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Gao LL, Gao DN, Yuan HT, Chen WQ, Yang J, Peng JQ. Combining anti-PD-1 antibodies with surufatinib for gastrointestinal neuroendocrine carcinoma: Two cases report and review of literature. World J Clin Oncol 2025; 16:102297. [DOI: 10.5306/wjco.v16.i4.102297] [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: 10/14/2024] [Revised: 12/20/2024] [Accepted: 02/27/2025] [Indexed: 03/26/2025] Open
Abstract
BACKGROUND Gastrointestinal neuroendocrine carcinoma (GI NEC) has a low incidence rate and poor prognosis. Most patients already have metastatic disease when they are diagnosed. Platinum chemotherapy is the main means of treating metastatic GI NECs. There is a lack of effective treatment methods after chemotherapy failure. Therefore, Therefore, selecting appropriate posterior-line treatment programs to improve the prognosis of patients is urgently needed.
CASE SUMMARY A 64-year-old female was diagnosed with stage IV NEC of the rectum due to abdominal pain and rectal bleeding. After multiline chemotherapy, the condition progressed, and the patient was treated with a combination of camrelizumab and surufatinib. The efficacy evaluation revealed partial remission (PR) and stable conditions, with the expression of the tumor marker neuron-specific enolase (NSE) returning to normal. The adverse reactions were controllable, and the overall condition was good, with weight gain achieved in the past four years. Another 51-year-old female experienced recurrence and metastasis of a duodenal NEC after surgery. After multiline chemotherapy, she received sintilimab combined with surufatinib. The curative effect fluctuated between PR and stability. During treatment, she recovered from immune-related diabetes and later died due to deterioration of her condition. During the treatment, the patient’s NSE level returned to normal.
CONCLUSION The combination of antiangiogenic targeted drugs and immunotherapy provides a new therapeutic approach for the treatment of metastatic GI-NECs.
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Affiliation(s)
- Lou-Lu Gao
- Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong Province, China
| | - Dong-Ni Gao
- Department of Oncology, Shandong Public Health Clinical Center, Jinan 250100, Shandong Province, China
| | - Hong-Tu Yuan
- Department of Pathology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250117, Shandong Province, China
| | - Wen-Qiang Chen
- Department of Cardiology, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
| | - Jing Yang
- Department of Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250117, Shandong Province, China
| | - Jie-Qiong Peng
- Department of Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250117, Shandong Province, China
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Li J, Yuan C, Pan Y, Yang Y, Lai N, Sheng X. Long-term survival after chemotherapy combined immunotherapy for recurrent mixed neuroendocrine-non-neuroendocrine neoplasms of the common bile duct. Clin J Gastroenterol 2025:10.1007/s12328-025-02128-9. [PMID: 40244371 DOI: 10.1007/s12328-025-02128-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2024] [Accepted: 04/01/2025] [Indexed: 04/18/2025]
Abstract
Mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) of the common bile duct (CBD) are extremely rare, with few literature reported. A 68-year-old male was admitted to our hospital with choledocholithiasis with acute cholangitis. Abdominal computed tomography showed that the CBD was occupied and clearly dilated. Consequently, the patient underwent pancreaticoduodenectomy with regional lymph node dissection. The resected tumor at the distal bile duct was 25 × 25 × 13 mm, consisting of 30% adenocarcinoma and 70% neuroendocrine carcinoma microscopically. The patient then received six cycles of adjuvant chemotherapy. Subsequently, regular monitoring of the patient's tumor marker CA19-9 showed progressive elevation. The patient was readmitted to hospital for tumor recurrence and metastasis and received palliative second-line Gemcitabine and cisplatin chemotherapy and three courses of combined immunochemotherapy (Tyvyt [Sintilimab] + Gemcitabine + Cisplatin). Throughout the treatment course, the tumor marker CA19-9 persistently remained elevated. The patient achieved an overall survival (OS) of 29 months. We found that the continuous elevation of the tumor marker CA19-9 during follow-up might suggest tumor recurrence and an unfavorable prognosis. For patients with multiple metastases of cholangiocarcinoma, combined immunotherapy could potentially assist in prolonging survival. Currently, there is no standardized treatment for biliary MiNENs, and larger scale studies are needed to establish diagnosis and treatment protocols to improve the overall survival of patients.
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Affiliation(s)
- Jia Li
- Department of Pathology, Minhang Hospital, Fudan University, No. 170, Xinsong Road, Minhang District, Shanghai, China
| | - Chunyan Yuan
- Department of Pathology, Minhang Hospital, Fudan University, No. 170, Xinsong Road, Minhang District, Shanghai, China
| | - Yulin Pan
- Department of Pathology, Minhang Hospital, Fudan University, No. 170, Xinsong Road, Minhang District, Shanghai, China
| | - Yuanyuan Yang
- Department of Pathology, Minhang Hospital, Fudan University, No. 170, Xinsong Road, Minhang District, Shanghai, China
| | - Nannan Lai
- Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer, Shanghai Municipal Health Commission (SMHC), Minhang Hospital, Fudan University, No. 170, Xinsong Road, Minhang District, Shanghai, China.
| | - Xia Sheng
- Department of Pathology, Minhang Hospital, Fudan University, No. 170, Xinsong Road, Minhang District, Shanghai, China.
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Sambataro D, Bellavia S, Di Mattia P, Centonze D, Emmanuele C, Bonasera A, Caputo G, Quattrocchi AMO, Vinci E, Gebbia V, Valerio MR. Combined Neuroendocrine Carcinoma and Hepatocellular Carcinoma of the Liver: Systematic Literature Review Suggests Implementing Biological Characterization to Optimize Therapeutic Strategy. Cancers (Basel) 2025; 17:1074. [PMID: 40227579 PMCID: PMC11988019 DOI: 10.3390/cancers17071074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2025] [Revised: 03/11/2025] [Accepted: 03/19/2025] [Indexed: 04/15/2025] Open
Abstract
BACKGROUND Mixed neuroendocrine-non-neuroendocrine tumors (MINEN) of the liver are exceptionally rare, with limited data available regarding their clinical behavior, pathogenesis, and optimal management. The coexistence of hepatocellular carcinoma (HCC) and neuroendocrine carcinoma (NEC) within the liver presents diagnostic and therapeutic challenges. METHODS A systematic literature search was conducted on PubMed, identifying cases of primary mixed HCC and NEC in the liver. The search adhered to PRISMA guidelines, and relevant studies were critically analyzed. A total of 45 documented cases were reviewed, focusing on patient demographics, clinical characteristics, treatment strategies, and outcomes. RESULTS Most patients (90%) were male, with a median age of 66.5 years. Hepatitis B or C infection was present in 74% of cases, and liver cirrhosis was reported in 38%. The combined type was the most frequently observed histological pattern (65%). Treatment modalities varied, including transarterial chemoembolization (TACE), radiofrequency ablation (RFA), surgery, and systemic therapies. The median overall survival was 10 months, highlighting the aggressive nature of these tumors. CONCLUSIONS Given the rarity and poor prognosis of hepatic MINEN tumors, multidisciplinary management is essential. Advanced molecular profiling may offer insights into tumor biology and potential therapeutic targets. Future research should explore novel systemic therapies, including immune checkpoint inhibitors, to improve patient outcomes.
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Affiliation(s)
- Daniela Sambataro
- Medical Oncology Unit, Umberto I Hospital, 94100 Enna, Italy; (A.B.); (G.C.); (A.M.O.Q.); (E.V.)
- Department of Medicine and Surgery, Kore University, 94100 Enna, Italy; (P.D.M.); (V.G.)
| | - Sandro Bellavia
- Pathology Unit, Umberto I Hospital, 94100 Enna, Italy; (S.B.); (C.E.)
| | - Paolo Di Mattia
- Department of Medicine and Surgery, Kore University, 94100 Enna, Italy; (P.D.M.); (V.G.)
- Surgery Unit, Umberto I Hospital, 94100 Enna, Italy;
| | | | - Carmela Emmanuele
- Pathology Unit, Umberto I Hospital, 94100 Enna, Italy; (S.B.); (C.E.)
| | - Annalisa Bonasera
- Medical Oncology Unit, Umberto I Hospital, 94100 Enna, Italy; (A.B.); (G.C.); (A.M.O.Q.); (E.V.)
| | - Giuseppe Caputo
- Medical Oncology Unit, Umberto I Hospital, 94100 Enna, Italy; (A.B.); (G.C.); (A.M.O.Q.); (E.V.)
| | | | - Ernesto Vinci
- Medical Oncology Unit, Umberto I Hospital, 94100 Enna, Italy; (A.B.); (G.C.); (A.M.O.Q.); (E.V.)
| | - Vittorio Gebbia
- Department of Medicine and Surgery, Kore University, 94100 Enna, Italy; (P.D.M.); (V.G.)
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Fottner C, Apostolidis L, Krug S, Rinke A, Grün B, Michl P, Gress TM, Wagner DC, Roth W, Mettler E, Topsch J, Ruckes C, Galle PR, Weber MM. Activity and Safety of Avelumab in High-Grade Neuroendocrine Tumors and Poorly Differentiated Neuroendocrine Carcinomas Progressive after Chemotherapy (AveNEC Trial). Clin Cancer Res 2025; 31:860-867. [PMID: 39786465 DOI: 10.1158/1078-0432.ccr-24-2461] [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: 08/05/2024] [Revised: 10/08/2024] [Accepted: 12/23/2024] [Indexed: 01/12/2025]
Abstract
PURPOSE Neuroendocrine neoplasms grade 3 (NEN G3) are rare tumors with poor prognosis and no established second-line therapy. The role of immune checkpoint blockade in these aggressive tumors remains unclear. PATIENTS AND METHODS The phase II AveNEC study evaluated the effect of avelumab (AVE, 10 mg/kg i.v. every 2 weeks) in 60 patients with well-differentiated high-grade neuroendocrine tumors (N = 22) or poorly differentiated neuroendocrine carcinomas (N = 38) progressing after ≥1 prior chemotherapy (excluding Merkel cell carcinoma and small cell lung cancer). RESULTS The best overall response according to immune-related Response Evaluation Criteria in Solid Tumors (iRECIST) was partial response (PR) in three (5%) and stable disease (SD) in nine (15%) patients, with a disease control rate at 16 weeks of 15% (3 PRs; 6 SDs) and a median duration of response of 4.3 months. Six (10%) patients achieved SD or PR for >6 months and two for >1 year. Response rates were similar regardless of differentiation, Ki-67 expression, or primary localization. The median progression-free survival was 1.9 months, and the overall survival was 6.6 months. After a median follow-up of 3.6 years, only four (7%) patients were still alive; 1- and 2-year survival rates were 33% and 17%, respectively. Responders had a significantly longer overall survival of 30.2 months compared with 4.8 months in nonresponders. AVE was well tolerated, with few treatment-related grade 3/4 adverse events, and the quality of life remained stable during treatment. CONCLUSIONS In patients with progressive high-grade NEN G3, AVE was well tolerated and provided disease control with significant clinical benefit in 15% of heavily pretreated patients.
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Affiliation(s)
- Christian Fottner
- Unit of Endocrinology, I Medical Department, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Leonidas Apostolidis
- Department of Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg, University Hospital Heidelberg, Heidelberg, Germany
| | - Sebastian Krug
- UKH-Universitätsklinikum Halle (Saale), Halle (Saale), Germany
| | - Anja Rinke
- Department of Gastroenterology, UKGM-Uniklinikum Giessen und Marburg-Standort Marburg, Marburg, Germany
| | - Barbara Grün
- Department of Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg, University Hospital Heidelberg, Heidelberg, Germany
| | - Patrick Michl
- Department of Internal Medicine IV, University Hospital Heidelberg, Heidelberg, Germany
| | - Thomas M Gress
- Department of Gastroenterology, UKGM-Uniklinikum Giessen und Marburg-Standort Marburg, Marburg, Germany
| | - Daniel-Christoph Wagner
- Institute of Pathology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Wilfried Roth
- Institute of Pathology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Esther Mettler
- Unit of Endocrinology, I Medical Department, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Jana Topsch
- Interdisciplinary Centre for Clinical Trials, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Christian Ruckes
- Interdisciplinary Centre for Clinical Trials, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Peter R Galle
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Matthias M Weber
- Unit of Endocrinology, I Medical Department, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
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Cui W, Yang C, Ding X, Liu J, Zhang H, Xu H. Fine Needle Aspiration Cytological Diagnosis of Primary Breast Large-Cell Neuroendocrine Carcinoma/Squamous Cell Carcinoma. Diagn Cytopathol 2025; 53:E38-E45. [PMID: 39635966 DOI: 10.1002/dc.25427] [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: 09/27/2024] [Revised: 11/02/2024] [Accepted: 11/22/2024] [Indexed: 12/07/2024]
Abstract
Primary breast large-cell neuroendocrine carcinoma (LCNEC)/squamous cell carcinoma (SCC), also referred to as mixed neuroendocrine/non-neuroendocrine neoplasms of the breast (Br-MiNENs), represents an exceedingly rare malignancy. We report the first case of primary breast LCNEC/SCC diagnosed via ultrasound-guided fine-needle aspiration (FNA) biopsy of the left supraclavicular and left internal mammary lymph nodes. The patient, a 40-year-old female, underwent a lumpectomy followed by breast-conserving surgery and was diagnosed with primary breast LCNEC. Notably, within merely four months following the breast-conserving surgery, PET-CT revealed lymph node enlargement, prompting the performance of FNA. FNA cytology of metastatic lymph nodes revealed two distinct tumor components, allowing for clear differentiation between LCNEC and SCC in the smear. The diagnosis was further corroborated by immunocytochemical (ICC) staining of the cell blocks. Subsequently, histopathological re-examination of the breast mass revealed occult SCC components comprising less than 1% of the tumor cells. Additionally, the case exhibited triple-negative breast cancer, with PIK3CA, TP53, RB1, and BCL2L11 mutations identified through next-generation sequencing (NGS). Br-MiNEN is exceedingly rare, and its cytological diagnosis poses significant challenges. It is recommended that a detailed and objective description of each tumor component and its proportion be provided. This report provides the first detailed description of the FNA cytology of LCNEC/SCC, thereby enhancing cytopathologists' comprehension of this tumor. Auxiliary studies, including ICC staining and molecular biology assays, are crucial for accurate diagnosis, therapy, and prognosis.
