Definition/General
Introduction:
Esophageal sarcomas are extremely rare malignancies representing 0.1-0.5% of all esophageal tumors and 1-2% of all sarcomas
Include various histological subtypes with leiomyosarcoma being most common (50-60%)
Show mesenchymal differentiation without epithelial features
Generally have poor prognosis due to late diagnosis and aggressive behavior.
Origin:
Arise from mesenchymal tissues of the esophageal wall
Most commonly from smooth muscle of muscularis propria
May arise from submucosa or adventitial connective tissue
Leiomyosarcomas develop from smooth muscle cells
Rhabdomyosarcomas from skeletal muscle differentiation
Undifferentiated sarcomas from pluripotent mesenchymal cells.
Classification:
WHO classification includes leiomyosarcoma (most common)
Rhabdomyosarcoma (second most common)
Fibrosarcoma
Malignant fibrous histiocytoma (undifferentiated pleomorphic sarcoma)
Synovial sarcoma
Kaposi sarcoma
Staging follows soft tissue sarcoma AJCC system.
Epidemiology:
Peak incidence in 5th-6th decades for leiomyosarcoma
Bimodal distribution for rhabdomyosarcoma (children and adults)
Male predominance (2:1 ratio)
No specific geographic predilection
No established risk factors for most types
Associated with previous radiation in some cases.
Clinical Features
Presentation:
Progressive dysphagia (80-90% cases)
Chest pain or retrosternal discomfort
Weight loss (60-70%)
Upper GI bleeding (hematemesis, melena)
Regurgitation
Respiratory symptoms (cough, dyspnea)
Hoarseness (recurrent laryngeal nerve involvement)
Palpable mass in neck or chest.
Symptoms:
Dysphagia initially to solids
Progressive dysphagia to liquids
Odynophagia (painful swallowing)
Constitutional symptoms (fatigue, anorexia)
Iron deficiency anemia
Respiratory symptoms from mediastinal involvement
Back pain from vertebral involvement
Superior vena cava syndrome (rare).
Risk Factors:
Previous radiation therapy (most established risk factor)
Genetic syndromes (Li-Fraumeni, neurofibromatosis)
Immunosuppression (HIV, transplant patients)
Chemical exposure (vinyl chloride, dioxin)
Age >50 years
Male gender
No association with smoking or alcohol.
Screening:
Upper endoscopy for suspicious symptoms
Contrast-enhanced CT chest and abdomen
MRI for local staging
PET-CT for metastatic evaluation
Endoscopic ultrasound for wall layer assessment
Tissue biopsy for definitive diagnosis.
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Gross Description
Appearance:
Large polypoid or intramural mass with smooth surface
Gray-white to tan cut surface with whorled appearance
Firm consistency typical
Areas of necrosis and hemorrhage
Well-circumscribed or infiltrative margins
May show cystic degeneration.
Characteristics:
Size ranges from 3-20 cm at presentation
Intramural growth expanding into lumen
Smooth muscle tumors show whorled cut surface
Rhabdomyosarcomas more heterogeneous appearance
Fish-flesh consistency common
Pseudocapsule may be present.
Size Location:
Most common in distal esophagus (50-60%)
Middle third involvement (30%)
Proximal third involvement (15-20%)
Average size at presentation 6-12 cm
Intramural location most common
May involve multiple anatomic levels.
Multifocality:
Unifocal disease typical
Satellite lesions rare
Skip lesions uncommon
Associated leiomyomas occasionally present
Multifocal disease suggests metastatic disease
Regional lymph node involvement less common than carcinomas.
Microscopic Description
Histological Features:
Leiomyosarcoma: intersecting fascicles of spindle cells with cigar-shaped nuclei
Rhabdomyosarcoma: round to spindle cells with cross-striations
Variable differentiation from well to poorly differentiated
High mitotic activity (>5 per 10 HPF)
Tumor necrosis common
Pleomorphic nuclei.
Cellular Characteristics:
Spindle cell morphology most common
Elongated nuclei with blunt ends (leiomyosarcoma)
Cross-striations in rhabdomyosarcoma
Nuclear pleomorphism and hyperchromatism
Eosinophilic cytoplasm
Multinucleated giant cells may be present
High nuclear-cytoplasmic ratio.
Architectural Patterns:
Fascicular pattern in leiomyosarcoma
Herringbone pattern in fibrosarcoma
Storiform pattern in undifferentiated pleomorphic sarcoma
Solid sheets in poorly differentiated areas
Myxoid areas in some variants
Vascular invasion common.
Grading Criteria:
FNCLCC grading system: differentiation (1-3 points), mitotic count (1-3 points), necrosis (0-2 points)
Grade 1 (2-3 points): well-differentiated
Grade 2 (4-5 points): moderately differentiated
Grade 3 (6-8 points): poorly differentiated
Most esophageal sarcomas are high-grade.
