Nonneoplastic Nonneoplastic polypspolypsDr MJ EhsaniDr MJ Ehsani

GastroenterologistGastroenterologist

April 16 2009April 16 2009

Nonneoplastic polypsNonneoplastic polyps

HyperplasticHyperplastic MucosalMucosal Inflammatory pseudopolyps Inflammatory pseudopolyps Submucosal Submucosal

Hyperplastic polypsHyperplastic polyps

The most common nonneoplastic The most common nonneoplastic polyp in the colonpolyp in the colon

Small nodules or polypoid lesions Small nodules or polypoid lesions Normal cellular componentsNormal cellular components Indistinguishable grossly from Indistinguishable grossly from

adenomatous polypsadenomatous polyps

Hyperplastic polypsHyperplastic polyps

No dysplasia No dysplasia Serrated ("saw tooth") pattern Serrated ("saw tooth") pattern Proliferation :in the basal portion of Proliferation :in the basal portion of

the crypt of hyperplastic polyps.the crypt of hyperplastic polyps. Rectosigmoid ,sessileRectosigmoid ,sessile less than 5 mm in size less than 5 mm in size Rarely, if ever, develop into Rarely, if ever, develop into

colorectal cancers.colorectal cancers.

Hyperplastic/Adenomatous Hyperplastic/Adenomatous polypspolyps

Hyperplastic colonic Hyperplastic colonic polyp polyp

Hyperplastic Hyperplastic polyps/polyps/prevalenceprevalence

CommonCommon Increased with ageIncreased with age In 9-10 % of asymptomatic,>50 y (up In 9-10 % of asymptomatic,>50 y (up

to 31 %)to 31 %) Autopsy data: 20-35 %Autopsy data: 20-35 % Hyperplastic > adenomatus in Hyperplastic > adenomatus in

diminutive polyps of rectum and diminutive polyps of rectum and sigmoid.sigmoid.

Hyperplastic Hyperplastic polyps/polyps/SignificanceSignificance

Proximal neoplasm :in 21-25 % of Proximal neoplasm :in 21-25 % of patients with distal polyp patients with distal polyp (systematic review)(systematic review)

Relative risk of any proximal Relative risk of any proximal neoplasia :1.3 (95 percent CI 0.9 to neoplasia :1.3 (95 percent CI 0.9 to 1.8). 1.8).

Risk elevation: not clear Risk elevation: not clear Magnitude of risk :small. Magnitude of risk :small.

Hyperplastic Hyperplastic polyps/polyps/ManagementManagement

Left-sided hyperplastic Left-sided hyperplastic polyps :not a significant marker polyps :not a significant marker of colon cancer risk of colon cancer risk

Finding them on a screening Finding them on a screening sigmoidoscopy is not a routine sigmoidoscopy is not a routine indication for colonoscopy.indication for colonoscopy.

Hyperplastic polyposis Hyperplastic polyposis syndromesyndromeDefinitionDefinition

Multiple (> 20) , large polyps (> Multiple (> 20) , large polyps (> 1 cm)1 cm)

Proximal hyperplastic polypsProximal hyperplastic polyps Serrated adenomas ,adenomasSerrated adenomas ,adenomas Mixed hyperplastic/adenomatous Mixed hyperplastic/adenomatous

polypspolyps

WHO CriteriaWHO Criteria

At least five hyperplastic polyps At least five hyperplastic polyps proximal to the sigmoid colon(two proximal to the sigmoid colon(two are greater than 1 cm in diameter).are greater than 1 cm in diameter).

Any number of hyperplastic polyps Any number of hyperplastic polyps occurring proximal to the sigmoid occurring proximal to the sigmoid colon in an individual who has a first colon in an individual who has a first degree relative with hyperplastic degree relative with hyperplastic polyposis,polyposis,

Greater than 30 hyperplastic polyps Greater than 30 hyperplastic polyps distributed throughout the colon.distributed throughout the colon.