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Affiliation(s)
- Wenjing Cui
- Department of Pathology, State Key Laboratory of Cancer Biology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Changwei Yang
- Department of Emergency Medicine, Xi'an Honghui Hospital, Xi'an, Shaanxi, China
| | - Xiaochen Ding
- Department of Experimental Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Jiayan Liu
- Department of Pathology, State Key Laboratory of Cancer Biology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Hongjuan Zhang
- Department of Pathology, State Key Laboratory of Cancer Biology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Hong Xu
- Department of Pathology, State Key Laboratory of Cancer Biology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University, Xi'an, Shaanxi, China
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Tang J, Wei S, Tang G, Zhao P. Development of a Nomogram-Based Online Calculator for Predicting Cancer-Specific Survival in Patients With Digestive Tract Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms (MiNENs): An Analysis of the SEER Database. Cancer Rep (Hoboken) 2025; 8:e70156. [PMID: 39972644 PMCID: PMC11839491 DOI: 10.1002/cnr2.70156] [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: 10/27/2024] [Revised: 01/28/2025] [Accepted: 02/07/2025] [Indexed: 02/21/2025] Open
Abstract
AIMS Mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) represent a rare and heterogeneous subgroup of neoplasms that typically consist of a neuroendocrine (NE) component, most commonly neuroendocrine carcinoma (NEC), alongside a non-neuroendocrine (non-NE) component. They commonly occur in the digestive tract, and their prognosis is influenced by multiple factors. This article aimed to identify factors that affect the cancer-specific survival (CSS) of MiNENs and develop an effective nomogram-based online calculator to validate its effectiveness. METHODS The clinical, pathological, epidemiological, and survival data of patients with digestive tract MiNENs were collected from the Surveillance, Epidemiology, and End Results (SEER) database spanning from 2000 to 2020. Then, the dataset was divided into a training cohort and a validation cohort. The χ2 test or Fisher's exact test was utilized to assess differences in demographic and clinicopathological characteristics between the two groups. Kaplan-Meier survival curves and log-rank tests were employed to conduct survival analysis. Additionally, univariate and multivariate Cox regression analyses were performed to identify potential prognostic factors and develop nomograms and an online calculator for predicting CSS at 1, 3, and 5 years. Lastly, the predictive ability of the online calculator was subsequently compared with the sixth edition of the American Joint Committee on Cancer (AJCC) TNM staging system using the Harrell concordance index (C-index), the area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA). RESULTS A total of 330 patients were randomly assigned to two groups, namely, the training cohort (n = 231) and the validation cohort (n = 99). The log-rank test revealed a significant association between the lower cumulative survival and age ≥ 65 years, poor tumor grade, lack of surgical treatment, TNM stages III and IV, and distant metastasis. In the training cohort, a nomogram incorporating grade, surgery, TNM stage, and tumor metastasis was developed, which demonstrated favorable calibration and discriminatory capabilities. Compared to TNM staging, the nomogram exhibited satisfactory performance in predicting 1-year, 3-year, and 5-year CSS rates. The C-index value was 0.787 in the training cohort and 0.738 in the validation cohort, respectively. In the training cohort, the nomogram achieved an AUC of 85.81%, 85.86%, and 87.32% for 1-year CSS, 3-year CSS, and 5-year CSS, respectively. In contrast, these AUC values were 78.46%, 81.50%, and 83.88% in the validation cohort, respectively. CONCLUSIONS The developed online calculator offers a novel approach to predicting the prognosis of patients with digestive tract MiNENs. Indeed, it can accurately predict the CSS of these patients over 1, 3, and 5 years, thereby assisting in enhancing prognosis and formulating appropriate treatment strategies.
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Affiliation(s)
- Jing Tang
- Department of GastroenterologyGuangyuan Central HospitalGuangyuanChina
| | - Siqi Wei
- Department of GastroenterologyGuangyuan Central HospitalGuangyuanChina
| | - Guobin Tang
- Department of GastroenterologyGuangyuan Central HospitalGuangyuanChina
| | - Ping Zhao
- Department of GastroenterologyGuangyuan Central HospitalGuangyuanChina
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Dabas S, Menon NN, Gurung B, Ranjan R, Shukla H, Tiwari S, Sharma A, Bassan BB, Jain K. MiNEN of base of tongue - first case report in literature. Eur Arch Otorhinolaryngol 2025; 282:1103-1109. [PMID: 39356359 DOI: 10.1007/s00405-024-09007-y] [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: 03/27/2024] [Accepted: 09/20/2024] [Indexed: 10/03/2024]
Abstract
INTRODUCTION Mixed neuroendocrine and non-neuroendocrine neoplasms (MiNENs) refer to a heterogenous group of rare neoplasms which is usually composed of a neuroendocrine population which is either well differentiated and more frequently poorly differentiated along with a non-neuroendocrine component, each of the above accounting for at least 30% of the tumour population. It is most commonly seen in the gastro-entero-pancreatic tract. MiNENs have an aggressive behaviour due to its high grade neuroendocrine component and have poor prognosis. This is the first case reported in literature of a MiNEN in the oropharynx. CASE REPORT 69 year old male patient with no co morbidities presented to the outpatient department with complains of odynophagia for 1 month. He had history of neoadjuvant chemotherapy followed by transoral robotic surgery (TORS) with right selective neck dissection (SND) done in 2019 for carcinoma base of tongue. On flexible laryngoscopy, an ulcerative lesion was noted over the left base of tongue. Although PET scan done showed no significant abnormalities. Biopsy from the lesion showed features of poorly differentiated carcinoma along with morphological features of poorly differentiated neuroendocrine carcinoma (small cell carcinoma). He was planned for upfront surgery (TORS with left SND). Post operatively recovery was uneventful and patient was on ryles tube feed for 12 days. Final histopathology report showed features of mixed neuroendocrine non neuroendocrine neoplasm. He has been on follow up for 1 year with no features of recurrence. CONCLUSION MiNEN is an aggressive tumour which has poor prognosis and is most commonly located in the gastrointestinal tract. This is the first case reported in oropharynx who has been successfully treated and has been on follow up.
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Affiliation(s)
- Surender Dabas
- Department of Surgical Oncology, BLK - MAX Superspeciality hospital, Delhi, India
| | - Nandini N Menon
- Department of Surgical Oncology, BLK - MAX Superspeciality hospital, Delhi, India.
| | - Bikas Gurung
- Department of Surgical Oncology, BLK - MAX Superspeciality hospital, Delhi, India
| | - Reetesh Ranjan
- Department of Surgical Oncology, BLK - MAX Superspeciality hospital, Delhi, India
| | - Himanshu Shukla
- Department of Surgical Oncology, BLK - MAX Superspeciality hospital, Delhi, India
| | - Sukirti Tiwari
- Department of Surgical Oncology, BLK - MAX Superspeciality hospital, Delhi, India
| | - Ashwani Sharma
- Department of Surgical Oncology, BLK - MAX Superspeciality hospital, Delhi, India
| | | | - Kunal Jain
- DNB Resident, Department of Pathology, BLK - MAX Superspeciality hospital, Delhi, India
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Sen T, Dotsu Y, Corbett V, Puri S, Sen U, Boyle TA, Mack P, Hirsch F, Aljumaily R, Naqash AR, Sukrithan V, Karim NA. Pulmonary neuroendocrine neoplasms: the molecular landscape, therapeutic challenges, and diagnosis and management strategies. Lancet Oncol 2025; 26:e13-e33. [PMID: 39756451 DOI: 10.1016/s1470-2045(24)00374-7] [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: 01/29/2024] [Revised: 05/20/2024] [Accepted: 06/25/2024] [Indexed: 01/07/2025]
Abstract
Lung neuroendocrine neoplasms are a group of diverse, heterogeneous tumours that range from well-differentiated, low-grade neuroendocrine tumours-such as typical and atypical carcinoids-to high-grade, poorly differentiated aggressive malignancies, such as large-cell neuroendocrine carcinoma (LCNEC) and small-cell lung cancer (SCLC). While the incidence of SCLC has decreased, the worldwide incidence of other pulmonary neuroendocrine neoplasms has been increasing over the past decades. In addition to the standard histopathological classification of lung neuroendocrine neoplasms, the introduction of molecular and sequencing techniques has led to new advances in understanding the biology of these diseases and might influence future classifications and staging that can subsequently improve management guidelines in the adjuvant or metastatic settings. Due to the rarity of neuroendocrine neoplasms, there is a paucity of prospective studies that focus on the lungs, especially in rare, well-differentiated carcinoids and LCNECs. In contrast with the success of targeted therapies in non-small-cell lung cancer (NSCLC), high-grade neuroendocrine carcinomas of the lung often only have a few specific targetable gene alterations. Optimal therapy for LCNECs is not well defined and treatment recommendations are based on extrapolating guidelines for the management of patients with SCLC and NSCLC. This Review explores the epidemiology, diagnosis, and staging of lung neuroendocrine neoplasms to date. In addition, we focus on the evolving molecular landscape and biomarkers, ranging from tumour phenotypes to functional imaging studies and novel molecular biomarkers. We outline the various clinical outcomes, challenges, the treatment landscape, ongoing clinical trials, and future directions.
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Affiliation(s)
- Triparna Sen
- Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
| | - Yosuke Dotsu
- Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Virginia Corbett
- Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Sonam Puri
- Division of Clinical Oncology, The Huntsman Cancer Institute at The University of Utah, Salt Lake City, UT, USA
| | - Utsav Sen
- Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | | | - Phil Mack
- Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Fred Hirsch
- Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Raid Aljumaily
- Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK, USA
| | - Abdul Rafeh Naqash
- Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK, USA
| | - Vineeth Sukrithan
- Ohio State University Comprehensive Cancer Center, Columbus, OH, USA
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Zhao X, Bocker Edmonston T, Miick R, Joneja U. Mixed pancreatic ductal adenocarcinoma and well-differentiated neuroendocrine tumor: A case report. World J Gastrointest Oncol 2024; 16:4738-4745. [PMID: 39678795 PMCID: PMC11577375 DOI: 10.4251/wjgo.v16.i12.4738] [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: 07/31/2024] [Revised: 10/05/2024] [Accepted: 10/22/2024] [Indexed: 11/12/2024] Open
Abstract
BACKGROUND Pancreatic mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) are rare malignancies affecting the pancreas. The World Health Organization defines MiNENs as neoplasms composed of morphologically recognizable neuroendocrine and non-neuroendocrine components, each constituting 30% or more of the tumor volume. Adenocarcinoma-neuroendocrine carcinoma is the most frequent MiNEN combination. A well-differentiated neuroendocrine tumor (NET) component is rarely reported in MiNENs. CASE SUMMARY Here we report a rare case with intermingled components of ductal adenocarcinoma and grade 1 well-differentiated NET in the pancreas. The two tumors show distinct histology and significant differentiation discrepancy (poorly differentiated high grade adenocarcinoma and well-differentiated low grade NET), and also present as metastases in separate lymph nodes. Next generation sequencing of the two components demonstrates KRAS and TP53 mutations in the ductal adenocarcinoma, but no genetic alterations in the NET, suggesting divergent origins for these two components. Although tumors like this meet the diagnostic criteria for MiNEN, clinicians often find the diagnosis and staging confusing and impractical for clinical management. CONCLUSION Mixed NET/non-NET tumors with distinct histology and molecular profiles might be better classified as collision tumors rather than MiNENs.
