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PA23.1-2 | Oral & Oesophageal Cancers — SDL Guide (Part 2)

Carcinoma Oesophagus — Overview and Types

A three-panel medical education diagram compares squamous cell carcinoma and adenocarcinoma of the oesophagus by location, risk factors, epidemiology, and pathogenesis. — **Panel A:** Oesophagus, upper third, middle third, lower third, gastro-oesophageal junction, stomach cardia, squamous cell carcinoma in upper/middle third, adenocarcinoma in lower third/GEJ, Barrett mucosa.. **Panel B:** Comparison of squamous cell carcinoma and adenocarcinoma by location, background mucosa, risk factors, geography, and trend.. **Panel C:** SCC pathway: normal squamous epithelium, tobacco/alcohol/hot beverage exposure, dysplasia, invasive squamous carcinoma; adenocarcinoma pathway: chronic GERD, Barrett metaplasia, dysplasia, adenocarcinoma..

Oesophageal carcinoma has two principal histological types with distinct epidemiology, aetiology, location, and pathogenesis:

Feature	Squamous Cell Carcinoma	Adenocarcinoma
Location	Upper/middle third	Lower third / GEJ
Background mucosa	Normal squamous	Barrett metaplasia
Risk factors	Tobacco, alcohol, hot beverages, achalasia, Plummer-Vinson, nitrosamines	Chronic GERD, obesity, Barrett oesophagus
Geography	Dominant type in India, China, Africa	Rising in Western countries
Trend	Stable/declining	Rapidly increasing in West

Squamous cell carcinoma (SCC) accounts for the majority of oesophageal cancer globally and is the predominant type in India. Risk factors reflect the same mucosal carcinogen exposure as oral SCC:
• Tobacco and alcohol (synergistic, as in oral cavity)
• Hot beverages (tea/mate) — thermal injury to mucosa
• Achalasia — chronic stasis of food carcinogens
• Plummer-Vinson syndrome (iron-deficiency anaemia + dysphagia + oesophageal web + koilonychia) — mucosal atrophy predisposes; predominantly in women
• Dietary nitrosamines (preserved foods)
• Prior caustic stricture

Adenocarcinoma arises almost exclusively on a background of Barrett oesophagus (see next block). Its incidence has increased dramatically in Western countries over the last 40 years, paralleling the obesity and GERD epidemic.

Barrett Oesophagus — The Metaplasia–Dysplasia–Carcinoma Sequence

A three-panel medical diagram shows GERD-related injury, Barrett oesophagus histology with goblet cells, and the progression from metaplasia through dysplasia to invasive adenocarcinoma. — **Panel A:** Lower oesophagus, gastro-oesophageal junction, stomach, acid + bile reflux, chronic GERD, recurrent squamous mucosal injury.. **Panel B:** Stratified squamous epithelium, transition zone, columnar intestinal metaplasia, goblet cells, alcian blue-positive acid mucin, lamina propria.. **Panel C:** Chronic GERD injury, Barrett intestinal metaplasia, low-grade dysplasia, high-grade dysplasia / carcinoma in situ, intact basement membrane, basement membrane breach, submucosal invasion, invasive adenocarcinoma..

Barrett oesophagus is defined as the replacement of the normal stratified squamous epithelium of the lower oesophagus by specialised intestinal metaplasia — a columnar epithelium containing goblet cells. It is an adaptive response to chronic gastro-oesophageal reflux (GERD): acid + bile reflux chronically injures the squamous mucosa, and the regenerating stem cells differentiate into a more acid-tolerant columnar phenotype.

Low-power Barrett oesophagus histology diagram showing squamous epithelium transitioning to columnar intestinal metaplasia with goblet cells near the gastro-oesophageal junction. — **Panel A:** Low-power H&E transition zone showing stratified squamous epithelium, columnar epithelium, goblet cells, lamina propria, and muscularis mucosae.. **Panel B:** Magnified intestinal metaplasia showing columnar epithelial cells and mucin-filled goblet cells.. **Panel C:** Lower oesophagus and gastro-oesophageal junction context showing Barrett mucosa and adenocarcinoma risk region..

