SERRATED LESIONS OF INTESTINE.pptx.G I T

Serrated lesions of intestine

1. SERRATED LESIONS OF INTESTINE PRESENTER – Dr. Megha Singh (JR1) MODERATOR – Dr. Pinki Pandey (Prof. & Head)

2. INTRODUCTION Colorectal cancer (CRC) is a major public healthcare problem, associated with a high rate of morbidity and mortality in the Western area and other countries with comparable lifestyle and dietary habits. The adenoma is the most frequent precursor of colorectal cancer (CRC) and it is high-risk adenomas of large size, with villous architecture and high-grade dysplasia that are more likely to progress to invasive adenocarcinoma.

3. ETIOLOGY & PATHOPHYSIOLOGY The conventional adenoma–carcinoma sequence is the most common pathway of colorectal neoplastic progression, accounting for around 70–80% of CRC development and it is associated with accumulation of mutations, DNA deletions/losses, DNA gains and amplifications etc. Molecular abnormalities Most frequent molecular alterations in colorectal tumourogenesis include those affecting APC which is mutated and sometimes deleted in around 80% conventional (non-serrated) adenomas and carcinomas.

4. KRAS mutations are found in around 40% colorectal adenomas and carcinomas mostly during the early stages of adenoma , can synergise either with APC mutations or defective mismatch repair (MMR) to accelerate colorectal tumour formation TP53 mutations are observed in approximately 50–60% cancers , often occurring as a late event around the time of transition from conventional adenoma to carcinoma 2–4% CRC due to inherited mutations in MMR genes in HNPCC/LS. MMR abnormalities, usually due to acquired MLH1 promoter hypermethylation in 15% sporadic CRC.

5. Microscopically, colorectal serrated lesions are defined by the presence of sawtooth like in-folding of the epithelial crypts. The differences between the main subtypes of serrated lesions dwell in cytological/architectural features and location/extent of proliferative zone.

6. WHO classification and their commonly used synonyms in histopathological interpretation of serrated polyps and serrated polyposis WHO classification Synonyms commonly used in histopathological practice Micro vesicular hyperplastic polyp (MVHP) Goblet-cell-rich hyperplastic polyp (GCHP) Mucin-poor hyperplastic polyp (MPHP) Hyperplastic polyp Sessile serrated adenoma/polyp Sessile serrated lesion (SSL) Sessile serrated adenoma/polyp with cytological atypia Mixed hyperplastic/adenomatous polyp Or Mixed SSL/serrated adenoma (usual type) Traditional serrated adenoma Traditional serrated adenoma Serrated polyposis syndrome Hyperplastic polyposis syndrome Or Serrated polyposis syndrome

7. BENIGN SERRATED POLYPS

8. HPs may occur due to – Decreased epithelial turnover or Delayed shedding of surface epithelial cells Resulting in piling up of goblet cells & absorptive cells HPs are most common serrated lesions, as they account for approximately 75% of all serrated polyps. Left colon > Right colon, < 5mm in diameter. As suggested by their name, GCHPs show, an increased number of goblet cells forming small polyps, whereas MVHPs are recognized by the presence of small droplets ( microvescicular ) of mucin within the cytoplasm of most cells.

9. a sawtooth or serrated architecture upper two-thirds more straight architecture in the lower third of the crypts mucin vescicles .

10. SESSILE SERRATED LESIONS SSLs, aka Sessile Serrated Polyps (SSP), previously called Sessile Serrated Adenomas, second most common type of serrated lesion and, along with TSAs, are considered significant precursor lesions of CRC more frequent in the right colon, common in females than males. Another key feature is the lack of conventional or genuine nuclear dysplasia , although the lesional cells may have some mild nuclear enlargement and ‘nuclear atypia ’ that does not amount to true dysplasia.

11. The major and pathognomonic histologic feature that distinguishes SSLs from HPs is the finding of architecturally distorted serrated crypts , In order to be considered diagnostic for SSL a crypt should show at least one of the following histologic features: (1) Horizontal growth along the muscularis mucosa (L-shaped or inverted T-shaped crypt); (2) Dilation of the crypt base (basal one-third of the crypt); (3) Serrations extending into the crypt base; (4) Asymmetrical proliferation (shift of the proliferation zone from the base to the lateral side)

12. They may express MUC5AC or MUC6 by immunohistochemistry. In some SSLs, there may be evidence of loss of MLH1 expression.

13. Sessile serrated lesion (SSL). This has elongated crypts with serrated architecture, but the basal parts of two crypts show a horizontal growth pattern just above the muscularis mucosae.

