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Sambataro D, Bellavia S, Di Mattia P, Centonze D, Emmanuele C, Bonasera A, Caputo G, Quattrocchi AMO, Vinci E, Gebbia V, Valerio MR. Combined Neuroendocrine Carcinoma and Hepatocellular Carcinoma of the Liver: Systematic Literature Review Suggests Implementing Biological Characterization to Optimize Therapeutic Strategy. Cancers (Basel) 2025; 17:1074. [PMID: 40227579 PMCID: PMC11988019 DOI: 10.3390/cancers17071074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2025] [Revised: 03/11/2025] [Accepted: 03/19/2025] [Indexed: 04/15/2025] Open
Abstract
BACKGROUND Mixed neuroendocrine-non-neuroendocrine tumors (MINEN) of the liver are exceptionally rare, with limited data available regarding their clinical behavior, pathogenesis, and optimal management. The coexistence of hepatocellular carcinoma (HCC) and neuroendocrine carcinoma (NEC) within the liver presents diagnostic and therapeutic challenges. METHODS A systematic literature search was conducted on PubMed, identifying cases of primary mixed HCC and NEC in the liver. The search adhered to PRISMA guidelines, and relevant studies were critically analyzed. A total of 45 documented cases were reviewed, focusing on patient demographics, clinical characteristics, treatment strategies, and outcomes. RESULTS Most patients (90%) were male, with a median age of 66.5 years. Hepatitis B or C infection was present in 74% of cases, and liver cirrhosis was reported in 38%. The combined type was the most frequently observed histological pattern (65%). Treatment modalities varied, including transarterial chemoembolization (TACE), radiofrequency ablation (RFA), surgery, and systemic therapies. The median overall survival was 10 months, highlighting the aggressive nature of these tumors. CONCLUSIONS Given the rarity and poor prognosis of hepatic MINEN tumors, multidisciplinary management is essential. Advanced molecular profiling may offer insights into tumor biology and potential therapeutic targets. Future research should explore novel systemic therapies, including immune checkpoint inhibitors, to improve patient outcomes.
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Affiliation(s)
- Daniela Sambataro
- Medical Oncology Unit, Umberto I Hospital, 94100 Enna, Italy; (A.B.); (G.C.); (A.M.O.Q.); (E.V.)
- Department of Medicine and Surgery, Kore University, 94100 Enna, Italy; (P.D.M.); (V.G.)
| | - Sandro Bellavia
- Pathology Unit, Umberto I Hospital, 94100 Enna, Italy; (S.B.); (C.E.)
| | - Paolo Di Mattia
- Department of Medicine and Surgery, Kore University, 94100 Enna, Italy; (P.D.M.); (V.G.)
- Surgery Unit, Umberto I Hospital, 94100 Enna, Italy;
| | | | - Carmela Emmanuele
- Pathology Unit, Umberto I Hospital, 94100 Enna, Italy; (S.B.); (C.E.)
| | - Annalisa Bonasera
- Medical Oncology Unit, Umberto I Hospital, 94100 Enna, Italy; (A.B.); (G.C.); (A.M.O.Q.); (E.V.)
| | - Giuseppe Caputo
- Medical Oncology Unit, Umberto I Hospital, 94100 Enna, Italy; (A.B.); (G.C.); (A.M.O.Q.); (E.V.)
| | | | - Ernesto Vinci
- Medical Oncology Unit, Umberto I Hospital, 94100 Enna, Italy; (A.B.); (G.C.); (A.M.O.Q.); (E.V.)
| | - Vittorio Gebbia
- Department of Medicine and Surgery, Kore University, 94100 Enna, Italy; (P.D.M.); (V.G.)
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Gao X, Wang H, Niu Z, Liu M, Kong X, Sun H, Ma C, Zhu H, Lu J, Zhou X. Case report: mixed large-cell neuroendocrine and hepatocellular carcinoma of the liver. Front Oncol 2024; 13:1309798. [PMID: 38264742 PMCID: PMC10803416 DOI: 10.3389/fonc.2023.1309798] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2023] [Accepted: 12/18/2023] [Indexed: 01/25/2024] Open
Abstract
Background Cases of large-cell neuroendocrine carcinoma (NEC) concomitant hepatocellular carcinoma (HCC) are very rare. Based on the microscopic characteristics, mixed HCC-NEC tumors can be divided into collision type and combined type. We report a patient with both collision and combined type HCC-NEC tumor at the same time. Case presentation A 58-year-old man with hepatitis B and cirrhosis was found to have two masses in segment 5 and segment 8 of the liver, respectively. Preoperative imaging diagnosis was primary liver cancer. Indocyanine green retention test (ICG R15) <10% suggested that the patient can tolerate surgery. Partial hepatectomy was performed under the guidance of 3D reconstruction. Postoperative pathology showed that most of the tumors in S5 were large-cell neuroendocrine carcinoma (90%), and a small part were hepatocellular carcinoma (10%). The tumor in S8 of the liver was diagnosed as HCC combined with immunohistochemistry. After surgery, the patient underwent genetic testing, which indicated mutations in TP53 gene. The test of immune markers of the sample suggest that the patient may benefit little from immune checkpoint inhibitor therapy. The cisplatin and etoposide chemotherapy protocol to the patient following their surgery. Eight month later after the operation, Enhanced CT showed there was no recurrence or metastasis of the tumor. Conclusion The case at hand augments the understanding of HCC-NEC mixed tumors, offering pivotal insights into their precise diagnosis and treatment modalities. Furthermore, we document a favorable prognosis, marked by an absence of recurrence signs thus far-a rarity in comparable instances. This enlightenment stands to facilitate the handling of ensuing cases and enhance patient prognoses.
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Affiliation(s)
- Xin Gao
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital, Shandong University, Jinan, China
| | - Heng Wang
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital, Shandong University, Jinan, China
| | - Zheyu Niu
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital, Shandong First Medical University, Jinan, China
- Department of Clinical Research, Qilu Synva Pharmaceutical Co. Ltd., Dezhou, China
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Meng Liu
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital, Shandong First Medical University, Jinan, China
| | - Xiaohan Kong
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital, Shandong First Medical University, Jinan, China
| | - Hongrui Sun
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital, Shandong First Medical University, Jinan, China
| | - Chaoqun Ma
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital, Shandong First Medical University, Jinan, China
| | - Huaqiang Zhu
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital, Shandong First Medical University, Jinan, China
| | - Jun Lu
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital, Shandong University, Jinan, China
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital, Shandong First Medical University, Jinan, China
| | - Xu Zhou
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital, Shandong University, Jinan, China
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital, Shandong First Medical University, Jinan, China
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Liang B, Huang T, Kuang SL, Xie GY, Liu TQ, Chen YY. Surgery after combination therapy with a tyrosine kinase inhibitor and anti-PD-1 antibody in sarcomatoid hepatocellular carcinoma: case report and literature review. Front Oncol 2023; 13:1212013. [PMID: 37869099 PMCID: PMC10585252 DOI: 10.3389/fonc.2023.1212013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Accepted: 09/18/2023] [Indexed: 10/24/2023] Open
Abstract
Introduction Although surgery is the preferred treatment for sarcomatoid hepatocellular carcinoma (SHC), the prognosis remains considerably poor due to early postoperative recurrence and metastasis. Reports on surgery after combined treatment with a tyrosine kinase inhibitor and anti-programmed cell death (PD)-1 antibody are unavailable. Case presentation A 69-year-old male patient with SHC was admitted to our hospital for treatment of a liver tumor that was detected on ultrasonography. Abdominal computed tomography with triple-phase enhancement revealed a lesion in the right hepatic lobe that measured 86.0 mm × 75.0 mm × 71.0 mm. Biopsy revealed a pathological diagnosis of liver sarcoma or sarcomatoid carcinoma. The patient subsequently received transcatheter arterial chemo-embolization, as he did not consent to surgery. More than two months later, he received a combination of lenvatinib with camrelizumab, as computed tomography showed an increase in the lesion size (to 123.0 mm × 90.0 mm × 80.0 mm) and lateral growth posterior to the upper pole of the right kidney. Liver resection was performed after 6 months of systemic therapy; pathological examination confirmed a diagnosis of SHC and showed extensive necrosis of tumor cells. Combined treatment with lenvatinib and camrelizumab was continued for 6 months after surgery. The patient has survived for over 24 months after initial diagnosis and is currently tumor-free. Conclusion Combined systemic therapy with a tyrosine kinase inhibitor and anti-PD-1 antibody may represent a feasible treatment strategy for improving resectability in cases of unresectable SHC. The outcomes with this combination may also be explored in cases of resectable SHC that have a high-risk of recurrence; this may improve the therapeutic effect.
