SURGERY-PATHOLOGY MEET adenocarcinoma ppt

Adenocarcinoma rectum

1. SURGERY-PATHOLOGY MEET Presenter: Dr. Farheen khan(Jr 1) Moderator: Dr. (Prof ) Nishi Tandon Department Of Pathology

2. INTRODUCTION Patient’s name: Mr. Satish Gupta Age/Sex: 27 yr / M ale PID No: 2681 244 Colonoscopy guided b iopsy which was taken from the rectosigmoid mass was sen t to histopathalogy on 5/ 05 /2024 Specimen received- Colonoscopy guided b iopsy Clinical diagnosis : Rectosigmoid malignancy,Acute intestinal obstruction Procedure done: c olonoscopy guided b iopsy

3. GROSS Received multiple, gray-white soft tissue pieces altogether measuring < 0.5 cm ( All processed )

4. MICROSCOPY Section from the biopsy tissue shows an infiltrating tumor composed of glands lined by atypical cells.These atypical cells having high nuclear-cytoplasmic ratio, nuclear pleomorphism, hyperchromasia and prominent nucleoli with amphophillic cytoplasm. The stroma shows chronic inflammatory infiltrates comprising of lymphocytes and plasma cells.  

5. Fig- 1 ADENOCARCINOMA - RECTUM 10x view Fig -2 ADENOCARCINOMA - RECTUM 40x view

6. HISTOPATHOLOGICAL IMPRESSION   HISTOMORPHOLOGY IS SUGGESTIVE OF MALIGNANT NEOPLASM FAVOURING ADENOCARCINOMA -RECTUM

7. DISCUSSION

8. INTRODUCTION Colorectal carcinoma (CRC) is the third most commonly diagnosed cancer worldwide Approximately 1.2 million new cases of colorectal adenocarcinoma and 600,000 associated deaths occur each year worldwide. Incidence rates for colon cancer are similar for men and women while rectal cancers occur more often in men. Advancing age,history of polyps,family history,dietry factors such as low intake of fibre high intake of animal protein and fat,cigarette smoking,alcohol intake and sedentary lifestyle are associated with increased risk of colorectal cancers. Genetic factors include high predisposition for CRC in patients with FAP (nearly 100% by the age of 50),HNPCC syndrome and related nonpolyposis associated hereditary conditions. NSAIDs and hormone replacement therapy protect against CRCs and substantially reduce its incidence.

9. COLORECTAL ADENOCARCINOMA Most common colorectal cancer It is a malignant epithelial tumor originating in the large bowel,showing glandular or mucinous differentiation. Localization - Right sided or proximal colon carcinomas ( including those in caecum,ascending and transverse colon). Left sided colon carcinomas(located anywhere from the splenic flexure up to the sigmoid). Rectal carcinomas.

10. ETIOLOGY & PATHOGENESIS Colorectal adenocarcinoma develops through a series of genetic and molecular changes that progressively transform normal colonic epithelial cells into cancerous cells. Here's an overview of its pathogenesis. 1. Genetic Susceptibility : Certain genetic factors can predispose individuals to colorectal cancer. These include inherited mutations in genes such as APC (adenomatous polyposis coli), MUTYH, and DNA mismatch repair genes (e.g., MLH1, MSH2, MSH6, PMS2), which are associated with Lynch syndrome and familial adenomatous polyposis (FAP). 2. Initiation : The process typically begins with the acquisition of mutations in proto-oncogenes and tumor suppressor genes. For example, mutations in APC are early events in the adenoma-carcinoma sequence.

11. 3. Adenoma Formation : Most colorectal adenocarcinomas arise from adenomatous polyps. These polyps initially form due to mutations that lead to dysregulation of cell growth and proliferation pathways (such as Wnt signaling pathway activation due to APC mutation). Adenomas are considered precursor lesions to adenocarcinoma. 4. Progression to Carcinoma : Over time, additional mutations accumulate within adenomatous polyps, leading to their progression to carcinoma. These mutations often affect genes involved in cell cycle regulation (e.g., TP53), DNA repair mechanisms, and pathways regulating apoptosis (programmed cell death). 5. Microsatellite Instability (MSI) : In some cases, colorectal adenocarcinomas develop due to microsatellite instability.

12. 6. Epigenetic Changes: Alongside genetic mutations, epigenetic alterations (changes in gene expression without altering the DNA sequence) also play a role. 7. Tumor Progression and Metastasis : As the carcinoma develops, it gains the ability to invade surrounding tissues and metastasize to distant organs, such as the liver and lungs. This involves further genetic and epigenetic changes that enhance the tumor's invasive and migratory capabilities. Understanding the pathogenesis of colorectal adenocarcinoma involves a complex interplay of genetic predisposition, environmental factors (such as diet and lifestyle), and molecular alterations within colonic epithelial cells that lead to the stepwise progression from normal tissue to adenoma and ultimately carcinoma.

13. Fig-1 ADENOCARCINOMA RECTUM

14. Fig - 2 Fig - 3 SIGNET RING ADENOCARCINOMA MUCINOUS ADENOCARCINOMA SUBTYPES

15. Fig-4 SERRATED ADENOCARCINOMA Fig-5 Poorly differentiated adenoca with micropapillary features

16. Fig-6 MEDULLARY ADENOCARCINOMA Fig 7 INVASIVE COLONIC ADENOCARCINOMA charaterised by stromal desmoplasia

17. Fig-8 COLONIC SMALL CELL NEUROENDOCRINE ADENOCARCINOMA Fig-9 SARCOMATOID TYPE

18. IHC MARKERS FOR COLO RECTAL CA NCER Mucin stains -MUC1 and MUC3 for conventional adenocarcinoma, MUC13 for poorly differentiated tumors,MUC5AC and MUC6 for serrated pathway of colon cancer Cytokeratins- CK7 CK20 CDX2 CEA-Carcinoembryonic antigen MLH1,MLSH2,MSH6,PMS2- Mismatch repair proteins(microsatellite instability)

19. PROGNOSTIC FACTORS Good prognostic factors: Low grade tumors (>50% gland formation) Microsatellite instability Prominent lymphoplasmacytic infiltrate (tumor infiltrating lymphocytes) Crohn like lymphoid reaction

20. Poor prognostic factors: Advanced stage, higher grade(<50% gland formation), lymphovascular and perineural invasion Positive margins Serum CEA levels >5 ng/ml High tumor budding CDX2 loss High stromal content

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