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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] [Download PDF] [Figures] [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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Tsuji K, Abe M, Wakamatsu S, Hoshi S, Hoshi N, Takagi C, Fukushima N, Hirabayashi K. Mixed hepatocellular carcinoma and high-grade neuroendocrine neoplasm with ambiguous histopathological features: a case report. Med Mol Morphol 2025; 58:62-68. [PMID: 39177817 DOI: 10.1007/s00795-024-00396-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2024] [Accepted: 07/01/2024] [Indexed: 08/24/2024]
Abstract
Well-differentiated neuroendocrine tumor (NET) and poorly differentiated neuroendocrine carcinoma (NEC) are distinct entities with different biological behavior. However, difficult cases showing equivocal morphology have been reported in some organs. Herein, we report a case of primary hepatic neuroendocrine neoplasm (NEN) with ambiguous histopathological features admixed with conventional hepatocellular carcinoma (HCC). A 70-year-old man with untreated chronic hepatitis B underwent left medial sectionectomy because of two incidental liver masses. On pathological examination, one of the resected tumors had intermingling NEN and HCC components. The NEN component consisted of relatively uniform tumor cells proliferating in trabecular, cord-like, or solid patterns with peripheral nuclear palisading. The tumor cells were immunopositive for synaptophysin, chromogranin A, cluster of differentiation 56 (CD56), and focally hepatocyte paraffin 1. p53 showed wild-type expression. The Ki-67 labeling index was 27% at the hot spot. Eleven months after the surgery, he died of a cerebral hemorrhage without evidence of recurrent liver cancer. The intermediate degree of differentiation and the modest proliferative activity can challenge the distinction between NEC and NET G3. While the coexisting HCC indicates NEC rather than NET in a pathogenetic viewpoint, such ambiguous tumor may not be as aggressive as typical NECs.
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Affiliation(s)
- Kentaro Tsuji
- Department of Diagnostic Pathology, Tochigi Cancer Center, Utsunomiya, Tochigi, 320-0834, Japan
- Department of Diagnostic Pathology, Jichi Medical University Hospital, Shimotsuke, Tochigi, Japan
| | - Makoto Abe
- Department of Diagnostic Pathology, Tochigi Cancer Center, Utsunomiya, Tochigi, 320-0834, Japan
| | - Saho Wakamatsu
- Department of Diagnostic Pathology, Tochigi Cancer Center, Utsunomiya, Tochigi, 320-0834, Japan
| | - Sayuri Hoshi
- Department of Diagnostic Pathology, Tochigi Cancer Center, Utsunomiya, Tochigi, 320-0834, Japan
| | - Nobuo Hoshi
- Department of Diagnostic Pathology, Tochigi Cancer Center, Utsunomiya, Tochigi, 320-0834, Japan
| | - Chisato Takagi
- Department of Hepato-Biliary-Pancreatic Surgery, Tochigi Cancer Center, Utsunomiya, Tochigi, Japan
| | - Noriyoshi Fukushima
- Department of Diagnostic Pathology, Jichi Medical University Hospital, Shimotsuke, Tochigi, Japan
| | - Kaoru Hirabayashi
- Department of Diagnostic Pathology, Tochigi Cancer Center, Utsunomiya, Tochigi, 320-0834, Japan.
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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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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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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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Murakami K, Kumata H, Miyagi S, Kamei T, Sasano H. The prognostic significance of neuroendocrine markers and somatostatin receptor 2 in hepatocellular carcinoma. Pathol Int 2021; 71:682-691. [PMID: 34320691 DOI: 10.1111/pin.13149] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Accepted: 07/15/2021] [Indexed: 12/17/2022]
Abstract
Prostatic and colon carcinomas with neuroendocrine differentiation are reported to behave more aggressively than those without such differentiation. In hepatocellular carcinomas (HCCs), however, only a few studies have reported the expression status of neuroendocrine markers and somatostatin receptor 2, the main target of a somatostatin analog. Furthermore, the prognostic significance of the markers in HCCs has not been fully explored. We evaluated the expression of the neuroendocrine makers (chromogranin A, synaptophysin, and CD56) and somatostatin receptor 2 (SSTR2) in 95 HCCs, and investigated the correlation between the expression of these markers and clinicopathological findings. Chromogranin A was immunolocalized in 2 cases, synaptophysin in 15 cases, CD56 in 11 cases, and SSTR2 in 19 cases. Immunoreactivity of synaptophysin and CD56 were the significant unfavorable prognostic factors in terms of 2-year disease-free survival (DFS) and the overall survival (OS) along with a high nuclear mitosis level (>10/10 high-power field), a larger tumor size (>5 cm), the presence of vascular and/or biliary invasion, and high TNM stage (III/IV). Multivariate Cox proportional hazards analysis identified synaptophysin as an independent prognostic factor for 2-year DFS and OS. Synaptophysin expression can be used to predict an unfavorable prognosis in patients with HCC.
