Hepatocholangiocarcinoma, fibrolamellar carcinoma, hepatic haemangioendothelioma and hepatic angiosarcoma represent less than 5% of primary liver cancers. Fibrolamellar carcinoma and hepatic haemangioendothelioma are driven by unique somatic genetic alterations (DNAJB1-PRKCA and CAMTA1-WWTR1 fusions, respectively), while the pathogenesis of hepatocholangiocarcinoma remains more complex, as suggested by its histological diversity. Histology is the gold standard for diagnosis, which remains challenging even in an expert centre because of the low incidences of these liver cancers. Resection, when feasible, is the cornerstone of treatment, together with liver transplantation for hepatic haemangioendothelioma. The role of locoregional therapies and systemic treatments remains poorly studied. In this review, we aim to describe the recent advances in terms of diagnosis and clinical management of these rare primary liver cancers.

Fibrolamellar Carcinoma (FLC) and Combined Hepatocellular- Cholangiocarcinoma (CHC) are rare primary liver tumours, which are related to different clinical settings. In both tumours, correlation with clinical data and laboratory tests are extremely important.

Typically, FLC is diagnosed in young patients without any chronic disease and with normal biochemical tests, whereas CHC arises in cirrhotic patients with elevated tumour markers: AFP and/or CA 19-9. The review describes epidemiology, aetiology, pathogenesis, radiological features and treatment of these tumours. Imaging features typical for FLC are: The presence of central scar, calcifications, the large size, heterogeneous and early contrast-enhancement.

The diagnosis of CHC may be suggested in case of elevation of both AFP and CA 19- 9 or inconsistency between elevated tumour markers and imaging findings (i.e., elevated CA 19-9 and radiological features of HCC, or elevated AFP with imaging findings characteristic of ICC).

Hepatocellular carcinoma (HCC) is the most common primary hepatic malignancy, which usually arises in cirrhotic liver. When the typical enhancement pattern, consisting of late arterial hyperenhancement followed by washout, is present in nodules larger than 1 cm, HCC can be confidently diagnosed without the need for tissue biopsy. Nevertheless, HCC can display an atypical enhancement pattern, either as iso or hypovascular lesion, or hypervascular lesion without washout. Not only the enhancement pattern of HCC could be atypical, but also a variety of histological types of HCC, such as steatotic, scirrhous, fibrolamellar, or combined hepatocellular-cholangiocellular carcinoma could raise diagnostic dilemmas. In addition, distinct morphological types of HCC or different growth pattern can occur. Awareness of these atypical and rare HCC presentations on magnetic resonance imaging is important for accurate differentiation from other focal liver lesions and timely diagnosis, which allows optimal treatment of patients.

Primary liver carcinomas with both hepatocytic and cholangiocytic differentiation have been referred to as "combined (or mixed) hepatocellular-cholangiocarcinoma." These tumors, although described over 100 years ago, have attracted greater attention recently because of interest in possible stem cell origin and perhaps because of greater frequency and clinical recognition. Currently, because of a lack of common terminology in the literature, effective treatment and predictable outcome data have been challenging to accrue. This article represents a consensus document from an international community of pathologists, radiologists, and clinicians who have studied and reported on these tumors and recommends a working terminology for diagnostic and research approaches for further study and evaluation.

It is recommended that diagnosis is based on routine histopathology with hematoxylin and eosin (H&E); immunostains are supportive, but not essential for diagnosis. (Hepatology 2018;68:113-126).

The Liver Imaging Reporting and Data System (LI-RADS) standardizes the interpretation, reporting, and data collection for imaging examinations in patients at risk for hepatocellular carcinoma (HCC). It assigns category codes reflecting relative probability of HCC to imaging-detected liver observations based on major and ancillary imaging features. LI-RADS also includes imaging features suggesting malignancy other than HCC. Supported and endorsed by the American College of Radiology (ACR), the system has been developed by a committee of radiologists, hepatologists, pathologists, surgeons, lexicon experts, and ACR staff, with input from the American Association for the Study of Liver Diseases and the Organ Procurement Transplantation Network/United Network for Organ Sharing. Development of LI-RADS has been based on literature review, expert opinion, rounds of testing and iteration, and feedback from users. This article summarizes and assesses the quality of evidence supporting each LI-RADS major feature for diagnosis of HCC, as well as of the LI-RADS imaging features suggesting malignancy other than HCC. Based on the evidence, recommendations are provided for or against their continued inclusion in LI-RADS. © RSNA, 2017 Online supplemental material is available for this article.

