteristics:
Heterogeneous appearance
Fascicular pattern on cut surface
Necrosis (especially high-grade)
Hemorrhage and cystic change
Infiltrative growth
Variable consistency.
Size Location:
Extremities (40-50%)
Retroperitoneum (15-20%)
Trunk wall (20%)
Head and neck (5%)
Size: Usually >5 cm
Can reach massive proportions (>20 cm).
Multifocality:
Usually solitary
Multifocal disease rare
Satellite nodules in aggressive tumors
Local recurrence common (30-50%)
Metastatic potential high (40-60%)
Skip lesions possible.
Microscopic Description
Histological Features:
FNAC shows atypical spindle cells with smooth muscle features
Nuclear pleomorphism
Hyperchromatic nuclei
Prominent nucleoli
Increased mitotic activity
Necrosis (high-grade tumors).
Cellular Characteristics:
Pleomorphic spindle cells
Elongated, atypical nuclei
Coarse chromatin
Prominent nucleoli
Abundant cytoplasm
Mitotic figures including atypical forms.
Architectural Patterns:
Cellular smears with fascicular arrangement
Loosely cohesive groups
Individual cells
Necrotic background (high-grade)
Streaming pattern
Nuclear molding.
Grading Criteria:
FNRS grading system: Differentiation (1-3 points)
Mitotic count (1-3 points)
Necrosis (0-2 points)
Grade I: 2-3 points
Grade II: 4-5 points
Grade III: 6-8 points.
Immunohistochemistry
Positive Markers:
Smooth muscle actin (SMA) - positive
Desmin - positive (70-80%)
Calponin - positive
h-Caldesmon - positive (specific)
Vimentin - positive
Muscle-specific actin - positive.
Negative Markers:
S-100 protein - negative
CD34 - negative
Cytokeratin - negative (usually)
EMA - negative
MyoD1 - negative
Myogenin - negative.
Diagnostic Utility:
SMA and h-caldesmon confirm smooth muscle differentiation
Desmin variable (70-80% positive)
Ki-67 correlates with grade (>10% high-grade)
p53 overexpression in high-grade
MDM2/CDK4 negative.
Molecular Subtypes:
Conventional: SMA+, desmin+, h-caldesmon+
Epithelioid: Same markers, epithelioid morphology
Myxoid: Same markers, myxoid background
Inflammatory: Inflammatory infiltrate present
Pleomorphic: High-grade features.
Molecular/Genetic
Genetic Mutations:
TP53 mutations (50-60%)
RB1 mutations (60-70%)
PTEN deletions
CDKN2A deletions
Complex karyotype
Chromosome instability
PIK3CA mutations.
Molecular Markers:
p53 pathway alterations
RB pathway disruption
PI3K/AKT pathway activation
DNA repair defects
Telomerase activation
High mutational burden.
Prognostic Significance:
Grade determines prognosis
Grade I: Good prognosis (>80% 5-year survival)
Grade II: Intermediate (60-70%)
Grade III: Poor (<50%)
Size >10 cm: Poor prognosis
Deep location: Worse outcome.
Therapeutic Targets:
Anthracycline-based chemotherapy
Trabectedin for advanced disease
Pazopanib (multi-kinase inhibitor)
Olaratumab (anti-PDGFR-α)
Immunotherapy (selected cases)
PI3K/mTOR inhibitors (investigational).
Differential Diagnosis
Similar Entities:
Leiomyoma
Fibrosarcoma
Malignant peripheral nerve sheath tumor
Synovial sarcoma
Gastrointestinal stromal tumor
Spindle cell carcinoma
Solitary fibrous tumor.
Distinguishing Features:
Leiomyosarcoma: SMA+, h-caldesmon+, nuclear atypia
Leiomyoma: No atypia, low Ki-67
Fibrosarcoma: SMA-, collagen production
MPNST: S-100+, nerve association
Synovial sarcoma: TLE1+, t(X;18)
GIST: CD117+, DOG1+
Spindle cell carcinoma: Cytokeratin+.
Diagnostic Challenges:
Distinguishing from benign leiomyoma (requires histology)
Grade assessment on FNAC
Other spindle cell sarcomas
Metastatic spindle cell carcinoma
Site-specific considerations
Sampling adequacy.
Rare Variants:
Epithelioid variant
Myxoid variant
Granular cell variant
Inflammatory variant
Dedifferentiated areas
Rhabdoid features.
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 soft tissue mass
Clinical History
[age]/[sex] with [duration] history of enlarging mass at [site]. Imaging shows [findings].
Gross Examination
Aspirated material: [amount] of hemorrhagic and cellular material
Microscopic Examination
Smears show high cellularity with atypical spindle cells showing nuclear pleomorphism, hyperchromatic nuclei, and prominent nucleoli. Mitotic activity: [count]/10 HPF. [Necrosis present/absent].
Immunocytochemistry
SMA: Positive, Desmin: [result], h-Caldesmon: Positive, S-100: Negative, Ki-67: [%]
Cytological Diagnosis
Cytological features consistent with LEIOMYOSARCOMA, Grade [I/II/III]
Comments
Histopathological examination recommended for definitive grading. Molecular studies may be helpful. Multidisciplinary oncology evaluation advised.