Microsatellite instability testing in colorectal patients with Lynch syndrome: lessons learned from a case report and how to avoid such pitfalls.

We present the case of a patient with Lynch syndrome and metastatic colorectal carcinoma (mCRC). The initial immunohistochemistry (IHC) test for deficient mismatch repair gave a false negative result. However, the same mutation has accurately been detected with IHC in other cancers with microsatellite instability (MSI). This supports the determining role of somatic missense mutations in MMR IHC. MSI-PCR testing confirmed MSI and the patient benefited from nivolumab with a complete metabolic response. We explain the rationale for immunotherapy in mCRC, current testing strategies and discuss future developments in MSI testing. We advocate for upfront testing using both IHC and MSI-PCR to direct therapy in mCRC, and a greater understanding of IHC and MSI-PCR testing pitfalls.

Bowel cancer that has spread is a serious condition that will often lead to loss of life. There is a new treatment called immunotherapy which helps extend the life of people with cancer that has spread beyond the bowel, but it does not work for everyone. Immunotherapy works best for people whose tumors have lost the ability to repair DNA. People with Lynch syndrome often have these types of tumors because they are born with an inherited predisposition for faulty DNA repair. We treated a patient with Lynch syndrome and bowel cancer, and wanted to use immunotherapy, but the test we used failed to give the right result. We think this is because the test is not very good at picking up unusual types of mutations that can occur and that using another test as well will prevent this mistake from happening to others.

Early and late-onset veno-occlusive disease/sinusoidal syndrome post allogeneic stem cell transplantation - a real-world UK experience.

Classical veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a serious complication post allogeneic hematopoietic stem cell transplantation (HSCT). Before the recently revised EBMT criteria, the Baltimore and modified Seattle criteria failed to recognize the syndrome of late-onset VOD. We present real-world experience from a large UK transplant center reporting on VOD/SOS in consecutive HSCT adult patients (n = 530), transplanted for hematological cancers. We identified 27 patients treated with Defibrotide for VOD/SOS diagnosis, where detailed data were available for final analysis. Using standard definitions including EBMT criteria, around 30% (n = 8/27) of cases classified as late-onset VOD presenting at median of 46 (22-93) days but with D100 survival (63% vs 58%, Log-rank; P = 0.81) comparable to classical VOD. Hazard ratio for D100 mortality was 2.82 (95% CI: 1.74-4.56, P < .001, Gray test) with all VOD/SOS events. Twenty percent (n = 2/8) of late-onset VOD patients were anicteric and 42% (n = 8) classical VOD patients presented with refractory thrombocytopenia, while less than half met EBMT criteria for classical VOD in adults, highlighting gaps in real-world diagnostic limitations using EBMT criteria. However, challenges remain about underrecognition and difficulties related to early defibrotide access for treatment of late-onset VOD in current treatment guidelines. Our report strongly supports early Defibrotide for the treatment of severe VOD/SOS in adults regardless of time of onset.