PATHOLOGY OF SMALL & LARGE INTESTINEPATHOLOGY OF SMALL & LARGE INTESTINE

DIVERTICULAR DISEASEDIVERTICULAR DISEASE Diverticulum= blind pouch leading off the alimentary tract, Diverticulum= blind pouch leading off the alimentary tract,

lined by mucosa, communicating with gut lumenlined by mucosa, communicating with gut lumen Acquired >> congenital (e.g. MeckelAcquired >> congenital (e.g. Meckel’’s)s) May arise anywhere in GIT; colon is the most common May arise anywhere in GIT; colon is the most common

sitesite Two main factors:Two main factors:– 1) Weakness in the wall: defects at site of bv entry; 1) Weakness in the wall: defects at site of bv entry;

congenital weakness (e.g. Marfancongenital weakness (e.g. Marfan’’s syndrome)s syndrome)– 2) Increased peristalsis and intra-luminal pressure: 2) Increased peristalsis and intra-luminal pressure:

hard stools due to low-fiber diet results in exaggerated hard stools due to low-fiber diet results in exaggerated peristaltic contractionsperistaltic contractions

PATHOLOGY OF PATHOLOGY OF

COLONIC DIVERTICULOSISCOLONIC DIVERTICULOSIS Colonic diverticulosis is common in the West Colonic diverticulosis is common in the West

(50% of adults >60 yrs); associated with low-(50% of adults >60 yrs); associated with low-fiber dietfiber diet

Multiple small 0.5-1 cm Multiple small 0.5-1 cm Sigmoid colon is involved in 95% of patientsSigmoid colon is involved in 95% of patients Gross examination: Prominent taeniae coli & Gross examination: Prominent taeniae coli &

circular muscle bundles due to muscular circular muscle bundles due to muscular hypertrophy; outpouching may be visible from hypertrophy; outpouching may be visible from serosal surfaceserosal surface

Histology: sacs with thin wall made of mucosa & Histology: sacs with thin wall made of mucosa & submucosa surrounded by fat or intact submucosa surrounded by fat or intact peritoneumperitoneum

CLINICAL FEATURES OFCLINICAL FEATURES OF

COLONIC DIVERTICULOSISCOLONIC DIVERTICULOSIS Usually asymptomaticUsually asymptomatic Intermittent cramping or continuous LLQ discomfort, Intermittent cramping or continuous LLQ discomfort,

sensation of incomplete emptying of rectumsensation of incomplete emptying of rectum Complications:Complications:– Diverticulitis: accentuates symptoms, tenderness, Diverticulitis: accentuates symptoms, tenderness,

feverfever– Peridiverticulitis, perforation, abscess or fistulaPeridiverticulitis, perforation, abscess or fistula– Fistula formationFistula formation– BleedingBleeding

Rx: High-fiber diet; surgeryRx: High-fiber diet; surgery

PATHOLOGY OF SMALL & LARGE INTESTINEPATHOLOGY OF SMALL & LARGE INTESTINE

BOWEL OBSTRUCTIONBOWEL OBSTRUCTION May occur at any level, but is more frequent in small May occur at any level, but is more frequent in small

intestineintestine May be acute or chronicMay be acute or chronic Clinical features: abdominal distension (+/- pain) , Clinical features: abdominal distension (+/- pain) ,

followed by vomiting, then constipationfollowed by vomiting, then constipation May present at birth, during infancy, childhood or May present at birth, during infancy, childhood or

adulthoodadulthood Obstruction may be in the lumen, wall or extramuralObstruction may be in the lumen, wall or extramural Tumors and infarction account for 10-15% of small Tumors and infarction account for 10-15% of small

bowel obstructionbowel obstruction Hernias, intestinal adhesions, intussusception, and Hernias, intestinal adhesions, intussusception, and

volvulus account for 80% of casesvolvulus account for 80% of cases

CLASSIFICATION OFCLASSIFICATION OF

BOWEL OBSTRUCTIONBOWEL OBSTRUCTION Mechanical:Mechanical:– Congenital: strictures, atresias, bands, imperforate Congenital: strictures, atresias, bands, imperforate

anus, meconium in cystic fibrosisanus, meconium in cystic fibrosis– Infants: hernias, intussusceptionInfants: hernias, intussusception– Adults: hernias, adhesions, tumors, inflammatory Adults: hernias, adhesions, tumors, inflammatory

strictures, obstructive gallstones, fecaliths, foreign strictures, obstructive gallstones, fecaliths, foreign bodies, volvulusbodies, volvulus

