Oesophageal Tumours

1. Oesophageal Tumours Dr M. Abrar Barakzai

2. Revision of basic tumour pathology • Definitions • Nomenclature • Benign versus Malignant • Histogenetic classification • Grade and Stage • How do tumours present?

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

4. 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)

5. Esophageal squamous cell carcinoma

6. 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

7. 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.

8. 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.

9. 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 esophagusfavor cervical lymph nodes • Middle third favormediastinal, and tracheobronchial nodes; • Lower third spread to gastric and celiac nodes.

10. Squamous Cell Carcinoma • DysplasiaIN-SITUInfiltration

13. Esophageal squamous carcinoma

14. Carcinoma of the esophagus

16. 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%

17. Esophageal Adenocarcinoma

18. 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.

19. Epidemiology • Esophagealadenocarcinoma 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

21. South West Cancer Registry, 1983-1992 Percent Adenocarcinoma Squamous cell carcinoma 83 84 85 86 87 88 89 90 91 92

22. 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 esophagealadenocarcinoma. • 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.

23. Adenocarcinoma

24. Barrett’s Esophagus

25. Biopsies from the lower oesophagus

28. Morphology • Esophagealadenocarcinoma 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.

29. 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)

30. Early carcinoma in CLO Late carcinoma in CLO

31. Esophageal Adenocarcinoma

32. 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

33. Thank you