★ Click on the top right "..." Listen to the full article
1
Primary liver cancer is currently the fourth most common malignant tumor and the second leading cause of cancer mortality in mainland China [1], which seriously threatens the lives and health of mainland people. Early diagnosis can significantly improve patient outcomes. Recently, Professor Zhao Weifeng from the First Affiliated Hospital of Soochow University shared "Diagnosis and Differential Diagnosis of Sub-centimeter Liver Cancer".
The disease burden of liver cancer in mainland China is very severe, and screening high-risk groups for liver cancer is conducive to early detection, early diagnosis and early treatment of liver cancer, which is the key to improving the efficacy of liver cancer.
In the study published in the LANCET sub-journal [2], the optimal thresholds of 0.21 and 0.65 were determined in the newly generated discovery cohort using x-tile software after SMOTE oversampling, and the patients were divided into three groups: high-risk, intermediate-risk, and low-risk. The results showed that the high-risk group (n=221, 11.9%) and the intermediate-risk group (n=433, 23.3%) accounted for 94.4% (84/89) of HCC patients, and the incidence of HCC was significantly higher than that in the low-risk group (n = 1204, 64.8%) (24.3% vs 6.4% vs 0.42%, P<0.001). The findings confirm that the novel ALARM model, based on deep learning radiomics and clinical variables, provides a reliable estimate of the development of HCC in patients with cirrhosis in the short term, and may have the potential to identify early changes from cirrhosis to HCC.
Professor Zhao Weifeng pointed out that the evolution process from liver nodules to liver cancer is a process of dynamic changes in blood supply and cells. In the context of cirrhosis, the liver undergoes regenerative nodules, low-grade dysplastic nodules, high-grade dysplastic nodules, early hepatocellular carcinoma (eHCC), small advanced HCC, and large advanced HCC.
According to the 2024 guidelines for the diagnosis and treatment of primary liver cancer, subcentimeter HCC (scHCC) (liver cancer with a diameter of ≤1 cm) has a better prognosis after radical hepatectomy compared with 1-2 cm HCC [1,3], i.e., 5-year OS is 98.5% and 89.5%, respectively, and 5-year RFS (Recurrence free survival (RFS) is 83.3% and 67.3%, respectively. Early diagnosis and treatment of HCC, especially at the scHCC stage, are particularly important.
The diagnostic value of imaging EOB-MRI in sub-centimeter liver cancer
In the Guidelines for the Diagnosis and Treatment of Primary Liver Cancer (2024 Edition) [1], the value of imaging is emphasized for the diagnosis of scHCC: that is, at least one of the enhanced MRI/enhanced CT/enhanced ultrasound + EOB-MRI with typical manifestations of liver cancer. Clinically, gadoxetate disodium (Gd-EOB-DTPA) enhanced MRI (EOB-MRI) can detect HCC with a detection rate of 98% and a sensitivity of 71%-77%. EOB-MRI can significantly <improve the diagnostic sensitivity of hepatobiliary-specific hepatobiliary phase hypointensity, arterial phase hyperenhancement, and diffusion restriction [4].
Guidelines for the diagnosis and treatment of primary liver cancer (2024 edition) Liver cancer diagnosis roadmap
Diagnostic performance of different imaging methods in the diagnosis of scHCC
Gadoxetate disodium (Gd-EOB-DTPA) is a hepatocyte-specific contrast agent, which enters hepatocytes through organic anion transporting polypeptides (OATP) on the surface of normal hepatocytes, forming a unique hepatobiliary-specific phase image. OATP expression decreases progressively from cirrhosis nodules to DN to eHCC and advanced HCC during carcinogenesis, usually during the HGDN and partial LGDN phases, and the decrease in OATP expression precedes tumor neovascular formation [6]. Therefore, the unique hepatobiliary phase is conducive to the early detection and diagnosis of scHCC.
Clinical value of the LI-RADS category
2024NCCN、ASSLD、EASL、OPTN的HCC指南推荐以LI-RADS（Liver Imaging Reporting And Data System，肝脏影像报告和数据系统）类别对HCC进行评估[8]。 LI-RADS将HCC高危人群中发现的每一个肝脏结节根据提示良恶性可能性的大小分为LR-1到LR-5、LR-M（可能或肯定为恶性，但非特指HCC）和LR-TIV（肿瘤血管浸润），用于指导更细微和个性化的临床决策。
CT/MRI LI-RASD诊断法则
CT/MRI Diagnostic Form
As shown in the table above, in the LI-RADS classification, the imaging features for scHCC include: non-annular hyperenhancement in the arterial phase, non-marginal clearance (washout), enhanced pseudocapsule, diameter < 10 mm, and threshold growth. In patients with LR-4, the probability of HCC is 74%; In patients with LR-5, HCC is as likely as high as 95%. For HCCs < 1 cm in diameter, attention should be paid to the condition of enhanced "envelope", non-marginal clearance, and threshold growth. In addition, hepatobiliary-specific hypointensity and transitional hypointensity can be used as auxiliary diagnostic signs for HCC when examined by EOB-MRI.
