Familial Adenomatous Familial Adenomatous Polyposis (FAP)Polyposis (FAP)

Most common, 1:10,000 individualsMost common, 1:10,000 individuals Risk of CA of affected patients: 100%Risk of CA of affected patients: 100% 100’s to 1,000’s, appear at average 16 100’s to 1,000’s, appear at average 16

y/o, most CA at 39 y/o-if untx 93% have y/o, most CA at 39 y/o-if untx 93% have CA before 50CA before 50

More than 90% also have duodenal More than 90% also have duodenal polyps, with lifetime risk of polyps, with lifetime risk of duodenal/periampullary CA of up to 10%duodenal/periampullary CA of up to 10%

Homozygous inactivation of APC gene Homozygous inactivation of APC gene on chromosome 5q-autosomal dominanton chromosome 5q-autosomal dominant

FAPFAP

Patient with few rectal polyps can Patient with few rectal polyps can have rectal preservation, but MUST have rectal preservation, but MUST be continuously monitored-more be continuously monitored-more than 50% will develop CA in this than 50% will develop CA in this area despite surveillancearea despite surveillance

Must evaluate upper GI tract at time Must evaluate upper GI tract at time of diagnosis and every 1-3 yearsof diagnosis and every 1-3 years Duodenal adenomasDuodenal adenomas Gastric adenomas, but Gastric adenomas, but most common most common

fundic gland polypsfundic gland polyps

Gastric Fundic Gland Gastric Fundic Gland PolypsPolyps

Benign cystic and polypoid Benign cystic and polypoid proliferation of oxyntic glandsproliferation of oxyntic glands

Have alterations of APC Beta catenin Have alterations of APC Beta catenin pathway in syndromic and sporadicpathway in syndromic and sporadic

Common, more than 50% of gastric Common, more than 50% of gastric polyps polyps

More common in females, single or More common in females, single or multiple.multiple.

-In FAP:-fundic gland polyps can have dysplasia—excellent marker of FAP -Can have over 100 polyps

-Can also Be seen in SporadicPolyps.

-Risk ofCAIs low

Attenuated FAPAttenuated FAP

Average of 30 polyps, typically right-Average of 30 polyps, typically right-sided, adenomas and CA arise 10 sided, adenomas and CA arise 10 yrs later than FAPyrs later than FAP

Can spare rectumCan spare rectum Can have numerous flat polypsCan have numerous flat polyps Mutations in the 5’ region of APC Mutations in the 5’ region of APC

genegene

Other adenomatous Other adenomatous polyposispolyposis

FAP can have extraintestinal FAP can have extraintestinal manifestations: desmoid tumors, fibromas, manifestations: desmoid tumors, fibromas, but if these are numerous:but if these are numerous:

Gardner's syndromeGardner's syndrome: polyposis, skin : polyposis, skin lesions (epidermal cysts), bony lesions lesions (epidermal cysts), bony lesions (osteomas), dental abnormalities- -soft (osteomas), dental abnormalities- -soft tissue lesions can precede polyps by years tissue lesions can precede polyps by years

Turcot’s syndromeTurcot’s syndrome: have brain tumors, : have brain tumors, particularly medulloblastomas- - high particularly medulloblastomas- - high mortality, can be seen before polypsmortality, can be seen before polyps

Second most common, incidence Second most common, incidence 1/10th of FAP1/10th of FAP

Autosomal dominant but with Autosomal dominant but with variable and incomplete penetrancevariable and incomplete penetrance

Two major components:Two major components: Hamartomatous polyps (jejunum, ileum, Hamartomatous polyps (jejunum, ileum,

colon, stomach, duodenum and appendix)colon, stomach, duodenum and appendix) Pigmented macules in mucous Pigmented macules in mucous

membranes and skinmembranes and skin

Peutz-Jeghers SyndromePeutz-Jeghers Syndrome

Peutz-Jegher polyp

PJ syndromePJ syndrome

Dx made in infancy because of Dx made in infancy because of pigmentation within 2 yrs. (can be pigmentation within 2 yrs. (can be present at birth, around mucosas of present at birth, around mucosas of face)face)

Small bowel polyps can be Small bowel polyps can be symptomatic- -intussusception and symptomatic- -intussusception and obstruction, in rectum can prolapse obstruction, in rectum can prolapse and bleed.and bleed.

