Squamous cell carcinoma or adenocarcinoma of the esophagus; presents late with dysphagia and weight loss.
Also known as: esophageal cancer, esophageal carcinoma, esophageal adenocarcinoma, squamous cell carcinoma esophagus
Overview
Malignant neoplasm arising from the esophageal epithelium. Two principal histologies: squamous cell carcinoma (SCC, ~30% in US, upper/mid esophagus) and adenocarcinoma (AC, ~70% in US, distal esophagus and GEJ, arising from Barrett mucosa).
Epidemiology
~21,000 new cases and ~16,000 deaths annually in the US. 5-year survival ~20% (improving with multimodal therapy in localized disease). Worldwide, SCC predominates (Asia, Africa); in Western countries, AC has overtaken SCC due to rising obesity and GERD.
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Adenocarcinoma: chronic GERD, Barrett esophagus, obesity (central), male sex, white race, smoking, age >50
Squamous cell carcinoma: smoking, heavy alcohol (synergistic), hot beverages, nitrosamine-rich diet, achalasia, caustic ingestion (lye), tylosis, HPV (some regions), Plummer-Vinson syndrome, low socioeconomic status
Both: prior thoracic radiation, family history
Pathophysiology
Adenocarcinoma: chronic acid reflux → Barrett intestinal metaplasia → low-grade dysplasia → high-grade dysplasia → invasive AC. Squamous cell: carcinogen-driven (tobacco, alcohol, nitrosamines, HPV) progression from dysplasia to invasion. Both spread submucosally via rich esophageal lymphatics, often with skip lesions.
Clinical presentation
Symptoms
Progressive solid-food dysphagia (initially solids, later liquids) — hallmark
Unintentional weight loss
Odynophagia
Anemia or occult/overt GI bleeding
Chest pain or retrosternal discomfort
Hoarseness (recurrent laryngeal nerve invasion)
Cough or aspiration (tracheoesophageal fistula — late finding)
Signs / physical exam
Cachexia, temporal wasting
Lymphadenopathy (supraclavicular — Virchow node)
Hepatomegaly if metastatic
Hoarseness from vocal cord paralysis
Classic findings
Older smoker or chronic GERD patient with progressive dysphagia for solids followed by liquids and >5% weight loss.
Differential diagnosis
Achalasia / pseudoachalasia — Progressive dysphagia to solids and liquids; manometry — but pseudoachalasia FROM esophageal cancer can mimic primary achalasia
Peptic stricture — Long-standing GERD, slow progression; smooth tapered narrowing on imaging; biopsy if any suspicion
Eosinophilic esophagitis — Young, atopic; biopsy with ≥15 eos/HPF
Schatzki ring — Intermittent solid-food dysphagia (steakhouse syndrome); thin ring at GEJ
Extrinsic compression (lung cancer, mediastinal mass, aortic aneurysm) — Imaging shows extrinsic mass; biopsy of esophagus normal
Esophageal motility disorder (DES, jackhammer) — Manometric abnormality; normal mucosa on EGD
Diagnostic workup
Diagnostic criteria
Histologic diagnosis on biopsy. Staging by AJCC 8th edition (TNM): T (depth: mucosa → submucosa → muscularis propria → adventitia → adjacent structures), N (regional nodes), M (distant). Stage 0-IV directs therapy.
Labs
CBC (anemia)
BMP, LFTs, albumin
Nutritional assessment
Imaging
Upper endoscopy with biopsy — establishes diagnosis; multiple biopsies of suspicious lesion
Endoscopic ultrasound (EUS) — most accurate for T and N staging
PET-CT (FDG) — distant metastases
CT chest/abdomen/pelvis with contrast — local extent and metastases
Bronchoscopy if upper/mid tumor near airway
Barium esophagram — apple-core lesion (not required for diagnosis)
Diagnostic algorithm
Feature
Adenocarcinoma
Squamous Cell Carcinoma
Location
Distal esophagus / GEJ
Upper and mid esophagus
Predominant region
US, Western Europe
Asia, Africa, Eastern Europe
Key risk factors
GERD, Barrett, obesity, smoking
Tobacco, alcohol, hot beverages, achalasia, lye injury
Precursor
Barrett intestinal metaplasia
Squamous dysplasia
Incidence trend
Rising in West
Declining in West
Response to chemoradiation
Good
Excellent (often more chemoradiosensitive)
Esophageal adenocarcinoma vs squamous cell carcinoma — epidemiology and risk factors.
Treatment
First-line
Multidisciplinary team (GI, surgical oncology, medical oncology, radiation oncology, nutrition)
Smoking and alcohol cessation; nutritional optimization
Stage-directed therapy (see by_subtype)
T1a (mucosal) — Stage 0/IA
Endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD)
Radiofrequency ablation of residual Barrett
5-year survival >90%
Locally advanced (T1b-T4a, N0-N3, M0)
Neoadjuvant chemoradiation (carboplatin + paclitaxel + 41.4 Gy — CROSS regimen) followed by esophagectomy
Definitive chemoradiation if not surgical candidate (cisplatin/5-FU or carboplatin/paclitaxel + 50.4 Gy)
Perioperative chemotherapy (FLOT — 5-FU/leucovorin/oxaliplatin/docetaxel) for GEJ adenocarcinoma — alternative to CROSS
Any patient ≥50 with new dysphagia or alarm features deserves prompt EGD — do not assume GERD.
Adenocarcinoma now outnumbers squamous cell in the US, mirroring the rise in GERD/obesity/Barrett.
Endoscopic resection (EMR/ESD) is curative for mucosal (T1a) disease and avoids esophagectomy in selected patients.
CROSS regimen (neoadjuvant chemoradiation + surgery) is standard of care for locally advanced disease (van Hagen, NEJM 2012).
FLOT4 trial established perioperative FLOT as standard for resectable GEJ adenocarcinoma over ECF.
PET-CT detects occult metastases in ~15% of patients deemed resectable by CT alone — essential before curative-intent therapy.
Virchow node (left supraclavicular) and Sister Mary Joseph nodule (periumbilical) suggest M1 disease.
References
NCCN 2024 — NCCN Guidelines Version 4.2024 — Esophageal and Esophagogastric Junction Cancers
CROSS Trial — van Hagen P et al. Preoperative Chemoradiotherapy for Esophageal or Junctional Cancer. NEJM 2012;366:2074-2084
FLOT4 — Al-Batran SE et al. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4). Lancet 2019;393:1948-1957
ACG 2022 Barrett — Shaheen NJ et al. Diagnosis and Management of Barrett's Esophagus: An Updated ACG Guideline. Am J Gastroenterol 2022;117:559-587
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