Primary hepatic neuroendocrine tumors (PHNETs) are an utterly rare subtype of neuroendocrine tumors (NETs) that arise from cells of the neuroendocrine system. Due to the rarity and lack of distinctive radiological features, diagnosis and management of this tumor are challenging. Herein, we report a case of PHNET in a 19-year-old previously healthy female patient whose diagnosis was confirmed by histopathology and immunohistochemistry. This case emphasizes the importance of considering PHNETs in the differential diagnosis of a hepatic mass, management of patients with this disease, and post-operative follow-up.

Primary hepatic neuroendocrine carcinoma (PHNEC) is a rare liver tumor, and there is no clear therapeutic recommendation for patients with advanced PHNEC. This study aims to compare the efficacy of platinum-based chemotherapy (etoposide combined with cisplatin/carboplatin, EP/EC) and transcatheter arterial chemoembolization (TACE) in patients with advanced PHNEC, and to evaluate the relevant prognostic factors.

The clinical data of 41 patients with advanced PHNEC from June 2014 to October 2019 were retrospectively reviewed.

At a median follow-up time of 13.9 months, the median overall survival (OS) was 14.8 months in the EP/EC group and 12.2 months in the TACE group (P = 0.040). The median progression-free survival (PFS) was 4.4 months and 2.7 months in the EP/EC group and the TACE group, respectively (P = 0.005). No significant differences in the overall response rate and disease control rate were observed between the EP/EC group and the TACE group (26.1% vs 11.1%, P = 0.429; 73.9% vs 44.4%, P = 0.055, respectively). A univariate analysis indicated that the Eastern Cooperative Oncology Group performance status (ECOG PS), Ki-67, tumor number, and treatment options were prognostic factors for OS. A multivariate analysis further showed that ECOG PS (P < 0.001), Ki-67 (P = 0.003), and treatment options (P = 0.022) were independent prognostic factors for OS.

Ki-67, ECOG PS, and treatment options were the independent prognostic factors for OS in patients with advanced PHNEC. EP/EC may be a better choice for patients with advanced PHNEC.

• chemotherapy
• hepatic neuroendocrine carcinoma
• prognosis
• transcatheter arterial chemoembolization

• Cystadenocarcinoma
• Liver neoplasms
• Mucinous
• Neurodendocrine tumors
• Neuroendocrine tumors

Neuroendocrine tumors usually originate from the neuroendocrine cells of gastrointestinal tract and their presence in the liver is mostly in the form of metastases. A primary neuroendocrine tumor in the liver concomitantly with hepatocellular carcinoma is an infrequent phenomenon. We present a 66-year-old woman with a remote history of breast cancer coming with postprandial fullness, later found to have multiple liver masses. After a thorough investigation, she was found to have a combined type of hepatocellular and primary neuroendocrine tumor of liver with pulmonary metastases. She was not a surgical candidate due to distant metastases. She was treated with chemotherapy, immunotherapy, and targeted therapies but continued to deteriorate clinically, and finally succumbed to her illness. The presence of this combined type of tumor in our patient is unique in many different ways: It is extremely rare, she did not have any risk factors for liver cancer, no genetic mutation till date could tie all these cancers (breast cancer, neuroendocrine tumor, and hepatocellular carcinoma) together, and not a lot of literatures/studies performed on this illness.

• breast cancer
• hepatocellular carcinoma
• primary neuroendocrine tumor of liver

• adult
• male
• asian - vietnamese
• viet nam
• liver
• endocrine-related cancer
• tumours and neoplasia
• gatroenterology
• oncology
• radiology/rheumatology
• novel diagnostic procedure
• june
• 2021

• Diagnosis
• Laparoscopic hepatectomy
• Liver neoplasms
• Primary hepatic neuroendocrine tumor

• HepG2 cells
• Proliferation
• Rosmarinic acid (RA)
• hepatocellular carcinoma (HCC)

• Antioxidants/pharmacology
• Apoptosis
• Carcinoma, Hepatocellular/drug therapy
• Carcinoma, Hepatocellular/metabolism
• Carcinoma, Hepatocellular/pathology
• Cell Movement
• Cell Proliferation
• Cinnamates/pharmacology
• Depsides/pharmacology
• Gene Expression Regulation, Neoplastic/drug effects
• Humans
• Liver Neoplasms/drug therapy
• Liver Neoplasms/metabolism
• Liver Neoplasms/pathology
• NF-kappa B/antagonists & inhibitors
• Phosphatidylinositol 3-Kinase/chemistry
• Proto-Oncogene Proteins c-akt/antagonists & inhibitors
• Signal Transduction
• Tumor Cells, Cultured
• Rosmarinic Acid

Primary hepatic neuroendocrine tumors (PHNETs), a group of neuroendocrine neoplasms, are extremely rare. There are only few case reports about PHNETs in the literature. The lack of large samples and multicenter research results in poor diagnostic and therapeutic approaches.