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Affiliation(s)
- Xiaofeng Zhao
- Department of Pathology, Cooper University Hospital, Camden, NJ 08103, United States
| | - Tina Bocker Edmonston
- Department of Pathology, Cooper University Hospital, Camden, NJ 08103, United States
| | - Ronald Miick
- Department of Pathology, Cooper University Hospital, Camden, NJ 08103, United States
| | - Upasana Joneja
- Department of Pathology, Cooper University Hospital, Camden, NJ 08103, United States
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Hong Q, Wu K, Chen C, Dang Y, Zhang Q, Zhang X, Wang L, Han R, Zhao C, Yi H, Li F, Zhang R, Mu J, Li J. Characterizing esophageal mixed neuroendocrine-non-neuroendocrine neoplasms: insights from a retrospective multicenter study of clinical outcomes and prognostic indicators. Ther Adv Med Oncol 2024; 16:17588359241303066. [PMID: 39649016 PMCID: PMC11624530 DOI: 10.1177/17588359241303066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Accepted: 11/11/2024] [Indexed: 12/10/2024] Open
Abstract
Background The esophageal mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) is an extremely rare but poor prognosis tumor. Objectives This retrospective study aimed to analyze the clinical characteristics of MiNEN and to investigate postoperative survival and prognostic factors. Design This retrospective study analyzed 69 patients diagnosed with esophageal MiNEN at two major esophageal cancer centers in China from January 2000 to December 2021. Methods We assessed demographic data, tumor characteristics, treatment modalities, and survival outcomes. Statistical analyses included Kaplan-Meier survival curves and Cox regression models to evaluate prognostic factors. Results The most common histological types were combinations of small-cell carcinoma and squamous carcinoma (91.3%). The correct diagnostic rate of preoperative pathologic biopsy was only 4.3%. The median overall survival (OS) was 24.0 months, and disease-free survival (DFS) was 16.6 months. The 1-, 3-, and 5-year survival rates were 84.1%, 34.8%, and 25.3%, respectively. A peak period of recurrence or metastasis occurs in the first year after surgery, and regional lymph node recurrence is the main route of postoperative recurrence or metastasis. Tumor size, T-stage, N-stage, and tumor, lymph node, metastasis (TNM) stage were significant prognostic factors. Subgroup analyses showed that in patients with limited-stage MiNEN in stages I-III, the postoperative adjuvant treatment modality failed to improve OS and DFS compared with surgery alone. Postoperative adjuvant therapy also failed to prolong OS and DFS in patients with lymph node-positive MiNEN. No significant survival benefits were observed with different surgical techniques or adjuvant chemotherapy regimens. Conclusion Esophageal MiNEN has aggressive behavior and a poor prognosis. In China, the pathologic type of esophageal MiNEN may be dominated by a combination of small-cell carcinoma and squamous carcinoma. Early-stage disease significantly correlated with improved survival outcomes. Current treatment protocols, similar to those for other esophageal cancers, show limited efficacy in improving patient survival.
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Affiliation(s)
- Qian Hong
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Kaiming Wu
- Department of Thoracic Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Chen Chen
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yan Dang
- Department of Thoracic Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Qiuju Zhang
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xue Zhang
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Liting Wang
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Rui Han
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Chenguang Zhao
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hang Yi
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Fang Li
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Renquan Zhang
- Department of Thoracic Surgery, The First Affiliated Hospital of Anhui Medical University, No. 218, Ji Xi Road, Hefei 230000, Anhui, China
| | - Juwei Mu
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuan Nanli, Chaoyang District, Beijing 100021, China
| | - Jiagen Li
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuan Nanli, Chaoyang District, Beijing 100021, China
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Surjan RCT, Paulino JFDA, Schleinstein HP, Pereira FMT, Figueira ERR, Ardengh JC. ROBOTIC PANCREATICODUODENECTOMY FOR THE TREATMENT OF A MIXED NEUROENDOCRINE-NON-NEUROENDOCRINE NEOPLASM (MINEN) OF THE AMPULLA OF VATER. ARQUIVOS BRASILEIROS DE CIRURGIA DIGESTIVA : ABCD = BRAZILIAN ARCHIVES OF DIGESTIVE SURGERY 2024; 37:e1840. [PMID: 39630841 DOI: 10.1590/0102-6720202400046e1840] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Accepted: 09/27/2024] [Indexed: 12/07/2024]
Abstract
Mixed neuroendocrine-non-neuroendocrine tumors (MiNEN) are a rare type of tumor formed by two components, a non-neuroendocrine component that is most often an adenocarcinoma and a neuroendocrine tumor, and each of these components must represent at least 30% of the tumor. The origin of this tumor on the ampulla of Vater or periampullary region is more infrequent. Usually, the lesions are highly aggressive and quickly metastasizing, and their biological behavior is dictated by the high grade of the neuroendocrine component. This is the first report of a patient with ampullary MiNEN treated employing a robotic pancreaticoduodenectomy. Although being submitted to aggressive treatment with complete surgical resection followed by systemic therapy, the patient developed early recurrence with hepatic metastatic disease, demonstrating the hostile nature of these tumors.
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Affiliation(s)
- Rodrigo Cañada Trofo Surjan
- Hospital Nove de Julho - São Paulo (SP), Brazil
- Universidade de São Paulo, Faculty of Medicine, Department of Gastroenterology, Pancreaticobiliar Surgery - São Paulo (SP), Brazil
| | | | | | | | - Estela Regina Ramos Figueira
- Hospital Nove de Julho - São Paulo (SP), Brazil
- Universidade de São Paulo, Faculty of Medicine, Department of Gastroenterology, Pancreaticobiliar Surgery - São Paulo (SP), Brazil
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Tsuchiyose E, Talanian M, Liao H, Holzwanger E. Endoscopic Ultrasound-Guided Diagnosis of Gallbladder Mixed Neuroendocrine Non-Neuroendocrine Tumor With an Anomalous Pancreaticobiliary Junction. ACG Case Rep J 2024; 11:e01566. [PMID: 39641104 PMCID: PMC11617348 DOI: 10.14309/crj.0000000000001566] [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: 09/15/2024] [Accepted: 11/07/2024] [Indexed: 12/07/2024] Open
Abstract
Mixed neuroendocrine non-neuroendocrine neoplasms are exceedingly rare tumors, especially those of gallbladder origin. Anomalous pancreaticobiliary junction is an uncommon congenital abnormality that can predispose various types of hepatobiliary malignancies. We present an unusual case of a 46-year-old woman with anomalous pancreaticobiliary junction who presented to the emergency department with nausea, vomiting, and right upper quadrant pain. Magnetic resonance imaging revealed a gallbladder mass concerning for primary malignancy and liver lesions. Endoscopic ultrasound and fine-needle biopsy were valuable diagnostic tools used to sample the gallbladder, liver lesions, and common hepatic duct under one minimally invasive procedure. Pathology showed a gallbladder mixed neuroendocrine non-neuroendocrine neoplasms, with neuroendocrine components in the liver and adenocarcinoma components in the common hepatic duct.
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Affiliation(s)
| | - Michael Talanian
- Department of Gastroenterology, Tufts Medical Center, Boston, MA
| | - Haihui Liao
- Department of Pathology and Laboratory Medicine, Tufts University School of Medicine, Boston, MA
| | - Erik Holzwanger
- Department of Gastroenterology, Tufts Medical Center, Boston, MA
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13
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Mattiolo P. Practical hints for the diagnosis of mixed neuroendocrine-non-neuroendocrine neoplasms of the digestive system. World J Gastrointest Oncol 2024; 16:4326-4332. [PMID: 39554731 PMCID: PMC11551634 DOI: 10.4251/wjgo.v16.i11.4326] [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: 03/26/2024] [Revised: 06/06/2024] [Accepted: 07/15/2024] [Indexed: 10/25/2024] Open
Abstract
In this editorial, a comment on the article by Díaz-López et al published in the recent issue of the 2024 is provided. We focus on the practical implications critical for providing a correct and complete diagnosis of mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) in the gastrointestinal system. The diagnosis of MiNEN begins with the recognition of neuroendocrine features in one component of a biphasic tumor. The non-neuroendocrine counterpart can be virtually represented by any neoplastic type, even though the most frequent histologies are glandular and squamous. However, qualification of the neuroendocrine component requires histological and immunohistochemical confirmation. Neuroendocrine tumors are characterized by a peculiar architectural organization and bland nuclei with granular "salt and pepper" chromatin. Although neuroendocrine carcinomas have multiple and variable presentations, they typically show a solid or organoid architecture. The histological aspect needs to be confirmed by immunohistochemistry, and a diagnosis is confirmed whenever the expression of keratin and neuroendocrine markers is observed. Once both histopathological and immunohistochemical features of neuroendocrine neoplasms are identified, it is important to consider the three major pitfalls of MiNEN diagnostics: (1) Entrapment of neuroendocrine non-neoplastic cells within the tumor mass; (2) Differential diagnosis with amphicrine neoplasms; and (3) Differential diagnosis of tumors that partially express neuroendocrine markers. According to the current guidelines for diagnosing digestive MiNEN, each component must represent at least 30% of the entire neoplastic mass. Although the high-grade histopathological subtype frequently determines disease prognosis, both components can significantly affect prognosis. Thus, if one of the components, either neuroendocrine or non-neuroendocrine, does not fulfill the volumetric criteria, the guidelines still encourage reporting it. These strict criteria are essential for correctly recognizing and characterizing digestive MiNENs. This task is essential because it has prognostic relevance and substantial potential value for guiding further studies in this field. In the future, systematic analyses should be performed to validate or reconsider the current 30% cutoff value.
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Affiliation(s)
- Paola Mattiolo
- Department of Diagnostics and Public Health, Section of Pathology, University of Verona, University and Hospital Trust of Verona, Verona 37134, Italy
- Department of Pathology, Heinrich Heine University and University Hospital of Duesseldorf, Duesseldorf 40225, Germany
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14
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Gao R, Zhang X, Chen X, Lin Y, Jin L, Zheng H, Yu X. Comparison of insulinoma-associated protein 1 (INSM1) with traditional neuroendocrine markers in gastrointestinal and pancreatic mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs). Diagn Pathol 2024; 19:144. [PMID: 39472993 PMCID: PMC11520864 DOI: 10.1186/s13000-024-01568-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Accepted: 10/24/2024] [Indexed: 11/02/2024] Open
Abstract
The traditional diagnostic markers for mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) are synaptophysin (SYP), chromogranin A (CHGA) and CD56. However, there is still a lack of a large series of article focused on the expression of insulinoma-associated protein 1 (INSM1) in gastrointestinal and pancreatic MiNENs. This study compared the expression of INSM1 and traditional neuroendocrine markers in MiNENs. In this study, we collected 46 cases of gastrointestinal and pancreatic MiNENs and performed immunohistochemical staining for INSM1, SYP, CHGA, and CD56. Histologically, the neuroendocrine components of MiNENs were all neuroendocrine carcinomas, with small cell neuroendocrine carcinomas accounting for 15.2% (7/46) and large cell neuroendocrine carcinomas accounting for 84.8% (39/46). With respect to immunohistochemical expression, the overall sensitivity of INSM1 was 80.4% (37/46), which was lower than that of SYP (100%, 46/46), but comparable to that of CHGA (67.4%, 31/46) or CD56 (73.9%, 34/46). The overall specificity of INSM1 was 91.3% (42/46), which was greater than that of SYP (63.0%, 29/46) and CD56 (69.6, 32/46), but was not significantly different from that of CHGA (82.6%, 38/46). The proportion of 3 + staining for SYP (100%, 46/46) was greater than that of INSM1 (71.7, 33/46), while the proportion of 3 + staining for CHGA (10.9, 5/46) or CD56 (21.7, 10/46) was lower than that of INSM1. In conclusion, INSM1 exhibited high sensitivity and specificity in the diagnosis of gastrointestinal and pancreatic MiNENs.