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Affiliation(s)
- Bin Liang
- Department of Hepatobiliary, Pancreatic and Spleen Surgery, Guangxi Academy of Medical Sciences, the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
| | - Tao Huang
- Department of Hepatobiliary, Pancreatic and Spleen Surgery, Guangxi Academy of Medical Sciences, the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
| | - Shao-Lei Kuang
- Department of Hepatobiliary, Pancreatic and Spleen Surgery, Guangxi Academy of Medical Sciences, the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
| | - Guang-Yuan Xie
- Department of Hepatobiliary, Pancreatic and Spleen Surgery, Guangxi Academy of Medical Sciences, the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
| | - Tian-Qi Liu
- Department of General Surgery, the Jiangbin Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
| | - Yuan-Yuan Chen
- Department of Hepatobiliary, Pancreatic and Spleen Surgery, Guangxi Academy of Medical Sciences, the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
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Spârchez Z, Crăciun R, Nenu I, Mocan LP, Spârchez M, Mocan T. Refining Liver Biopsy in Hepatocellular Carcinoma: An In-Depth Exploration of Shifting Diagnostic and Therapeutic Applications. Biomedicines 2023; 11:2324. [PMID: 37626820 PMCID: PMC10452389 DOI: 10.3390/biomedicines11082324] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Revised: 08/17/2023] [Accepted: 08/19/2023] [Indexed: 08/27/2023] Open
Abstract
The field of hepatocellular carcinoma (HCC) has faced significant change on multiple levels in the past few years. The increasing emphasis on the various HCC phenotypes and the emergence of novel, specific therapies have slowly paved the way for a personalized approach to primary liver cancer. In this light, the role of percutaneous liver biopsy of focal lesions has shifted from a purely confirmatory method to a technique capable of providing an in-depth characterization of any nodule. Cancer subtype, gene expression, the mutational profile, and tissue biomarkers might soon become widely available through biopsy. However, indications, expectations, and techniques might suffer changes as the aim of the biopsy evolves from providing minimal proof of the disease to high-quality specimens for extensive analysis. Consequently, a revamped position of tissue biopsy is expected in HCC, following the reign of non-invasive imaging-only diagnosis. Moreover, given the advances in techniques that have recently reached the spotlight, such as liquid biopsy, concomitant use of all the available methods might gather just enough data to improve therapy selection and, ultimately, outcomes. The current review aims to discuss the changing role of liver biopsy and provide an evidence-based rationale for its use in the era of precision medicine in HCC.
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Affiliation(s)
- Zeno Spârchez
- Department of Gastroenterology, “Prof. Dr. O. Fodor” Regional Institute of Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania; (Z.S.); (I.N.); (T.M.)
- Department of Internal Medicine, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400162 Cluj-Napoca, Romania
| | - Rareș Crăciun
- Department of Gastroenterology, “Prof. Dr. O. Fodor” Regional Institute of Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania; (Z.S.); (I.N.); (T.M.)
- Department of Internal Medicine, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400162 Cluj-Napoca, Romania
| | - Iuliana Nenu
- Department of Gastroenterology, “Prof. Dr. O. Fodor” Regional Institute of Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania; (Z.S.); (I.N.); (T.M.)
- Department of Physiology, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania
| | - Lavinia Patricia Mocan
- Department of Histology, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania;
| | - Mihaela Spârchez
- 2nd Pediatric Department, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400124 Cluj-Napoca, Romania;
| | - Tudor Mocan
- Department of Gastroenterology, “Prof. Dr. O. Fodor” Regional Institute of Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania; (Z.S.); (I.N.); (T.M.)
- UBBMed Department, Babeș-Bolyai University, 400349 Cluj-Napoca, Romania
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Ahmed Z, Divatia MK, Crumley S, Victor DW, Kodali S. Combined Hepatocellular Neuroendocrine Carcinoma: A Rare Tumor. ACG Case Rep J 2023; 10:e00931. [PMID: 37434660 PMCID: PMC10332823 DOI: 10.14309/crj.0000000000000931] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2022] [Accepted: 11/07/2022] [Indexed: 07/13/2023] Open
Abstract
Neuroendocrine tumors originate from neuroendocrine cells primarily located in the gastrointestinal tract. These tumors often metastasize to the liver. Primary hepatic neuroendocrine carcinomas are uncommon, and combined hepatocellular neuroendocrine carcinomas are exceedingly rare. There is a lack of data on the management of these rare tumors. Most cases have very poor prognosis secondary to aggressive behavior of the neuroendocrine tumor component. It is important for clinicians to be aware of this rare carcinoma to allow for early diagnosis and optimize potential treatment options.
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Affiliation(s)
- Zunirah Ahmed
- Division of Gastroenterology and Hepatology, Houston Methodist, Houston, TX
| | - Mukul K. Divatia
- Department of Pathology and Genomic Medicine, Houston Methodist, Houston, TX
| | - Suzanne Crumley
- Department of Pathology and Genomic Medicine, Houston Methodist, Houston, TX
| | - David W. Victor
- Division of Gastroenterology and Hepatology, Houston Methodist, Houston, TX
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston Methodist Hospital, TX
| | - Sudha Kodali
- Division of Gastroenterology and Hepatology, Houston Methodist, Houston, TX
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston Methodist Hospital, TX
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Mixed Primary Hepatocellular Carcinoma and Hepatic Neuroendocrine Carcinoma: Case Report and Literature Review. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:medicina59020418. [PMID: 36837619 PMCID: PMC9959776 DOI: 10.3390/medicina59020418] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Revised: 02/15/2023] [Accepted: 02/17/2023] [Indexed: 02/23/2023]
Abstract
Mixed hepatocellular carcinoma with neuroendocrine carcinoma (HCC-NEC) is extremely rare, comprising about 0.46% of primary hepatic tumors. A 63-year-old man who was a chronic alcoholic presented with a nine-centimeter-sized hepatic mass. His serum alpha-fetoprotein and protein induced by vitamin K antagonist-II levels were 22,815 ng/mL and 183 mAU/mL, respectively. The patient underwent a right hemihepatectomy, including the middle hepatic vein. The tumor consisted of poorly differentiated HCC (20%) and large- and small-cell-type NEC (80%) components as per the pathological examination. Immunohistochemically chromogranin and synaptophysin were positive in the areas of NEC and negative in the areas of HCC. Adjuvant chemotherapy with a combination of cisplatin and etoposide was administered after surgery. At postoperative 5 months, the patient complained of right flank pain, and CT showed a new mass measuring 7.3 cm in the right adrenal gland. Postoperatively, after 6.5 months, more recurred masses were noted on the posterior aspect of the right kidney and both lungs. Although the regimen was changed from etoposide to irinotecan, additional recurred masses were developed in the liver, lung, and brain. He passed away 12 months after the surgery. After reviewing and analyzing previous literature, the 1 and 2 year overall survival rates are 57.3 and 43.6%, respectively, and the 1 and 2 year disease-free survival rates are 36.2 and 29.0%, respectively. Mixed HCC-NEC is a very rare tumor, and the surgical outcome is poor.
