Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a tumour that exhibits both hepatocytic and biliary differentiation. Classical risk factors for hepatocellular carcinoma (HCC) seem to also ...predispose patients to the development of cHCC-CCA. The pathological definition of cHCC-CCA has significantly evolved over time. The last 2019 WHO classification highlighted that the diagnosis of cHCC-CCA should be primarily based on morphology using routine stainings, with additional immunostaining used to refine the identification of subtypes. Among them, “intermediate cell carcinoma” is recognised as a specific subtype, while “cholangiolocellular carcinoma” is now considered a subtype of iCCA. Increasing molecular evidence supports the clonal nature of cHCC-CCA and parallels its biphenotypic histological appearance, with genetic alterations that are classically observed in HCC and/or iCCA. That said, the morphological diagnosis of cHCC-CCA is still challenging for radiologists and pathologists, especially on biopsy specimens. Identification of cHCC-CCA’s cell of origin remains an area of active research. Its prognosis is generally worse than that of HCC, and similar to that of iCCA. Resection with lymph node dissection is unfortunately the only curative option for patients with cHCC-CCA. Thus, there remains an urgent need to develop specific therapeutic strategies for this unique clinical entity.
Hepatocellular adenoma (HCA) is a rare benign liver neoplasm which predominantly occurs in women in the reproductive age group taking oral contraception. Since 2002, the terminology HCA has defined ...an heterogeneous group of neoplastic benign hepatocellular proliferations composed of different subtypes. The genotype-phenotype classification led to the description of 5 well-recognized subtypes based on morphological and immunophenotypical features, that are currently used in practice: HNF1A inactivated HCA, inflammatory HCA, β-catenin mutated HCA, sonic hedgehog HCA, and unclassified HCA. The main complications observed in HCAs are bleeding and malignant transformation. Risk of malignant transformation into hepatocellular carcinoma (HCC), more frequent in men, is also dependent to tumor size and HCA subtype, reaching 40% in β-catenin mutated HCA. The distinction of HCA from well-differentiated HCC remains difficult in some cases, leading to the diagnosis of so-called “atypical/borderline HCA”. The management of HCA is now based on multidisciplinary approach including clinicians, radiologists, and pathologists integrating gender, tumor size, and HCA subtyping.
•Hepatocellular adenoma is a rare benign liver neoplasm which predominatly occurs in women.•The genotype-phenotype classification led to the description of 5 well-recognized subtypes.•The main complications observed in hepatocellular adenomas are bleeding and malignant transformation.•Risk of malignant transformation into hepatocellular carcinoma is dependent to gender, tumor size and subtype.
Aims
Immunotherapies represent a new alternative therapeutic approach for hepatocellular carcinomas (HCCs), and have shown promising results when used in combination therapy. The aim of this study ...was to evaluate the potential of transarterial chemoembolisation (TACE) to modulate programmed death‐1 (PD‐1) and programmed death‐ligand 1 (PD‐L1) expression profiles in a cohort of surgically treated HCCs.
Methods and results
A total of 82 surgically treated HCCs from patients who had undergone (n = 32) or not undergone (n = 50) preoperative TACE were included in the study. Immunohistochemical expression of PD‐1 and of PD‐L1 were analysed and compared according to TACE treatment. Pretreatment biopsies, which were available for 30 cases (20 with TACE and 10 without), were similarly analysed. Follow‐up data were retrieved from patients' charts. PD‐1 expression (≥1%) in intratumoral inflammatory cells (ICs) was observed in 46% of HCCs, and PD‐L1 expression (≥1%) in ICs and PD‐L1 expression in tumour cells (TCs) were observed in 46% and 16% of HCCs, respectively. A low level of PD‐1 expression (<1%) was associated with strong and diffuse glutamine synthetase overexpression (8% versus 27%, P = 0.024). HCCs from patients with TACE pretreatment showed significantly higher PD‐L1 expression in TCs than those from patients without TACE pretreatment (2% versus 0.4%, P = 0.027). PD‐1 expression in ICs and PD‐L1 expression in both ICs and TCs were higher in TACE‐resected tumours than in corresponding pre‐TACE biopsies (respectively: 1.8% versus 8.1%, P = 0.034; 0.8% versus 7.1%, P = 0.032; and 0% versus 2.4%, P = 0.043).
