Pink-on-pink: hepatocellular carcinoma metastatic to oncocytic carcinoma of the thyroid.

Hepatocellular carcinoma typically metastasizes within the liver and may involve extrahepatic sites such as the lungs, adrenal glands, and bones at advanced stages. However, hepatocellular carcinoma metastasis to the thyroid is very uncommon and tumor-to-tumor metastasis from a hepatocellular cancer to a thyroid neoplasm is extremely rare. In this report, we present a case of a 70-year-old man with a hepatocellular carcinoma metastasizing to oncocytic thyroid carcinoma, emphasizing the importance of clinical history and of a multidisciplinary approach, as well as the usefulness of site-specific immunohistochemical markers, in diagnosing and managing cases of Rosai's metastasis, especially when donor and recipient neoplasms share similar histologic features.

Transcriptomic and genomic characteristics of intrahepatic metastases of primary liver cancer.

BACKGROUND: Patients with primary multifocal hepatocellular carcinoma (HCC) have a poor prognosis and often experience a high rate of treatment failure. Multifocal HCC is mainly caused by intrahepatic metastasis (IM), and though portal vein tumor thrombosis (PVTT) is considered a hallmark of IM, the molecular mechanism by which primary HCC cells invade the portal veins remains unclear. Therefore, it is necessary to recognize the early signs of metastasis of HCC to arrange better treatment for patients. RESULTS: To determine the differential molecular features between primary HCC with and without phenotype of metastasis, we used the CIBERSORTx software to deconvolute cell types from bulk RNA-Seq based on a single-cell transcriptomic dataset. According to the relative abundance of tumorigenic and metastatic hepatoma cells, VEGFA+ macrophages, effector memory T cells, and natural killer cells, HCC samples were divided into five groups: Pro-T, Mix, Pro-Meta, NKC, and MemT, and the transcriptomic and genomic features of the first three groups were analyzed. We found that the Pro-T group appeared to retain native hepatic metabolic activity, whereas the Pro-Meta group underwent dedifferentiation. Genes highly expressed in the group Pro-Meta often signify a worse outcome. CONCLUSIONS: The HCC cohort can be well-typed and prognosis predicted according to tumor microenvironment components. Primary hepatocellular carcinoma may have obtained corresponding molecular features before metastasis occurred.

Orbital Metastasis as the First Manifestation of Hepatocellular Carcinoma, and Its Effective Treatment with Combined Dual Immunotherapy: A Case Report and Review of the Literature.

BACKGROUND Orbital metastasis originating from hepatocellular carcinoma (HCC), particularly as an initial manifestation in patients without a known history of HCC, is rare. Few reports exist on the treatment of patients having HCC with orbital metastasis using targeted therapy or immunotherapy. CASE REPORT We report a case of advanced-stage HCC in a 65-year-old man who first presented with progressive, painless blurred vision and proptosis of the right eye for 2 weeks. The patient had no history of chronic liver disease or cancer. Computed tomography revealed an enhancing hyperdense extraconal mass in the right orbit; a biopsy revealed metastatic HCC. Abdominal CT, which was performed to investigate the primary cancer, revealed a 1.2×1.6-cm arterial-enhancing nodule with venous washout in hepatic segment 5, associated with liver cirrhosis. The patient's serum alpha-fetoprotein level was 70.27 ng/dL. Chest computed tomography revealed lung metastasis. Thus, first-line systemic therapy combining durvalumab and tremelimumab was initiated alongside palliative radiotherapy targeting the right orbit, which began 1 week after the first dose of dual immunotherapy. The patient had significant clinical improvement, reduced proptosis, and serum alpha-fetoprotein levels. CONCLUSIONS Although orbital metastasis is a rare manifestation of HCC, physicians should recognize and consider aggressive investigations for early diagnosis, especially in patients with existing risk factors for HCC. Dual immunotherapy with durvalumab and tremelimumab in combination with radiotherapy can be considered a potential treatment option for managing advanced HCC with orbital metastasis.

