In the US there are an estimated 140,250 colon cancers per year with about 3% associated with Lynch syndrome.1 There is a total of 7100 UTUC cases per year with 5% of them being associated with Lynch syndrome.2 In this syndrome, the cancers usually occur at an earlier age, and their diagnosis requires changing of screening practices. It is important to find a family member and assess for carriers, as for every index patients, 3 additional family members are carriers.3 These tumors have a different unique biological behavior, which must be recognized.
Colon cancer is the most common cancer among patients with Lynch syndrome. It usually occurs at a younger age, and predominantly affects the right side. It is more likely to have multifocal lesions at presentation, and the appearing colon polyps have villous components with more contiguous cancer, responding better to chemotherapy.
UTUC associated with Lynch syndrome is more common in women and at a younger age, with more ureteral involvement, when compared to sporadic UTUC patients. The tumor grading and staging are the same and there probably isn’t any increased rate of bilateral tumors.
There are distinct clinical criteria to identify Lynch syndrome patients. The Amsterdam 2 criteria are the most commonly used, although they are cumbersome to remember (Table 1). They include a personal family history of extra-colonic malignancies, which is a limitation, as not all patients know their family history, and therefore it is possible to miss approximately 12-28% of cases.
Table 1 – Amsterdam 2 criteria for Lynch syndrome diagnosis:
One of the distinct features of Lynch syndrome is the Muir-Torre syndrome, which is a variant of Lynch syndrome and is manifested by sebaceous adenomas, with benign yellow papules found on the face (Figure 1). Once these are diagnosed, an immediate referral to a genetics clinic is required.
Figure 1 - Muir-Torre syndrome, a variant of Lynch syndrome, manifested by sebaceous adenomas, with benign yellow papules found on the face:
One of the possible ways of identifying Lynch syndrome patients is through immunohistochemistry (IHC). The tumor is examined for deficiency of MMR proteins. Nuclear expression is lost in tumor tissue and there is normal nuclear staining in adjacent tissue. IHC is classically done on surgical specimens, including ureteroscopic and colonoscopy biopsies.
In conclusion, urologists need to identify UTUC patients with Lynch syndrome. Ureteroscopic biopsies provide a substrate for tissue testing with IHC. It is critical that these patients are referred for genetic testing, as this will enable the patients to know their personal cancer risk, their response to therapy, and the implications for their family members.
References:
1. Hampel et al. 2005 NEJM (352) 1851
2. Metcalfe et al. 2018 J Urol (199) 60-65
3. Le et al. 2015 NEJM (372) 2509-20
Presented by: Scott Hubosky, MD, Thomas Jefferson University Hospital, Philadelphia, PA, USA
Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre @GoldbergHanan at the 2018 FOIU 4th Friends of Israel Urological Symposium, July 3-5. 2018, Tel-Aviv, Israel