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Fukuda M, Takahashi N, Ishikawa Y, Toya N, Sasuga K, Handa S, Sato S, Yano F, Eto K. Successful Conversion Surgery Following S-1 Plus Oxaliplatin Combined with Nivolumab Therapy for a Preoperatively Diagnosed Gastric Adenocarcinoma with Enteroblastic Differentiation: A Case Report. Surg Case Rep 2025; 11:24-0134. [PMID: 40230827 PMCID: PMC11994458 DOI: 10.70352/scrj.cr.24-0134] [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: 12/15/2024] [Accepted: 03/20/2025] [Indexed: 04/16/2025] Open
Abstract
INTRODUCTION Gastric adenocarcinoma with enteroblastic differentiation (GAED) is a rare subtype of gastric cancer known for its aggressive nature compared to conventional gastric adenocarcinoma. Due to its rarity and high malignancy, reports of successful medication therapy for Stage IV GAED are scarce. In this case, we report a GAED patient with peritoneal dissemination who responded well to combination chemotherapy with nivolumab, leading to the possibility of conversion surgery. CASE PRESENTATION A 74-year-old man presented with anemia and was diagnosed with GAED involving pancreatic infiltration and peritoneal dissemination. As first-line treatment, he underwent 9 cycles of S-1 and oxaliplatin chemotherapy combined with nivolumab. The tumor showed remarkable shrinkage. Staging laparoscopy revealed the disappearance of peritoneal nodules, and negative peritoneal cytology was confirmed intraoperatively. Consequently, conversion surgery was performed, involving laparoscopic distal gastrectomy with D2 lymph node dissection and Roux-en-Y reconstruction. Pathological examination showed ypT2N0M0, ypStage IB, with a chemotherapy response graded at 2a. Although peritoneal dissemination recurred 4 months after surgery, restarting nivolumab monotherapy significantly reduced ascites, and the patient maintained a partial response. CONCLUSIONS Stage IV GAED is associated with a poor prognosis; however, the advent of immune checkpoint inhibitors has expanded treatment options for these patients. In this case, we propose a personalized treatment strategy for GAED with peritoneal metastases that may improve clinical outcomes.
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Affiliation(s)
- Mizuki Fukuda
- Department of Surgery, The Jikei University, Kashiwa Hospital, Kashiwa, Chiba, Japan
| | - Naoto Takahashi
- Department of Surgery, The Jikei University, Kashiwa Hospital, Kashiwa, Chiba, Japan
| | - Yoshitaka Ishikawa
- Department of Surgery, The Jikei University, Kashiwa Hospital, Kashiwa, Chiba, Japan
| | - Naoki Toya
- Department of Surgery, The Jikei University, Kashiwa Hospital, Kashiwa, Chiba, Japan
| | - Kosuke Sasuga
- Department of Pathology, The Jikei University, Kashiwa Hospital, Kashiwa, Chiba, Japan
| | - Shoko Handa
- Department of Pathology, The Jikei University, Kashiwa Hospital, Kashiwa, Chiba, Japan
| | - Syun Sato
- Department of Pathology, The Jikei University, Kashiwa Hospital, Kashiwa, Chiba, Japan
| | - Fumiaki Yano
- Department of Gastrointestinal Surgery, The Jikei University School of Medicine, Tokyo, Japan
| | - Ken Eto
- Department of Gastrointestinal Surgery, The Jikei University School of Medicine, Tokyo, Japan
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Feng ZY, Wang AJ, Liu GY, Hu S, Xu C, Xu W. Hepatoid adenocarcinoma of the stomach with enteroblast differentiation: A case report. Shijie Huaren Xiaohua Zazhi 2025; 33:245-250. [DOI: 10.11569/wcjd.v33.i3.245] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2024] [Revised: 01/19/2025] [Accepted: 03/16/2025] [Indexed: 03/28/2025] Open
Abstract
BACKGROUND Hepatoid adenocarcinoma of the stomach (HAS) is a rare subtype of stomach carcinoma without specific clinical or endoscopic manifestations. The pathology is characterized by the presence of both gastric adenocarcinoma and hepatocellular carcinoma differentiation regions in the tumor tissue with some characteristic immunohistochemical markers. Here, we report a rare case of HAS with enteroblast differentiation in an elderly woman.
CASE SUMMARY A patient was found to have elevated alpha-fetoprotein during a physical examination. The patient was pathologically confirmed to have HAS with enteroblast differentiation after subtotal gastrectomy.
CONCLUSION HAS represents an uncommon subclassification of gastric cancer devoid of distinctive clinical manifestations. It is distinguished by the coexistence of gastric adenocarcinoma and hepatocellular carcinomatoid differentiation within the tumor tissue, presenting a unique histopathological profile. Given its scarcity in clinical practice, pathological diagnosis remains the definitive gold standard for identifying this entity.
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Affiliation(s)
- Zi-Yan Feng
- Department of Gastroenterology, Shenzhen Hospital, Southern Medical University, Shenzhen 518000, Guangdong Province, China
| | - An-Jiang Wang
- Department of Gastroenterology, Shenzhen Hospital, Southern Medical University, Shenzhen 518000, Guangdong Province, China
- Shenzhen Clinical Research Center for Digestive Disease, Shenzhen 518000, Guangdong Province, China
| | - Guang-Yu Liu
- Department of Gastrointestinal Surgery, Shenzhen Hospital, Southern Medical University, Shenzhen 518000, Guangdong Province, China
| | - Shan Hu
- Department of Nuclear Medicine, Shenzhen Hospital, Southern Medical University, Shenzhen 518000, Guangdong Province, China
| | - Cui Xu
- Department of Imaging, Shenzhen Hospital, Southern Medical University, Shenzhen 518000, Guangdong Province, China
| | - Wen Xu
- Department of Gastroenterology, Shenzhen Hospital, Southern Medical University, Shenzhen 518000, Guangdong Province, China
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Irizato M, Minamiguchi K, Fujita Y, Yamaura H, Onaya H, Taiji R, Tanaka T, Inaba Y. Distinctive imaging features of liver metastasis from gastric adenocarcinoma with enteroblastic differentiation: A case report. World J Radiol 2025; 17:104518. [DOI: 10.4329/wjr.v17.i2.104518] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2024] [Revised: 01/23/2025] [Accepted: 02/19/2025] [Indexed: 02/26/2025] Open
Abstract
BACKGROUND Gastric adenocarcinoma with enteroblastic differentiation (GAED) is one of the common subtypes of alpha-foetoprotein (AFP)-producing gastric cancer. GAED frequently results in venous invasion and liver metastasis, the latter being particularly linked to a poor prognosis. So far, the evidence for liver metastases from AFP-producing gastric cancer is only focused on those from gastric hepatoid adenocarcinoma, owing to their imaging similarities with hepatocellular carcinoma. This case report describes the characteristic diagnostic imaging findings of liver metastasis from GAED.
CASE SUMMARY A 65-year-old man who had undergone a pyloric gastrectomy for GAED two years ago was found to have a liver tumor in the hepatic segment 7, accompanied by elevated serum AFP levels. Dynamic contrast-enhanced computed tomography revealed the tumor showing peripheral-dominant enhancement in the arterial phase with persistent central enhancement in the delayed phase. Gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid-enhanced magnetic resonance imaging demonstrated a signal drop in the tumor periphery in chemical shift imaging, along with arterial enhancement. Additionally, rim-like hypointensity surrounding the tumor was observed in the hepatobiliary phase. Postresection examination confirmed the tumor to be a metastasis from GAED. Histopathological examination revealed severe invasion of the tumor into the portal vein and hepatic vein surrounding the tumor, which explained the imaging features.
CONCLUSION The imaging features of blood flow alternations resulting from vascular invasion may be crucial to diagnosing liver metastases from GAED.
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Affiliation(s)
- Mariko Irizato
- Department of Diagnostic and Interventional Radiology, Aichi Cancer Center Hospital, Nagoya 464-8681, Aichi, Japan
- Department of Diagnostic and Interventional Radiology, Nara Medical University, Kashihara 634-8522, Nara, Japan
| | - Kiyoyuki Minamiguchi
- Department of Diagnostic and Interventional Radiology, Nara Medical University, Kashihara 634-8522, Nara, Japan
| | - Yasuko Fujita
- Department of Diagnostic Pathology, Aichi Cancer Center Hospital, Nagoya 464-8681, Aichi, Japan
| | - Hidekazu Yamaura
- Department of Diagnostic and Interventional Radiology, Aichi Cancer Center Hospital, Nagoya 464-8681, Aichi, Japan
| | - Hiroaki Onaya
- Department of Diagnostic and Interventional Radiology, Aichi Cancer Center Hospital, Nagoya 464-8681, Aichi, Japan
| | - Ryosuke Taiji
- Department of Diagnostic and Interventional Radiology, Nara Medical University, Kashihara 634-8522, Nara, Japan
| | - Toshihiro Tanaka
- Department of Diagnostic and Interventional Radiology, Nara Medical University, Kashihara 634-8522, Nara, Japan
| | - Yoshitaka Inaba
- Department of Diagnostic and Interventional Radiology, Aichi Cancer Center Hospital, Nagoya 464-8681, Aichi, Japan
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Matsuyama S, Fukuda A, Matsumoto A, Ueo T, Ohana M, Seno H. Gastric Adenocarcinoma with Enteroblastic Differentiation which Demonstrated Rapid Progressive Courses. Intern Med 2025; 64:381-386. [PMID: 38925967 PMCID: PMC11867746 DOI: 10.2169/internalmedicine.3913-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Accepted: 05/06/2024] [Indexed: 06/28/2024] Open
Abstract
We herein report two extremely rare cases of gastric adenocarcinoma with enteroblastic differentiation (GAED) that underscore the aggressive nature of GAED. Case 1: endoscopic submucosal dissection (ESD) was scheduled for early-stage gastric cancer, however, the tumor increased in size drastically and the morphology changed to type "0-I + IIc" in one month. Surgery was performed and the patient was diagnosed with GAED. Case 2: ESD was performed for early-stage gastric cancer, and the pathological findings revealed GAED. The horizontal margin was positive for clear cells in the muscularis mucosa. Additional surgery was performed; however, recurrence occurred one year later. Therefore, the treatment strategies should be carefully considered for GAED.
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Affiliation(s)
- Sho Matsuyama
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Japan
- Department of Gastroenterology, Tenri Hospital, Japan
| | - Akihisa Fukuda
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Japan
| | | | - Taro Ueo
- Department of Gastroenterology, Tenri Hospital, Japan
| | - Masaya Ohana
- Department of Gastroenterology, Tenri Hospital, Japan
| | - Hiroshi Seno
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Japan
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Suzuki N, Odawara N, Fujisawa G, Ishibashi R, Hata M, Oya Y, Tamada K, Hayashi T, Abe S, Miyakawa Y, Hayakawa Y, Shinozaki-Ushiku A, Ushiku T, Boku N, Fujishiro M. Sustained Clinical Complete Response after Discontinuation of Trastuzumab-deruxetecan Due to Interstitial Pneumonia for HER2-positive Gastric Adenocarcinoma with Enteroblastic Differentiation (GAED). Intern Med 2025; 64:101-107. [PMID: 38839335 PMCID: PMC11781934 DOI: 10.2169/internalmedicine.3155-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2023] [Accepted: 04/17/2024] [Indexed: 06/07/2024] Open
Abstract
Trastuzumab deruxtecan (T-DXd) has demonstrated remarkable efficacy as a third- or later-line chemotherapy for human epidermal growth factor receptor 2 (HER2)-positive advanced gastric and gastroesophageal junction adenocarcinomas. However, it may cause pneumonitis, and its efficacy in rare histologies such as gastric adenocarcinoma with enteroblastic differentiation (GAED) remains unclear. A 74-year-old woman with unresectable HER2-positive GAED and lung metastasis received T-DXd as a fifth-line chemotherapy. Treatment was discontinued after 15 cycles owing to drug-induced pneumonitis; however, the patient achieved a sustained complete response for 14 months without subsequent chemotherapy or the exacerbation of pneumonitis. T-DXd was effective in HER2-positive GAED.
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Affiliation(s)
- Nobumi Suzuki
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Japan
| | - Nariaki Odawara
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Japan
| | - Gota Fujisawa
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Japan
| | - Rei Ishibashi
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Japan
| | - Masahiro Hata
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Japan
| | - Yukiko Oya
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Japan
| | - Kenji Tamada
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Japan
| | - Takeshi Hayashi
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Japan
| | - Sohei Abe
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Japan
| | - Yu Miyakawa
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Japan
| | - Yoku Hayakawa
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Japan
| | | | - Tetsuo Ushiku
- Department of Pathology, The University of Tokyo Hospital, Japan
| | - Narikazu Boku
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Japan
- Department of Oncology and General Medicine, IMSUT Hospital, Institute of Medical Science, The University of Tokyo, Japan
| | - Mitsuhiro Fujishiro
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Japan
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Shen X, Zhang H, Wang Z, Chen X, Qian A. Early gastric adenocarcinoma with enteroblastic differentiation diagnosed synchronously with a conventional gastric adenocarcinoma. Endoscopy 2024; 56:E983-E985. [PMID: 39537135 PMCID: PMC11560353 DOI: 10.1055/a-2443-3937] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2024]
Affiliation(s)
- Xiaonan Shen
- Department of Gastroenterology, Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital, Shanghai, China
| | - Heng Zhang
- Department of Pathology, Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital, Shanghai, China
| | - Zhengting Wang
- Department of Gastroenterology, Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital, Shanghai, China
| | - Xi Chen
- Department of Gastroenterology, Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital, Shanghai, China
| | - Aihua Qian
- Department of Gastroenterology, Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital, Shanghai, China
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Morais R, Moreira J, Gaspar R, Santos-Antunes J, Marques M, Coelho R, Alves R, Ferreira-Silva J, Dias E, Pereira P, Lopes S, Cardoso H, Sousa-Pinto B, Faria-Ramos I, Gullo I, Carneiro F, Liberal R, Macedo G. Higher frequency of gastric neoplasia in advanced chronic liver disease patients: Impact of screening endoscopy in an intermediate-high risk country. Dig Liver Dis 2024; 56:2133-2142. [PMID: 38811247 DOI: 10.1016/j.dld.2024.04.035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2023] [Revised: 04/28/2024] [Accepted: 04/29/2024] [Indexed: 05/31/2024]
Abstract
BACKGROUND The Baveno VII guidelines were proposed to identify which patients could safely avoid screening esophagogastroduodenoscopy (EGD) for gastroesophageal varices. We aimed to evaluate the frequency of gastric neoplasia in compensated advanced chronic liver disease (cACLD) patients who underwent EGD for screening of gastroesophageal varices (GOEV) compared to a healthy population. METHODS Retrospective study that enrolled all cACLD patients who underwent EGD for GOEV screening (January 2008-June 2018) in a tertiary reference center. cACLD patients were compared with asymptomatic healthy individuals who underwent EGD in a private hospital setting (April 2017-March 2018). RESULTS We evaluated 1845 patients (481 cACLD patients, 1364 healthy individuals). A significantly higher frequency of gastric neoplasia was observed in patients with cACLD compared to healthy individuals (4.0% vs. 1.0 %; p < 0.001). Rare histopathological subtypes (WHO Classification) accounted for 28.7 % of gastric carcinoma cases in the cACLD cohort. Seven cases of gastric neoplasia (36.8 % of gastric neoplasia cases in the cACLD patients) were diagnosed in patients who, according to the Baveno VII criteria, would have not been submitted to EGD. CONCLUSION We found an increased frequency of gastric neoplasia in patients with cACLD in comparison with healthy individuals. In countries with intermediate-high risk for GC, continuing to perform EGD could be beneficial.