Liver Resection Under Total Hepatic Vascular Exclusion with In Situ Hypothermic Isolated Hepatic Perfusion for Advanced Liver Tumors.

PURPOSE: Continuous dissection or simultaneous reconstruction of the hepatic vein (HV) and inferior vena cava (IVC) was achieved under total hepatic vascular exclusion (THVE) with in situ hypothermic isolated hepatic perfusion (HIHP) in two cases. CASE 1: The patient previously underwent liver resections with the right HV for colorectal liver metastasis (CRLM). This time, the CRLM had invaded the left HV and IVC, and five courses of FOLFILI plus ramucirumab were given, resulting in stable disease. Due to expected high HV pressure, liver parenchymal transection was started under THVE. Sub-segmentectomy with patch graft plasty of the IVC and reconstruction of the left HV using a jugular vein graft were performed under THVE and HIHP. This patient died at home 3 months after surgery; the cause of death was unknown. CASE 2: Hepatocellular carcinoma in the caudate lobe was in extensive contact with the roots of three main HVs and the IVC, and pressed the hepatocaval confluence, with high HV pressure expected. In addition, tumor thrombosis extended to both the main portal vein and the common bile duct, resulting in the inability to introduce chemotherapy. After tumor thrombectomy, liver parenchymal transection was started under THVE. Extended left hepatectomy with wedge resection, and primary suture of the right HV and IVC was performed under THVE and HIHP. Recurrence-free and overall survivals were 8 months (lung metastasis) and 31 months, respectively. CONCLUSIONS: In liver resection for liver tumors located in the hepatocaval confluence, THVE with HIHP is useful for ensuring the safety.

[Construction and Validation of Prediction Models of Risk Factors for Early Death in Patients With Metastatic Melanoma]. / è½¬ç§»æ€§é»‘è‰²ç´ ç˜¤æ‚£è€ æ—©æœŸæ­»äº¡é£Žé™©çš„é¢„æµ‹æ¨¡åž‹æž„å»ºåŠéªŒè¯.

Objective: To construct nomogram models to predict the risk factors for early death in patients with metastatic melanoma (MM). Methods: The study covered 2138 cases from the Surveillance, Epidemiology, and End Results Program (SEER) database and all these patients were diagnosed with MM between 2010 and 2015. Logistic regression was performed to identify independent risk factors affecting early death in MM patients. These risk factors were then used to construct nomograms of all-cause early death and cancer-specific early death. The efficacy of the model was assessed with receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). In addition, external validation of the model was performed with clinicopathologic data of 105 patients diagnosed with MM at Sichuan Cancer Hospital between January 2015 and January 2020. Results: According to the results of logistic regression, marital status, the primary site, N staging, surgery, chemotherapy, bone metastases, liver metastases, lung metastases, and brain metastases could be defined as independent predictive factors for early death. Based on these factors, 2 nomograms were plotted to predict the risks of all-cause early death and cancer-specific early death, respectively. For the models for all-cause and cancer-specific early death, the areas under the curve (AUCs) for the training group were 0.751 (95% confidence interval [CI]: 0.726-0.776) and 0.740 (95% CI: 0.714-0.765), respectively. The AUCs for the internal validation group were 0.759 (95% CI: 0.722-0.797) and 0.757 (95% CI: 0.718-0.780), respectively, while the AUCs for the external validation group were 0.750 (95% CI: 0.649-0.850) and 0.741 (95% CI: 0.644-0.838), respectively. The calibration curves showed high agreement between the predicted and the observed probabilities. DCA analysis indicated high clinical application value of the models. Conclusion: The nomogram models demonstrated good performance in predicting early death in MM patients and can be used to help clinical oncologists develop more individualized treatment strategies.

Simultaneous gastric, pancreatic, and renal metastasis from poorly differentiated hepatocellular carcinoma.

