Epidemiological and Clinical Characteristics of Five Rare Pathological Subtypes of Hepatocellular Carcinoma

Abstract

BackgroundHepatocellular carcinoma (HCC) is a highly heterogeneous tumor with several rare pathological subtypes and which is still poorly understood. This study aimed to describe the epidemiological and clinical spectrum of five rare HCC subtypes and develop a competing risk nomogram for cancer-specific survival prediction.MethodsThe study cohort was recruited from the Surveillance, Epidemiology, and End Results database. The clinicopathological data of 50,218 patients histologically diagnosed with classic HCC and five rare subtypes (ICD-O-3 Histology Code = 8170/3-8175/3) between 2004 and 2018 were reviewed. The annual percent change (APC) was calculated utilizing Joinpoint regression. The nomogram was developed based on multivariable competing risk survival analyses. Akaike information criterion, Bayesian information criterion, C-index, calibration curve, and area under the receiver operating characteristic curve were obtained to evaluate the prognostic performance. A decision curve analysis was introduced to examine the clinical value of the models.ResultsDespite scirrhous carcinoma, which showed a decreasing trend (APC = -6.8%, P = 0.025), the morbidity of other rare subtypes remained stable from 2004 to 2018. The incidence-based mortality was plateau in all subtypes during the period. Clear cell carcinoma is the most common subtype (n = 551, 1.1%), followed by subtypes of fibrolamellar (n = 241, 0.5%), scirrhous (n = 82, 0.2%), spindle cell (n = 61, 0.1%), and pleomorphic (n = 17, ~0%). The patients with fibrolamellar carcinoma were younger and more likely to have a non-cirrhotic liver and better prognoses. Scirrhous carcinoma shared almost the same macro-clinical characteristics and outcomes as the classic HCC. Clear cell carcinoma tended to occur in the Asia-Pacific elderly male population, and more than half of them were large HCC (Size>5cm). Sarcomatoid (including spindle cell and pleomorphic) carcinoma was associated with a larger tumor size, poorer differentiation, and more dismal prognoses. The pathological subtype, T stage, M stage, surgery, alpha-fetoprotein, and cancer history were confirmed as the independent predictors in patients with rare subtypes. The nomogram showed good calibration, discrimination, and net benefits in clinical practice.ConclusionThe rare subtypes had unique clinicopathological features and biological behaviors compared with the classic HCC. Our findings could provide a valuable reference for clinicians. The constructed nomogram could predict the prognoses with good performance, which is meaningful to individualized management.

Favorable outcome of immunotherapy in a rare subtype of hepatocellular carcinoma: a case report and literature review

“…Chen XY et al. reported that the median cancer-specific survival times of the classic HCC and rare S-HCC were comparable at 15 and 13 months, respectively ( 11 ).…”

Construction and validation of a survival prognostic model for stage III hepatocellular carcinoma: a real-world, multicenter clinical study

“…This model was highly reliable, with a consistency index of 0.781 in the training cohort and 0.793 in the verification cohort. The model is a new approach that can be extended to clinical practice and guide individualized therapy [ 7 ].…”

“…According to the global cancer statistics report, there will be about 840,000 new cases of hepatocellular carcinoma worldwide in 2020, and about 780,000 new deaths worldwide [ 1 ]. Data from a national survey in the United States showed that in 2022, liver cancer related deaths in males and females ranked the 7th and 5th among all malignant tumors, while studies in China showed that liver cancer ranked the first among all malignant tumors in disability-adjusted years [ 2 – 7 ]. In 2014, a survey data released by the World Health Organization showed that the prevalence rate of hepatitis B surface antigen in the general population in China was about 5.49%, and there were about 74 million cases of hepatitis B carriers in China.…”

Rare histotypes of epithelial biliary tract tumors: A literature review

“…Sarcomatous variants of carcinomas have been described in many cancer types, including the liver, even more frequently in hepatocellular carcinoma than in biliary tract carcinoma (Chen et al, 2022). Sarcomatous cholangiocarcinoma (SICC) represents about 4.5 % of intrahepatic cholangiocarcinomas (Zhang et al, 2018b) and is more common in Asian Countries (Boonsinsukh et al, 2018).…”