Interpreting IHC mismatch repair proteins in GI cancers

 

• Concurrent loss of MLH1 and PMS2 suggests MLH1 inactivation, which may be due to either germline mutation (Lynch syndrome) or somatic MLH1 promoter hypermethylation (sporadic cases). BRAF V600E mutation or MLH1 methylation testing can help distinguish sporadic from hereditary cases.

• Loss of MSH2 and MSH6 indicates MSH2 gene inactivation, which is highly specific for Lynch syndrome, but can also result from EPCAM deletions.

• Isolated loss of MSH6 or PMS2 typically reflects a germline mutation in the respective gene.

• Partial or clonal loss may also be significant and warrants further genetic evaluation.

Reference: https://www.nejm.org/doi/full/10.1056/NEJMcp1714533

https://pmc.ncbi.nlm.nih.gov/articles/PMC9300166/

Hepatic, pancreatic, gastric toxicity of immunotherapy

Incidence: Hepatotoxicity can be severe in less than 1% ( single agent) or 10% ( combination). All grades less than 5% ( single) or upto 20% ( combination).

Presentation: Mostly presents as AST/ALT elevation ( hepatocellular injury pattern). Less likely to see ALKP and bili elevation( cholestatic) 

When to expect: 2-3 months after starting rx.

Differential: rule out viral infections( hepatitis, EBV, CMV), drug toxicity ( chemo drug,  ETOH), liver mets and obstruction, review all meds including pain meds and tylenol, oTC meds, alternative medicine ( ask about ivermectin which can cause hepatotoxicity)

Early rectal cancer

 

Reference: https://www.mdpi.com/2072-6694/16/11/2093

https://www.sciencedirect.com/science/article/abs/pii/S0002961024006974