Atypical Manifestation of Primary Hepatocellular Carcinoma and Hepatic Malignancy Mimicking Lesions

Intrahepatic mass-forming cholangiocarcinoma (IHCC) is the second most common primary liver malignancy. Typical imaging findings of IHCC are lobulated contoured masses with hypo-enhancement or peripheral rim enhancement ( 34 35 ). However, atypical IHCCs can show diffused arterial hyperenhancement mimicking HCC, especially when the mass is small (< 3 cm in diameter) and arises from the cirrhotic liver ( 34 ). Because hypervascular IHCC usually shows progressive or persistent enhancement in delayed phases, lack of washout is an important clue for distinguishing it from HCC ( Fig. 10 ) ( 35 ). Combined HCC-cholangiocarcinoma (cHCC-CC) is a rare and aggressive primary hepatic malignancy and one of the most false-positive imaging diagnoses for HCC ( 36 37 ). Because cHCC-CC contains histological components of both HCC and CC, it generally shows indeterminate imaging features and variable enhancement patterns reflecting the proportion and distribution of HCC and CC mixtures ( Fig. 11 ) ( 36 38 ). Therefore, differentiation of cHCC-CC from HCC is challenging based on imaging studies alone. Metastasis is the most common malignant liver lesion, and the liver is the most common organ involved in metastatic disease ( 39 40 ). Most liver metastases are typically hypoattenuating on unenhanced CT and poorly enhanced during the arterial phase ( 39 ). However, some primary malignancies, such as neuroendocrine tumor, renal cell carcinoma, and melanoma, tend to have hypervascular metastases ( 40 ). Hypervascular hepatic metastases show arterial hyperenhancement and a variable degree of washout on delayed images, mimicking HCC ( Fig. 12 ). Therefore, the radiologist should suspect hypervascular metastases for arterial-enhancing hepatic lesions, especially when the patient has a primary tumor origin.

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and the second leading cause of worldwide cancer-related deaths ( 1 ). The typical imaging features of HCC are arterial phase hyperenhancement (APHE) and portal/delayed washout on dynamic CT or MRI, and its unique features allow for a non-invasive diagnosis solely based on imaging studies in patients with chronic liver disease ( 2 3 ). However, some HCCs may present with atypical image features that mimic benign or other malignant masses. On the other hand, intrahepatic cholangiocarcinoma and sclerosing hemangioma are often confused with HCC by radiologists on CT and MRI ( 4 ). Awareness of these atypical hepatic malignant or benign nodule presentations on images is crucial for accurate differentiation from other focal liver lesions, which allows adequate treatment. Therefore, we reviewed various atypical manifestations of primary hepatic malignancy and benign lesions with radiologic findings.

Hepatocellular adenoma (HCA) is the third most common benign liver tumor, with female predominance associated to the use of oral contraceptives ( 41 ). Most HCAs demonstrate hypervascular features and hypointensity in the HBP, mimicking HCC. In particular, β-catenin–activated HCA, a subtype of HCA, typically presents arterial hyperenhancement with washout and iso- or high SI in the HBP owing to increased expression of nuclear β-catenin, glutamine synthetase, and OATP1B3 ( Fig. 13 ) ( 42 ). Although the majority of HCA typically occurs in noncirrhotic livers in female of child-bearing age, it remains difficult to distinguish early HCCs from HCAs. Focal nodular hyperplasia (FNH) is the second most common benign hepatic tumor and usually occurs in the non-cirrhotic liver of middle-aged female ( 42 43 ). FNH usually presents with arterial hyperenhancement and central scar enhancement in the delayed phase, and shows ring-like enhancement in the HBP owing to surrounding hyperplastic hepatocytes with decreased OATP expression ( Fig. 14 ) ( 43 ). Because atypical HCCs can also show hyperintensity on HBP, it may be necessary for differentiating FNHs from HCCs with hyperintensity on HBP images. Extrauterine adenomyomas are extremely rare and located outside the uterus, such as in the abdominal wall or liver ( 44 ). Hepatic extrauterine adenomyoma appears as a solid mass with small cystic lesions, hemorrhagic foci, and weak persistent enhancement ( Fig. 15 ) ( 45 ). Most patients with extrauterine adenomyoma have a prior history of pelvic endometriosis, and the lesions are typically in the subcapsular location of the right hemiliver in all previously reported cases ( 45 ). Nonetheless, HCC can also show a solid mass with cystic lesions and intratumoral hemorrhage, which needs to be evaluated carefully. Sclerosed hemangioma is a rare subtype of hepatic hemangioma characterized by degeneration and fibrous replacement ( 46 ). Given that the imaging findings of sclerosed hemangiomas are nonspecific, it is often challenging to differentiate them from other lesions, such as atypical HCC or IHCC, before pathologic confirmation ( 46 47 ). There are some helpful imaging findings suggestive of sclerosed hemangiomas, including capsular retraction, geographic pattern, decrease or unchanged in size over time, decrease in previously seen regions of enhancement ( Fig. 16 ) ( 47 ). Angiomyolipoma (AML) is a benign mesenchymal tumor comprising vessels, smooth muscle cells, and varying amounts of fat ( 48 ). AML often shows arterial enhancement and washout, mimicking HCC. The presence of fat is one of the key diagnostic features of AML; however other hepatic lesions, such as HCC, can also contain fat components ( 48 49 ). AML presents with marked low SI in the HBP on gadoxetic acid-enhanced MRI ( Fig. 17 ) in patients without risk factors for HCC due to the absence of hepatocytes in AML in comparison with HCC, which may consist of dysplastic foci showing mild hypointensity in the HBP. Thus, marked homogeneous low SI in the HBP could be helpful in distinguishing AML from HCC ( 49 ).

HCC is the only malignancy diagnosed on non-invasive imaging criteria without histological confirmation in at-risk patients. However, some HCCs reveal atypical imaging features, which poses a diagnostic challenge for radiologists. And we reviewed the presence of HCC mimicking lesions such as hemangioma, AP shunt, hepatic metastasis, IHCC, cHCC-CC, etc. The interpretation should be made carefully, not only using MR imaging and enhancement pattern on dynamic study, but also considering the patient’s history, laboratory findings, and demographic characteristics. In addition, radiologists should be aware of the diverse imaging characteristics of HCC and other hepatic neoplasms as a differential diagnosis and should be able to suggest proper management and better patient outcomes.