Functional:Functional:– Paralytic ileus: electrolyte imbalance, neural injury, or Paralytic ileus: electrolyte imbalance, neural injury, or

reflex atony secondary to peritonitisreflex atony secondary to peritonitis– bowel infarction, bowel infarction, – myopathies & neuropathathies (e.g. Hirschsprungmyopathies & neuropathathies (e.g. Hirschsprung’’s)s)

BOWEL OBSTRUCTIONBOWEL OBSTRUCTION

HERNIASHERNIAS Weakness or defect in wall of peritoneal cavity with Weakness or defect in wall of peritoneal cavity with

protrusion of a serosa-lined sac of peritoneumprotrusion of a serosa-lined sac of peritoneum Inguinal & femoral canals, umbilicus & surgical Inguinal & femoral canals, umbilicus & surgical

scarsscars Segments of viscera may protrude & become Segments of viscera may protrude & become

entrapped, mostly in inguinal herniasentrapped, mostly in inguinal hernias If small bowel is involved, partial or complete If small bowel is involved, partial or complete

obstruction of its lumen may followobstruction of its lumen may follow Incarceration: permenant trapping of hernial sac Incarceration: permenant trapping of hernial sac

contents due to venous stasis & edemacontents due to venous stasis & edema Strangulation: Venous & arterial supply to Strangulation: Venous & arterial supply to

entrapped viscus is compromised leading to entrapped viscus is compromised leading to infarction or gangreneinfarction or gangrene

BOWEL OBSTRUCTIONBOWEL OBSTRUCTION

INTESTINAL ADHESIONSINTESTINAL ADHESIONS Due to localized or generalized peritonitis Due to localized or generalized peritonitis

secondary to:secondary to: – Surgical proceduresSurgical procedures– InfectionInfection– EndometriosisEndometriosis

Rarely due to congenital fibrous bandsRarely due to congenital fibrous bands May result in intestinal obstruction, incarceration May result in intestinal obstruction, incarceration

and strangulationand strangulation Fibrous bridges which develop between bowel Fibrous bridges which develop between bowel

segments creating closed loops through which segments creating closed loops through which viscera may slide & become entrapped (internal viscera may slide & become entrapped (internal hernias)hernias)

BOWEL OBSTRUCTIONBOWEL OBSTRUCTION

INTUSSESCEPTIONINTUSSESCEPTION Uncommon disorder where a segment of small Uncommon disorder where a segment of small

intestine, constricted by a a wave of peristalsis, intestine, constricted by a a wave of peristalsis, suddenly becomes telescoped into the suddenly becomes telescoped into the immediately distal segment of bowelimmediately distal segment of bowel

Intussusceptum: trapped bowel segmentIntussusceptum: trapped bowel segment Intussuscipiens: bowel segment which envelops itIntussuscipiens: bowel segment which envelops it Mostly in infants & children of unknown Mostly in infants & children of unknown

pathogenesis pathogenesis In adults, an intraluminal tumor may act as point In adults, an intraluminal tumor may act as point

of traction, pulling along a segment of bowelof traction, pulling along a segment of bowel Intestinal obstruction Intestinal obstruction Intestinal infarction due to trapping of mesenteric Intestinal infarction due to trapping of mesenteric

blood vesselsblood vessels

INTUSSESCEPTIONINTUSSESCEPTION

BOWEL OBSTRUCTIONBOWEL OBSTRUCTION

VOLVULUSVOLVULUS Complete twisting of a loop of bowel about its Complete twisting of a loop of bowel about its

mesenteric base of attachmentmesenteric base of attachment Mostly in small intestine; large intestine especially Mostly in small intestine; large intestine especially

sigmoid & cecum, and other structures (e.g. ovary) sigmoid & cecum, and other structures (e.g. ovary) may be involvedmay be involved

Constriction of venous outflow &/or arterial supplyConstriction of venous outflow &/or arterial supply Intestinal obstruction and infarctionIntestinal obstruction and infarction Uncommon disorder, occuring in all ages when an Uncommon disorder, occuring in all ages when an

intestinal segment becomes longer & the mesentary intestinal segment becomes longer & the mesentary narrowernarrower