Common extrahepatic metastasis sites of hepatocellular carcinoma (HCC) are the lungs, adrenal glands, and bones. Herein, we report a rare case of metastatic gastric, pancreatic, and renal tumors from HCC simultaneously, and review the relevant literature. A 75-year-old woman presented with right hypochondralgia, appetite loss, and weight loss. Computed tomography revealed suspected metastatic liver, lung, and renal tumors. A blood test revealed a leukocyte count of 26,210/µL and a high inflammatory reaction. As sepsis was suspected, the patient was referred to our hospital. Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging revealed a hypovascular liver tumor that was suspected to be metastatic. Upper gastrointestinal endoscopy revealed two suspected metastatic gastric tumors. Liver and gastric tumor biopsies revealed poor carcinoma in both. The patient's condition gradually worsened and she died on day 8 of the illness. Based on autopsy findings, the patient was finally diagnosed with metastatic gastric and renal tumors originating from HCC. Additionally, a metastatic pancreatic tumor originating from the HCC was identified during autopsy. The pathological diagnosis of the pulmonary lesion was primary lung adenocarcinoma. In conclusion, HCC should be suspected in cases with multiple metastases of unknown primary lesions.

Spontaneous rupture of splenic hilar lymph node metastasis from hepatocellular carcinoma.

Spontaneous rupture of a primary hepatocellular carcinoma (HCC) is a frequently observed and fatal complication. However, the rupture of lymph node (LN) metastases from HCC is rare. A 79 year-old male with hepatitis B underwent three liver resections for HCC. Two years and 6 months after the last liver resection, enhanced computed tomography (CT) revealed a nodule with a diameter of 3 cm in the lower pole of the spleen. Splenic metastasis of HCC was suspected, and splenectomy was scheduled. During our hospital stay for a urinary tract infection before the scheduled operation, he complained of acute left-sided abdominal pain, and CT showed intra-abdominal hemorrhage due to rupture of the splenic tumor. Emergency splenectomy was performed, and the postoperative course was uneventful. Histopathological examination revealed a poorly differentiated HCC in the lower splenic pole lesion, which contained LN structures. The ruptured lesion was diagnosed as splenic hilar LN metastasis of HCC. Although laparoscopic partial liver resection was performed for intrahepatic recurrence, and atezolizumab plus bevacizumab therapy was administered for peritoneal metastases, the patient was alive 25 months after the splenectomy. Our case suggests that emergency surgery for LN metastatic rupture can achieve hemostasis and lead to improved survival outcomes.

Pituitary metastasis arising from hepatocellular carcinoma: a case report and update of the literature.

Hepatocellular carcinoma (HCC) is the sixth most common neoplasia and the third leading cause of cancer-associated deaths worldwide. Most cases arise in patients with cirrhosis, and early detection through periodic screening can make it potentially curable. The presence of extrahepatic metastases (EHM) affects treatment decisions and curability. The lungs are the most common site for EHM, followed by lymph nodes, bones, and the adrenal glands. Interestingly, approximately only 15 cases of HCC metastasizing to the pituitary gland have been reported so far.The most common symptoms of pituitary metastasis (PM) arising from HCC are nerve palsies affecting the third, fourth, and sixth cranial nerves. Other symptoms, such as diabetes insipidus or pituitary insufficiencies, are present in a minority of cases. Detecting PM is difficult given its rarity. Gold-standard treatments for these patients have not yet been established, but the prognosis is dismal, with a median overall survival of only 4.5 months. In this paper, we present an interesting case of PM as the first symptom of an HCC in a 75-year-old female. We also present an overview of all cases reported to date with emphasis on symptom presentation and survival after diagnosis.Given the improvement of systemic therapy, more cases are diagnosed in both oligometastatic and palliative conditions. Therefore, better approaches and treatment modalities for extrahepatic metastases due to HCC should be defined.

Metastatic lung tumor from hepatocellular carcinoma with tumor thrombus invasion in the pulmonary vein: a case report.