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Affiliation(s)
- Keigo Murakami
- Division of Pathology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai, Miyagi, Japan.,Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Hiroyuki Kumata
- Division of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University School of Medicine, Sendai, Miyagi, Japan
| | - Shigehito Miyagi
- Division of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University School of Medicine, Sendai, Miyagi, Japan
| | - Takashi Kamei
- Division of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University School of Medicine, Sendai, Miyagi, Japan
| | - Hironobu Sasano
- Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
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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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10
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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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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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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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13
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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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14
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Huang HF, Jin PP, Yang HJ, Zhang CJ, Zhang X, Wang JS, Yu JJ, Zhang B, Zhang Y, Hu QD. Primary Hepatic Neuroendocrine Tumor Mimicking Ruptured Hepatocellular Carcinoma with AFP Elevation: A Case Report and Literature Review. Onco Targets Ther 2020; 13:975-979. [PMID: 32099400 PMCID: PMC7007302 DOI: 10.2147/ott.s236728] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Accepted: 01/10/2020] [Indexed: 12/11/2022] Open
Abstract
Liver cancer is a common malignant disease in China, while the primary hepatic neuroendocrine tumor (PHNET) is extremely rare presented with various manifestations. We herein describe an interesting PHNET case, which was clinically diagnosed as hepatocellular carcinoma (HCC) based on strong clinical evidence and the national guideline, but confirmed to be PHNET by pathology. A42-year-old Chinese male was admitted for persistent upper abdominal pain, and CT scan revealed a huge liver tumor in the left lobe. The tumor presented attributes of tumor rupture, portal vein tumor thrombus, elevated serum AFP level, background hepatitis B virus infection history, and radiological features mimicking typical HCC. After left semi-hepatectomy was performed for curative treatment of the primary "HCC", the pathology demonstrated the correct diagnosis be poorly differentiated neuroendocrine carcinoma (NEC). The immunohistochemistry assays showed positive neuroendocrine markers of CgA and Syn and negative HCC markers of Hep Par 1 and GPC3, ruling out concurrent HCC. This case and literature review suggest that in spite of rare incidence, PHNET should be considered as a possible diagnosis when lacking a confirmative pathology result, even when sufficient evidence of typical presentation exist to establish the clinical diagnosis of HCC.
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Affiliation(s)
- Hai-Feng Huang
- Department of Surgery, Shengzhou People's Hospital, Shengzhou 312400, People's Republic of China
| | - Piao-Piao Jin
- Health Management Center, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, People's Republic of China
| | - Han-Jin Yang
- Department of Pathology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, People's Republic of China
| | - Chun-Jun Zhang
- Department of Surgery, Shengzhou People's Hospital, Shengzhou 312400, People's Republic of China
| | - Xin Zhang
- Department of Radiology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, People's Republic of China
| | - Jun-Sen Wang
- Department of Pathology, Shengzhou People's Hospital, Shengzhou 312400, People's Republic of China
| | - Jia-Jie Yu
- Department of Surgery, Shengzhou People's Hospital, Shengzhou 312400, People's Republic of China
| | - Bo Zhang
- Department of Surgery, Shengzhou People's Hospital, Shengzhou 312400, People's Republic of China
| | - Yun Zhang
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, People's Republic of China
| | - Qi-da Hu
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, People's Republic of China
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15
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Park JH, Kim JH. Pathologic differential diagnosis of metastatic carcinoma in the liver. Clin Mol Hepatol 2019; 25:12-20. [PMID: 30300991 PMCID: PMC6435968 DOI: 10.3350/cmh.2018.0067] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2018] [Accepted: 08/10/2018] [Indexed: 12/18/2022] Open
Abstract
The liver is one of the most common sites to which malignancies preferentially metastasize. Although a substantial number of liver malignancies are primary tumors, including hepatocellular carcinoma and intrahepatic cholangiocarcinoma, the metastasis of carcinomas to the liver is relatively common and frequently encountered in clinical settings. Representative carcinomas that frequently metastasize to the liver include colorectal carcinoma, breast carcinoma, neuroendocrine tumors, lung carcinoma, and gastric carcinoma. The diagnostic confirmation of suspected metastatic lesions in the liver is generally achieved through a histopathologic examination of biopsy tissues. Although morphology is the most important feature for a pathologic differential diagnosis of metastatic carcinomas, immunohistochemical studies facilitate the differentiation of metastatic carcinoma origins and subtypes. Useful immunohistochemical markers for the differential diagnosis of metastatic carcinomas in the liver include cytokeratins (CK7, CK19, and CK20), neuroendocrine markers (CD56, synaptophysin, and chromogranin A), and tissue-specific markers (CDX2, SATB2, TTF-1, GCDFP-15, mammaglobin, etc.). Here, we provide a brief review about the pathologic differential diagnosis of major metastatic carcinomas in the liver.
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Affiliation(s)
- Jeong Hwan Park
- Department of Pathology, Seoul Metropolitan Government-Seoul National Uiversity Boramae Medical Center, Seoul, Korea
- Department of Pathology, Seoul National University College of Medicine, Seoul, Korea
| | - Jung Ho Kim
- Department of Pathology, Seoul National University College of Medicine, Seoul, Korea
- Department of Pathology, Seoul National University Hospital, Seoul, Korea
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16
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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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17
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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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18
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Jiang K, Al-Diffhala S, Centeno BA. Primary Liver Cancers-Part 1: Histopathology, Differential Diagnoses, and Risk Stratification. Cancer Control 2018; 25:1073274817744625. [PMID: 29350068 PMCID: PMC5933592 DOI: 10.1177/1073274817744625] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) are the 2 most common primary malignant liver tumors, with hepatocellular and bile ductular differentiation, respectively. This article reviews the key histopathological findings of these 2 primary liver cancers and includes a review of the role of ancillary testing for differential diagnosis, risk stratification according to the American Joint Committee on Cancer (AJCC) staging recommendation, and a review of precancerous lesions. A literature review was conducted to identify articles with information relevant to precancerous precursors, current histopathological classification, ancillary testing, and risk stratification of primary malignant liver tumors. The histomorphology of normal liver, preinvasive precursors, primary malignancies, and morphological variants, and the utilization of ancillary tests for the pathological diagnosis are described. Dysplastic nodules are the preinvasive precursors of HCC, and intraductal papillary neoplasms of bile ducts and biliary intraepithelial neoplasia are the preinvasive precursors of CC. Benign liver nodules including focal nodular hyperplasia and adenomas are included in this review, since some forms of adenomas progress to HCC and often they have to be differentiated from well-differentiated HCC. A number of morphological variants of HCC have been described in the literature, and it is necessary to be aware of them in order to render the correct diagnosis. Risk stratification is still dependent on the AJCC staging system. The diagnosis of primary liver carcinomas is usually straightforward. Application of the appropriate ancillary studies aids in the differential diagnosis of difficult cases. The understanding of the carcinogenesis of these malignancies has improved with the standardization of the pathological classification of preinvasive precursors and studies of the molecular pathogenesis. Risk stratification still depends on pathological staging.