May be caused by colon malrotation & peritoneal May be caused by colon malrotation & peritoneal bandsbands

SMALL & LARGE INTESTINESMALL & LARGE INTESTINE

TUMORSTUMORS Colonic tumors are much more common than Colonic tumors are much more common than

small intestinal tumorssmall intestinal tumors May arise from any layer of GIT wall (mucosa, May arise from any layer of GIT wall (mucosa,

submucosa, muscularis or serosa); most are of submucosa, muscularis or serosa); most are of epithelial originepithelial origin

The majority are benign; however, colonic cancers The majority are benign; however, colonic cancers are a major cause of morbidity & mortalityare a major cause of morbidity & mortality

Clinical presentation:Clinical presentation:– Asymptomatic; incidental findingAsymptomatic; incidental finding– Blood per rectum; anemiaBlood per rectum; anemia– Bowel obstructionBowel obstruction

INTESTINALINTESTINAL

TUMORSTUMORS Benign:Benign:– Stromal tumorsStromal tumors– Hyperplastic & adenomatous polypsHyperplastic & adenomatous polyps– LipomasLipomas

Malignant:Malignant:– AdenocarcinomaAdenocarcinoma– Carcinoid tumorsCarcinoid tumors– LymphomaLymphoma

– SarcomaSarcoma

PATHOLOGY OF SMALL & LARGE INTESTINEPATHOLOGY OF SMALL & LARGE INTESTINE

CARCINOID TUMORSCARCINOID TUMORS Tumors of neuroendocrine cells, which are widely Tumors of neuroendocrine cells, which are widely

distributed cells of epithelial stem cell origin distributed cells of epithelial stem cell origin capable of producing a variety of bioactive capable of producing a variety of bioactive compoundscompounds

Tumors may produce multiple compounds or a Tumors may produce multiple compounds or a predominant product, causing a clinical syndrome predominant product, causing a clinical syndrome such as gastrinoma, insulinoma ...such as gastrinoma, insulinoma ...

Tumors arrise in GIT, lung, biliary tree & pancreasTumors arrise in GIT, lung, biliary tree & pancreas 50% of small intestinal & 2% of colonic tumors50% of small intestinal & 2% of colonic tumors Any age, peak incidence in 6th decadeAny age, peak incidence in 6th decade Carcinoids are well differentiated tumors that are Carcinoids are well differentiated tumors that are

potentially malignant tumors and may metastasizepotentially malignant tumors and may metastasize

CLINICAL FEATURES OFCLINICAL FEATURES OF

CARCINOID TUMORSCARCINOID TUMORS Sites: appendix>small intestine (ileum)>rectum> Sites: appendix>small intestine (ileum)>rectum>

stomach>colonstomach>colon Most are asymptomatic (particularly appendix) Most are asymptomatic (particularly appendix) May cause local symptoms (angulation or obstrcution May cause local symptoms (angulation or obstrcution

of small intestine)of small intestine) Secretory products may produce a variety of Secretory products may produce a variety of

endocrinopathies, e.g. Zollinger-Ellison syndrome, endocrinopathies, e.g. Zollinger-Ellison syndrome, CushingCushing’’s syndrome, hyperinsulinism s syndrome, hyperinsulinism

Carcinoid syndrome: 1% of patients & 20% of those with Carcinoid syndrome: 1% of patients & 20% of those with widespread metastasis; due to serotonin secretion; widespread metastasis; due to serotonin secretion; vasomotor disturbances, intestinal hypermotility, vasomotor disturbances, intestinal hypermotility, hepatomegaly and systemic fibrosishepatomegaly and systemic fibrosis

PATHOLOGY OF PATHOLOGY OF

CARCINOID TUMORSCARCINOID TUMORS Gross: usually small tumors, rarely >3 cm, forming Gross: usually small tumors, rarely >3 cm, forming

an intramural or submucosal yellow-tan firm an intramural or submucosal yellow-tan firm elevation or polypoid lesionelevation or polypoid lesion

Histology: monomorphous population of cells with Histology: monomorphous population of cells with scant granular cytoplasm & round nuclei. scant granular cytoplasm & round nuclei. Neoplastic cells form islands, nests, strands or Neoplastic cells form islands, nests, strands or glands. Intact or ulcerated overlying mucosa.glands. Intact or ulcerated overlying mucosa.

