When to Consider Lynch Syndrome in Non-Colon and Non-Endometrial Malignancies.

Lynch syndrome (LS) is a common genetic syndrome characterized by pathogenic mutations of DNA mismatch repair genes resulting in a hereditary predisposition to cancer. While typically associated with colonic and endometrial cancer, LS additionally influences the development of many other malignancies. The Amsterdam II and Revised Bethesda Guidelines are the established clinical criteria for diagnosing LS. These guidelines are based on the most general characteristics of LS and do not address specific characteristics of the less commonly LS-associated malignancies. For individuals that present initially with a non-colon and non-endometrial malignancy, recommendations and guidelines on when to consider screening for LS are limited. Therefore, it is essential that clinicians are familiar with distinct LS-associated patient- and tumor-specific characteristics, especially of the less common LS-associated cancers, so that LS's diagnosis is not missed. In this review article, we focus on extra-colonic and extra-endometrial LS-associated cancers, paying particular attention to any established or currently investigated cancer features that help raise suspicion for LS and potentially lead to its earlier diagnosis. This review will also discuss current guidelines specific to each LS-associated malignancy.

Forty-eight-year-old female MUTYH carrier presenting with five concurrent primary cancers.

BACKGROUND: MUTYH-associated polyposis is a rare disorder resulting from mutations involved in DNA mismatch repair. This results in an increased susceptibility to colonic adenomatosis and other cancers. Studies have examined the resulting frequency of extracolonic manifestations; however, these typically occur alone, concurrently, or temporally separate from an already diagnosed colorectal cancer in individuals with a biallelic mutation. CASE: Reported here is a case of five distinct primary neoplasms presenting simultaneously in a patient monoallelic for an MYH mutation. These neoplasms included squamous cell carcinoma of the vulva, rectal adenocarcinoma, synchronous anal adenocarcinoma, papillary thyroid carcinoma, and ovarian serous psammocarcinoma. Throughout her course, she underwent multiple surgical procedures, neoadjuvant chemoradiation, with further adjuvant therapy, and treatment ongoing. Due to her unique presentation, she underwent genetic testing that demonstrated she was monoallelic for an MYH mutation. CONCLUSION: The patient had a positive response to her treatment and surgical procedures with ongoing adjuvant therapy. She will continue to undergo further genetic testing, and testing for her children is being considered. This case demonstrates a unique presentation associated with a monoallelic MYH mutation that is not described in the current literature and warrants further investigation.

Merkel Cell Polyomavirus Antibody Titer Predicts Recurrence-Free Survival.

BACKGROUND: Merkel cell polyomavirus (MCPyV) is associated with the development of Merkel cell carcinoma (MCC). Antibody (MCPyV-Ab) titers may have prognostic implications. This study evaluated the impact of the presence or absence of MCPyV-Ab on the 2-year overall survival (OS) and disease-free survival (DFS) of MCC patients. METHODS: This single-center, IRB-approved, retrospective cohort study evaluated 51 adult patients with MCC from 2014 to 2021 using a prospectively maintained database. Patients were compared by MCPyV-Ab status, and Kaplan-Meier analysis was used to evaluate 2-year OS and DFS. RESULTS: Of the 51 patients, 13 (25.4%) were seropositive, 41 (80.4%) underwent wide excision, 40 (80.0%) received radiotherapy, and 43 (84.3%) received multimodal therapy. The median follow-up period was 15.5 months (range 1-69.5 months). The median 2-year OS of the entire cohort was not reached. The median 2-year OS was not reached for either the seronegative or the seropositive patients. The difference in 2-year OS between the groups was not statistically significant (p = 0.37). Eight patients, all seronegative, were never rendered disease-free and were removed from recurrence analysis. The seropositive patients experienced no recurrences. Of the 30 seronegative patients, 9 (30.0%) experienced recurrence. The median 2-year DFS of the entire cohort was not reached. The median 2-year DFS of the seronegative group was 22.2 months. The 2-year DFS was not reached for the seropositive cohort. Seropositivity conferred a significantly better 2-year DFS than seronegativity (p = 0.04). CONCLUSION: The MCPyV-Ab seropositive patients demonstrated improved 2-year DFS. The seropositive patients showed a strong trend toward improved 2-year OS, although the difference not statistically significant. This study substantiated the value of MCPyV-Ab assessment for MCC.

Autogenous Bone Cranioplasty: Review of a 42-Year Experience by a Single Surgeon.

BACKGROUND: Autogenous bone is frequently espoused as the gold standard material for cranioplasty procedures, yet alloplastic cranioplasty continues to persist in the search, presumably, for a simpler technique. Although short-term outcomes can be successful using foreign materials, long-term follow-up in these patients often demonstrates increased rates of failure because of exposure or late infection. Autogenous bone grafts, however, integrate and revascularize, and are thus more resistant to infection than alloplastic materials. METHODS: This is a retrospective review of all patients that underwent reconstructive cranioplasty for full-thickness defects, as performed by the senior author (S.A.W.) between 1975 and 2018. All procedures were performed with autogenous bone. RESULTS: One hundred fifty-four patients met criteria for inclusion in the report. Cranioplasties were performed for both congenital and secondary indications. Split calvaria was used in 115 patients (74.7 percent), rib graft was used in 12 patients (7.8 percent), iliac crest graft was used in 10 patients (6.5 percent), and combinations of donor-site grafts were used in 17 patients (11.0 percent). In the entire series, none of the patients suffered from complications related to infection of either the donor site or transferred bone graft. None of the patients required secondary operations to fill in defects created by the postoperative resorption. CONCLUSIONS: Although autologous bone is widely considered the gold standard material for cranioplasty procedures, some argue against its use, mainly citing unpredictable resorption as the purported disadvantage. However, it is less susceptible to infection, and results in fewer long-term complications than alloplastic materials. There is no alloplastic material that has matched these outcomes, and thus autogenous bone should be considered as the primary option for cranioplasty procedures. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.