14. Traditional Serrated Adenomas Least common of the serrated polyps comprising <6% of serrated polyps and <1% of all colorectal polyps, tend to occur in older adults particularly females Macroscopically, these lesions are pedunculated and are almost exclusively limited to the left side of the colon and in the rectum

15. Microscopically, these lesions usually show prominent serration and diffuse low-grade dysplasia with approximately 10% showing high-grade dysplasia [20]. The dysplastic epithelium shows luminal infoldings aligned perpendicular to the main axis of the crypt, termed ectopic crypt formation or short ectopic budding crypts [19]. Cellular features include prominent eosinophilic cytoplasm with no maturation towards the surface, stratification and nuclear hyperchromasia with elongated nuclei (pencil-like nuclei)

16. typical appearances of dysplastic epithelium with luminal infoldings aligned perpendicular to the main axis of the crypt prominent eosinophilic cytoplasm, elongated (pencil-like) nuclei with hyperchromasia and low-grade dysplasia

17. Definition of Hyperplastic Polyposis Syndrome (HPS), also called Serrated Polyposis Syndrome , includes the findings of either: (1) >5 hyperplastic polyps proximal to the sigmoid colon, of which two are >10 mm in diameter; or (2) >30 hyperplastic polyps of any size, proximal to the sigmoid colon; or (3) any number of hyperplastic polyps with a first-degree relative with known HPS. The hyperplastic polyps may sometimes be large, villous, show a complex architecture with polyp branching, may sometimes resemble atypical juvenile polyps Serrated Polyposis Syndrome / Hyperplastic Polyposis Syndrome

18. Other syndromic forms of polyposis should be excluded, including Familial Adenomatous Polyposis (FAP) and its attenuated variant (AFAP), MUTYH-associated Polyposis, Peutz – Jeghers Syndrome, Juvenile Polyposis Syndrome And Cowden’s Syndrome.

19. BENIGN ADENOCARCINOMA

20. The Serrated Neoplastic Pathways Left colon Traditional serrated neoplasia pathway Right colon Sessile serrated neoplasia pathway KRAS mutation BRAF mutation Hyperplastic polyp Hyperplastic polyp Traditional serrated adenoma Sessile serrated lesion Silencing of Tumor suppressor genes MSS (CIMP-L) MLH1 hypermethylation MSI-H (CIMP-H) Serrated Adenoma MSS / CIMP positive, Non-HNPCC, serrated Adenocarcinoma

21. The right-sided sessile serrated neoplasia pathway involves formation of hyperplastic polyps, sessile serrated lesions (SSLs) and serrated adenomas (of usual type), which may progress to serrated adenocarcinoma, Left-sided traditional serrated neoplasia pathway includes hyperplastic polyps and traditional serrated adenomas (TSAs) which may evolve into invasive serrated adenocarcinomas The serrated pathway lesions are also characterized by particular genetic and molecular characteristics, including MSI and CIMP.

22. serrated adenoma of usual type, with some low-grade dysplasia high-grade dysplastic epithelium there is an early invasive adenocarcinoma, just invading through the muscularis mucosae This case illustrates the progression from sessile serrated lesion (SSL) to serrated adenoma to serrated adenocarcinoma

23. Serrated adenocarcinoma. invasion of the muscularis propria by malignant epithelium forming markedly elongated, serrated cryptlike structures

24. The Role Of Immunohistochemistry In The Diagnosis Of Serrated Lesions Ki-67 immunostaining patterns can be helpful in distinguishing HPs, SSLs and TSAs. In HPs, the Ki-67 staining is predominantly limited to the lower third or so of the crypts SSLs showed a similar pattern to HPs but with only slightly increased Ki-67 staining within the middle third of the crypts. TSAs have more uniform Ki-67 staining throughout the length of the crypts. Other immunohistochemical markers such as cytokeratin 20, MGMT, MLH1, CDX2, b-catenin and P53 were found not to be helpful in subtyping serrated lesions

25. REFERENCES Mezzapesa , M.; Losurdo , G.; Celiberto , F.; Rizzi , S.; d’Amati , A.; Piscitelli , D.; Ierardi , E.; Di Leo, A. Serrated Colorectal Lesions: An Up-to-Date Review from Histological Pattern to Molecular Pathogenesis. Int. J. Mol. Sci. 2022, 23, 4461 Fred T Bosman ,  Ivan Damjanov ; Recent Advances in Histopathology: 25; September 30, 2022 ; Chapter 8; Pg no. 103 – 113. Kumar, V., Abbas, A. K., & Aster, J. C. (2017).  Robbins Basic Pathology  10th ed. Vol II Pg no. 807-817 Elsevier - Health Sciences Division.

26. THANKYOU

27. Next PG Activity Journal Club on 222/05/24 – Presenter - Dr. Soha Akhtar Moderator – Dr. Rashmi