Polyposis Syndromes Flashcards
Colorectal polyps can be classified as
adenomatous
hamartomatous
hyperplastic
neoplastic
inflammatory.
Colorectal Polyposis Syndromes Summary
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Colorectal Polyposis Syndromes 2
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Colorectal Polyposis Syndromes 3
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Familial adenomatous polyposis (FAP)
- Autosomal dominant
- mutation in the adenomatous polyposis coli (APC) tumor suppressor gene
- located on chromosome 5q21.
- Most mutations are found between codons 168 and 1640
- Two of the most significant being 1061 and 1309.
FAP is defined as
- greater than 100 synchronous adenomas
or
fewer than 100 with a positive family history. - Polyps, predominately found in the rectum and left colon, develop in adolescence
If untreated, the risk of colorectal malignancy is nearly
100% by 35 to 40 years of age.
screening colonoscopy should be performed at
10 to 12 years of age and continue annually.
With the predilection for polyp development in the left colon and rectum, a yearly flexible proctosigmoidoscopy can be completed instead of a formal colonoscopy. If adenomatous polyps are appreciated on sigmoidoscopy, a formal colonoscopy should ensue.
A screening esophagogastroduodenoscopy (EGD) is typically performed around
20 years of age
Gastric Lesions in FAP
- Hyperplastic gastric fundic glad polyps
> low malignant potential > 30% to 90% of patients - Gastric adenomas > potential malignant progression > 10%– 30% > occur in the antrum.
Where is Duodenal adenomas Mostly Found
- Most commonly found around the ampulla of Vater
What is the percentage of Patients with FAP will have Dudenal adenoma ? When will it appear ? and how much will have Cancer
- Found in more than 95% of patients with FAP
- Develop approximately 15 years later than colonic polyps
- Duodenal cancer, typically diagnosed around 50 years of age, occurs in 5% to 10% of Patients
The risk of developing cancer after 10 years of follow-up for each stage
Stage I is 0
Stage II and III 2%
Stage IV 36%
Spigelman stage
see
Low Risk Adenomas
Small tubular adenomas
low-grade dysplasia,
> can be biopsied and observed.
High-risk adenomas, and Tx ?
villous
> 1 cm
severe duodenal polyposis
high-grade dysplasia
or stage IV disease
> offered a pancreas-preserving duodenectomy
Those with cancer, Tx
- Pancreaticoduodenectomy.
- Chemoprevention with nonsteroidal antiinflammatory agents (sulindac, celecoxib) can result in polyp regression
Suggested Interval to Next Duodenoscopy (Years)
see
Common extraintestinal manifestations of FAP
- osteomas
- congenital hypertrophy of the retinal pigmented epithelium (CHRPE)
- epidermoid cyst
- dermoids.
- Benign osteomas of the mandible, skull, and tibia are the most common extraintestinal finding occurring in upward of 80% of patients.
- CHRPE is not specific to FA
> four or more areas of large patchy fundic discoloration is pathognomonic - Epidermoid cysts occur approximately 50%
Other extraintestinal manifestations, though rare, include
supernumerary teeth
cerebellar medulloblastoma
cancers of the liver, biliary tree, adrenal glands, and thyroid.
The second leading cause of death associated with FAP.
Duodenal cancer
What Percentage of FAP will Develop Desmoid
Desmoids develop in 15% to 30% of patients
What is the Third Most Common of death in FAP
Desmoid
Risk factors associated with the development of desmoids are
- mutations in the 3 ΄ end of the APC gene
- female gender
- extraintestinal manifestations
- family history of desmoid disease.
Extraabdominal desmoids are best treated with
- Surgical extirpation with a 1-cm margin
> recurrence is high with documented rates of 20% to 50%.
> Early excision is recommended to decrease the size of the resultant abdominal wall defect.
Intraabdominal/ retroperitoneal desmoids Tx
- The primary treatment is medical and includes
> nonsteroidal antiinflammatory agents (sulindac, celecoxib)
estrogen antagonists (tamoxifen, toremifene, raloxifene)
chemotherapy (vinblastine, methotrexate, doxorubicin, Adriamycin, dacarbazine)
Radiotherapy can be used for palliative measures
Resection with completely uninvolved margins (R0) will result in recurrence, what percentage
50%
Attenuated FAP (aFAP) Difference from FAP
- presents at a later age (30s– 40s)
- fewer than 100 polyps
- predominantly found in the right colon
- If untreated, the risk of colorectal malignancy is nearly 100% by 59 years of age.
- gastric adenomas, desmoids, and CHRPE are typically not seen in aFAP.
For aFAP, Screening Colonoscopy and EGD, WHEN ?