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Affiliation(s)
- Rui Gao
- Department of Pathology, Fujian Provincial Hospital, Provincial Clinical Medical College of Fujian Medical University, Fuzhou University Affiliated Provincial Hospital, NO.134 East Street, Gulou District, Fuzhou, Fujian, 350001, P.R. China.
| | - Xi Zhang
- Department of Gastroenterology, Fujian Provincial Hospital, Provincial Clinical Medical College of Fujian Medical University, Fuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian, P.R. China
| | - Xin Chen
- Department of Pathology, Fujian Provincial Hospital, Provincial Clinical Medical College of Fujian Medical University, Fuzhou University Affiliated Provincial Hospital, NO.134 East Street, Gulou District, Fuzhou, Fujian, 350001, P.R. China
| | - Ying Lin
- Department of Pathology, Fujian Provincial Hospital, Provincial Clinical Medical College of Fujian Medical University, Fuzhou University Affiliated Provincial Hospital, NO.134 East Street, Gulou District, Fuzhou, Fujian, 350001, P.R. China
| | - Long Jin
- Department of Pathology, Fujian Provincial Hospital, Provincial Clinical Medical College of Fujian Medical University, Fuzhou University Affiliated Provincial Hospital, NO.134 East Street, Gulou District, Fuzhou, Fujian, 350001, P.R. China.
| | - Huawei Zheng
- Department of Pathology, Fujian Provincial Hospital, Provincial Clinical Medical College of Fujian Medical University, Fuzhou University Affiliated Provincial Hospital, NO.134 East Street, Gulou District, Fuzhou, Fujian, 350001, P.R. China
| | - Xunbin Yu
- Department of Pathology, Fujian Provincial Hospital, Provincial Clinical Medical College of Fujian Medical University, Fuzhou University Affiliated Provincial Hospital, NO.134 East Street, Gulou District, Fuzhou, Fujian, 350001, P.R. China
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15
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You MW, Kim SW. Tumor recurrence with disseminated liver metastases in a patient with resected early gastric cancer: a case of mixed adenoneuroendocrine carcinoma (MANEC). Quant Imaging Med Surg 2024; 14:7775-7779. [PMID: 39429616 PMCID: PMC11485334 DOI: 10.21037/qims-23-1791] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2023] [Accepted: 05/23/2024] [Indexed: 10/22/2024]
Affiliation(s)
- Myung-Won You
- Department of Radiology, Kyung Hee University College of Medicine, Kyung Hee University Hospital, Seoul, Korea
| | - So-Woon Kim
- Department of Pathology, Kyung Hee University College of Medicine, Kyung Hee University Hospital, Seoul, Korea
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16
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Spada F, Milione M, Maisonneuve P, Prinzi N, Smiroldo V, Bolzacchini E, Pusceddu S, Carnaghi C, Sessa F, La Rosa S, Uccella S, Fazio N. An Italian real-world multicenter study of patients with advanced mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) of the gastro-entero-pancreatic system treated with chemotherapy. J Endocrinol Invest 2024; 47:2279-2294. [PMID: 38402360 DOI: 10.1007/s40618-024-02314-5] [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: 12/11/2023] [Accepted: 01/12/2024] [Indexed: 02/26/2024]
Abstract
PURPOSE The aim of this study is to describe the clinical management of an Italian series of patients with advanced gastro-entero-pancreatic (GEP) MiNENs treated in clinical practice. METHODS Clinical records of patients from four Italian referral Centers were retrospectively analyzed to correlate clinical/biological data with clinical outcomes. All the surgical specimens were centrally reviewed. RESULTS Clinical data and surgical samples of 51 patients during 1995-2015 were analyzed. Sites of origin were: 32 colorectal, 14 gastro-esophageal, and 5 pancreatobiliary. Twenty-one out of fifty-one (42.2%) developed metachronous distant metastases. Only 5/51 (9.8%) patients received peri-operative therapy, and 23/51 (45.1%) first-line chemotherapy, mostly fluoropyrimidines/oxaliplatin. The NEN component was poorly differentiated in the whole population. Patients with Ki67 index < 55% in the NEC component had a significantly longer median overall survival (OS) (35.3 months; 95% CI 27.1-41.0) than those with Ki67 ≥ 55% (11.9 months; 95% CI 9.1-14.0) P = 0.0005. The median OS was 14 months (95% CI 10.1-19.1) in the whole cohort, with 11.4 months (95% CI 6.2-20.2) in patients who received a first-line therapy. CONCLUSION This study confirms that GEP-MiNENs represent a complex disease and that over the past years the clinical management has been predominantly guided by the subjective judgment of the clinicians. Although, in this series, the NEC component appeared mostly responsible for the systemic spread and prognosis on the whole neoplasm, the lack of strong prognostic and predictive factors universally recognized seems to condition their management so far. Future prospective clinical and biomolecular studies could help clinicians to improve clinical management of GEP-MiNENs.
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Affiliation(s)
- Francesca Spada
- Division of Gastrointestinal Medical Oncology, Neuroendocrine Tumors, IEO, European Institute of Oncology, IRCCS, Milan, Italy
| | - Massimo Milione
- Division of Pathology, Department of Pathology and Laboratory Medicine, IRCCS Foundation National Cancer Institute, Milan, Italy
| | - Patrick Maisonneuve
- Division of Epidemiology and Biostatistics, IEO, European Institute of Oncology, IRCCS, Milan, Italy
| | - Natalie Prinzi
- Department of Medical Oncology, IRCCS Foundation National Cancer Institute, Milan, Italy
- First Department of Internal Medicine, San Matteo Hospital Foundation, Pavia, Italy
| | - Valeria Smiroldo
- Medical Oncology Unit, Istituto Clinico Humanitas, IRCCS, via Manzoni 56, Rozzano, Italy
- Oncology Unit, ASST Rhodense, Rho, Italy
| | - Elena Bolzacchini
- Department of Oncology, Ospedale Di Circolo, Varese, Italy
- Oncology Unit, Ospedale Sant'Anna, ASST Lariana, Como, Italy
| | - Sara Pusceddu
- Department of Medical Oncology, IRCCS Foundation National Cancer Institute, Milan, Italy
| | - Carlo Carnaghi
- Medical Oncology Unit, Istituto Clinico Humanitas, IRCCS, via Manzoni 56, Rozzano, Italy
- Medical Oncology, Humanitas Istituto Clinico Catanese, Catania, Sicilia, Italy
| | - Fausto Sessa
- Unit of Pathology, Department of Medicine and Technological Innovation, University of Insubria, Varese, Italy
- Unit of Pathology, Department of Oncology, ASST Sette Laghi, Varese, Italy
| | - Stefano La Rosa
- Unit of Pathology, Department of Medicine and Technological Innovation, University of Insubria, Varese, Italy
- Unit of Pathology, Department of Oncology, ASST Sette Laghi, Varese, Italy
| | - Silvia Uccella
- Pathology Unit, Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
- Pathology Service, Humanitas Clinical and Research Center, IRCCS, Rozzano, Milan, Italy
| | - Nicola Fazio
- Division of Gastrointestinal Medical Oncology, Neuroendocrine Tumors, IEO, European Institute of Oncology, IRCCS, Milan, Italy.
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Adepoju J, Toms JA, O'Neill ES, Grievous M, Hasan J, Tragos C, Doscher M. Mixed Neuroendocrine-Squamous Cell Carcinoma of the Hand With Metastatic Dissemination: A Case Report. EPLASTY 2024; 24:e45. [PMID: 39224411 PMCID: PMC11367163] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 09/04/2024]
Abstract
Cutaneous manifestations of mixed neuroendocrine non-neuroendocrine neoplasms remain a diagnostic rarity. Predominantly identified within internal glandular organs, the digestive tract, and in the hepatobiliary system, this case report illustrates a unique occurrence of a mixed squamous cell and neuroendocrine tumor in the index finger of a justice-affected patient. We discuss the complexities of diagnosis and complications as well as emphasize the importance for hand surgeons to recognize presentations like this and the need for vigilant follow-up and improved care coordination.
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Affiliation(s)
- Jubril Adepoju
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Rush University Medical Center, Chicago, Illinois
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Cook County Health and Hospitals System, Chicago, Illinois
| | - John A. Toms
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Rush University Medical Center, Chicago, Illinois
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Cook County Health and Hospitals System, Chicago, Illinois
| | - Elizabeth S. O'Neill
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Rush University Medical Center, Chicago, Illinois
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Cook County Health and Hospitals System, Chicago, Illinois
| | - Mark Grievous
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Rush University Medical Center, Chicago, Illinois
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Cook County Health and Hospitals System, Chicago, Illinois
| | - Jafar Hasan
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Rush University Medical Center, Chicago, Illinois
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Cook County Health and Hospitals System, Chicago, Illinois
| | - Christina Tragos
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Rush University Medical Center, Chicago, Illinois
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Cook County Health and Hospitals System, Chicago, Illinois
| | - Matthew Doscher
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Rush University Medical Center, Chicago, Illinois
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Cook County Health and Hospitals System, Chicago, Illinois
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Hu YF, Wang JK, Ma WJ, Hu HJ, Gu HF, Liu F, Lv TR, Yang SQ, Dai YS, Zou RQ, Jin YW, Li FY. Does the size of the neuroendocrine-carcinoma component determine the prognosis of gallbladder cancer? Front Endocrinol (Lausanne) 2024; 15:1217250. [PMID: 39104815 PMCID: PMC11298461 DOI: 10.3389/fendo.2024.1217250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Accepted: 01/29/2024] [Indexed: 08/07/2024] Open
Abstract
Background Gallbladder mixed neuroendocrine-non-neuroendocrine neoplasm generally consists of a gallbladder neuroendocrine tumor and a non-neuroendocrine component. The World Health Organization (WHO) in 2019 established a guideline requiring each component, both neuroendocrine and non-neuroendocrine, to account for a minimum of 30% of the tumor mass. Methods Patients after surgery resection and diagnosed at microscopy evaluation with pure gallbladder neuroendocrine carcinoma (GBNEC), gallbladder mixed adeno-neuroendocrine carcinoma (GBMANEC, GBNEC≥30%), and gallbladder carcinoma mixed with a small fraction of GBNEC (GBNEC <30%) between 2010 and 2022 at West China Hospital of Sichuan University were collated for the analyses. Demographic features, surgical variables, and tumor characteristics were evaluated for association with patients' overall and recurrence-free survival (OS and RFS). Results The study included 26 GBNEC, 11 GBMANEC, 4 gallbladder squamous-cell carcinoma (GBSCC), and 7 gallbladder adenocarcinoma (GBADC) mixed with a small fraction of GBNEC. All patients had stage III or higher tumors (AJCC8th edition). The majority of included patients (79.17%) underwent curative surgical resection (R0), with only ten patients having tumoral resection margins. In the analysis comparing patients with GBNEC percentage (GBNEC≥30% vs. GBNEC<30%), the basic demographics and tumor characteristics of most patients were comparable. The prognosis of these patients was also comparable, with a median OS of 23.65 months versus 20.40 months (P=0.13) and a median RFS of 17.1 months versus 12.3 months (P=0.24). However, patients with GBADC or GBSCC mixed with GBNEC <30% had a statistically significant decreased OS and RFS (both P<0.0001)) compared with GBNEC and GBMANEC. Patients with GBNEC who exhibited advanced tumor stages and lymphovascular invasion had a higher risk of experiencing worse overall survival (OS) and recurrence-free survival (RFS). However, a 30% GBNEC component was not identified as an independent risk factor. Conclusion Patients with GBNEC were frequently diagnosed at advanced stages and their prognosis is poor. The 30% percentage of the GBNEC component is not related to the patient's survival.
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Affiliation(s)
- Ya-Fei Hu
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, China
- Department of Biliary Disease Research Center, West China Hospital of Sichuan University, Chengdu, China
| | - Jun-Ke Wang
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, China
- Department of Biliary Disease Research Center, West China Hospital of Sichuan University, Chengdu, China
| | - Wen-Jie Ma
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, China
- Department of Biliary Disease Research Center, West China Hospital of Sichuan University, Chengdu, China
| | - Hai-Jie Hu
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, China
- Department of Biliary Disease Research Center, West China Hospital of Sichuan University, Chengdu, China
| | - Han-Fei Gu
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, China
- Department of Biliary Disease Research Center, West China Hospital of Sichuan University, Chengdu, China
| | - Fei Liu
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, China
- Department of Biliary Disease Research Center, West China Hospital of Sichuan University, Chengdu, China
| | - Tian-Run Lv
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, China
- Department of Biliary Disease Research Center, West China Hospital of Sichuan University, Chengdu, China
| | - Si-Qi Yang
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, China
- Department of Biliary Disease Research Center, West China Hospital of Sichuan University, Chengdu, China
| | - Yu-Shi Dai
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, China
- Department of Biliary Disease Research Center, West China Hospital of Sichuan University, Chengdu, China
| | - Rui-Qi Zou
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, China
- Department of Biliary Disease Research Center, West China Hospital of Sichuan University, Chengdu, China
| | - Yan-Wen Jin
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, China
- Department of Biliary Disease Research Center, West China Hospital of Sichuan University, Chengdu, China
| | - Fu-Yu Li
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, China
- Department of Biliary Disease Research Center, West China Hospital of Sichuan University, Chengdu, China
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Kawakami M, Nakazato H, Tokisawa H, Tomiyama T, Miyagi J, Nagayoshi S, Tamashiro K, Yoshimi N, Ohmine Y. Preoperative Diagnostic Dilemma in Rapidly Progressive Mixed Neuroendocrine-Nonendocrine Neoplasm of the Ascending Colon: A Case Report. Case Rep Gastroenterol 2024; 18:361-366. [DOI: 10.1159/000539978] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2025] Open
Abstract
Introduction: Mixed neuroendocrine-nonendocrine neoplasms (MiNENs) of the digestive tract are rare. They contain both neuroendocrine and nonendocrine components. We here report a rare case of a metastatic MiNEN originating in the ascending colon. Case Presentation: An 80-year-old man presented with abdominal pain and vomiting. Colonoscopy showed an obstructing mass in the ascending colon, and a biopsy resulted in diagnosis of an adenocarcinoma. A CT scan revealed multiple liver metastases. Thus, our diagnosis was stage IV colon adenocarcinoma (cT4aN1bM1a according to TNM Classification of Malignant Tumors). The primary lesion was resected to alleviate symptoms. Histopathological and immunohistochemical examination revealed a well-differentiated adenocarcinoma and a small-cell neuroendocrine carcinoma, leading to the diagnosis of a MiNEN. The patient declined postoperative treatment and died approximately 2 months after the surgery. Conclusion: The incidence of MiNENs may be underestimated because they lack typical symptoms or imaging features and are therefore often only diagnosed after resection. Awareness of colonic MiNENs and further accumulation of cases are necessary to improve the outcomes.
