Rare Liver Tumor Research Articles

CT and MR imaging characteristics of primary hepatic lymphoma

BackgroundPrimary hepatic lymphoma (PHL) is a rare primary liver tumor. The purpose of this study was to investigate the crucial imaging characteristics of PHL.MethodsCT/MR data and clinical features of 16 patients with pathologically proven PHL were retrospectively reviewed. The assessed imaging characteristics included lesion distribution, growth appearance, density or signal characteristics, and typical signs during the dynamic enhancement.ResultsA total of sixteen patients were included in this study, ranging in age from 27 to 86 years (nine men and seven women; mean age, 62 years). Right upper abdominal pain, malaise, or first detection during physical examination were the chief complaint. Dynamic contrast-enhanced CT and MRI demonstrated focal masses in thirteen patients (13/16, 81%), and multiple nodules in three patients (3/16, 19%). The lesions showed vascular floating sign in 10 patients (10/16, 63%) and biliary pass-through sign in 6 patients (6/16, 37%). Necrosis in PHLs were observed in 10 patients (10/16, 63%) and presented target sign on T2WI in 5 out of 11 patients (5/11, 45%) undergoing MRI. After enhancement, PHLs had multinodular sign in the arterial phase in 10 patients (10/16, 63%), and presented washout of contrast medium in the portal-venous or delayed phase in 12 patients (12/16, 75%), pseudocapsule in the delayed phase in 15 patients (15/16, 94%), and double-ring sign in the delayed phase in 8 patients (8/16, 50%).ConclusionPHL is generally seen in elderly patients with elevated beta-2-microglobulin levels. Its distinctive imaging features including obviously low ADC value, biliary/vascular floating sign, multinodular sign and double-ring sign in the delayed phase, may help to diagnose and differentiate PHL.

A Lymphoepithelioma-Like Intrahepatic Cholangiocarcinoma With Massive Multinucleated Giant Cell Reaction.

Lymphoepithelioma-like intrahepatic cholangiocarcinoma (LEL-ICC) is a rare liver tumor that appears as a hepatic nodule on imaging with a specific pathological pattern, and the definitive diagnosis relies on its pathological histomorphology, immunophenotype, and Epstein-Barr encoding region test. Radical surgical resection is the primary treatment modality, and immunotherapy is expected to be a new adjuvant treatment option. LEL-ICC with massive multinucleated giant cell infiltration has not been reported so far. In this article, we report a patient with LEL-ICC showing massive multinucleated giant cell infiltration, review the relevant literature, and analyze its clinicopathological features and prognosis to accumulate experience for the accurate diagnosis of LEL-ICC.

Hepatocellular adenomas with severe intra-abdominal bleeding, related to an underlying coagulation disorder: a case report

BackgroundHepatocellular adenoma is a rare benign liver tumor. Typically, hepatocellular adenomas are solitary and are found in young women who use estrogen-containing contraceptives. The occurrence of multiple hepatocellular adenoma has been linked to higher body mass index, and as the prevalence of overweight increases, multiple hepatocellular adenomas are seen more often. An hepatocellular adenoma does not always necessitate treatment, as they can regress under conservative strategies. In incidental cases, an adenoma presents owing to bleeding, which is mostly self-limiting. If it is not, embolization of hepatic involved vessels is indicated.Case presentationIn this case report, we discuss a 42-year old Caucasian woman with multiple hepatocellular bleeds, treated by multiple endovascular procedures. After the first embolization of an adenoma in the right liver lobe, a second bleed occurred in the left lobe, necessitating additional endovascular intervention. During admittance, treatment was complicated by pulmonary embolism and a pneumonia. During follow-up, our patient was diagnosed with antiphospholipid syndrome.ConclusionHepatocellular adenoma is a rare diagnosis that requires centralized expertise. This particular case illustrates the complexity of treatment strategies for associated intra-abdominal bleeding and possible complications. Although liver adenoma is often an incidental finding, it can also result in significant morbidity. Centralization of treatment leads to expertise in managing complex treatment strategies.

MRI features of combined hepatocellular-cholangiocarcinoma.