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Affiliation(s)
- Kun Jiang
- 1 Department of Anatomic Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.,2 Department of Oncologic Sciences, Morsani College of Medicine at University of South Florida, Tampa, FL, USA
| | - Sameer Al-Diffhala
- 3 Division of Anatomic Pathology, Department of Pathology, University of Alabama School of Medicine, Birmingham, AL, USA
| | - Barbara A Centeno
- 1 Department of Anatomic Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.,2 Department of Oncologic Sciences, Morsani College of Medicine at University of South Florida, Tampa, FL, USA
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19
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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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20
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Lu JG, Farukhi MA, Mayeda D, French SW. Hepatocellular carcinoma with neuroendocrine differentiation: a case report. Exp Mol Pathol 2017; 103:200-203. [DOI: 10.1016/j.yexmp.2017.09.004] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2017] [Accepted: 09/18/2017] [Indexed: 12/17/2022]
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21
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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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22
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Okumura Y, Kohashi K, Wang H, Kato M, Maehara Y, Ogawa Y, Oda Y. Combined primary hepatic neuroendocrine carcinoma and hepatocellular carcinoma with aggressive biological behavior (adverse clinical course): A case report. Pathol Res Pract 2017. [PMID: 28647212 DOI: 10.1016/j.prp.2017.06.001] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Combined primary hepatic neuroendocrine carcinoma (PHNEC) and hepatocellular carcinoma (HCC) is a very rare malignant hepatic tumor. Its prognosis and histological features are uncertain. Here we report the case of such a tumor in a 70-year-old male Japanese patient with adverse prognosis. The patient underwent a right hepatic lobectomy for a tumor mass that measured 11×10cm in diameter located in the right lobe of the liver, treated with transcatheter arterial chemoembolization (TACE) and percutaneous transhepatic portal vein embolization (PTPE) therapy five weeks before the operation. Histologically, the hepatic tumor was composed of predominantly HCC and admixed with a small part of neuroendocrine carcinoma (NEC). The NEC component was distributed as a collision-type tumor separated by fibrous bands from HCC and the combined-type tumor, focally intermingling with HCC. One month after the surgery, metastasis to abdominal lymph nodes and the lumbar vertebra was detected. Although the additional treatments of systematic chemotherapy and radiation therapy were performed, the patient died 3 months after the initial surgery.
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Affiliation(s)
- Yukihiko Okumura
- Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan
| | - Kenichi Kohashi
- Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan
| | - Huanlin Wang
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan
| | - Masaki Kato
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan
| | - Yoshihiko Maehara
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan
| | - Yoshihiro Ogawa
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan
| | - Yoshinao Oda
- Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan.
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23
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Yun EY, Kim TH, Lee SS, Kim HJ, Kim HJ, Jung WT, Lee OJ, Song DH. [A Case of Composite Hepatocellular Carcinoma and Neuroendocrine Carcinoma in a Patient with Liver Cirrhosis Caused by Chronic Hepatitis B]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2017; 68:109-13. [PMID: 27554219 DOI: 10.4166/kjg.2016.68.2.109] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Primary hepatic neuroendocrine carcinoma (PHNEC) is rare and its origin is not clearly understood. The coexistence of PHNEC and hepaotcellular carcinoma has been reported in only a few cases. We report a rare case of combined PHNEC and hepaotcellular carcinoma in a patient with liver cirrhosis caused by chronic hepatitis B that resulted in aggressive behavior and poor prognosis.
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Affiliation(s)
- Eun Young Yun
- Department of Internal Medicine, Gyeongsang National University School of Medicine, Jinju, Korea
| | - Tae Hyo Kim
- Department of Internal Medicine, Gyeongsang National University School of Medicine, Jinju, Korea.,Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Korea
| | - Sang Soo Lee
- Department of Internal Medicine, Gyeongsang National University School of Medicine, Jinju, Korea
| | - Hong Jun Kim
- Department of Internal Medicine, Gyeongsang National University School of Medicine, Jinju, Korea
| | - Hyun Jin Kim
- Department of Internal Medicine, Gyeongsang National University School of Medicine, Jinju, Korea.,Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Korea
| | - Woon Tae Jung
- Department of Internal Medicine, Gyeongsang National University School of Medicine, Jinju, Korea.,Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Korea
| | - Ok Jae Lee
- Department of Internal Medicine, Gyeongsang National University School of Medicine, Jinju, Korea.,Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Korea
| | - Dae Hyun Song
- Department of Pathology, Gyeongsang National University School of Medicine, Jinju, Korea
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24
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Jian J, Zhang W, Yang H, Zhao X, Xuan R, Li D, Hu C. Phase-contrast CT: Qualitative and Quantitative Evaluation of Capillarized Sinusoids and Trabecular Structure in Human Hepatocellular Carcinoma Tissues. Acad Radiol 2017; 24:67-75. [PMID: 27818006 DOI: 10.1016/j.acra.2016.08.028] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2016] [Revised: 08/14/2016] [Accepted: 08/25/2016] [Indexed: 12/17/2022]
Abstract
