Misdiagnosis of hepatocellular carcinoma in patients receiving no local‐regional therapy prior to liver transplant: An analysis of the Organ Procurement and Transplantation Network explant pathology form

Abstract

Patients with T1 hepatocellular carcinoma (HCC) are not eligible for Model for End Stage Liver Disease (MELD) exception for liver transplant (LT) in part due to a high rate of misdiagnosis (no HCC on explant). The likelihood of misdiagnosis for T2 HCC and factors associated with misdiagnosis are unknown. We analyzed the Organ Procurement and Transplantation Network database including 5664 adults who underwent LT from 2012 to 2015 with MELD exception for T2 HCC, and searched for no evidence of HCC in the explant pathology file. We focused on those (n = 324) receiving no local-regional therapy (LRT) to evaluate the probability of no HCC found in explant. Median waiting time was short at 1.7 months, and 35 (11%) had no HCC on explant. On multivariable logistic regression, factors associated with no HCC on explant were age <50 (OR: 17.3, P < .001), non-HCV (OR: 5.4, P = .001), and alpha-fetoprotein <10 (OR: 2.9, P = .04). Tumor size and number were not different between groups. The proportion of misdiagnosis did not change significantly after implementation of Liver Imaging Reporting and Data System (LI-RADS) for HCC diagnosis. Conclusion: The rate of misdiagnosis was 11% among T2 HCC patients who underwent LT without receiving LRT prior to LT and did not change significantly after implementation of LI-RADS. More efforts are needed to eliminate unnecessary LT for patients without HCC.

Adult African Americans undergoing cadaveric liver transplantation for hepatocellular carcinoma within the Milan criteria have the lowest 5-year survival among all the ethnic groups in the United States: analysis of USA national data between January 2002

“…First of all, we included only patients who had documented HCC in their explanted livers. Confirmation that all recipients in this study had HCC is important because up to 11% of patients who are diagnosed with HCC by imaging tests without biopsy prior to LT end up having no pathological evidence of neoplastic lesions in their explanted livers [52] . Second, before we analyzed the longterm outcomes, we confirmed that there were no significant differences in perioperative mortality between African Americans and other ethnic groups.…”

Survival and prognostic factors after transplantation, resection and ablation in a national cohort of early hepatocellular carcinoma

“…15 The lack of histopathology in many ablation patients is important to keep in mind, as benign lesions might be misdiagnosed as HCC. 17 The interaction pattern regarding liver function parameters in the cohorts with Child A only (Table 1, Suppl. 3 and 4) remained after adjustment with available tumour factors.…”

“…15,16 However, the lack of tumour confirmation by histopathology when ablation is used, might influence results and affect the prerequisites for prognostication and preventive treatment strategies. 17,18 Since it is difficult to anticipate all influencing factors on short and long term, patients with limited HCC and well-preserved liver function, eligible for more than one treatment alternative are hard to advice. Results might differ between cohorts and countries, related to varying donor pools and waiting times for transplantation, as well as tumour factors and patient characteristics.…”

Overdiagnosis of hepatocellular carcinoma: Prevented by guidelines?

“…[54,55] Although biopsy can be used in some cases with atypical imaging features, histologic confirmation is not required in most cases-which some argue increases the likelihood of misdiagnoses. [56,57] The Liver Imaging Reporting and Data (LI-RADS) system, proposed by the American College of Radiology to standardize classification of liver nodules on diagnostic CT or MRI in at-risk patients, [58] categorizes liver nodules on an ordinal scale from LR-1 (definitely benign) to LR-5 (definitely HCC) based on imaging features including size, arterial phase hyperenhancement, delayed phase washout, and capsule appearance. The presence of arterial phase hyperenhancement and delayed washout in lesions ≥1 cm is reported to have a ~95% positive predictive value for the presence of HCC, whereas subcentimeter lesions with these features have a substantially lower risk of HCC.…”