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Affiliation(s)
- Rui Morais
- Faculty of Medicine of the University of Porto (FMUP), Portugal; Gastroenterology Department, Centro Hospitalar Universitário São João, Porto, Portugal.
| | - João Moreira
- Faculty of Medicine of the University of Porto (FMUP), Portugal
| | - Rui Gaspar
- Faculty of Medicine of the University of Porto (FMUP), Portugal; Gastroenterology Department, Centro Hospitalar Universitário São João, Porto, Portugal
| | - João Santos-Antunes
- Faculty of Medicine of the University of Porto (FMUP), Portugal; Gastroenterology Department, Centro Hospitalar Universitário São João, Porto, Portugal; i3S - Instituto de Investigação e Inovação em Saúde and Institute of Molecular Pathology and Immunology, University of Porto (Ipatimup), Portugal
| | - Margarida Marques
- Faculty of Medicine of the University of Porto (FMUP), Portugal; Gastroenterology Department, Centro Hospitalar Universitário São João, Porto, Portugal
| | - Rosa Coelho
- Faculty of Medicine of the University of Porto (FMUP), Portugal; Gastroenterology Department, Centro Hospitalar Universitário São João, Porto, Portugal
| | - Rosa Alves
- Internal Medicine Department, Centro Hospitalar Barreiro Montijo, Portugal
| | - Joel Ferreira-Silva
- Faculty of Medicine of the University of Porto (FMUP), Portugal; Gastroenterology Department, Centro Hospitalar Universitário São João, Porto, Portugal
| | - Emanuel Dias
- Faculty of Medicine of the University of Porto (FMUP), Portugal; Gastroenterology Department, Centro Hospitalar Universitário São João, Porto, Portugal
| | - Pedro Pereira
- Faculty of Medicine of the University of Porto (FMUP), Portugal; Gastroenterology Department, Centro Hospitalar Universitário São João, Porto, Portugal
| | - Susana Lopes
- Faculty of Medicine of the University of Porto (FMUP), Portugal; Gastroenterology Department, Centro Hospitalar Universitário São João, Porto, Portugal
| | - Hélder Cardoso
- Faculty of Medicine of the University of Porto (FMUP), Portugal; Gastroenterology Department, Centro Hospitalar Universitário São João, Porto, Portugal
| | - Bernardo Sousa-Pinto
- MEDCIDS-Department of Community Medicine, Information and Health Decision Sciences; Faculty of Medicine, University of Porto, Porto, Portugal; CINTESIS@RISE-Health Research Network, Faculty of Medicine, University of, Porto, Porto, Portugal
| | - Isabel Faria-Ramos
- Gastroenterology Department, Centro Hospitalar Universitário São João, Porto, Portugal
| | - Irene Gullo
- Faculty of Medicine of the University of Porto (FMUP), Portugal; Department of Pathology, Centro Hospitalar Universitário de São João, Portugal; i3S - Instituto de Investigação e Inovação em Saúde and Institute of Molecular Pathology and Immunology, University of Porto (Ipatimup), Portugal
| | - Fátima Carneiro
- Faculty of Medicine of the University of Porto (FMUP), Portugal; Department of Pathology, Centro Hospitalar Universitário de São João, Portugal; i3S - Instituto de Investigação e Inovação em Saúde and Institute of Molecular Pathology and Immunology, University of Porto (Ipatimup), Portugal
| | - Rodrigo Liberal
- Faculty of Medicine of the University of Porto (FMUP), Portugal; Gastroenterology Department, Centro Hospitalar Universitário São João, Porto, Portugal
| | - Guilherme Macedo
- Faculty of Medicine of the University of Porto (FMUP), Portugal; Gastroenterology Department, Centro Hospitalar Universitário São João, Porto, Portugal
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Liu CE, Cui H, Sun Q, Xin Q. An uncommon early gastric cancer with enteroblastic differentiation. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2024. [PMID: 39446098 DOI: 10.17235/reed.2024.10726/2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/25/2024]
Abstract
A 73-year-old man with a 25-year history of liver cirrhosis has been treated for liver cancer for 13 years. His cancer is currently well-controlled, and his AFP is normal. The gastroscopy revealed a clearly-border whitish mucosa with a frost-like coating in the greater curvature of gastric body. Under magnification, the lesion revealed that the micro-structure(MS) of the mucosal surface are faintly discernible, with the marginal crypt epithelium(MCE) showing irregular and closely spaced villous projections. The color tone of the IIb region appears the same with the surrounding mucosa. The micro-vascular(MV) structure is invisible. The crystal violet staining reveals the presence of micro-structures. Considering early-stage lesions, we successfully performed ESD treatment. The final diagnosis was gastric adenocarcinoma with enteroblastic differentiation (tub2>por1). We did the mapping to better evaluate the lesion. The main lesion is located in the mucosal layer, with small foci-infiltrating into the submucosal layer to a depth of 196um. Pathology about specimen No.A7 showed biopsy position. The epithelial cells were cubic, the atypia was significant, and the cytoplasm was transparent and vacuole-like. Immunohistochemistry supported the diagnosis of GAED. The additional surgery was recommended to reduce the risk of lymph node metastasis. However, the patient and their family refused it because of the complexity of the patient's condition. 14months after endoscopic treatment, there has been no recurrence of the lesion, and the patient is living well without any digestive discomfort.
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Affiliation(s)
- Chang-En Liu
- Gastroenterology and Hepatology, Tianjin Third Central Hospital. Tianjin Institute of Hepatobiliary Disease, China
| | - Hao Cui
- Gastroenterology and Hepatology, Tianjin Third Central Hospital. Tianjin Institute of Hepatobiliary Disease
| | - Qi Sun
- Pathology, Nanjing Drum Tower Hospital. The Affiliated Hospital of Nanjing University Medical School
| | - Qi Xin
- Pathology, Tianjin Third Central Hospital. Tianjin Institute of Hepatobiliary Disease
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Kővári B, Carneiro F, Lauwers GY. Epithelial tumours of the stomach. MORSON AND DAWSON'S GASTROINTESTINAL PATHOLOGY 2024:227-286. [DOI: 10.1002/9781119423195.ch13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Ge X, Hua M, Zhan Y. Gastric adenocarcinoma with intestinal progenitor cell differentiation: a morphologically underdiagnosed and more invasive distinctive type of gastric adenocarcinoma. Am J Cancer Res 2024; 14:3885-3895. [PMID: 39267675 PMCID: PMC11387865 DOI: 10.62347/rrhg4189] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Accepted: 08/12/2024] [Indexed: 09/15/2024] Open
Abstract
This study aims to explore the clinical and pathological characteristics, prognosis, diagnosis, and differential diagnosis of gastric adenocarcinoma with enteroblastic differentiation (GAED) in elderly patients. A total of 16 cases of GAED diagnosed from August 2019 to August 2022 at the First Affiliated Hospital of Nanchang University were retrospectively collected to analyze their clinical and pathological features. A control group of 360 cases of conventional gastric adenocarcinoma diagnosed during the same period was used for comparison. Among the 16 GAED patients, 11 were male and 5 were female, with ages ranging from 64 to 89 years (median age 75.5 years). Clinical manifestations of these patients included symptoms such as abdominal pain, bloating, hematemesis, and melena. The macroscopic classification revealed 11 cases of ulcerative lesions, 4 protruded lesions, and 1 diffusely infiltrative lesion. Tumor sizes varied from 3 to 9.5 cm in diameter, with a median diameter of 4.75 cm. Microscopically, the tumor cells exhibited tubular, papillary, and cribriform arrangements, with cuboidal or columnar morphology, relatively distinct cell boundaries, and cytoplasm that appeared clear or weakly acidophilic. Immunophenotyping analysis revealed the expression of SALL4 (15/16), Glypican-3 (12/16), CDX2 (12/16), CD10 (10/16), and p53 (12 cases exhibiting mutant expression, 4 cases exhibiting wild-type expression) within the tumor cells. There was no loss of mismatch repair proteins (MLH1, PMS2, MSH2, MSH6). The Ki-67 proliferation index ranged from 50% to 95%. In comparison to conventional gastric adenocarcinoma, GAED was frequently found in the gastric antrum (P<0.001) and exhibited a higher incidence of intravascular cancer emboli (P<0.001). Significant differences were noted in the Lauren classification, invasion depth, differentiation degree (P<0.01), and macroscopic type (P<0.05). However, no significant differences were found regarding age, gender, tumor diameter, neural invasion, or lymph node metastasis (P>0.05). The postoperative follow-up ranging from 5 to 29 months revealed one death and 15 cases of disease-free survival. GAED is a special subtype of gastric adenocarcinoma characterized by a combination of embryonal and intestinal differentiation immunophenotypes, as well as its increased propensity for biological invasion. Accurate identification of GAED is crucial in pathological practice, as it helps differentiate between GAED and conventional adenocarcinoma and aids in the evaluation of tumor malignancy. Furthermore, it is imperative to conduct a differential diagnosis that involves hepatoid adenocarcinoma, yolk sac tumor-like adenocarcinoma, and metastatic hepatocellular carcinoma.
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Affiliation(s)
- Xian Ge
- Jiangxi Provincial Key Laboratory for Precision Pathology and Intelligent Diagnosis, Department of Pathology and Institute of Molecular Pathology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University Nanchang 330006, Jiangxi, China
| | - Meiling Hua
- Jiangxi Provincial Key Laboratory for Precision Pathology and Intelligent Diagnosis, Department of Pathology and Institute of Molecular Pathology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University Nanchang 330006, Jiangxi, China
| | - Yuan Zhan
- Jiangxi Provincial Key Laboratory for Precision Pathology and Intelligent Diagnosis, Department of Pathology and Institute of Molecular Pathology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University Nanchang 330006, Jiangxi, China
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Kodama T, Tani A, Yamane H, Itoh T. A case of pancreatic ductal adenocarcinoma with enteroblastic, neuroendocrine, and squamous differentiation with p53 overexpression and loss of Rb expression. Int J Surg Case Rep 2024; 120:109854. [PMID: 38851063 PMCID: PMC11215098 DOI: 10.1016/j.ijscr.2024.109854] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2024] [Revised: 05/31/2024] [Accepted: 06/01/2024] [Indexed: 06/10/2024] Open
Abstract
INTRODUCTION Herein we report a case of an extremely rare pancreatic adenocarcinoma with enteroblastic differentiation (AED), an underrecognized histological subtype. Moreover, the tumor was mixed with a neuroendocrine carcinoma (NEC), which is also a rare malignancy in the pancreas. CASE PRESENTATION The patient was an elderly male who was incidentally diagnosed with a 35 mm-sized pancreatic head tumor and underwent pancreatoduodenectomy. Histopathologically, the tumor was composed of four different types: conventional ductal adenocarcinoma, AED, NEC, and squamous cell carcinoma. Interestingly, p53 overexpression and loss of Rb expression, which are characteristic findings of NEC, were observed in all components. He had been received adjuvant chemotherapy after the surgery, however, he died of bath-related cardiac arrest 14 months after surgery. DISCUSSION In the stomach, AED, a carcinoma resembling fetal gut epithelium, is a rare but established subtype and is considered a related entity of hepatoid carcinoma (HAC). However, gastric AED and HAC differ to some extent. In contrast to the stomach, extragastric AED, including pancreatic AED, is extremely rare, and its biological features are unclear. A mixed tumor with NEC is a complex phenomenon, but it is occasionally reported in extragastric AED. The histogenesis of mixed AED-NEC can be resolved by determining p53 and Rb status. CONCLUSION Owing to their rare and novel nature, extragastric AED is under-recognized or confused with HAC. Further studies and the establishment of an extragastric AED classification are required.
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Affiliation(s)
- Takayuki Kodama
- Division of Pathology, Department of Pathology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan; Department of Diagnostic Pathology, Kobe University Hospital, Kobe 650-0017, Japan.
| | - Akiho Tani
- Department of Diagnostic Pathology, Kobe University Hospital, Kobe 650-0017, Japan.
| | - Hisoka Yamane
- Department of Hepato-Biliary-Pancreatic Surgery, Kobe University Hospital, Kobe 650-0017, Japan; Department of Surgery, Seirei Mikatahara General Hospital, Hamamatsu 433-8558, Japan
| | - Tomoo Itoh
- Department of Diagnostic Pathology, Kobe University Hospital, Kobe 650-0017, Japan.
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Kraemer M, Zander T, Alakus H, Buettner R, Lyu SI, Simon AG, Schroeder W, Bruns CJ, Quaas A. Fetal gut cell-like differentiation in esophageal adenocarcinoma defines a rare tumor subtype with therapeutically relevant claudin-6 positivity and SWI/SNF gene alteration. Sci Rep 2024; 14:13474. [PMID: 38866822 PMCID: PMC11169473 DOI: 10.1038/s41598-024-64116-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Accepted: 06/05/2024] [Indexed: 06/14/2024] Open
Abstract
Esophageal adenocarcinoma (EAC) is one of the deadliest tumor entities worldwide, with a 5-year survival rate of less than 25%. Unlike other tumor entities, personalized therapy options are rare, partly due to the lack of knowledge about specific subgroups. In this publication, we demonstrate a subgroup of patients with EAC in a large screening cohort of 826 patients, characterized by specific morphological and immunohistochemical features. This subgroup represents approximately 0.7% (6/826) of the total cohort. Morphological features of this subgroup show a striking clear cytoplasm of the tumour cells and the parallel existence of rare growth patterns like yolk sac-like differentiation and enteroblastic differentiation. Immunohistochemistry reveals expression of the fetal gut cell-like proteins Sal-like protein 4 (SALL4), claudin-6, and glypican 3. Interestingly, we find a correlation with alterations of SWI/SNF-complex associated genes, which are supposed to serve as tumor suppressor genes in various tumour entities. Our results suggest a possible implication of rare tumour subtypes in the WHO classification for EACs according to the classification for gastric cancer. Furthermore, claudin-6 positive tumors have shown promising efficacy of CAR T cell therapy in the recently published BNT-211-01 trial (NCT04503278). This represents a personalized therapeutic option for this tumor subtype.
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Affiliation(s)
- Max Kraemer
- Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Gastrointestinal Cancer Group Cologne GCGC, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.
| | - Thomas Zander
- Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Gastrointestinal Cancer Group Cologne GCGC, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany
| | - Hakan Alakus
- Department of General, Visceral, Cancer and Transplantation Surgery, University Hospital Cologne, Cologne, Germany
| | - Reinhard Buettner
- Faculty of Medicine, University Hospital of Cologne, Institute of Pathology, University of Cologne, Cologne, Germany
| | - Su Ir Lyu
- Faculty of Medicine, University Hospital of Cologne, Institute of Pathology, University of Cologne, Cologne, Germany
| | - Adrian Georg Simon
- Faculty of Medicine, University Hospital of Cologne, Institute of Pathology, University of Cologne, Cologne, Germany
| | - Wolfgang Schroeder
- Department of General, Visceral, Cancer and Transplantation Surgery, University Hospital Cologne, Cologne, Germany
| | - Christiane J Bruns
- Department of General, Visceral, Cancer and Transplantation Surgery, University Hospital Cologne, Cologne, Germany
| | - Alexander Quaas
- Faculty of Medicine, University Hospital of Cologne, Institute of Pathology, University of Cologne, Cologne, Germany
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13
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Li M, Chen J, Wang W, Hou C. Gastric Adenocarcinoma with Enteroblastic Differentiation in the Presence of Calcification: A Case Report and Review of the Literature. Int J Surg Pathol 2024; 32:845-850. [PMID: 37715642 DOI: 10.1177/10668969231195078] [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] [Indexed: 09/18/2023]
Abstract
Gastric adenocarcinoma with enteroblastic differentiation is a specific subtype of gastric cancer that is rare and highly malignant, usually presenting at an early stage with lymphovascular invasion, lymph node, and distant metastases, resulting in a poor prognosis. The pathology of this patient showed a classic tubular adenocarcinoma infiltrating into the mucosal layer, with the presence of cytoplasmic translucent tumor cells below the mucosal layer. It is noteworthy that this patient did not exhibit lymphovascular invasion, lymph node, and distant metastasis. Additionally, a large amount of calcification was observed; therefore, it remains unclear whether there exists any correlation between the two factors. To the best of our knowledge, this is the first case report demonstrating massive calcification in gastric adenocarcinoma with enteroblastic differentiation, which may have implications for future diagnosis of this rare subtype of gastric cancer.