HPS/HPS/CourseCourse

Risk of colorectal cancer: Risk of colorectal cancer: increasedincreased

Natural history :unclearNatural history :unclear Careful surveillance, surgery Careful surveillance, surgery Germline mutation :not known Germline mutation :not known

Management strategiesManagement strategies

Not been well-defined. Not been well-defined. Proximal polyps: should be resected Proximal polyps: should be resected Increased colonoscopic surveillance Increased colonoscopic surveillance

: has been proposed : has been proposed Frequency of surveillance: no Frequency of surveillance: no

consensusconsensus

HPS/HPS/ScreeningScreening

First-degree relatives of affected First-degree relatives of affected individuals : Screening colonoscopy individuals : Screening colonoscopy

Beginning at age 40 (or 10 years Beginning at age 40 (or 10 years earlier than the earliest age at earlier than the earliest age at diagnosis in the family)diagnosis in the family)

A surveillance interval : five years A surveillance interval : five years for relatives (if no polyps are found).for relatives (if no polyps are found).

Mucosal polypsMucosal polyps

Small (usually <5 mm) Small (usually <5 mm) excrescences of tissueexcrescences of tissue

Endoscopically resemble the Endoscopically resemble the adjacent flat mucosaadjacent flat mucosa

Histology: normal mucosa. Histology: normal mucosa. No clinical significance.No clinical significance.

Inflammatory Inflammatory pseudopolypspseudopolyps

Irregularly shaped islands of residual Irregularly shaped islands of residual intact colonic mucosaintact colonic mucosa

Mucosal ulceration and regenerationMucosal ulceration and regeneration Multiple, often filiform and scattered Multiple, often filiform and scattered

throughout the colitic region of the throughout the colitic region of the colon. colon.

Risk factor for colon cancer?Risk factor for colon cancer? Associated with surrounding dysplasia Associated with surrounding dysplasia

Pseudopolyps in inflammatory Pseudopolyps in inflammatory

bowel diseasebowel disease

Submucosal polypsSubmucosal polyps

Lymphoid aggregates Lymphoid aggregates Lipomas, leiomyomas Lipomas, leiomyomas Pneumatosis cystoid intestinalis Pneumatosis cystoid intestinalis Colitis cystica profunda/solitary/< 3 Colitis cystica profunda/solitary/< 3

cmcm Hemangiomas Hemangiomas Fibromas Fibromas CarcinoidsCarcinoids Metastatic lesionsMetastatic lesions

LipomaLipoma

Colon:the most common GI siteColon:the most common GI site Yellow colorYellow color SoftnessSoftness Pillow sign(indentation on gentle Pillow sign(indentation on gentle

pressure) pressure) Endoscopic ultrasoundEndoscopic ultrasound

Lymphoid polypsLymphoid polyps

Hypertrophied folliclesHypertrophied follicles Pain,bleedingPain,bleeding PedunculatePedunculate Distinction from malignant lymphoid Distinction from malignant lymphoid

lesionslesions

lymphoid polypslymphoid polyps

Lymphoid polyps of the colon in a Lymphoid polyps of the colon in a child. child.

Hamartomatous polyps Hamartomatous polyps Juvenile polypsJuvenile polyps

Hamartomatous lesions Hamartomatous lesions Consist of a lamina propria and Consist of a lamina propria and

dilated cystic glands rather than dilated cystic glands rather than increased numbers of epithelial cellsincreased numbers of epithelial cells

Retention polyp (distended,mucus Retention polyp (distended,mucus filled glands,inflammatory cells)filled glands,inflammatory cells)

Any age, more common in Any age, more common in childhood(1-2 %).childhood(1-2 %).

Juvenile polypsJuvenile polyps

AcquiredAcquired SingleSingle 3 mm-2 cm3 mm-2 cm Bleeding,prolapseBleeding,prolapse Malignancy risk: not increasedMalignancy risk: not increased Removal is suggestedRemoval is suggested

Juvenile polypsJuvenile polyps

Multiple juvenile polypsMultiple juvenile polyps Rare(< 1 out of 100,000 live births)Rare(< 1 out of 100,000 live births) Autosomal dominant inheritance Autosomal dominant inheritance

(familial juvenile polyposis (FJP)(familial juvenile polyposis (FJP) Germ-line mutations : SMAD4 gene Germ-line mutations : SMAD4 gene

on chromosome 18q21.1, or in the on chromosome 18q21.1, or in the gene BMPR1A. gene BMPR1A.