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Jeng KS, Huang CC, Chung CS, Chang CF. Liver collision tumor of primary hepatocellular carcinoma and neuroendocrine carcinoma: A rare case report. World J Clin Cases 2022; 10:13129-13137. [PMID: 36569002 PMCID: PMC9782927 DOI: 10.12998/wjcc.v10.i35.13129] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2022] [Revised: 11/08/2022] [Accepted: 11/22/2022] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) can occasionally develop with other non-HCC cell types, either in a combined type or collision type. A collision tumor is defined as two histopathologically distinct tumors of the same organ lacking a clear transition zone. Hepatic collision tumors are rare. Among them, “hepatocellular carcinoma-hepatic neuroendocrine carcinoma” (HCC-NEC) collision tumors are especially rare and information about them is rarely published.
CASE SUMMARY A 48-year-old man with typical findings of HCC underwent consecutive therapies, including radiofrequency ablation and embolization prior to resection. Diagnosis of the HCC-NEC collision tumor in the right liver and another HCC in the left liver was established following surgical resection. The patient displayed NEC metastasis following resection and succumbed to septicemia after 2 more rounds of chemotherapy. To our knowledge, this is the 25th reported case of mixed HCC-NEC tumor. The rarity of HCC-NEC collision tumors and the absence of diagnostic criteria make it difficult to differentiate this condition from simple liver tumors, especially in patients with chronic liver disease.
CONCLUSION Our case highlights the difficulty in accurately diagnosing HCC-NEC in the absence of histological evidence. The prognosis is poor for this condition, although ultrasound-guided liver biopsy can be helpful to establish a prompt diagnosis. Further accumulation of such cases could help establish an accurate diagnosis earlier. Early discovery of NEC may allow for better treatment strategies and better prognoses.
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Affiliation(s)
- Kuo-Shyang Jeng
- Department of General Surgery, Far Eastern Memorial Hospital, New Taipei 220, Taiwan
| | - Chun-Chieh Huang
- Department of Radiology, Far Eastern Memorial Hospital, New Taipei 220, Taiwan
| | - Chen-Shuan Chung
- Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei 220, Taiwan
| | - Chiung-Fang Chang
- Department of Medical Research, Far Eastern Memorial Hospital, New Taipei 220, Taiwan
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Zhang X, Yang H, Xin Y, Yang Y, Lu H, Zhou X. Complete Response After Pre-Operative Transcatheter Arterial Chemoembolization for Unresectable Primary Hepatic Neuroendocrine Tumour: A Case Report and Literature Review. Front Oncol 2022; 12:893403. [PMID: 35692743 PMCID: PMC9174540 DOI: 10.3389/fonc.2022.893403] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Accepted: 04/26/2022] [Indexed: 11/13/2022] Open
Abstract
Background Primary hepatic neuroendocrine tumours (PHNET) are extremely rare. Currently, no evidence-based guidelines are available for PHNET treatment, especially for unresectable tumours. Case Presentation We present the case of a 43-year-old man who was admitted to our hospital with complaints of backache for more than 1 month. The imaging examination showed a 5.5×5.3 cm lesion in the liver and no extrahepatic lesions, which was confirmed as a grade 2 PHNET by the pathological results and exclusion of non-hepatic origins. A multidisciplinary team (MDT) consultation revealed that the lesion was an unresectable primary hepatic neuroendocrine tumour (uPHNET) but could be potentially treated by conversion surgery. The patient was initially administered four cycles of chemotherapy with temozolomide, 5-fluorouracil, and ondansetron, and was evaluated as stable disease (SD) according to the Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1). Because of the limited clinical benefit of chemotherapy, the patient subsequently underwent transcatheter arterial chemoembolisation (TACE) treatment, which reduced the tumour size and converted uPHNET to resectable tumours. A complete response (CR) was achieved after surgery, and the patient has been disease-free. Conclusions This case was reported by a patient with uPHNET who benefited from the pre-operative TACE, providing a potentially effective management strategy for refractory tumours.
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Affiliation(s)
- Xinyuan Zhang
- Department of Interventional Therapy, National Cancer Centre/National Clinical Research Centre for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Huiru Yang
- Department of Pathology, National Cancer Centre/National Clinical Research Centre for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yujing Xin
- Department of Interventional Therapy, National Cancer Centre/National Clinical Research Centre for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yi Yang
- Department of Interventional Therapy, National Cancer Centre/National Clinical Research Centre for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Haizhen Lu
- Department of Pathology, National Cancer Centre/National Clinical Research Centre for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiang Zhou
- Department of Interventional Therapy, National Cancer Centre/National Clinical Research Centre for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Khanam R, Pachika PS, Arya P, Bierenbaum J, Kane K, Saha P. "A Tale of 2 Demons"-Concomitant Presence of Hepatocellular Carcinoma and Primary Neuroendocrine Tumor of Liver: A Case Report and Review of Literatures. J Investig Med High Impact Case Rep 2021; 9:23247096211043397. [PMID: 34472368 PMCID: PMC8419549 DOI: 10.1177/23247096211043397] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
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.
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Affiliation(s)
| | | | - Payam Arya
- University of Pittsburgh Medical Center, PA, USA
| | | | - Kevin Kane
- UPMC Hillman Cancer Center, McKeesport, PA, USA
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Wang H, Yang D, Wu Z, Luo Y, Ling W. Contrast-Enhanced Ultrasound Findings of Hepatocellular Carcinoma With Neuroendocrine Carcinoma: A Case Report. Front Med (Lausanne) 2021; 8:602346. [PMID: 34485317 PMCID: PMC8415301 DOI: 10.3389/fmed.2021.602346] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Accepted: 07/13/2021] [Indexed: 02/05/2023] Open
Abstract
Hepatocellular carcinoma (HCC) with the concurrent occurrence of primary hepatic neuroendocrine carcinoma (NEC) of the liver is extremely rare. Preoperative diagnosis of HCC combined with NEC is very difficult. Here, we presented a case report of HCC combined with NEC. A 33-year-old male was admitted to our hospital due to focal liver lesion. To further the diagnosis, he received laboratory tests, conventional ultrasound, contrast-enhanced ultrasound (CEUS), and magnetic resonance imaging (MRI). Grayscale ultrasound showed a hypoechoic nodule with peripheral hypoechoic halo and central small patches of anechoic area in the hepatic segment VI, and the liver background was cirrhosis. In the CEUS, the solid component of the nodule was rapidly homogeneous hyper-enhancement in the arterial phase. Then, the enhancement of the nodule was washed out slowly and gradually; the nodule presented heterogeneously mild enhancement in the portal phase, and slight hypo-enhancement was showed in the late phase. The hypo-enhanced area was mainly located in the surrounding space. Meanwhile, there was a small piece of non-enhanced area within the lesion center in the whole three-phase imaging. MRI showed a lobular contoured mass in segment VI. The patient underwent middle liver resection, splenectomy, and cholecystectomy. The pathological diagnosis was a HCC with NEC. At the time of the preparation of this manuscript, the patient has been alive without recurrence or distant metastases for 6 months since the surgery. We mainly focus on the ultrasound imaging characteristics, especially its enhancement manifestations on CEUS. In this report, since this article is a case report, which is based on the clinical information of the patient and does not involve the patient's privacy, informed consent is not necessary. In addition, the patient agreed to publish the case. To the best of our knowledge, this report is the first to describe the CEUS patterns of the HCC combined with NEC. Herein, we report a case that provides novel insights that will improve clinicians' awareness of the clinical and ultrasound manifestations of this mixed tumor, resulting in improved diagnosis, treatment, and outcomes.