Conclusion
Our results, showing increases in PD‐1 expression and PD‐L1 expression in HCCs following TACE, support the use of TACE in combination with immunotherapy in selected cases to optimise tumour response.
Cystic fibrosis (CF) is the most common autosomal recessive disease in the Caucasian population. Cystic fibrosis-related liver disease (CFLD) is defined as the pathogenesis related to the underlying ...CFTR defect in biliary epithelial cells. CFLD needs to be distinguished from other liver manifestations that may not have any pathological significance. The clinical/histological presentation and severity of CFLD vary. The main histological presentation of CFLD is focal biliary fibrosis, which is usually asymptomatic. Portal hypertension develops in a minority of cases (about 10%) and may require specific management including liver transplantation for end-stage liver disease. Portal hypertension is usually the result of the progression of focal biliary fibrosis to multilobular cirrhosis during childhood. Nevertheless, non-cirrhotic portal hypertension as a result of porto-sinusoidal vascular disease is now identified increasingly more frequently, mainly in young adults. To evaluate the effect of new CFTR modulator therapies on the liver, the spectrum of hepatobiliary involvement must first be precisely classified. This paper discusses the phenotypic features of CFLD, its underlying physiopathology and relevant diagnostic and follow-up approaches, with a special focus on imaging.
With the development of chemotherapy regimens, targeted therapies, and hepatic surgery, the survival of patients with colorectal liver metastases (CRLM) has dramatically improved. Imaging plays a ...central role for the diagnosis, staging, and treatment allocation in these patients. To interpret CRLM on imaging, radiologists must be familiar with the main imaging features of untreated tumors as well as the modifications induced by systemic therapies, and their meaning in relation to pathological tumor response and tumor biology. CRLM have the same histological features as the primary tumor. Most are “non-otherwise specified” (NOS) adenocarcinomas. The mucinous tumor is the most common of the rare subtypes. In NOS tumors, imaging usually differentiates central areas of necrosis from peripheral proliferating tumors and desmoplastic reaction. Areas of mucin mixed with fibrosis are seen in mucinous subtypes to help differentiate the metastases from other tumors cysts or hemangiomas. After treatment, the viable tumor is gradually replaced by ischemic-like necrosis and fibrosis, and remnants cells are mainly located on the periphery of tumors. Imaging can help predict the degree of tumor response, but changes can be difficult to differentiate from the pretherapeutic appearance. When chemotherapy is interrupted or in case of resistance to treatment, a peripheral infiltrating halo of tumor growth may appear. The purpose of the article is to illustrate the significance of the imaging features of colorectal liver metastases during systemic therapy, using radiopathological correlations.
Microvascular invasion (MVI), a major risk factor for tumor recurrence after surgery in hepatocellular carcinoma (HCC), is only detectable by microscopic examination of the surgical specimen. We ...aimed to define a transcriptomic signature associated with MVI in HCC than can be applied to formalin-fixed paraffin-embedded (FFPE) biopsies for use in clinical practice.
To identify a gene expression signature related to MVI by using NanoString technology, we selected a set of 200 genes according to the literature and RNA-sequencing data obtained from a cohort of 150 frozen HCC samples previously published. We used 178 FFPE-archived HCC samples, including 109 surgical samples for the training set and 69 paired pre-operative biopsies for the validation set. In 14 cases of the training set, a paired biopsy was available and was also analyzed.
We identified a 6-gene signature (ROS1, UGT2B7, FAS, ANGPTL7, GMNN, MKI67) strongly associated with MVI in the training set of FFPE surgical HCC samples, with 82% accuracy (sensitivity 82%, specificity 81%, AUC 0.82). The NanoString gene expression was highly correlated in 14 paired surgical/biopsy HCC samples (mean R: 0.97). In the validation set of 69 FFPE HCC biopsies, the 6-gene NanoString signature predicted MVI with 74% accuracy (sensitivity 73%, specificity 76%, AUC 0.74). Moreover, on multivariate analysis, the MVI signature was associated with overall survival in both sets (hazard ratio 2.29; 95% CI 1.03-5.07; p = 0.041).