BACKGROUND: Metastatic lung tumor with a tumor thrombus in the peripheral pulmonary vein is very rare. We present a case of a metastatic lung tumor from hepatocellular carcinoma (HCC) with tumor thrombus invasion in the pulmonary vein that was diagnosed preoperatively and underwent complete resection by segmentectomy. CASE PRESENTATION: A 77-year-old man underwent laparoscopic lateral segment hepatectomy for HCC eight years ago. Protein induced by vitamin K absence or antagonist-II remained elevated from two years ago. Contrast-enhanced chest computed-tomography (CT) showed a 27 mm nodule in the right apical segment (S1). He was pathologically diagnosed with a metastatic lung tumor from HCC via transbronchoscopic biopsy. We planned to perform right S1 segmentectomy. Before surgery, contrast-enhanced CT in the pulmonary vessels phase for three-dimensional reconstruction showed that the tumor extended into the adjusting peripheral pulmonary vein, and we diagnosed tumor thrombus invasion in V1a. The surgery was conducted under 3-port video-assisted thoracic surgery. First, V1 was ligated and cut. A1 and B1 were cut. The intersegmental plane was cut with mechanical staplers. Pathological examination revealed moderately-differentiated metastatic HCC with tumor thrombus invasions in many pulmonary veins, including V1a. No additional postoperative treatments were performed. CONCLUSIONS: As malignant tumors tend to develop a tumor thrombus in the primary tumor, it might be necessary to perform contrast-enhanced CT in the pulmonary vessel phase to check for a tumor thrombus before the operation for metastatic lung tumors.

Repeated surgery for hemorrhagic brain metastases from hepatocellular carcinoma: palliation or effective part of a multimodal treatment? A case-based approach.

Brain metastases from hepatocellular carcinoma (HCCBM) are encountered very rarely in clinical practice, especially in western countries. Only a minority of patients undergoes resective surgery, as clinical picture is usually complex and presentation is often catastrophic with intra-cerebral hemorrhage (ICH). Neurosurgical intervention can be not only life-saving but may also alleviate significantly the burden of symptoms. We present the case of a patient with six metachronous hemorrhagic HCCBM in which emergent surgery extended survival by 9 months, of which seven spent in near-normal life quality, stressing the role of neurosurgery in the evaluation of HCCBM patients.

LncRNA CEBPA-DT promotes liver cancer metastasis through DDR2/ß-catenin activation via interacting with hnRNPC.

BACKGROUND: Hepatocellular carcinoma (HCC) is the world's third leading cause of cancer-related death; due to the fast growth and high prevalence of tumor recurrence, the prognosis of HCC patients remains dismal. Long non-coding RNA CEBPA-DT, a divergent transcript of the CCAAT Enhancer Binding Protein Alpha (CEBPA) gene, has been shown to participate in multiple tumor progression. However, no research has established its cancer-promoting mechanism in HCC yet. METHODS: CEBPA-DT was identified in human HCC tissues through RNA sequencing. The expression level of CEBPA-DT was assessed by quantitative real-time PCR. The biological effects of CEBPA-DT were evaluated in vitro and in vivo through gain or loss of function experiments. RNA fluorescence in situ hybridization (FISH), RNA immunoprecipitation (RIP) and RNA pull-down assays were applied to investigate the downstream target of CEBPA-DT. Immunofluorescence, subcellular protein fractionation, western blot, and co-immunoprecipitation were performed to analyze the subcellular location of ß-catenin and its interaction with Discoidin domain-containing receptor 2 (DDR2). RESULTS: CEBPA-DT was upregulated in human HCC tissues with postoperative distant metastasis and intimately related to the worse prognosis of HCC patients. Silencing of CEBPA-DT inhibited the growth, migration and invasion of hepatoma cells in vitro and in vivo, while enhancement of CEBPA-DT played a contrasting role. Mechanistic investigations demonstrated that CEBPA-DT could bind to heterogeneous nuclear ribonucleoprotein C (hnRNPC), which facilitated cytoplasmic translocation of hnRNPC, enhanced the interaction between hnRNPC and DDR2 mRNA, subsequently promoted the expression of DDR2. Meanwhile, CEBPA-DT induced epithelial-mesenchymal transition (EMT) process through upregulation of Snail1 via facilitating nuclear translocation of ß-catenin. Using DDR2 inhibitor, we revealed that the CEBPA-DT induced the interaction between DDR2 and ß-catenin, thus promoting the nuclear translocation of ß-catenin to activate transcription of Snail1, contributing to EMT and HCC metastasis. CONCLUSIONS: Our results suggested that CEBPA-DT promoted HCC metastasis through DDR2/ß-catenin mediated activation of Snail1 via interaction with hnRNPC, indicating that the CEBPA-DT-hnRNPC-DDR2/ß-catenin axis may be used as a potential therapeutic target for HCC treatment.

