Defining the adenoma burden in lynch syndrome.

BACKGROUND: Patients with 10 or more lifetime adenomas are candidates for genetic counseling and testing for polyposis syndromes. Lynch syndrome falls under the umbrella of hereditary nonpolyposis colorectal cancer, and it is assumed that patients with Lynch syndrome do not develop multiple adenomas. OBJECTIVE: The objective of this study was to document the number of adenomas in patients with Lynch syndrome. DESIGN: This was a retrospective review of clinical, colonoscopy, and pathology records of patients with Lynch syndrome in a prospectively maintained hereditary colorectal cancer database. SETTINGS: The study was conducted at a single-institution tertiary care center with specialized practice in hereditary colorectal cancer syndromes. PATIENTS: We included 263 patients with a germline mutation in 1 of the 4 DNA mismatch repair genes. INTERVENTIONS: Colonoscopy and polypectomy were the study interventions. MAIN OUTCOME MEASURES: The lifetime cumulative number of colorectal adenomas and their characteristics were measured. RESULTS: A total of 107 of the 263 patients had 1 or more adenomas. Sixty-one patients had 1 adenoma, 29 (11%) had 2 to 5 adenomas, 6 (2%) had 6 to 9 adenomas, and 11 patients (4%) had 10 or more cumulative adenomas. The maximum number of synchronous adenomas in any individual was 22, and the maximum number of cumulative adenomas in any individual was 24. Twenty-four of the 107 patients with adenomas underwent a total colectomy or proctocolectomy and were excluded from long-term follow-up. In the remaining 83 patients with adenomas, 426 colonoscopies were performed. A total of 220 (54%) were normal or had hyperplastic polyps; 313 adenomas were found in 206 examinations (46%), and 123 (39%) of the adenomas were advanced. LIMITATIONS: There was variability in the interval of colonoscopy surveillance. Some patients had a variant of unknown significance and were separated from those with a deleterious mutation. CONCLUSIONS: Although 10 or more adenomas prompt testing for polyposis syndromes, Lynch syndrome should also be considered in the differential diagnosis.

Prevalence of occult gynecologic malignancy at the time of risk reducing and nonprophylactic surgery in patients with Lynch syndrome.

OBJECTIVE: The primary aim of this study was to determine the prevalence of occult gynecologic malignancy at the time of risk reducing surgery in patients with Lynch Syndrome. A secondary aim was to determine the prevalence of occult gynecologic malignancy at the time of surgery for non-prophylactic indications in patients with Lynch Syndrome. METHODS: A retrospective review of an Inherited Colorectal Cancer Registry found 76 patients with Lynch syndrome (defined by a germline mutation in a DNA mismatch repair gene) or hereditary nonpolyposis colorectal cancer (HNPCC) (defined by Amsterdam criteria) who had undergone hysterectomy and/or salpingo-oophorectomy for a prophylactic or non-prophylactic indication. Indications for surgery and the prevalence of cancer at the time of each operation were reviewed. RESULTS: 24 of 76 patients underwent prophylactic hysterectomy and/or bilateral salpingo-oophorectomy for Lynch syndrome or HNPCC. In 9 of these patients, a benign indication for surgery was also noted. 4 of 24 patients (17%, 95% CI = 5-38%) were noted to have cancer on final pathology. 20 of 76 patients (26%) undergoing operative management for any indication were noted to have occult malignancy on final pathology. CONCLUSIONS: Patients should be counseled about the risks of finding gynecologic cancer at the time of prophylactic or non-prophylactic surgery for Lynch syndrome and HNPCC, and the potential need for additional surgery.

Hereditary non-polyposis colorectal cancer/Lynch syndrome in three dimensions.

BACKGROUND: Hereditary non-polyposis colorectal cancer (HNPCC) is defined by family history, and Lynch syndrome (LS) is defined genetically. However, universal tumour testing is now increasingly used to screen for patients with defective mismatch repair. This mixing of the results of family history, tumour testing and germline testing produces multiple permutations and combinations that can foster confusion. We wanted to clarify hereditary colorectal cancer using the three dimensions of classification: family history, tumour testing and germline testing. METHODS: Family history (Amsterdam I or II criteria versus not Amsterdam criteria) was used to define patients and families with HNPCC. Tumour testing and germline testing were then performed to sub-classify patients and families. The permutations of these classifications are applied to our registry. RESULTS: There were 234 HNPCC families: 129 had LS of which 55 were three-dimensional Lynch (family history, tumour testing and germline testing), 66 were two-dimensional Lynch and eight were one-dimensional Lynch. A total of 10 families had tumour Lynch (tumours with microsatellite instability or loss of expression of a mismatch repair protein but an Amsterdam-negative family and negative germline testing), five were Lynch like (Amsterdam-positive family, tumours with microsatellite instability or loss of expression of a mismatch repair protein on immunohistochemistry but negative germline testing), 26 were familial colorectal cancer type X and 95 were HNPCC. CONCLUSION: Hereditary colorectal cancer can be confusing. Sorting families in three dimensions can clarify the confusion and may direct further testing and, ultimately, surveillance.