PJ syndromePJ syndrome In adults, can have carcinoma involving GI In adults, can have carcinoma involving GI

tract and multiple organ sites ( breast, lung, tract and multiple organ sites ( breast, lung, pancreas, uterus, ovaries (SCTAT), cervix and pancreas, uterus, ovaries (SCTAT), cervix and testes) testes)

93% lifetime risk of cancer, mean age 43 yrs., 93% lifetime risk of cancer, mean age 43 yrs., mostly in colon, stomach and pancreasmostly in colon, stomach and pancreas

Most of the reported carcinomas of the Most of the reported carcinomas of the gastrointestinal tract in PJS patients have gastrointestinal tract in PJS patients have not had evidence of origin from a not had evidence of origin from a hamartoma but rather derive from co-hamartoma but rather derive from co-existing adenomasexisting adenomas

Periodic surveillance of high risk organsPeriodic surveillance of high risk organs

Juvenile PolyposisJuvenile Polyposis

Multiple juvenile or inflammatory polyps in Multiple juvenile or inflammatory polyps in GI tract and/or colonGI tract and/or colon

Third most common, sporadic or autosomal Third most common, sporadic or autosomal dominant, on average 9.5 yrs old, slight male dominant, on average 9.5 yrs old, slight male predominancepredominance

Most common polyp diagnosed in pediatric Most common polyp diagnosed in pediatric population, so for dx: population, so for dx: more than 5 polyps at more than 5 polyps at a time, extracolonic polyps, juvenile polyps a time, extracolonic polyps, juvenile polyps in patient with a family history of JPin patient with a family history of JP

Usually present with painless rectal bleedingUsually present with painless rectal bleeding

JPSJPS

Significant risk for colon CA, as well as Significant risk for colon CA, as well as gastric, duodenal and pancreatic cancer. gastric, duodenal and pancreatic cancer. Screening upper endo and colonoscopy in Screening upper endo and colonoscopy in adolescenceadolescence

Two forms:Two forms: Autosomal dominant familial type w/o Autosomal dominant familial type w/o

anomaliesanomalies Nonfamilial with congenital anomaliesNonfamilial with congenital anomalies

20% have congenital heart disease, hydrocephalus, 20% have congenital heart disease, hydrocephalus, intestinal malrotationintestinal malrotation

Digital clubbing, failure to thriveDigital clubbing, failure to thrive

Cowden’s SyndromeCowden’s Syndrome

Multiple hamartoma syndrome, autosomal Multiple hamartoma syndrome, autosomal dominantdominant

Face and oral cavity lesions: strict criteriaFace and oral cavity lesions: strict criteria Macrocephaly, breast (most common CA in Macrocephaly, breast (most common CA in

females), thyroid CA(most common), females), thyroid CA(most common), endometrial CA, Lhermite-Duclos disease endometrial CA, Lhermite-Duclos disease (cerebellar gangliocytoma): major criteria(cerebellar gangliocytoma): major criteria

GI lesions: minor criteria- -NO increased GI lesions: minor criteria- -NO increased risk GI cancerrisk GI cancer

80% of families have PTEN mutation80% of families have PTEN mutation

All types of polyps…JP, PJ, lipomas, ganglioneuromas, leiomyomas

Hyperplastic Polyposis Hyperplastic Polyposis SyndromeSyndrome

Multiple hyperplastic polyps in GI Multiple hyperplastic polyps in GI tract, increased risk of colorectal CAtract, increased risk of colorectal CA

More than 5 proximal to sigmoid, two More than 5 proximal to sigmoid, two of which are larger than 1cmof which are larger than 1cm

Any number of HP proximal to Any number of HP proximal to sigmoid in patient with 1sigmoid in patient with 1stst degree degree relative with hx of HPS (at least one relative with hx of HPS (at least one large polyp)large polyp)

30 or more of any size but evenly 30 or more of any size but evenly distributed throughout colorectumdistributed throughout colorectum

HPSHPS Spectrum includes HP (most common), Spectrum includes HP (most common),

serrated adenomas, mixed ta-hp and serrated adenomas, mixed ta-hp and tubular adenomastubular adenomas

May be greater than 100, but often in tens, May be greater than 100, but often in tens, sessile, large polyps have been reportedsessile, large polyps have been reported

Have some degree of cellular and Have some degree of cellular and architectural atypiaarchitectural atypia

Low levels of microsatellite instabilityLow levels of microsatellite instability Up to 35% have synchronous colon CAUp to 35% have synchronous colon CA Pancolonoscopy every 1 to 3 years Pancolonoscopy every 1 to 3 years