RATIONALE AND OBJECTIVES Capillarization of sinusoids and change of trabecular thickness are the main histologic features in hepatocellular carcinoma (HCC). Of particular interest are the three-dimensional (3D) visualization and quantitative evaluation of such alterations in the HCC progression. X-ray phase-contrast computed tomography (PCCT) is an emerging imaging method that provides excellent image contrast for soft tissues. This study aimed to explore the potential of in-line PCCT in microstructure imaging of capillarized sinusoids and trabecular structure in human HCC tissues and to quantitatively evaluate the alterations of those fine structures during the development of HCC. MATERIALS AND METHODS This project was designed as an ex vivo experimental study. The study was approved by the institutional review board, and informed consent was obtained from the patients. Eight human resected HCC tissue samples were imaged using in-line PCCT. After histologic processing, PCCT images and histopathologic data were matched. Fine structures in HCC tissues were revealed. Quantitative analyses of capillarized sinusoids (ie, percentage of sinusoidal area [PSA], sinusoidal volume) and trabecular structure (ie, trabecular thickness, surface-area-to-volume ratio [SA/V]) in low-grade (well or moderately differentiated) and high-grade (poorly differentiated) HCC groups were performed. RESULTS Using PCCT, the alterations of capillarized sinusoids and trabecular structure were clearly observed in 3D geometry, which was confirmed by the corresponding histologic sections. The 3D qualitative analyses of sinusoids in the high-grade HCC group were significantly different (P < 0.05) in PSA (7.8 ± 2.5%) and sinusoidal volume (2.9 ± 0.6 × 107 µm3) from those in the low-grade HCC group (PSA, 12.9 ± 2.2%; sinusoidal volume, 2.4 ± 0.3 × 107 µm3). Moreover, the 3D quantitative evaluation of the trabecular structure in the high-grade HCC group showed a significant change (P < 0.05) in the trabecular thickness (87.8 ± 15.6 µm) and SA/V (2.2 ± 1.3 × 103 µm-1) compared to the low-grade HCC group (trabecular thickness, 75.9 ± 7.1 µm; SA/V, 7.5 ± 1.3 × 103 µm-1). CONCLUSIONS This study provides insights into the 3D alterations of microstructures such as capillarized sinusoids and the trabecular structure at a micrometer level, which might allow for an improved understanding of the development of HCC.
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25
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La Rosa S, Sessa F, Uccella S. Mixed Neuroendocrine-Nonneuroendocrine Neoplasms (MiNENs): Unifying the Concept of a Heterogeneous Group of Neoplasms. Endocr Pathol 2016; 27:284-311. [PMID: 27169712 DOI: 10.1007/s12022-016-9432-9] [Citation(s) in RCA: 143] [Impact Index Per Article: 15.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
The wide application of immunohistochemistry to the study of tumors has led to the recognition that epithelial neoplasms composed of both a neuroendocrine and nonneuroendocrine component are not as rare as traditionally believed. It has been recommended that mixed neuroendocrine-nonneuroendocrine epithelial neoplasms are classified as only those in which either component represents at least 30 % of the lesion but this cutoff has not been universally accepted. Moreover, since their pathogenetic and clinical features are still unclear, mixed neuroendocrine-nonneuroendocrine epithelial neoplasms are not included as a separate clinicopathological entity in most WHO classifications, although they have been observed in virtually all organs. In the WHO classification of digestive tumors, mixed neuroendocrine-nonneuroendocrine neoplasm is considered a specific type and is defined as mixed adenoneuroendocrine carcinoma, a definition that has not been accepted for other organs. In fact, this term does not adequately convey the morphological and biological heterogeneity of digestive mixed neoplasms and has created some misunderstanding among both pathologists and clinicians. In the present study, we have reviewed the literature on mixed neuroendocrine-nonneuroendocrine epithelial neoplasms reported in the pituitary, thyroid, nasal cavity, larynx, lung, digestive system, urinary system, male and female genital organs, and skin to give the reader an overview of the most important clinicopathological features and morphological criteria for diagnosing each entity. We also propose to use the term "mixed neuroendocrine-nonneuroendocrine neoplasm (MiNEN)" to define and to unify the concept of this heterogeneous group of neoplasms, which show different characteristics mainly depending on the type of neuroendocrine and nonneuroendocrine components.
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Affiliation(s)
- Stefano La Rosa
- Department of Pathology, Ospedale di Circolo, viale Borri 57, 21100, Varese, Italy.
| | - Fausto Sessa
- Department of Surgical and Morphological Sciences, University of Insubria, Varese, Italy
| | - Silvia Uccella
- Department of Surgical and Morphological Sciences, University of Insubria, Varese, Italy
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26
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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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27
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Choi GH, Ann SY, Lee SI, Kim SB, Song IH. Collision tumor of hepatocellular carcinoma and neuroendocrine carcinoma involving the liver: Case report and review of the literature. World J Gastroenterol 2016; 22:9229-9234. [PMID: 27895410 PMCID: PMC5107604 DOI: 10.3748/wjg.v22.i41.9229] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2016] [Revised: 07/21/2016] [Accepted: 08/23/2016] [Indexed: 02/07/2023] Open
Abstract
Primary hepatic neuroendocrine carcinoma (NEC) with concurrent occurrence of hepatocellular carcinoma (HCC) of the liver is very rare. Only 8 cases have been reported in the literature. Concurrent occurrence of HCC and NEC in the liver is classified as combined type or collision type by histological distributional patterns; only 2 cases have been reported. Herein, we report a case of collision type concurrent occurrence of HCC and NEC, in which primary hepatic NEC was in only a small portion of the nodule, which is different from the 2 previously reported cases. A 72-year-old male with chronic hepatitis C was admitted to our hospital for a hepatic mass detected by liver computed tomography (CT) at another clinic. Because the nodule was in hepatic segment 3 and had proper radiologic findings for diagnosis of HCC, including enhancement in the arterial phase and wash-out in the portal and delay phases, the patient was treated with laparoscopic left lateral sectionectomy. The pathology demonstrated that the nodule was 2.5 cm and was moderately differentiated HCC. However, a 3 mm-sized focal neuroendocrine carcinoma was also detected on the capsule of the nodule. The tumor was concluded to be a collision type with HCC and primary hepatic NEC. After the surgery, for follow-up, the patient underwent a liver CT every 3 mo. Five multiple nodules were found in the right hepatic lobe on the follow-up liver CT 6 mo post-operatively. As the features of the nodules in the liver CT and MRI were different from that of HCC, a liver biopsy was performed. Intrahepatic recurrent NEC was proven after the liver biopsy, which showed the same pathologic features with the specimen obtained 6 mo ago. Palliative chemotherapy with a combination of etoposide and cisplatin has been administered for 4 months, showing partial response.