Combined hepatocellular cholangiocarcinoma (cHCC-CCA) is a rare liver tumor which has a more aggressive behavior and worse survival outcome than hepatocellular carcinoma (HCC), with a prognosis similar to that of intrahepatic cholangiocarcinoma (iCCA). With limited literature on the appearance of this tumor on MRI, it remains a diagnostic challenge. In this review, we looked at the currently described MRI findings in this uncommon entity. Based on studies conducted to date, a mixed pattern at imaging has demonstrated the highest specificity, seen as a combination of areas showing progressive enhancement of the lesion, arterial enhancement with washout, and areas of arterial enhancement without washout and/or hypovascularity. Tumor markers may aid in identification, particularly in cases where the imaging appearance mimics that of isolated HCC or iCCA. Intratumoral heterogeneity leads to difficulties with pathologic diagnosis from sampling due to the possibility of an incorrect diagnosis if the biopsy specimen does not contain adequate tissue comprising both histologic components.

Congenital hepatoblastoma: Expanding knowledge, improving outcomes.

Hepatoblastoma (HB) is a rare liver tumour, and its congenital counterpart (CHB) is even less frequent. CHB has a clinically challenging management and a generally perceived worse outcome. This study aims to review the literature on CHB to better define presentation, diagnosis, available treatments and management options. The analysis of outcomes suggests that a significant portion of mortality is unrelated to the malignant nature of the tumour. Key factors influencing overall outcomes were identified: mortality linked to the 'mass effect' during both the prenatal (22%) and perinatal (32%) stages, as well as 'oncological' mortality encompassing tumour and/or treatment-related factors (46%). Overall, after birth, CHB does not seem to confer a worse oncological prognosis per se, and should be managed similarly to older children, if patients are stable enough to undergo proper staging and treatment. A deeper knowledge and better outcomes would come from a large, homogeneous, collection of data possibly allowing a global protocol, focusing on a comprehensive management of CHB.

Hepatocellular Adenoma: A Life-Threatening Presentation of a Rare Liver Tumor – Case Report and Literature Review

Hepatocellular adenoma is a rare benign liver tumor that occurs predominantly in young women who use exogenous estrogens. We describe a case of a 40-year-old woman on birth control pill who presented with acute right hypochondrial pain and signs of hemodynamical instability triggered by a large bleeding tumor in the right liver lobe. Arterial embolization was performed with cessation of bleeding. To determine etiology, magnetic resonance imaging was conducted with findings suggestive of a hepatocellular adenoma. The tumor was surgically resected, and histologic examination made the definite diagnosis of an inflammatory hepatocellular adenoma. This is a noteworthy case of a rare but potentially fatal complication of liver tumors, whose diagnosis requires a high index of suspicion. Clinicians should consider this diagnosis in young women on oral contraceptive pills who present with severe unexplained abdominal pain and hemodynamical instability. This case aimed to raise awareness of this condition, while reviewing important aspects concerning the management of hepatocellular adenomas.

FusionVAC22_01: a phase I clinical trial evaluating a DNAJB1-PRKACA fusion transcript-based peptide vaccine combined with immune checkpoint inhibition for fibrolamellar hepatocellular carcinoma and other tumor entities carrying the oncogenic driver fusion.

EU CT Number: 2022-502869-17-01 and ClinicalTrials.gov Registry (NCT05937295).

Reversing immunosuppression in the tumor microenvironment of fibrolamellar carcinoma via PD-1 and IL-10 blockade

Fibrolamellar carcinoma (FLC) is a rare liver tumor driven by the DNAJ-PKAc fusion protein that affects healthy young patients. Little is known about the immune response to FLC, limiting rational design of immunotherapy. Multiplex immunohistochemistry and gene expression profiling were performed to characterize the FLC tumor immune microenvironment and adjacent non-tumor liver (NTL). Flow cytometry and T cell receptor (TCR) sequencing were performed to determine the phenotype of tumor-infiltrating immune cells and the extent of T cell clonal expansion. Fresh human FLC tumor slice cultures (TSCs) were treated with antibodies blocking programmed cell death protein-1 (PD-1) and interleukin-10 (IL-10), with results measured by cleaved caspase-3 immunohistochemistry. Immune cells were concentrated in fibrous stromal bands, rather than in the carcinoma cell compartment. In FLC, T cells demonstrated decreased activation and regulatory T cells in FLC had more frequent expression of PD-1 and CTLA-4 than in NTL. Furthermore, T cells had relatively low levels of clonal expansion despite high TCR conservation across individuals. Combination PD-1 and IL-10 blockade signficantly increased cell death in human FLC TSCs. Immunosuppresion in the FLC tumor microenvironment is characterized by T cell exclusion and exhaustion, which may be reversible with combination immunotherapy.

