High Tumor Mutational Burden in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and one of the leading causes of cancer-related deaths worldwide. Tumor mutational burden (TMB) in a cancer specimen represents the number of mutations within a pre-determined length of genetic material. This value is increasingly investigated as it may correlate with both prognosis and cancer response to developing immunotherapies. Its role in HCC, however, is still unclear as it tends to exist in a lower range. We present the case of a 72-year-old female diagnosed with HCC that was diffusely spread throughout the liver without evidence of metastatic disease. Genetic analysis of a liver biopsy revealed a TMB of 87 mutations per megabase which is extremely high for HCC. The patient was treated with tremelimumab and durvalumab but passed away shortly afterward due to decompensation from her disease. This case highlights the importance of continuing to research TMB and its correlation with this cancer. An HCC case with an exceptionally high TMB that progressed rapidly, like this one, indicates the continued need to study markers such as TMB, especially in outlier cases, for prognostication and appropriate stratification of immunotherapy response. This case shows an instance of a non-metastatic but still aggressive HCC that was diagnosed too late for assessing therapy response. In this instance, the high TMB would point toward a worse prognosis, but further study of high-TMB cases is necessary to support a correlation. Given the prevalence of HCC worldwide, any potential avenues that could help guide clinical decision-making should be explored.