The patient underwent a partial hepatectomy of the segment 2 lesion with pathology showing a moderately differentiated HCC…A missense mutation was reported in POLE (4102G>A) resulting in a V1368M mutant with a variant allele frequency of 44%....Additional missense mutations were identified in ERBB3, TNFAIP3, PRKN, and TSC2 (Fig. 1). The cancer was also microsatellite stable and had a TMB of 1 mut/Mb....Although the patient had Child-Pugh A liver disease, monotherapy with pembrolizumab...Radiographic evaluation after 4 months of treatment demonstrated a complete response, which was consistent with further declines in AFP levels...The patient experienced no adverse events attributed to immune-related toxicities and remains on therapy 8 months after starting pembrolizumab.