audio enabled ppt on colorectal ca and associated disease.compatible on wps office on mobile and microsoft powerpoint on pc

1. DR SRABANI CHAKRABARTI
ASSOCIATE PROFESSOR
DEPT OF
PATHOLOGY , CNMC

2. Gastro intestinal stromal tumor
(GIST)
 Most common mesenchymal tumor of GIT
 Differentiation along the line of INTESTINAL CELLS OF
CAJAL.
 Most common location stomach 60% ,jejunum & ilium
30% duodenum 5% colorectum 5%.
 common in 5th-8th decade of age
 most cases of GIST show mutation in the receptor tyrosine
kinase KIT
 may be associated with CARNEY TRIAD
 about 50% of these tumors ulcerate and bleed.
 IHC is done for KIT CD117

3. GIST specimen is polypoid and has a
central scar

4. GIST microscopic feature
interlacing bundle of spindle cells

5. GI carcinoid
 GI carcinoid is the most common primary tumor of
small bowel mostly in the APPENDIX.
 GI carcinoid arise from ENTEROCHROMAFFIN
CELLS OF KULCHITSKY.
 GROSS intramural or submucosal masses – small
polypoid lesion YELLOW OR TAN IN COLOR.
 IHC tumor cells are positive for SYNAPTOPHYSIN ,
CHROMOGRANIN A.

6. GI carcinoid microscopy
uniform cells in groups with scant
cytoplasm & stippled nucleus

7. GI LYMPHOMA
 GI tract is the most common extranodal site for
lymphoma.
 majority of GI lymphoma are B cell lymphoma in
response to infection or autoimmune process.
 Seen in stomach 70%
 small intestine 20%
 ileocecal 10%

8. GASTRIC LYMPHOMA
microscopic picture

9. COLORECTAL CARCINOMA

10. NEW TERMS
 CRC colorectal carcinoma
 FAP familial adenomatous polyposis
 HNPCC hereditory nonpolyposis colon cancer

11. CRC
 RISK FACTOR
 PATHOGENESIS
 MORPHOLOGY
 CLASSIFICATION
 CLINICAL FEATURE
 SPREAD
 INVESTIGATION
 PROGNOSTIC FACTOR
 CLINICAL PROBLEM

12. RISK FACTOR
 INCREASING AGE OF THE PATIENT
 DIET
 HEREDITY
 FAMILY HISTORY OF CRC IN 1ST DEGREE RELATIVE
 PRIOR CRC OF THE PATIENT
 H/O IBD OF THE PATIENT
 IRRADIATION AND IMMUNOSUPRESSION OF THE
PATIENT
 PHYSICAL INACTIVITY, OBESITY, SMOKING

13. Dietary factor, drug
 low intake of dietary fiber less stool bulk slow
transit of stool bulk altered composition of intestinal
micro biota increased synthesis of toxic
oxidative(mutagen) , which remains in contact with the
colonic mucosa for long time.
 Dietary high intake of refined carbohydrate and fat
increases chance of CRC.
 Diet rich in cauliflower and cabbage and VIT A decreases
risk of CRC.
 ASPIRIN OR NSAID reduces risk of CRC.

14. RISK FACTOR for colon cancer
GENETIC FACTOR
 FAP patients have very high risk of colorectal cancer
 FAP is autosomal dominant inherited syndrome
characterised by hundreds to thousands of polyps
throughout the colorectum. ( At least 100 polyps)
 All untreated FAP patients develop colorectal cancer often
before age of 30 years.
 HNPCC colorectal cancer in 1st degree relative of a patient
of colonic cancer is due to germline mutation in one of
the genes responsible for repair of DNA mismatch.
There is increased risk of colorectal cancer.


15. FAMILIAL ADENOMATOUS
POLYPOSIS intestine

16. Neoplastic polyp of colon
 ARCHITECTURE
 Tubular adenoma ( adenomatous polyp,)
 Villous adenoma
 tubulovillous
sessile serrated adenoma
GROWTH PATTERN
Pedunculated
Sessile
Flat or depressed

17. Risk factor for malignant change in
polyps of colon
PRE EXISTING NEOPLASTIC POLYPS INCREASES CHANCE
OF CRC
 CRITERIA FOR INCREASED CHANCE OF CRC
 large size of polyp( more than 2 cm)
 villous architecture
 dysplasia
 multiple polyps ( more than 4 in number )
FAP patient will develop carcinoma in 95-100% cases (
highest malignant potential)
HNPCC patients will develop colorectal carcinoma in 70-75% of
cases

18. Pathogenesis of colon ca
 Multiple molecular alterations are responsible
 GENETIC ABNORMALITIES (that activate
oncogenes or inactivate tumor supressor gene).
 EPIGENETIC ABNORMALITIES.

