Esophageal carcinoma

Esophageal carcinoma is relatively uncommon. It tends to present with increasing dysphagia, initially to solids and progressing to liquids as the tumor increases in size, obstructing the lumen of the esophagus.

Epidemiology

Esophageal cancer is responsible for <1% of all cancers and 4-10% of all gastrointestinal malignancies. There is recognized male preponderance with the squamous cell subtype, M:F 4:1. 

The incidence of the subtypes has regional variation. The squamous cell subtype has the greatest worldwide incidence (~90%), but the adenocarcinoma subtype is more common in many parts of North America and Europe. In addition, there are certain regions where individuals are at particularly high risk of developing esophageal cancer, e.g. Iran, Malawi, Zimbabwe, Mongolia, Italy, and China.

Predisposing factors include ⁸:

• alcohol and smoking: for squamous cell carcinoma and adenocarcinoma

• achalasia

• asbestosis

• Barrett esophagus: for adenocarcinoma

• celiac disease

• ionizing radiation

• caustic stricture/lye stricture

• Plummer-Vinson syndrome

• obesity: for adenocarcinoma

• history of oral or pharyngeal cancer

• human papillomavirus (HPV)

• tylosis (Howel–Evans syndrome): rare autosomal dominant disease with hyperkeratosis of the palms and soles with a high incidence of esophageal squamous cell carcinoma

Clinical presentation

Patients present with progressive dysphagia, weight loss, chronic worsening gastro-esophageal reflux and hoarseness, cough, vocal cord paralysis, or other signs and symptoms of mediastinal invasion.

Pathology

Histological types

• squamous cell carcinoma of esophagus: 81-95% (worldwide)

• adenocarcinoma of esophagus: 4-19% (worldwide)

  • arising from mucosal/submucosal glands, heterotopic gastric mucosa, or columnar-lined epithelium

  • >90% related to Barrett esophagus

  • tend to occur at the gastro-esophageal junction

• other types

  • mucoepidermoid carcinoma

  • adenoid cystic carcinoma (ACC)

  • spindle-cell squamous carcinoma

  • leiomyosarcoma

  • rhabdomyosarcoma

  • fibrosarcoma

  • lymphoma

* in the western world adenocarcinoma is as common or even slightly more common than squamous cell carcinoma

Macroscopic appearance

• polypoid/fungating (most common)

  • sessile/pedunculated tumor

  • lobulated surface protruding

  • irregular, polycyclic, overhanging, step-like "apple core" lesion

• ulcerating: large ulcer niche within a bulging mass

• infiltrating: gradual narrowing with a smooth transition

• superficial spreading carcinoma

Staging

See the separate articles by histology:

• esophageal and esophagogastric junction adenocarcinoma (staging)

• esophageal and esophagogastric junction squamous cell carcinoma (staging)

• esophageal and esophagogastric junction neuroendocrine tumor (staging)

Metastases

• lymphatic

  • anterior jugular chain and supraclavicular nodes (primary in upper 1/3)

  • para-esophageal and subdiaphragmatic nodes (primary in middle 1/3)

  • mediastinal and paracardiac and celiac trunk nodes (primary in lower 1/3)

• hematogenous: lung, liver, adrenal glands

Radiographic features

A combination of CT scan, transesophageal ultrasound, and PET-CT are used for staging of the disease. CT is the best initial modality for detection of the distant metastasis, gross direct invasion, and enlarged lymph nodes. Ultrasound is the most sensitive modality for assessment of the depth of invasion and regional enlarged lymph nodes. PET can be useful for restaging after the initial neoadjuvant therapy ⁷. 

Plain radiograph

Chest radiograph

Many indirect signs can be sought on a chest radiograph and these include:

• widened azygo-esophageal recess with convexity toward right lung (in 30% of distal and mid-esophageal cancers)

• thickening of posterior tracheal stripe and right paratracheal stripe >4 mm (if tumor located in the upper third of esophagus)

• tracheal deviation or posterior tracheal indentation/mass

• retrocardiac or posterior mediastinal mass

• esophageal gas-fluid level

• lobulated mass extending into gastric bubble (Kirklin sign)

• repeated aspiration pneumonia (with tracheo-esophageal fistula)

Fluoroscopy

Contrast swallow

• irregular stricture

• prestricture dilatation with 'hold up'

• shouldering of the stricture

US

Endoscopic ultrasound

The most accurate imaging modality for the T staging of esophageal cancer. It defines the layers of the esophageal wall hence can differentiate T1, T2, and T3 tumors.

The esophagus consists of five layers:

1. first hyperechoic layer represents the interface between the balloon and the superficial mucosa

2. second hypoechoic layer represents the lamina propria and muscularis mucosae

3. third hyperechoic layer represents the submucosa

4. fourth hypoechoic layer represents the muscularis propria

5. fifth layer represents the interface between the adventitia and surrounding tissues

CT

• eccentric or circumferential wall thickening >5 mm

• periesophageal soft tissue and fat stranding

• dilated fluid- and debris-filled esophageal lumen is proximal to an obstructing lesion

• tracheobronchial invasion appears as a displacement of the airway (usually the trachea or left mainstem bronchus) as a result of mass effect by the esophageal tumor

• aortic invasion

PET-CT

FDG PET-CT is useful for detecting esophageal primary tumors yet it has little role in helping determine the specific T classification because it provides limited information about the depth of tumor invasion.

PET-CT is also superior to CT for detecting lymph node metastases and can depict metastases in normal-sized lymph nodes through the uptake of FDG. 

PET-CT has a primary role in the depiction of distant sites of metastatic disease.

The most common sites of distant metastases detected at PET (but frequently missed at CT) are the bones and liver. 

Treatment and prognosis

The 5-year mortality depends on the stage of the tumor. Unfortunately, most cases present with regional or distant metastatic disease (30% and 40% respectively).

• localized disease: ~40% 5-year survival

• distant metastatic disease: ~5% 5-year survival

Endoscopic mucosal resection, without or with localized ablation is an option for localized (T1a) disease. These epithelial tumors are usually <2 cm, asymptomatic, and noncircumferential.

For T1b tumors and above, surgical options are mostly limited to esophagectomy (including sometimes with palliative colonic interposition (see case 19)).

Complications

• fistula formation to the trachea (5-10%), bronchi or mediastinum: can be either due to direct tumor progression or iatrogenic effects (e.g. radiation therapy) 

• esophageal perforation

Differential diagnosis

Imaging differential considerations include:

• benign tumors of the esophagus

  • esophageal leiomyoma

  • esophageal leiomyomatosis

• non-malignant conditions (e.g. diffuse inflammation)