NIPBL::NACC1 Fusion Hepatic Carcinoma.

Several reports describing a rare primary liver tumor with histologic features reminiscent of follicular thyroid neoplasms have been published under a variety of descriptive terms including thyroid-like, solid tubulocystic, and cholangioblastic cholangiocarcinoma. Although these tumors are considered to represent histologic variants, they lack classic features of cholangiocarcinoma and have unique characteristics, namely immunoreactivity for inhibin and NIPBL::NACC1 fusions. The purpose of this study is to present clinicopathologic and molecular data for a large series of these tumors to better understand their pathogenesis. We identified 11 hepatic tumors with these features. Immunohistochemical and NACC1 and NIPBL fluorescence in situ hybridization assays were performed on all cases. Four cases had available material for whole-genome sequencing (WGS) analysis. Most patients were adult women (mean age: 42y) who presented with abdominal pain and large hepatic masses (mean size: 14cm). Ten patients had no known liver disease. Of the patients with follow-up information, 3/9 (33%) pursued aggressive behavior. All tumors were composed of bland cuboidal cells with follicular and solid/trabecular growth patterns in various combinations, were immunoreactive for inhibin, showed albumin mRNA by in situ hybridization, and harbored the NIPBL::NACC1 fusion by fluorescence in situ hybridization. WGS corroborated the presence of the fusion in all 4 tested cases, high tumor mutational burden in 2 cases, and over 30 structural variants per case in 3 sequenced tumors. The cases lacked mutations typical of conventional intrahepatic cholangiocarcinoma. In this report, we describe the largest series of primary inhibin-positive hepatic neoplasms harboring a NIPBL::NACC1 fusion and the first WGS analysis of these tumors. We propose to name this neoplasm NIPBL:NACC1 fusion hepatic carcinoma.

Unusual Case of Primary Hepatic Squamous Carcinoma on 18F-FDG PET/CT.

Primary hepatic squamous carcinoma is an extremely rare liver tumor type with high malignancy and poor prognosis. We present 18F-FDG PET/CT findings of primary squamous carcinoma of the liver in a 65-year-old man, who was admitted to the hospital with subxiphoid pain in the epigastric region radiating to the left lower back for 2 months. 18F-FDG PET/CT demonstrated a large heterogeneous mild enhancing mass in the left lobe of the liver, with intense circumferential 18F-FDG activity.

A Rare Autopsy Case of Aggressive Combined Hepatocellular-Cholangiocarcinoma with Stem Cell Features in A 59-Year-Old Female

Abstract Introduction/Objective Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a rare liver tumor with histologic and phenotypic features of both hepatocellular carcinoma and intrahepatic cholangiocarcinoma. It is believed to arise from hepatic progenitor cells. It consists of intermingled malignant biliary and hepatic tissue and thus is a distinct entity, rather than two separate coexisting malignancies. Methods/Case Report A 59-year-old female with a history of hepatitis C and cirrhosis presented with abdominal pain, shortness of breath, and altered mental status. She developed hematemesis and went into cardiac arrest. Massive transfusion and cardiopulmonary resuscitation were initiated. She was intubated, and an esophageal/gastric balloon was placed. She then underwent a procedure to relieve portal hypertension and related gastrointestinal bleeding. Despite extensive interventions, her condition continued to deteriorate. She expired one day after her initial presentation. Results (if a Case Study enter NA) At autopsy, the liver was diffusely and markedly fibrotic with numerous nodules of varying size with invasion into adjacent vasculature. Microscopic examination of the nodules revealed cHCC-CC with stem cell features and lymphovascular invasion. Further examination revealed tumor emboli scattered throughout the right lung. The patient’s history of chronic hepatitis C may have contributed to the development of her cHCC-CC. Although gross appearance resembled cirrhosis, upon microscopic inspection the nodules showed excessive tumor burden. Ultimately the patient had end stage liver disease due to the accumulation of damage and consequent fibrosis. This led to portal hypertension with subsequent massive gastrointestinal bleeding, hemorrhagic shock, and death. Conclusion cHCC-CC is a rare aggressive primary liver tumor with a poor prognosis. It can present with a cirrhotomemetic pattern with small nodules that can evade clinical and radiographic detection. Autopsy findings can provide valuable insights into the pathogenesis and clinical course of cHCC-CC, highlight the aggressive nature of the disease, and may inform future diagnostic and therapeutic strategies. Accurate diagnosis of this tumor is important for patient management and prognostication.

