GI TRACT SURGICAL PATHOLOGY

1. GI TRACT SURGICAL PATHOLOGY Dr Rasti

2. Case 1:lower esopahgus mucosal biopsy • (tubular esophagus )

4. What is diagosis: 1)Fundal glands intestinal aplasia 2)Barrets esophagus without dysplasia 3)Barrets esophus with low gade dysplasia

5. Hematoxylin & eosin shows the deeper portions of glands found in Barrett mucosa. These display some nuclear changes that can be overinterpreted as dysplasia on tangentially embedded samples. Note the prominent goblet cells.

6. Case 2 lower :esopahgus mucosa

9. Hematoxylin & eosin of mucosa displays features of both squamous and columnar mucosa, which has been termed "multilayered epithelium." It demonstrates mucin profiles like to those of Barrett mucosa. (

10. Lower esophagus mucosa Endoscopic findings are consist with Barret’s esophagus

13. Diagnosis: • 1)Barrets with low grade dysplasia • 2)barrets IFD 3)Barrets mucosa without dysplasia 4)Regnerative changes

14. These may be reactive (neutrophils in the adjacent squamous mucosa), but the nuclei are hyperchromatic. This might be regarded as IFD by some observers but reactive by others.

16. Lower esophagus 1)low garde dysplasia 2)High garde dysplasia 3)IFD

17. Hematoxylin & eosin shows the architectural appearance of LGD. There is poor surface maturation, but nuclei remain aligned with their long axes perpendicular to the basement membrane (maintained nuclear polarity).

18. Lower esophagus 1)low garde dysplasia 2)High garde dysplasia 3)IFD

20. Hematoxylin & eosin shows LGD at the surface in , Notice the size and chromatin density of the nuclei. These are larger and darker. The inverted goblet cell

21. Lower esophagus 1)low garde dysplasia 2)High garde dysplasia 3)IFD

23. Hematoxylin & eosin high-grade dysplasia shows hyperchromatic glands that are crowded, and there are several markedly enlarged nuclei~. There is no surface maturation, and nuclear polarity is lost at the surface.

24. Lower esophagus 1)low garde dysplasia 2)High garde dysplasia 3)IFD

26. The glands are dysplastic and composed of tiny hyperchromatic cells. This "small cell" pattern is unrelated to endocrine differentiation. There is also prominent inflammation; a subset of HCD cases display prominent inflammation. In such cases, labeling with p53 can be helpful.

27. COLORECTALCARCINOMA CRC

29. Hematoxylin & eosin shows a low-power view of moderately differentiated microsatellite stable colorectal adenocarcinoma with dirty or garland necrosis ~

31. Hematoxylin & eosin highpower view shows infiltrative growth pattern and lack of host response, 2 findings more typical of microsate/lite stable tumors than of unstable tumors.

37. poorly differentiated MSI-H colorectal carcinoma with large numbers of tumor infiltrating lymphocytes~. MSI-H colorectal carcinoma with histologic heterogeneity. mucinous differentiation, poorly differentiated tumor with increased numbers of tumor infiltrating lymphocytes.

38. Molecular Genetics · 85-88% of CRCs are microsatellite stable (MSS)tumors, many arise via mutations in Wnt signaling pathway o Adenoma-carcinoma sequence · ·12-15% of CRCs are microsatellite unstable (MSIH) tumors that arise due to errors in DNA mismatch repair o Serrated pathway: Sessile serrated adenomas give rise to sporadic MSI-H cancers · Methylation of hMLHl key molecular event · Often have BRAF mutation o 10% of MSI-H tumors arise via germline mutations in mismatch repair genes (Lynch syndrome/HNPCC) · serrated lesions) · Lynch tumors are thought to grow much faster o MSI-H tumors have better prognosis than MSS tumors (stage for stage)

39. Microsatellite instability (MSI) is the condition of genetic hypermutability that results from impaired DNA Mismatch Repair (MMR). In other words, MSI is the phenotypic evidence that MMR isn't functioning normally. DNA MMR corrects errors that spontaneously occur during DNA replication like single base mismatches or short insertions and deletions. The proteins involved in MMR form a complex that binds to the mismatch, identifies the correct strand of DNA, then subsequently excises the error and repairs the mismatch.[

40. Cells with abnormally functioning MMR tend to accumulate errors rather than correcting those errors. As a result, gene sequences are not preserved faithfully through DNA replication, and novel Microsatellites fragments are created. Microsatellite instability is detected by PCR based assays that reveal these novel microsatellites.

42. COLOSCOPIC BIOPSY

48. Microscopic Pathology . Basal lymphoplasmacytosis, crypt branching/dropout ·Crypt abscesses, polypoid granulation tissue ·Paneth cell and pseudopyloric gland metaplasia ·Fissuring ulcers to muscularis propria ·.Transmural lymphoid aggregates Submucosal fibrosis, muscle and nerve hypertrophy · Large, well-formed epithelioid cell granulomas o Mostly in submucosa, subserosa;

49. DIFFERENTIAL DIAGNOSIS • Ulcerative Colitis • · Diffuse, primarily mucosal involvement of colorectum ·Absence of skip lesions (unless treated), transmural • inflammation (except near ulcer), granulomas (except • due to foreign body or crypt-rupture), upper GI/ileal • disease (except nonspecific duodenitis, pediatric UC) • · "Backwash" ileitis • : Only seen in severe right-sided UC • o No severe activity or chronic inflammatory changes • Indeterminate Colitis (lC) • ·Not a specific disease entity: No diagnostic criteria • o Impossible to distinguish CD vs. UC (5-15% of IBD) • o Overlapping features of both CD, UC (resections) ·Used by some if insufficient clinical, histologic data • o Instead: "Active chronic (ileo)colitis, type unknown" • o 80% of IC: Underlying IBD type eventually apparent • 5