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Affiliation(s)
- Mengyao Li
- Department of Pathology, Shaoxing People's Hospital, Shaoxing, China
| | - Jiajun Chen
- Department of Urology, Shaoxing People's Hospital, Shaoxing, China
| | - Weihao Wang
- Department of Urology, Shaoxing People's Hospital, Shaoxing, China
| | - Chuanling Hou
- Department of Pathology, Shaoxing People's Hospital, Shaoxing, China
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14
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Nakayama H, Ida T, Hasegawa Y, Sakamoto A, Umezawa Y, Inaba Y, Nakada H. Stage IV gastric adenocarcinoma with enteroblastic differentiation with 5-year relapse-free survival after D2 gastrectomy and chemotherapy: A case report. Surg Case Rep 2024; 10:123. [PMID: 38744791 PMCID: PMC11093955 DOI: 10.1186/s40792-024-01921-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Accepted: 05/06/2024] [Indexed: 05/16/2024] Open
Abstract
BACKGROUND Gastric adenocarcinoma with enteroblastic differentiation (GACED), a rare subtype of gastric cancer, is associated with a more aggressive behavior than conventional gastric adenocarcinomas. We report a rare case of stage IV GACED treated with D2 gastrectomy and postoperative chemotherapy. CASE PRESENTATION A 39-year-old woman with acute upper abdominal pain immediately underwent surgery for gastric perforation. Afterward she was diagnosed with adenocarcinoma of the pylorus. D2 gastrectomy was performed and the final pathological diagnosis was stage IV GACED with positive peritoneal cytology. Postoperative chemotherapy was initiated with S1 plus oxaliplatin for 1 year, which was ceased thereafter to enhance her quality of life. The patient survived more than 5 years without relapse after gastrectomy. CONCLUSIONS Stage IV GACED, determined by positive spalt-like transcription factor 4, can be successfully treated with surgery and chemotherapy.
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Affiliation(s)
- Hiroshi Nakayama
- Department of Gastroenterological Surgery, Digestive Disease Center, NHO Tokyo National Hospital, 3-1-1 Takeoka, Kiyose-shi, Tokyo, 204-8431, Japan.
- Department of Surgery, Omori Red Cross Hospital, 4-30-1 Chuo, Ota-ku, Tokyo, 143-8527, Japan.
| | - Tomonori Ida
- Department of Gastroenterology, Omori Red Cross Hospital, 4-30-1 Chuo, Ota-ku, Tokyo, 143-8527, Japan
| | - Yui Hasegawa
- Department of Surgery, Omori Red Cross Hospital, 4-30-1 Chuo, Ota-ku, Tokyo, 143-8527, Japan
| | - Atsuhiko Sakamoto
- Department of Pathology and Laboratory Medicine, Omori Red Cross Hospital, 4-30-1 Chuo, Ota-ku, Tokyo, 143-8527, Japan
| | - Yoko Umezawa
- Department of Pathology and Laboratory Medicine, Omori Red Cross Hospital, 4-30-1 Chuo, Ota-ku, Tokyo, 143-8527, Japan
- Department of Pathology, Fukushima Medical University Hospital, 1 Hikariga-Oka, Fukushima, 960-1295, Japan
| | - Yuki Inaba
- Department of Surgery, Omori Red Cross Hospital, 4-30-1 Chuo, Ota-ku, Tokyo, 143-8527, Japan
| | - Hiroshi Nakada
- Department of Gastroenterological Surgery, Digestive Disease Center, NHO Tokyo National Hospital, 3-1-1 Takeoka, Kiyose-shi, Tokyo, 204-8431, Japan
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15
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Choi JH, Thung SN. Recent Advances in Pathology of Intrahepatic Cholangiocarcinoma. Cancers (Basel) 2024; 16:1537. [PMID: 38672619 PMCID: PMC11048541 DOI: 10.3390/cancers16081537] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Revised: 04/10/2024] [Accepted: 04/16/2024] [Indexed: 04/28/2024] Open
Abstract
Intrahepatic cholangiocarcinoma (ICCA) is a malignant epithelial neoplasm characterized by biliary differentiation within the liver. ICCA is molecularly heterogeneous and exhibits a broad spectrum of histopathological features. It is a highly aggressive carcinoma with high mortality and poor survival rates. ICCAs are classified into two main subtypes: the small-duct type and large-duct types. These two tumor types have different cell origins and clinicopathological features. ICCAs are characterized by numerous molecular alterations, including mutations in KRAS, TP53, IDH1/2, ARID1A, BAP1, BRAF, SAMD4, and EGFR, and FGFR2 fusion. Two main molecular subtypes-inflammation and proliferation-have been proposed. Recent advances in high-throughput assays using next-generation sequencing have improved our understanding of ICCA pathogenesis and molecular genetics. The diagnosis of ICCA poses a significant challenge for pathologists because of its varied morphologies and phenotypes. Accurate diagnosis of ICCA is essential for effective patient management and prognostic determination. This article provides an updated overview of ICCA pathology, focusing particularly on molecular features, histological subtypes, and diagnostic approaches.
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Affiliation(s)
- Joon Hyuk Choi
- Department of Pathology, Yeungnam University College of Medicine, Daegu 42415, Republic of Korea
| | - Swan N. Thung
- Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, 1468 Madison Avenue, New York, NY 10029, USA;
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16
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Rodríguez-Villena A, Veliz-Domínguez A, González-García I, Ruz-Caracuel I. Enteroblastic adenocarcinoma of the ampulla of Vater. REVISTA ESPANOLA DE PATOLOGIA : PUBLICACION OFICIAL DE LA SOCIEDAD ESPANOLA DE ANATOMIA PATOLOGICA Y DE LA SOCIEDAD ESPANOLA DE CITOLOGIA 2024; 57:151-155. [PMID: 38599738 DOI: 10.1016/j.patol.2024.01.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Revised: 12/11/2023] [Accepted: 01/09/2024] [Indexed: 04/12/2024]
Abstract
Adenocarcinoma with enteroblastic differentiation is a rare histologic subtype of adenocarcinoma of the gastrointestinal tract that shows unique histologic and immunohistochemical features that resemble fetal intestinal epithelium. This histological subtype has been widely described in the stomach, where it most frequently appears, but, in other locations, it is misdiagnosed because of the poor experience in routine diagnostic setting. Here we present a case of an 87-year-old male with an adenocarcinoma of the ampulla of Vater with enteroblastic differentiation with a literature review of the cases described of this subtype in this location to date. The anatomical peculiarity of the ampulla, joined with the infrequent nature of this histological subtype, makes this case of great interest to aid to better characterize the biological behavior of these tumors.
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Affiliation(s)
- Amanda Rodríguez-Villena
- Servicio de Anatomía Patológica, Hospital Universitario Ramón y Cajal, IRYCIS, 28034 Madrid, Spain
| | | | - Irene González-García
- Servicio de Anatomía Patológica, Hospital del Mar, Hospital del Mar Research Institute, 08003 Barcelona, Spain
| | - Ignacio Ruz-Caracuel
- Servicio de Anatomía Patológica, Hospital Universitario Ramón y Cajal, IRYCIS, 28034 Madrid, Spain; CIBER-ONC, Instituto de Salud Carlos III, 28029 Madrid, Spain.
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17
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Cui Y, Liu Y, Du B, Li Y, Li X. Gallbladder's Adenocarcinoma With Enteroblastic Differentiation Revealed by 18 F-FDG PET/CT. Clin Nucl Med 2024; 49:258-259. [PMID: 38271224 PMCID: PMC11444348 DOI: 10.1097/rlu.0000000000005055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2024]
Abstract
ABSTRACT Gallbladder's adenocarcinoma with enteroblastic differentiation (GAED) is extremely rare. A 43-year-old woman complained of pain in the right upper abdomen, and enhanced CT showed a cystic and solid mixed mass in the hepatic hilar region. Adenocarcinoma with enteroblastic differentiation was pathologically identified. 18 F-FDG PET/CT revealed a lesion in the gallbladder neck with increased FDG uptake, accompanied by a cystic and solid mixed mass in the hepatic hilar region with liver and lymph node metastases. Gallbladder biopsy was also carried out, and GAED was confirmed. 18 F-FDG PET/CT may assist in the evaluation of GAED and guide biopsy.
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Affiliation(s)
- Yan Cui
- From the Department of Nuclear Medicine, The First Hospital of China Medical University, Shenyang, Liaoning, China
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18
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Takayama-Isagawa Y, Kanetaka K, Kobayashi S, Yoneda A, Ito S, Eguchi S. High serum alpha-fetoprotein and positive immunohistochemistry of alpha-fetoprotein are related to poor prognosis of gastric cancer with liver metastasis. Sci Rep 2024; 14:3695. [PMID: 38355790 PMCID: PMC10866906 DOI: 10.1038/s41598-024-54394-1] [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: 06/24/2023] [Accepted: 02/12/2024] [Indexed: 02/16/2024] Open
Abstract
Liver metastasis in gastric cancer is incurable. Alpha-fetoprotein-producing gastric cancer has a poor prognosis and is prone to liver metastasis. We investigated the association between preoperative serum alpha-fetoprotein levels, liver metastasis, and expression of primitive enterocyte phenotype markers. We reviewed the medical records of 401 patients with gastric cancer who underwent curative surgical resection and immunohistochemically evaluated the primitive phenotype markers. The preoperative serum alpha-fetoprotein levels were elevated and normal in 8 and 393 patients, respectively. Liver metastasis was more frequent in patients with higher preoperative alpha-fetoprotein levels. The 5-year postoperative recurrence-free survival and overall survival rates were significantly worse in patients with higher preoperative serum alpha-fetoprotein levels. Although alpha-fetoprotein and Glypican3 and Spalt-like transcription factor 4 tended to be stained with high preoperative serum alpha-fetoprotein levels, these markers were also positive in some patients with normal alpha-fetoprotein levels. In summary, patients with gastric cancer and high preoperative serum alpha-fetoprotein levels have a poor prognosis and high incidence of liver metastasis. Alpha-fetoprotein can help detect liver metastasis relating to the primitive enterocyte phenotype.
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Affiliation(s)
- Yuriko Takayama-Isagawa
- Department of Pathology, Jichi Medical University Hospital, Shimotsuke, Japan
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto 1-7-1, Nagasaki, 8528501, Japan
| | - Kengo Kanetaka
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto 1-7-1, Nagasaki, 8528501, Japan.
| | - Shinichiro Kobayashi
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto 1-7-1, Nagasaki, 8528501, Japan
| | - Akira Yoneda
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto 1-7-1, Nagasaki, 8528501, Japan
| | - Shinichiro Ito
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto 1-7-1, Nagasaki, 8528501, Japan
| | - Susumu Eguchi
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto 1-7-1, Nagasaki, 8528501, Japan
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19
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Chun J, Moore M, Kelly P, Kanzawa M, Itoh T, Hong SM, Zen Y. Enteroblastic cholangiocarcinoma: An uncommon, underrecognized subtype of bile duct cancer. Hum Pathol 2024; 144:46-52. [PMID: 38301963 DOI: 10.1016/j.humpath.2024.01.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2023] [Revised: 01/26/2024] [Accepted: 01/29/2024] [Indexed: 02/03/2024]
Abstract
Enteroblastic carcinoma is clinically characterized by an elevated serum level of alpha-fetoprotein (AFP) and is histologically characterized by cancer cells with a clear cytoplasm and 'blastic' coarse chromatin. It sometimes has an element of hepatoid carcinoma; therefore, these two neoplasms are often regarded as sister entities. Although hepatoid carcinoma in the biliary tree has been reported, enteroblastic cholangiocarcinoma is extremely uncommon. In the present study, four cases of enteroblastic cholangiocarcinoma were examined. Tumors were located inside the liver (n = 2) or common bile duct (n = 2). The two intrahepatic cases had a history of primary sclerosing cholangitis, and serum AFP levels were elevated in both. One unresectable case was diagnosed by needle liver biopsy, while the remaining three underwent surgical resection. Histologically, all cases showed similar microscopic features. Cuboidal or polygonal cancer cells with the characteristic clear cytoplasm and subnuclear vacuoles were arranged in a papillary, micropapillary, tubular, or solid architecture. One case had an element of pancreatobiliary-type adenocarcinoma, while a hepatoid carcinoma element was not observed in any cases. All cases were positive for AFP, glypican 3, and SALL4, with SALL4 being the most widely expressed. Heppar-1 and arginase-1 were negative, except for one case, which was positive for Heppar-1. In conclusion, enteroblastic cholangiocarcinoma is an uncommon subtype of biliary tract malignancy. These cases may have been categorized as 'clear cell' cholangiocarcinoma. Although enteroblastic cholangiocarcinoma seems to occur more commonly in extrahepatic regions, including the gallbladder, it may also develop in the liver, particularly in patients with primary sclerosing cholangitis.
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Affiliation(s)
- Jihyun Chun
- Institute of Liver Studies, King's College Hospital, London, SE5 9RS, UK; Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea
| | - Michelle Moore
- Cellular Pathology, Royal Victoria Hospital, Belfast Health and Social Care Trust, Belfast, BT12 6BA, UK
| | - Paul Kelly
- Cellular Pathology, Royal Victoria Hospital, Belfast Health and Social Care Trust, Belfast, BT12 6BA, UK
| | - Maki Kanzawa
- Department of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe, 650-0017, Japan
| | - Tomoo Itoh
- Department of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe, 650-0017, Japan
| | - Seung-Mo Hong
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea
| | - Yoh Zen
- Institute of Liver Studies, King's College Hospital, London, SE5 9RS, UK.
