Oesophageal Tumours

Dr M. Abrar Barakzai

Revision of basic tumour pathology

• Definitions

• Nomenclature– Benign versus Malignant– Histogenetic classification

• Grade and Stage

• How do tumours present?

Benign Tumors• Uncommon• <5% of esophageal tumours• Papillomas• Leiomyomas• Fibrovascular Polyps• Condylomas (HPV)• Lipomas• “Granulation” Tissue

(Pseudotumor)

Malignant tumours of the esophagus

• World wide distribution (but variations)• Increase with increasing age • Links with environmental factors• Two types– Squamous cell carcinoma • (falling incidence)

– Adenocarcinoma • (increasing incidence and link to Barrett’s esophagus)

Esophageal squamous cell carcinoma

Epidemiology

• Male > female,• Adult over 45 years• Variation in incidence worldwide – (from 1 to 30 per 100000)– Calvados region of France very high– Iran, China, Hong kong, Brazil and South

Africa• Six fold more common in African American

Pathogenesis

– Strong alcohol, smoking, tannic acid, betel nuts, fungi in food, nitrosamine, polycyclic hydrocarbons

– Previous radiation therapy in the mediatinum

– Increase evidence for HPV having a role

– loss of several tumor suppressor genes, including p53 and p16/INK4a, is involved.

Morphology.• Half of squamous cell carcinomas occur in the middle third of

the esophagus. • It begins as an in situ lesion termed squamous dysplasia

• Early lesions appear as small, gray-white, plaque-like thickenings.

• Over months to years develop polypoid or exophytic mass and protrude into and obstruct the lumen.

• Other tumors are either ulcerated or diffusely infiltrative

• These may invade surrounding structures including the respiratory tree, mediastinum and pericardium.

Morphology.• Most squamous cell carcinomas are moderately to well-differentiated.

• Less common histologic variants include verrucous squamous cell carcinoma, spindle cell carcinoma, and basaloid squamous cell carcinoma.

• Symptomatic tumors are generally very large at diagnosis and have already invaded the esophageal wall.

• Circumferential and longitudinal spread of the tumour into submucosal lymph nodes

– Upper third cancer of the esophagus favor cervical lymph nodes

– Middle third favor mediastinal, and tracheobronchial nodes;

– Lower third spread to gastric and celiac nodes.

Squamous Cell Carcinoma

• DysplasiaIN-SITUInfiltration

Esophageal squamous carcinoma

Carcinoma of the esophagus

Clinical Features

• Dysphagia, odynophagia (pain on swallowing), and obstruction.

• Patients adjust diet from solid to liquid foods.

• Extreme weight loss and debilitation result from both impaired nutrition and effects of the tumor itself.

• Hemorrhage and sepsis may accompany tumor ulceration. • The tumour has poor prognosis.

• The overall 5-year survival remains a dismal 9%

Esophageal Adenocarcinoma

Esophageal adenocarcinoma

• More likely to be lower third (squamous middle third )

• Usually arise in the back ground of Barrett’s esophagus

• Usually preceded by dysplasia in the metaplastic glandular [intestinal] mucosa

• High grade dysplasia has higher risk than low grade dysplasia

• Risk of adenocarcinoma is reduced by diets rich in fresh fruits and vegetables.

Epidemiology• Esophageal adenocarcinoma occurs most frequently in

Caucasians.

• Sevenfold more common in men.

• Highest in certain developed Western countries, including the US, UK, Canada, Australia, the Netherlands, and Brazil.

• Lowest in Korea, Thailand, Japan, and Ecuador.

• The incidence has increased markedly since 1970

• As a result, now accounts for half of all esophageal cancers in the United States

South West Cancer Registry, 1983-1992

30

35

40

45

50

55

60

65

Adenocarcinoma

Squamous cell carcinoma

83 84 85 86 87 88 89 90 91 92

Percent

Pathogenesis• Progression of Barrett esophagus to adenocarcinoma occurs

through the stepwise acquisition of genetic and epigenetic changes.

• Barrett metaplasia --- progression to dysplasia--- and invasive carcinoma.

• Mutation of p53 are present at early stages of esophageal adenocarcinoma.

• Amplification of c-ERB-B2, cyclin D1, and cyclin E genes;

• Mutation of the retinoblastoma tumor suppressor gene;

• Allelic loss of the cyclin-dependent kinase inhibitor p16/INK4a.

Adenocarcinoma

Barrett’s Esophagus

Biopsies from the lower oesophagus

Morphology

• Esophageal adenocarcinoma usually occurs in the distal third of the esophagus.

• Barrett esophagus is frequently present adjacent to the tumor.

• Initially appearing as flat or raised patches,

• large masses of 5 cm or more in diameter may develop.

Morphology

• Tumors may infiltrate diffusely or ulcerate and invade deeply.

• Tumors most commonly produce mucin and form glands(intestinal-type)

• less frequently tumors are composed of diffusely infiltrative signet-ring cells

• In rare cases, small poorly differentiated cells (similar to small-cell Ca of the lung)

Early carcinoma in CLO Late carcinoma in CLO

Esophageal Adenocarcinoma

Clinical Features• Presentation is as with squamous tumours, progressive

dysphagia, vomiting

• Can be ulcerating lesion with blood loss (including hematemesis)

• May be weight loss – not eating and cancer cachexia

• Spread: direct into adjacent structures and lymph node and further metastasis

• Despite treatment, prognosis is poor!

• 5% survival at 5 years

Thank you