Lynch Syndrome

How to Cite This Chapter: McKechnie T, Talwar G, Eskicioglu C, Reguła J, Bugajski M, Szczepanek M, Bartnik W. Lynch Syndrome. McMaster Textbook of Internal Medicine. Kraków: Medycyna Praktyczna. https://empendium.com/mcmtextbook/chapter/B31.II.4.72.6.5.1. Accessed November 02, 2024.
Last Updated: July 12, 2023
Last Reviewed: July 12, 2023
Chapter Information

DefinitionTop

Lynch syndrome (hereditary nonpolyposis colorectal cancer [HNPCC]) is the most common hereditary colon cancer syndrome. It is inherited in an autosomal dominant pattern and caused by a mutation of one of the mismatch repair (MMR) genes (MLH1, MSH2, MSH6, PMS1, PMS2) or the EPCAM gene.

Colorectal cancer in Lynch syndrome usually develops in the right part of the colon (the risk of occurrence is 70%-80% throughout a patient’s lifetime). Moreover, it is also associated with the risk of developing cancers of the endometrium (30%-60%), ovary, stomach, small intestine (3%-5%), and pancreas, as well as transitional cell carcinoma of the ureters and renal pelvis.

DiagnosisTop

The diagnosis of Lynch syndrome requires confirmation of the MMR gene mutation. Genetic tests should be performed in adult relatives of patients with diagnosed Lynch syndrome and in people who meet the clinical criteria for suspecting this syndrome (ie, Amsterdam II criteria: ≥3 relatives with histologically confirmed colorectal cancer or other neoplasm falling within the scope of Lynch syndrome [including ≥1 first-degree relative]; cancer occurring in ≥2 generations of the same family; ≥1 occurrence at an age <50 years; exclusion of familial adenomatous polyposis. If a patient has an MLH1 mutation, they must subsequently undergo BRAF testing, as BRAF mutations can drive MLH1 mutations, in which case colon cancer is not associated with Lynch syndrome but is rather sporadic (this has important implications for treatment).

TreatmentTop

The occurrence of colorectal cancer associated with Lynch syndrome is an indication for total abdominal colectomy (due to an increased risk of metachronous [independent] colon cancer) with ileorectal anastomosis and annual endoscopic evaluation of the rectum. In the case of microsatellite instability, which is a characteristic genetic feature of Lynch syndrome, immunotherapy (nivolumab, pembrolizumab) can be used either in the neoadjuvant setting (for locally advanced disease [ie, T4 stage]) or, more commonly, in the adjuvant setting.

SurveillanceTop

Colonoscopy should be performed every 2 years (or immediately if symptoms are present), starting from the age of 20 to 25 years (depending on the mutation found); in women aged 20 to 25 years, the annual evaluation of serum cancer antigen (CA)-125 concentration and gynecologic examination with transvaginal ultrasonography of the reproductive organ and biopsy of the uterine mucosa are recommended. As part of cancer prevention, consideration should be given to hysterectomy with oophorectomy in women aged >40 years with a confirmed mutation who are not planning pregnancy.

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