Clinically, the LI-RADS classification is applicable to patients with liver cirrhosis, patients with chronic hepatitis B virus, patients with current or previous diagnosis of HCC, adults who are suitable for liver transplantation, and patients after liver transplantation. It is not suitable for those without HCC risk factors, age < 18 years, cirrhosis caused by congenital liver fibrosis, cirrhosis caused by vascular diseases, such as hereditary hemorrhagic telangiectasia, Budd-Chiari syndrome, chronic portal vein occlusion, cardiac congestion or diffuse nodular hyperplasia.
Sub-centimeter liver cancer: lack of typical "fast-in, fast-out" imaging features
The typical manifestations of HCC are obvious enhancement of lesions in the arterial phase (late stage of the main artery), clearance in the portal vein phase and delayed phase, and a "fast in and fast out" enhancement mode [1], compared with 1 to 2 cm HCC, the spread of scHCC is limited, and the typical "fast in and fast out" pattern is relatively less [3], suggesting the specificity of scHCC. The 2024 edition of the guidelines for the diagnosis and treatment of primary liver cancer points out that in high-risk populations, Gd-EOB-DTPA-enhanced MRI is recommended for the diagnosis of scHCC after excluding identified benign lesions (level of evidence 2, recommendation B), especially for patients with cirrhosis, and is helpful to distinguish from precancerous lesions such as high-grade dysplastic nodules.
<1cm的scHCC与1-2cmHCC的影像学区别
Clinical practice
The patient is a 59-year-old female with HBV-associated cirrhosis. According to the 2024 guidelines for primary liver cancer, "fast out" in the transition phase or hepatobiliary phase of EOB-MRI can also be considered and pathologically confirmed Edmondson-Steiner grade II HCC [5].
a: T2WI hyperintensity, b: limited diffusion of DWI, c: non-annular enhancement in the arterial phase, d: no obvious clearance in the portal phase, e: hypointensity in the transitional phase, f: hypointensity in the hepatobiliary phase, 7.6 mm in diameter.
If alpha-fetoprotein is elevated alone, is there liver cancer?
Clinical practice
The patient is a 63-year-old female with elevated alpha-fetoprotein. In this case, HCC would not be diagnosed with non-marginal APHE+ portal phase clearance, but scHCC could be diagnosed with transitional phase clearance when transitional phase clearance was included in the diagnostic criteria, and Edmondson-Steiner grade II HCC was pathologically confirmed.
a: T2WI hyperintensity, b: limited diffusion of DWI, c: non-annular enhancement in the arterial phase, d: no significant clearance in the portal phase, e: transitional hypointensity, f: transitional hypointensity, 7.3 mm in diameter [5].
DSA联合锥形线束CT（CBCT）诊断scHCC
DSA联合CBCT（Cone beam Computer Tomography，CBCT）可更清楚地显示肿瘤病灶、提高scHCC的检出率，并明确肿瘤供血动脉分支的三维关系、指导肿瘤供血动脉分支的超选择性插管。
DSA联合CBCT诊断scHCC
Sharing of HCC cases that are prone to misdiagnosis
Case 1
The patient was a 36-year-old male with HBV-associated liver cirrhosis, and MR showed abnormal liver segment VI signals; Splenomegaly.
Characteristics: In this case, the arterial phase was strengthened, and the portal and equilibrium phases were slightly hyperintense, but there was no clearance in the portal phase.
How to distinguish sub-centimeter high-flow hemangiomas (cavernous hemangiomas) from scHCC
MRI of nodules: slightly hyperintense on T2WI, hyperintense on diffusion-weighted imaging, arterial phase enhancement, transition phase and other signals or slightly lower intensity, hepatobiliary-specific phase hypointensity.
It is important to rule out benign lesions, such as high-flow hemangiomas, when diagnosing liver cancer
HCC：表观扩散系数图（Apparent Diffusion Coefficient，ADC）呈低信号，动脉期强化+门脉期或移行期非边缘廓清（等信号或稍低信号）。
HCC
Cavernous hemangioma: ADC hyperintensity, arterial phase enhancement + portal or transitional phase further enhancement (slightly hyperintense or isosignal).