Immunohistochemistry
Positive Markers:
Leiomyosarcoma: smooth muscle actin, desmin, caldesmon, calponin
Rhabdomyosarcoma: desmin, myogenin, MyoD1, skeletal muscle actin
Fibrosarcoma: vimentin
Synovial sarcoma: TLE1, CD99, bcl-2
All sarcomas: vimentin positive.
Negative Markers:
Cytokeratins negative (AE1/AE3, CK7, CK20)
S-100 negative (except nerve sheath tumors)
CD45 negative
CD117 negative (differentiates from GIST)
DOG1 negative
Chromogranin A negative
TTF-1 negative.
Diagnostic Utility:
Smooth muscle markers confirm leiomyosarcoma
Skeletal muscle markers confirm rhabdomyosarcoma
Negative epithelial markers exclude carcinoma
CD117/DOG1 negative excludes GIST
Specific translocations in certain subtypes (synovial sarcoma).
Molecular Subtypes:
Leiomyosarcoma subtypes based on molecular alterations
Rhabdomyosarcoma: alveolar (translocation-positive) vs embryonal
Synovial sarcoma: SS18-SSX fusion
Undifferentiated sarcomas with complex karyotypes
Radiation-associated sarcomas with specific alterations.
Molecular/Genetic
Genetic Mutations:
TP53 mutations common in high-grade sarcomas
RB1 mutations in some cases
PTEN loss in subset
PIK3CA mutations occasional
Complex chromosomal aberrations typical
Specific translocations in certain subtypes (synovial sarcoma: t(X;18)).
Molecular Markers:
p53 overexpression in high-grade tumors
MDM2 amplification in some cases
CDK4 amplification
High proliferation indices (Ki-67 >20%)
VEGF expression associated with angiogenesis
PDGFR expression in some cases.
Prognostic Significance:
Tumor grade most important prognostic factor
Size >5 cm indicates worse prognosis
Deep location (intramural) worse than mucosal
Positive margins indicate poor prognosis
Metastatic disease indicates very poor prognosis
Age >60 years worse prognosis.
Therapeutic Targets:
Anthracycline-based chemotherapy standard treatment
Ifosfamide combinations
Pazopanib for advanced soft tissue sarcomas
Trabectedin for leiomyosarcoma
Targeted therapy limited options
Immunotherapy under investigation.
Differential Diagnosis
Similar Entities:
Gastrointestinal stromal tumor (GIST)
Leiomyoma (benign smooth muscle tumor)
Poorly differentiated carcinoma
Melanoma
Lymphoma
Solitary fibrous tumor
Inflammatory myofibroblastic tumor.
Distinguishing Features:
Sarcoma: cytokeratin negative
Sarcoma: CD117/DOG1 negative
GIST: CD117/DOG1 positive
Leiomyoma: low mitotic activity (<2 per 10 HPF)
Carcinoma: cytokeratin positive
Melanoma: S-100, melanoma markers positive
Lymphoma: CD45 positive.
Diagnostic Challenges:
Differentiating high-grade sarcoma from poorly differentiated carcinoma
Distinguishing leiomyosarcoma from GIST
Small biopsy specimens may be inadequate
Separating different sarcoma subtypes
Crush artifact affecting morphology.
Rare Variants:
Epithelioid leiomyosarcoma
Myxoid leiomyosarcoma
Pleomorphic rhabdomyosarcoma
Alveolar rhabdomyosarcoma with t(2;13) or t(1;13)
Radiation-associated sarcoma
Kaposi sarcoma (especially in HIV patients)
Angiosarcoma.
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
Esophagectomy specimen with intramural tumor in [location], measuring [size] cm
Diagnosis
[Sarcoma subtype] of esophagus
Histological Features
Shows [spindle cell/other] morphology with [differentiation level] features
Grading (FNCLCC System)
Differentiation: [1-3]. Mitotic count: [1-3]. Necrosis: [0-2]. Total grade: [1-3]
Size and Extent
Tumor size: [X] cm. Location: [intramural/other]. Growth pattern: [description]
Mitotic Activity
Mitotic count: [X] per 10 HPF. Necrosis: [X]% of tumor
Margins
Margins: [positive/negative]. Distance to closest margin: [X] mm
Invasion Status
Vascular invasion: [present/absent]. Lymphatic invasion: [present/absent]
Lymph Node Status
Lymph nodes: [X] negative out of [X] examined (sarcomas rarely metastasize to lymph nodes)
Special Studies
IHC: [specific markers based on subtype], Vimentin [+/-], CK [negative]
Molecular studies: [if performed]
Final Diagnosis
[Sarcoma subtype], [grade], [size] cm