To describe imaging findings in biphenotypic hepatic tumors (BPT) and a proposal for new imaging classification based on contrast-enhanced imaging.

Retrospective review of CT, MRI, PET/CT, and ultrasound findings in 39 patients with histologically confirmed BPT was performed. Tumor markers including AFP, L3 fraction, CA 19.9, CA 125, and CEA were recorded. Based on the dynamic enhancement features, BPT were categorized into 4 enhancement patterns (Types 1-4). Enhancement patterns were correlated with other imaging findings and tumor markers. Imaging features and tumor markers that were not consistent with diagnosis of hepatocellular carcinoma or intrahepatic cholangiocarcinoma based on enhancement pattern were considered discordant findings.

Enhancement patterns in 29 patients (CT/MR) included 23 Type 2 (continuous peripheral rim of late arterial hyperenhancement with washout or fade in portal venous and/or delayed phases, ±delayed central enhancement) and 2 of each Types 1, 2, and 3. Discordant imaging findings were present in two patients with Type 2 pattern and in one patient with Type 1 pattern. Both AFP and CA 19.9 were elevated in 15 of 33 of patients. Tumor markers AFP and CA 19.9 were discordant in 17 of 21 patients with Type 2 pattern, two of two patients with Type 3 pattern. Most BPTs were markedly PET avid with average SUV max of 8.2. Most frequent ultrasound appearance is peripheral hypoechogenicity and central hyperechogenicity.

BPT most commonly present with imaging features similar to cholangiocarcinoma or metastases. BPT can be suggested when imaging findings or tumor markers are discordant with the most likely diagnosis based on enhancement pattern.

Combined hepatocellular-cholangiocarcinoma is a rare primary hepatic tumour, showing both hepatocellular as well as biliary epithelium differentiation. Its diagnosis is often delayed, as it occurs in young patients without comorbidities and with non-specific symptoms. Most cases are confused with other types of cancer, especially fibrolamellar liver cancer, which is more frequent and has similar clinical and radiological features.

The case is presented of a 26 year old woman with a giant combined hepatocellular-cholangiocarcinoma with difficulties in its diagnosis and a complicated surgical approach.

The definitive diagnosis of this disease is defined by the histological demonstration of cholangiolar and hepatocellular differentiation, with surgical treatment always being the best choice, but with lower survival than classic hepatocellular carcinoma and cholangiocarcinoma. In some patients with unfavourable prognostic factors, adjuvant chemotherapy mainly directed cholangiolar component can be given.

The current incidence of combined hepatocellular-cholangiocarcinoma varies from 2 to 5% of cases, and is one of the rarest histological types in the world. The large size and hypervascularisation of the tumour makes a surgical approach difficult in these patients, while the rare histological features require a more detailed study of the piece and the application of immunohistochemical techniques to confirm the diagnosis.

