GASTROINTESTINAL CARCINOMAS PRESENTATION.pptx

Presentation on GI carcinoma based on Robbins

1. GASTROINTESTINAL CARCINOMAS

2. ORAL CAVITY OESOPHAGUS STOMACH INTESTINE

3. PRECANCEROUS LESION OF ORAL CAVITY LEUKOPLAKIA Leukoplakia is defined by the World Health Organization as “ a white patch or plaque that cannot be scraped off and cannot be characterized clinically or pathologically as any other disease . Seen in adults at any age, but they are usually found in persons 40 to 70 years of age, with a 2 :1 male preponderance. May occur anywhere in the oral cavity (favored locations are buccal mucosa, floor of the mouth, ventral surface of the tongue, palate, and gingiva). They appear as solitary or multiple white patches or plaques, often with sharply demarcated borders. On histologic examination, they present a spectrum of epithelial changes ranging from hyperkeratosis overlying a thickened, acanthotic but orderly mucosal epithelium to lesions with markedly dysplastic changes, sometimes merging into carcinoma in situ.

4. ERYTHROPLAKIA A red, velvety , possibly eroded area within the oral cavity that usually remains level with or may be slightly depressed relative to the surrounding mucosa. The risk of malignant transformation is much higher than is leukoplakia. The histologic changes in erythroplakia only rarely demonstrate orderly epidermal maturation. Virtually all (approximately 90%) display severe dysplasia, carcinoma in situ, or minimally invasive carcinoma.

5. Approximately 95% of cancers of the head and neck are SCCs. Head and neck squamous cell carcinoma (HNSCC) is the sixth most common neoplasm in the world. The pathogenesis of SCC is multifactorial, Infection with high-risk human papillomavirus (HPV) is now the primary cause of SCC of the oropharynx. In India and Asia, the chewing of betel quid and paan is a major regional predisposing influence. Actinic radiation (sunlight) and pipe smoking are known predisposing influences for cancer of the lower lip. In the oropharynx, as many as 80% of SCCs, particularly those involving the tonsils, the base of the tongue, and the pharynx, harbor oncogenic variants of HPV, particularly HPV-16. SQUAMOUS CELL CARCINOMA ORAL CANCEROUS LESIONS

6. Keratinizing SCCs begin as dysplastic lesions, which may or may not progress to full-thickness dysplasia (carcinoma in situ) before invading the underlying connective tissue stroma. Keratinizing SCCs range from well-differentiated to anaplastic, and sometimes sarcomatoid , tumors. The cervical lymph nodes are favored sites of local metastasis, and the most common sites of distant metastasis are mediastinal lymph nodes, lungs, liver, and bones.

7. The histology of HPV-associated SCC is characterized by the proliferation of nests and lobules of nonkeratinizing and basaloid cells growing within sheets of lymphocytes. Immunohistochemical detection of strong p16 protein expression can serve as a marker for HPV-associated SCC .

8. OESOPHAGEAL CARCINOMAS ADENOCARCINOMAS SQUAMOUS CELL CARCINOMA

9. ADENOCARCINOMA OF OESOPHAGUS Esophageal adenocarcinoma typically arises in the background of Barrett esophagus and long-standing GERD. Other major risk factors include tobacco use and exposure to radiation. Molecular studies indicate that progression of Barrett esophagus to adenocarcinoma occurs over an extended period through the stepwise acquisition of genetic and epigenetic changes . Chromosomal abnormalities and mutations of the tumor suppressor genes TP53 and CDKN2A are detected at early stages. With progression, there may be amplification of several oncogenes, including the EGFR, ERBB2, MET, cyclin D1, and cyclin E genes. Esophageal adenocarcinoma usually occurs in the distal third of the esophagus and may invade the adjacent gastric cardia. Microscopically, tumors typically produce mucin and form glands often with intestinal-type morphology; less frequently, tumors are composed of diffusely infiltrative signet-ring cells.

