Definition/General
Introduction:
Cutaneous leiomyosarcoma is a rare malignant smooth muscle tumor of skin
It constitutes 2-3% of all soft tissue sarcomas
It demonstrates smooth muscle differentiation
It shows better prognosis than deep leiomyosarcomas
It has low metastatic potential compared to deeper counterparts.
Origin:
Arises from smooth muscle cells in skin
Most commonly from arrector pili muscles
Can originate from vascular smooth muscle
May arise from dartos muscle (scrotal/labial)
Shows malignant transformation of smooth muscle elements
Involves dermis and subcutis.
Classification:
WHO classifies under smooth muscle tumors
Superficial leiomyosarcoma (cutaneous/subcutaneous)
Deep leiomyosarcoma (muscular/retroperitoneal)
Low-grade cutaneous leiomyosarcoma
High-grade cutaneous leiomyosarcoma
Conventional type
Inflammatory leiomyosarcoma.
Epidemiology:
Peak incidence in 5th-6th decades
Male predominance (2:1 ratio)
Most common on extremities (60-70%)
Trunk (20-30%)
Head and neck (10%)
Indian population shows similar age and gender distribution.
Clinical Features
Presentation:
Slowly enlarging skin nodule
Firm to hard consistency
Skin-colored to red-brown
Well-circumscribed appearance
Mobile over deeper structures
May show ulceration (advanced cases).
Symptoms:
Pain or tenderness (50-60% of cases)
Slow growth over months to years
Firmness on palpation
Occasional bleeding (ulcerated lesions)
Patients report gradually enlarging lump
Functional impairment (large lesions).
Risk Factors:
Previous radiation therapy
Immunosuppression
Genetic syndromes (rare)
Chronic irritation
Pre-existing leiomyoma (controversial)
Most cases are sporadic.
Screening:
No specific screening guidelines
Clinical examination of suspicious lesions
Imaging studies (MRI for extent)
Core biopsy for diagnosis
Multidisciplinary team approach.
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Gross Description
Appearance:
Well-circumscribed nodular mass
Firm consistency
Gray-white cut surface
Size typically 2-5 cm
May show areas of necrosis
Whorled appearance on cut section.
Characteristics:
Lobulated contour
Firm to hard consistency
Homogeneous appearance
May show focal hemorrhage
Encapsulated or well-demarcated
Cut surface shows fascicular pattern.
Size Location:
Size ranges from 1-10 cm (median 3 cm)
Most common on lower extremities (40%)
Upper extremities (25%)
Trunk (20%)
Head and neck (15%)
Genital area (scrotal/labial).
Multifocality:
Usually solitary lesions
Local recurrence if incompletely excised
Distant metastases rare (<5%)
Regional lymph node involvement uncommon
Synchronous lesions extremely rare.
Microscopic Description
Histological Features:
Interlacing fascicles of spindle cells with smooth muscle differentiation
Elongated nuclei with blunt ends
Eosinophilic cytoplasm
Mitotic activity variable
Cellular pleomorphism
Focal necrosis may be present.
Cellular Characteristics:
Elongated spindle cells
Cigar-shaped nuclei with blunt ends
Abundant eosinophilic cytoplasm
Longitudinal striations in cytoplasm
Nuclear pleomorphism variable
Prominent nucleoli
Mitotic figures present.
Architectural Patterns:
Fascicular growth pattern
Intersecting bundles at right angles
Storiform pattern in some areas
Pushing or infiltrative margins
Vascular invasion occasionally seen
Hyalinization of stroma.
Grading Criteria:
FNCLCC grading system
Grade I: Low cellularity, <2 mitoses/10 HPF, no necrosis
Grade II: Moderate cellularity, 2-10 mitoses/10 HPF, <50% necrosis
Grade III: High cellularity, >10 mitoses/10 HPF, >50% necrosis.
