December 21st - LBJ - Colorectal Carcinoma/Familial Cancer Syndromes

Today at LBJ morning report our first case was of a 37 year old African American Male with Rectal Carcinoma and multiple polyps on colonoscopy. Also, he had multiple hyperpigmented macules scattered throughout his body.  This brings up a good point to discuss the various inherited colorectal cancer syndromes that you'll need to know for boards. All together these inherited syndromes are responsible for approximately 10% of cases of Colorectal Cancer in the US (the other 90% are from sporadic polyp formation)

Familial Adenomatous Polyposis (FAP):

-Most cases are autosomal dominant, and result from a mutation in the APC gene on Chromosome 5

-By the age of 14-15 patients start developing polyps throughout the colon, and most patients get colorectal cancer from these polyps by the age of 35-40.  At this time, in most patients, thousands of polyps are present in the colon. There is a form of FAP that is inherited in an AR fashion, and they have less polyps by this age- only in the hundreds

- Patients also get desmoid tumors scattered thoughout their GI tract - leading to obstructive/compressive symptoms. 
- Cancer of the ampulla of Vater occurs in about 10% of patients. Other malignancies seen
   in patients with FAP include thyroid, pancreatic and gastric cancer.

 - Another finding is retinal epithelial hyperpigmentation. (This is a favorite one-liner for
    boards!)
- Patients need surveillance sigmoidoscopy/colonoscopy starting at age 10-12, and most
   patients undergo prophylactic colectomy by the age of 30.
- All Patients need Genetic Counseling and screening. Surveillance
   EGDs and thyroid U/S are recommended

Variants of FAP:

Gardner's Syndrome - Skull/Mandible Osteomas, Supernumary Teeth, Epidermoid Cysts and/or Lipomas along with polyps/colorectal cancer. + high incidence of retinal epithelial hyperpigmentation. (and a picture of what epidermoid cysts look like to the left)

Turcot's Syndrome - Polyps/Colorectal Cancer combined with CNS Dz (esp meduloblastoma/glioblastoma)

Lynch Syndrome/Hereditary Non-Polyposis Coli Syndrome

Autosomal Dominant Inheritance. Patients have about an 80% lifetime risk of developing colorectal cancer.  2/3rds of colorectal cancers occur in the region proximal to the splenic flexure (unlike most malignancies in the US - which are predominantly left-Sided) Patients develop colon cancer in their 40's. Other malignancies seen in patients with HNPCC include ovarian, endometrial, gastric and a slew of other rare cancers.

The most recent Amsterdam Criteria establishes the guidelines for suspicion/diagnosis of HNPCC:
One or more of the HNPCC-related cancers diagnosed younger than 50 years
Two successive affected generations
Three or more family members with HNPCC-related cancers
 
So if your patient fits this criteria, or has synchronous or metachronous colorectal cancer along with any other cancer that is seen in patients with HNPCC - be suspicious that this is occuring!!! 
 
Family members need to be screened, and they have to get colonoscopies starting at age 25. Females get aggressive screening for endometrial cancer, and some clinicians send CA-125 regularly. 

Peutz-Jehgers Syndrome

This is more of a disease of "adolescents", but just to know because it is fair game on the boards:

- Hyperpigmented macules on the lips/mucosa

- Multiple hamartomatous polyps in the small intestine, large
  intestine and stomach.  These have low malignancy
  potential, and usually causes symptoms such as
  hematochezia and even intussusception

- Patients still have an overall increased risk of colorectal
   adenocarcinoma, and other malignancies such as
   breast, gastric, pancreatic, lung, and many others.