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20
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Yang X, Wu Y, Wang A, Ma X, Zhou K, Ji K, Ji X, Zhang J, Wu X, Li Z, Bu Z. Immunohistochemical characteristics and potential therapeutic regimens of hepatoid adenocarcinoma of the stomach: a study of 139 cases. J Pathol Clin Res 2024; 10:e343. [PMID: 37974386 PMCID: PMC10766033 DOI: 10.1002/cjp2.343] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2023] [Revised: 08/13/2023] [Accepted: 08/28/2023] [Indexed: 11/19/2023]
Abstract
Hepatoid adenocarcinoma of stomach (HAS) is a special subtype of gastric cancer with poor prognosis. Immunohistochemical analysis could provide important clues for the treatment of HAS. A total of 159 patients were diagnosed as HAS and 139 were enrolled in this study. Statistical differences were determined using relative test methods and survival analyses were performed by the Kaplan-Meier method to find survival differences. All tumors in this study were negative for Epstein-Barr virus-encoded small RNAs (EBERs) and almost all showed no loss of mismatch repair (MMR) proteins and were positive for alpha fetoprotein (AFP or spalt like transcription factor 4 (SALL4). About half of the tumors had a positive programmed death-ligand 1 combined positive score (CPS) and 17.3% were positive for human epidermal growth factor receptor 2 (HER2). In addition, there was a relatively high proportion of cmet expression. We also found that HAS patients with recurrent disease treated by emerging therapy had a better survival than those treated with traditional chemotherapy (p = 0.002, median recurrence-to-death survival: 23 months versus 6 months); HAS patients who received anti-HER2 therapy or harbored MMR deficiency had favorable prognosis. Overall, high proportions of MMR protein proficiency, positivity for AFP or SALL4, overexpression of HER2, CPS and cmet, as well as negative EBER findings, are distinctive characteristics of HAS patients. While negative EBER and MMR proficiency indicate molecular features of HAS, positivity for AFP or SALL4 could aid in the diagnosis of HAS. In addition, HAS patients could benefit from anti-HER2 therapy, immunotherapy, and anti-angiogenesis therapy.
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Affiliation(s)
- Xuesong Yang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Center of Gastrointestinal CancerPeking University Cancer Hospital & InstituteBeijingPR China
| | - Yan Wu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of PathologyPeking University Cancer Hospital & InstituteBeijingPR China
| | - Anqiang Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Center of Gastrointestinal CancerPeking University Cancer Hospital & InstituteBeijingPR China
| | - Xiuli Ma
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of PathologyPeking University Cancer Hospital & InstituteBeijingPR China
| | - Kai Zhou
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Center of Gastrointestinal CancerPeking University Cancer Hospital & InstituteBeijingPR China
| | - Ke Ji
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Center of Gastrointestinal CancerPeking University Cancer Hospital & InstituteBeijingPR China
| | - Xin Ji
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Center of Gastrointestinal CancerPeking University Cancer Hospital & InstituteBeijingPR China
| | - Ji Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Center of Gastrointestinal CancerPeking University Cancer Hospital & InstituteBeijingPR China
| | - Xiaojiang Wu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Center of Gastrointestinal CancerPeking University Cancer Hospital & InstituteBeijingPR China
| | - ZhongWu Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of PathologyPeking University Cancer Hospital & InstituteBeijingPR China
| | - Zhaode Bu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Center of Gastrointestinal CancerPeking University Cancer Hospital & InstituteBeijingPR China
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21
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Chang WC, Zhang YZ, Nicholson AG. Pulmonary invasive mucinous adenocarcinoma. Histopathology 2024; 84:18-31. [PMID: 37867404 DOI: 10.1111/his.15064] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2023] [Revised: 09/13/2023] [Accepted: 09/24/2023] [Indexed: 10/24/2023]
Abstract
Invasive mucinous adenocarcinoma (IMA) is a relatively rare subtype of lung adenocarcinoma, composed of goblet and/or columnar tumour cells containing abundant intracytoplasmic mucin vacuoles. While a majority of IMAs are driven by KRAS mutations, recent studies have identified distinct genomic alterations, such as NRG1 and ERBB2 fusions. IMAs also more frequently present as a pneumonic-like pattern with multifocal and multilobar involvement, and comparative genomic profiling predominantly shows a clonal relationship, suggesting intrapulmonary metastases rather than synchronous primary tumours. Accordingly, these unique features require different therapeutic approaches when compared to nonmucinous adenocarcinomas in general. In this article, we review recent updates on the histopathological, clinical, and molecular features of IMAs, and also highlight some unresolved issues for future studies.
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Affiliation(s)
- Wei-Chin Chang
- Department of Pathology, Taipei Medical University Hospital, Taipei, Taiwan
- Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Yu Zhi Zhang
- Department of Histopathology, Royal Brompton and Harefield Hospitals, Guy's and St Thomas' NHS Foundation Trust, London, UK
- National Heart and Lung Institute, Imperial College, London, UK
| | - Andrew G Nicholson
- Department of Histopathology, Royal Brompton and Harefield Hospitals, Guy's and St Thomas' NHS Foundation Trust, London, UK
- National Heart and Lung Institute, Imperial College, London, UK
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22
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Shin J, Park YS. Unusual or Uncommon Histology of Gastric Cancer. J Gastric Cancer 2024; 24:69-88. [PMID: 38225767 PMCID: PMC10774758 DOI: 10.5230/jgc.2024.24.e7] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Revised: 12/06/2023] [Accepted: 12/07/2023] [Indexed: 01/17/2024] Open
Abstract
This review comprehensively examines the diverse spectrum of gastric cancers, focusing on unusual or uncommon histology that presents significant diagnostic and therapeutic challenges. While the predominant form, tubular adenocarcinoma, is well-characterized, this review focuses on lesser-known variants, including papillary adenocarcinoma, micropapillary carcinoma, adenosquamous carcinoma, squamous cell carcinoma (SCC), hepatoid adenocarcinoma, gastric choriocarcinoma, gastric carcinoma with lymphoid stroma, carcinosarcoma, gastroblastoma, parietal cell carcinoma, oncocytic adenocarcinoma, Paneth cell carcinoma, gastric adenocarcinoma of the fundic gland type, undifferentiated carcinoma, and extremely well-differentiated adenocarcinoma. Although these diseases have different nomenclatures characterized by distinct histopathological features, these phenotypes often overlap, making it difficult to draw clear boundaries. Furthermore, the number of cases was limited, and the unique histopathological nature and potential pathogenic mechanisms were not well defined. This review highlights the importance of understanding these rare variants for accurate diagnosis, effective treatment planning, and improving patient outcomes. This review emphasizes the need for ongoing research and case studies to enhance our knowledge of these uncommon forms of gastric cancer, which will ultimately contribute to more effective treatments and better prognostic assessments. This review aimed to broaden the pathological narrative by acknowledging and addressing the intricacies of all cancer types, regardless of their rarity, to advance patient care and improve prognosis.
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Affiliation(s)
- Jinho Shin
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Young Soo Park
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
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23
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Ishikawa A, Nakamura K. Gastric Adenocarcinoma with Enteroblastic Differentiation Resected through Endoscopic Submucosal Dissection: A Case Report. Case Rep Gastroenterol 2024; 18:68-73. [PMID: 38333765 PMCID: PMC10852983 DOI: 10.1159/000535954] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2023] [Accepted: 12/19/2023] [Indexed: 02/10/2024] Open
Abstract
Introduction Gastric adenocarcinoma with enteroblastic differentiation (GAED) is a rare histological type of gastric adenocarcinoma that occurs in the stomach and is known for its aggressive behavior. GAED is diagnosed histopathologically and is often advanced at the time of diagnosis. Case Presentation We report the case of a 70-year-old male with a 20-mm superficial depressed lesion on the anterior wall of the antrum. Histological examination of the endoscopic submucosal dissection specimen revealed that the tumor was composed of dilated or slit-like branching tubules; additionally, the tumor cells had clear cytoplasm resembling that of the fetal digestive tract. Immunohistochemically, the tumor cells were positive for Glypican-3 and alpha-fetoprotein. A pathological diagnosis of GAEDs was established. GAED was found in approximately 30% of all the tumor cells and showed lymphatic invasion. The patient has been under recurrence-free follow-up for approximately 1 year after the endoscopic submucosal dissection. Conclusion In order to detect a large number of cases, immunostaining should be aggressively performed if morphological findings are suspicious for GAED.
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Affiliation(s)
- Akira Ishikawa
- Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Koki Nakamura
- Department of Gastroenterology, Miyoshi Central Hospital, Miyoshi, Japan
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24
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Wang Z, Wang Q, Chen C, Zhao X, Wang H, Xu L, Fu Y, Huang G, Li M, Xu J, Zhang Q, Wang B, Xu G, Wang L, Zou X, Wang S. NNMT enriches for AQP5 + cancer stem cells to drive malignant progression in early gastric cardia adenocarcinoma. Gut 2023; 73:63-77. [PMID: 36977555 DOI: 10.1136/gutjnl-2022-328408] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Accepted: 03/15/2023] [Indexed: 03/30/2023]
Abstract
OBJECTIVE Early gastric cardia adenocarcinoma (EGCA) is a highly heterogeneous cancer, and the understanding of its classification and malignant progression is limited. This study explored the cellular and molecular heterogeneity in EGCA using single-cell RNA sequencing (scRNA-seq). DESIGN scRNA-seq was conducted on 95 551 cells from endoscopic biopsies of low-grade intraepithelial neoplasia, well/moderately/poorly differentiated EGCA and their paired adjacent nonmalignant biopsy samples. Large-scale clinical samples and functional experiments were employed. RESULTS Integrative analysis of epithelial cells revealed that chief cells, parietal cells and enteroendocrine cells were rarely detected in the malignant epithelial subpopulation, whereas gland and pit mucous cells and AQP5+ stem cells were predominant during malignant progression. Pseudotime and functional enrichment analyses showed that the WNT and NF-κB signalling pathways were activated during the transition. Cluster analysis of heterogeneous malignant cells revealed that NNMT-mediated nicotinamide metabolism was enriched in gastric mucin phenotype cell population, which was associated with tumour initiation and inflammation-induced angiogenesis. Furthermore, the expression level of NNMT was gradually increased during the malignant progression and associated with poor prognosis in cardia adenocarcinoma. Mechanistically, NNMT catalysed the conversion of nicotinamide to 1-methyl nicotinamide via depleting S-adenosyl methionine, which led to a reduction in H3K27 trimethylation (H3K27me3) and then activated the WNT signalling pathway to maintain the stemness of AQP5+ stem cells during EGCA malignant progression. CONCLUSION Our study extends the understanding of the heterogeneity of EGCA and identifies a functional NNMT+/AQP5+ population that may drive malignant progression in EGCA and could be used for early diagnosis and therapy.
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Affiliation(s)
- Zhangding Wang
- Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, People's Republic of China
| | - Qiang Wang
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People's Republic of China
| | - Chen Chen
- Medical School of Nanjing University, Nanjing, Jiangsu Province, People's Republic of China
| | - Xiaoya Zhao
- Medical School of Nanjing University, Nanjing, Jiangsu Province, People's Republic of China
| | - Honggang Wang
- Department of Gastroenterology, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huai'an, Jiangsu Province, People's Republic of China
| | - Lei Xu
- Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, People's Republic of China
| | - Yao Fu
- Department of Pathology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, People's Republic of China
| | - Guang Huang
- Center for Global Health, Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu Province, People's Republic of China
| | - Mengmeng Li
- Medical School of Nanjing University, Nanjing, Jiangsu Province, People's Republic of China
| | - Jiawen Xu
- Medical School of Nanjing University, Nanjing, Jiangsu Province, People's Republic of China
| | - Qianyi Zhang
- Medical School of Nanjing University, Nanjing, Jiangsu Province, People's Republic of China
| | - Bo Wang
- Department of Hepatobiliary Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, People's Republic of China
| | - Guifang Xu
- Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, People's Republic of China
| | - Lei Wang
- Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, People's Republic of China
| | - Xiaoping Zou
- Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, People's Republic of China
- Department of Gastroenterology, Affiliated Taikang Xianlin Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu Province, People's Republic of China
| | - Shouyu Wang
- Department of Hepatobiliary Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, People's Republic of China
- Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing, Jiangsu Province, People's Republic of China
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Wang Y, Wei X, Ke B, Liu J, Guo Y, Liu Y, Chen Y, Ding T, Wang Y, Meng B, Sun B, Zang F. Exploring the molecular characteristics of the malignant potential of gastric adenocarcinoma with enteroblastic differentiation. Histopathology 2023; 83:631-646. [PMID: 37356975 DOI: 10.1111/his.14998] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2023] [Revised: 05/24/2023] [Accepted: 06/06/2023] [Indexed: 06/27/2023]
Abstract
AIMS Gastric adenocarcinoma with enteroblastic differentiation (GAED) is a rare subset of alpha-fetoprotein (AFP)-producing carcinomas with poor prognosis. However, the molecular features associated with the malignant potential of GEAD remain partially elucidated. METHODS AND RESULTS In this study, the relationship between clinicopathological parameters and aggressive biological behaviour was analysed in 37 patients with GAED. The results showed that GAED tended to infiltrate the deep layer of the gastric wall and possessed more frequent vascular invasion than conventional gastric adenocarcinoma (CGA) (P < 0.001). All distant metastases were observed in the GAED group, not the CGA group (P < 0.001). High HER2 expression was found in nearly 24.32% of the informative cases, and none showed EBV-encoded RNA positivity or deficient mismatch repair. The most frequently mutated gene in GAED was p53. Programmed cell death-ligand 1 (PD-L1) immunostaining revealed 13 patients with a combined positive score (CPS) ≥ 5 (65%, 13 of 20). Thus, based on these molecular markers (immunostaining, in situ hybridisation and mutation analysis), GAED may be classified as a unique subgroup of the chromosomal instability subtype with HER2+ /EBV- /MSS/TP53+ /PD-L1+ . Next-generation sequencing analyses showed that mutations in the TOPI, ELOA and NOTCH3 genes were found only in GAED, and abnormally expressed genes in GAED were significantly enriched in hepatocellular carcinoma-, gland development-, and gastric cancer-related pathways. CONCLUSION The HER2+ /EBV- /MSS/TP53+ /PD-L1+ profile and hepatocellular carcinoma-related pathways may be significant in the malignant potential of GAED. In addition to anti-HER2 therapy, immune check-point inhibitors may be an effective treatment option for patients with GAED.
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Affiliation(s)
- Yong Wang
- Department of Pathology, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Xiyin Wei
- Public Laboratory, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Bin Ke
- Department of Gastric Oncology, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Jia Liu
- Department of Colorectal Oncology, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Yuhong Guo
- Department of Pathology, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Yanxue Liu
- Department of Pathology, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Yongzi Chen
- Department of Tumor Cell Biology, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Tingting Ding
- Department of Pathology, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Yalei Wang
- Department of Pathology, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Bin Meng
- Department of Pathology, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Baocun Sun
- Department of Pathology, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Fenglin Zang
- Department of Pathology, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
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26
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Abe D, Akazawa Y, Yatagai N, Hayashi T, Ueyama H, Mine S, Fukunaga T, Nagahara A, Yao T, Saito T. Clinicopathological characteristics of gastric adenocarcinoma with enteroblastic differentiation and gastric adenocarcinoma with enteroblastic marker expression. Virchows Arch 2023; 483:405-414. [PMID: 37581693 DOI: 10.1007/s00428-023-03623-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Revised: 07/17/2023] [Accepted: 08/07/2023] [Indexed: 08/16/2023]
Abstract
Gastric adenocarcinoma (GA) with enteroblastic differentiation (GAED) is an aggressive carcinoma histologically characterized by a glycogen-rich clear cytoplasm and fetal gut-like structures. GAED shows the expression of at least one of the following enteroblastic markers (EMs): glypican-3 (GPC3), spalt-like transcription factor 4 (SALL4), and α-fetoprotein (AFP). Despite the absence of clear cytoplasm, we often encounter GA with EMs expression (GA with EM); however, the clinicopathological characteristics of GA with EM remain unclear. Immunohistochemical (IHC) expression of three EMs (AFP, GPC3, and SALL4) was examined on tissue microarray. According to the status of the clear cytoplasm of tumor cells, GAs showing IHC expression of EMs were classified as either GAED or GA with EM, and this analysis categorized 688 GAs into 94 GAEDs (13.7%), 58 GAs with EM (8.4%), and 536 conventional GAs (CGAs). Both GAED and GA with EM showed frequent lymphovascular invasion, lymph node metastasis, and liver metastasis compared to CGA. However, a higher frequency of venous invasion, but not of lymphatic invasion, was noted for GAED in comparison to CGA. GAED and GA with EM showed similar overall survival. GAED had significantly poorer prognosis than CGA; however, not for GA with EM. Furthermore, GA showing EM expression had a worse prognosis than CGA. Interestingly, GA showing EM-positive group was more aggressive than CGA group as they had frequent venous invasion and liver metastasis despite its smaller tumor size. GAED and GA with EM can be clinically classified as aggressive tumors but pathologically they seem to be slightly different.