Short-term prognosis for hepatocellular carcinoma patients with lung metastasis: A retrospective cohort study based on the SEER database.

Our study aimed to develop a prediction model to predict the short-term mortality of hepatocellular carcinoma (HCC) patients with lung metastasis. The retrospective data of HCC patients with lung metastasis was from the Surveillance, Epidemiology, and End Results registration database between 2010 and 2015. 1905 patients were randomly divided into training set (n = 1333) and validation set (n = 572). There were 1092 patients extracted from the Surveillance, Epidemiology, and End Results database 2015 to 2019 as the validation set. The variable importance was calculated to screen predictors. The constructed prediction models of logistic regression, random forest, broad learning system, deep neural network, support vector machine, and naïve Bayes were compared through the predictive performance. The mortality of HCC patients with lung metastasis was 51.65% within 1 month. The screened prognostic factors (age, N stage, T stage, tumor size, surgery, grade, radiation, and chemotherapy) and gender were used to construct prediction models. The area under curve (0.853 vs. 0.771) of random forest model was more optimized than that of logistic regression model in the training set. But, there were no significant differences in testing and validation sets between random forest and logistic regression models. The value of area under curve in the logistic regression model was significantly higher than that of the broad learning system model (0.763 vs. 0.745), support vector machine model (0.763 vs. 0.689) in the validation set, and higher than that of the naïve Bayes model (0.775 vs. 0.744) in the testing model. We further chose the logistic regression prediction model and built the prognostic nomogram. We have developed a prediction model for predicting short-term mortality with 9 easily acquired predictors of HCC patients with lung metastasis, which performed well in the internal and external validation. It could assist clinicians to adjust treatment strategies in time to improve the prognosis.

A Rare Case of Metastatic Hepatocellular Carcinoma to the Hard Palate.

Extrahepatic metastasis of hepatocellular carcinoma (HCC) to the head and neck is unusual, especially the oral cavity/maxillofacial region. Metastatic HCC to the hard palate, however, is particularly rare. The most common site of HCC metastasis is the lung, followed by lymph nodes, bone, and adrenal gland. Importantly, oral cavity metastatic HCC may be misdiagnosed as a primary malignancy, such as a salivary gland carcinoma. In this article, we describe a young woman with metastatic HCC to the hard palate that was initially diagnosed as an acinic cell carcinoma.

Hemorrhagic Brain Metastasis as an Initial Presentation of Hepatocellular Carcinoma in a Patient With Alcohol-Related Liver Cirrhosis: A Case Report and Review of Literature.

Hepatocellular carcinoma (HCC) is the most common primary hepatic cancer. Although it usually presents as a liver mass, rarely HCC can have an initial presentation at an extrahepatic site before the diagnosis of the primary lesion in the liver. Even rarely was that brain metastasis as initial extrahepatic presentations. Furthermore, the initial presentation of HCC as brain metastases has been with most cases being secondary to hepatitis-related hepatoma. In this case report, we are presenting a rare and unusual case of hemorrhagic cerebral metastasis as an initial extrahepatic presentation of an alcohol-related hepatoma. Our case is the second case in the English literature that has been presented in such a way. Due to the uncommonness of presentation, there can be diagnostic dilemmas and delay in treatment. Therefore, a high level of suspicion is needed in the high-risk patients of HCC who present with unexplained or new neurological signs and symptoms. More exploration is warranted for clinical research and treatment guidelines for brain metastases of HCC to help improve survival and quality of life.