- Colonoscopy between 18 to 20 years of age and repeated every 1 to 2 years.
- EGD between the ages of 20 to 25, or before colectomy, with repeat interval based on Spigelman
Mutation Y-homolog (MYH)-associated polyposis (MAP)
- Autosomal recessive
- Biallelic mutation in the MYH gene located on chromosome 1p34.
- tens to hundreds Polyps with a median around 50.
- most commonly found in the left colon
- present at a median age of 48.
When to Perform Genetic Testing
- When no APC mutation is detected
- there are fewer than 100 adenomatous polyps
- and the family history is irrelevant or does not reveal a dominant mode of inheritance.
When to perform Screening
- Colonoscopy > 18 to 20 and repeated every 1 to 2 years.
- Screening EGD > 30 to 35,
or before colectomy, with repeat interval based on Spigelman stage.
Situations where chemoprevention can be entertained include
- treating ileal pouch anal anastomosis (IPAA) polyps
- a high family risk of desmoid tumors
- delayed surgery
- unwillingness or inability to tolerate polypectomy or completion proctectomy.
When surgery should be offered as early as possible.
- Severe polyposis (> 1000 colonic or 20 rectal polyps)
AND - APC mutations between codons 1250– 1464
carry a higher risk of cancer
Symptomatic Patient
When should surgery be delayed as long as possible
- For those with a high risk of desmoid disease to decrease the chance of desmoid tumors developing
For patients with classic FAP, Surgery should occur at what age
16 to 20 years of age
Indications for Proctocolectomy with End Ileostomy
- patient preference
- low rectal cancer requiring an abdominoperineal resection
- rectal cancer requiring postoperative pelvic radiation
- inability to create an IPAA (inadequate mesenteric length)
- Poor Sphincter function
Proctocolectomy with Continent Ileostomy
For Patient Not Candidate for IPAA
Contraindications to construction of a continent ileostomy include
Crohn’s disease
obesity
marginal small bowel length
and anyone with a psychological or physical disability
When to perform Total Abdominal Colectomy with Ileorectal Anastomosis
- cases of attenuated or mild polyposis
(< 20 rectal, < 1000 colonic adenomas) - rectal polyps less than 3 cm in size
- no colorectal dysplasia or cancer
- a distensible and compliant rectum
- and in patients with an intact sphincter mechanism who are willing to adhere to strict follow-up
Patient with Total Abdominal Colectomy with Ileorectal Anastomosis should follow Strict rectal surveillance
every 6– 12 months
Indications for Restorative Proctocolectomy/ Ileal Pouch Anal Anastomosis
- severe polyposis (> 20 rectal, > 1000 colonic adenomas),
- rectal polyps larger than 3 cm in size
- colonic dysplasia or cancer
- dysplastic rectal polyps
- patients with an intact sphincter mechanism willing to adhere to strict follow-up.
To Creat IPAA , Resection Sites
ileum is transected flush with the cecum
transection of the rectum with a 30- to 40-mm transverse stapler should occur 2 to 3 cm above the dentate line in the anal transition zone (ATZ)
Strategies to decrease tension at the anastomosis include
- complete mobilization of the small bowel mesentery to the root of the superior mesenteric artery cephalad to the head of the pancreas
- proximal division of the ileocolic artery
- and relaxing incisions of the mesentery over tension points along the superior mesenteric artery
Lifelong interval lower endoscopic surveillance is required for adenomas, dysplasia, and carcinomas
- at 1- to 2-year > Adenomas
- or 6-month to 1-year intervals > Cancer/Dysplasia
> random biopsies and polyps should be performed
> Severe dysplasia and villous adenomas > 1 cm in size > completion proctectomy in those with an IRA.
- Following TPC with end ileostomy, yearly stoma site surveillance > rare development of ileal adenocarcinoma, most commonly near the mucocutaneous junction in the setting of long-standing ileostomies
Peutz-Jeghers Syndrome
- autosomal dominant
- mutation in the LKB1 (STK11) tumor suppressor gene located on chromosome 19p13.
Hamartomatous polyps, Most commonly where ?
are found throughout the GI tract
though most commonly in the small intestine.
hallmark phenotypic feature in adolescence being
- Mucocutaneous hyperpigmentation
perioral and buccal region, eyes, nostrils, perianal region, fingers and toes, and hands and feet.
How to confirm the Diagnosis
Hamartomatous polyps and mucocutaneous pigmentation confirms a diagnosis of PJS.
What increases the Risk for Malignancy, and what are the MC cancers
The risk of malignancy increases with age (13-fold higher than the general population)
the most common cancers being colorectal, breast, pancreatic, and genitourinary.