We defined a 6-gene signature that can accurately predict MVI in FFPE HCC biopsy samples, which is also associated with overall survival, although its survival impact must be confirmed by extensive study with further clinical data.
Microvascular invasion, a major risk factor for tumor recurrence after surgery in hepatocellular carcinoma, is only detectable by microscopic examination of a surgical specimen. In this study, we defined a relevant surrogate signature of microvascular invasion in hepatocellular carcinoma that may be applied in clinical practice with routine tumor biopsy and integrated into the therapeutic strategy.
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•Excellent gene-expression correlation was observed between paired biopsy and surgical specimens.•We defined a 6-gene signature strongly associated with microvascular invasion.•The signature showed good performance for predicting microvascular invasion in formalin-fixed paraffin-embedded biopsies.•The 6-gene signature was associated with overall survival.
According to the last WHO classification, steatohepatitic hepatocellular carcinoma (SH-HCC) is recognized as a distinct HCC subtype, even though a consensual definition is still lacking. The ...objectives of the study were to carefully describe the morphological features of SH-HCC and evaluate its impact on prognosis.
We conducted a single-centre retrospective study including 297 surgically resected HCC. Pathological features including SH criteria (steatosis, ballooning, Mallory-Denk bodies, fibrosis, and inflammation) were assessed. SH-HCC was defined by the presence of at least four of the five SH criteria and the SH component represented >50% of the tumour area. According to this definition, 39 (13%) HCC cases corresponded to SH-HCC and 30 cases (10%) corresponded to HCC with an SH component (<50%). SH criteria in SH-HCC and non-SH-HCC were distributed as follows: ballooning (100% versus 11%), fibrosis (100% versus 81%), inflammation (100% versus 67%), steatosis (92% versus 8%), and Mallory-Denk bodies (74% versus 3%). Inflammation markers (c-reactive protein CRP and serum amyloid A SAA) were significantly more expressed in SH-HCC compared to non-SH-HCC (82% versus 14%, P = <0.001). Five-year recurrence-free survival (RFS) and 5-year overall survival (OS) were similar for SH-HCC and non-SH-HCC (P = 0.413 and P = 0.866, respectively). The percentage of SH component does not impact OS and RFS.
We confirm in a large cohort the relatively high prevalence (13%) of SH-HCC. Ballooning is the most specific criteria for this subtype. The percentage of the SH component does not impact prognosis.
Combined hepato-cholangiocarcinomas (cHCC-CCA) belong to the spectrum of primary liver carcinomas, which include hepatocellular carcinomas (HCC) and intrahepatic cholangiocarcinomas (iCCA) at both ...ends of the spectrum. Mainly due to the high intratumor heterogeneity of cHCC-CCA, its diagnosis and pathological description remain challenging. Taking advantage of in situ non-targeted molecular mapping provided by MALDI (Matrix Assisted Laser Desorption Ionization) imaging, we sought to develop a multiscale and multiparametric morphological approach, integrating molecular and conventional pathological analysis. MALDI imaging was applied to five representative cases of resected cHCC-CCA. Principal component analysis and segmentations with MALDI imaging techniques identified areas related to either iCCA or HCC and also hidden tumor areas not visible microscopically. In addition, the overlap between MALDI segmentation and immunostaining provided a comprehensive description of cHCC-CCA tumor heterogeneity by identifying transitional and micro-metastatic areas. Moreover, a list of peptides derived from in silico digestion was obtained for each immunohistochemical marker and was matched within the peptide peak list acquired by MALDI. Comparison of immunostaining images with ions from in silico digestion revealed an accurate identification of iCCA and HCC areas. Our study provides further evidence on the performance of MALDI imaging in exploring intratumor heterogeneity and offering virtual multiplex immunostaining through a single acquisition.
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