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Affiliation(s)
- Hong Wang
- Department of Ultrasound, West China Hospital of Sichuan University, Chengdu, China
| | - Dan Yang
- Department of Ultrasound, West China Hospital of Sichuan University, Chengdu, China
| | - Zhenru Wu
- Key Laboratory of Transplantation Engineering and Transplantation Immune, The Ministry of Health, West China Hospital of Sichuan University, Chengdu, China
- Laboratory of Pathology, West China Hospital of Sichuan University, Chengdu, China
| | - Yan Luo
- Department of Ultrasound, West China Hospital of Sichuan University, Chengdu, China
| | - Wenwu Ling
- Department of Ultrasound, West China Hospital of Sichuan University, Chengdu, China
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11
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Lan J, Guo D, Qin X, Chen B, Liu Q. Mixed Neuroendocrine Carcinoma and Hepatocellular Carcinoma: A Case Report and Literature Review. Front Surg 2021; 8:678853. [PMID: 34336917 PMCID: PMC8316597 DOI: 10.3389/fsurg.2021.678853] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Accepted: 06/14/2021] [Indexed: 12/19/2022] Open
Abstract
Background: Neuroendocrine tumors are heterogeneous malignancies that originate from the neuroendocrine system. Previous studies show that this cancer type mainly localizes in the gastrointestinal tract and often metastasizes to the liver. Primary liver neuroendocrine tumors are very rare and primary hepatic neuroendocrine tumors (PHNET) with concurrent hepatocellular carcinoma (HCC) are extremely rare. To the best of our knowledge, only few PHNET cases have been identified, making their diagnosis difficult. Here, we report the biggest ever reported and “deceiving” lesion of a mixed neuroendocrine-non-neuroendocrine neoplasm in the liver, aiming to raise awareness and improve treatment of the disease. Case Presentation: Here, we report a preoperative misdiagnosed case that presented with hepatocellular carcinoma clinical features and no extrahepatic tumors. Postoperative pathology confirmed that it was a mixed neuroendocrine-non-neuroendocrine neoplasm. The patient was then referred for etoposide and cisplatin-based chemotherapy. No disease recurrence was observed at the 6-month follow-up. Conclusion: We report a very rare and easily misdiagnosed case and we speculate that there were “undifferentiated cells” undergoing neuroendocrine and hepatocellular carcinoma differentiation, during which some hepatocellular carcinoma cells express neuroendocrine features. We recommend proper surgery and postoperative platinum-based chemotherapy in the management of this disease.
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Affiliation(s)
- Jianwei Lan
- Department of Hepatobiliary and Pancreatic Surgery, Research Center of Digestive Diseases, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Deliang Guo
- Department of Hepatobiliary and Pancreatic Surgery, Research Center of Digestive Diseases, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Xian Qin
- Department of Hepatobiliary and Pancreatic Surgery, Research Center of Digestive Diseases, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Baiyang Chen
- Department of General Surgery, Xiangyang Central Hospital, Affiliated of Hubei University of Arts and Science, Xiangyang, China
| | - Quanyan Liu
- Department of Hepatobiliary and Pancreatic Surgery, Research Center of Digestive Diseases, Zhongnan Hospital of Wuhan University, Wuhan, China.,Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China
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12
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Nakano A, Hirabayashi K, Yamamuro H, Mashiko T, Masuoka Y, Yamamoto S, Ozawa S, Nakagohri T. Combined primary hepatic neuroendocrine carcinoma and hepatocellular carcinoma: case report and literature review. World J Surg Oncol 2021; 19:78. [PMID: 33726764 PMCID: PMC7968236 DOI: 10.1186/s12957-021-02187-5] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2020] [Accepted: 03/04/2021] [Indexed: 12/14/2022] Open
Abstract
Background Hepatocellular carcinoma (HCC) can grow in a mosaic pattern, often combined with various non-hepatocellular cells. However, HCC combined with a neuroendocrine carcinoma (NEC) component is rarely reported, and its clinical features, origin, diagnosis, and behavior have not been established. In the literature, mixed HCC–NEC tumors are categorized as either collision type or combined type, depending on their microscopic features. Here, we report a patient with a combined-type HCC–NEC tumor. Case presentation An asymptomatic 84-year-old woman was found to have a solid mass in the right lobe of the liver. Laboratory and radiologic examinations showed typical findings of HCC, including arterial-phase enhancement, and portal- and delay-phase washout. She was treated by partial laparoscopic hepatectomy of segment 5. Pathological examination showed that the tumor was predominantly HCC, partly admixed with an NEC component. A transitional zone between the HCC and NEC tissues was also observed. The tumor was finally diagnosed as a combined-type primary mixed NEC–HCC tumor. After the preoperative diagnosis, the patient underwent somatostatin receptor scintigraphy to detect the primary NEC lesion, but no accumulation was found in any other part of her body. She has been free of recurrence for 9 months since the surgery. Conclusion Mixed HCC–NEC tumors are extremely rare, and correct diagnosis requires multidisciplinary collaboration. The accumulation of further cases is needed to help understand the exact pathology, diagnosis, and treatment of this disease.
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Affiliation(s)
- Akira Nakano
- Department of Digestive Surgery, Tokai University Hospital, Shimokasuya 143, Isehara, Kanagawa, 259-1143, Japan.
| | - Kenichi Hirabayashi
- Department of Pathology, Tokai University Hospital, Shimokasuya 143, Isehara, Kanagawa, 259-1143, Japan
| | - Hiroshi Yamamuro
- Department of Radiology, Tokai University Hospital, Shimokasuya 143, Isehara, Kanagawa, 259-1143, Japan
| | - Taro Mashiko
- Department of Digestive Surgery, Tokai University Hospital, Shimokasuya 143, Isehara, Kanagawa, 259-1143, Japan
| | - Yoshihito Masuoka
- Department of Digestive Surgery, Tokai University Hospital, Shimokasuya 143, Isehara, Kanagawa, 259-1143, Japan
| | - Seiichiro Yamamoto
- Department of Digestive Surgery, Tokai University Hospital, Shimokasuya 143, Isehara, Kanagawa, 259-1143, Japan
| | - Soji Ozawa
- Department of Digestive Surgery, Tokai University Hospital, Shimokasuya 143, Isehara, Kanagawa, 259-1143, Japan
| | - Toshio Nakagohri
- Department of Digestive Surgery, Tokai University Hospital, Shimokasuya 143, Isehara, Kanagawa, 259-1143, Japan
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13
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Mixed hepatocellular carcinoma-neuroendocrine carcinoma—A diagnostic and therapeutic challenge. CURRENT PROBLEMS IN CANCER: CASE REPORTS 2020. [DOI: 10.1016/j.cpccr.2020.100020] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
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14
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Mao JX, Teng F, Sun KY, Liu C, Ding GS, Guo WY. Two-in-one: A pooled analysis of primary hepatic neuroendocrine carcinoma combined/collided with hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int 2020; 19:399-403. [PMID: 32359724 DOI: 10.1016/j.hbpd.2020.03.012] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2019] [Accepted: 03/23/2020] [Indexed: 02/05/2023]
Affiliation(s)
- Jia-Xi Mao
- Department of Liver Surgery and Organ Transplantation, Changzheng Hospital, Navy Medical University, Shanghai 200003, China
| | - Fei Teng
- Department of Liver Surgery and Organ Transplantation, Changzheng Hospital, Navy Medical University, Shanghai 200003, China
| | - Ke-Yan Sun
- Department of Liver Surgery and Organ Transplantation, Changzheng Hospital, Navy Medical University, Shanghai 200003, China
| | - Cong Liu
- Department of Liver Surgery and Organ Transplantation, Changzheng Hospital, Navy Medical University, Shanghai 200003, China
| | - Guo-Shan Ding
- Department of Liver Surgery and Organ Transplantation, Changzheng Hospital, Navy Medical University, Shanghai 200003, China
| | - Wen-Yuan Guo
- Department of Liver Surgery and Organ Transplantation, Changzheng Hospital, Navy Medical University, Shanghai 200003, China.
