Lynch syndrome (LS) is defined by germline mutations in DNA mismatch repair (MMR) genes, and affected patients are at high risk for multiple cancers. Reflexive testing for MMR protein loss by immunohistochemistry (IHC) is currently only recommended for colorectal and endometrial cancers, although upper tract urothelial carcinoma (UTUC) is the third-most common malignancy in patients with LS. To study the suitability of universal MMR IHC screening for UTUC, we investigated MMR expression and microsatellite status in UTUC in comparison to bladder UC (BUC), and evaluated the clinicopathologic features of UTUC. We found that 9% of UTUC showed MMR IHC loss (8 MSH6 alone; 1 MSH2 and MSH6; 1 MLH1 and PMS2; n=117) compared with 1% of BUC (1 MSH6 alone; n=160) (P=0.001). Of these, 4/10 (40%) of UTUC (3% overall; 3 MSH6 alone; 1 MLH1 and PMS2) and none (0%) of BUC had high microsatellite instability on molecular testing (P=0.03). The only predictive clinicopathologic feature for MMR loss was a personal history of colorectal cancer (P=0.0003). However, UTUC presents at a similar age to colon carcinoma in LS and thus UTUC may be the sentinel event in some patients. Combining our results with those of other studies suggests that 1% to 3% of all UTUC cases may represent LS-associated carcinoma. LS accounts for 2% to 6% of both colorectal and endometrial cancers. As LS likely accounts for a similar percentage of UTUC, we suggest that reflexive MMR IHC screening followed by microsatellite instability testing be included in diagnostic guidelines for all UTUC.

An understanding of the role of inherited cancer predisposition syndromes in pediatric tumor diagnoses continues to develop as more information is learned through the application of genomic technology. Identifying patients and their relatives at an increased risk for developing cancer is an important step in the care of this patient population. The purpose of this review is to highlight various tumor types that arise in the pediatric population and the cancer predisposition syndromes associated with those tumors. The review serves as a guide for recognizing genes and conditions to consider when a pediatric cancer referral presents to the genetics clinic.

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Aim Precancer identification of women with hereditary breast and ovarian cancer (HBOC) could prevent 20% of these ovarian cancers. The objective was to determine whether standardized Facing Our Risk of Cancer Empowered (FORCE) materials are acceptable, improve knowledge of HBOC and increase disclosure to family members. Methods A prospective cohort of women with breast or ovarian cancer was identified prior to genetic testing. Subjects completed a baseline knowledge survey and were provided three communication aids. Knowledge, acceptability and communication to family members were reassessed at 6 months and compared to a retrospective cohort who had undergone genetic testing for breast or ovarian cancer prior to the intervention. The primary outcome was increase in HBOC knowledge, requiring 20 pre‐ and postknowledge scores to detect a 10% difference. Results Forty women were enrolled. The median age at cancer diagnosis was 50 years and 55% had a family history of breast or ovarian cancer. Though subjects found the resources acceptable, knowledge scores did not improve after their use. Disclosure rates were of no different between cohorts (83% preintervention vs 77% postintervention, P = 0.26) though there was an increase in deleterious mutation carriers, 0% (0/6) preintervention vs 100% (22/22) postintervention. Rates of subsequent testing in relatives were low in both preintervention and postintervention cohorts (0% vs 4.5%). Conclusion Inclusion of standardized communication tools is acceptable to patients. Knowledge did not improve after their use. In deleterious mutation carriers, disclosure rates increased postintervention.