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 esophagus favor cervical lymph nodes – Middle third favor mediastinal, 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 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

21. South West Cancer Registry, 1983-1992 Adenocarcinoma Squamous cell carcinoma 83848586878889909192 Percent

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 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.

23. Adenocarcinoma

24. Barrett’s Esophagus

25. Biopsies from the lower oesophagus

28. 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.

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 CLOLate 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