Single-center experience in the diagnosis and treatment of lymphoepithelioma-like hepatic carcinoma.

Lymphoepithelioma-like hepatic carcinoma (LELC) is a rare malignant liver tumor and its preoperative diagnosis is challenging. The aim of this study was to optimize the diagnosis and treatment of LELC in a single large center. We conducted this retrospective analysis of 16 patients diagnosed with LELC in the First Affiliated Hospital of Zhejiang University between 2010 and 2022. Thirty-two cases of cholangiocarcinoma (ICC) and 48 cases of hepatocellular carcinoma (HCC) served as controls. Most of the 16 patients with LELC included in this study had no specific symptoms. Histologically, 9 patients had lymphoepithelioma-like hepatocellular carcinoma (LEL-HCC), 5 had lymphoepithelioma-like cholangiocarcinoma (LEL-ICC) and 2 had LEL-HCC-ICC. LEL-HCC was usually accompanied by hepatitis B virus infection, while LEL-ICC was often accompanied by Epstein Barr virus (EBV) infection. During the follow-up period, no complication and deaths were observed and only one patient experienced recurrence. These results were obviously better than those in patients with HCC and ICC. LELC is a rare malignant hepatic tumor. There are no specific symptoms or imaging modalities for accurate preoperative diagnosis of LELC. The diagnosis can be confirmed by pathology; however, the prognosis of LELC after resection is promising.

Occurrence of Hepatoblastomas in Patients with Beckwith-Wiedemann Spectrum (BWSp).

Patients with Beckwith-Wiedemann syndrome (BWS), an epigenetic imprinting disorder involving alterations in genes at the 11p15 chromosomal location, are predisposed to develop hepatoblastomas (HBs), which are rare embryonal liver tumors. Tumors can develop after a BWS diagnosis or, conversely, can be the presenting feature leading to a subsequent diagnosis. While HBs are the cardinal tumors of BWS, not all patients with the BWS spectrum will develop HBs. This observation has led to many hypotheses, including genotype-associated risk, tissue mosaicism, and tumor-specific second hits. To explore these hypotheses, we present the largest cohort of patients with BWS and HBs to date. Our cohort comprised 16 cases, and we broadened our sample size by searching the literature for all cases of BWS with HBs. From these isolated case studies, we amassed another 34 cases, bringing the total number to 50 cases of BWS-HB. We observed that paternal uniparental isodisomy (upd(11)pat) was the most common genotype, representing 38% of cases. The next most common genotype was IC2 LOM, representing 14% of cases. Five patients had clinical BWS without a molecular diagnosis. To investigate the potential mechanism of HBs in BWS, we analyzed normal liver and HB samples from eight cases and isolated tumor samples from another two cases. These samples underwent methylation testing, and 90% of our tumor samples underwent targeted cancer next-generation sequencing (NGS) panels. These matched samples provided novel insights into the oncogenesis of HBs in BWS. We found that 100% of the HBs that underwent NGS panel testing had variants in the CTNNB1 gene. We further identified three distinct groups of BWS-HB patients based on epigenotype. We also demonstrated epigenotype mosaicism, where 11p15 alterations can differ between the blood, HB, and normal liver. In light of this epigenotype mosaicism, tumor risk assessment based on blood profiling may not be accurate. Therefore, universal screening is recommended for all patients with BWS.

Characteristic contrast‑enhanced ultrasound findings of hepatic epithelioid haemangioendothelioma: A case report and literature review.