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15
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Xin Q, Lv R, Lou C, Ma Z, Liu GQ, Zhang Q, Yu HB, Zhang CS. Primary hepatic neuroendocrine carcinoma coexisting with distal cholangiocarcinoma: A case report and review of the literature. Medicine (Baltimore) 2020; 99:e20854. [PMID: 32590784 PMCID: PMC7328923 DOI: 10.1097/md.0000000000020854] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
INTRODUCTION Although primary hepatic neuroendocrine carcinomas, whose prognostic mechanisms remain unclear, are rare, coexistence of neuroendocrine carcinomas and other tumors is rarer. In this report, we describe a unique case of coexistence between primary hepatic neuroendocrine carcinoma and a distal cholangiocarcinoma in the pancreas. PATIENT CONCERNS A 64-year-old woman with a history of diabetes, but none of hepatitis, was admitted to hospital because of intermittent epigastric distension and pain discomfort for more than 1 month aggravated 1 day. A contrast-enhanced computed tomography (CT) scan of the upper abdomen and abdominal magnetic resonance imaging (MRI) revealed a thickening of the bile duct wall in the middle and lower segment of common bile duct and the corresponding lumen is narrow and low-density tumors with ring enhancement (1.83 cm × 1.9 cm) in lobi hepatis dexte. DIAGNOSIS Primary neuroendocrine carcinoma of the liver was diagnosed to be coexisting with a distal cholangiocarcinoma, which had invaded the pancreas. Immunohistochemical examination revealed that the neoplastic cells strongly expressed chromogranin A, synaptophysin, and CD56 proteins. The tumor cells did not express HepPar-1, glypican-3, S-100, CK7, and CK19 in the liver tumor. A distal bile duct in pancreatic tissues shows the characteristics of typical bile duct carcinoma, as an invasion of carcinoma is also seen in the pancreatic tissues. Gastrointestinal endoscopy, chest and abdominal CT, abdominal MRI, and positron emission tomography (PET)-CT were used to exclude metastatic neuroendocrine tumors of the liver. INTERVENTIONS Resection of the pancreas-duodenum, the right anterior lobe of the liver, and regional lymph nodes was performed in patients. OUTCOMES The patient had survived for 5 months after the operation. CONCLUSION A unique case of a coexistence of primary hepatic neuroendocrine carcinoma and a distal cholangiocarcinoma, which had invaded the pancreas. No treatment guidelines are established for the treatment of the unique case.
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Affiliation(s)
- Qi Xin
- Department of Pathology, Third Central Hospital of Tianjin, Tianjin Third Central Hospital affiliated to Nankai University, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases
- Tianjin Key Laboratory of Brain Science and Neural Engineering, Academy of Medical Engineering and Translational Medicine, Tianjin University
| | | | - Cheng Lou
- Department of Hepatobiliary Surgery, Tianjin third central hospital, Tianjin Third Central Hospital affiliated to Nankai University, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases
| | - Zhe Ma
- Department of Pathology, Third Central Hospital of Tianjin, Tianjin Third Central Hospital affiliated to Nankai University, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases
| | - Gui-Qiu Liu
- Department of Pathology, Third Central Hospital of Tianjin, Tianjin Third Central Hospital affiliated to Nankai University, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases
| | - Qin Zhang
- Department of Pathology, Third Central Hospital of Tianjin, Tianjin Third Central Hospital affiliated to Nankai University, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases
| | - Hai-Bo Yu
- Kidney Disease and Blood Purification Treatment Department, the Second Hospital of Tianjin Medical University, Tianjin, China
| | - Chuan-Shan Zhang
- Department of Pathology, Third Central Hospital of Tianjin, Tianjin Third Central Hospital affiliated to Nankai University, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases
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16
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Molecular and histological correlations in liver cancer. J Hepatol 2019; 71:616-630. [PMID: 31195064 DOI: 10.1016/j.jhep.2019.06.001] [Citation(s) in RCA: 353] [Impact Index Per Article: 58.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2019] [Revised: 05/22/2019] [Accepted: 06/01/2019] [Indexed: 02/07/2023]
Abstract
Hepatocellular carcinoma (HCC) is a highly heterogeneous cancer, both at the molecular and histological level. High-throughput sequencing and gene expression profiling have identified distinct transcriptomic subclasses and numerous recurrent genetic alterations; several HCC subtypes characterised by histological features have also been identified. HCC phenotype appears to be closely related to particular gene mutations, tumour subgroups and/or oncogenic pathways. Non-proliferative tumours display a well-differentiated phenotype. Among this molecular subgroup, CTNNB1-mutated HCCs constitute a homogeneous subtype, exhibiting cholestasis and microtrabecular and pseudoglandular architectural patterns. Another non-proliferative subtype has a gene expression pattern similar to that of mature hepatocytes (G4) and displays a steatohepatitic phenotype. In contrast, proliferative HCCs are most often poorly differentiated, and notably include tumours with progenitor features. A novel morphological variant of proliferative HCC - designated "macrotrabecular-massive" - was recently shown to be associated with angiogenesis activation and poor prognosis. Altogether, these findings may help to translate our knowledge of HCC biology into clinical practice, resulting in improved precision medicine for patients with this highly aggressive malignancy. This manuscript reviews the most recent data in this exciting field, discussing future directions and challenges.
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17
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Low SK, Giannis D, Bahaie NS, Trong BLH, Moris D, Huy NT. Competing Mortality in Patients With Neuroendocrine Tumors. Am J Clin Oncol 2019; 42:668-674. [PMID: 31343423 DOI: 10.1097/coc.0000000000000575] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
OBJECTIVES Patients with neuroendocrine tumors (NETs) are at increased risk of mortality from competing causes in light of the improvement in overall survival over recent decades. The purpose of this study was to explore the competing causes of deaths and the risk factors associated with competing mortality. MATERIALS AND METHODS The Surveillance, Epidemiology, and End Results database was used to identify patients diagnosed with NETs between 1973 and 2015. Risk of competing mortality was estimated by the standardized mortality ratios (SMRs) and by using the Fine and Gray multivariate regression model. RESULTS Of the 29,981 NET patients, 42.5% of the deaths that occurred during follow-up were attributed to competing causes (83.9% from noncancer causes and 16.1% from second primary neoplasms). Overall SMR of competing mortality was 2.50 (95% confidence interval [CI]: 2.43-2.56). The SMR of noncancer causes was 2.65 (95% CI: 2.58-2.73), with the highest risk present within the first year of diagnosis. The SMR of second primary neoplasms was 1.91 (95% CI: 1.79-2.04), with the highest risk observed after 10-year postdiagnosis. A drastic rise in competing mortality was observed in the last decade between 2005 and 2015. Advanced age, black race, small intestinal and gastric NETs, and surgery were significantly associated with competing mortality. Female, pancreatic and recto-anal NETs, distant and regional spread, chemotherapy and radiotherapy were significantly associated with lower competing mortality. CONCLUSIONS Competing mortality plays an increasingly significant role over the years and may hamper efforts made to improve survival outcomes in NET patients.
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Affiliation(s)
- Soon Khai Low
- Faculty of Health and Medical Sciences, School of Medicine, Taylor's University, Selangor, Malaysia
- Online Research Club, Nagasaki, Japan
| | - Dimitrios Giannis
- Online Research Club, Nagasaki, Japan
- Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece
| | - Nourelhoda Sami Bahaie
- Online Research Club, Nagasaki, Japan
- Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Bao Long Hoang Trong
- Online Research Club, Nagasaki, Japan
- Faculty of Medicine, Pham Ngoc Thach University of Medicine
| | | | - Nguyen Tien Huy
- Evidence Based Medicine Research Group
- Faculty of Applied Sciences, Ton Duc Thang University, Ho Chi Minh City, Vietnam
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18
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Abstract
Many advances have developed in the pathology of liver tumors in the recent decade. Examples of these advances include the use of glutamine synthetase in the diagnosis of focal nodular hyperplasia, subtyping of hepatocellular adenomas using molecular and immunohistochemical methods, the unraveling of the fusion transcript between the DNAJB1 gene and the PRKACA gene in fibrolamellar carcinoma, and the more unified classification and terminology in intrahepatic bile duct tumors and their precursor lesions. Nevertheless, challenges still remain, e.g., the differential diagnosis between well-differentiated hepatocellular carcinoma and hepatocellular adenoma; distinction among poorly differentiated hepatocellular carcinoma, cholangiocarcinoma and metastatic neoplasm; terminology of the combined hepatocellular carcinoma-cholangiocarcinoma, etc. This review aims to address updates in the pathologic diagnosis and clinical relevance of tumors of the liver and intrahepatic bile ducts in adults and their differential diagnosis and diagnostic pitfalls.