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20
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Shenoy S. Mixed neuroendocrine and adenocarcinoma of gastrointestinal tract: A complex diagnosis and therapeutic challenge. World J Gastrointest Oncol 2024; 16:2295-2299. [PMID: 38994166 PMCID: PMC11236242 DOI: 10.4251/wjgo.v16.i6.2295] [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: 01/08/2024] [Revised: 03/05/2024] [Accepted: 04/10/2024] [Indexed: 06/13/2024] Open
Abstract
In this editorial we comment on the manuscript describing a case of adenocarcinoma mixed with a neuroendocrine carcinoma of the gastroesophageal junction. Mixed neuroendocrine and non-neuroendocrine neoplasms of the gastrointestinal system are rare heterogeneous group of tumors characterized by a high malignant potential, rapid growth, and poor prognosis. Due to the rarity of these cancers, the standard therapy is poorly defined. The diagnosis of these tumors is based on combination of morphological features, immunohistochemical and neuroendocrine and epithelial cell markers. Both endocrine and epithelial cell components can act independently of each other and thus, careful grading of each component separately is required. These cancers are aggressive in nature and the potential of each component has paramount importance in the choice of treatment and response. Regardless of the organ of origin, these tumors portend poor prognosis with increased proportion of neuroendocrine component. Multidisciplinary services and strategies are required for the management of these mixed malignancies to provide the best oncological outcomes. The etiopathogenesis of these mixed tumors remains obscure but poses interesting question. We briefly discuss a few salient points in this editorial.
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Affiliation(s)
- Santosh Shenoy
- Department of General Surgery, Kansas City VA Medical Center, University of Missouri - Kansas City, Kansas City, MO 64128, United States
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21
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Alamin F, Sage H, Torres I, Parikh J, Zayat V. Unveiling the Rarity: A Case of a Mixed Neuroendocrine-Non-Neuroendocrine Tumor of the Gastroesophageal Junction. Cureus 2024; 16:e63141. [PMID: 39055477 PMCID: PMC11272183 DOI: 10.7759/cureus.63141] [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] [Accepted: 06/24/2024] [Indexed: 07/27/2024] Open
Abstract
Mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) are a rare group of heterogeneous tumors, consisting of an endocrine and a nonendocrine component, which can develop throughout the gastrointestinal (GI) tract. This case presents a 70-year-old man with a complex medical history who initially presented with an upper GI bleed. After being stabilized, he underwent an esophagogastroduodenoscopy (EGD) that revealed a suspicious gastroesophageal junction (GEJ) mass. Histopathological studies paired with immunohistochemical investigations of the mass confirmed the rare diagnosis of MiNENs. He then underwent an endoscopic submucosal dissection (ESD) with subsequent chemotherapy and adjunct radiotherapy, with no recurrence noted on post-treatment surveillance. This case highlights the need for an EGD, histopathological examination, and immunohistochemical staining for detecting the underlying etiology of an upper GI bleed.
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Affiliation(s)
- Faris Alamin
- Internal Medicine, University of Central Florida/HCA Osceola Hospital, Orlando, USA
| | - Hannah Sage
- Pathology, University of Central Florida College of Medicine, Orlando, USA
| | - Isabel Torres
- Pathology, University of Central Florida College of Medicine, Orlando, USA
| | - Jignesh Parikh
- Pathology, Orlando Veterans Affairs Medical Center, Orlando, USA
| | - Vania Zayat
- Pathology, Orlando Veterans Affairs Medical Center, Orlando, USA
- Pathology, University of Central Florida College of Medicine, Orlando, USA
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22
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Díaz-López S, Jiménez-Castro J, Robles-Barraza CE, Ayala-de Miguel C, Chaves-Conde M. Mixed neuroendocrine non-neuroendocrine neoplasms in gastroenteropancreatic tract. World J Gastrointest Oncol 2024; 16:1166-1179. [PMID: 38660639 PMCID: PMC11037054 DOI: 10.4251/wjgo.v16.i4.1166] [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: 12/06/2023] [Revised: 01/17/2024] [Accepted: 02/18/2024] [Indexed: 04/10/2024] Open
Abstract
Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) are a heterogeneous group of malignant neoplasms that can settle in the gastroenteropancreatic tract. They are composed of a neuroendocrine (NE) and a non-NE component in at least 30% of each tumour. The non-NE component can include different histological combinations of glandular, squamous, mucinous and sarcomatoid phenotypes, and one or both of the components can be low-or high grade malignant. Recent changes in the nomenclature of these neoplasms might lead to great deal of confusion, and the lack of specific clinical trials is the main reason why their management is difficult. The review aims to clarify the definition of MiNEN and analyze available evidence about their diagnosis and treatment options according to their location and extension through careful analysis of the available data. It would be important to reach a general consensus on their diagnosis in order to construct a classification that remains stable over time and facilitates the design of clinical trials that, due to their low incidence, will require long recruitment periods.
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Affiliation(s)
- Sebastián Díaz-López
- Medical Oncology Department, Hospital Universitario Valme, Seville 41014, Andalucía, Spain
| | | | | | - Carlos Ayala-de Miguel
- Medical Oncology Department, Hospital Universitario Valme, Seville 41014, Andalucía, Spain
| | - Manuel Chaves-Conde
- Medical Oncology Department, Hospital Universitario Valme, Seville 41014, Andalucía, Spain
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23
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Liu L, Li Q, Liu W, Qiu Z, Wu Z, Yu D, Deng W. Gastric mixed neuroendocrine non-neuroendocrine neoplasms. Front Oncol 2024; 14:1335760. [PMID: 38655135 PMCID: PMC11036886 DOI: 10.3389/fonc.2024.1335760] [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: 12/05/2023] [Accepted: 03/26/2024] [Indexed: 04/26/2024] Open
Abstract
The uncommon tumour known as gastric mixed neuroendocrine-non-neuroendocrine neoplasms (G-MiNENs) is made up of parts of neuroendocrine carcinoma and adenocarcinoma. The biological and clinical features are different from those of gastric adenocarcinoma. Their pathophysiology, diagnostic standards, and clinical behaviour have all been the subject of lengthy debates, and their nomenclature has undergone multiple changes. Its emergence has created new challenges in the classification and diagnosis of gastric tumours. This review will update information on the topic, covering molecular aspects, diagnostic criteria, treatment, and prognostic factor discovery. It will also provide a historical context that will aid in understanding the evolution of the idea and nomenclature of mixed gastric tumours. Additionally, it will provide the reader a thorough understanding of this difficult topic of cancer that is applicable to real-world situations.
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Affiliation(s)
- Li Liu
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Qian Li
- Department of Ultrasound Imaging, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Wenxuan Liu
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Zhendong Qiu
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Zhongkai Wu
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Danli Yu
- Department of Ultrasound Imaging, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Wenhong Deng
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
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24
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Cîmpeanu RC, Salmen T, Boldeanu L, Mustață ML, Forțofoiu D, Cazacu SM, Pirici DN, Boldeanu MV, Vere CC. Epidemiological, Clinical and Biological Hemogram Features in a Cohort of Neuroendocrine Tumor Patients. CURRENT HEALTH SCIENCES JOURNAL 2024; 50:256-266. [PMID: 39371064 PMCID: PMC11447499 DOI: 10.12865/chsj.50.02.11] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Accepted: 04/18/2024] [Indexed: 10/08/2024]
Abstract
We conducted a retrospective study based on 55 patients diagnosed with gastroenteropancreatic neuroendocrine tumors (GEP-NETs)-gastric (G-NET), small bowel (SB-NET) and colonic (C-NET), hospitalized and evaluated within the Surgical, Gastroenterology and Internal Medicine Clinics, in The Clinical Emergency County Hospital Craiova, between May 2016 and April 2024. We aimed in this study to analyze the epidemiological aspects and clinical characteristics of patients with GEP-NETs. In our study group, the patients' ages were between 39-82 years, with a mean of 66.40 (±12.46) years. The incidence of GEP-NETs cases in young patients was insignificant low-1 case. 45.46% of all patients lived in urban areas. 16.36% were G-NET, 14,54 were SB-NET and 69.09% were C-NET. The GEP-NETs diagnosis was established by immunohistochemistry features. Also, we observed that the most frequency localization was on the ascending colon, while the rarest on the colon it is located on the transverse colon and the rarest is on the small bowel, in spite of the generally literature data. From the C-NET group, 49.09% have been presented arterial hypertension probable explained by serotonin and dopamine secretion an inflammatory through phenotype expression and just one patient has been presented an erythematous psoriasis, which could be also explained by the same neurotransmitter's involvement as a possible purposed mechanism. The results obtained in our study demonstrate that could be a common profile of GEP-NETs patients through epidemiological general information and clinical characteristics. Also, we demonstrate that, in the last years, the incidence increased for the GEP-NETs.
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Affiliation(s)
| | - Teodor Salmen
- Doctoral School of Carol Davila University of Medicine and Pharmacy from Bucharest, Romania
| | - Lidia Boldeanu
- Microbiology Department, University of Medicine and Pharmacy of Craiova, Romania
| | | | - Dragoș Forțofoiu
- Doctoral School of University of Medicine and Pharmacy of Craiova, Romania
| | - Sergiu-Marian Cazacu
- Gastroenterology Department, University of Medicine and Pharmacy of Craiova, Romania
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25
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Sripodok P, Kouketsu A, Kuroda K, Miyashita H, Sugiura T, Kumamoto H. Primary Oral Mixed Neuroendocrine-Non-neuroendocrine Neoplasm (MiNEN): A Rare Case Report and Review of the Literature. Head Neck Pathol 2024; 18:13. [PMID: 38393494 PMCID: PMC10891016 DOI: 10.1007/s12105-024-01613-w] [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: 11/21/2023] [Accepted: 01/10/2024] [Indexed: 02/25/2024]
Abstract
Mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) are rare tumors recently characterized by the presence of both neuroendocrine and non-neuroendocrine components within the same tumor tissue. Although MiNEN found their place in the WHO classification for various organs, this composite tumor in the head and neck region remains exceptionally rare. We present a case of primary oral MiNEN in a 64-year-old male located on the left side of lower gingiva. Biopsy raised suspicion of neuroendocrine carcinoma (NEC) and the patient underwent partial mandibulectomy. The resected specimen showed two distinct components of NEC and squamous cell carcinoma (SCC) with the confirmation of immunohistochemical markers. There has been no sign of recurrence nor metastasis 6 years after the surgery. In addition, we have conducted a review of published cases with potential relevance to this entity, resulting in five cases. The diverse terminology reinforces the need for a standardized classification system of oral/head and neck MiNENs.
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Affiliation(s)
- Pawat Sripodok
- Division of Oral and Maxillofacial Oncology and Surgical Sciences, Department of Disease Management Dentistry, Tohoku University Graduate School of Dentistry, Miyagi, Japan.