Hepatic epithelioid hemangioendothelioma (HEHE) is a rare liver tumor, which is usually diagnosed by pathological examination, since the diagnostic imaging criteria remain to be defined. However, contrast-enhanced ultrasound (CEUS) may reveal the characteristic features of HEHE to aid diagnosis. In the present study, two-dimensional ultrasound examination of a 38-year-old male patient showed a mass in the right liver. CEUS showed an S5 segment hypoechoic nodule, and imaging features resulted in the diagnosis of HEHE. Surgery was shown to be an appropriate and successful treatment for HEHE. In conclusion, CEUS may be valuable for the diagnosis of HEHE, thereby avoiding the serious consequences of misdiagnosis.

Surgical Strategies for Combined Hepatocellular-Cholangiocarcinoma (cHCC-CC).

Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a tumor entity presenting features of hepatocellular and cholangiocellular epithelial differentiation. Due to the likeness between cHCC-CC, HCC and CC, accurate pretherapeutical diagnosis is challenging and advanced stages are prevalent. Radical oncological surgery is the only curative therapeutical option in patients with cHCC-CC. To reach this goal a profound understanding of this rare liver tumor is crucial. Factors such as clinicopathological characteristics, growth patterns and biological behavior are of central importance. To explore onco-surgical strategies and aspects for complete resection of cHCC-CC and to answer important key questions, an extensive review of the literature was conducted to answer the following questions: What are the best surgical options? Is there a significance for nonanatomical resections? Is there a prognostic value of concomitant lymphadenectomy? What about multimodal concepts in local advanced cHCC-CC? The role of minimally invasive liver surgery (MILS) including the role of robotic liver surgery for cHCC-CC will be discussed. While liver transplantation (LT) is standard for patients with unresectable HCC, the role of LT in cHCC-CC patients is still controversial. How can patients with high risk for early tumor recurrence be identified to avoid aggressive surgical treatment without clinical benefit? The comprehensive understanding of this challenging liver tumor will help to improve future treatment options for these patients.

Genetic and epigenetic analysis of hepatocellular adenomas with atypical morphological features.

Hepatocellular adenoma (HCA) is a rare liver tumour, which can have atypical morphological features such as cytological atypia, pseudoglandular architecture, and altered reticulin framework. Little is known about the genetic and epigenetic alterations of such HCAs and whether they show the alterations classically found in hepatocellular carcinoma (HCC) or in HCA without atypical morphology. We analysed five HCAs with atypical morphological features and one HCA with transition to HCC. Every tumour was subtyped by immunohistochemistry, sequenced by a targeted NGS panel, and analysed on a DNA methylation microarray. Subtyping of the five HCAs with atypical features revealed two β-catenin mutated HCA (b-HCA), two β-catenin mutated inflammatory HCA (b-IHCA), and one sonic hedgehog activated HCA (shHCA). None of them showed mutations typically found in HCC, such as, e.g. TERT or TP53 mutations. The epigenomic pattern of HCAs with atypical morphological features clustered with reference data for HCAs without atypical morphological features but not with HCC. Similarly, phyloepigenetic trees using the DNA methylation data reproducibly showed that HCAs with morphological atypia are much more similar to nonmalignant samples than to malignant samples. Finally, atypical HCAs showed no relevant copy number variations (CNV). In our series, mutational, DNA methylation, as well as CNV analyses, supported a relationship of atypical HCAs with nonatypical HCAs rather than with HCC. Therefore, in cases with difficult differential diagnosis between HCC and HCA, it might be advisable to perform targeted sequencing and/or combined methylation/copy number profiling.

Incidental combined hepatocellular-cholangiocarcinoma in liver transplant patients: Does it have a worse prognosis?

Combined hepatocellular-cholangiocarcinoma (CHC) requires attention clinically and pathologically after liver transplantation (LT) because of its unique biology, difficulties in diagnosis, and being rare. We aimed to present our single-center experience for this incidental combined tumor. It is aimed to present our single-center experience for this incidental combined tumor. Seventeen patients with CHC were included in the study. There were 260 hepatocellular carcinoma (HCC) patients determined as the control group. Patients were evaluated for demographic, etiological, pathological features, and survival. Macrovascular and microvascular invasion levels were significantly higher in the CHC group (p<0.05). P53, CK19, and CK7 levels were significantly higher in the CHC group (p<0.05). Hepatocyte-specific antigen level was significantly higher in the HCC group. The mean overall survival was significantly higher in the HCC group (p<0.05). Even though CHC is a rare liver tumor, it has features that need to be clarified regarding both survival and tumor biology. İnvestigating prognostic factors, especially in terms of survival and recurrence, will be very beneficial to identify candidates who will benefit from LT and be included in the indications for LT for CHC. This study evaluated the outcomes of patients showing combined HCC-intrahepatic cholangiocarcinoma in explant pathology.