To discuss the clinical characteristics, diagnosis, and treatment of PHNETs and risk factors related to survival.

We retrospectively analyzed the clinical data, imaging features, immunohistochemistry data, and treatment efficacy of 40 patients who were pathologically diagnosed with PHNETs and admitted to The First Affiliated Hospital of Zhengzhou University from January 1, 2014 to November 15, 2019. Finally, survival analysis was performed to identify the risk factors for survival.

The main symptoms and signs included intermittent abdominal pain (19 patients, 47.5%) and bloating (8 patients, 20.0%). The positive rates of tested tumor markers were recorded as follows: Carbohydrate antigen 19-9 (CA19-9) (6 patients, 15.0%), CA72-4 (3 patients, 7.5%), carcinoembryonic antigen (7 patients, 17.5%), and alpha-fetoprotein (6 patients, 15.0%). Immunohistochemical staining results showed positivity for Syn in 38 (97.4%) of 39 patients, for chromogranin A in 17 (65.4%) of 26 patients, for CD56 in 35 (94.6%) of 37 patients, for AE1/AE3 in 28 (87.5%) of 32 patients, and for Ki-67 in all 40 (100.0%) patients. The overall survival rate was significantly related to the tumor grade, AE1/AE3, and Ki-67. No significant correlation was found between other parameters (age, gender, tumor number, tumor size, metastasis, and treatment) and overall survival.

Higher grade, negative AE1/AE3, and higher Ki-67 are associated with a worse survival rate. Kinds of treatment and other parameters have no significant influence on overall survival.

• Neuroendocrine tumors
• Primary hepatic neuroendocrine tumors
• Diagnosis
• Survival analysis
• Tumor grade
• Treatment

• Hepatic neuroendocrine neoplasms
• Neuroendocrine neoplasms
• Pancreatic neuroendocrine neoplasms
• Prognosis
• Survival

• Adult
• Aged
• Carcinoma, Neuroendocrine/mortality
• Carcinoma, Neuroendocrine/pathology
• Carcinoma, Neuroendocrine/therapy
• China/epidemiology
• Female
• Humans
• Liver Neoplasms/mortality
• Liver Neoplasms/pathology
• Liver Neoplasms/therapy
• Male
• Middle Aged
• Pancreatic Neoplasms/mortality
• Pancreatic Neoplasms/pathology
• Pancreatic Neoplasms/therapy
• Retrospective Studies
• Risk Assessment
• Risk Factors
• Time Factors
• Treatment Outcome

• Carcinoid tumor
• Chalazion
• Eyelid
• Histopathology
• Immunostaining
• Metastasis

EndMT has an important effect on metastasis and progression of tumor. This work will elucidate the effect of miR-494 on EndMT and development of HCC. Therefore, the differential miRNA expression among non-tumorous, para-tumorous and tumorous tissues was analyzed. Moreover, luciferase activities of SIRT3 3′UTR treated with miR-494 were determined. Then human hepatoma cell lines were dealt with mimics or inhibitors of miR-494, migration and proliferation ability were assessed. The expression of SIRT3 and markers of mesenchymal cell were analyzed. The influences of miR-494 on development of HCC through inducing EndMT by targeting SIRT3 and TGF-β/SMAD signaling pathways in hepatoma cell lines were investigated. Xenograft mice were used to explore the potential roles of miR-494 on EndMT and development of HCC in vivo. Our results showed that, compared with non-tumorous tissues, 17 miRNAs were upregulated and 3 miRNAs were down-regulated in tumor tissues. In tumor tissues, the miR-494 expression level was much more than the expression of para-tumorous and non-tumorous tissues. MiR-494 suppressed SIRT3 expression, additionally enhanced expression of mesenchymal cell markers, while exerted effects on cell proliferation and migration of hepatoma cell lines. Moreover, the antagomir of miR-494 could protect against development process in xenogarft murine model. In conclusions, our work demonstrated that miR-494 targeted to SIRT3, and was a crucial mediator of EndMT and development of HCC through regulating SIRT3/TGF-β/SMAD signaling pathway. It suggested that aim at SIRT3/TGF-β/SMAD signaling pathway through suppressing the miR-494 expression level, was a feasible therapy strategy for HCC.