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Affiliation(s)
- Daiki Abe
- Department of Human Pathology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan
- Department of Gastroenterology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan
| | - Yoichi Akazawa
- Department of Gastroenterology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan
| | - Noboru Yatagai
- Department of Gastroenterology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan
| | - Takuo Hayashi
- Department of Human Pathology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan
| | - Hiroya Ueyama
- Department of Gastroenterology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan
| | - Shinji Mine
- Department of Gastroenterological Surgery, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan
| | - Tetsu Fukunaga
- Department of Gastroenterological Surgery, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan
| | - Akihito Nagahara
- Department of Gastroenterology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan
| | - Takashi Yao
- Department of Human Pathology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan
| | - Tsuyoshi Saito
- Department of Human Pathology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan.
- Intractable Disease Research Center, Graduate School of Medicine, Juntendo University, Tokyo, 113-8421, Japan.
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27
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Ngan RKC. Outcomes of Third-Line Trastuzumab Deruxtecan in a Patient with De Novo Stage 4 HER2-Positive Gastric Adenocarcinoma with Enteroblastic Differentiation: A Case Report. Life (Basel) 2023; 13:1851. [PMID: 37763255 PMCID: PMC10533056 DOI: 10.3390/life13091851] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Revised: 08/29/2023] [Accepted: 08/30/2023] [Indexed: 09/29/2023] Open
Abstract
This case report describes the treatment of a patient diagnosed with de novo stage 4 human epidermal growth factor 2 (HER2)-positive gastric adenocarcinoma with enteroblastic differentiation (GAED), a rare and aggressive form of gastric cancer characterized by a tubulopapillary growth pattern and enteroblastic cell lineage markers such as GPC3, SALL4, and alpha fetoprotein. Given the patient's symptomatic, advanced-stage cancer, treatment objectives were focused on effectively deterring disease progression and ameliorating symptoms throughout the anticipated multiple lines of therapy. Subsequent to standard first- and second-line therapies for HER2-positive metastatic GC, third-line treatment using the antibody-drug conjugate trastuzumab deruxtecan (T-DXd) for seven cycles resulted in satisfactory tumor control and well-preserved physical performance and quality of life, with minimal hematologic and pulmonary toxicities. The patient retained acceptable physical performance to receive subsequent lines of therapies, and still showed a tumor marker response to 5L trastuzumab-based chemotherapy. As the tumor was positive for both HER2 and programmed death-ligand 1 (PD-L1) expressions, the selection and sequencing of anti-HER2 and anti-PD-L1 therapies were discussed in relation to the latest U.S. Food and Drug Administration approvals and trial results.
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28
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Ferreira JE, Mbagwu E, Lee EY, Shelman NR, Allison DB. Cytopathological features of gastroesophageal junction adenocarcinoma with enteroblastic differentiation and histopathological correlation. Cytopathology 2023; 34:250-253. [PMID: 36524296 DOI: 10.1111/cyt.13198] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Accepted: 12/06/2022] [Indexed: 12/23/2022]
Abstract
The authors report a case of gastroesophageal adenocarcinoma with enteroblastic differentiation (GAED) presenting as an unknown primary and offer the first description of this tumour on cytological preparation with histopathological correlation. Although challenging, a specific diagnosis can be made in the right clinical scenario.
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Affiliation(s)
- Juanita E Ferreira
- Department of Pathology & Laboratory Medicine, College of Medicine, University of Kentucky, Lexington, Kentucky, USA
| | - Emmy Mbagwu
- Department of Pathology & Laboratory Medicine, College of Medicine, University of Kentucky, Lexington, Kentucky, USA
| | - Eun Y Lee
- Department of Pathology & Laboratory Medicine, College of Medicine, University of Kentucky, Lexington, Kentucky, USA
| | - Nathan R Shelman
- Department of Pathology & Laboratory Medicine, College of Medicine, University of Kentucky, Lexington, Kentucky, USA
| | - Derek B Allison
- Department of Pathology & Laboratory Medicine, College of Medicine, University of Kentucky, Lexington, Kentucky, USA
- Department of Urology, College of Medicine, University of Kentucky, Lexington, Kentucky, USA
- Markey Cancer Center, University of Kentucky, Lexington, Kentucky, USA
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Sugawara K, Fukuda T, Kishimoto Y, Oka D, Kawashima Y, Inoshita N, Kanda H. Combined tubular adenocarcinoma, neuroendocrine carcinoma and adenocarcinoma with enteroblastic differentiation arising in Barrett esophagus. Clin J Gastroenterol 2023:10.1007/s12328-023-01791-0. [PMID: 37027114 DOI: 10.1007/s12328-023-01791-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Accepted: 03/26/2023] [Indexed: 04/08/2023]
Abstract
Adenocarcinoma (AC) with neuroendocrine carcinoma (NEC) or enteroblastic (ENT) differentiation rarely develops in Barrett's esophagus (BE). A 76-year-old man was diagnosed with Barrett's AC (cT1bN0M0) and underwent thoracoscopic esophagectomy. A type 0-IIc + 0-Is lesion measuring 26 × 21 mm was macroscopically observed on a background of long segment BE (pT1bN0M0). The tumor comprised three different histological types of carcinoma (NEC, AC with ENT differentiation and moderately differentiated AC). NEC showed positivity for synaptophysin, chromogranin A and insulinoma-associated protein 1 with a Ki-67 index of 60.6%. ENT tumors were immunopositive for AFP and sal-like protein 4, and focally immunopositive for human chorionic gonadotrophin. The amounts of NEC, ENT and AC were 40%, 40% and 20%, respectively. p53 expression was positive throughout the tumor. Rb expression was negative at the NEC, but positive at the ENT and AC. CD4 and CD8 densities were lower in the NEC segment than in the AC and ENT segments, and PD-L1 expression was negative throughout the tumor. Early cancer arising in BE with a combination of tubular AC, ENT tumors and NEC is very rare. Our observations might contribute to understanding the carcinogenetic pathways and tumor microenvironment of NEC and ENT tumors.
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Affiliation(s)
- Kotaro Sugawara
- Department of Gastroenterological Surgery, Saitama Cancer Center Hospital, Saitama, Japan
| | - Takashi Fukuda
- Department of Gastroenterological Surgery, Saitama Cancer Center Hospital, Saitama, Japan
| | - Yutaka Kishimoto
- Department of Gastroenterological Surgery, Saitama Cancer Center Hospital, Saitama, Japan
| | - Daiji Oka
- Department of Gastroenterological Surgery, Saitama Cancer Center Hospital, Saitama, Japan
| | - Yoshiyuki Kawashima
- Department of Gastroenterological Surgery, Saitama Cancer Center Hospital, Saitama, Japan
| | - Naoko Inoshita
- Department of Pathology, Moriyama Memorial Hospital, Tokyo, Japan
- Department of Pathology, Saitama Cancer Center Hospital, 780 Komuro Inamachi, Kitaadachi-Gun, Saitama, 362-0806, Japan
| | - Hiroaki Kanda
- Department of Pathology, Saitama Cancer Center Hospital, 780 Komuro Inamachi, Kitaadachi-Gun, Saitama, 362-0806, Japan.
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30
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Kuriyama S, Yano M, Kusaba T, Zaitsu S, Nishida H, Yasuda M, Nasu K. Immunohistochemical and molecular analysis of an α-fetoprotein-producing cervical adenocarcinoma with clear cell morphology. Med Mol Morphol 2023; 56:20-27. [PMID: 36183278 DOI: 10.1007/s00795-022-00336-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2022] [Accepted: 09/26/2022] [Indexed: 11/24/2022]
Abstract
Adenocarcinomas with clear cell morphology may be associated with elevated serum alpha-fetoprotein levels in various organs. We report the case of an alpha-fetoprotein-producing cervical adenocarcinoma with clear cell morphology and compare it immunohistochemically, molecularly, and virologically with cervical clear cell carcinoma, gastric-type mucinous carcinoma, and ovarian clear cell carcinoma. A 51-year-old Japanese woman was initially diagnosed with cervical clear cell carcinoma. The tumor was resistant to standard surgery, radiotherapy, and chemotherapy. Serum carcinoembryonic antigen and alpha-fetoprotein were elevated. The tumor was immunohistochemically positive for alpha-fetoprotein, human chorionic gonadotropin, cytokeratin 20, spalt-like transcription factor 4, glypican 3, MUC6, and HIK1083. Gene panel testing revealed CCNE1 amplification, CDKN2A loss, and TP53 R282W. We compared the present case with 120 ovarian clear cell carcinoma cases using a tissue microarray. Only one case (0.8%) showed very limited immunohistochemical positivity for alpha-fetoprotein. Of the 54 cases in which serum carcinoembryonic antigen was measured, only one (1.9%) was elevated (19.9 ng/mL). We diagnosed the case as alpha-fetoprotein-producing cervical gastric-type mucinous carcinoma with enteroblastic differentiation. In conclusion, alpha-fetoprotein-producing cervical adenocarcinoma is a rare but aggressive tumor. Clinicians and pathologists should be aware of this unfamiliar tumor, its diagnostic clues, prognostic markers, and treatment strategies.
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Affiliation(s)
- Shu Kuriyama
- Department of Obstetrics and Gynecology, Faculty of Medicine, Oita University, Idaigaoka 1-1, Hasama-machi, Yufu-shi, Oita, 879-5593, Japan
| | - Mitsutake Yano
- Department of Obstetrics and Gynecology, Faculty of Medicine, Oita University, Idaigaoka 1-1, Hasama-machi, Yufu-shi, Oita, 879-5593, Japan. .,Department of Pathology, Saitama Medical University International Medical Centre, Saitama, Japan.
| | - Takahiro Kusaba
- Department of Diagnostic Pathology, Faculty of Medicine, Oita University, Oita, Japan
| | - Sumika Zaitsu
- Department of Obstetrics and Gynecology, Faculty of Medicine, Oita University, Idaigaoka 1-1, Hasama-machi, Yufu-shi, Oita, 879-5593, Japan
| | - Haruto Nishida
- Department of Diagnostic Pathology, Faculty of Medicine, Oita University, Oita, Japan
| | - Masanori Yasuda
- Department of Pathology, Saitama Medical University International Medical Centre, Saitama, Japan
| | - Kaei Nasu
- Department of Obstetrics and Gynecology, Faculty of Medicine, Oita University, Idaigaoka 1-1, Hasama-machi, Yufu-shi, Oita, 879-5593, Japan.,Division of Obstetrics and Gynecology, Support System for Community Medicine, Faculty of Medicine, Oita University, Oita, Japan
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Liu XL, Ding L, Lu X, Hu YJ, Zhou XL, Lin DL. Yolk Sac Tumor Originating From Cervical Adenocarcinoma: A Case Predominated by Enteroblastic Differentiation. Int J Gynecol Pathol 2023; 42:212-216. [PMID: 35639370 DOI: 10.1097/pgp.0000000000000891] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
The fetal gut-like phenotype can be found in yolk sac tumors and adenocarcinomas with enteroblastic differentiation (AEBDs). We report a cervical yolk sac tumor in a 44-yr-old woman. The tumor has similar morphology, immunophenotype, and molecular features to the AEBD of the digestive system. The tumor showed a glandular-predominant growth pattern, composed of columnar cells with clear glycogen-rich cytoplasm. The microcystic/reticular architecture or Schiller-Duval bodies were not found in the tumor. Immunohistochemically, the tumor cells were positive for p16, glypican-3 (GPC3), spalt-like transcription factor 4 (SALL4), CDX-2, and p53. TP53 mutation was identified by next-generation sequencing, and human papillomavirus (HPV) 35 was detected by HPV DNA polymerase chain reaction. In the present case, the adenocarcinoma cells in the superficial cervical glandular epithelium and the nonclear glandular components proved the existence of somatic components. The positivity of p16 and HPV also supports that the present case originates from an HPV-associated adenocarcinoma. The yolk sac tumor should be thought of as "germ cell differentiation" from a somatic carcinoma. This kind of yolk sac tumor arising from somatic-type adenocarcinoma in the female genital tract may be the counterpart of AEBD in the digestive tracts and adenocarcinomas with fetal gut-like morphology in other organs. The tumor might be more aggressive than conventional adenocarcinoma, pathologists should highlight the existence of the enteroblastic component in the pathologic report.
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Zhao Y, Zhou T, Li Z. A rare case of gastric adenocarcinoma with enteroblastic differentiation presenting as pancreatic hepatoid adenocarcinoma metastases. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2023; 30:e12-e14. [PMID: 35749218 DOI: 10.1002/jhbp.1203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Revised: 05/09/2022] [Accepted: 06/01/2022] [Indexed: 11/06/2022]
Affiliation(s)
- Yusha Zhao
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, China
- Laboratory of Translational Gastroenterology, Qilu Hospital of Shandong University, Jinan, China
- Robot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumor, Qilu Hospital of Shandong University, Jinan, China
| | - Tao Zhou
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, China
- Laboratory of Translational Gastroenterology, Qilu Hospital of Shandong University, Jinan, China
- Robot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumor, Qilu Hospital of Shandong University, Jinan, China
| | - Zhen Li
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, China
- Laboratory of Translational Gastroenterology, Qilu Hospital of Shandong University, Jinan, China
- Robot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumor, Qilu Hospital of Shandong University, Jinan, China
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Relationships of tumor differentiation and immune infiltration in gastric cancers revealed by single-cell RNA-seq analyses. Cell Mol Life Sci 2023; 80:57. [PMID: 36729271 PMCID: PMC9894979 DOI: 10.1007/s00018-023-04702-1] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Revised: 01/08/2023] [Accepted: 01/17/2023] [Indexed: 02/03/2023]
Abstract
Gastric cancers are highly heterogeneous malignant tumors. To reveal the relationship between differentiation status of cancer cells and tumor immune microenvironments in gastric cancer, single-cell RNA-sequencing was performed on normal mucosa tissue, differentiated gastric cancer (DGC) tissue, poorly differentiated gastric cancer (PDGC) tissue and neuroendocrine carcinoma (NEC) tissue sampled from surgically resected gastric cancer specimens. We identified the signature genes for both DGC and PDGC, and found that signature genes of PDGC strongly enriched in the epithelial-mesenchymal transition (EMT) program. Furthermore, we found that DGC tends to be immune-rich type whereas PDGC tends to be immune-poor type defined according to the density of tumor-infiltrating CD8+ T cells. Additionally, interferon alpha and gamma responding genes were specifically expressed in the immune-rich malignant cells compared with immune-poor malignant cells. Through analyzing the mixed adenoneuroendocrine carcinoma, we identified intermediate state malignant cells during the trans-differentiation process from DGC to NEC, which showed double-negative expressions of both DGC marker genes and NEC marker genes. Interferon-related pathways were gradually downregulated along the DGC to NEC trans-differentiation path, which was accompanied by reduced CD8+ cytotoxic T-cell infiltration. In summary, molecular features of both malignant cells and immune microenvironment cells of DGC, PDGC and NEC were systematically revealed, which may partially explain the strong tumor heterogeneities of gastric cancer. Especially along the DGC to NEC trans-differentiation path, immune-evasion was gradually enhanced with the decreasing activities of interferon pathway responses in malignant cells.
