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Submucosal Tumors (SMTs) of the Esophagus and Gastroesophageal Junction (GEJ)

Introduction

  • Definition: SMTs are rare, benign lesions originating beneath the mucosal layer of the esophagus and GEJ.
  • Prevalence:
    • Overall prevalence of benign esophageal tumors and cysts is about 0.5%.
    • 18% of all esophageal tumors are benign; 82% are malignant.
    • Occur in all ages, most commonly between the 4th and 6th decades.
    • Male predominance is observed.

Clinical Presentation

  • Symptoms (largely size-dependent):
    • Dysphagia and regurgitation due to intraluminal obstruction.
    • Pain.
    • Pulmonary symptoms from extramural compression.
    • Bleeding.
  • Physical Examination:
    • Usually unrevealing unless the tumor is large.
    • Approximately 50% of SMTs are asymptomatic and found incidentally.

Diagnosis

  • Imaging Studies:
    • Chest X-ray: May show mediastinal prominence for large tumors.
    • Computed Tomography (CT): Detects small lesions or esophageal wall thickening.
    • Contrast Esophagram: Reveals smooth-walled indentation.
  • Differential Diagnosis:
    • Benign solid tumors.
    • Cysts.
    • Vascular anomalies.
    • Cancer.

  • Biopsy Challenges:

    • Standard endoscopic biopsies may be inadequate due to submucosal location.
    • Endoscopic Ultrasound (EUS)-guided Fine-Needle Aspiration (FNA) may be indeterminate.

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Treatment Considerations

  • Surgical Resection:
    • Recommended for large or symptomatic SMTs.
  • Observation vs. Surgery:
    • Small, asymptomatic tumors may be surveilled.
    • Observation is generally recommended for asymptomatic lesions less than 3 cm.
    • Concerns include patient compliance, cost, potential delayed malignancy diagnosis, and patient anxiety.

Advances in Management

  • Imaging:
    • Improved technology enhances confidence in non-invasive diagnosis.
  • Medical Therapy:
    • Targeted molecular therapy (e.g., imatinib) has improved outcomes for certain tumors like GIST.
  • Surgical Techniques:
    • Shift from open surgery to minimally invasive techniques:
      • Laparoscopy.
      • Video-Assisted Thoracoscopic Surgery (VATS).
      • Robotic surgery.
    • Development of endoscopic resection techniques for select SMTs.

Surgical Management of SMTs

Indications for Surgical Resection

  • Symptomatic lesions.
  • Inability to rule out malignancy.
  • Atypical imaging findings.
  • Overlying mucosal erosion or dysplasia.
  • Regional lymphadenopathy.
  • Large tumors (size criteria vary).
  • Tumor growth during surveillance.

Traditional Surgical Approaches

  • Open Thoracotomy or Laparotomy:
    • Enucleation Procedure:
      • Localization of tumor via visualization and palpation.
      • Incision of overlying pleura and muscle layers.
      • Tumor is enucleated from the mucosa.
      • Mucosal injuries are repaired.
    • Outcomes:
      • Mortality less than 1.3%.
      • 90% of patients symptom-free after 5 years.
  • Esophagectomy:
    • Indicated for tumors larger than 8 cm or diffuse leiomyomatosis.
    • Historically required in 5-10% of leiomyoma cases.

Minimally Invasive Techniques

  • Laparoscopy, VATS, Robotic Surgery:
    • Benefits:
      • Reduced postoperative pain.
      • Fewer pulmonary complications.
      • Shorter hospital stay.
    • Techniques:
      • Use of intraoperative endoscopy for tumor localization and mucosal integrity testing.
      • Laparoscopic Transgastric Approach:
        • For posteriorly located GEJ tumors.
        • Trocar placement through the gastric lumen.
      • Robotic Surgery:
        • Improved dexterity and precision.
        • Considerations include cost and equipment availability.

Endoscopic Resection Techniques

Endoscopic Mucosal Resection (EMR)

  • Indications: Small, superficial tumors (<2 cm, confined to mucosa or submucosa).
  • Technique:
    • Injection of lifting solution to create a pseudopolyp.
    • Lesion is captured and resected using a snare.
  • Advantages:
    • Minimally invasive.
    • Suitable for superficial lesions.

