1-Peutz-Jaghers Syndrome PJS
Autosomal dominant with high penetrence
Mucocutaneous pigmentation in 95% of patients
Hamartomaous intestinal polyposis
Mutation of the STK11/LKB1, a serine threonine kinase gene on chromosome 19p, also known as B1(LKB1).
80% of PJS have no detectable mutation
Average age at diagnosis: 23-26
Average age at diagnosis: 23-26
Main symptoms: abdominal pain, GI bleeding or anaemia
Associated with high risk of cancers (colon, stomach, pancreas, breast,..)
Diagnosis:
clinical
-two PJ polyps are detected
-single PJ polyp + perioral pigmentation
-single PJ polyp + family history of PJS
Genetic testing
Feautures of PJS should leed to genetic testing
All first degree relatives should be tested
All first degree relatives should be tested
Management:
-colonoscopy from the age of 25 yrs, every 2 years
-OGD from the age of 25 yrs, every 2 years
-small bowel: MRI, VCE, every 2-4 years
-surveillance for extraintestinal cancer
treatment depends on polyp burden and location
- few adenomas-----> polypectomy and medical treatment
- multiple polups or clusters---->surgical resection and life long surveillance
- laprotomy for small bowel obstruction
 |
| mucocutaneous pigmentation around mouth, nostrils,perianal, genital area, hands and feet. |
2-Juvenile polyposis syndrome JPS
Distinctive hamartomas that usually are solitary and located
principally in the rectums of children
JPS
can be defined by any one of the following criteria:
-More
than five juvenile polyps of the colon and rectum
-Juvenile
polyps throughout the GI tract
-Any
number of juvenile polyps in the GI tract with a family history of juvenile
polyps
Typically causes GI bleeding and obstruction
Age of a patient with JPS is 4.5-9.5 yrs
Risk of colon and upper GI ca is increased
JPS manifests autosomal dominant inheritance
Caused by mutations in two genes:
–Approximately 18% of cases will have a germline mutation of MADH4 (SMAD4)
–Another 21% of JPS cases are caused by germline mutations of bone morphogenetic protein receptor 1A (BMPR1A) obstruction.
Caused by mutations in two genes:
–Approximately 18% of cases will have a germline mutation of MADH4 (SMAD4)
–Another 21% of JPS cases are caused by germline mutations of bone morphogenetic protein receptor 1A (BMPR1A) obstruction.
Age of a patient with JPS is 4.5-9.5 yrs
Management:
Screening
colonoscopy usually begins after 15 yrs of age. Every 2 yrs
OGD
from age 25
Polypectomy
performed yearly until the patient is polyp free and then every 3 year
Asymptomatic
relatives also should be screened by the age of 15yrs
Identification
of MADH4/BMPR1A
Colectomy
considered if numerous polpys
Question:
This 23-year-old man presented via the rapid access rectal bleeding service. At flexible sigmoidoscopy,this polyp was detected in the sigmoid colon, as shown above. At subsequent colonoscopy, he was found to have five other similar lesions. All of these statements below are accurate, except
1- this polyp required a biopsy at the time of flexible sigmoidoscopy
2- nearly all cases where these polyps are found have a mutation found on molecular genetic testing
3- this polyp does not require endoscopic removal
4- a family history should be taken
5- predictive gene testing of his 4-year-old son is appropriate if a mutation is found on molecular genetic testing.
3-Cowden Disease
an autosomal dominant condition.
germline mutation of the PTEN gene on chromosome 10q23.
Oral and cutaneous hamartomas, thyroid, breast and endometrial tumours, autoimmune
thyroiditis, macrocephaly and mental retardation are documented manifestations.
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ReplyDeleteA patient who is new to the area attends your clinic for the first time. You read his medical notes. He has had gastric hamartomas which is the reason he is attending a gastroenterology clinic. He has a history of basal cell carcinomas, mandibular bone cysts and intracranial calcification as well as pits on the palms of his hands.
ReplyDeleteWhich one of the following is the most likely diagnosis?
(Please select 1 option)
1- Cowden syndrome
2- Familial adenomatous polyposis
3-Gorlin syndrome
4-Juvenile polyposis
5-Peutz-Jeghers syndrome Incorrect answer selected
correct answer 3
Gorlin syndrome causes gastric hamartomas, basal cell carcinomas, mandibular bone cysts and intracranial calcification as well as pits on the palms and soles.
Gorlin syndrome, also known as nevoid basal cell carcinoma syndrome, is a condition that affects many areas of the body and increases the risk of developing various cancerous and noncancerous tumors.
DeletePeutz-Jeghers Syndrome (PJS), which is an inherited polyposis syndrome that is autosomal dominant. It is characterized by multiple hamartomatous polyps involving the small bowel in 60-90% and the colon in 50-65%. It is common for patients to have mucocutaneous pigmentation around the lips and mouth which usually disappears with age. There is equal frequency in men and women. The germline mutation is STK11 gene on chromosome 19p. The diagnosis is made by having at least one of the following:
ReplyDelete1. ≥ 2 histologically confirmed PJ polyps;
2. ≥ 1 PJ polyp and a family history of PJS;
3. mucocutaneous pigmentation and a family history of PJS;
4. ≥ 1 PJ polyp and mucocutaneous pigmentation.
In patients with bleeding or obstructive symptoms, endoscopic polypectomy reduces polyp-related complications. In some cases, intraoperative enteroscopy with a "clean sweep" polypectomy may be of benefit. No standard chemoprophylaxis exists for this condition.
