Definition/General
Introduction:
Colorectal leiomyosarcoma is a malignant smooth muscle tumor arising from the muscularis propria of the colorectum
It represents <1% of all colorectal malignancies
It is the second most common primary sarcoma of the colorectum after GIST
Shows aggressive behavior with potential for metastasis.
Origin:
Arises from smooth muscle cells of the muscularis propria
Can originate from blood vessel walls (angioleiomyosarcoma)
Rarely from muscularis mucosae
Shows malignant transformation of smooth muscle cells
Demonstrates invasive growth pattern with metastatic potential.
Classification:
WHO classification: Malignant smooth muscle tumor
French grading system: Grade 1-3 based on differentiation, mitoses, necrosis
Primary vs secondary (metastatic)
Conventional leiomyosarcoma vs epithelioid variant
Myxoid variant also recognized.
Epidemiology:
Peak incidence in 6th-7th decades
Slight female predominance
More common in rectum than colon
Extremely rare in Indian population
Associated with poor prognosis
5-year survival ranges from 30-50%.
Clinical Features
Presentation:
Abdominal mass (most common presentation)
Rectal bleeding
Change in bowel habits
Abdominal pain or discomfort
Bowel obstruction
Weight loss
Perforation in advanced cases.
Symptoms:
Abdominal pain (60-70% cases)
Rectal bleeding (40-50%)
Constipation or diarrhea
Palpable mass
Constitutional symptoms (fever, weight loss)
Anemia due to bleeding
Tenesmus in rectal location.
Risk Factors:
Age >50 years
Previous radiation therapy
Genetic syndromes (Li-Fraumeni, NF1)
Immunosuppression
EBV infection (in immunocompromised)
No clear environmental factors
Rare familial cases.
Screening:
No specific screening guidelines
CT scan for abdominal masses
MRI for local staging
Colonoscopy for mucosal lesions
Biopsy required for diagnosis
PET scan for staging and follow-up.
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Gross Description
Appearance:
Large, bulky mass (usually >5 cm)
Gray-white to tan cut surface
Firm to hard consistency
Irregular margins
Areas of necrosis and hemorrhage common
Whorled pattern may be present.
Characteristics:
Poorly circumscribed
Infiltrative margins
Heterogeneous cut surface
Necrosis in 40-60% cases
Hemorrhage and cystic change
Calcification occasionally present.
Size Location:
Size typically >5 cm at presentation
Rectum most common (50-60%)
Cecum and ascending colon (30%)
Sigmoid colon (15%)
Other sites rare
Intramural location predominant.
Multifocality:
Usually solitary
Multifocal disease rare
Metastases to liver, lung, peritoneum
Local recurrence common if incompletely excised
Synchronous tumors rare.
Microscopic Description
Histological Features:
Fascicles of spindle cells with malignant features
Marked nuclear pleomorphism
High mitotic rate (>2/10 HPF)
Tumor necrosis common
Infiltrative growth pattern
Vascular invasion frequently present.
Cellular Characteristics:
Pleomorphic spindle cells
Enlarged hyperchromatic nuclei
Prominent nucleoli
Abundant eosinophilic cytoplasm
Bizarre giant cells may be present
Atypical mitoses.
Architectural Patterns:
Intersecting fascicles
Storiform pattern in some areas
Herringbone pattern
Loss of fascicular arrangement in high-grade areas
Myxoid change in some cases
Epithelioid areas occasionally.
Grading Criteria:
French grading system: Grade 1 (well-differentiated), Grade 2 (moderately differentiated), Grade 3 (poorly differentiated)
Based on differentiation, mitotic rate, and necrosis
Mitoses >10/10 HPF indicates high grade
Coagulative necrosis indicates high grade.
Immunohistochemistry
Positive Markers:
Smooth muscle actin (SMA) positive (90-95%)
Desmin positive (80-85%)
Calponin positive
h-Caldesmon positive
Vimentin positive
Muscle-specific actin positive.
Negative Markers:
c-KIT (CD117) negative
DOG1 negative
S-100 negative
CD34 negative (except vessels)
Cytokeratins negative
EMA negative.
Diagnostic Utility:
Differentiates from GIST (c-KIT negative)
Confirms smooth muscle origin
Rules out other sarcomas
SMA most reliable marker
Desmin may be lost in high-grade tumors.
Molecular Subtypes:
No specific molecular subtypes
Ki-67 high proliferation index (>20%)
p53 overexpression common
MDM2 amplification rare
Rb protein loss in some cases.
Molecular/Genetic
Genetic Mutations:
Complex karyotype with multiple abnormalities
p53 mutations common (40-50%)
Rb pathway alterations
PIK3CA mutations occasionally
ATRX mutations in some cases
Chromosomal instability.
Molecular Markers:
High Ki-67 (>20-30%)
p53 overexpression
Loss of p16
MDM2 amplification uncommon
Cyclin D1 overexpression
VEGF expression common.
Prognostic Significance:
High grade indicates poor prognosis
Size >5 cm adverse factor
Deep location (intramural) worse prognosis
High mitotic rate predicts recurrence
Necrosis associated with metastasis
Ki-67 >30% poor prognostic factor.
Therapeutic Targets:
Complete surgical excision primary treatment
Adjuvant chemotherapy for high-grade tumors
Doxorubicin-based regimens
Ifosfamide combinations
Pazopanib for metastatic disease
Radiation therapy for local control.
Differential Diagnosis
Similar Entities:
Gastrointestinal stromal tumor (GIST) - c-KIT positive, different morphology
Leiomyoma - low mitotic rate, no atypia
Fibrosarcoma - collagenous matrix, different IHC
Rhabdomyosarcoma - myogenin positive
Undifferentiated sarcoma - negative smooth muscle markers.
Distinguishing Features:
GIST: c-KIT/DOG1 positive, spindle/epithelioid cells
Leiomyoma: <2 mitoses/10 HPF, no atypia, size <2 cm
Fibrosarcoma: herringbone pattern, collagen-rich
Rhabdomyosarcoma: myogenin/MyoD1 positive, cross-striations
Undifferentiated sarcoma: lacks specific markers.
Diagnostic Challenges:
High-grade tumors may lose muscle markers
Small biopsy samples may not show typical features
Dedifferentiated areas lack muscle differentiation
Epithelioid variant mimics carcinoma
Myxoid variant mimics myxoid sarcomas.
Rare Variants:
Epithelioid leiomyosarcoma - epithelioid morphology
Myxoid leiomyosarcoma - myxoid stroma
Pleomorphic leiomyosarcoma - marked pleomorphism
Inflammatory leiomyosarcoma - inflammatory infiltrate
Granular cell variant - granular cytoplasm.
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
Colorectal resection specimen containing a [size] cm intramural mass
Diagnosis
Colorectal Leiomyosarcoma
Classification
Malignant smooth muscle tumor, French Grade [1-3]
Histological Features
Shows fascicles of pleomorphic spindle cells with high mitotic rate ([X]/10 HPF) and tumor necrosis
Size and Extent
Size: [X] cm, extends into [muscularis propria/serosa]
Margins
Margins: [involved/uninvolved], closest margin [X] mm
Lymphovascular Invasion
Lymphovascular invasion: [present/absent]
Immunohistochemistry
SMA: positive, Desmin: positive, c-KIT: negative, Ki-67: [%]
Prognostic Factors
Grade: [1-3], Size: [X] cm, Necrosis: [present/absent], Mitoses: [X]/10 HPF
Final Diagnosis
Colorectal leiomyosarcoma, French Grade [1-3], pT[X]