May be multicentric (stomach, ileum)May be multicentric (stomach, ileum) May be localized or have local spread &/or May be localized or have local spread &/or

metastasis to lymph nodes or more distant sites, metastasis to lymph nodes or more distant sites, particularly liverparticularly liver

CLINICAL BEHAVIOUR OFCLINICAL BEHAVIOUR OF

CARCINOID TUMORSCARCINOID TUMORS Clinical behaviour is difficult to predict from Clinical behaviour is difficult to predict from

histologic featureshistologic features Behaviour but generally depends on:Behaviour but generally depends on:– 1) Size: >2 cm and those invading >1/2 wall 1) Size: >2 cm and those invading >1/2 wall

thicknessthickness– 2) Site: appendiceal & rectal carcinoids almost 2) Site: appendiceal & rectal carcinoids almost

never metastasizenever metastasize 5 years survival rate is excellent: 90%5 years survival rate is excellent: 90% 5 years survival rate for small intestinal tumors with 5 years survival rate for small intestinal tumors with

liver metastasis: 50%liver metastasis: 50% Widespread disease usually causes deathWidespread disease usually causes death

SMALL INTESTINALSMALL INTESTINAL

ADENOCARCINOMAADENOCARCINOMA Most arise in duodenum, including ampulla of Most arise in duodenum, including ampulla of

VaterVater Polypoid fungating tumor growing in a napkin-Polypoid fungating tumor growing in a napkin-

ring encircling patternring encircling pattern Early on, tumor is asymptomaticEarly on, tumor is asymptomatic Signs & symptoms usually appear late, when Signs & symptoms usually appear late, when

tumor has already penetrated bowel wall into tumor has already penetrated bowel wall into mesentery, other bowel segments or spread to mesentery, other bowel segments or spread to LN, or metastasize to liver or more widely LN, or metastasize to liver or more widely

c/o symptoms of abdominal obstruction (pain, c/o symptoms of abdominal obstruction (pain, nausea, vomiting, and weight loss)nausea, vomiting, and weight loss)

5 yrs survival with wide en bloc excision: 70%5 yrs survival with wide en bloc excision: 70%

SMALL & LARGE INTESTINESMALL & LARGE INTESTINE

POLYPSPOLYPS Polyp= a tumorous mass protruding into the lumen of the Polyp= a tumorous mass protruding into the lumen of the

gut; may be pedunculated or sessilegut; may be pedunculated or sessile Major types:Major types:– Non-neoplastic polyps: about 90% of polyps; formed Non-neoplastic polyps: about 90% of polyps; formed

as a result of abnormal mucosal maturation, as a result of abnormal mucosal maturation, inflammation or architectureinflammation or architecture» Hyperplastic polypsHyperplastic polyps» Hamartomatous polypsHamartomatous polyps» Inflammatory polypsInflammatory polyps

– Neoplastic polyps: formed as a result of epithelial Neoplastic polyps: formed as a result of epithelial proliferation and dysplasia, i.e. pre-cancerousproliferation and dysplasia, i.e. pre-cancerous» Adenomatous polypsAdenomatous polyps

INTESTINAL POLYPSINTESTINAL POLYPS

HYPERPLASTIC POLYPSHYPERPLASTIC POLYPS Majority of polyps Majority of polyps Site: mostly in colon, >50% in rectosigmoidSite: mostly in colon, >50% in rectosigmoid Patients: increase in frequency with agePatients: increase in frequency with age Appearance: Most are small <5 mm, nipple-like Appearance: Most are small <5 mm, nipple-like

protrusion; multiple or singleprotrusion; multiple or single Pathology: histologically consist of abundant Pathology: histologically consist of abundant

crypts lined by well-differentiated goblet or crypts lined by well-differentiated goblet or absorptive epithelial cells, seperated by scant absorptive epithelial cells, seperated by scant lamina proprialamina propria

Asymptomatic or blood &/or mucus per rectumAsymptomatic or blood &/or mucus per rectum No malignant potentialNo malignant potential

INTESTINAL POLYPSINTESTINAL POLYPS

HAMAHAMARTOMATOUS POLYPSRTOMATOUS POLYPS Juvenile polyps:Juvenile polyps:– Hamartomatous proliferation of lamina propria Hamartomatous proliferation of lamina propria

surrounding cystically dilated glandssurrounding cystically dilated glands– Patients: usually <5 yrs; in adults called Patients: usually <5 yrs; in adults called