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Weng W, Zhang M, Ni S, Tan C, Xu M, Wang X, Sun H, Wang L, Huang D, Sheng W. Decreased expression of claudin-18.2 in alpha-fetoprotein-producing gastric cancer compared to conventional gastric cancer. J Gastrointest Oncol 2022; 13:1035-1045. [PMID: 35837176 PMCID: PMC9274048 DOI: 10.21037/jgo-22-462] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Accepted: 06/14/2022] [Indexed: 12/02/2024] Open
Abstract
BACKGROUND Alpha-fetoprotein-producing gastric cancer (AFPGC) is a subtype of gastric cancer (GC) with more aggressive biological behavior. As a highly specific tight junction component exclusively present in gastric mucosa and gastric adenocarcinomas, claudin-18.2 (CLDN18.2) has become an emerging target in GC. In this study, we aimed to provide insight into AFPGC and investigate the expression and the clinical implications of CLDN18.2 in AFPGC. METHODS We retrospectively collected 98 cases of AFPGC and reviewed their clinical, morphological, and immunohistochemical features. Another 356 patients with stage-matched conventional GC (cGC) were enrolled as a control group. We further surveyed CLDN18.2 expression by immunohistochemistry (IHC) in 51 AFPGC tissues and explained its association with the clinicopathological parameters of AFPGC. RESULTS Our results showed that AFPGC was a unique GC type with elevated serum alpha-fetoprotein (AFP), which was a predictor of a worse prognosis. AFPGC showed typical morphological features and positive staining of at least 1 hepatocytic or enteroblastic marker. The expression rate of CLDN18.2 was low, with a positivity rate of 21.6%, which was much lower than that observed in cGC tissues (38.5%). A significant correlation was found between CLDN18.2 expression and the differentiation of AFPGC. CLDN18.2 expression was negatively correlated with the serum AFP level of AFPGC. We also found that AFPGC with a hepatoid type (HPT) component showed a significantly lower CLDN18.2 expression than those without. CONCLUSIONS This study demonstrated that CLDN18.2 was significantly decreased in AFPGC and was negatively correlated with the patient's preoperative serum AFP level. The negative correlation between AFP and CLDN18.2 could be explained by retro-differentiation of AFPGC. Special treatment strategies might be needed for this unique tumor type.
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Affiliation(s)
- Weiwei Weng
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Institute of Pathology, Fudan University, Shanghai, China
| | - Meng Zhang
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Institute of Pathology, Fudan University, Shanghai, China
| | - Shujuan Ni
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Institute of Pathology, Fudan University, Shanghai, China
| | - Cong Tan
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Institute of Pathology, Fudan University, Shanghai, China
| | - Midie Xu
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Institute of Pathology, Fudan University, Shanghai, China
| | - Xin Wang
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Institute of Pathology, Fudan University, Shanghai, China
| | - Hui Sun
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Institute of Pathology, Fudan University, Shanghai, China
| | - Lei Wang
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Institute of Pathology, Fudan University, Shanghai, China
| | - Dan Huang
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Institute of Pathology, Fudan University, Shanghai, China
| | - Weiqi Sheng
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Institute of Pathology, Fudan University, Shanghai, China
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Chen Z, Ding C, Zhang T, He Y, Jiang G. Primary Hepatoid Adenocarcinoma of the Lung: A Systematic Literature Review. Onco Targets Ther 2022; 15:609-627. [PMID: 35676912 PMCID: PMC9167841 DOI: 10.2147/ott.s364465] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Accepted: 05/16/2022] [Indexed: 12/15/2022] Open
Abstract
Background Hepatoid adenocarcinoma (HAC) of the lung (HAL) is a rare and aggressive extrahepatic adenocarcinoma with an unknown etiology and unfavorable prognosis, which is similar to the pathophysiological characteristics of hepatocellular carcinoma (HCC). Methods We first presented a 67-year-old patient diagnosed with HAC in the right middle lobe of the lung. Then, a systematic literature search was performed for HAL cases recorded between 1990 and 2020 based on three databases. The clinicopathological features, therapeutic method, and prognosis of this rare disease were reviewed, and corresponding prognostic factors were explored using Kaplan–Meier (K-M) curve and Cox proportional hazards regression model. Additionally, the potential biological mechanisms of HAL were further explored and compared with HCC and lung adenocarcinoma (LUAD) based on online databases. Results In the present study, we reported an HAL patient who underwent surgical resection combined with chemotherapy and succumbed to disease 13 months after surgery. Additionally, a total of 43 experimental studies with 49 HAL patients, including the present case, met the inclusion criteria and were included in the present review. We found that HAL is characterized by a male-dominated incidence and is more common in the right lung. Patients in the surgical subgroup have a better prognosis than those in the non-surgical subgroup (p = 0.034). Moreover, the Cox proportional hazards regression model demonstrated that surgical resection can significantly improve the prognosis of HAL patients (p = 0.016). HAL is a rare disease associated with gene mutations that has a distinctive cause and unique pathogenesis. Additionally, Afatinib and Gefitinib may be new effective agents to better combat HAL. Conclusion In conclusion, males may exhibit an increased risk of developing HAL and poorer prognosis than females. Surgical resection combined with chemotherapy may prolong the survival of patients with HAL. HAL has its unique clinicopathological characteristics and biological mechanisms.
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Affiliation(s)
- Zhitao Chen
- Department of Hepatobiliary Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou, People’s Republic of China
| | - Chenchen Ding
- Department of Hepatobiliary Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou, People’s Republic of China
| | - Ting Zhang
- Department of Hepatobiliary Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou, People’s Republic of China
| | - Yahui He
- Department of Hepatobiliary Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou, People’s Republic of China
- School of Medicine, Zhejiang Shuren University, Hangzhou, People’s Republic of China
| | - Guoping Jiang
- Department of Hepatobiliary Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou, People’s Republic of China
- Correspondence: Guoping Jiang, Department of Hepatobiliary Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, 848# Dongxin Road, Hangzhou City, Zhejiang Province, People’s Republic of China, Tel +86-0571-87236570, Email
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Okura K, Esaki M, Nara S, Ban D, Takamoto T, Shimada K, Hiraoka N. Hepatoid carcinoma and related entities of the extrahepatic bile duct: A clinicopathological study of four cases. Pathol Int 2022; 72:332-342. [PMID: 35472251 DOI: 10.1111/pin.13226] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Accepted: 04/02/2022] [Indexed: 01/01/2023]
Abstract
Hepatoid carcinoma or related entities (HPC/RTs) are extremely rare, especially in the extrahepatic bile duct (EHBD). Only a few case reports have been published. We analyzed the clinicopathological features of HPCs/RTs in EHBD. HPC/RT of extrahepatic cholangiocarcinoma (eCCA) cases were selected based on the histological characteristics and immunohistochemical detection of spalt-like transcription factor 4 (SALL4) and/or alpha-fetoprotein (AFP). Four HPC/RT cases arose in the distal but not in the perihilar EHBD. The four patients with HPC/RT included one female and three males with a median age of 77 years. There are various macroscopic types of HPC/RT. The predominant histological features were two solid-type carcinomas that mimicked hepatocellular carcinoma and two well-differentiated tubular adenocarcinomas. Immunohistochemically, SALL4 and glypican-3 were expressed in all cases, and AFP was expressed in one case. Cancer cell phenotypes included intestinal, pancreatobiliary, and mixed pancreatobiliary and intestinal types. Focal neuroendocrine differentiation and severe perineural and lymphovascular invasions were also observed. HPC/RT recurred in two patients within 2 years, and one patient died 13 months postoperatively. It is suggested that the HPC/RT of EHBD shares common characteristics with HPC/RT arising in various organs, and has some unique characteristics. HPC/RT of EHBD might be more aggressive than conventional eCCA.
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Affiliation(s)
- Keisuke Okura
- Department of Analytical Pathology, National Cancer Center Research Institute, Tokyo, Japan
| | - Minoru Esaki
- Hepatobiliary and Pancreatic Surgery Division, National Cancer Center Hospital, Tokyo, Japan
| | - Satoshi Nara
- Hepatobiliary and Pancreatic Surgery Division, National Cancer Center Hospital, Tokyo, Japan
| | - Daisuke Ban
- Hepatobiliary and Pancreatic Surgery Division, National Cancer Center Hospital, Tokyo, Japan
| | - Takeshi Takamoto
- Hepatobiliary and Pancreatic Surgery Division, National Cancer Center Hospital, Tokyo, Japan
| | - Kazuaki Shimada
- Hepatobiliary and Pancreatic Surgery Division, National Cancer Center Hospital, Tokyo, Japan
| | - Nobuyoshi Hiraoka
- Department of Analytical Pathology, National Cancer Center Research Institute, Tokyo, Japan
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Kurosawa T, Murakami T, Yamashiro Y, Terukina H, Hayashi T, Saito T, Nojiri S, Sakamoto K, Nagahara A, Yao T. Mucin phenotypes and clinicopathological features of colorectal adenocarcinomas: Correlation with colorectal adenocarcinoma with enteroblastic differentiation. Pathol Res Pract 2022; 232:153840. [PMID: 35303523 DOI: 10.1016/j.prp.2022.153840] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Revised: 03/08/2022] [Accepted: 03/09/2022] [Indexed: 10/18/2022]
Abstract
BACKGROUND The mucin phenotypes of colorectal carcinoma (CRC) is related to the biological behavior and prognosis. But there has been no studies evaluating phenotypic characteristics in a large number of cases. Furthermore, colorectal adenocarcinoma with enteroblastic differentiation (CAED) is a rare subtype of CRC and having poor prognosis. The aims of this study were to clarify the correlation between mucin phenotypes and tumor development, including biological behavior in CRC, as well as to investigate characteristic of mucin phenotypes in CAED. METHODS AND RESULTS 974 CRC cases and 42 CAED cases of CRCs were classified five types (large-intestinal, small-intestinal, gastric, mixed, and unclassified) of mucin phenotypes by using immunohistochemistry (IHC). IHC was performed on tissue microarrays with antibodies against followings: MUC2, MUC5AC, MUC6, and CD10. In CRCs, large-intestine type has a relatively better prognosis, small-intestinal type frequently shows venous invasions, and liver metastases, gastric type has more high-histological grades and lymphatic invasions, mixed type shows originating from the right side of the colon, larger tumor size and mucinous type, but less venous invasions and liver metastasis, whereas the unclassified type showed poorer prognosis in overall survival with statistical significance. The majority of CAED were found to be small-intestinal type or unclassified type. CONCLUSIONS The phenotypic classification is useful for predicting the prognosis of CRCs. Small-intestinal type and unclassified type showed dismal prognosis in CRCs. We speculate that CAED having aggressive behavior and poor prognosis might reflect characteristics of small-intestinal and unclassified types.
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Affiliation(s)
- Taro Kurosawa
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan; Department of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan
| | - Takashi Murakami
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
| | - Yuya Yamashiro
- Department of Gastroenterology and Hepatology, Tokyo Metropolitan Tama Medical Center, Tokyo, Japan
| | - Hiroyuki Terukina
- Department of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan
| | - Takuo Hayashi
- Department of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan
| | - Tsuyoshi Saito
- Department of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan
| | - Shuko Nojiri
- Department of Medical Technology Innovation Center, Juntendo University School of Medicine, Tokyo, Japan
| | - Kazuhiro Sakamoto
- Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Akihito Nagahara
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
| | - Takashi Yao
- Department of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan.
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Sun Y, Chang W, Yao J, Liu H, Zhang X, Wang W, Zhao K. Effect of immune checkpoint inhibitors in patients with gastric hepatoid adenocarcinoma: a case report and literature review. J Int Med Res 2022; 50:3000605221091095. [PMID: 35469480 PMCID: PMC9087251 DOI: 10.1177/03000605221091095] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Accepted: 03/14/2022] [Indexed: 12/15/2022] Open
Abstract
Gastric hepatoid adenocarcinoma (GHAC) is a highly aggressive histological subtype of gastric cancer (GC) with similar tissue morphology to hepatocellular carcinoma. GHAC frequently produces alpha-fetoprotein (AFP) and has a poor prognosis; however, standardized treatment remains elusive. We report a male patient in his early 60s with GHAC who received immunotherapy, and the curative effect was evaluated. He was admitted because of progressive fatigue and dizziness for 2 months. He had experienced spontaneous epigastric pain with muscular defense of the epigastrium and accompanying tenderness 1 year earlier and underwent radical gastrectomy. Immunohistochemistry showed that hepatocyte-specific marker (Hep) was highly-expressed, indicating probable GHAC. Additionally, imaging suggested GC recurrence or gastric stump cancer. Radioimmunoassay indicated an AFP level of >1210.00 µg/L, and liver biopsy was performed following abdominal contrast-enhanced computed tomography. Pathology showed a few hepatocytes and proliferative fibrous connective tissue. The patient received three cycles of chemotherapy, with no obvious improvement. The possibility of surgical treatment was excluded, and immunotherapy or palliative treatment was selected. He received 11 cycles of a programed death-1 (PD-1) monoclonal antibody, and the effect of treatment was satisfactory. The mechanism of action of immunotherapy in GHAC warrants further investigation.
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Affiliation(s)
- Yansha Sun
- Department of Oncology, Huaian Hospital of Huaian
City, No. 161 Zhenhuailou East Road, Huaian 223200, Jiangsu Province,
People's Republic of China
| | - Wanhua Chang
- Department of Gastroenterology, Huaian Hospital of
Huaian City, No. 161 Zhenhuailou East Road, Huaian 223200, Jiangsu
Province, People's Republic of China
| | - Juan Yao
- Department of Oncology, Huaian Hospital of Huaian
City, No. 161 Zhenhuailou East Road, Huaian 223200, Jiangsu Province,
People's Republic of China
| | - Haiyan Liu
- Department of Pathology, The Affiliated Huai'an No. 1
People's Hospital of Nanjing Medical University, No. 1 Huanghe West
Road, Jiangsu Province, People's Republic of China
| | - Xiaofei Zhang
- Department of Pathology, Huaian Hospital of Huaian
City, No. 161 Zhenhuailou East Road, Huaian 223200, Jiangsu Province,
People's Republic of China
| | - Wei Wang
- Department of Oncology, Huaian Hospital of Huaian
City, No. 161 Zhenhuailou East Road, Huaian 223200, Jiangsu Province,
People's Republic of China
| | - Kun Zhao
- Department of Oncology, Huaian Hospital of Huaian
City, No. 161 Zhenhuailou East Road, Huaian 223200, Jiangsu Province,
People's Republic of China
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Wang B, Du C, Li L, Xie Y, Hu C, Li Z, Zhu Y, Yuan Y, Liu X, Lu N, Xue L. New substituted molecular classifications of advanced gastric adenocarcinoma: characteristics and probable treatment strategies. JOURNAL OF THE NATIONAL CANCER CENTER 2022; 2:50-59. [PMID: 39035211 PMCID: PMC11256717 DOI: 10.1016/j.jncc.2021.11.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Background Gastric adenocarcinoma (GA) is a heterogeneous tumor, and the accurate classification of GA is important. Previous classifications are based on molecular analysis and have not focused on GA with the primitive enterocyte phenotype (GAPEP), a unique subtype with a poor prognosis and frequent liver metastases. New substituted molecular (SM) classifications based on immunohistochemistry (IHC) are needed. Methods According to the IHC staining results, we divided 582 cases into six types: mismatch repair deficient (dMMR), Epstein-Barr virus associated (EBVa), the primitive enterocyte phenotype (PEP), the epithelial mesenchymal transition (EMT) phenotype, not otherwise specified/P53 mutated (NOS/P53m) and not otherwise specified/P53 wild-type (NOS/P53w). We analyzed the clinicopathological features, the immune microenvironment (PD-L1, CD8) and expression of HER2 and VEGFR2 of those types. Results There were 31 (5.3%) cases of the dMMR type, 13 (2.2%) cases of the EBVa type, 44 (7.6%) cases of the PEP type, 122 (21.0%) cases of the EMT type, 127 (21.8%) cases of the NOS/P53m type and 245 (42.1%) cases of the NOS/P53w type. Patients with the dMMR type had the best survival (P < 0.001). Patients with the EBVa type were younger (P < 0.001) and had higher PD-L1 and CD8 expression (P < 0.001) than other patients. Patients with the EMT type exhibited poor differentiation and a higher rate of abdominal metastasis. Patients with the NOS/P53m and PEP types had the worst survival rates and the highest PD-L1/HER2/VEGFR2 expression levels among all patients (P < 0.001). Conclusion Different SM classifications have different clinicopathological features and expression patterns, which indicate the probable clinical treatment strategies for these subtypes.