A rare primary liver tumour case report: 53-year-old man with primary hepatic leiomyosarcoma

A rare primary liver tumour case report: 53-year-old man with primary hepatic leiomyosarcoma

A Case Review on Combined Hepatocellular Cholangiocarcinoma

Abstract Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary liver tumor with neoplastic components of both hepatocytic and cholangiocytic differentiation within the same tumor, such as the case reported herein. There is a need to standardize the pathological diagnosis of cHCC-CCA and to improve the concordance of diagnosis among pathologists based on consensus paper because of its histological and phenotypic diversity that leads to confusion in terminology and classification. This case review addresses the terminology, classification, and clinical and pathological characteristics of cHCC-CCA and its differential diagnosis.

Update in Pathology of Practically Encountered Lesions and Diseases in the Liver

This issue of the American Journal of Surgical Pathology, Reviews and Reports is devoted to recent advances and update in the pathology of the liver. The articles provide insights into the current nomenclature, classification, diagnosis, differential diagnoses, clinical and prognostic aspects of various liver diseases, and lesions that are informative to pathologists in their daily practice. Hepatocellular adenomas (HCAs) is generally a benign liver neoplasm that typically arises in the noncirrhotic liver; however, malignant transformation does occur, and hence, subtyping is critical. Drs Jung and Liu present a case of HCA that was initially diagnosed as inflammatory HCA on a biopsy and subsequently was confirmed to be β-catenin–activated inflammatory HCA on the resection specimen. They then comprehensively review recent updates on molecular classification and the key histologic features of each subtype and discuss common diagnostic pitfalls. Over the past decades, hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA) have been recognized to be heterogeneous in morphology, molecular features, and biological behavior. Recent World Health Organization classification describes various histomorphological subtypes of HCC and iCCA, some with characteristic molecular profiles, clinical correlates, and prognostic implications. In their review, Drs Hwang and Kim nicely discuss recently described subtypes of HCC and iCCA: macrotrabecular HCC, steatohepatitic HCC, scirrhous HCC, and small duct iCCA. Congestive hepatopathy shows a unique pattern of fibrosis, that is, pericentral fibrosis at early stage, which may progress to bridging fibrosis and cirrhosis. Making a diagnosis of congestive hepatopathy and staging its fibrosis are important tasks for pathologists, as patients may undergo liver biopsies before cardiac transplantation to assess the degree of liver fibrosis, which may impact clinical decision-making. Besides patients' own cardiac dysfunction, congestive hepatopathy can also be seen after a Fontan procedure. Drs Gosse and Bosch describe a case of congestive hepatopathy due to altered circulation with a Fontan procedure. They then discuss the fibrosis scoring systems recently described for Fontan-associated liver disease and congestive heart disease–associated hepatopathy. Combined hepatocellular-cholangiocarcinoma is a rare primary liver tumor with neoplastic components of both hepatocytic and cholangiocytic differentiation within the same tumor. There is recent consensus paper and World Health Organization classification of this unique tumor. Drs Kondo, Akiba, and Yano herein report a case of this tumor and thoughtfully review the terminology, classification, and clinical and pathological characteristics of combined hepatocellular-cholangiocarcinoma and its differential diagnosis. Hemophagocytic lymphohistiocytosis is a rare disease with a high mortality. Liver involvement is common, with most patients demonstrating acute hepatitis. Therefore, liver biopsies are frequently performed when this entity is suspected. Dr Xiong and colleagues summarize the clinical features of hemophagocytic lymphohistiocytosis, emphasizing its hepatic manifestations. They describe the highly variable histologic patterns and address difficulties encountered by pathologists. We are extremely grateful to all the contributors for sharing their expertise and knowledge in forming this issue. We hope that the information provides highlights and elucidates the practically encountered lesions in the liver. Guest Editors