““retention polypretention polyp””

– Appearance:1-3 cm in children; smaller in Appearance:1-3 cm in children; smaller in adultsadults

– Single rounded or lobulated, +/- stalkSingle rounded or lobulated, +/- stalk– Bleeding per rectum; stalk may twist and Bleeding per rectum; stalk may twist and

undergo painful infarctionundergo painful infarction– No malignant potentialNo malignant potential

INTESTINAL POLYPSINTESTINAL POLYPS

HAMAHAMARTOMATOUS POLYPSRTOMATOUS POLYPS Peutz-Jeghers polyps:Peutz-Jeghers polyps:– Rare autosomal dominant syndrome, characterized Rare autosomal dominant syndrome, characterized

by GIT polyps, melanotic mucosal and cutaneous by GIT polyps, melanotic mucosal and cutaneous pigmentation around lips, oral mucosa, face, pigmentation around lips, oral mucosa, face, genitalia & palmar surfaces of handsgenitalia & palmar surfaces of hands

– Site: polyps may occur in stomach (25%), colon Site: polyps may occur in stomach (25%), colon (30%) and small intestine (100%)(30%) and small intestine (100%)

– Appearance: large peduculated lobulated polypsAppearance: large peduculated lobulated polyps– Pathology: branching framework of connective Pathology: branching framework of connective

tissue & smooth muscletissue & smooth muscle– Polyps have no malignant potential, but PJS Polyps have no malignant potential, but PJS

patients have increased riskpatients have increased risk of developing of developing carcinoma of pancreas, breast, lung, ovary & carcinoma of pancreas, breast, lung, ovary & uterusuterus

INTESTINAL POLYPSINTESTINAL POLYPS

AADENOMATOUS POLYPSDENOMATOUS POLYPS Vast majority of adenomas arise in colonVast majority of adenomas arise in colon Variable in size; pedunculated or sessileVariable in size; pedunculated or sessile Results from epithelial proliferation and dysplasia, Results from epithelial proliferation and dysplasia,

which may range from mild to carcinoma in situwhich may range from mild to carcinoma in situ Three architectural types:Three architectural types:– 1) Tubular adenoma1) Tubular adenoma– 2) Villous adenoma2) Villous adenoma– 3) Tubulovillous adenoma3) Tubulovillous adenoma

Risk of malignant transformation depends on:Risk of malignant transformation depends on:– Polyp size: <1 cm (v. rare); 1-2 cm (10%); >2 cm Polyp size: <1 cm (v. rare); 1-2 cm (10%); >2 cm

(45%)(45%)– Histologic architecture: proportion of villous Histologic architecture: proportion of villous

componentcomponent– Severity of dysplasiaSeverity of dysplasia

INTESTINAL POLYPSINTESTINAL POLYPS

AADENOMATOUS POLYPSDENOMATOUS POLYPS Tubulovillous adenoma: 5-10% of adenomatous Tubulovillous adenoma: 5-10% of adenomatous

polyps; mixture of tubular & villous (20-50%) polyps; mixture of tubular & villous (20-50%) areas; intermediate in frequency of having a stalk, areas; intermediate in frequency of having a stalk, size, degree of dysplasia & risk of carcinomasize, degree of dysplasia & risk of carcinoma

Clinical features: 20-30% are <40 yrs; 50% after 60Clinical features: 20-30% are <40 yrs; 50% after 60– Small polyps: asymptomaticSmall polyps: asymptomatic– Occult bleeding, anemia, hypoproteinemia & Occult bleeding, anemia, hypoproteinemia &

hypokalemiahypokalemia– Intestinal obstruction or biliary obstructionIntestinal obstruction or biliary obstruction

Rx: Most are cured by adequate endoscopic Rx: Most are cured by adequate endoscopic excisionexcision

Px:Px: Annual endoscopic follow-upAnnual endoscopic follow-up

ADENOMATOUS POLYPSADENOMATOUS POLYPSTUBULAR ADENOMA VILLOUS TUBULAR ADENOMA VILLOUS

ADENOMAADENOMA >85% of adenomas>85% of adenomas Majority in distal Majority in distal

colon; 50% in colon; 50% in rectosigmoidrectosigmoid

Most are small (few Most are small (few mm-2 cm) with a stalk mm-2 cm) with a stalk (-2 cm)(-2 cm)