Esophageal PolypsEsophageal Polyps

Squamous papilloma-Reflux-Some related to HPV

Leiomyoma: most common benign lesion in esophagus

Granular Cell TumorGranular Cell Tumor

Most common site in GI tract for these tumorsMost common site in GI tract for these tumors #2 most common stromal tumor of esophagus #2 most common stromal tumor of esophagus

after leiomyomaafter leiomyoma Usually incidental, in lower esophagus, 90% Usually incidental, in lower esophagus, 90%

solitarysolitary May cause obstruction if largeMay cause obstruction if large May be of Schwannian origin—S-100 positiveMay be of Schwannian origin—S-100 positive Commonly women in 40’s, blacksCommonly women in 40’s, blacks May be underdiagnosed on superficial May be underdiagnosed on superficial

biopsies that lack lamina propriabiopsies that lack lamina propria

Gastric Polyps: AdenomaGastric Polyps: Adenoma

Represents 10% of polypoid lesions in Represents 10% of polypoid lesions in stomach.stomach.

Is a precursor lesion of gastric Is a precursor lesion of gastric adenocarcinoma, but NOT the major one:adenocarcinoma, but NOT the major one: Can contain focus of carcinoma at time Can contain focus of carcinoma at time

of diagnosisof diagnosis 30% risk of carcinoma in adjacent 30% risk of carcinoma in adjacent

mucosa—marker for CAmucosa—marker for CA

Intestinal Type:-More common

-Usually in background of atrophy or intestinal metaplasia MORE likely to have:

-HGD -Adenocarcinoma

Foveolar type:-gastric foveolar-type lining

Reactive changes

XanthomaLipid-laden histiocytes, CD68 +: bile reflux, H. pylori, hypercholesterolemia

Signet ring CA

Inflammatory/Regenerative Inflammatory/Regenerative PolypPolyp

22ndnd most common gastric polyp most common gastric polyp Due to H.pylori gastritis, mucosal Due to H.pylori gastritis, mucosal

damage (reflux, s/p surgery)damage (reflux, s/p surgery) Most common polyp seen in Most common polyp seen in

autoimmune gastritis autoimmune gastritis 1.5-3% can undergo malignant 1.5-3% can undergo malignant

transformationtransformation Adenomatous changesAdenomatous changes More likely in polyps greater than 2cmMore likely in polyps greater than 2cm

Carcinoid TumorCarcinoid Tumor

Most common primary tumor of the Most common primary tumor of the small bowel and appendix. small bowel and appendix.

Accounts for more than 95% of all Accounts for more than 95% of all carcinoids.carcinoids.

Arise from enterochromaffin cells, Arise from enterochromaffin cells, which are considered neural crest cells which are considered neural crest cells situated in GI glands.situated in GI glands.

Gastrointestinal carcinoids account for Gastrointestinal carcinoids account for 1.5% of all gastrointestinal tumors 1.5% of all gastrointestinal tumors

-Chromogranin-Synaptophysin

--positive

In stomach: Type I: autoimmune gastritis

Type II: ZES Type III: sporadic

In Small Bowel:-2/3 are gastrinomas

-1/3 are functional--ZES -1/3 are somatostatinomas -1/3 von Recklinghausen dx

Chronic DuodenitisChronic Duodenitis

Heterotopic Gastric Heterotopic Gastric MucosaMucosa

Duodenal PolypsDuodenal Polyps

Adenomas

Heterotopic pancreas

Vanek Polyp Vanek Polyp (inflammatory fibroid polyp) (inflammatory fibroid polyp) Stomach, small bowel, colonStomach, small bowel, colon Can cause gastric outlet obstruction Can cause gastric outlet obstruction

and intussusceptionand intussusception Rare benign lesion, 1-4 cm in sizeRare benign lesion, 1-4 cm in size CD34 positiveCD34 positive

Histology:-submucosa with reactive changes

-spindle cells-onion skin around vessels-eosinophils

Suggested Reference Suggested Reference MaterialMaterial

pathologyoutlines.compathologyoutlines.com http://kathrin.unibas.ch/polyp/index.html

Serrated polyp quizSerrated polyp quiz Books:Books:

Odze, R—Surgical Pathology of the GI TractOdze, R—Surgical Pathology of the GI Tract Montgomery, E-GI and Liver PathologyMontgomery, E-GI and Liver Pathology Greenson, J—Diagnostic Pathology Greenson, J—Diagnostic Pathology

GastrointestinalGastrointestinal AmyrsysAmyrsys