Endoscopic Submucosal Dissection (ESD)

  • Indications: Larger tumors (>2 cm) or those involving deeper layers.
  • Technique:
    • Marking the lesion margins.
    • Submucosal injection of lifting solution.
    • Circumferential mucosal incision.
    • Submucosal dissection around the lesion.
  • Variations:
    • Submucosal Tunneling:
      • Creation of a tunnel to access and resect the tumor.
      • Allows for mucosal defect closure post-resection.
  • Considerations:
    • Steeper learning curve.
    • Potential complications: perforation, bleeding, strictures.
    • Requires expertise and careful patient selection.

Specific Pathologies of SMTs

Leiomyoma

  • Most common benign esophageal tumor (60-70% of benign cases).
  • Epidemiology:
    • Rare, representing 0.4-1% of all esophageal tumors.
    • Male-to-female ratio of 2:1.
    • Can occur at any age; diffuse leiomyomatosis more common in children.
  • Location:
    • Predominantly in the distal two-thirds of the esophagus.
  • Pathophysiology:
    • Originates from smooth muscle cells.
    • Typically solitary and encapsulated.
    • Sizes range from a few millimeters to 29 cm ("giant" if over 1000 g).
  • Histology:
    • Fascicles of spindle-shaped smooth muscle cells.
    • Immunohistochemistry:
      • Positive for Smooth Muscle Actin (SMA), Desmin, Estrogen Receptors.
      • Negative for CD117 and CD34 (distinguishes from GIST).
  • Clinical Presentation:
    • Often asymptomatic when small.
    • Symptoms include:
      • Dysphagia.
      • Substernal or epigastric pain.
      • Heartburn.
      • Rarely, bleeding or respiratory symptoms.
      • A/w:
        • Li fraumeni = multiple leomyomatosis
        • Alport Syndrome = X linked = glomerular nephropathy, sensory neural deafness, occular myopathy [multiple leomyomatosis]
  • Diagnosis:
    • Barium Esophagram: Smooth, intraluminal filling defect.
    • CT Scan: Eccentric esophageal wall thickening.
    • Endoscopy: Submucosal bulge with intact mucosa.
    • EUS: Hypoechoic, homogeneous mass.
    • Biopsy: Controversial due to risks and potential for inconclusive results.
  • Treatment:
    • Observation:
      • Acceptable for asymptomatic lesions less than 2-5 cm. [<2cm]

    • Surgical Resection:

      • Indicated for symptomatic or larger tumors.
      • Enucleation via open or minimally invasive approaches.

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Leiomyosarcoma

  • Malignant transformation of leiomyoma (rare, 0.2% risk).
  • Prognosis:
    • Poorer outcomes compared to benign leiomyoma.
    • Survival rates at 1, 3, and 5 years are 60.2%, 42.8%, and 32.1%, respectively.
  • Treatment:
    • Surgical Resection is primary.
    • Radiotherapy may be considered for unresectable cases.

Gastrointestinal Stromal Tumor (GIST)

  • Definition: Mesenchymal tumor with c-KIT or PDGFRA mutations.
  • Epidemiology:
    • Most common GI mesenchymal tumor.
    • Esophageal GISTs are rare (~1% of GISTs).
    • Slight male predominance.
  • Location:
    • Typically in the lower third of the esophagus.
  • Histology:
    • Spindle cell or epithelioid patterns.
    • Immunohistochemistry:
      • Positive for CD117 (c-KIT), CD34.
      • DOG1 [calcium dependent channel] may be used if KIT-negative.
  • Clinical Presentation:
    • Similar to leiomyoma (dysphagia, pain, bleeding).
  • Diagnosis:
    • Imaging: CT and PET scans for staging.
    • EUS with FNA Biopsy: Essential for diagnosis and risk stratification.

  • Risk Stratification:

    • Based on tumor size, mitotic rate, and location.

