What is a real-life case study for a patient presenting with Lynch syndrome (Hereditary Nonpolyposis Colorectal Cancer)?

From the Guidelines

A real-life case study of Lynch syndrome involves a patient presenting with a strong family history of colorectal and endometrial cancer, necessitating comprehensive genetic testing and surveillance protocols to reduce morbidity and mortality. According to the ESMO clinical practice guidelines for diagnosis, treatment, and follow-up of hereditary gastrointestinal cancers 1, tumour testing with IHC for MMR proteins and/or MSI is recommended in individuals with CRC.

Key Points in Diagnosis

• Clinical risk can be assessed using Amsterdam criteria II or the revised Bethesda guidelines
• MMR IHC and/or MSI screening, with MLH1 promotor hypermethylation analysis in cases of MLH1 expression loss, is recommended for women with endometrial cancer 1
• Full germline genetic testing should include DNA sequencing and large rearrangement analysis 1

Management and Surveillance

• Follow-up recommendations in mutation carriers include colonoscopy every 1–2 years 1, and gynaecological examination (with TV US, CA 125 and endometrial biopsy) on a yearly basis from age 30 to 35 years
• High-quality colonoscopy carried out in dedicated centres is advised 1
• UGI endoscopy surveillance (every 1–3 years, from age 30–35 years) may be considered in patients at high risk
• Prophylactic gynaecological surgery might be an option for female carriers who have completed childbearing or are postmenopausal 1 For instance, a 42-year-old woman with a family history of colon and endometrial cancer, diagnosed with right-sided colon cancer, would undergo genetic testing to confirm a pathogenic mutation in the MLH1 gene, establishing a diagnosis of Lynch syndrome. Her management plan would include a total colectomy with ileorectal anastomosis, prophylactic hysterectomy and bilateral salpingo-oophorectomy, and annual surveillance with upper endoscopy and urinalysis, as well as recommendations for first-degree relatives to undergo genetic testing, as suggested by the guidelines 1.

From the Research

Case Study for Lynch Syndrome

A real-life case study for a patient presenting with Lynch syndrome can be constructed based on the provided evidence.

• A 35-year-old woman with a family history of colorectal and endometrial cancer is referred for genetic counseling and testing for Lynch syndrome 2.
• The patient's mother and grandmother had colorectal cancer, and her sister had endometrial cancer, suggesting a possible inherited cancer syndrome 3.
• The patient undergoes genetic testing, which reveals a mutation in one of the mismatch repair (MMR) genes, confirming the diagnosis of Lynch syndrome 4.
• The patient is informed of her increased risk for colorectal and endometrial cancer, as well as other extracolonic tumors, and is advised to undergo regular screening and surveillance 5.
• The patient's family members are also offered genetic testing and counseling to identify other individuals who may be at risk for Lynch syndrome 2, 6.

Management and Screening

The patient's management plan includes:

• Regular colonoscopy and endometrial cancer screening 5
• Consideration of risk-reducing surgery options, such as hysterectomy and salpingo-oophorectomy 2
• Chemoprevention and intensive cancer surveillance 2
• Genetic counseling and testing for at-risk family members 6

Importance of Genetic Counseling

Genetic counseling plays a critical role in the evaluation and management of Lynch syndrome, as it allows for:

• Identification of at-risk individuals and families 3
• Provision of accurate risk assessment and screening recommendations 6
• Discussion of risk-reducing options and management plans 2
• Coordination of care among healthcare providers 6