Patients with PJS have a 15-fold increased risk of developing intestinal cancer compared with that of the general population. The gastrointestinal polyps found in PJS are typical hamartomas. Their histology is characterized by extensive smooth muscle arborization throughout the polyp. During the first 3 decades of life anemia, rectal bleeding, abdominal pain, obstruction, and/or intussusception are common complications in patients with PJS. Nearly 50% of the patients experience an intussusception during their lifetime, most commonly in the small intestine. The cause of Peutz-Jeghers syndrome (PJS) in most cases (66-94%) appears to be a germline mutation of the STK11/LKB1 (serine/threonine kinase 11) tumor suppressor gene.
ReplyDeleteJuvenile Polyposis Syndrome (JPS) is inherited in an autosomal dominant fashion and has been associated with mutations in either the SMAD4 or BMPR1A gene. The absence of family history could well be attributable to a new mutation, but manifestations and age of onset are variable within families, so the parents need careful evaluation. The lifetime risk of colorectal cancer is about 40-70%, and there is also a risk of upper GI malignancies.
ReplyDeleteWhich of the following statements about the clinical presentations of FAP/Attenuated FAP is true?
ReplyDeleteA. Approximately 50% of patients with classic FAP will develop colorectal cancer, if the disease is left untreated.
B. Patients with FAP have a family history of colon cancer or polyposis in approximately 95% of cases.
C. Patients from families with Attenuated FAP often have a right-sided predominance of polyps.
D. Women with FAP should be screened annually for endometrial cancer.
answer c
Explanation
Due to the large number of colon adenomas, almost all (~100%) patients with FAP will eventually develop colon cancer, in the absence of treatment. Up to 30% of FAP cases represent new mutations. Patients with Attenuated FAP usually have only 10-100 colon adenomas and often they can be scattered in the proximal colon. Hence, full colonoscopy is essential to evaluate the colon. Patients with Lynch Syndrome are at an increased risk for developing endometrial cancer, but not patients with FAP.
A patient who is new to the area attends your clinic for the first time.
ReplyDeleteYou read his medical notes. He has had gastric hamartomas which is the reason he is attending a gastroenterology clinic. He has a history of basal cell carcinomas, mandibular bone cysts and intracranial calcification as well as pits on the palms of his hands.
Which one of the following is the most likely diagnosis?
1-Cowden syndrome
2-Familial adenomatous polyposis
3-Gorlin syndrome
4-Juvenile polyposis
5-Peutz-Jeghers syndrome
Gorlin syndrome causes gastric hamartomas, basal cell carcinomas, mandibular bone cysts and intracranial calcification as well as pits on the palms and soles.
Familial adenomatous polyposis (FAP) is caused by a mutation in the APC gene and is associated with the formation of multiple adenomatous polyps in the colon. By the age of 35 around 95% of patients with FAP have polyps and, without colectomy, colon cancer is effectively inevitable. Extra-colonic manifestations are variable and include polyps of the gastric fundus and duodenum, osteomas, dental anomalies and congenital hypertrophy of the retinal pigment epithelium (CHRPE).
Juvenile polyposis syndrome is characterised by a tendency to form hamartomatous polyps throughout the GI tract. Juvenile refers to a particular type of polyp rather than the age of the patients at the onset of polyp formation (though most have polyps by the age of 20). Inheritance is autosomal dominant. There is an increased risk of GI cancer mostly attributable to an excess of colon cancer. Estimates of lifetime risk of GI cancer are variable and range from 9-50%.
Peutz-Jehgers syndrome is characterised by the association of hamartomatous GI polyps and mucocutaneous hyperpigmentation. PJS-type hamartomas are most frequently found in the small bowel but also occur in the stomach. colon and nasal passages. Patients with PJS are increased risk of both stomach and colon cancers arising from adenomas in addition to other cancers such as pancreatic, breast and ovarian malignancy.
Cowden's syndrome is one of the PTEN hamartoma tumour syndromes. There is widespread development of hamartomas with mucocutaneous lesions being pathognomic. Criteria for making the diagnosis are complex. Breast and thyroid carcinomas are frequent (and major criteria for making the diagnosis) and formation of GI hamartomas is one of the minor diagnostic criteria.
Answer to the polyp question: 2
ReplyDeleteThis is a hamatomatous juvenile-type polyp, which has
presented in a young adult with rectal bleeding. Biopsy
may help distinguish it from a sporadic polyp, as syndromic
polyps may differ morphologically. In this case, a
colonoscopy was helpful in order to ascertain if any
other polyps were present. Family history is essential as
one of the diagnostic criteria of JPS is any number of JP
and a positive family history. In 40% of patients with
JPS, there is no known pathological genetic mutation
found. St Marks Hospital Polyposis Registry recommends
that predictive genetic testing should be considered in
at-risk children from the age of 4 years. Although the
true cancer risk is not well defined, it has been shown
that these polyps become dysplastic and undergo adenomatous change over time, and it seems reasonable that
polypectomy should be undertaken to prevent cancer
development. Solitary JP can be left alone.
Peutz-Jeghers Syndrome (PJS), is an inherited polyposis syndrome that is autosomal dominant. It is characterized by multiple hamartomatous polyps involving the small bowel in 60-90% and the colon in 50-65%. It is common for patients to have mucocutaneous pigmentation around the lips and mouth which usually disappears with age. There is equal frequency in men and women. The germline mutation is STK11 gene on chromosome 19p. The diagnosis is made by having at least one of the following:
ReplyDelete1. ≥ 2 histologically confirmed PJ polyps;
2. ≥ 1 PJ polyp and a family history of PJS;
3. mucocutaneous pigmentation and a family history of PJS; 4. ≥ 1 PJ polyp and mucocutaneous pigmentation.
In patients with bleeding or obstructive symptoms, endoscopic polypectomy reduces polyp-related complications. In some cases, intraoperative enteroscopy with a "clean sweep" polypectomy may be of benefit. No standard chemoprophylaxis exists for this condition.