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28
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Baker E, Jacobs C, Martinie J, Iannitti DA, Vrochides D, Swan RZ. Mixed Hepatocellular Carcinoma, Neuroendocrine Carcinoma of the Liver. Am Surg 2016. [DOI: 10.1177/000313481608201130] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
We present the case of a 76-year-old male found to have a large tumor involving the left lateral lobe of the liver, presumed to be hepatocellular carcinoma (HCC). After resection, pathologic features demonstrated both high-grade HCC and high-grade neuroendocrine carcinoma (NEC). Areas of NEC stained strongly for synaptophysin, which was not present in HCC component. The HCC component stained strongly for Hep-Par 1, which was not present in the NEC component. The patient underwent genetic analysis for biomarkers common to both tumor cell types. Both tumor components contained gene mutations in CTNNB1 gene (S33F located in exon 3). They also shared mutations in PD-1, PGP, and SMO. Mixed HCC/NEC tumors have been rarely reported in the literature with generally poor outcomes. This patient has been referred for adjuvant platinum-based chemotherapy; genetic biomarker analysis may provide some insight to guide targeted chemotherapy.
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Affiliation(s)
- Erin Baker
- Department of General Surgery, Division of Hepato-pancreato-biliary Surgery, Carolinas Medical Center, Charlotte, North Carolina; Department of Pathology, Division of Gastrointestinal and Liver Pathology, Carolinas Medical Center, Charlotte, North Carolina; Department of General Surgery, Division of Hepato-pancreato-biliary Surgery, Carolinas Medical Center, Charlotte, North Carolina
| | - Carl Jacobs
- Department of General Surgery, Division of Hepato-pancreato-biliary Surgery, Carolinas Medical Center, Charlotte, North Carolina; Department of Pathology, Division of Gastrointestinal and Liver Pathology, Carolinas Medical Center, Charlotte, North Carolina; Department of General Surgery, Division of Hepato-pancreato-biliary Surgery, Carolinas Medical Center, Charlotte, North Carolina
| | - John Martinie
- Department of General Surgery, Division of Hepato-pancreato-biliary Surgery, Carolinas Medical Center, Charlotte, North Carolina; Department of Pathology, Division of Gastrointestinal and Liver Pathology, Carolinas Medical Center, Charlotte, North Carolina; Department of General Surgery, Division of Hepato-pancreato-biliary Surgery, Carolinas Medical Center, Charlotte, North Carolina
| | - David A. Iannitti
- Department of General Surgery, Division of Hepato-pancreato-biliary Surgery, Carolinas Medical Center, Charlotte, North Carolina; Department of Pathology, Division of Gastrointestinal and Liver Pathology, Carolinas Medical Center, Charlotte, North Carolina; Department of General Surgery, Division of Hepato-pancreato-biliary Surgery, Carolinas Medical Center, Charlotte, North Carolina
| | - Dionisios Vrochides
- Department of General Surgery, Division of Hepato-pancreato-biliary Surgery, Carolinas Medical Center, Charlotte, North Carolina; Department of Pathology, Division of Gastrointestinal and Liver Pathology, Carolinas Medical Center, Charlotte, North Carolina; Department of General Surgery, Division of Hepato-pancreato-biliary Surgery, Carolinas Medical Center, Charlotte, North Carolina
| | - Ryan Z. Swan
- Department of General Surgery, Division of Hepato-pancreato-biliary Surgery, Carolinas Medical Center, Charlotte, North Carolina; Department of Pathology, Division of Gastrointestinal and Liver Pathology, Carolinas Medical Center, Charlotte, North Carolina; Department of General Surgery, Division of Hepato-pancreato-biliary Surgery, Carolinas Medical Center, Charlotte, North Carolina
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29
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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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30
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Primary hepatic neuroendocrine carcinoma with a cholangiocellular carcinoma component in one nodule. Clin J Gastroenterol 2014; 7:449-54. [PMID: 26184027 DOI: 10.1007/s12328-014-0521-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2014] [Accepted: 08/03/2014] [Indexed: 12/13/2022]
Abstract
Primary neuroendocrine carcinomas (NECs) in the liver are very rare; however, several reports have described cases of a primary hepatic NEC combined with a hepatocellular carcinoma (HCC). We present the first report of a primary hepatic NEC with a cholangiocellular carcinoma (CCC) component in one nodule in a patient with a metachronous liver HCC. A 73-year old man who had received partial hepatectomy surgery because of a primary HCC and a primary CCC two years prior was diagnosed with a primary hepatic NEC after surgical treatment. Histological analysis of the resected tumor revealed that the tumor consisted of a predominant NEC area with a partial CCC component in one nodule and that the NEC cells were negative for markers of pancreatic NEC. Neoplastic cells in both the NEC and CCC component focally expressed CD44, a representative marker for cancer-initiating cells, and the CD44-positive cells in the NEC component were seen in the vicinity of those in the CCC component of one nodule. This case report provides suggestive information for the origin of primary hepatic NECs.
