Definition/General
Introduction:
Small intestinal leiomyosarcoma is a malignant smooth muscle tumor arising from smooth muscle cells of the intestinal wall
It shows high mitotic activity and cellular atypia
It represents rare primary small bowel malignancy
It has aggressive behavior with metastatic potential.
Origin:
Arises from smooth muscle cells of muscularis propria or muscularis mucosae
Results from malignant transformation of smooth muscle cells
Genetic alterations in cell cycle control
May arise de novo or from pre-existing leiomyoma.
Classification:
WHO Classification: high-grade sarcoma
Based on size and mitoses: low-grade vs high-grade
Location: jejunum most common
Primary vs metastatic
Spindle cell vs epithelioid variants.
Epidemiology:
Very rare tumors (<1% of small bowel malignancies)
Female predominance (2:1 ratio)
Peak incidence: 50-70 years
Jejunum most common site
Worse prognosis than gastric leiomyosarcoma.
Clinical Features
Presentation:
Abdominal mass (most common)
Abdominal pain
GI bleeding
Small bowel obstruction
Weight loss and fatigue
Perforation (rare but serious).
Symptoms:
Palpable abdominal mass
Crampy abdominal pain
Iron deficiency anemia (chronic bleeding)
Melena or hematochezia
Constitutional symptoms
Intestinal obstruction signs.
Risk Factors:
Previous radiation therapy
Genetic syndromes: Li-Fraumeni, hereditary retinoblastoma
Female sex
Advanced age
Immunosuppression.
Screening:
CT abdomen/pelvis (heterogeneous mass)
MRI (T2 heterogeneous signal)
PET-CT (metabolically active)
Upper endoscopy (duodenal lesions)
Biopsy for diagnosis.
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Gross Description
Appearance:
Large, lobulated mass
Gray-white cut surface
Areas of necrosis and hemorrhage
Fleshy consistency
Infiltrative margins
Central necrosis common.
Characteristics:
Poorly circumscribed mass
Heterogeneous appearance
Necrotic and cystic areas
Hemorrhage frequently present
Invasion into adjacent structures
Soft to firm consistency.
Size Location:
Jejunum (50% cases)
Ileum (30%)
Duodenum (20%)
Size: 5-20 cm (average 8-10 cm)
Larger than leiomyomas
Extramural growth common.
Multifocality:
Usually solitary
Local invasion common
Metastases: liver (most common), lungs, peritoneum
Lymph node involvement less common
Aggressive local behavior.
Microscopic Description
Histological Features:
Malignant spindle cells
High mitotic activity (>5 mitoses per 10 HPF)
Nuclear atypia and pleomorphism
Tumor necrosis
Fascicular growth pattern
Vascular invasion.
Cellular Characteristics:
Spindle-shaped cells with elongated nuclei
Nuclear hyperchromasia
Prominent nucleoli
Increased nuclear-cytoplasmic ratio
Atypical mitoses
Cellular pleomorphism.
Architectural Patterns:
Intersecting fascicles
Storiform pattern
Areas of necrosis
Hemorrhage and cystic change
Infiltrative growth
Loss of architecture.
Grading Criteria:
FNCLCC grading system: Grade 1 (low), Grade 2 (intermediate), Grade 3 (high)
Mitotic count: >5 per 10 HPF
Necrosis: <50% (Grade 1), >50% (Grade 2)
Nuclear atypia: moderate to severe.
Immunohistochemistry
Positive Markers:
Desmin (positive in 90% cases)
Smooth muscle actin (SMA, positive)
Caldesmon (positive)
Vimentin (positive)
h-Caldesmon (specific marker).
Negative Markers:
CD117 (KIT) (negative, excludes GIST)
DOG1 (negative)
S-100 (negative, excludes MPNST)
CD34 (negative)
Cytokeratins (negative).
Diagnostic Utility:
Confirms smooth muscle differentiation
Distinguishes from GIST (most important differential)
Excludes other sarcomas
Ki-67 shows high proliferation index
Essential for diagnosis.
Molecular Subtypes:
Conventional leiomyosarcoma: typical smooth muscle markers
Epithelioid variant: similar immunoprofile
Pleomorphic variant: variable marker expression.
Molecular/Genetic
Genetic Mutations:
TP53 mutations (60-70% cases)
RB1 mutations
PTEN loss
MDM2 amplification
Complex karyotype with multiple chromosomal aberrations.
Molecular Markers:
p53 overexpression
High Ki-67 index (>20%)
Loss of p16
MDM2 overexpression
Aneuploidy.
Prognostic Significance:
Size >5 cm: worse prognosis
High mitotic rate: aggressive behavior
Tumor necrosis: poor prognostic factor
Grade: most important prognostic factor
Complete resection: better outcome.
Therapeutic Targets:
Complete surgical resection
Doxorubicin-based chemotherapy
Ifosfamide
Pazopanib (advanced disease)
Radiation therapy (adjuvant)
Clinical trials.
Differential Diagnosis
Similar Entities:
Gastrointestinal stromal tumor (GIST)
Leiomyoma
Malignant peripheral nerve sheath tumor
Synovial sarcoma
Fibrosarcoma
Undifferentiated sarcoma.
Distinguishing Features:
Leiomyosarcoma: desmin+, high mitoses
GIST: CD117+, DOG1+
Leiomyoma: low mitoses (<2/10 HPF)
MPNST: S-100+
Synovial sarcoma: t(X;18), TLE1+.
Diagnostic Challenges:
Distinguishing from high-grade GIST
Separating from leiomyoma (mitotic count crucial)
Identifying epithelioid variant
Immunohistochemistry essential
Molecular testing may be helpful.
Rare Variants:
Epithelioid leiomyosarcoma
Myxoid leiomyosarcoma
Pleomorphic leiomyosarcoma
Inflammatory leiomyosarcoma
Radiation-induced leiomyosarcoma.
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
Small bowel resection with tumor, measuring [size] cm
Diagnosis
Leiomyosarcoma of small intestine
Histological Grade
FNCLCC Grade: [1/2/3] (low/intermediate/high grade)
Histological Features
Malignant spindle cell tumor with smooth muscle differentiation
Mitotic Count
Mitotic count: [X] per 10 high-power fields
Tumor Necrosis
Tumor necrosis: [percentage]% of tumor volume
Size and Location
Tumor size: [X] cm, location: [jejunum/ileum/duodenum]
Margins
Resection margins: [negative/positive], closest margin: [X] mm
Special Studies
Desmin: positive, SMA: positive, CD117: negative, DOG1: negative
Ki-67 proliferation index: [percentage]%
[other study]: [result]
Pathologic Stage
pT[stage], based on size and invasion
Final Diagnosis
Small intestinal leiomyosarcoma, FNCLCC Grade [grade], [size] cm