Increased risk for colorectal cancer, Increased risk for colorectal cancer, and in some families, gastric cancer, and in some families, gastric cancer, especiallyespecially

Multiple juvenile Multiple juvenile polyps/FJPpolyps/FJP

Symptoms: 4 – 14 ySymptoms: 4 – 14 y 10 or more juvenile polyps10 or more juvenile polyps Rectal bleeding/anemia(75 Rectal bleeding/anemia(75

%),prolapse,…%),prolapse,… Adenomatous changes: 8 - 47 %Adenomatous changes: 8 - 47 % Colon cancer risk : up to 20 % ?Colon cancer risk : up to 20 % ? Cancer risk: greatest if > 3 polyps or Cancer risk: greatest if > 3 polyps or

FH of juvenile polyps.FH of juvenile polyps.

FJP/ FJP/ ScreeningScreening

No consensus.No consensus. Asymptomatic first degree relatives : should be Asymptomatic first degree relatives : should be

screened screened Annual FOB and flexible sigmoidoscopy or Annual FOB and flexible sigmoidoscopy or

colonoscopy every three to five years beginning at colonoscopy every three to five years beginning at age 12 and continuing until approximately age 40.age 12 and continuing until approximately age 40.

Symptomatic patients :evaluation regardless of age.Symptomatic patients :evaluation regardless of age.

Colonoscopy every one to two years beginning at Colonoscopy every one to two years beginning at age 15 to 18 (or earlier in patients who presented age 15 to 18 (or earlier in patients who presented with symptoms) . { British Society of with symptoms) . { British Society of Gastroenterology }Gastroenterology }

FJP/ FJP/ SurveillanceSurveillance Gene carriers or affected cases : surveillance Gene carriers or affected cases : surveillance

until age 70. until age 70. Colonoscopic polypectomy with regular Colonoscopic polypectomy with regular

surveillance : if only a small number of polyps surveillance : if only a small number of polyps are present . are present .

Prophylactic surgery :With a large number of Prophylactic surgery :With a large number of polyps ,multiple polyps with adenomatous polyps ,multiple polyps with adenomatous change and high-grade dysplasia, polyps cannot change and high-grade dysplasia, polyps cannot be removed endoscopically , complications (such be removed endoscopically , complications (such as bleeding) are not easily controlled, colorectal as bleeding) are not easily controlled, colorectal cancer is a feature of the family history cancer is a feature of the family history

FJP/ Surveillance, FJP/ Surveillance, cont..cont..

UGI surveillance has been UGI surveillance has been recommended every one to recommended every one to two years beginning at age two years beginning at age 25 by upper 25 by upper endoscopy/enteroscopy or endoscopy/enteroscopy or UGI with SBFTUGI with SBFT

Peutz-Jeghers polyps Peutz-Jeghers polyps 

Hamartomatous lesionHamartomatous lesion Almost always with the Peutz-Jeghers Almost always with the Peutz-Jeghers

syndrome. syndrome. Gastrointestinal (gastric, small bowel, Gastrointestinal (gastric, small bowel,

colon, pancreas) cancer risk: colon, pancreas) cancer risk: increasedand increasedand

Nongastrointestinal cancers risk : Nongastrointestinal cancers risk : increasedincreased

Cumulative cancer risk :50 % by age 60. Cumulative cancer risk :50 % by age 60.

Colonic Peutz-Jeghers Colonic Peutz-Jeghers polyppolyp

PJSPJS

Autosomal dominant. Autosomal dominant. Males /females :equal. Males /females :equal. Rare (prevalence between 1:25,000 Rare (prevalence between 1:25,000

and 1:280,000). and 1:280,000). The PJ gene :chromosomal 19p13.3The PJ gene :chromosomal 19p13.3

Clinical manifestationsClinical manifestations

Pigmented mucocutaneous maculesPigmented mucocutaneous macules Multiple gastrointestinal polypsMultiple gastrointestinal polyps Polyps : benign, grow Polyps : benign, grow

progressively ,then progressively ,then symptoms ,malignant symptoms ,malignant transformation. transformation.