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19
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Yılmaz DB, Bayramoğlu Z, Ünay G, Ayık E, Başsorgun Cİ, Elpek GÖ. Incidental Collision Tumor of Hepatocellular Carcinoma and Neuroendocrine Carcinoma. J Clin Transl Hepatol 2018; 6:339-344. [PMID: 30271748 PMCID: PMC6160311 DOI: 10.14218/jcth.2017.00076] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2017] [Revised: 04/03/2018] [Accepted: 04/06/2018] [Indexed: 02/05/2023] Open
Abstract
The composite tumors of the liver are very rare, including the coexistence of HCC (hepatocellular carcinoma) with NEC (neuroendocrine carcinoma). The rare occurrence of these tumors necessitates more reported cases in order to fully understand their clinical characteristics, behaviors and treatments. Herein is described an incidental collision tumor of HCC-NEC, along with a review of the literature focusing on their clinicopathological findings and prognosis. The tumor presented here was found incidentally in the hepatectomy specimen of a 56-year-old man who had undergone liver transplantation for rapidly progressive liver failure because of alcoholic hepatitis and cirrhosis. Imaging and laboratory examinations did not demonstrate tumor-related findings. During macroscopic examination, two sharply defined and distinctive areas (1.7 cm and 0.6 cm dimension respectively) were detected among the cirrhotic nodules. The characteristic histopathological features and immunohistochemical findings allowed a diagnosis of HCC-NEC to be made. There was no evidence of recurrence and metastasis after 10 months following surgery. The present case and review revealed that these tumors are frequently found in older ages and males. Although serum markers are valuable in the discrimination of malignant tumors, their absence cannot completely rule out composite HCC-NEC. Diagnosis requires a comprehensive histopathological evaluation together with immunohistochemistry. The NEC component might influence the treatment strategy and eventually the outcome of the patient. In conclusion, the rare occurrence of HCC-NEC and the lack of diagnostic clinical signs and symptoms do not exclude their consideration in the differential diagnosis of liver tumors, especially in patients with the chronic liver disease.
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Affiliation(s)
- Düriye Betül Yılmaz
- Department of Pathology, Akdeniz University Medical School, Konyaalti/Antalya, Turkey
| | - Zeynep Bayramoğlu
- Department of Pathology, Akdeniz University Medical School, Konyaalti/Antalya, Turkey
| | - Gülşah Ünay
- Department of Pathology, Akdeniz University Medical School, Konyaalti/Antalya, Turkey
| | - Erdem Ayık
- Department of Pathology, Akdeniz University Medical School, Konyaalti/Antalya, Turkey
| | | | - Gülsüm Özlem Elpek
- Department of Pathology, Akdeniz University Medical School, Konyaalti/Antalya, Turkey
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20
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Kwon HJ, Kim JW, Kim H, Choi Y, Ahn S. Combined Hepatocellular Carcinoma and Neuroendocrine Carcinoma with Ectopic Secretion of Parathyroid Hormone: A Case Report and Review of the Literature. J Pathol Transl Med 2018; 52:232-237. [PMID: 29794961 PMCID: PMC6056365 DOI: 10.4132/jptm.2018.05.17] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2018] [Accepted: 05/15/2018] [Indexed: 12/19/2022] Open
Abstract
Primary combined hepatocellular carcinoma (HCC) and neuroendocrine carcinoma is a rare entity, and so is hypercalcemia due to ectopic parathyroid hormone (PTH) secretion by tumor. A 44-year old man with hepatitis B virus associated chronic liver disease presented with a hepatic mass. Hemihepatectomy discovered the mass as combined HCC and poorly differentiated cholangiocarcinoma. During adjuvant chemoradiation therapy, he presented with nausea, and multiple systemic metastases were found. Laboratory tests revealed hypercalcemia with markedly elevated PTH and neuron specific enolase. Parathyroid scan showed normal uptake in parathyroid glands, suggestive of ectopic PTH secretion. Subsequently, immunohistochemistry of neuroendocrine marker was performed on the primary lesion, and confirmed the neuroendocrine differentiation in non-HCC component. The patient died 71 days after surgery. This report may suggest the possibility of ectopic PTH secretion by neuroendocrine carcinoma of hepatic origin causing hypercalcemia. Caution for neuroendocrine differentiation should be exercised when diagnosing poorly differentiated HCC.
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Affiliation(s)
- Hyun Jung Kwon
- Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Ji-Won Kim
- Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Haeryoung Kim
- Department of Pathology, Seoul National University Hospital, Seoul, Korea
| | - YoungRok Choi
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Soomin Ahn
- Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea
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21
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Yu Y, Zhong Y, Wang J, Wu D. Sarcomatoid hepatocellular carcinoma (SHC): a case report. World J Surg Oncol 2017; 15:219. [PMID: 29233162 PMCID: PMC5728015 DOI: 10.1186/s12957-017-1286-1] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2017] [Accepted: 12/04/2017] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Sarcomatoid hepatocellular carcinoma (SHC) is a rare malignant hepatic tumor. Recurrent interventional therapies such as transcatheter arterial chemo-embolization (TACE), radiofrequency ablation (RFA), and percutaneous ethanol injection have been reported previously utilized in a majority of SHC cases. To date, the exact pathogenic mechanisms underlying sarcomatoid transformation of hepatocellular carcinoma (HCC) remain unknown. CASE PRESENTATION In this study, we report a 68-year-old female SHC patient admitted to our hospital due to discrete abdominal distention for more than 20 days. Abdominal computed tomography (CT) with tri-phase enhancement revealed portal vein tumor thrombi (PVTT) and a left hepatic lobe lesion measuring 110.0 mm × 160.0 mm. The patient subsequently underwent liver resection, after which pathological examination revealed proliferation of spindle-shaped SHC cells. A sarcomatoid, T4 stage carcinoma was eventually diagnosed. Forty-seven days after the operation, tri-phase enhanced CT detected extensive lesions in the liver, spleen, peritoneum, omentum majus, and mesentery, indicating SHC recurrence and metastases. Combination chemotherapy with pirarubicin and cisplatin was initiated for 1 cycle, but terminated due to resultant severe myelosuppression and medication intolerance. The patient was lost to therapy after 3 months of follow-up. CONCLUSIONS This case is unique because of hepatitis C virus infection. We should consider the possibility of this disease in patients with atypical clinical presentation.