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31
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Masunaga A, Inoue K, Mizukami H, Hayashi T, Mitsuya T. Neuroendocrine carcinoma arising in a hepatitis C virus-infected liver: mechanism of the tumor development may be similar to that of development of pancreatic neuroendocrine cells. Pathol Int 2014; 64:81-85. [PMID: 24629176 DOI: 10.1111/pin.12138] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2013] [Accepted: 01/15/2014] [Indexed: 12/17/2022]
Abstract
We experienced a case of neuroendocrine carcinoma (NC). The tumor developed in the cirrhotic liver of a 62-year-old Japanese man who had been infected with hepatitis C virus. The tumor cells showed high N/C ratio, formed many rosettes, and expressed CD56, synaptophysin, HepPar1 and pancreatic and duodenal homeobox 1. MIB1 expression was 65%. Because both liver and pancreas are derived from a common endodermal layer during fetal development, we speculated that the tumor may have formed via the interaction of neurogenin 3, insulinoma-associated 1 gene and NeuroD/beta2, which are involved in the stage at which some pancreatic cells commit to becoming endocrine cells. Molecular analysis revealed that the NC had higher relative expression levels of mRNA of the three molecules than did the nontumorous liver. The results indicate that the NC in this patient may have formed via the same mechanism that acts in the development of pancreatic neuroendocrine cells.
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Affiliation(s)
- Atsuko Masunaga
- Department of Surgical Pathology, Showa University Fujigaoka Hospital, Yokohama, Japan
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32
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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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33
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Nakanishi C, Sato K, Ito Y, Abe T, Akada T, Muto R, Sakashita K, Konno T, Kato H, Satomi S. Combined hepatocellular carcinoma and neuroendocrine carcinoma with sarcomatous change of the liver after transarterial chemoembolization. Hepatol Res 2012; 42:1141-5. [PMID: 23094854 DOI: 10.1111/j.1872-034x.2012.01017.x] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Primary hepatic neuroendocrine carcinoma is rare and its origin is not clearly understood. An admixture of hepatocellular carcinoma (HCC) and neuroendocrine carcinoma is particularly rare. Here, we report a patient with an extremely rare combination of HCC and neuroendocrine carcinoma of the liver. To our knowledge, this is the first reported case in which the carcinoma showed sarcomatous change. The patient was a 76-year-old man who had received outpatient treatment for chronic hepatitis C. On abdominal computed tomography (CT), the hepatic tumor was enhanced in the arterial phase but its density was lower than that of normal liver in the portal phases. His serum α-fetoprotein (AFP) level was very high. Therefore, transarterial chemoembolization (TACE) was performed based on the diagnosis of HCC. Ten months after TACE, his serum AFP level had increased to the level measured before TACE. Partial hepatectomy was performed because CT revealed poor enhancement of the recurrent tumor. Histopathologically, the tumor consisted of two distinct components: moderately differentiated HCC was intermingled with a neuroendocrine carcinoma, which was accompanied by sarcomatous changes. Immunohistochemically, the neuroendocrine carcinoma cells were positive for CD56, chromogranin A and neuron-specific enolase, and negative for AFP. The sarcomatous area was positive for AE1/3 and CD56, consistent with sarcomatous change of neuroendocrine carcinoma. The neuroendocrine carcinoma and/or sarcomatous change may have been due to phenotypic changes and/or dedifferentiation of HCC induced by TACE. Six months after surgery, the patient was diagnosed with metastasis of the neuroendocrine carcinoma to sacral bone. He died 7 months after surgery.
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Affiliation(s)
- Chikashi Nakanishi
- Department of Surgery, Iwate Prefectural Iwai Hospital, Ichinoseki Division of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, Sendai, Japan
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34
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Gastric composite tumor of alpha fetoprotein-producing carcinoma/hepatoid adenocarcinoma and endocrine carcinoma with reference to cellular phenotypes. PATHOLOGY RESEARCH INTERNATIONAL 2012; 2012:201375. [PMID: 22482081 PMCID: PMC3317075 DOI: 10.1155/2012/201375] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/15/2011] [Revised: 11/14/2011] [Accepted: 12/12/2011] [Indexed: 12/17/2022]
Abstract
Alpha-fetoprotein-producing carcinoma (AFPC)/hepatoid adenocarcinoma (HAC) and neuroendocrine carcinoma (NEC) are uncommon in the stomach. Composite tumors consisting of these carcinomas and their histologic phenotypes are not well known. Between 2002 and 2007, to estimate the prevalence of composite tumors consisting of tubular adenocarcinoma, AFPC/HAC and NEC, we reviewed specimens obtained from 294 consecutive patients treated surgically for gastric cancer. We examined histological phenotype of tumors of AFPC or NEC containing the composite tumor by evaluating immunohistochemical expressions of MUC2, MUC5AC, MUC6, CDX2, and SOX2. Immunohistochemically, AFPC/HAC dominantly showed the intestinal or mixed phenotype, and NEC frequently showed the gastric phenotype. In the composite tumor, the tubular and hepatoid components showed the gastric phenotype, and the neuroendocrine component showed the mixed type. The unique composite tumor predominantly showed the gastric phenotype, and the hepatoid and neuroendocrine components were considered to be differentiated from the tubular component.