Pigmented spotsPigmented spots

Mucocutaneous pigmentations :> 95 %Mucocutaneous pigmentations :> 95 % Flat, blue-gray to brown spots 1 to 5 Flat, blue-gray to brown spots 1 to 5

mm in size mm in size Freckles /onset and location.Freckles /onset and location. PJS lesions on the lips and perioral PJS lesions on the lips and perioral

region (94%), hands (74%), buccal region (94%), hands (74%), buccal mucosa (66%) and feet (62%)mucosa (66%) and feet (62%)

Pigmented spotsPigmented spots

Nose, perianal area, and genitalsNose, perianal area, and genitals Intestines:rareIntestines:rare Occur during the first one to two years of life, Occur during the first one to two years of life,

increase in size and number over the ensuing increase in size and number over the ensuing years, and finally fade after puberty with the years, and finally fade after puberty with the exception of those on the buccal mucosa.exception of those on the buccal mucosa.

Freckles:sparse near the nostrils and mouth, Freckles:sparse near the nostrils and mouth, are absent at birth, and never appear on the are absent at birth, and never appear on the buccal mucosa. buccal mucosa.

Malignant degeneration :extremely rare.Malignant degeneration :extremely rare.

Oral lesions in Peutz-Oral lesions in Peutz-Jeghers syndromeJeghers syndrome

Gastrointestinal polypsGastrointestinal polyps

Present in most patients with PJSPresent in most patients with PJS Proliferation of smooth muscle Proliferation of smooth muscle

extending into the lamina propria in an extending into the lamina propria in an arborization-like fashion; the overlying arborization-like fashion; the overlying epithelium is normalepithelium is normal

Sessile, pedunculated, lobulated Sessile, pedunculated, lobulated Small intestine — 64 percent Small intestine — 64 percent Colon — 64 percent Colon — 64 percent Stomach — 49 percent Stomach — 49 percent Rectum — 32 percentRectum — 32 percent

Polyps in PJSPolyps in PJS

Number : 1 to >20 per segment Number : 1 to >20 per segment of bowelof bowel

Size : variable (0.1 > 5 cm)Size : variable (0.1 > 5 cm) Grow in the first decade of lifeGrow in the first decade of life Symptoms : between the age of Symptoms : between the age of

10 and 3010 and 30

PJS/ Presenting PJS/ Presenting gastrointestinal symptoms gastrointestinal symptoms

Obstruction :43% Obstruction :43% (intussusception ,occlusion of the lumen) (intussusception ,occlusion of the lumen)

Abdominal pain :23% (infarction)Abdominal pain :23% (infarction) Acute or chronic rectal bleeding :14%Acute or chronic rectal bleeding :14%

(ulceration)(ulceration) Extrusion of the polyp through the Extrusion of the polyp through the

rectum :7 %rectum :7 % Intussusception: Nearly one-half of the Intussusception: Nearly one-half of the

patientspatients

Duodenal peutz-Jeghers Duodenal peutz-Jeghers polyp polyp

Peutz-Jeghers polyp Peutz-Jeghers polyp

Diagnosis /Diagnosis /Clinical Clinical CriteriaCriteria

For individuals with a For individuals with a histopathologically confirmed histopathologically confirmed hamartoma, a definite diagnosis of hamartoma, a definite diagnosis of PJS requires two of the following PJS requires two of the following three findings:three findings:

1. Family history consistent with 1. Family history consistent with autosomal dominant inheritanceautosomal dominant inheritance

2. Mucocutaneous hyperpigmentation2. Mucocutaneous hyperpigmentation 3. Small-bowel polyposis 3. Small-bowel polyposis

Diagnosis /Diagnosis /Clinical Clinical CriteriaCriteria

For individuals For individuals without histopathologicwithout histopathologic verification of hamartomatous polyps, a verification of hamartomatous polyps, a probableprobable diagnosis of PJS can be made based diagnosis of PJS can be made based on the presence of two of the three clinical on the presence of two of the three clinical criteria above. criteria above.

For individuals For individuals without a family historywithout a family history of PJS, of PJS, diagnosis depends upon the presence of diagnosis depends upon the presence of two or two or more histologically verified Peutz-Jeghers-typemore histologically verified Peutz-Jeghers-type hamartomatous polyps. hamartomatous polyps.