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Affiliation(s)
- Yingying Yu
- Department of Oncology, First Hospital of Jilin University, 71 Xinmin St., Changchun, Jilin 130012 China
| | - Yanping Zhong
- Department of Pathology, First Hospital of Jilin University, Changchun, Jilin 130012 China
| | - Jingyu Wang
- Department of Radiology, First Hospital of Jilin University, Changchun, Jilin 130012 China
| | - Di Wu
- Department of Oncology, First Hospital of Jilin University, 71 Xinmin St., Changchun, Jilin 130012 China
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22
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Liu YJ, Ng KF, Huang SC, Wu RC, Chen TC. Composite hepatocellular carcinoma and small cell carcinoma with early nodal metastasis: A case report. Medicine (Baltimore) 2017; 96:e7868. [PMID: 28834900 PMCID: PMC5572022 DOI: 10.1097/md.0000000000007868] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
RATIONALE Hepatocellular carcinoma (HCC) is known to grow in a mosaic pattern, and it can sometimes be combined with non-hepatocellular cells. Despites the variety of combination, HCC with a significant neuroendocrine carcinoma (NEC) component remains very rare. Most of the reported cases were treated as conventional HCC with a relatively poor prognosis. Early diagnosis may lead to a better treatment modality. Here, we report a case of composite HCC and small cell carcinoma (SCC) with nodal metastasis of the SCC component alone. PATIENT CONCERNS A 65-year-old man with chronic viral hepatitis C presented with abdominal discomfort for 2 months. Computed tomography and angiography of the liver showed a 4.3 cm hypervascular tumor in segment 4 and enlargement of the perihilar and paracaval lymph nodes. INTERVENTIONS Extended left lobectomy and regional lymph node dissection were performed. DIAGNOSIS The hepatic tumor was heterogeneous with two distinct gross components. The green part showed a grade III hepatocellular carcinoma with an immunoreaction to Hep Par 1, glypican 3 and α-fetoprotein, whereas the white part exhibited a small cell carcinoma, as evidenced by expressions of chromogranin A and synaptophysin. The lymph node was metastasized by the SCC component. The SCC part was also positive for vimentin with perivascular accentuation. ß-catenin immunostain showed reduced membranous expression in the SCC component, as compared to HCC. OUTCOMES The patient expired 39 days after the surgical intervention. LESSONS Clinicians should be highly alert to a composite hepatic tumor, especially in dealing with a small heterogeneous tumor (< 5 cm) with early lymph node metastasis.
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Affiliation(s)
- Yu-Jen Liu
- Department of Pathology, Chang Gung Memorial Hospital, Guishan
| | - Kwai-Fong Ng
- Department of Pathology, Chang Gung Memorial Hospital, Guishan
- Department of Pathology, Chang Gung University School of Medicine, Taoyuan, Taiwan
| | - Shih-Chiang Huang
- Department of Pathology, Chang Gung Memorial Hospital, Guishan
- Department of Pathology, Chang Gung University School of Medicine, Taoyuan, Taiwan
| | - Ren-Chin Wu
- Department of Pathology, Chang Gung Memorial Hospital, Guishan
- Department of Pathology, Chang Gung University School of Medicine, Taoyuan, Taiwan
| | - Tse-Ching Chen
- Department of Pathology, Chang Gung Memorial Hospital, Guishan
- Department of Pathology, Chang Gung University School of Medicine, Taoyuan, Taiwan
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23
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Nomura Y, Nakashima O, Akiba J, Ogasawara S, Fukutomi S, Yamaguchi R, Kusano H, Kage M, Okuda K, Yano H. Clinicopathological features of neoplasms with neuroendocrine differentiation occurring in the liver. J Clin Pathol 2016; 70:563-570. [PMID: 27881473 DOI: 10.1136/jclinpath-2016-203941] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2016] [Revised: 10/10/2016] [Accepted: 10/27/2016] [Indexed: 12/14/2022]
Abstract
BACKGROUND/AIMS We investigated the clinicopathological features of hepatic neuroendocrine tumours (NET) and neuroendocrine carcinoma (NEC), which remain largely unknown. MATERIAL AND METHODS We examined 1235 tumours from 1048 patients who had undergone curative hepatectomy for liver neoplasms at Kurume University Hospital. Pathological diagnoses were based on the 2010 WHO Classification of Tumours of the Digestive System. We performed immunostaining for hepatocyte markers (eg, hepatocyte paraffin (HepPar)-1), neuroendocrine markers (eg, chromogranin A (CGA)) and the proliferation marker (Ki-67). RESULTS There were four cases of NET G2 (0.38%) and five of hepatic malignant tumours with an NEC component (HNEC) (0.48%). HNEC cases were classified into three types, that is, transitional, intermediate and separate types, according to their histological and immunohistochemical features. In the former two types, the NEC component intermingled with the moderately to poorly differentiated hepatocellular carcinoma (HCC) component or intermediate component consisting of tumour cells showing the colocalisation of CGA and HepPar-1. In the separate type, the NEC and poorly differentiated HCC components were present separately, whereas the sarcomatous HCC component was detected in the vicinity of the NEC component. Ki-67 labelling indices of the NET G2, HCC and NEC components of HNEC were 6.8%, 14.9% and 58.9%, respectively. CONCLUSIONS Primary hepatic NET and NEC are very rare tumours. The NEC component in HNEC showed high proliferative activity and influenced patient prognoses.
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Affiliation(s)
- Yoriko Nomura
- Department of Diagnostic Pathology, Kurume University Hospital, Kurume, Fukuoka, Japan.,Department of Surgery, Kurume University School of Medicine, Kurume, Fukuoka, Japan.,Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan
| | - Osamu Nakashima
- Clinical Laboratory Medicine, Kurume University Hospital, Kurume, Fukuoka, Japan
| | - Jun Akiba
- Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan
| | - Sachiko Ogasawara
- Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan
| | - Shogo Fukutomi
- Department of Diagnostic Pathology, Kurume University Hospital, Kurume, Fukuoka, Japan
| | - Rin Yamaguchi
- Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan
| | - Hironori Kusano
- Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan
| | - Masayoshi Kage
- Department of Diagnostic Pathology, Kurume University Hospital, Kurume, Fukuoka, Japan
| | - Koji Okuda
- Department of Surgery, Kurume University School of Medicine, Kurume, Fukuoka, Japan
| | - Hirohisa Yano
- Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan
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Nishino H, Hatano E, Seo S, Shibuya S, Anazawa T, Iida T, Masui T, Taura K, Haga H, Uemoto S. Histological features of mixed neuroendocrine carcinoma and hepatocellular carcinoma in the liver: a case report and literature review. Clin J Gastroenterol 2016; 9:272-9. [PMID: 27384317 DOI: 10.1007/s12328-016-0669-0] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2016] [Accepted: 06/22/2016] [Indexed: 12/14/2022]
Abstract
Primary hepatic neuroendocrine carcinoma (NEC) is rare, and its origin, clinical features, diagnosis and treatment have not been clarified. Primary mixed NEC and hepatocellular carcinoma (HCC) is even rarer and is divided into either combined type or collision type. We report a patient with the combined type of mixed NEC and HCC. A 72-year-old male was diagnosed with HCC and underwent hepatectomy because of the presence of two tumors in his liver. Histological examination demonstrated that one of the tumors had both NEC and HCC components. The transitional zone was noted in the immunohistological examination, and the tumor was determined to be the combined type of primary mixed NEC and HCC. This was the first description of an HCC component being found in an NEC-dominant area in a primary mixed NEC and HCC tumor. Three weeks after hepatectomy, an abdominal computed tomography scan showed extensive regional and para-aortic lymphadenopathy, and early relapse was suspected in the patient. The patient died 3 months after the operation despite treatment with combination chemotherapy. This report describes an unfavorable case and summarizes all the primary mixed NEC and HCC tumor cases that have been previously reported.