The sequence — must know each step:
1. Chronic GERD → recurrent squamous mucosal injury
2. Squamous → columnar intestinal metaplasia (Barrett change) — reversible in early stages
3. Metaplasia → low-grade dysplasia: nuclear crowding, hyperchromatism, loss of polarity confined to lower crypt
4. Low-grade → high-grade dysplasia (= carcinoma in situ): full-thickness dysplasia without invasion
5. High-grade dysplasia → invasive adenocarcinoma: basement membrane breach, submucosal invasion

Key points:
• Barrett is identified by goblet cells on biopsy (alcian blue stain highlights the acid mucin in goblet cells)
• Annual malignant transformation risk from Barrett without dysplasia: ~0.1–0.3 %/year; from high-grade dysplasia: ~6–10 %/year
• Barrett patients are enrolled in surveillance endoscopy programmes with biopsy every 1–2 years to catch high-grade dysplasia before invasion
• Obesity increases intra-abdominal pressure → GERD → Barrett → adenocarcinoma; this pathway explains the Western epidemic

SELF-CHECK

A 58-year-old man with a 15-year history of heartburn undergoes endoscopy. Biopsy of the lower oesophagus shows columnar epithelium with goblet cells. The MOST likely long-term complication if this lesion is not surveilled is:

A. Oesophageal squamous cell carcinoma

B. Oesophageal adenocarcinoma

C. Gastric MALT lymphoma

D. Achalasia cardia

Reveal Answer

Answer: B. Oesophageal adenocarcinoma

The biopsy description — columnar epithelium with goblet cells in the lower oesophagus — defines Barrett oesophagus (specialised intestinal metaplasia). Barrett is the established precursor of oesophageal adenocarcinoma (not SCC, which arises from normal squamous epithelium). Without surveillance, the metaplasia → dysplasia → adenocarcinoma sequence may go undetected until the tumour is advanced.

Oesophageal Carcinoma — Gross Patterns and Microscopy

Textbook-style diagram comparing gross patterns of oesophageal carcinoma and side-by-side microscopy of squamous cell carcinoma and adenocarcinoma. — **Panel A:** Fungating/polypoid SCC in middle third; exophytic mass projecting into lumen; central ulceration; upper third; middle third; lower third; oesophageal lumen.. **Panel B:** Ulcerative adenocarcinoma at lower oesophagus/GEJ; irregular ulcer; raised hardened margins; gastro-oesophageal junction; stomach; lower third.. **Panel C:** Infiltrative/scirrhous pattern; diffuse wall thickening; circumferential spread; annular luminal narrowing; muscular wall; residual lumen.. **Panel D:** Oesophageal SCC microscopy; invasive squamous nests; keratin pearls; intercellular bridges; nuclear pleomorphism; desmoplastic stroma.. **Panel E:** Oesophageal adenocarcinoma microscopy; malignant gland formation; mucin secretion; columnar tumour cells; intestinal metaplasia; dysplasia at margin..

Gross patterns (apply to both SCC and adenocarcinoma):
• Fungating/polypoid: exophytic mass projecting into the lumen — may ulcerate at centre; most common pattern for SCC
• Ulcerative: flat ulcer with irregular edges, hardened margins; invades deeply
• Infiltrative/scirrhous: diffuse wall thickening without a discrete mass → linitis plastica-like stiffening; circumferential spread causes annular narrowing of the lumen

Side-by-side gross specimen diagram comparing fungating squamous cell carcinoma in the middle third of the oesophagus with ulcerative adenocarcinoma at the lower oesophagus and gastro-oesophageal junction. — **Panel A:** Opened oesophageal specimen labelled upper third, middle third, lower third, fungating SCC, irregular exophytic mass, and luminal narrowing.. **Panel B:** Opened distal oesophagus and proximal stomach labelled lower third, gastro-oesophageal junction (GEJ), ulcerative adenocarcinoma, raised rolled margins, ulcer base, and proximal stomach..

Microscopy of SCC: same as oral SCC — invasive nests of squamous cells, keratin pearls (well-diff), intercellular bridges, nuclear pleomorphism. Graded I–III as in oral SCC.

Microscopy of adenocarcinoma: gland-forming structures, mucin secretion, variable tubular/papillary/mucinous architecture, on a background of intestinal metaplasia and dysplasia at the margins.

Side-by-side H&E histology comparison of oesophageal squamous cell carcinoma with keratin pearls and oesophageal adenocarcinoma with malignant gland formation and mucin. — **Panel A:** Oesophageal squamous cell carcinoma showing squamous tumour nests, keratin pearls, intercellular bridges, pleomorphic nuclei, and desmoplastic stroma.. **Panel B:** Oesophageal adenocarcinoma showing malignant gland formation, columnar tumour cells, intracellular and luminal mucin, Barrett mucosa, and desmoplastic stroma..

Spread of oesophageal carcinoma:
• Intramural: longitudinal spread in the submucosal lymphatics — tumour extends well beyond visible margins (surgical implication: wide resection margins needed)
• Direct: trachea/bronchi (SCC), aorta, pericardium, recurrent laryngeal nerve (hoarseness)
• Lymphatic: cervical nodes (upper SCC), mediastinal nodes (mid SCC), coeliac/gastric nodes (lower third/adenocarcinoma)
• Haematogenous: liver, lung (late)