Histology shows Histology shows neoplastic epithelium neoplastic epithelium forming glands & forming glands & tubulestubules

Variable degrees of Variable degrees of dysplasia to CIS dysplasia to CIS

Invasive carcinoma Invasive carcinoma rarerare

1% of adenomas1% of adenomas Rectum & rectosigmoid Rectum & rectosigmoid

75%, followed by cecum 75%, followed by cecum & ascending colon& ascending colon

Sessile ranging from Sessile ranging from 1-10 cm (most are 1-3 1-10 cm (most are 1-3 cm)cm)

Histology shows Histology shows neoplastic cells neoplastic cells forming villi (>50% forming villi (>50% villous)villous)

Carcinoma Carcinoma in situ 10% in situ 10%

Invasive carcinoma Invasive carcinoma 30%30%

INTESTINAL POLYPSINTESTINAL POLYPSFAMILIAL POLYPOSIS SYNDROMESFAMILIAL POLYPOSIS SYNDROMES

Familial adenomatous polyposis (FAP):Familial adenomatous polyposis (FAP):– Rare autosomal dominant traitRare autosomal dominant trait– Dx: at least 100 polyps (average 1000)Dx: at least 100 polyps (average 1000)– Most are tubular adenomatous polypsMost are tubular adenomatous polyps– Genetic defect of APC gene localized to chromosome 5q21Genetic defect of APC gene localized to chromosome 5q21– Risk of colon cancer: 100% at 30 yearsRisk of colon cancer: 100% at 30 years– Rx: Prophylactic colectomyRx: Prophylactic colectomy

GardnerGardner’’s syndrome:s syndrome:– + osteomas, epidermal cysts, fibromatosis, thyroid Ca..+ osteomas, epidermal cysts, fibromatosis, thyroid Ca..

TurcotTurcot’’s syndrome:s syndrome:– + CNS tumors (gliomas)+ CNS tumors (gliomas)

INTESTINAL POLYPSINTESTINAL POLYPSFAMILIAL POLYPOSIS SYNDROMESFAMILIAL POLYPOSIS SYNDROMES

LynchLynch’’s syndrome:s syndrome:– aka: Hereditary nopolyposis colorectal cancer aka: Hereditary nopolyposis colorectal cancer

(HNPCC)(HNPCC)– Autosomal dominant syndrome characterized by an Autosomal dominant syndrome characterized by an

increased risk of colorectal cancer and extra-increased risk of colorectal cancer and extra-intestinal cancer, particularly endometrial carcinomaintestinal cancer, particularly endometrial carcinoma

– Multiple recurrent colorectal adenomatous polyps Multiple recurrent colorectal adenomatous polyps which present ar an early agewhich present ar an early age

– Mutations in any of 4 genes (MSH2, MLH1, PMS1 & Mutations in any of 4 genes (MSH2, MLH1, PMS1 & PMS2) involved in DNA repair, located in chromo-PMS2) involved in DNA repair, located in chromo-somes 2, 3 & 7, resulting in microsatellite instabilitysomes 2, 3 & 7, resulting in microsatellite instability

– Colonic carcinoma is typically located proximal to Colonic carcinoma is typically located proximal to splenic flexure, often multiple, and not arising in splenic flexure, often multiple, and not arising in preexisting adenomaspreexisting adenomas

TUMORS OF LARGE INTESTINETUMORS OF LARGE INTESTINECOLORECOLORECTAL ADENOCARCINOMACTAL ADENOCARCINOMA

More than 98% of colonic malignanciesMore than 98% of colonic malignancies Second most common cancerSecond most common cancer Peak incidence 60-70 yrs; <20% before age of 50 yrsPeak incidence 60-70 yrs; <20% before age of 50 yrs Wide geographic variation in incidence; more Wide geographic variation in incidence; more

frequent in Western industrialized nationsfrequent in Western industrialized nations Environmental dietary factors have been implicated:Environmental dietary factors have been implicated:– Low unabsorbable vegetable fiber contentLow unabsorbable vegetable fiber content– High refined crabohydrate contentHigh refined crabohydrate content– High fat contentHigh fat content– Low protective micronutrients content (vit. A, C & Low protective micronutrients content (vit. A, C &