Screening ?
Colonoscopy and EGD should be initiated at 8 years of age.
- If polyps are detected, endoscopic evaluation should continue every 2 to 3 years.
- If no polyps are found, repeat endoscopy and small bowel follow-through or capsule enteroscopy should be initiated by 20 years of age and repeated every 2 to 3 years.
Other surveillance recommendations with low levels of evidence include
annual clinical exam
annual testicular ultrasound starting at age 10
monthly breast exam
annual breast MRI starting at 18 years of age
cervical smear starting at age 25
MRCP of the pancreas starting at 25 years of age.
when to Do Surgery ?
- GI surgery is reserved for symptomatic disease or cancer.
- Any polyp larger than 1.5 cm should be removed, if possible, at the time of surgery.
Juvenile Polyposis Syndrome
- Autosomal dominant inherited disease resulting most commonly from mutations in the SMAD4 and BMPR1A genes
- Respectively located on chromosomes 18q21 and 10q22.
- Polyps can be found throughout the GI system with the colon being affected 100% of the time.
Extraintestinal manifestations
- Occur around 15% of the time
Include cleft lip and palate
polydactyly
genitourinary anomalies
intestinal malrotation
hydrocephalus
congenital heart disease.
What else associated with some SMAD4 mutations
Hereditary hemorrhagic telangiectasia
and bleeding arteriovenous malformations (AVMs)
are found in the GI tract, lungs, brain, and mediastinum.
Diagnosis of JPS
- Five or more juvenile polyps are found in the colon or rectum
- Multiple polyps are appreciated in other regions of the GI tract
- or after identification of polyps with a positive family history.
They can present with
passage of autoamputated or prolapsed polyps.
MC Associated Malignany
- CRC
Other Malignancies :
Gastric
Duodenal
Pancreas
Asymptomatic Patient Screening
12 to 15 Years
And Earlier for Symptomatic
If no Polyps detected > Repeat Every 2-3 Years
Otherwise Annually
EGD at Age 15
SMAD4 Mutation Periodic Screening For AVM
When To Do Colorectal Surgery ?
Cancer
Dysplasia
Symptomatic
> 100 Polyps
What surgery to Do ?
If Rectum Spared > TAC and IRA
If not Spared > TPC and IPAA
Cowden’s Syndrome
- Autosomal Dominant
- Mutation in PTEN Tumor Suppressor Gene
- Chromosome 10 q 23
- Typically on Colon and Stomach
- Polyps Include Hamartomas, Adenomas, Lipomas, Neurofibromas and Fibromas
Extra intestinal Manifestations
- Pathognomonic Trichilemmomas
- Macrocephaly
- and Variaty of Hamartomas and Tumors
in Breast, Thyroid and Uterus
Screening
Colonoscopy > 35
thyroid US > 15
Annual Mammo and MRI > 30
Bannayan-Riley-Ruvalcaba Syndrome
autosomal dominant disorder
mutation in the PTEN tumor suppressor gene
located on chromosome 10q23.
Findings with BRSS
pigmented penile macules, macrocephaly, hamartomas, hemangiomas, and mental retardation in upward of 50%.
The risk of developing colon and rectal cancer is thought to be no greater than the general population.
Cronkhite-Canada Syndrome
noninherited disorder resulting from a mutation in the PTEN tumor suppressor gene located on chromosome 10q23.
Common Findings
Hamartomatous GI polyps in addition to alopecia, macrocephaly, onycholysis, and cutaneous pigmentation are common findings.
Diffuse GI inflammation resulting in malabsorption, diarrhea, and protein-losing enteropathy can occur.
Hereditary Mixed Polyposis Syndrome
autosomal dominant inherited syndrome, though a specific mutation has yet to be identified.
multiple different colon and rectal polyps
Screening colonoscopy should begin between the ages of 25 to 30.
Serrated polyposis syndrome (SPS)
multiple polyps (hyperplastic or serrated) throughout the colon. A heritable pattern and genetic cause has not been identified.
two criteria for diagnosing SPS, of which diagnosis is made upon fulfillment of either of the criteria. The criteria include (1) at least five serrated polyps, all greater than 5 mm in size and proximal to the rectum, two of which are greater than 10 mm in diameter, or (2) more than 20 serrated polyps of any size distributed throughout the large intestine with five being proximal to the rectum.
Strict surveillance with colonoscopy every 1 to 2 years is advisable. First-degree relatives are at an increased risk of SPS and developing colon and rectal cancer (5-fold), and should be offered the same surveillance starting at 40 years of age or 10 years younger than the index case