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  • Treatment:

    • <2cm = observe
    • Surgical Resection:
      • Goal is complete resection with negative margins.
      • Organ-sparing techniques preferred.
    • Medical Therapy:
      • Imatinib (tyrosine kinase inhibitor) for unresectable or high-risk tumors.
      • Adjuvant therapy recommended for high-risk cases.
    • Considerations:
      • Avoid tumor rupture to prevent dissemination.
      • Lymphadenectomy generally not required.
      • Re resection not required if microscopic positive disease present

Schwannoma

  • Least common esophageal mesenchymal tumor.
  • Epidemiology:
    • Occurs in 4th to 6th decades.
    • No gender preference.
  • Histology:
    • Composed of spindle cells.
    • Immunohistochemistry:
      • Positive for S-100 and Glial Fibrillary Acidic Protein (GFAP).
      • Negative for c-KIT, CD34, SMA.
  • Clinical Presentation:
    • Similar to other SMTs.
    • May cause respiratory symptoms if proximal.
  • Diagnosis:
    • EUS: Hypoechoic mass in submucosa or muscularis propria.
  • Treatment:
    • Surgical Resection via enucleation.
    • Excellent prognosis with low recurrence rates.

Granular Cell Tumor (GCT)

  • Rare SMT that can occur throughout the body.
  • Epidemiology:
    • Typically presents in the 4th decade.
    • No gender predominance.
    • 2-3% are malignant.
  • Histology:
    • Cells with granular cytoplasm and small nuclei.
    • Positive for S-100 protein.
  • Clinical Presentation:
    • Size-dependent symptoms; 50% are symptomatic.
  • Diagnosis:
    • Endoscopy: Submucosal bulge, sometimes with yellow coloration.
    • EUS: Hyperechoic mass within submucosa.
  • Treatment:
    • Resection for symptomatic or larger lesions.
    • Endoscopic resection is increasingly accepted.

Hemangioma

  • Rare, benign vascular tumor of the esophagus.
  • Epidemiology:
    • Very low prevalence (0.04%).
    • Slight male predominance.
  • Clinical Presentation:
    • Dysphagia, bleeding, rarely massive hemorrhage.
  • Diagnosis:
    • Endoscopy: Bluish, compressible submucosal lesion.
    • EUS with Doppler: May detect vascular flow.
    • Biopsy: Generally avoided due to bleeding risk.
  • Treatment:
    • Observation for asymptomatic cases.
    • Surgical Resection for symptomatic tumors.
    • Ablative therapies (e.g., laser, sclerotherapy) as alternatives.

Fibrovascular Polyps

  • Most common intraluminal esophageal tumor.
  • Epidemiology:
    • Slight male predominance.
    • Common in the 5th to 7th decades.
  • Pathophysiology:
    • Originate near the cricopharyngeus muscle.
    • Elongate due to peristalsis and luminal pressure.
  • Clinical Presentation:
    • Dysphagia, respiratory symptoms.
    • Potential for regurgitation into the oropharynx.
    • Risk of aspiration or asphyxiation.
  • Diagnosis:
    • May be missed on imaging or endoscopy due to proximal location.
    • CT Scan: Heterogeneous intraluminal mass.
  • Treatment:
    • Surgical Resection is recommended to prevent airway obstruction.
    • Transcervical excision or endoscopic removal.
    • Ensuring complete removal to prevent recurrence.

Conclusion

  • SMTs of the esophagus and GEJ present unique diagnostic and therapeutic challenges due to their rarity and diversity.
  • Management Strategies:
    • Should be individualized based on tumor type, size, symptoms, and potential malignancy risk.
    • Advances in minimally invasive and endoscopic techniques have significantly improved patient outcomes.
  • Multidisciplinary Approach:
    • Involving gastroenterologists, surgeons, oncologists, and radiologists is crucial for optimal care.
  • Patient Monitoring:
    • Regular follow-up with imaging and endoscopy is essential, especially for lesions under surveillance or after resection.

Note: Always consult current clinical guidelines and multidisciplinary teams when managing SMTs, as recommendations may evolve with ongoing research and technological advancements.