Cavernous hemangioma
ADC is hyperintense, hemangioma
Case 2
患者男，55岁，肝功能异常，AFP 6.71ug/ml（0-8.78），异常凝血酶原10.95mAU/ml（13.62-40.38）。
Implication: For example, MRI alone can easily be misdiagnosed as HCC. For the clinical diagnosis of HCC, it is necessary to diagnose two imaging methods simultaneously, such as combining ultrasound and MRI.
Case 3
The patient, a 36-year-old male, was found to have a liver mass on physical examination, and there was no difference in clinical and laboratory tests.
Summary: T1 hypointensity, T2 hyperintensity, DWI diffusion signal, arterial phase enhancement, but portal phase hyperintensity, hepatobiliary-specific scarring hypointensity, did not meet the performance of fast in and fast out, and the final pathological diagnosis was FNH.
Case 4
Imaging and pathology of sub-centimeter hepatic nodules PEComa
brief summary
The imaging diagnosis of scHCC requires enhanced MRI/enhanced CT/enhanced ultrasound/+EOB-MRI to present the typical manifestations of liver cancer at the same time: the lesions in the enhanced arterial phase (advanced stage of the main artery) are significantly enhanced, and the portal vein or transitional phase is cleared, showing a "fast in and out" enhancement mode. Combining the imaging features of scHCC (primary diagnostic indicators and auxiliary indicators) with serum markers of liver cancer (AFP, DCP liquid biopsy) can improve accuracy.
References Swipe up to read
[1] People's Republic of China Department of Medical Administration, National Health Commission. Guidelines for the diagnosis and treatment of primary liver cancer (2024 edition)[J]. Medical Journal of Peking Union Medical College Hospital,2024,15(3):532-558. DOI:10.12290/xhyxzz.2024-0304.
[2] Guo L, Hao X, Chen L, et al. Early warning of hepatocellular carcinoma in cirrhotic patients by three-phase CT-based deep learning radiomics model: a retrospective, multicentre, cohort study[J]. Eclinicalmedicine, 2024, 74.
[3] Huang P, Shi Q, Ni X, et al. Subcentimeter hepatocellular carcinoma （HCC） on gadoxetic-acid-enhanced MRI: less frequent typical imaging features compared to 1–2 cm HCC but better prognosis after surgical resection[J]. Abdominal Radiology, 2023, 48（11）: 3391-3400.
[4] Adeniji N, Dhanasekaran R. Current and emerging tools for hepatocellular carcinoma surveillance[J]. Hepatology communications, 2021, 5（12）: 1972-1986.
[5] Huang P, Zhou C, Wu F, et al. An improved diagnostic algorithm for subcentimeter hepatocellular carcinoma on gadoxetic acid–enhanced MRI[J]. European Radiology, 2023, 33（4）: 2735-2745.
[6] Joo I, Kim S Y, Kang T W, et al. Radiologic-pathologic correlation of hepatobiliary phase hypointense nodules without arterial phase hyperenhancement at gadoxetic acid–enhanced MRI: a multicenter study[J]. Radiology, 2020, 296（2）: 335-345.
[7] Jin-Young Choi,et al. CT and MR imaging diagnosis and staging of hepatocellular carcinoma: part I. Development, growth, and spread: key pathologic and imaging aspects. Radiology. 2014 Sep; 272（3）:635-54.
[8] LI-RADS2018, https://www.acr.org/.
Professor Zhao Weifeng
The First Affiliated Hospital of Soochow University
• Director of the Department of Infectious Diseases, The First Affiliated Hospital of Soochow University
• Chief Physician and Doctoral Supervisor
• Member of the Infectious Diseases Branch of the Chinese Medical Doctor Association
• Chairman of the Hepatology Branch of Jiangsu Medical Association
• Vice Chairman of the Infectious Diseases Branch of Jiangsu Medical Association
• President-elect of the Infectious Diseases Branch of Jiangsu Medical Doctor Association
• Chairman of the Infectious Diseases Branch of Suzhou Medical Association
• Member of the Liver Cancer Medical Medicine Committee of the Chinese Medical Doctor Association
• Member of the Infectious Disease Committee of the Chinese Association of Integrative Medicine
• Member of the China-Japan-Korea Infectious Disease Professional Committee
• Visiting Scholar at the University of Montpellier, France
• 《Lancet Oncology》等SCI杂志发表论文二十余篇
Source: Liver Cancer Online