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Affiliation(s)
- Bingzhi Wang
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Chunxia Du
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Lin Li
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Yibin Xie
- Department of Abdominal Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Chunfang Hu
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Zhuo Li
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Yongjian Zhu
- Department of Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Yanling Yuan
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Xiuyun Liu
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Ning Lu
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Liyan Xue
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
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Dedifferentiation-like tubular and solid carcinoma of the stomach shows phenotypic divergence and association with deficient SWI/SNF complex. Virchows Arch 2022; 480:771-781. [PMID: 35122125 DOI: 10.1007/s00428-022-03288-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Revised: 01/17/2022] [Accepted: 01/21/2022] [Indexed: 12/24/2022]
Abstract
Gastric carcinoma showing an abrupt transition from a tubular to solid pattern is an unusual phenomenon reminiscent of dedifferentiation. The phenotypic and molecular characteristics of this transition are still unclear. We retrospectively collected 41 gastric carcinomas exhibiting dedifferentiation-like tubular to solid transition and applied an array of immunohistochemical stains, including neuroendocrine and hepatocytic markers, to delineate their lineage. The status of Epstein-Barr virus (EBV) infections, mismatch repair proteins, SWI/SNF complex proteins and p53 expression levels were examined. The clinicopathologic differences were assessed by statistical analysis. Except for 10 cases with neuroendocrine differentiation and 2 EBV-associated carcinomas, we identified 8 hepatoid carcinomas and 21 solid adenocarcinomas with loss of CDX2 and/or hep-par1 expression in solid part (12/29). A subset of solid adenocarcinoma was associated with MSI (8) and mutant p53 expression was frequent in non-MSI cases (10/13). We found hepatoid carcinomas usually harbored SMARCA2 loss (5/8), MSI-associated cases commonly had ARID1A loss (6/8), and non-MSI solid adenocarcinomas frequently showed SMARCA2/A4 loss (7/13) with a high rate of concurrent ARID1A loss (4/7). Spatial correlation between solid transition and loss of SWI/SNF complex subunits were seen in 63% of tumors (12/19). Dedifferentiation-like tubular and solid carcinoma was associated with a propensity to inferior survival outcomes (p = 0.034), especially hepatoid carcinoma and in the non-MSI/EBV intestinal subgroup. In conclusion, gastric cancer exhibiting dedifferentiation-like tubular to solid transition is a phenotypically divergent group that shares common alterations in the SWI/SNF complex.
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Yang A, Patterson A, Pavlock T, Chen KS, Gagan J, Hatley ME, Frazier AL, Amatruda JF, Laetsch TW, Rakheja D. Pitfalls in the diagnosis of yolk sac tumor: Lessons from a clinical trial. Pediatr Blood Cancer 2022; 69:e29451. [PMID: 34866303 PMCID: PMC9359435 DOI: 10.1002/pbc.29451] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Revised: 10/05/2021] [Accepted: 10/25/2021] [Indexed: 02/03/2023]
Abstract
Though outcomes for patients with recurrent/refractory malignant germ cell tumors (mGCTs) are poor, therapies targeting mTOR and EGFR inhibition have shown promise in vitro. We hypothesized that the combination of sirolimus and erlotinib will show activity in patients with recurrent/refractory mGCTs. Patients were enrolled in a prospective phase II clinical trial; central review of existing pathology specimens was performed. Of the five patients evaluated, two had their diagnoses revised to pancreatic acinar cell carcinoma and alpha-fetoprotein (AFP)-secreting gastric adenocarcinoma, respectively. Although mGCTs are common AFP-secreting neoplasms, recurrence or refractoriness to standard regimens should prompt histologic reevaluation for other diagnoses.
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Affiliation(s)
- Adeline Yang
- Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA,Children's Health, Children's Medical Center, Dallas, TX 75235, USA
| | - Alison Patterson
- Children's Health, Children's Medical Center, Dallas, TX 75235, USA
| | - Tara Pavlock
- Children's Health, Children's Medical Center, Dallas, TX 75235, USA
| | - Kenneth S. Chen
- Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA,Children's Health, Children's Medical Center, Dallas, TX 75235, USA,Pauline Allen Gill Center for Cancer and Blood Disorders, Children's Health Medical Center, Dallas, TX, 75235, USA
| | - Jeffrey Gagan
- Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
| | - Mark E. Hatley
- Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
| | - A. Lindsay Frazier
- Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, MA, 02215, USA
| | - James F. Amatruda
- Division of Hematology-Oncology, Cancer and Blood Disease Institute, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, CA 90027, USA
| | - Theodore W. Laetsch
- Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA,Children's Health, Children's Medical Center, Dallas, TX 75235, USA,Pauline Allen Gill Center for Cancer and Blood Disorders, Children's Health Medical Center, Dallas, TX, 75235, USA,Division of Oncology and Center for Childhood Cancer Research, Children’s Hospital of Philadelphia and Department of Pediatrics and Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Dinesh Rakheja
- Children's Health, Children's Medical Center, Dallas, TX 75235, USA,Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
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Abada E, Anaya IC, Abada O, Lebbos A, Beydoun R. Colorectal adenocarcinoma with enteroblastic differentiation: diagnostic challenges of a rare case encountered in clinical practice. J Pathol Transl Med 2022; 56:97-102. [PMID: 35051325 PMCID: PMC8935001 DOI: 10.4132/jptm.2021.10.28] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2021] [Accepted: 10/27/2021] [Indexed: 11/17/2022] Open
Abstract
Colorectal adenocarcinoma with enteroblastic differentiation (CAED) is a rare subtype of colonic adenocarcinoma characterized by increased α-fetoprotein (AFP) production and the expression of at least one enteroblastic marker including AFP, glypican 3 (GPC3), or Spalt like transcription factor 4 (SALL4). We report a case of a 26-year-old female who presented with low back pain and constipation which persisted despite supportive measures. Imaging revealed multiple liver lesions and enlarged retroperitoneal nodes. Tumor markers including AFP were markedly elevated. On biopsy, samples from the liver revealed infiltrating glands lined by columnar-type epithelium with mostly eosinophilic granular to focally clear cytoplasm. By immunohistochemistry, the tumor showed immunoreactivity with AFP, hepatocyte antigen, GPC3, SALL4, CDX2, SATB2, and cytokeratin 20. A colonoscopy performed subsequently revealed a mass in the sigmoid colon and biopsy of this mass revealed a similar histology as that seen in the liver. A diagnosis of CAED was made, following the results of gene expression profiling by the tumor with next-generation sequencing which identified pathogenic variants in MUTYH, TP53, and KDM6A genes and therefore supported its colonic origin. Cases such as this underscores the use of ancillary diagnostic techniques in arriving at the correct diagnosis in lesions with overlapping clinicopathologic characteristics.
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Affiliation(s)
- Evi Abada
- Department of Pathology, Wayne State University School of Medicine/Detroit Medical Center, Detroit, MI, USA
| | | | | | | | - Rafic Beydoun
- Department of Pathology, Wayne State University School of Medicine/Detroit Medical Center, Detroit, MI, USA
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Lu J, Jin M, Zhou X, Chen X, Shao Y, Jiang X. Clinicopathological and molecular characteristics of the alpha-fetoprotein-producing gastric cancer: emphasis on two major subtypes. APMIS 2021; 130:169-180. [PMID: 34862662 DOI: 10.1111/apm.13196] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2021] [Accepted: 11/22/2021] [Indexed: 11/26/2022]
Abstract
Alpha-fetoprotein-producing gastric cancer (AFPGC) is associated with high invasion and poor prognosis, but has not been well-documented due to its rarity. To develop the understanding of AFPGC, and further facilitate its clinical decision-making and treatment, we performed clinicopathological and molecular characterization of AFPGC and its two major subtypes, namely, gastric adenocarcinoma with enteroblastic differentiation (GAED) and hepatoid adenocarcinoma (HAC). The clinicopathological and molecular characteristics of AFPGC patients (n = 54) were mainly investigated by immunohistochemistry and next-generation sequencing (NGS) approaches. AFPGC exhibited a higher incidence of lymphatic and vascular invasion than conventional gastric adenocarcinoma (CGA). Despite various morphological patterns, there was mostly no evident difference in clinicopathological characteristics between the GAED and HAC subtypes. Target-enriched NGS profiling of disease mutation landscapes discovered 17 differentially mutated genes between AFPGC and CGA. The AFPGC patients carrying ZNF217 mutations had poorer overall survival than the ZNF217 wildtype. Furthermore, ATR showed a significantly higher mutation rate in GAED than in HAC. Overall, our study of clinicopathological characteristics shed light on the differences between CGA and AFPGC, as well as the relationships between the GAED and HAC subtypes of AFPGC. Furthermore, mutation landscape profiling revealed potential diagnostic and prognostic markers for AFPGC and its two subtypes.
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Affiliation(s)
- Jun Lu
- Department of Pathology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Mulan Jin
- Department of Pathology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Xiang Zhou
- Department of Pathology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Xin Chen
- Geneseeq Research Institute, Nanjing Geneseeq Technology Inc., Nanjing, China
| | - Yang Shao
- Geneseeq Research Institute, Nanjing Geneseeq Technology Inc., Nanjing, China.,School of Public Health, Nanjing Medical University, Nanjing, China
| | - Xingran Jiang
- Department of Pathology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
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Yoshikawa M, Tamario M, Obatake M, Sato K, Yagi S, Otani H, Kito K. A case of early gastric cancer with a single giant lymph node metastasis. Surg Case Rep 2021; 7:243. [PMID: 34792649 PMCID: PMC8602634 DOI: 10.1186/s40792-021-01328-y] [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: 09/09/2021] [Accepted: 11/09/2021] [Indexed: 08/30/2023] Open
Abstract
Background Early gastric cancer (EGC) is often associated with lymphatic metastasis, but it is extremely rare to be found as a single giant lymph node. Cancer often becomes more malignant in metastatic lesions than in primary lesions, and retrodifferentiation to the fetal gastrointestinal tract during the metastatic process has been reported in gastric cancer. We report an extremely rare case of EGC with a 13-cm giant lymph node metastasis in which an adenocarcinoma with enteroblastic differentiation and yolk sac tumor-like components was observed. Case presentation The case was a 70-year-old man who visited his local doctor with right hypochondrial pain, which was identified by computed tomography (CT) as a giant mass. Upper endoscopy revealed a 30-mm-sized 0-IIc lesion in the greater curvature of the angular incisure and a 15-mm-sized 0-IIa lesion in the anterior wall of the lower body of the gastric body. Endoscopic biopsy revealed tubular adenocarcinoma in both lesions. The gastric lesion and the giant tumor were clinically regarded as independent lesions (gastrointestinal stromal tumor, [GIST], and EGCs), and distal gastrectomy and D1 + dissection were performed to comprehensively treat all lesions. Pathological examination revealed that the giant tumor was tubular adenocarcinoma with an intestinal phenotype and was considered a lymph node metastasis of EGCs. To exclude the possibility of metastasis of adenocarcinoma other than EGCs, postoperative positron emission tomography-computed tomography (PET-CT) and colonoscopy were performed; however, no primary site other than the stomach was found. Metastatic lymph nodes have an increased degree of atypia compared with the primary tumor, and yolk sac tumor-like carcinoma morphology was observed along with α-fetoprotein (AFP) and Spalt-like 4 (SALL4) expression in this case. It was considered that retrodifferentiation to a fetal phenotype occurred during the metastatic process. Liver metastasis occurred 6 months after surgery, and chemotherapy is currently being introduced. Conclusions We experienced a case of EGC with a single giant lymph node metastasis. Retrodifferentiation to the fetal gastrointestinal tract during metastasis was speculated to be involved in the formation of giant lymph node metastasis and liver metastasis in this case.
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Affiliation(s)
- Masato Yoshikawa
- Institute of Ehime Prefectural Central Hospital, Department of Digestive Surgery, Matsuyama, Ehime, 790-0024, Japan.
| | - Misaki Tamario
- Institute of Ehime Prefectural Central Hospital, Department of Digestive Surgery, Matsuyama, Ehime, 790-0024, Japan
| | - Masayoshi Obatake
- Institute of Ehime Prefectural Central Hospital, Department of Digestive Surgery, Matsuyama, Ehime, 790-0024, Japan
| | - Koichi Sato
- Institute of Ehime Prefectural Central Hospital, Department of Digestive Surgery, Matsuyama, Ehime, 790-0024, Japan
| | - Shigehiko Yagi
- Institute of Ehime Prefectural Central Hospital, Department of Digestive Surgery, Matsuyama, Ehime, 790-0024, Japan
| | - Hiromi Otani
- Institute of Ehime Prefectural Central Hospital, Department of Digestive Surgery, Matsuyama, Ehime, 790-0024, Japan
| | - Katsumi Kito
- Department of Pathology, Ehime Prefectural Central Hospital, Matsuyama, 790-0024, Japan
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Wang B, Xie Y, Zheng L, Zheng X, Gao J, Liu X, Yuan Y, Li Z, Lu N, Xue L. Both the serum AFP test and AFP/GPC3/SALL4 immunohistochemistry are beneficial for predicting the prognosis of gastric adenocarcinoma. BMC Gastroenterol 2021; 21:408. [PMID: 34706681 PMCID: PMC8555135 DOI: 10.1186/s12876-021-01986-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Accepted: 10/18/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Both gastric adenocarcinoma with primitive enterocyte phenotype (GAPEP) (including hepatoid adenocarcinoma) and alpha-fetoprotein (AFP)-producing gastric adenocarcinoma have poor prognoses. However, the value of the serum AFP test and AFP/glypican-3 (GPC3)/spalt-like transcription factor 4 (SALL4) immunohistochemistry is still not clear, and these two methods have not yet been thoroughly compared. METHODS We collected 421 consecutive non-neoadjuvant surgically or endoscopically resected gastric adenocarcinoma patients with serum AFP results before surgery (group A). We divided these cases into serum AFP-high (sAFP-H) and serum AFP-normal (sAFP-N) by serum AFP levels, and into GAPEP (expressing AFP, GPC3, or SALL4) and non-GAPEP (nGAPEP) by AFP/GPC3/SALL4 immunohistochemistry results. We also collected 12 non-resected gastric adenocarcinoma patients with serum AFP ≥ 7 ng/mL before treatment (group B). We analyzed these patients' clinicopathological characteristics and prognoses. RESULTS Seventeen (4.04%) patients in group A were sAFP-H. These patients were younger and mainly had tubular adenocarcinoma with later pT (P = 0.014) and pN (P = 0.047) categories and more lymphovascular invasion (P < 0.001), perineural spread (P = 0.008), and metastases or recurrence (P < 0.001). For immunohistochemistry, 34 (8.08%) cases were GAPEP, and GAPEP cases also had later pT categories than nGAPEP cases (P = 0.001). Most group B patients with elevated serum AFP (especially > 1000 ng/mL) had simultaneous metastases, mainly liver metastases. Both the serological method and immunohistochemical method were useful for predicting prognosis (AUC sAFP = 0.625, AUC A/G/S-IHC = 0.723, z statistic = 1.726, P = 0.084). The serum AFP level (especially > 1000 ng/mL) is more specific (100%), and immunohistochemistry is more sensitive (50%). CONCLUSION Both the serum AFP level and immunohistochemical expression of AFP/GPC3/SALL4 can be used to indicate a poor prognosis for gastric adenocarcinoma.