10. SQUAMOUS CELL CARCINOMA OF OESOPHAGUS Risk factors include alcohol and tobacco use, poverty, caustic oesophageal injury, achalasia, Plummer-Vinson syndrome, diets that are deficient in fruits or vegetables, and frequent consumption of very hot beverages. Previous radiation to the mediastinum also predisposes individuals to oesophageal carcinoma. Half of squamous cell carcinomas occur in the middle third of the oesophagus . Squamous cell carcinoma begins as an in situ lesion termed squamous dysplasia . 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. Squamous cell carcinoma is composed of nests of malignant cells that partially recapitulate the organization of squamous epithelium.

11. Adenocarcinoma Squamous cell carcinoma

12. GASTRIC ADENOCARCINOMA Adenocarcinoma is the most common malignancy of the stomach, comprising more than 90% of all gastric cancers.

13. Majority of gastric cancers are not hereditary. Familial gastric cancer is strongly associated with germline loss-of-function mutations in the tumor suppressor gene CDH1, which encodes the cell adhesion protein E-cadherin. E-cadherin loss is a key step in the development of diffuse gastric cancer. Intestinal-type gastric cancers are strongly associated with mutations that result in increased signaling via the Wnt pathway . Gastric tumors with an intestinal morphology form bulky tumors and are composed of glandular structures. Cancers with a diffuse infiltrative growth pattern are typically composed of signet-ring cells . Intestinal-type adenocarcinomas frequently grow along broad cohesive fronts to form either an exophytic mass or an ulcerated infiltrative tumor. The neoplastic cells often contain apical mucin vacuoles , and abundant mucin may be present in gland lumina. In contrast, diffuse cancers permeate the gastric wall as small clusters and individual discohesive cells due to the absence of E-cadherin. These cells do not form glands but instead have large mucin vacuoles that expand the cytoplasm and push the nucleus to the periphery, creating a signet-ring cell morphology.

14. When there are large areas of infiltration, diffuse rugal flattening and a rigid, thickened wall may impart a leather bottle appearance termed linitis plastica . INTESTINAL TYPE DIFFUSE TYPE

15. Intestinal-type adenocarcinoma composed of columnar, gland-forming cells infiltrating through desmoplastic stroma. In infiltrative tumors, signet-ring cells can be recognized by their large cytoplasmic mucin vacuoles and peripherally displaced, crescent-shaped, thin nuclei.

16. COLONIC ADENOCARCINOMA Adenocarcinoma of the colon is the most common malignancy of the GI tract and is a major cause of morbidity and mortality worldwide. Colorectal adenocarcinoma is responsible for nearly 10% of all cancer deaths worldwide. The dietary factors most closely associated with increased risk of colorectal cancer are low intake of unabsorbable vegetable fiber and high intake of refined carbohydrates and fat. High fat intake also enhances hepatic synthesis of cholesterol and bile acids, which can be converted into carcinogens by intestinal bacteria. Aspirin and other NSAIDs have a protective effect. The combination of molecular events that lead to colonic adenocarcinoma is heterogeneous and includes genetic and epigenetic abnormalities. At least two genetic pathways have been described: the APC/β-catenin pathway , which is activated in the classic adenoma-carcinoma sequence, and the MSI pathway, which is associated with defects in DNA mismatch repair and accumulation of mutations in microsatellite repeat regions of the genome.

17. The classic adenoma-carcinoma sequence accounts for up to 80% of sporadic cancers and typically includes mutation of APC early in the neoplastic process.

18. Defects in mismatch repair genes result in microsatellite instability and permit accumulation of mutations in numerous genes.

19. Overall, adenocarcinomas are distributed approximately equally over the entire length of the colon. Tumors in the proximal colon often grow as polypoid, exophytic masses. Carcinomas in the distal colon tend to be annular lesions that produce “napkin-ring” constrictions and luminal narrowing. Most tumors are composed of tall columnar cells that resemble dysplastic epithelium found in adenomas. The invasive component of these tumors elicits a strong stromal desmoplastic response, which is responsible for their characteristic firm consistency. The two most important prognostic factors are depth of invasion and the presence of lymph node metastases.

20. Well-differentiated adenocarcinoma Circumferential, ulcerated rectal cancer Mucinous adenocarcinoma with signet-ring cells and extracellular mucin pools

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