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