Definition/General
Introduction:
Gastric leiomyosarcoma is a malignant smooth muscle tumor of the gastric wall
It is extremely rare in the stomach (<1% of gastric malignancies)
Represents less than 3% of gastric mesenchymal tumors
Must be distinguished from GIST and other sarcomas.
Origin:
Arises from smooth muscle cells of the gastric wall
Most commonly from the muscularis propria
Can originate from muscularis mucosae or vascular smooth muscle
May arise de novo or from malignant transformation of leiomyoma (rare).
Classification:
Classified as conventional leiomyosarcoma (spindle cell)
Epithelioid leiomyosarcoma (rare variant)
Myxoid leiomyosarcoma
Pleomorphic leiomyosarcoma
Graded as low-grade vs high-grade based on morphology.
Epidemiology:
Peak incidence in 5th-7th decades
Slight female predominance
Extremely rare in children
No geographic predilection
Sporadic occurrence in vast majority of cases.
Clinical Features
Presentation:
Abdominal pain and mass (70-80%)
Gastrointestinal bleeding (50-60%)
Weight loss and anorexia (40-50%)
Nausea and vomiting (30-40%)
Early satiety
Bowel obstruction in advanced cases.
Symptoms:
Severe epigastric pain
Massive GI bleeding (hematemesis, melena)
Rapid weight loss (>10% body weight)
Palpable abdominal mass
Constitutional symptoms (fever, night sweats)
Dysphagia if cardia involvement.
Risk Factors:
Previous radiation therapy
Genetic syndromes (Li-Fraumeni, hereditary retinoblastoma)
Immunodeficiency states
Previous leiomyoma (malignant transformation rare)
Carcinogenic exposure
Advanced age.
Screening:
No specific screening protocols
CT imaging for large abdominal masses
Upper endoscopy for GI bleeding
PET-CT for staging
MRI for local extent assessment
Biopsy essential for diagnosis.
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Gross Description
Appearance:
Large, bulky mass (typically >5 cm)
Gray-white to tan cut surface
Areas of necrosis and hemorrhage common
Infiltrative borders
Firm to hard consistency.
Characteristics:
Heterogeneous cut surface with areas of necrosis
Hemorrhage and cystic degeneration
Loss of fascicular pattern seen in leiomyomas
Infiltration into surrounding structures.
Size Location:
Usually large at presentation (mean 8-12 cm)
Fundus and body most common
Transmural involvement frequent
Extension beyond gastric wall common.
Multifocality:
Usually solitary
Multifocal disease rare
Metastases to liver, lung, peritoneum
Local recurrence common if incompletely excised.
Microscopic Description
Histological Features:
Spindle cells with eosinophilic cytoplasm
Significant nuclear pleomorphism
High mitotic activity (>5/10 HPF)
Coagulative necrosis
Infiltrative growth pattern.
Cellular Characteristics:
Pleomorphic spindle cells
Vesicular nuclei with prominent nucleoli
Atypical mitoses
Variable cell size
Eosinophilic to amphophilic cytoplasm.
Architectural Patterns:
Fascicular pattern with intersecting bundles
Storiform pattern
Solid sheets in high-grade areas
Geographic necrosis
Vascular invasion.
Grading Criteria:
FNCLCC system: Differentiation, mitotic count, necrosis
Low-grade: Well-differentiated, <10 mitoses/10 HPF, <50% necrosis
High-grade: Poorly differentiated, >20 mitoses/10 HPF, >50% necrosis.
Immunohistochemistry
Positive Markers:
Smooth muscle actin (90-95%)
Desmin (80-90%)
Caldesmon (70-80%)
Muscle-specific actin
Vimentin
h-Caldesmon (more specific).
Negative Markers:
KIT (CD117) negative
DOG-1 negative
CD34 negative
S-100 negative
Cytokeratins negative
Myogenin negative.
Diagnostic Utility:
Smooth muscle markers essential for diagnosis
KIT negativity distinguishes from GIST
High Ki-67 (>20%) indicates high grade
p53 overexpression in high-grade tumors.
Molecular Subtypes:
No established molecular subtypes
Complex karyotype common
TP53 mutations in high-grade tumors
RB1 alterations
PTEN loss.
Molecular/Genetic
Genetic Mutations:
Complex chromosomal aberrations
TP53 mutations (60-70%)
RB1 mutations (40-50%)
PTEN loss (30-40%)
ATRX mutations
Chromothripsis patterns.
Molecular Markers:
p53 overexpression (50-60%)
Rb loss (40-50%)
High Ki-67 (>20%)
MDM2 amplification (subset)
VEGF overexpression.
Prognostic Significance:
Size >5 cm indicates poor prognosis
High grade associated with worse outcome
Necrosis >50% indicates aggressive behavior
p53 mutations correlate with poor survival.
Therapeutic Targets:
Surgical resection primary treatment
Doxorubicin-based chemotherapy
Gemcitabine/docetaxel combination
Pazopanib for advanced disease
Radiation therapy adjuvant.
Differential Diagnosis
Similar Entities:
GIST
Other sarcomas (undifferentiated pleomorphic)
Metastatic leiomyosarcoma
Inflammatory myofibroblastic tumor
Dedifferentiated liposarcoma.
Distinguishing Features:
Leiomyosarcoma: Desmin positive, KIT negative
GIST: KIT/DOG-1 positive
UPS: Lack of smooth muscle markers
IMT: ALK positive (50%)
Metastatic: Clinical history, imaging.
Diagnostic Challenges:
Distinguishing from high-grade GIST
Separating from undifferentiated pleomorphic sarcoma
Primary vs metastatic determination
Adequate sampling for grading.
Rare Variants:
Epithelioid leiomyosarcoma
Myxoid leiomyosarcoma
Pleomorphic leiomyosarcoma
Inflammatory 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
[specimen type], [size] cm
Diagnosis
Leiomyosarcoma, [grade]
Size and Extent
Size: [X] cm, [transmural involvement]
FNCLCC Grade
Grade [1/2/3]: Differentiation [score], Mitoses [count/10 HPF], Necrosis [%]
Immunohistochemistry
Desmin: +, SMA: +, KIT: -, Ki-67: [%]%
Margins
Margins: [status], closest: [X] mm
Final Diagnosis
Gastric leiomyosarcoma, FNCLCC Grade [X], [size] cm