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35
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Tazi EM, Essadi I, M'rabti H, Errihani H. Hepatocellular Carcinoma and High Grade Neuroendocrine Carcinoma: A Case Report and Review of the Literature. World J Oncol 2011; 2:37-40. [PMID: 29147223 PMCID: PMC5649886 DOI: 10.4021/wjon276e] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/25/2011] [Indexed: 12/14/2022] Open
Abstract
We describe a rare hepatic collision tumor composed of a hepatocellular carcinoma and a high-grade neuroendocrine carcinoma. The patient, a 68-year-old man, underwent a partial hepatectomy because of a 4.0 cm mass. The tumor had two distinctive patterns. The majority of the tumor was a high-grade neuroendocrine carcinoma with features of a small cell carcinoma that was positive for chromogranin, synaptophysin, and cytokeratin 19 and negative for hepatocellular antigen and alpha-fetoprotein (AFP). The second component was a moderately differentiated hepatocellular carcinoma that was positive for hepatocellular antigen and AFP and negative for neuroendocrine markers. The two tumors were separated by fibrous bands. In areas where they collided, there was no transition or intermingling of cells between the two components, thus, it is different from the combined type of tumors. After removal of the tumor, the patient underwent four courses of chemotherappy which included etoposide and cisplatin with a follow-up period of 28 months.
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Affiliation(s)
- El Mehdi Tazi
- Department of Medical Oncology, National Institute of Oncology, Rabat, Morocco
| | - Ismail Essadi
- Department of Medical Oncology, National Institute of Oncology, Rabat, Morocco
| | - Hind M'rabti
- Department of Medical Oncology, National Institute of Oncology, Rabat, Morocco
| | - Hassan Errihani
- Department of Medical Oncology, National Institute of Oncology, Rabat, Morocco
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36
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Yang CS, Wen MC, Jan YJ, Wang J, Wu CC. Combined primary neuroendocrine carcinoma and hepatocellular carcinoma of the liver. J Chin Med Assoc 2009; 72:430-3. [PMID: 19686999 DOI: 10.1016/s1726-4901(09)70400-9] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
We report a unique case of combined primary neuroendocrine carcinoma (NEC) and hepatocellular carcinoma (HCC) of the liver in a 65-year-old male patient. The patient underwent segmental resection of the liver and regional lymph node dissection for a tumor mass that measured 7.5 cm in diameter in the right lobe, with regional lymphadenopathy. Histologically, the hepatic tumor was composed of predominantly small-cell NEC, but admixed with a small island of moderately differentiated HCC. We speculate that the NEC originated from a poorly differentiated tumor clone of an HCC that underwent neuroendocrine differentiation, and that this tumor was now at the end stage of the transitional period from HCC to NEC, based on the small amount of disappearing HCC. Ki-67 and p53 expression were higher in the NEC than in the HCC, and the lymph nodes showed only metastatic NEC. Therefore, this kind of tumor had a more aggressive clinical course in accordance with being an NEC rather than a conventional HCC. Three months after operation, the patient had multiple recurrent tumor nodules within the liver, spreading the metastasis to the adrenal glands and para-aortic lymph nodes. The patient died 1 year after operation.
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Affiliation(s)
- Chii-Shuenn Yang
- Department of Pathology, Taichung Veterans General Hospital, Taichung, Taiwan, R.O.C
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37
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Ewertsen C, Henriksen BM, Hansen CP, Knigge U. Synchronous gastric neuroendocrine carcinoma and hepatocellular carcinoma: a case report. BMJ Case Rep 2009; 2009:bcr03.2009.1667. [PMID: 21918674 DOI: 10.1136/bcr.03.2009.1667] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
UNLABELLED Gastric neuroendocrine carcinomas (NECs) are rare tumours that are divided into four subtypes depending on tumour characteristics. Patients with NECs are known to have an increased risk of synchronous and metachronous cancers mainly located in the gastrointestinal tract. A case of synchronous gastric NEC and hepatocellular carcinoma in a patient with several other precancerous lesions is presented. The patient had anaemia, and a gastric tumour and two duodenal polyps were identified on upper endoscopy. A CT scan of the abdomen revealed several lesions in the liver. The lesions were invisible on B-mode sonography and real-time sonography fused with CT was used to identify and biopsy one of the lesions. Histology showed hepatocellular carcinoma. A literature search showed that only one case of a hepatocellular carcinoma synchronous with a gastric NEC has been reported previously. TRIAL REGISTRATION NUMBER NCT00781924.
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Affiliation(s)
- Caroline Ewertsen
- Rigshospitalet, Copenhagen University Hospital, Department of Radiology, Section of Ultrasound, Blegdamsvej 9, Copenhagen OE, 2100, Denmark
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Garcia MT, Bejarano PA, Yssa M, Buitrago E, Livingstone A. Tumor of the liver (hepatocellular and high grade neuroendocrine carcinoma): a case report and review of the literature. Virchows Arch 2006; 449:376-81. [PMID: 16896889 DOI: 10.1007/s00428-006-0251-0] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2006] [Accepted: 06/07/2006] [Indexed: 12/12/2022]
Abstract
We describe a rare hepatic collision tumor composed of a hepatocellular carcinoma and a high-grade neuroendocrine carcinoma. The patient, a 50-year-old man, underwent a partial hepatectomy because of a 5.0-cm mass. The tumor had two distinctive patterns. The majority of the tumor was a high-grade neuroendocrine carcinoma with features of a small cell carcinoma that was positive for chromogranin, synaptophysin, and cytokeratin 19 and negative for hepatocellular antigen and alpha-fetoprotein (AFP). The second component was a moderately differentiated hepatocellular carcinoma that was positive for hepatocellular antigen and AFP and negative for neuroendocrine markers. The two tumors were separated by fibrous bands. In areas where they collided, there was no transition or intermingling of cells between the two components, thus, it is different from the combined type of tumors. After removal of the tumor, the patient had intrahepatic and mesenteric recurrences within a follow-up period of 16 months.
