Pathophysiology of Lynch Syndrome
1) carcinoma usually arising in proximal (right) colon 2) one of the following criteria must be met for diagnosis – colorectal cancer occurring in at least two generations, patient less than 50 years old, three or greater relatives with colon cancer (at least 2 of which are first-degree relatives)
Histology/Gross Pathology
usually a poorly differentiated colon carcinoma
Associated Conditions
increased incidence of ovarian cancer and endometrial cancer
Biochemistry
tumors have a high level of genomic instability (microsatellites)
Inheritance/Epidemiology
1) autosomal dominant 2) despite poorly differentiated histology and early age of onset, the prognosis is better than with sporadically occurring colon cancer 3) onset is 15 years earlier than sporadically occurring colon cancers 4) associated with “mismatch” mutations in hMSH2 on chromosome 2 and hMLH1 on chromosome 3, causing errors in DNA replication
Treatment
1) colonoscopy every 6 months starting at age 25 yers 2) regular screening pelvic ultrasound and endometrial biopsy in women 3) colectomy if tumor is found 4) genetic screening tests are available 5) aspirin prophylaxis may decrease incidence by up to 50%
Tips for USMLE
even though the tumors are poorly differentiated, they have a better prognosis than sporadicallly occurring tumors
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