Immunohistochemistry
Positive Markers:
Smooth muscle actin (95-100%)
Desmin (80-90%)
Calponin (85-95%)
Smooth muscle myosin heavy chain (90-95%)
h-Caldesmon (80-90%)
Vimentin (positive)
Muscle-specific actin (80-85%).
Negative Markers:
Cytokeratins (negative)
EMA (negative)
S-100 protein (negative)
CD34 (negative)
CD68 (negative)
Factor VIII (negative)
Melanoma markers (negative).
Diagnostic Utility:
Smooth muscle actin most sensitive
Desmin highly specific
h-Caldesmon distinguishes from myofibroblasts
Essential for differential diagnosis
Combination of markers recommended
Useful in poorly differentiated cases.
Molecular Subtypes:
TP53 mutations (50-70%)
RB1 alterations (30-40%)
PTEN loss (20-30%)
PIK3CA mutations (10-15%)
ATRX mutations (subset)
Complex karyotype common.
Molecular/Genetic
Genetic Mutations:
TP53 mutations (50-70%)
RB1 mutations/deletions (30-40%)
PTEN mutations (20-30%)
PIK3CA mutations (10-15%)
ATRX mutations (10-20%)
CDKN2A deletions
MYC amplification (subset).
Molecular Markers:
p53 protein accumulation
Rb protein loss
PTEN loss of expression
PIK3CA activation
Cyclin D1 overexpression
MDM2 amplification (subset)
High genomic instability.
Prognostic Significance:
TP53 mutations associated with higher grade
RB1 loss correlates with aggressive behavior
PTEN loss indicates poor prognosis
Size and grade most important prognostic factors
Cutaneous location has better prognosis than deep.
Therapeutic Targets:
Doxorubicin (standard chemotherapy)
Ifosfamide
Gemcitabine/docetaxel
Pazopanib (multi-kinase inhibitor)
Olaratumab (PDGFRA inhibitor)
mTOR inhibitors (investigational).
Differential Diagnosis
Similar Entities:
Leiomyoma (benign smooth muscle tumor)
Fibrosarcoma (fibroblastic tumor)
Malignant peripheral nerve sheath tumor
Dermatofibrosarcoma protuberans
Spindle cell melanoma
Atypical fibroxanthoma.
Distinguishing Features:
Leiomyosarcoma: Desmin positive
Leiomyosarcoma: SMA positive
Leiomyoma: Low mitotic rate
Fibrosarcoma: Smooth muscle markers negative
MPNST: S-100 positive
DFSP: CD34 positive
Melanoma: Melanoma markers positive.
Diagnostic Challenges:
Distinguishing leiomyoma from low-grade leiomyosarcoma
Poorly differentiated leiomyosarcoma vs other sarcomas
Smooth muscle markers may be focal
Atypical smooth muscle tumors (STUMP equivalent)
Size criteria in diagnosis.
Rare Variants:
Inflammatory leiomyosarcoma (prominent inflammatory infiltrate)
Myxoid leiomyosarcoma (myxoid matrix)
Granular cell leiomyosarcoma
Epithelioid leiomyosarcoma
Pleomorphic leiomyosarcoma
Dedifferentiated 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
Wide local excision from [site], measuring [X x Y x Z] cm
Diagnosis
Cutaneous Leiomyosarcoma
Histological Grade
Grade: [I/II/III] (FNCLCC system)
Microscopic Features
Shows fascicles of spindle cells with smooth muscle differentiation and [grade-specific features]
Size and Depth
Tumor size: [X] cm; Depth: [dermal/subcutaneous/deeper]
Mitotic Count
Mitotic count: [X] mitoses per 10 HPF
Necrosis
Necrosis: [present/absent]; if present: [<50%/>50%]
Margins
Margins: [involved/uninvolved], closest margin [X] mm
Immunohistochemistry
SMA: [positive/negative]; Desmin: [positive/negative]; h-Caldesmon: [positive/negative]
Risk Assessment
Risk: [low/intermediate/high] based on size, grade, and location
Final Diagnosis
Cutaneous Leiomyosarcoma, Grade [I/II/III], [size] cm