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Affiliation(s)
- Bingzhi Wang
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Yibin Xie
- Department of Abdominal Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Li Zheng
- Department of General Surgery, the First People's Hospital of Dongcheng District, Beijing, 100075, China
| | - Xiaohao Zheng
- Department of Abdominal Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Jia Gao
- Department of Clinical Laboratory, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Xiuyun Liu
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Yanling Yuan
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Zhuo Li
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Ning Lu
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Liyan Xue
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
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Dias E, Santos-Antunes J, Nunes AC, Rodrigues JA, Pinheiro J, Macedo G. Gastric adenocarcinoma with enteroblastic differentiation: an unexpected cause of upper gastrointestinal bleeding. Acta Gastroenterol Belg 2021; 84:678-679. [PMID: 34965054 DOI: 10.51821/84.4.022] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
A 78-year-old male with previous medical history of hypertension, dyslipidemia, benign prostatic hyperplasia and colectomy for colon adenocarcinoma 16 years earlier presented to emergency department with melena for approximately 2 weeks. He denied hematemesis or hematochezia. He also denied other symptoms including abdominal pain, nausea, vomiting, fever, anorexia or weight loss. Usual medications included silodosin, simvastatin, losartan, hydrochlorothiazide, pantoprazole and midazolam. He denied recent intake of iron supplements or non-steroidal anti-inflammatory drugs. Physical examination was unremarkable except for pale skin. Laboratory studies revealed the presence of anemia (hemoglobin level: 7.1 g/dL). Leukocyte and platelet counts, liver tests, renal function, electrolyte levels, C-reactive protein and coagulation studies were all normal. Upper digestive endoscopy revealed red blood and blood clots in gastric lumen and a polypoid lesion with a diameter of approximately 20 mm located at the greater curvature of the proximal body with active oozing hemorrhage (Figure 1). Bleeding was successfully controlled with injection of diluted epinephrine at the base of the polyp and the patient was admitted in intermediate care unit for close monitoring. During the following days,
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Affiliation(s)
- E Dias
- Gastroenterology Department, Centro Hospitalar de São João, Porto, Portugal
| | - J Santos-Antunes
- Gastroenterology Department, Centro Hospitalar de São João, Porto, Portugal
| | - A C Nunes
- Gastroenterology Department, Centro Hospitalar de São João, Porto, Portugal
| | - J A Rodrigues
- Pathology Department, Centro Hospitalar de São João, Porto, Portugal
| | - J Pinheiro
- Pathology Department, Centro Hospitalar de São João, Porto, Portugal
| | - G Macedo
- Gastroenterology Department, Centro Hospitalar de São João, Porto, Portugal
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Zhou ZY, Sun J, Guo Q, Zhao HB, Zhou ZH. Clinicopathological significance of primitive phenotypes in early gastric cancer with differentiated histology. Diagn Pathol 2021; 16:66. [PMID: 34332604 PMCID: PMC8325828 DOI: 10.1186/s13000-021-01128-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Accepted: 07/12/2021] [Indexed: 11/28/2022] Open
Abstract
Background Certain gastric cancers exhibit some primitive phenotypes, which may indicate a high malignancy. In histologically differentiated early gastric cancer (EGC), the presence and the clinicopathological significance of the primitive phenotype remain unclear. Methods Using immunohistochemical staining we detected the expression of three primitive phenotypic markers SALL4, Glypican-3(GPC3), and AFP in whole tissue sections of differentiated EGC (gastrectomy specimens, n = 302). For those cases with primitive phenotypes, we analyzed their clinicopathological features and evaluated whether the criteria for endoscopic resection were met. Results We found that 9.3% (28/302) of all differentiated EGC cases have primitive phenotypes, and most of these cases (25/28) exhibit a histomorphology similar to conventional differentiated EGC. Patients with primitive phenotypes had a deeper invasion, a higher rate of ulcer and lymphatic invasion than cases without primitive phenotype. Moreover, patients with primitive phenotypes displayed a significantly higher frequency of LNM than those without (57.1% vs 8.8%, P < 0.001). Multivariate analysis revealed that presence of primitive phenotypes was an independent risk factor for LNM (P = 0.001, HR 6.977, 95% CI: 2.199–22.138). Interestingly, we found 2 cases with primitive phenotypes developed LNM, and they both met the expanded indications of endoscopic resection for differentiated EGC. Conclusions A small number of differentiated EGC have primitive phenotypes, which were closely related to LNM and were an independent risk factor for LNM. Given its highly aggressive behavior, differentiated EGC with primitive phenotypes should be evaluated with stricter criteria before endoscopic resection, or considered to give an additional surgical operation after endoscopic resection.
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Affiliation(s)
- Zhi-Yi Zhou
- Department of Pathology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, Jiangsu Province, China
| | - Jie Sun
- Center of Clinical Research, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, Jiangsu Province, China
| | - Qing Guo
- Department of Pathology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, Jiangsu Province, China
| | - Hai-Bin Zhao
- Department of Pathology, The 904 Hospital of Joint Logistic Support Force of People's Liberation Army, North Xinyuan Road 101, Wuxi, 214044, Jiangsu Province, China
| | - Zhi-Hua Zhou
- Department of Pathology, The 904 Hospital of Joint Logistic Support Force of People's Liberation Army, North Xinyuan Road 101, Wuxi, 214044, Jiangsu Province, China.
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48
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Lu J, Ding Y, Chen Y, Jiang J, Chen Y, Huang Y, Wu M, Li C, Kong M, Zhao W, Wang H, Zhang J, Li Z, Lu Y, Yu X, Jin K, Zhou D, Zhou T, Teng F, Zhang H, Zhou Z, Wang H, Teng L. Whole-exome sequencing of alpha-fetoprotein producing gastric carcinoma reveals genomic profile and therapeutic targets. Nat Commun 2021; 12:3946. [PMID: 34168152 PMCID: PMC8225795 DOI: 10.1038/s41467-021-24170-0] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Accepted: 06/01/2021] [Indexed: 02/05/2023] Open
Abstract
Alpha-fetoprotein producing gastric carcinoma (AFPGC) is a rare and aggressive subtype of gastric cancer. However, little is known about the genomic features of this disease. We perform whole-exome sequencing analysis of AFPGC, and identify 34 significantly mutated genes. Somatic copy number alterations analysis reveals several significant focal amplifications (e.g. 19q12, 17q12) and focal deletions (e.g. 1p36.11, 9p21.3), and some of these negatively affect the patient prognosis. Comparative analyses reveal that AFPGC has distinct genomic features from gastric cancer of The Cancer Genome Atlas as well as four molecular subtypes. Several frequently altered genes with potential as therapeutic targets are identified in AFPGC. Further analysis reveals that AFPGC with amplification of CCNE1 at 19q12 and/or ERBB2 at 17q12 show poorer survival and more aggressive. Subsequently, based on our established patient-derived xenograft models for AFPGC, translational research is performed and the therapeutic value of targeting CCNE1 and ERBB2 is validated. In this work, we provide an understanding of genomic characteristics of AFPGC and propose a platform to explore and validate the genome-guided personalized treatment for this disease.
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Affiliation(s)
- Jun Lu
- Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Yongfeng Ding
- Department of Medical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Yanyan Chen
- Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Junjie Jiang
- Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Yiran Chen
- Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Yingying Huang
- Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Mengjie Wu
- Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Chengzhi Li
- Department of Pathology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Mei Kong
- Department of Pathology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Wenyi Zhao
- Innovation Institute for Artificial Intelligence in Medicine and Zhejiang Provincial Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences and Alibaba-Zhejiang University Joint Research Center of Future Digital Healthcare, Zhejiang University, Hangzhou, China
| | - Haohao Wang
- Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Jing Zhang
- Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Zhongqi Li
- Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Yimin Lu
- Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Xiongfei Yu
- Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Ketao Jin
- Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Donghui Zhou
- Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Tianhua Zhou
- Institute of Gastroenterology, Cancer center, Zhejiang University, Hangzhou, China
| | - Fei Teng
- Hangzhou Oncocare Co. Ltd, Hangzhou, China
| | - Haibin Zhang
- Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Zhan Zhou
- Innovation Institute for Artificial Intelligence in Medicine and Zhejiang Provincial Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences and Alibaba-Zhejiang University Joint Research Center of Future Digital Healthcare, Zhejiang University, Hangzhou, China.
| | - Haiyong Wang
- Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
| | - Lisong Teng
- Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
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Kato T, Hikichi T, Nakamura J, Takasumi M, Hashimoto M, Kobashi R, Takagi T, Suzuki R, Sugimoto M, Sato Y, Okubo Y, Satake S, Oka Y, Yamada S, Kobayakawa M, Hashimoto Y, Ohira H. Two cases of gastric adenocarcinoma with enteroblastic differentiation resected by endoscopic submucosal dissection. Clin J Gastroenterol 2021; 14:736-744. [PMID: 33629257 DOI: 10.1007/s12328-021-01356-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Accepted: 02/01/2021] [Indexed: 02/07/2023]
Abstract
Gastric adenocarcinoma with enteroblastic differentiation (GAED) is rare, highly malignant, and has higher vascular invasion and metastasis rates than conventional differentiated gastric cancer (CDGC). We report two cases of GAED that underwent curative resection by endoscopic submucosal dissection (ESD). Case 1 was an 82-year-old man with an elevated lesion in the gastric cardia. Biopsy revealed well-differentiated tubular adenocarcinoma. Pathological diagnosis of the ESD specimen revealed intramucosal gastric cancer without lymphovascular invasion (LVI). Although the surface layer of the lesion showed well and moderately differentiated tubular adenocarcinoma, clear cytoplasmic cancer cells positive for Sal-like protein-4 (SALL4) and Glypican-3 were found in a part of the deep layer. Therefore, GAED was diagnosed as present in a part of the whole lesion and covered with CDGC. Case 2 was an 83-year-old man with an elevated lesion in the gastric angulus. Biopsy revealed papillary and well-differentiated tubular adenocarcinomas. Pathological diagnosis of the ESD specimen revealed intramucosal gastric cancer without LVI. The entire lesion was occupied by papillary and tubular cancer cells, and had clear vesicles. Pure GAED was diagnosed, because the cells were SALL4 positive. In both cases, resection was curative despite the difference in pathological features.
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Affiliation(s)
- Tsunetaka Kato
- Department of Endoscopy, Fukushima Medical University Hospital, 1 Hikarigaoka, Fukushima, Japan
- Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Takuto Hikichi
- Department of Endoscopy, Fukushima Medical University Hospital, 1 Hikarigaoka, Fukushima, Japan.
| | - Jun Nakamura
- Department of Endoscopy, Fukushima Medical University Hospital, 1 Hikarigaoka, Fukushima, Japan
- Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Mika Takasumi
- Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Minami Hashimoto
- Department of Endoscopy, Fukushima Medical University Hospital, 1 Hikarigaoka, Fukushima, Japan
- Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Ryoichiro Kobashi
- Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Tadayuki Takagi
- Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Rei Suzuki
- Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Mitsuru Sugimoto
- Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Yuki Sato
- Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Yoshinori Okubo
- Department of Endoscopy, Fukushima Medical University Hospital, 1 Hikarigaoka, Fukushima, Japan
- Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Shunsuke Satake
- Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Yuka Oka
- Department of Diagnostic Pathology, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Shoki Yamada
- Department of Diagnostic Pathology, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Masao Kobayakawa
- Department of Endoscopy, Fukushima Medical University Hospital, 1 Hikarigaoka, Fukushima, Japan
- Department of Medical Research Center, Fukushima Medical University, Fukushima, Japan
| | - Yuko Hashimoto
- Department of Diagnostic Pathology, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Hiromasa Ohira
- Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan
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Lobo J, Leão R, Jerónimo C, Henrique R. Liquid Biopsies in the Clinical Management of Germ Cell Tumor Patients: State-of-the-Art and Future Directions. Int J Mol Sci 2021; 22:ijms22052654. [PMID: 33800799 PMCID: PMC7961393 DOI: 10.3390/ijms22052654] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Revised: 02/25/2021] [Accepted: 03/02/2021] [Indexed: 02/06/2023] Open
Abstract
Liquid biopsies constitute a minimally invasive means of managing cancer patients, entailing early diagnosis, follow-up and prediction of response to therapy. Their use in the germ cell tumor field is invaluable since diagnostic tissue biopsies (which are invasive) are often not performed, and therefore only a presumptive diagnosis can be made, confirmed upon examination of the surgical specimen. Herein, we provide an overall review of the current liquid biopsy-based biomarkers of this disease, including the classical, routinely used serum tumor markers—the promising microRNAs rapidly approaching the introduction into clinical practice—but also cell-free DNA markers (including DNA methylation) and circulating tumor cells. Finally, and importantly, we also explore novel strategies and challenges for liquid biopsy markers and methodologies, providing a critical view of the future directions for liquid biopsy tests in this field, highlighting gaps and unanswered questions.
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Affiliation(s)
- João Lobo
- Cancer Biology and Epigenetics Group, IPO Porto Research Center (GEBC CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto) & Porto Comprehensive Cancer Center (P.CCC), R. Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal;
- Department of Pathology, Portuguese Oncology Institute of Porto (IPOP), R. Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal
- Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), Rua Jorge Viterbo Ferreira 228, 4050-513 Porto, Portugal
| | - Ricardo Leão
- Faculty of Medicine, University of Coimbra, Rua Larga, 3000-370 Coimbra, Portugal;
| | - Carmen Jerónimo
- Cancer Biology and Epigenetics Group, IPO Porto Research Center (GEBC CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto) & Porto Comprehensive Cancer Center (P.CCC), R. Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal;
- Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), Rua Jorge Viterbo Ferreira 228, 4050-513 Porto, Portugal
- Correspondence: (C.J.); (R.H.); Tel.: +351-22-225084000 (C.J. & R.H.); Fax: +351-22-5084199 (C.J. & R.H.)
| | - Rui Henrique
- Cancer Biology and Epigenetics Group, IPO Porto Research Center (GEBC CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto) & Porto Comprehensive Cancer Center (P.CCC), R. Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal;
- Department of Pathology, Portuguese Oncology Institute of Porto (IPOP), R. Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal
- Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), Rua Jorge Viterbo Ferreira 228, 4050-513 Porto, Portugal
- Correspondence: (C.J.); (R.H.); Tel.: +351-22-225084000 (C.J. & R.H.); Fax: +351-22-5084199 (C.J. & R.H.)
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