E)E) Almost always arise in adenomatous polypsAlmost always arise in adenomatous polyps

COLORECTAL ADENOCARCINOMACOLORECTAL ADENOCARCINOMATHE ADENOMA-CARCINOMA SEQUENCETHE ADENOMA-CARCINOMA SEQUENCE

Cumulative alterations in the genome lead to progressive Cumulative alterations in the genome lead to progressive increase size, dysplasia & invasive potentialincrease size, dysplasia & invasive potential

““Multi-hitMulti-hit”” concept for colon cancer carcniognesis: concept for colon cancer carcniognesis:– First hit: germline or somatic mutations of cancer First hit: germline or somatic mutations of cancer

suppressor genes i.e. APC & mismatch repair genessuppressor genes i.e. APC & mismatch repair genes– Second hit: Methylation abnormalities & inactivation of Second hit: Methylation abnormalities & inactivation of

of normal alleles of APC & mismatch repair genesof normal alleles of APC & mismatch repair genes– Protooncogene mutation, e.g. K-ras at 12p12Protooncogene mutation, e.g. K-ras at 12p12– Homozygous loss of addtional cancer suppressor Homozygous loss of addtional cancer suppressor

genes, e.g. DCC at 18q21 and p53 at 17p13genes, e.g. DCC at 18q21 and p53 at 17p13– Additional mutations of many genes will occur in Additional mutations of many genes will occur in

carcinomacarcinoma

PATHOLOGY & CLINICAL FEATURES OFPATHOLOGY & CLINICAL FEATURES OFCOLORECTAL ADENOCARCINOMACOLORECTAL ADENOCARCINOMA

Majority are sporadic; 1-3% in patients with FAP or IBDMajority are sporadic; 1-3% in patients with FAP or IBD Mostly single; location is shifting to the right colonMostly single; location is shifting to the right colon Proximal colon: fungating polypoid tumorsProximal colon: fungating polypoid tumors Distal colon: annular encircling tumors (napkin-ring)Distal colon: annular encircling tumors (napkin-ring) Tumors penetrate colonic wall layer into serosal surfaceTumors penetrate colonic wall layer into serosal surface Histology range from well differentiated to Histology range from well differentiated to

undifferentiated; may be mucin-secretingundifferentiated; may be mucin-secreting Asymptomatic for yearAsymptomatic for year– Right: fatigue, weakness, iron-deficiency anemiaRight: fatigue, weakness, iron-deficiency anemia– Left: occult bleeding, change in bowel habit, Left: occult bleeding, change in bowel habit,

discomfortdiscomfort Dx: PE, lab, X-ray, endoscopy and biopsyDx: PE, lab, X-ray, endoscopy and biopsy

COLORECTAL ADENOCARCINOMACOLORECTAL ADENOCARCINOMAModified Dukes’ (Astler-Coller) Staging SystemModified Dukes’ (Astler-Coller) Staging SystemTUMORSTAGE

HISTOLOGIC FEATURES 5-YEARSURVIVAL

A Limited to mucosa 100%

B1 Extending to muscularis propria butnot penetrating thru it; uninvolved LN

67%

B2 Penetrating thru muscularis propria;uninvolved LN

54%

C1 Extending into muscularis propria butnot penetrating thru it; involved LN

43%

C2 Penetrating thru muscularis propria;involved LN

22%

D Distant metastasis Very low

TUMORS OF SMALL & LARGE INTESTINETUMORS OF SMALL & LARGE INTESTINE

INTESTINAL LYMPHOMAINTESTINAL LYMPHOMA The GIT is the most common extranodal location The GIT is the most common extranodal location

of lymphomasof lymphomas May be primary or secondaryMay be primary or secondary Primary GI lymphoma: no evidence of liver, Primary GI lymphoma: no evidence of liver,

spleen or bone marrow involvement at diagnosisspleen or bone marrow involvement at diagnosis Adults, M=F, stomach>small intestine>colonAdults, M=F, stomach>small intestine>colon Classification similar to nodal lymphomas: Classification similar to nodal lymphomas:

MALTomas, large cell lymphoma, MALTomas, large cell lymphoma, …… etc. etc. Nonspecific symptomsNonspecific symptoms Rx: surgery, chemo- and radiotherapyRx: surgery, chemo- and radiotherapy Px: better than nodal lymphomasPx: better than nodal lymphomas