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MESH Headings
- Aged
- Carcinoma, Hepatocellular/diagnostic imaging
- Carcinoma, Hepatocellular/pathology
- Carcinoma, Hepatocellular/surgery
- Carcinoma, Neuroendocrine/diagnostic imaging
- Carcinoma, Neuroendocrine/pathology
- Carcinoma, Neuroendocrine/surgery
- Hepatectomy/methods
- Humans
- Liver Neoplasms/diagnostic imaging
- Liver Neoplasms/pathology
- Liver Neoplasms/surgery
- Magnetic Resonance Imaging
- Male
- Neoplasms, Multiple Primary/diagnostic imaging
- Neoplasms, Multiple Primary/pathology
- Neoplasms, Multiple Primary/surgery
- Positron Emission Tomography Computed Tomography
- Tomography, X-Ray Computed
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Affiliation(s)
- Hiroto Nishino
- Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Etsuro Hatano
- Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
| | - Satoru Seo
- Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Shinsuke Shibuya
- Department of Diagnostic Pathology, Kyoto University Hospital, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Takayuki Anazawa
- Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Taku Iida
- Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Toshihiko Masui
- Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Kojiro Taura
- Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Hironori Haga
- Department of Diagnostic Pathology, Kyoto University Hospital, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Shinji Uemoto
- Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
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Leng Q, Xiang XI, Tang Y, Yang Y, Qiu LI. Primary hepatic sarcomatoid carcinoma: A case report. Exp Ther Med 2015; 10:1145-1148. [PMID: 26622454 DOI: 10.3892/etm.2015.2599] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2014] [Accepted: 06/01/2015] [Indexed: 02/05/2023] Open
Abstract
Sarcomatoid carcinoma (SC) is a malignant tumor type of unclear pathogenesis, which rarely occurs in the liver. The present study reports the case of a 60-year-old woman who presented with multiple masses in her liver, with no fever, abdominal pain or jaundice. Serological markers for hepatitis B and C virus were negative, as was the test for α fetoprotein. Abdominal enhanced magnetic resonance imaging examination confirmed multiple lesions in the liver, and liquefactive necrosis was observed. The patient underwent a right hepatectomy, in addition to a cholecystectomy. Cytokeratin 8 (CK8), cluster of differentiation 117, pancytokeratin and vimentin were positively detected using immunohistochemistry, and thus the diagnosis of primary hepatic SC (PHSC) was established. During the follow-up period, characteristic imaging manifestations of tumor recurrence were detected, including peripheral enhancement, central necrosis, variable enhancement, venous invasion and intrahepatic metastasis. The immunohistochemical detection of CK, epithelial membrane antigen and vimentin, with CK8 as a critical indicator, may be useful for the diagnosis of PHSC. The preferred treatment for PHSC is surgical resection and the prognosis is poor.
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Affiliation(s)
- Qianying Leng
- Department of Ultrasound, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, P.R. China ; Department of Ultrasound, No.4 West China Teaching Hospital of Sichuan University, Chengdu, Sichuan 610041, P.R. China
| | - X I Xiang
- Department of Ultrasound, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, P.R. China
| | - Yuanjiao Tang
- Department of Ultrasound, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, P.R. China
| | - Yujia Yang
- Department of Ultrasound, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, P.R. China
| | - L I Qiu
- Department of Ultrasound, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, P.R. China
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Aboelenen A, El-Hawary AK, Megahed N, Zalata KR, El-Salk EM, Fattah MA, Sorogy ME, Shehta A. Right hepatectomy for combined primary neuroendocrine and hepatocellular carcinoma. A case report. Int J Surg Case Rep 2013; 5:26-29. [PMID: 24394859 PMCID: PMC3907205 DOI: 10.1016/j.ijscr.2013.10.018] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2013] [Revised: 10/24/2013] [Accepted: 10/30/2013] [Indexed: 12/14/2022] Open
Abstract
INTRODUCTION Cases of primary neuroendocrine tumors in the liver combined with hepatocellular carcinoma are scarce. Such cases could present either as combined-type tumor or collision type. PRESENTATION OF CASE A 51-year-old man presented with a mass in the right hemiliver. Serum level of alpha-fetoprotein was slightly elevated (2.3ng/ml), with normal CA19-9 and CA125. The patient underwent right hepatectomy. The resected specimen showed a well-defined and heterogeneous gray-white to brown friable tumor, 20cm in diameter. Microscopically, the tumor consisted predominantly of monotonous small- to medium-sized neoplastic cells arranged in trabeculea separated by sinusoidal spaces. Immunohistochemically, the tumor cells were strongly positive for synaptophysin and focally positive for chromogranin-A. Interestingly, the tumor cells showed patchy positive coarse granular staining of HerPar-1 involving about 1% of the tumor cells. Glypican-3 staining was negative. These immunohistochemical findings supported the diagnosis of combined high grade neuroendocrine carcinoma and hepatocellular carcinoma. DISCUSSION Cases of primary neuroendocrine tumors in the liver combined 82 with hepatocellular carcinoma are scarce. The uniqueness of this case lies in the fact that the neuroendocrine carcinoma component comprised more than 99% of the tumor area, and the minor hepatocellular carcinoma component was detected only by the immunohistochemical staining for HepPar-1. CONCLUSION To the best of our knowledge, this is the first case of combined neuroendocrine carcinoma and hepatocellular carcinoma in Egypt.
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Affiliation(s)
- Ahmed Aboelenen
- Gastroenterology Surgical Center, Mansoura University, Egypt
| | | | - Nirmeen Megahed
- Gastroenterology Surgical Center, Mansoura University, Egypt
| | | | - Eman M El-Salk
- Gastroenterology Surgical Center, Mansoura University, Egypt
| | | | | | - Ahmed Shehta
- Gastroenterology Surgical Center, Mansoura University, Egypt
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Xu LF, Ni JY, Sun HL, Chen YT, Wu YD. Effects of hypoxia-inducible factor-1α silencing on the proliferation of CBRH-7919 hepatoma cells. World J Gastroenterol 2013; 19:1749-1759. [PMID: 23555163 PMCID: PMC3607751 DOI: 10.3748/wjg.v19.i11.1749] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2012] [Revised: 01/04/2013] [Accepted: 01/19/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To study the effects of hypoxia-inducible factor-1α (HIF-1α) silencing on the proliferation of hypoxic CBRH-7919 rat hepatoma cells.
METHODS: The CBRH-7919 rat hepatoma cell line was used in this study and the hypoxic model was constructed using CoCl2. The HIF-1α-specific RNAi sequences were designed according to the gene coding sequence of rat HIF-1α obtained from GeneBank. The secondary structure of the HIF-1α gene sequence was analyzed using RNA draw software. The small interfering RNA (siRNA) transfection mixture was produced by mixing the siRNA and Lipofectamine2000TM, and transfected into the hypoxic hepatoma cells. Real time reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting assay were used to detect the expression levels of mRNA and protein. HIF-1α and vascular endothelial growth factor (VEGF) mRNA was determined using real time RT-PCR; the protein expression levels of AKT, p-AKT, p21 and cyclinD1 were determined using Western blotting. The proliferation of hepatoma cells was observed using the methyl thiazolyl tetrazolium (MTT) assay and the bromodeoxyuridine (BrdU) incorporation cell proliferation assay.
RESULTS: Under induced hypoxia, the viability of the hepatoma cells reached a minimum at 800 μmol/L CoCl2; the viability of the cells was relatively high at CoCl2 concentrations between 100 μmol/L and 200 μmol/L. Under hypoxia, the mRNA and protein expression levels of HIF-1α and VEGF were significantly higher than that of hepatoma cells that were cultured in normaxia. HIF-1α-specific RNAi sequences were successfully transfected into hepatoma cells. The transfection of specific siRNAs significantly inhibited the mRNA and protein expression levels of HIF-1α and VEGF, along with the protein expression levels of p-AKT and cyclinD1; the protein expression of p21 was significantly increased, and there was no significant difference in the expression of AKT. The MTT assay showed that the amount of hepatoma cells in S phase in the siRNA transfection group was obviously smaller than that in the control group; in the siRNA transfection group, the amount of hepatoma cells in G1 phase was more than that in the control group. The BrdU incorporation assay showed that the number of BrdU positive hepatoma cells in the siRNA transfection group was less than that in the control group. The data of the MTT assay and BrdU incorporation assay suggested that HIF-1α silencing using siRNAs significantly inhibited the proliferation of hepatoma cells.
CONCLUSION: Hypoxia increases the expression of HIF-1α, and HIF-1α silencing significantly inhibits the proliferation of hypoxic CBRH-7919 rat hepatoma cells.
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