- Department of Oral and Maxillofacial Pathology, Faculty of Dentistry, Mahidol University, Bangkok, Thailand.
| | - Atsumu Kouketsu
- Division of Oral and Maxillofacial Oncology and Surgical Sciences, Department of Disease Management Dentistry, Tohoku University Graduate School of Dentistry, Miyagi, Japan
| | - Kanako Kuroda
- Division of Oral and Maxillofacial Oncology and Surgical Sciences, Department of Disease Management Dentistry, Tohoku University Graduate School of Dentistry, Miyagi, Japan
| | - Hitoshi Miyashita
- Department of Dentistry and Oral Surgery, Tohoku Medical and Pharmaceutical University Hospital, Miyagi, Japan
| | - Tsuyoshi Sugiura
- Division of Oral and Maxillofacial Oncology and Surgical Sciences, Department of Disease Management Dentistry, Tohoku University Graduate School of Dentistry, Miyagi, Japan
| | - Hiroyuki Kumamoto
- Division of Oral Pathology, Department of Disease Management Dentistry, Tohoku University Graduate School of Dentistry, Miyagi, Japan
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Baía CAQ, Sousa A, Sousa F, Santos P, Varelas AI, Afonso LP, Monteiro J, Fernandes JM, Santos LL, Abreu de Sousa J. Unexpected pancreatic mixed neuroendocrine-nonneuroendocrine neoplasms (MiNEN)-reflection on a case report. J Surg Case Rep 2024; 2024:rjae026. [PMID: 38322359 PMCID: PMC10838674 DOI: 10.1093/jscr/rjae026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Revised: 01/08/2024] [Accepted: 01/11/2024] [Indexed: 02/08/2024] Open
Abstract
The authors present a case involving a 51-year-old male who was diagnosed with a 4-cm mass in the body of the pancreas, initially suspected to be a ductal adenocarcinoma due to an elevated Ca 19.9 during routine analysis. Subsequent imaging studies confirmed a resectable disease without suspicious lymph nodes or distant metastasis, leading to the proposal of surgery. The patient underwent a laparoscopic distal splenopancreatectomy, which was uneventful. The histopathological examination revealed a 3.7-cm pancreatic mixed neuroendocrine neoplasia (MiNEN) with a predominant high-grade ductal adenocarcinoma component and a concurrent high-grade neuroendocrine carcinoma, with negative margins. Two lymph node metastases were identified, each representing metastasis of one of the components. The tumor was classified as pT2N1M0. Currently, the patient is undergoing chemotherapy with FOLFIRINOX. This case prompts reflection on the optimal treatment strategy for pancreatic MiNEN and raises the question of how the preoperative diagnosis could influence the patient's outcome.
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Affiliation(s)
- Catarina Alexandra Quintas Baía
- Surgical Oncology Department, Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Centre (P.CCC), 4200-072 Porto, Portugal
| | - Alexandre Sousa
- Surgical Oncology Department, Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Centre (P.CCC), 4200-072 Porto, Portugal
| | - Fernanda Sousa
- Surgical Oncology Department, Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Centre (P.CCC), 4200-072 Porto, Portugal
| | - Pedro Santos
- General Surgery Department, Torres Vedras Hospital, West Hospital Centre, 2560-295 Torres Vedras, Portugal
| | - Ana Isabel Varelas
- Pathology Department, Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Centre (P.CCC), 4200-072 Porto, Portugal
| | - Luís Pedro Afonso
- Pathology Department, Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Centre (P.CCC), 4200-072 Porto, Portugal
| | - Joana Monteiro
- Medical Oncology Department, Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Centre (P.CCC), 4200-072 Porto, Portugal
| | - José Manuel Fernandes
- Surgical Oncology Department, Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Centre (P.CCC), 4200-072 Porto, Portugal
| | - Lúcio Lara Santos
- Surgical Oncology Department, Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Centre (P.CCC), 4200-072 Porto, Portugal
| | - Joaquim Abreu de Sousa
- Surgical Oncology Department, Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Centre (P.CCC), 4200-072 Porto, Portugal
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27
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Verdasca FR, Ferreira R, Montenegro A, Mendes JL, Furtado I, Escaleira R, Fernandes V, Seladas M, Cristovão M, da Luz R, Guerreiro I. Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms of the Rectum: A Case Report. Case Rep Oncol 2024; 17:587-595. [PMID: 39015645 PMCID: PMC11249797 DOI: 10.1159/000538384] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Accepted: 03/04/2024] [Indexed: 07/18/2024] Open
Abstract
Introduction Mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) represent roughly 1-2% of all colorectal malignancies. Given the rareness and heterogeneity of these mixed tumors, recognition and accurate diagnosis remain a challenge. In the absence of established guidelines, they are treated according to the standard of care for pure neuroendocrine carcinomas or adenocarcinomas from similar sites of origin. Case Presentation We herein report a case of a rectal MiNEN in a 55-year-old male. He underwent colonoscopy for rectal bleeding and mucus emission, which revealed a vegetating lesion located approximately 8 cm from the anal verge, corresponding to a moderately differentiated low-grade adenocarcinoma of the rectum. Computed tomography scan and magnetic resonance imaging uncovered the presence of lung, lymph node, and subcutaneous implant metastases. The biopsy of the cutaneous implant showed neuroendocrine carcinoma Ki-67 90%. The patient underwent systemic chemotherapy. Conclusion High-grade MiNEN tumors are the most commonly encountered in clinical practice and have an aggressive biological behavior. Little is known about the genetic drivers of this neoplasm and its pathogenesis remains controversial. Clinical and pathological awareness of this rare entity is a key step to design future targeted therapies and improve treatment options. The aim of this case report is to further our understanding regarding the clinical presentation, radiological features, pathology, management, and prognosis of MiNEN.
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Affiliation(s)
| | - Rita Ferreira
- Oncology Department, Unidade Local de Saúde São José, Lisboa, Portugal
| | | | - José Leão Mendes
- Oncology Department, Unidade Local de Saúde São José, Lisboa, Portugal
| | - Ivánia Furtado
- Oncology Department, Unidade Local de Saúde São José, Lisboa, Portugal
| | - Rui Escaleira
- Oncology Department, Unidade Local de Saúde São José, Lisboa, Portugal
| | - Válter Fernandes
- Oncology Department, Unidade Local de Saúde São José, Lisboa, Portugal
| | - Marta Seladas
- Oncology Department, Unidade Local de Saúde São José, Lisboa, Portugal
| | - Miguel Cristovão
- Pathology Department, Unidade Local de Saúde São José, Lisboa, Portugal
| | - Ricardo da Luz
- Oncology Department, Unidade Local de Saúde São José, Lisboa, Portugal
| | - Inês Guerreiro
- Oncology Department, Unidade Local de Saúde São José, Lisboa, Portugal
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Hu YF, Ma WJ, Hu HJ, Gu HF, Jin YW, Li FY. Comparison of the clinical features and long-term prognosis of gallbladder neuroendocrine carcinoma versus gallbladder adenocarcinoma: A propensity score-matched analysis. BIOMOLECULES & BIOMEDICINE 2023; 23:1096-1107. [PMID: 37724922 PMCID: PMC10655887 DOI: 10.17305/bb.2023.9582] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Revised: 09/07/2023] [Accepted: 09/07/2023] [Indexed: 09/21/2023]
Abstract
Gallbladder neuroendocrine carcinoma (GBNEC) is rare and characterized by a low degree of tumor differentiation. The clinical features of GBNEC versus gallbladder adenocarcinoma (GBADC) remain a subject of debate. A total of 201 GBADC and 36 GBNEC cases that underwent surgery resection between January 2010 and 2022 at the Department of Biliary Surgery, West China Hospital, Sichuan University were included. A 1:1 propensity score matching (PSM) was performed based on seven predefined variables: age, sex, the American Joint Committee on Cancer (AJCC) stage, resection status, perineural invasion (PNI), lymphovascular invasion (LVI), and degree of tumor differentiation. Compared with GBADC, GBNEC patients were younger (median age 56.0 vs 64.0 years; P = 0.001), and more patients presented with advanced stages of tumor (P = 0.003). Patients with GBNEC also had a higher rate of PNI (55.6% vs 22.4%; P < 0.001), and LVI (63.9% vs 45.80%; P = 0.658). Before PSM, GBNEC patients had inferior prognoses compared with GBADC patients with a shorter median overall survival (mOS) (15.02 vs 20.11 months; P = 0.0028) and a shorter median recurrence-free survival (mRFS) (10.30 vs 15.17 months; P = 0.0028). However, after PSM analyses, there were no differences in OS (mOS 18.6 vs 18.0 months; P=0.24) or RFS (mRFS 10.98 vs 12.02 months; P = 0.39) between the GBNEC and GBADC cases. After multivariate analysis, tumor diagnosis (GBNEC vs GBADC) was not identified as an independent risk factor for shorter RFS (P = 0.506) or OS (P = 0.731). Unfavorable pathological features, including advanced AJCC tumor stages, poor differentiation, presence of LVI, and positive resection margins (all P < 0.05), were independent risk factors for inferior OS and RFS. GBNEC is difficult to diagnose early and has a prognosis comparable to stage-matched poorly differentiated GBADC. Tumor diagnosis (either GBADC or GBNEC) was not an independent risk factor for the patient's OS. Unfavorable pathological features of the neoplasm are the main determinants.
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Affiliation(s)
- Ya-Fei Hu
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, China
- Department of Biliary Disease Research Center, West China Hospital, Sichuan University, Chengdu, China
| | - Wen-Jie Ma
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, China
- Department of Biliary Disease Research Center, West China Hospital, Sichuan University, Chengdu, China
| | - Hai-Jie Hu
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, China
- Department of Biliary Disease Research Center, West China Hospital, Sichuan University, Chengdu, China
| | - Han-Fei Gu
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, China
- Department of Biliary Disease Research Center, West China Hospital, Sichuan University, Chengdu, China
| | - Yan-Wen Jin
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, China
- Department of Biliary Disease Research Center, West China Hospital, Sichuan University, Chengdu, China
| | - Fu-Yu Li
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, China
- Department of Biliary Disease Research Center, West China Hospital, Sichuan University, Chengdu, China
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29
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Xu B, Zhang F, Wu R, Peng Y, Mao Z, Tong S. Incidence, survival, and prognostic factors for patients with gastrointestinal mixed neuroendocrine non-neuroendocrine neoplasms: a SEER population-based study. J Cancer Res Clin Oncol 2023; 149:15657-15669. [PMID: 37656242 PMCID: PMC10620255 DOI: 10.1007/s00432-023-05356-z] [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: 07/08/2023] [Accepted: 08/25/2023] [Indexed: 09/02/2023]
Abstract
BACKGROUND Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) are a group of rare tumors with limited research currently available. This study aimed to analyze the incidence, survival, and prognostic factors of gastrointestinal MiNENs. METHODS We included data from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2019. We compared the clinicopathologic characteristics and survival rates between MiNENs and neuroendocrine tumors (NETs), and calculated the incidence of MiNENs. We utilized univariate and multivariate Cox analysis to assess independent factors of prognosis and established a nomogram to predict 1-, 2-, and 3-year cancer-specific survival (CSS). Calibration and receiver operating characteristic (ROC) curves were drawn to validate the accuracy and reliability of the model. Decision curve analysis (DCA) was used to assess the clinical utility of the model. RESULTS Patients with gastrointestinal MiNENs had a poorer prognosis than those with NETs. The overall incidence of gastrointestinal MiNENs has been increasing annually. Multivariate Cox regression analysis revealed that tumor size, lymph node metastasis, distant metastasis, and surgery were independent risk factors for CSS in MiNENs patients. Based on these risk factors, the 1-, 2-, and 3-year CSS nomogram model for MiNENs patients was established. Calibration, ROC, and DCA curves of the training and validation sets demonstrated that this model had good accuracy and clinical utility. CONCLUSION Gastrointestinal MiNENs are rare tumors with an increasing incidence rate. The nomogram model is expected to be an effective tool for personalized prognosis prediction in MiNENs patients, which may benefit clinical decision-making.
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Affiliation(s)
- Boqi Xu
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Fan Zhang
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Runda Wu
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Yao Peng
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Zhongqi Mao
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Shan Tong
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China.
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30
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Pan WX, Zhang XM, Hao SL, Han W. Progress in immunotherapy for neuroendocrine neoplasm of the digestive system. World J Gastroenterol 2023; 29:4174-4185. [PMID: 37475845 PMCID: PMC10354576 DOI: 10.3748/wjg.v29.i26.4174] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Revised: 05/29/2023] [Accepted: 06/13/2023] [Indexed: 07/10/2023] Open
Abstract
Neuroendocrine neoplasms (NENs) are rare heterogeneous tumors that can develop in almost any organ, with the digestive organs, including the gastrointestinal tract and pancreas being the most commonly affected sites. Despite the fact that advances in initial therapies have progressed, there is presently no recognized effective treatment for advanced NEN. Immune checkpoint inhibitors (ICIs) have shown superior efficacy in treating several types of solid tumors. Despite their successful role in the treatment of partial NENs, such as small cell lung cancer, and Merkel cell carcinoma, the role of ICIs in most of the NENs remains limited. Nevertheless, due to their specific anti-tumor mechanisms and acceptable safety profile, ICIs are a promising avenue for further study in NENs therapy. Recent clinical trials have illustrated that combination therapy with ICI is more efficient than monotherapy, and multiple clinical trials are constantly ongoing to evaluate the efficacy and safety of these combination therapies. Therefore, the purpose of this review is to provide a comprehensive summary of the clinical progress of immunotherapy in NENs affecting the digestive system, with a specific emphasis on the application of programmed cell death protein 1/programmed death receptor ligand 1 inhibitor. Furthermore, this review has an exploration of the potential beneficiary population and the inherent value of utilizing immunotherapy in the management of NENs.