• associating liver partition and portal vein ligation for staged hepatectomy
• primary hepatic neuroendocrine tumors
• surgery treatment

• Aged
• Female
• Hepatectomy/methods
• Humans
• Ligation/methods
• Liver/blood supply
• Liver/surgery
• Liver Neoplasms/surgery
• Neuroendocrine Tumors/surgery
• Portal Vein/surgery
• Treatment Outcome

Neuroendocrine tumors (NETs) of the gastrointestinal tract often spread to the liver, while primary hepatic NETs (PHNETs), first described by Edmondson in 1958, are very rare. The majority of existing reports regarding PHNETs have small sample sizes, and the clinicopathological characteristics and prognostic factors are still unclear. The aim of the present study was to analyze the clinicopathological features and explore the prognostic factors of PHNETs. From March 2012 to March 2017, 28 cases of PHNETs were retrospectively evaluated to analyze the clinicopathological features and explore the prognostic factors of PHNETs. The 28 PHNETs patients were males (n=15) and females (n=13) aged between 32 and 76 years (mean=53 years). Among them, 16 patients had clinical symptoms. The remaining 12 patients had no obvious clinical symptoms, only hepatoncus was observed during physical examination. Single-factor analysis showed that carbohydrate antigen 125 (CA125), alanine aminotransferase (ALT), aspartate aminotransferase (AST), hemoglobin (HB), Ki-67 positive index (PI), surgical treatment and pathological grading were correlated to PHNET prognosis (P<0.05); multifactor analysis revealed that Ki-67 PI was associated with the prognosis (P<0.05). Thus, the prognosis of PHNETs may be effectively predicted using the indexes of CA125, ALT, AST, HB, Ki-67 PI, pathological grading and surgical treatment. Pathological classification of grade 3, high expression of Ki-67 PI, abnormal elevation of CA125, abnormalities of ALT and AST, anemia and lack of radical operation indicated a poor prognosis. High expression of Ki-67 PI was an independent prognostic factor for PHNETs.

• liver neuroendocrine carcinoma
• liver neuroendocrine tumor
• primary
• prognosis

Primary hepatic neuroendocrine carcinoma (PHNEC) is extremely rare. The diagnosis of PHNEC remains challenging—partly due to its rarity, and partly due to its lack of unique clinical features. Available treatment options for PHNEC include surgical resection of the liver tumor(s), radiotherapy, liver transplant, transcatheter arterial chemoembolization (TACE), and administration of somatostatin analogues.

We report two male PHNEC cases and discuss the diagnosis and treatment options. Both cases presented with abdominal pain; case two also presented with symptoms of jaundice. The initial diagnosis for both cases was poorly differentiated grade 3 small-cell neuroendocrine carcinoma, based on imaging characteristics and the pathology of liver biopsies. Final diagnoses of PHNEC were arrived at by ruling out non-hepatic origins. Case one presented with a large tumor in the right liver lobe, and the patient was treated with TACE. Case two presented with tumors in both liver lobes, invasions into the left branch of hepatic portal vein, and metastasis in the hepatic hilar lymph node. This patient was ineligible for TACE and was allergic to the somatostatin analogue octreotide. This limited treatment options to supportive therapies such as albumin supplementation for liver protection. Patient one and two died at 61 and 109 days, respectively, following initial hospital admission.

We diagnosed both cases with poorly differentiated grade 3 small-cell PHNEC through imaging characteristics, immunohistochemical staining of liver biopsies, and examinations to eliminate non-hepatic origins. Neither TACE nor liver protection appeared to significantly extend survival time of the two patients, suggesting these treatments may be inadequate to improve survival of patients with poorly differentiated grade 3 small-cell PHNEC. The prognosis of poorly differentiated grade 3 small-cell PHNEC is poor due to limited and ineffective treatment options.

The online version of this article (10.1186/s12907-018-0070-7) contains supplementary material, which is available to authorized users.

• Immunohistochemical staining
• Liver biopsy
• Primary hepatic neuroendocrine carcinoma
• Somatostatin analogue
• Transcatheter arterial chemoembolization

Primary hepatic neuroendocrine tumors (PHNETs) are extremely rare and difficult to distinguish from other liver tumors, such as hepatocellular carcinoma (HCC) and cholangiocarcinoma, based on medical imaging findings. A 70-year-old man was referred for evaluation of liver mass incidentally discovered on abdominal computed tomography. The characteristic finding from dynamic liver magnetic resonance imaging led to a diagnosis of HCC. The patient underwent right hepatectomy. Histopathological and immunohistochemical examination revealed grade 2 neuroendocrine tumor. The postoperative 24-h urinary excretion of 5-hydroxy-indolacetic acid was within the normal range. Further imaging investigations were performed. No other lesions were found making probable the diagnosis of PHNET. This case shows that the diagnosis of PHNET is a medical challenge, requiring differentiation of PHNETs other hepatic masses and exclusion of occult primary neuroendocrine tumors. The diagnosis of PHNET can be ascertained after long term follow-up to exclude another primary origin.

• Primary hepatic neuroendocrine tumor
• Neuroendocrine tumor
• Liver
• Hepatocelluar carcinoma

• Glomus tumor
• differential diagnosis
• immunohistochemistry
• trachea

• Biomarkers, Tumor/analysis
• Glomus Tumor/pathology
• Humans
• Immunohistochemistry
• Male
• Middle Aged
• Tracheal Neoplasms/pathology