The main findings of our study were: 1) neither MELD nor the etiology of cirrhosis were associated with extrahepatic incidentalomas, 2) only MELD and the discovery of an incidentaloma were predictors of liver transplantation after adjusting for potential confounders, 3) the discovery of an incidentaloma did not affect the median time to liver transplantation, and 4) the discovery of a malignant incidentaloma was rare but led to cures in all but one patient.
Few studies have studied the frequency and outcomes of incidentalomas discovered on screening MRI. Ibrahim et al., reported the frequency of incidentalomas on MRI was assessed in individuals at high risk (IARs) for PDAC (14). A total of 459 incidentalomas were discovered, eleven of which were cancerous (1.9%) and six metastatic at diagnosis. The early detection of cancer was beneficial in five of eleven IARs. In another study, whole-body MRI was performed to detect the frequency of incidentalomas in 118 healthy volunteers (mean age 47.4 years, range 20–81) (15). Seventy percent of volunteers had an incidental finding detected, and a total of 103 benign lesions were found. Only 2 malignant lesions (1.9%) were found. In contrast to others, our study is the first to determine the frequency, and clinical outcomes of extrahepatic incidentalomas in patients with cirrhosis undergoing MRI for the screening of HCC. Like prior studies, we found that incidental malignancies were rare, and that their detection led to cure in most patients.
To our knowledge, our study is the only one to have explored the association between extrahepatic incidentalomas and liver transplantation. It remains unclear why the discovery of an incidentaloma was found to be a significant predictor of liver transplantation. Incidental findings on imaging have been reported to lead to a “cascade effect”, whereby the incidentaloma leads to further testing by providers.(16, 17) In a national survey of U.S. physicians, 99.4% of respondents reported having experienced “cascades of care” whereby incidental findings led respondents to perform additional testing.(18) In a retrospective study of 592 patients with head and neck squamous cell cancer (HNSCC) who underwent staging with PET/CT, incidental findings occurred in 61.5% of patients. The discovery of an incidental finding was a significant predictor of treatment delay in this cohort.(19) Liver transplantation requires an extensive evaluation of the recipient’s comorbidities and contraindications to transplantation, which include extrahepatic malignancy.(20) Although non-significant, patients with incidentalomas appeared to have a longer time to liver transplantation than those without incidentalomas, indicating a possible treatment delay due to more extensive evaluation as seen in the study of patients with HNSCC.
Although current guidelines by the AASLD recommend TUS over MRI for HCC screening, the former has multiple limitations, that may lead to failure to detect early-stage cancer when it is the most curable (21). Studies suggest MRI has a higher sensitivity for detecting early-stage HCC and may be more cost-effective in certain populations (5, 8–11, 22). Curing HCC becomes increasingly difficult when the size of the HCC becomes greater than 2 to 2.5 cm (23–25). TUS has a sensitivity between 27.3–63% for detecting early-stage lesions that are less than 2 cm (7, 8). Additionally, abnormal liver parenchyma, obesity, ascites or hepatic steatosis may further decrease the sensitivity for the detection of HCC by attenuating ultrasound waves (21). By 2030, 51% of the United states population will be obese (26). With the increasing incidence of obesity, NASH and steatosis are likely to increase as well, further limiting the utility of TUS. Therefore, the use of MRI for screening of HCC will likely increase in the future, leading to a higher number of extrahepatic incidentalomas.
Our study has several limitations. First, the retrospective nature of the study limited our ability to determine the thought process behind the management of extrahepatic incidentalomas, which may have led to potential confounders. These potential confounders could have contributed to the “cascade effect” leading to higher rates of liver transplantation in those with incidentalomas. Second, most patients in our cohort were White, therefore, our findings on the benign nature of extrahepatic incidentalomas may not be generalizable to other racial backgrounds, who have a higher incidence of certain cancers, such as lung, prostate and colorectal malignancies in African Americans (27). Third, we were unable to measure, and adjust for the potential confounding of MRI sensitivity over time. Over the long course of this study, the MRI scanners in our institution have been upgraded and replaced several times, and it is likely that increases in magnet field strength and improved imaging software application that were used in our most recent scans allow for better detection of smaller extrahepatic incidentalomas. Fourth, the average MELD score of our patient population was relatively low and may not be generalizable to other liver transplant programs across the country. Fifth, the presence of incidentalomas was determined through retrospective review of the imaging report, and not by manual re-read of every scan. This approach was felt to be sufficient given imaging reports are the standard means by which imaging findings are communicated in clinical practice. Finally, although our study identified a large proportion of patients with cirrhosis who underwent MRI for HCC surveillance at our institution, it was not exhaustive of all patients.
We believe our study provides insight into the impact of extrahepatic incidentalomas on liver transplantation. Given the worsening obesity epidemic, the prevalence of liver disease and HCC is expected to increase (28). With higher failure rates for HCC detection in obese patients, TUS may not be the preferred screening modality for HCC in the coming years, leading to increased utilization of MRIs and a higher prevalence of extrahepatic incidentalomas. The increase in incidentalomas may have a “cascade effect” which could potentially lead to increases in the total number of liver transplantation, thereby, increasing the demand of a limited resource.