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Affiliation(s)
- Wei-Xuan Pan
- Department of General Surgery, Beijing Luhe Hospital, Capital Medical University, Beijing 101100, China
| | - Xin-Mu Zhang
- Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Shao-Long Hao
- Department of General Surgery, Beijing Luhe Hospital, Capital Medical University, Beijing 101100, China
| | - Wei Han
- Department of General Surgery, Beijing Luhe Hospital, Capital Medical University, Beijing 101100, China
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31
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Qiu MZ, Chen Q, Zheng DY, Zhao Q, Wu QN, Zhou ZW, Yang LQ, Luo QY, Sun YT, Lai MY, Yuan SS, Wang FH, Luo HY, Wang F, Li YH, Zhang HZ, Xu RH. Precise microdissection of gastric mixed adeno-neuroendocrine carcinoma dissects its genomic landscape and evolutionary clonal origins. Cell Rep 2023; 42:112576. [PMID: 37285266 DOI: 10.1016/j.celrep.2023.112576] [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: 09/22/2022] [Revised: 03/02/2023] [Accepted: 05/15/2023] [Indexed: 06/09/2023] Open
Abstract
Gastric mixed adenoneuroendocrine carcinoma (MANEC) is a clinically aggressive and heterogeneous tumor composed of adenocarcinoma (ACA) and neuroendocrine carcinoma (NEC). The genomic properties and evolutionary clonal origins of MANEC remain unclear. We conduct whole-exome and multiregional sequencing on 101 samples from 33 patients to elucidate their evolutionary paths. We identify four significantly mutated genes, TP53, RB1, APC, and CTNNB1. MANEC resembles chromosomal instability stomach adenocarcinoma in that whole-genome doubling in MANEC is predominant and occurs earlier than most copy-number losses. All tumors are of monoclonal origin, and NEC components show more aggressive genomic properties than their ACA counterparts. The phylogenetic trees show two tumor divergence patterns, including sequential and parallel divergence. Furthermore, ACA-to-NEC rather than NEC-to-ACA transition is confirmed by immunohistochemistry on 6 biomarkers in ACA- and NEC-dominant regions. These results provide insights into the clonal origin and tumor differentiation of MANEC.
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Affiliation(s)
- Miao-Zhen Qiu
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou 510060, P.R. China
| | - Qingjian Chen
- Department of Basic Research, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou 510060, P.R. China; State Key Laboratory of Systems Medicine for Cancer, Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, P.R. China
| | - Dan-Yang Zheng
- Department of Pathology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou 510060, P.R. China; Department of Clinical Oncology, LKS Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong
| | - Qi Zhao
- Department of Basic Research, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou 510060, P.R. China
| | - Qi-Nian Wu
- Department of Pathology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou 510060, P.R. China
| | - Zhi-Wei Zhou
- Department of Gastric Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou 510060, P.R. China
| | - Li-Qiong Yang
- Department of Basic Research, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou 510060, P.R. China
| | - Qiu-Yun Luo
- Department of Basic Research, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou 510060, P.R. China
| | - Yu-Ting Sun
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou 510060, P.R. China
| | - Ming-Yu Lai
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou 510060, P.R. China
| | - Sha-Sha Yuan
- Department of Pathology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou 510060, P.R. China
| | - Feng-Hua Wang
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou 510060, P.R. China
| | - Hui-Yan Luo
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou 510060, P.R. China
| | - Feng Wang
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou 510060, P.R. China
| | - Yu-Hong Li
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou 510060, P.R. China
| | - Hui-Zhong Zhang
- Department of Pathology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou 510060, P.R. China
| | - Rui-Hua Xu
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou 510060, P.R. China; Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou 510060, P.R. China.
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Cattaneo L, Centonze G, Sabella G, Lagano V, Angerilli V, Pardo C, Bertani E, Spada F, Prinzi N, Pusceddu S, Fassan M, Fazio N, Milione M. Digestive MiNENs: Could histological classification and molecular characterization drive clinical outcome and therapeutic approach? Crit Rev Oncol Hematol 2023:104044. [PMID: 37268174 DOI: 10.1016/j.critrevonc.2023.104044] [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: 03/01/2023] [Revised: 05/19/2023] [Accepted: 05/30/2023] [Indexed: 06/04/2023] Open
Abstract
Mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) are epithelial neoplasms in which neuroendocrine and non-neuroendocrine discrete components are combined, each of which constitutes ≥ 30% of the neoplasm. The finding of an additional neuroendocrine component seems to characterize the tumor's biological behavior. Few studies have proved MiNENs histogenetic and molecular characterization, and the development of molecular markers for more accurate classification of MiNENs represents a clinical need. However, a common origin of the neuroendocrine and non-neuroendocrine components from a pluripotent cancer stem cell could be suggested. The optimal clinical management of MiNENS is largely unknown. Whenever feasible, curative-intent resection should be performed for localized disease; in advanced disease, the treatment should be targeted to the component responsible for the metastatic spreading. This paper provides a revision of the current knowledge on MiNENs, focusing on available evidence about their molecular characterization to suggest a prognostic stratification of these rare forms.
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Affiliation(s)
- Laura Cattaneo
- Pathology First Division, Department of Pathology and Laboratory Medicine, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan, Italy
| | - Giovanni Centonze
- Pathology First Division, Department of Pathology and Laboratory Medicine, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan, Italy; Department of Research, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan, Italy
| | - Giovanna Sabella
- Pathology First Division, Department of Pathology and Laboratory Medicine, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan, Italy
| | - Vincenzo Lagano
- Pathology First Division, Department of Pathology and Laboratory Medicine, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan, Italy
| | - Valentina Angerilli
- Department of Medicine - DIMED, University of Padua, Padua, Italy; Veneto Institute of Oncology, IOV-IRCCS, Padua, Italy
| | - Carlotta Pardo
- Pathology First Division, Department of Pathology and Laboratory Medicine, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan, Italy
| | - Emilio Bertani
- Division of Gastrointestinal Surgery, European Institute of Oncology, Milan, Italy
| | - Francesca Spada
- Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology (IEO) IRCCS, Milan
| | - Natalie Prinzi
- Medical Oncology and Hematology Department, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Sara Pusceddu
- Medical Oncology and Hematology Department, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Matteo Fassan
- Department of Medicine - DIMED, University of Padua, Padua, Italy; Veneto Institute of Oncology, IOV-IRCCS, Padua, Italy
| | - Nicola Fazio
- Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology (IEO) IRCCS, Milan
| | - Massimo Milione
- Pathology First Division, Department of Pathology and Laboratory Medicine, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan, Italy.
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Drozdov ES, Grishchenko MY, Kharitonkin VI, Lyan NI, Borodin OY, Fesik EA, Korotkevich AG. A rare clinical case of a patient with mixed neuroendocrine-non-neuroendocrine neoplasms of the ampulla of vater. SIBERIAN JOURNAL OF ONCOLOGY 2023; 22:168-174. [DOI: 10.21294/1814-4861-2023-22-2-168-174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
Abstract
Background. Neuroendocrine tumors are rare neoplasias accounting for 1 % of all digestive malignancies. In 2010, mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) were classified by the World Health Organization This type of tumor is extremely rare and most commonly occurs in the appendix, colon, and rectum. To date, only 30 clinical cases of MINEN of the major duodenal papilla (MDP) have been described in the available world literature, while we have not found a description of this pathology in the domestic literature.Description of the clinical case. We present a case of a 64-year-old male patient with MiNEN MDP. The first clinical manifestation of the disease was obstructive jaundice. To eliminate the jaundice, papillosphincterotomy, transpapillary stenting of the choledochus with a plastic stent was performed. MDP tumor was verifed as adenocarcinoma by histological examination. The patient underwent gastropancreatoduodenal resection. Postoperative immunohistochemical examination showed the expression of antibodies in tumor cells: Synaptophysin (clone 27G12) +++, Chromogranin A (5H7) +, CD 57 (NK-1) ++, Ki 67 (Mib 1) 80 %.Conclusion: mixed neuroendocrine (G3) non-neuroendocrine carcinoma (G2) of the major duodenal papilla with growth within the wall of the duodenum; metastases of the neuroendocrine component in three lymph nodes, adenocarcinoma metastasis in 1 out of 15 lymph nodes examined; pT2N2M0, MiNEN high grade (classified by S. La Rosa). Conclusion. Mixed neuroendocrine-non-neuroendocrine tumors of MDP are an extremely rare pathology. The accuracy of preoperative morphological diagnostics is not high, therefore, this diagnosis can be easily missed at the preoperative stage. In the morphological study of malignant tumors of MDP, a pathologist should take into account the feasibility of a combination of a neuroendocrine tumor with adenocarcinoma.
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Affiliation(s)
- E. S. Drozdov
- Tomsk Regional Oncology Hospital;
Siberian State Medical University of the Ministry of Health of Russia
| | | | | | | | - O. Yu. Borodin
- Tomsk Regional Oncology Hospital;
Research Institute of Cardiology, Тomsk National Research Medical Center, Russian Academy of Sciences
| | | | - A. G. Korotkevich
- Novokuznetsk State Institute for Advanced Training of Doctors – branch of the Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russia
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34
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Das S, Prakash S, Shaikh O, Reddy A, Kumbhar U. Small Cell Carcinoma of the Gallbladder. Cureus 2023; 15:e38444. [PMID: 37273321 PMCID: PMC10234611 DOI: 10.7759/cureus.38444] [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] [Accepted: 05/02/2023] [Indexed: 06/06/2023] Open
Abstract
Primary neuroendocrine carcinoma of the gallbladder (GB) is a rare, highly dismal lethal disease with a fatal prognosis. A 45-year-old female presented with right upper abdomen pain and multiple vomiting episodes. Imaging studies showed diffuse thickening of the wall of the GB with locoregional invasion into the nearby structures with extensive abdominal lymph node metastasis and arteriovenous encasements. Ultrasound-guided fine-needle aspiration was done, which was diagnostic of small cell carcinoma of the GB. The patient was planned for palliative chemotherapy. A small cell variant of neuroendocrine carcinoma of the GB is a rare entity with a moribund lethality associated with it. Patients are diagnosed in advanced stages with not many treatment modalities to offer. Usually, patients are treated with palliative chemotherapy.
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Affiliation(s)
- Snehasis Das
- Surgery, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, IND
| | - Sagar Prakash
- Surgery, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, IND
| | - Oseen Shaikh
- Surgery, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, IND
| | - Abhinaya Reddy
- Surgery, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, IND
| | - Uday Kumbhar
- Surgery, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, IND
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35
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Fick A, Tran K, Kandpal H, Burge M, Chandrasegaram M. An Unusual Case of Large Cell Neuroendocrine Cancer of the Gallbladder With Mixed Adenocarcinoma Component in a Patient With Pancreatobiliary Maljunction. Cureus 2023; 15:e37398. [PMID: 37056222 PMCID: PMC10089643 DOI: 10.7759/cureus.37398] [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] [Accepted: 03/29/2023] [Indexed: 04/15/2023] Open
Abstract
Gallbladder neuroendocrine tumors (GB-NETs) and gallbladder neuroendocrine carcinomas (GB-NECs) are rare forms of neuroendocrine neoplasms (NENs). Most GB-NENs present as incidental findings or as gallbladder polyps in the course of investigation of nonspecific symptoms such as upper abdominal pain and nausea. Given the rarity of GB-NENs, only a few small case series are currently available describing this entity, and even fewer guiding consensus on standard treatment and the role of adjuvant therapy. We present the case of a 65-year-old South American female referred for a chronic history of intermittent post-prandial epigastric pain, bloating, nausea, and occasional diarrhea. Pancreaticobiliary maljunction with dilation was present and she was diagnosed with primary gallbladder large cell neuroendocrine carcinoma (GB-LCNEC) mixed with a minor component of gallbladder adenocarcinoma.