For individuals with a For individuals with a first-degree relativefirst-degree relative with with PJS, presence of PJS, presence of mucocutaneousmucocutaneous hyperpigmentation is sufficient for presumptive hyperpigmentation is sufficient for presumptive diagnosis.diagnosis.

Risk of malignancyRisk of malignancy The overall risk of developing cancer at The overall risk of developing cancer at

ages 20, 30, 40, 50, 60, and 70 was 1, 3, ages 20, 30, 40, 50, 60, and 70 was 1, 3, 19, 32, 63, and 81 percent, respectively. 19, 32, 63, and 81 percent, respectively.

The most common The most common cancers :gastrointestinal in origin cancers :gastrointestinal in origin

The risk for these cancers at ages 30, The risk for these cancers at ages 30, 40, 50 and 60 was estimated to be 1, 40, 50 and 60 was estimated to be 1, 10, 18, and 42 percent, respectively. 10, 18, and 42 percent, respectively.

Breast cancer : increased (32 percent Breast cancer : increased (32 percent by age 60).by age 60).

Non-gastrointestinal Non-gastrointestinal cancerscancers

lung lung breastbreast uterusuterus ovary ovary cervix cervix testiestesties

ChemoprophylaxisChemoprophylaxis

Not establishedNot established COX-2 inhibitorsCOX-2 inhibitors Rapamycin(Sirolimus)Rapamycin(Sirolimus)

PJS/PJS/ScreeningScreening

All GI cancers 2-13%All GI cancers 2-13% Colonoscopy at symptom onset, or in late Colonoscopy at symptom onset, or in late

teenage years if the individual is teenage years if the individual is asymptomaticasymptomatic

Interval is determined by the number of Interval is determined by the number of polyps but at least q 3 yr polyps but at least q 3 yr

Upper GI endoscopy q 2 yr; start at age 10 yrUpper GI endoscopy q 2 yr; start at age 10 yr Small intestinal cancer RR, 13 Annual Hgb; Small intestinal cancer RR, 13 Annual Hgb;

small bowel series or capsule endoscopy q 2 small bowel series or capsule endoscopy q 2 yr; start at age 10 yryr; start at age 10 yr

PJS/ScreeningPJS/Screening Pancreatic cancer RR, 100 Endoscopic or Pancreatic cancer RR, 100 Endoscopic or

abdominal ultrasound q 1-2 yr; start at age 30 yrabdominal ultrasound q 1-2 yr; start at age 30 yr Breast cancer RR, 8.8 Annual breast Breast cancer RR, 8.8 Annual breast

examination; mammogram q 1-3 yr; start at age examination; mammogram q 1-3 yr; start at age 25 yr25 yr

Uterine; ovarian cancer RR, 8.0; 13 Annual Uterine; ovarian cancer RR, 8.0; 13 Annual pelvic examination; Pap smear and pelvic pelvic examination; Pap smear and pelvic ultrasound; start at age 20 yrultrasound; start at age 20 yr

Sertoli cell tumor (testis)Uncommon Annual Sertoli cell tumor (testis)Uncommon Annual testicular examination beginning at age 10 yr; testicular examination beginning at age 10 yr; testis ultrasound if the patient has feminizing testis ultrasound if the patient has feminizing featuresfeatures

Screening and surveillanceScreening and surveillance

Genetic testing :not yet widely availableGenetic testing :not yet widely available For asymptomatic first degree relatives of For asymptomatic first degree relatives of

patients with known PJS : screening is patients with known PJS : screening is recommended recommended

Have not been validated in clinical trialsHave not been validated in clinical trials Beginning at birth with an annual history, Beginning at birth with an annual history,

physical examination, and evaluation for physical examination, and evaluation for melanotic spots, precocious puberty, and melanotic spots, precocious puberty, and testicular tumors. testicular tumors.

Predictive genetic testing can be offered at age Predictive genetic testing can be offered at age eight years (in at-risk individuals in whom the eight years (in at-risk individuals in whom the diagnosis is not already apparent clinically). diagnosis is not already apparent clinically).

