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Case History

image A 30-year-old woman presented to her GP with a four month history of lethargy and worsening abdominal pain. A full blood count revealed a haemoglobin level of 66 g/l with no obvious signs of bleeding. She was referred to her local surgical assessment unit where a CT of the abdomen and pelvis revealed an annular lesion at the splenic flexure concerning for a locally advanced primary colonic tumour. This was confirmed on colonoscopy and biopsy. She underwent a left hemicolectomy and end-to-end anastomosis with the final histopathology report describing a pT3 N1a (1 of 37 lymph nodes involved) R0 moderately differentiated adenocarcinoma. Immunohistochemical analysis of the tumour specimen for the mismatch repair proteins MLH1, MSH2, MSH6 and PMS2 revealed a loss of expression of MSH2 and a significant reduction in staining for MSH6 in comparison with background stromal cells. She was reviewed in the oncology clinic where 3 months of adjuvant chemotherapy with capecitabine, and oxaliplatin was recommended. Her oncologist explored her and her husband’s priorities regarding fertility. They had not yet started a family but had been intending to in the near future. They viewed any potential reduction in fertility as a significant concern. Prior to commencing chemotherapy, the couple attended the fertility clinic for egg harvesting, in vitro fertilization (IVF) and embryo cryopreservation. They secured 12 embryos at two-pronuclear (2PN) stage. Chemotherapy was completed without incident. In view of the deficiency in the mismatch repair proteins within the tumour specimen, the patient was referred to the genetics service for counselling and germline testing to investigate the possibility of Lynch syndrome. She agreed to testing, which confirmed a diagnosis of Lynch syndrome. Following this, the patient was seen again in the oncology clinic where she asked her doctor about the risks, benefits and optimal timing of risk reducing surgery.

What is Lynch syndrome and what risks does it pose?

Who should be tested for Lynch syndrome and how is it diagnosed?

What are the special considerations regarding female fertility prior to and immediately after adjuvant chemotherapy for colorectal cancer?

Can any interventions be offered to patients with Lynch syndrome to prevent transmission to future children?

What steps can be taken to mitigate the cancer risks associated with Lynch syndrome? When should these be considered?

What is Lynch syndrome and what risks does it pose?

Lynch syndrome is an autosomal dominant condition with incomplete penetrance where cancer develops in the context of a germline loss of function mutation in any of the genes for the mismatch repair (MMR) proteins: MLH1, MSH2, MSH6 and/or PMS2.1 The related condition, hereditary non-polyposis colorectal cancer (HNPCC) is defined clinically and, while it includes many patients with Lynch syndrome, identifies a wider population with a personal and/or familial history of HNPCC-related malignancies.2

MMR proteins correct DNA mismatches that develop during DNA replication, preventing somatic mutations from persisting ...

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