19. Genetic& epigenetic pathway
GENETIC PATHWAY
 A classic adenoma-carcinoma sequence
 B microsatellite instability pathway
EPIGENETIC ABNORMALITY
 CpG island hypermethylation phenotype (CIMP )
 Epigenetics is a reversible,heritable alteration in gene
expression which do not involve alteration in the DNA
sequence or it occurs without mutation
eg methylation of DNA

20. GENETIC FACTOR
Adenoma carcinoma sequence
 Seen in 80% colonic carcinoma
 This pathway is accompanied by a series of multiple
molecular alterations
 According to this pathway the morphological
progression is a specific stepwise sequence from
normal mucosa to adenoma to invasive carcinoma

21. PATHOLOGY
Adenoma-carcinoma sequence

22. Adenoma-carcinoma sequence
MECHANISMS ARE
 inactivation of APC tumour suppressor gene
 K-RAS mutation
 SMAD2 and SMAD4 mutation
 mutation of TP53 tumour suppressor gene
 activation of telomerase

23. Inactivation of APC tumor
supressor gene
 APC gene or adenomatous polyposis coli gene
encodes a tumour suppressor protein
 Normally APC causes degradation of β catenin in the
β catenin/WNT signalling pathway thus prevents
proliferation of cells
 When APC gene is inactivated ABNORMAL
proliferation of cells takes place as in FAP

24. K-RAS mutation and SMAD2
SMAD4
 Loss of APC function is followed by mutation of
K-RAS proto oncogene to K-RAS oncogene so
 Cell proliferation increases
 APOPTOSIS decreases
 (KRAS kirsten rat sarcoma viral oncogene homolog)
 SMAD2 AND SMAD4 are tumour suppressor gene and
inhibitor of cell proliferation loss of these genes may lead
to CRC .

25. GENETIC FACTOR
Microsatellite instability (due to
defective DNA repair )
 microsatellites are repeated sequences of 1-6 nucleotides
in the genome. they become unstable during normal
cellular replication leading to insertion or deletion of bases
within these region.
 DNA MISMATCH REPAIR GENE(MMR ) RAPIDLY
CORRECT THESE ERRORS TO MAINTAIN
MICROSATELLITE LENGTH.
 Mutation in normal DNA repair genes ( mismatch repair
defect ) leads to accumulation of microsatellites referred to
as MSI about six MMR genes have been identified.

26. morphology
COLORECTAL CARCINOMA MAY BE
 Located in any area of colon
IT MAY BE
 exophytic cauliflower like polypoid mass in the
right side of colon
 annular,constricting tumor in the left side of colon
 diffuse,tubular tumor
 infiltrative and ulcerating tumor

28. Morphology cont.
• all colorectal carcinomas begin as in situ lesions
• tumors in the proximal colon: polypoid, exophytic
masses that extend along one wall of the cecum and ascending
colon

29. Morphology
cont.
• in the distal colon: annular, encircling lesions that
produce “napkin-ring” constrictions of the bowel and
narrowing of the lumen

30. Macroscopic
appearance of
colorectal
cancer

31. microscopic picture of colorectal
adenocarcinoma (malignant cells are
arranged in glandular pattern)

32. WHO classification according to
microscopic type
 Adenocarcinoma 95% ( usually infiltrating type)
 Mucinous adeno carcinoma
 Signet ring cell carcinoma
 Adenosquamous carcinoma
 Medullary carcinoma
 Undifferentiated carcinoma
 lymphoma

33. Clinical features of CRC
CARCINOMA OF THE LEFT SIDE
 Alteration of bowel habit
 Bleeding per rectum
 Weight loss
 Lower and LIF pain
CARCINOMA OF THE RIGHT SIDE
 pain and palpable mass in RIF
 Anaemia
 melena in ulcerative form
 Weight loss,nausea,vomiting,anorexia

34. Change in bowel habit in CRC
CLINICAL FEATURES
 RIGHT COLON RECTUM LEFT COLON
Anaemia Tenesmus Constipation
Diarrhoea Blood & mucus PR Bleeding PR

35. Spread
 1 DIRECT transverse,longitudinal ,radial spread to
adjacent organ
 2 LYMPHATIC to regional lymph nodes
 3 HAEMATOGENOUS to liver,lung ,brain
 4 TRANSCOELOMIC via subperitoneal lymphatics to
other structures in the peritoneal cavity

36. Investigation in CRC
 OCCULT BLOOD TEST IN STOOL
 TUMOR MARKERS elevated level of
serum CEA (carcinoembryonic antigen) and serum
CA 19-9
 sigmoidoscopy
 colonoscopy
 radiology DOUBLE CONTRAST BARIUM ENEMA
shows ‘ apple core appearance’
 USG OF ABDOMEN
 ABDOMINAL CT SCAN

37. PROGNOSTIC factor
 Gross finding ( tumour size,local tumour extent, residual
tumour, circumferential margin)
 TNM staging
 Non-nodal tumour deposit
 Tumour regression after neo adjuvant therapy
 Lympho vascular ,perineural invasion
 Histological type, grade of differentiation
 Tumour border
 Preoperative serum CEA level
 MOST IMP PROGNOSTIC FACTORS ARE DEPTH OF
INVASION& PRESENCE OR ABSENCE OF LYMPH NODE
METASTASIS

38. Clinical problem
 60 yrs old man having hypochromic anaemia
 Stool shows presence of blood
 In colonoscopy 4 cm bulky exophytic cauliflower like
polypoid mass seen projecting into caecum
 biopsy and microscopic exam done DIAGNOSIS???
 70 yr old man c/o change of bowel habit
 Bleeding PR
 In colonoscopy annular lesion encircling descending colon
is seen
 Biopsy and microscopic exam done DIAGNOSIS???