Screening and Screening and surveillancesurveillance

What type of screening :unsettled. What type of screening :unsettled. upper gastrointestinal series every two upper gastrointestinal series every two

years until age 25 ?years until age 25 ? upper endoscopy, colonoscopy, and small upper endoscopy, colonoscopy, and small

bowel series at ages 12, 18, and 24 years ?bowel series at ages 12, 18, and 24 years ? Endoscopic polypectomy :for polyps >1 cmEndoscopic polypectomy :for polyps >1 cm Surgery for large polypsSurgery for large polyps Clearing the small bowel of polyps at Clearing the small bowel of polyps at

laparotomy laparotomy

Surveillance of affected Surveillance of affected individualsindividuals

Regular surveillance : recommended. Regular surveillance : recommended. Surveillance :detecting cancers of the breast, Surveillance :detecting cancers of the breast,

colon, pancreas, stomach and small bowel, colon, pancreas, stomach and small bowel, ovaries, uterus and cervix, and testicles. ovaries, uterus and cervix, and testicles.

From birth to age 12. In male patients: From birth to age 12. In male patients: history and physical examination with history and physical examination with attention to the testicles. attention to the testicles.

Routine blood tests annually (ultrasound of Routine blood tests annually (ultrasound of the testicles every two years until age 12 the testicles every two years until age 12 offeredoffered as an option). as an option).

Surveillance of affected Surveillance of affected individualsindividuals

For female patients(at age 8): History and For female patients(at age 8): History and physical examination with routine blood tests physical examination with routine blood tests annually. annually.

For males and females: upper endoscopy and For males and females: upper endoscopy and small bowel series; if positive, continue every small bowel series; if positive, continue every two to three years(From age 18)two to three years(From age 18)

In male patients: colonoscopy, upper In male patients: colonoscopy, upper endoscopy, and small bowel series every two endoscopy, and small bowel series every two to three years. to three years.

In female patients: Colonoscopy, upper In female patients: Colonoscopy, upper endoscopy, and small bowel series every two endoscopy, and small bowel series every two to three years; breast self-exam monthly. to three years; breast self-exam monthly.

Surveillance of affected Surveillance of affected individualsindividuals

From age 21 on. For female patients: pelvic From age 21 on. For female patients: pelvic examination with a Papanicolaou smear annually. examination with a Papanicolaou smear annually.

From age 25 on. For male patients: endoscopic From age 25 on. For male patients: endoscopic ultrasound of the pancreas every one to two ultrasound of the pancreas every one to two years (CT scan and/or CA19-9 offered as options). years (CT scan and/or CA19-9 offered as options).

For female patients: endoscopic ultrasound of For female patients: endoscopic ultrasound of the pancreas every one to two years (CT scan the pancreas every one to two years (CT scan and/or CA 19-9 offered as options); clinical breast and/or CA 19-9 offered as options); clinical breast exam semiannually; mammography annually exam semiannually; mammography annually (MRI offered as an alternative); transvaginal (MRI offered as an alternative); transvaginal ultrasound and serum CA-125 annually. ultrasound and serum CA-125 annually.

Cronkhite-Canada Cronkhite-Canada syndrome syndrome 

Rare, nonfamilial /Unknown etiologyRare, nonfamilial /Unknown etiology Alopecia, cutaneous hyperpigmentation, GI Alopecia, cutaneous hyperpigmentation, GI

polyposis(hamartomas), onychodystrophy, polyposis(hamartomas), onychodystrophy, diarrhea, weight loss and abdominal pain. diarrhea, weight loss and abdominal pain.

Do not appear neoplastic pathologically.Do not appear neoplastic pathologically. Characteristic features :myxoid expansion of Characteristic features :myxoid expansion of

the lamina propria and increased eosinophils the lamina propria and increased eosinophils in the polyps in the polyps

Five-year mortality rates up to 55 %Five-year mortality rates up to 55 % Deaths due to GIB, sepsis, and CHFDeaths due to GIB, sepsis, and CHF Treatment :nutritional support, Treatment :nutritional support,

corticosteroids, acid suppression, and corticosteroids, acid suppression, and antibiotics?antibiotics?

Thanks for your Thanks for your attentionattention