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Affiliation(s)
- Monica T Garcia
- Department of Pathology, University of Miami, Miller School of Medicine--Jackson Memorial Hospital, 1611 NW 12th Avenue, Holtz Building, Room 2042 G, Miami, FL 33136, USA.
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Abstract
Mixed endocrine tumors are tumors composed of at least two distinct tumor populations, one of which is endocrine. Because of their rarity and unusual presentation, endocrine mixed tumors raise many problems of diagnosis, management and therapy. Three main types of endocrine mixed tumors are recognized: The existence of these various types has been confirmed by recent molecular studies, even if the same studies have also shown that the histogenesis of a mixed endocrine tumor cannot be predicted from its histological features. Composite tumors are the less rare mixed tumors. The recent WHO classification recommends to restrict the term of composite endocrine tumor to the epithelial tumors containing at least 30% of obviously tumoral endocrine cells; some authors recommend to use higher thresholds, of at least 50%, in order to avoid overdiagnosis. The endocrine component is usually well differentiated, easily identified by its suggestive histological features; the endocrine nature of tumor cells is confirmed by the immunodetection of specific endocrine and neuro-endocrine markers (such as chromogranin A and synaptophysin). In some cases, the endocrine component is poorly differentiated: the demonstration of neuro-endocrine markers is necessary to confirm the diagnosis. Mixed tumors can occur in every anatomical site; they are more frequent in organs containing endocrine cells in the normal state (especially the digestive tract and the pancreas), but they can also be observed in organs devoid of endocrine cells (such as the mammary gland). The management of mixed endocrine tumors must take into account the more aggressive component. Mixed tumors containing a well differentiated endocrine component and an adenocarcinomatous component are to be treated like adenocarcinomas. Mixed tumors containing a poorly differentiated endocrine component must be considered as poorly differentiated endocrine carcinomas.
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Affiliation(s)
- Valérie Hervieu
- Service Central d'Anatomie et Cytologie Pathologiques, Hôpital Edouard Herriot, 3 place d'Arsonval, 69437 Lyon cedex
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Hiraoka A, Kurose K, Kumagi T, Hirooka M, Yokota T, Fujiwara T, Utsunomiya S, Hirata M, Ohtani H, Michitaka K, Horiike N, Kobayashi N, Onji M. Carcinoma with shared pathologic characteristics of both hepatocellular carcinoma and cholangiocarcinoma. CURRENT THERAPEUTIC RESEARCH 2005; 66:589-97. [PMID: 24678077 PMCID: PMC3966015 DOI: 10.1016/j.curtheres.2005.12.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 11/30/2005] [Indexed: 12/17/2022]
Abstract
BACKGROUND α-Fetoprotein (AFP) is a useful marker of hepatocellular carcinoma (HCC), and protein induced by vitamin K absence or antagonist II (PIVKA-II) and fucosylated AFP (AFP-L3) are specific tumor markers. OBJECTIVE The aim of this article was to report a case of intrahepatic cholangiocarcinoma (CC) with high levels of expression of AFP, AFP-L3, and PIVKA-II. METHODS A 70-year-old man weighing 66 kg with a diagnosis of intrahepatic CC presented with a liver tumor 4.0 cm in diameter and elevated concentrations of carbohydrate antigen 19-9 (575 U/mL), PIVKA-II (379 mAU/mL), and AFP (497 ng/mL; AFP-L3, 88.1%). On extended medial hepatic segmentectomy, microscopy showed that the tumor was a CC without HCC. The patient subsequently underwent immunohistochemical assessments using cytokeratin-19, epithelial membrane antigen (EMA), hepatocyte paraffin-1 (HP-1), PIVKA-II, and AFP. RESULTS In all specimens, desmoplasia was observed. However, results of immunohistochemistry showed positive results for cytokeratin-19 and EMA; HP-1 results were negative. Results of PIVKA-II and AFP testing in the tumor were positive. CONCLUSIONS The case presented here showed characteristics of CC and HCC, whereas the histologic expression of the tumor suggested CC. Based on the literature search, this is the first known report of a case of a CC expressing AFP and PIVKA-II confirmed on immunohistochemical staining. This case is interesting with regard to the ability of the progenitor cells to differentiate HCC and CC.
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Affiliation(s)
- Atsushi Hiraoka
- Third Department of Internal Medicine, Ehime University School of Medicine, Ehime, Japan
| | - Kiyotaka Kurose
- Third Department of Internal Medicine, Ehime University School of Medicine, Ehime, Japan
| | - Teru Kumagi
- Third Department of Internal Medicine, Ehime University School of Medicine, Ehime, Japan
| | - Masashi Hirooka
- Third Department of Internal Medicine, Ehime University School of Medicine, Ehime, Japan
| | - Tomoyuki Yokota
- Third Department of Internal Medicine, Ehime University School of Medicine, Ehime, Japan
| | - Toshiteru Fujiwara
- Third Department of Internal Medicine, Ehime University School of Medicine, Ehime, Japan
| | - Sachiko Utsunomiya
- Third Department of Internal Medicine, Ehime University School of Medicine, Ehime, Japan
| | - Mami Hirata
- Department of Internal Medicine, Matsuyama Johto Hospital, Ehime, Japan
| | - Hiromi Ohtani
- First Department of Surgery, Ehime University School of Medicine, Ehime, Japan
| | - Kojiro Michitaka
- Third Department of Internal Medicine, Ehime University School of Medicine, Ehime, Japan
| | - Norio Horiike
- Third Department of Internal Medicine, Ehime University School of Medicine, Ehime, Japan
| | - Nobuaki Kobayashi
- First Department of Surgery, Ehime University School of Medicine, Ehime, Japan
| | - Morikazu Onji
- Third Department of Internal Medicine, Ehime University School of Medicine, Ehime, Japan
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