Coincidental occurrence of hepatocellular carcinoma (HCC) and cholangiocarcinoma, known as "collision tumors", within a cirrhotic liver is rare. Herein, we report a case of liver transplantation (LT) in a patient with such collision tumors. Our patient was a 56-year-old woman with hepatitis C virus-related cirrhosis and 2 focal hepatic lesions, measuring 1.5 and 3 cm, in the liver segments 8 and 5, respectively. The lesion on segment 8 showed the typical radiological characteristics of HCC; however, the lesion in segment 5 showed an atypical vascular pattern and was closely associated with the inferior vena cava. Serum alpha-fetoprotein level was normal and serum carbohydrate antigen 19-9 (CA19-9) level was slightly elevated (63 U/mL); the extrahepatic spread of HCC was ruled out. The patient underwent an uneventful deceased-donor LT. Histopathological examination of the explant confirmed that the lesion on segment 8 was an HCC, but surprisingly, the lesion on segment 5 was found to be a cholangiocarcinoma. Six months after LT, the serum CA19-9 level was markedly elevated (255 U/mL), and the patient began experiencing abdominal pain. Magnetic resonance imaging showed enlarged hilar and paraaortic lymph nodes that were suggestive of metastases; histopathological analysis using ultrasound (US)-guided biopsy confirmed recurrent cholangiocarcinoma. Unfortunately, the patient died because of tumor recurrence 9 months after LT.Collision tumor resulting from the co-existence HCC and cholangiocarcinoma in a cirrhotic liver is rare and has a negative impact on the outcome of LT. Atypical vascular pattern and elevated serum CA19-9 levels are suggestive of such tumors; patients with these findings should undergo a targeted biopsy to rule out the coincidental occurrence of HCC and cholangiocarcinoma.

To describe the magnetic resonance imaging (MRI) appearance of hepatic combined hepatocellular-cholangiocarcinoma (cHCC-CC) in 11 patients.

The database of the Department of Pathology was cross-referenced with the MRI database to identify patients with confirmed cHCC-CC who had undergone MRI. Eleven consecutive patients were included (seven female, mean age 57.6 years). All patients were Caucasian. Five of 11 had a clinical history of chronic liver disease. Two radiologists retrospectively analyzed the images in consensus.

cHCC-CC was a single mass in 10/11 patients. Margins were well-defined in 6/11. All tumors showed heterogeneous hyperintensity on T2. On postcontrast imaging, 6/11 showed early ring-enhancement (four noncirrhotic), with progressive enhancement in central portions, and 5/11 patients showed a diffuse heterogeneous early enhancement. Three of these five were cirrhotic and displayed partial washout with portions of contrast retention on later phases. Other findings included: late capsule enhancement (two patients), biliary dilatation (one), venous invasion (three), lymphadenopathy (six), and findings of cirrhosis (five).

cHCC-CC presents most commonly as a single mass. Five of 11 had MR findings of cirrhosis. Clues to the diagnosis were moderately high signal on T2, portions of tumor that show progressive enhancement/contrast retention, and frequent lack of capsule. Early enhancement patterns included early ring-enhancement and diffuse heterogeneous enhancement.

Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) is an uncommon subtype of primary hepatic carcinoma, and its prognosis is poor. This study was undertaken to investigate the prognosis and the clinicopathological characteristics of cHCC-CC, including their possible cellular origin.

Among 852 patients with a primary hepatic carcinoma who underwent hepatectomy from January 1998 to April 2008 at our hospital, cHCC-CC was identified in 14 patients. The clinicopathological characteristics of the 14 patients were analyzed retrospectively. The expression of the liver stem cell markers (c-kit, CD90, CD133 and CK19) in the tumor tissue was detected by immunohistochemistry, and the Kaplan-Meier method was used to evaluate survival.

Among the 14 patients, 9 presented with abdominal pain, 3 with anorexia and debilitation, and the remaining two patients were asymptomatic. The mean age was 53.6+/-3.0 (range 38-74) years. Among the included patients, 11 had an elevated serum alpha-fetoprotein level, 13 were infected with hepatitis B virus, 9 had vascular invasion and 1 had lymph node metastasis. The average diameter of the tumors was 9.9+/-1.1 (range 5.0-16.0) cm. The median overall survival time was 7.9+/-1.0 months. In addition, the presence of the liver stem cell markers, c-kit, CD90, CD133 and CK19 was 71.4%, 85.7%, 92.9% and 78.6%, respectively. All four markers were simultaneously expressed in eight cases.

cHCC-CC has aggressive characteristics and the prognosis is extremely dismal. The high expression of liver stem cell markers in the tumor tissue suggests that these tumors may derive from liver stem cells.