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Affiliation(s)
- Anton Fick
- General Surgery, The Prince Charles Hospital, Brisbane, AUS
| | - Kayla Tran
- Pathology, The Prince Charles Hospital, Brisbane, AUS
| | - Harsh Kandpal
- Radiology, The Prince Charles Hospital, Brisbane, AUS
| | - Matthew Burge
- Medical Oncology, The Prince Charles Hospital, Brisbane, AUS
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36
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Shi JG, Zhao L, Yang Q. Mixed tumor of nasal cavity: A case report. Asian J Surg 2023; 46:1684-1685. [PMID: 36334996 DOI: 10.1016/j.asjsur.2022.09.122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Accepted: 09/26/2022] [Indexed: 04/03/2023] Open
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Gutierrez Olivares VM, Benavides González MA, Márquez Barrios GV, Gutiérrez Cura AM, Polo Nieto JF, Millán C, Gallo Bonilla DL. Carcinoma adenoneuroendocrino mixto en la ampolla de Váter: reporte de caso. REVISTA COLOMBIANA DE GASTROENTEROLOGÍA 2023; 38:100-105. [DOI: 10.22516/25007440.903] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
Abstract
La neoplasia neuroendocrina no neuroendocrina mixta es una neoplasia mixta con un componente neuroendocrino combinado con un componente no neuroendocrino. Esta presenta una incidencia baja y estudios limitados, pero con evidencia de ser una entidad agresiva asociada a una pobre supervivencia. Presentamos el caso de una mujer de 58 años que ingresó por un cuadro clínico de dolor abdominal en el hipocondrio izquierdo asociado a ictericia generalizada y picos febriles con diagnóstico imagenológico de dilatación de la vía biliar secundaria a coledocolitiasis distal, por lo que se realizó una colangiopancreatografía retrógrada endoscópica (CPRE) en la que se encontró una papila mayor de aspecto neoplásico a la cual se le realizó una biopsia analizada histopatológicamente y se confirmó el diagnóstico de carcinoma mixto con componente de carcinoma neuroendocrino pobremente diferenciado de alto grado y componente de carcinoma mucinoso, por lo cual se decidió programar una pancreatoduodenectomía.
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38
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Clinicopathological characteristics of mixed neuroendocrine-non-neuroendocrine neoplasms in gastrointestinal tract. Pathol Res Pract 2023; 243:154373. [PMID: 36791563 DOI: 10.1016/j.prp.2023.154373] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Revised: 01/26/2023] [Accepted: 02/10/2023] [Indexed: 02/13/2023]
Abstract
BACKGROUND In 2019, the World Health Organization (WHO) classification system updated the definition of mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs), previously known as mixed adenoneuroendocrine carcinomas (MANECs). The clinicopathological characteristics of this new definition remains to be clarified. METHODS We analyzed the clinical data of 43 patients diagnosed with MiNENs in Wuhan Union Hospital from 2011 to 2020 according to the definition of MiNENs proposed in 2019. RESULTS Among the 43 patients with MiNENs, the top two most common sites were stomach and colon, and 69.8% were males. Nearly half (21/43) of the patients were diagnosed at TNM stage III, and about 53.5% (23/43) of patients were the neuroendocrine neoplasm dominant type. Among the non-neuroendocrine tumor components of 43 MiNENs patients, adenocarcinoma accounted for 95.3% (41/43) and squamous cell carcinoma accounted for 4.7% (2/43)；95.3% (41/43) of the neuroendocrine neoplasm components were neuroendocrine carcinoma (NEC) and 4.7% (2/43) were neuroendocrine tumor (NET). Approximately 60.5% (26/43) neuroendocrine components had a Ki-67 index ≥ 55%. In addition, we further compared the prognosis of different subtypes of the MiNENs based on the neuroendocrine neoplasm component and non-neuroendocrine neoplasm component, and the results showed that there was no significant difference in survival between different subtypes of MiNENs (P > 0.05). CONCLUSIONS MiNENs can exhibit diverse clinicopathological characteristics, and there is no significant difference in prognosis among MiNENs subtypes, indicating that the definition of MiNENs can well summarize the prognosis of this type of tumor.
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Pereira D, White D, Mortellaro M, Jiang K. Unusual Microsatellite-Instable Mixed Neuroendocrine and Non-neuroendocrine Neoplasm: A Clinicopathological Inspection and Literature Review. Cancer Control 2023; 30:10732748231160992. [PMID: 36840617 PMCID: PMC9969423 DOI: 10.1177/10732748231160992] [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] [Indexed: 02/26/2023] Open
Abstract
BACKGROUND Mixed neuroendocrine and non-endocrine neoplasms (MiNENs) are challenging to diagnose and manage clinically. The current understanding of MiNENs' pathobiology, molecular mechanisms, and management is incomplete. Though microsatellite instability (MSI) is known to impact carcinogenesis, reports examining MSI mechanisms for MiNENs are rare. METHODS We report an unusual colonic MSI-MiNEN uncovered in an 89-year-old woman and the review of the literature. RESULTS Pathologic inspection revealed a high-grade carcinoma composed of tumor cells with neuroendocrine histologic traits and immunophenotype intermixed with mucin-containing signet ring-like cells arranged in nested and micronodular patterns. Loss of MLH1 and PMS2 mismatch repair proteins was detected in tumor cells. INSM1 immunostaining highlighted about 50% of the tumour, further reinforcing the MiNEN diagnosis. Next-generation sequencing identified multiple carcinogenic mutations. Because of the advanced stage of the tumor and its adhesion to the adjacent organs, surgical resection was aborted; immunotherapy was initiated. The tumor is in remission 30 months following initiation of treatment, and the patient remains asymptomatic. CONCLUSION This unique MSI MiNEN was characterized by its immunohistochemical and molecular signatures and illustrated how correctly diagnosing MSI can strongly improve a patient's outcomes.
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Affiliation(s)
- Daniela Pereira
- Anatomic Pathology, Instituto Português de Oncologia de
Lisboa Francisco Gentil, Lisboa, Portugal
| | - Daley White
- Biomedical Library, Moffitt Cancer Center, Tampa, FL, USA
| | | | - Kun Jiang
- Morsani College of Medicine
University of South Florida, Tampa, FL, USA,Anatomic Pathology, Moffitt Cancer Center, Tampa, FL, USA,Kun Jiang, Department of Anatomic
Pathology, Moffitt Cancer Center, 12902 USF Magnolia Drive, Tampa, FL 33612,
USA.
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40
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Zhong Y, Zhang H, Wang X, Sun Z, Ge Y, Dou W, Hu S. CT and MR imaging features of mixed neuroendocrine-non-neuroendocrine neoplasm of the pancreas compared with pancreatic ductal adenocarcinoma and neuroendocrine tumor. Insights Imaging 2023; 14:15. [PMID: 36690735 PMCID: PMC9871080 DOI: 10.1186/s13244-023-01366-0] [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: 09/09/2022] [Accepted: 12/24/2022] [Indexed: 01/25/2023] Open
Abstract
OBJECTIVE This study aimed to assess the computed tomography (CT) and magnetic resonance imaging (MRI) features of pancreatic mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) and compare them with those of pancreatic ductal adenocarcinoma (PDAC) and neuroendocrine tumor (NET). METHODS Twelve patients with pancreatic MiNEN, 24 patients with PDAC, and 24 patients with NET, who underwent both contrast-enhanced CT and MRI, were included. Clinical data and the key imaging features were retrospectively evaluated by two independent readers and compared between MiNEN and PDAC or NET. Univariate and multivariable logistic regression analyses were performed to obtain predictors for pancreatic MiNEN. RESULTS Patients with pancreatic MiNEN more frequently presented with large size and heterogeneous and cystic components compared with PDAC (p < 0.031) and ill-defined irregular margins, progressive enhancement, and adjacent organ involvement compared with NET (p < 0.036). However, vascular invasion was less commonly seen in MiNEN than PDAC (p = 0.010). Moderate enhancement was observed more frequently in MiNEN than in PDAC or NET (p < 0.001). Multivariate logistic analyses demonstrated that moderate enhancement and ill-defined irregular margin were the most valuable features for the prediction of pancreatic MiNEN (p ≤ 0.044). The combination of the two features resulted in a specificity of 93.8%, sensitivity of 83.3%, and accuracy of 91.7%. CONCLUSIONS We have mainly described the radiological findings of pancreatic MiNEN with ill-defined irregular margin and moderate enhancement compared with PDAC and NET. The combination of imaging features could improve diagnostic efficiency and help in the selection of the correct treatment method.
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Affiliation(s)
- Yanqi Zhong
- grid.258151.a0000 0001 0708 1323Department of Radiology, Affiliated Hospital, Jiangnan University, No. 1000, Hefeng Road, Wuxi, 214122 Jiangsu China
| | - Heng Zhang
- grid.258151.a0000 0001 0708 1323Department of Radiology, Affiliated Hospital, Jiangnan University, No. 1000, Hefeng Road, Wuxi, 214122 Jiangsu China
| | - Xian Wang
- grid.440785.a0000 0001 0743 511XDepartment of Radiology, Affiliated Renmin Hospital, Jiangsu University, No. 8, Dianli Road, Zhenjiang, 212002 Jiangsu China
| | - Zongqiong Sun
- grid.258151.a0000 0001 0708 1323Department of Radiology, Affiliated Hospital, Jiangnan University, No. 1000, Hefeng Road, Wuxi, 214122 Jiangsu China
| | - Yuxi Ge
- grid.258151.a0000 0001 0708 1323Department of Radiology, Affiliated Hospital, Jiangnan University, No. 1000, Hefeng Road, Wuxi, 214122 Jiangsu China
| | - Weiqiang Dou
- GE Healthcare, MR Research China, Beijing, 100176 China
| | - Shudong Hu
- grid.258151.a0000 0001 0708 1323Department of Radiology, Affiliated Hospital, Jiangnan University, No. 1000, Hefeng Road, Wuxi, 214122 Jiangsu China ,grid.440785.a0000 0001 0743 511XDepartment of Radiology, Affiliated Renmin Hospital, Jiangsu University, No. 8, Dianli Road, Zhenjiang, 212002 Jiangsu China
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41
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Song H, Yang S, Zhang Y, Hua Y, Kleeff J, Liu Q, Liao Q. Comprehensive analysis of mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs): A SEER database analysis of 767 cases. Front Oncol 2023; 12:1007317. [PMID: 36698410 PMCID: PMC9868580 DOI: 10.3389/fonc.2022.1007317] [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: 07/30/2022] [Accepted: 12/08/2022] [Indexed: 01/11/2023] Open
Abstract
Background Mixed neuroendocrine non-neuroendocrine neoplasm (MiNEN) is an extremely rare entity, consisting of neuroendocrine and non-neuroendocrine components. It can occur in various organs throughout the body, with a rising incidence. Its clinical management is a rapidly growing field of interest; however, large-scale patient cohorts are still missing to guide clinical practice. Patients and methods The demographic, clinicopathological, and survival information of all patients diagnosed with MiNEN in the national Surveillance, Epidemiology, and End Results (SEER) program database (2000-2017) were extracted and further analyzed. The information of the patients before and after 2010 was compared to understand the epidemiological changes of MiNEN. The characteristics of MiNEN originating in different organs were compared. The clinical significance of surgical resection for metastatic MiNENs was also analyzed. Results A total of 1081 patients were screened, and after applying the exclusion criteria, 767 patients were finally analyzed. There was no obvious sex preference (49.2% vs 50.8%, p>0.05) and the majority of the patients were Caucasians (n=627, 81.7%). A total of 88.3% of the patients were older than 50 years old, and the median age was 60 years. 79.3% of the tumors are located in the distal digestive tract, and 67.7% were grade 3/4. Distant metastasis was presented in 33.9% of the patients at diagnosis. A total of 88% of the patients underwent surgical treatments. The number of patients increased 10-fold between 2000 and 2017. There was no significant difference in sex, race, stage, or surgical treatments among the patients diagnosed before and after 2010. More patients older than 60 years were diagnosed after 2010 (p=0.009). The median survival was 61.0 ± 9.8 months for the whole cohort. After multivariate analysis, older age (>60 years, p<0.01), more advanced stage (p<0.01), grade 3/4 (p<0.01), and non-surgical treatment (p<0.01) were independent risk factors for poorer survival. The appendiceal MiNENs showed the best prognosis. A total of 260 metastatic MiNENs were further analyzed. Only patients with metastatic MiNENs originating from the appendix had a potential benefit from surgical resection, compared to other sites (p=0.05). Conclusion This study provides the epidemiological, clinicopathological, and survival information of the largest number of MiNEN patients. Although MiNEN is an extremely rare malignant neoplasm, its incidence increases rapidly. The majority of the patients suffered from advanced-stage disease, which highlights the need for improvement of early detection in the future. The appendix is the most common primary site of MiNEN, and surgical resection for selected metastatic MiNEN originating in the appendix has favorable survival outcomes.
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Affiliation(s)
- Huixin Song
- Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.,Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Sen Yang
- Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Yalu Zhang
- Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Yuze Hua
- Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Jorg Kleeff
- Department of Visceral, Vascular and Endocrine Surgery, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany
| | - Qiaofei Liu
- Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Quan Liao
- Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
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Nguyen THC, Nguyen Tran BS, Nguyen TP, Ha TMT, Pham NC, Nguyen TGT, Hoang H, Dang Cong T. Deficient Mismatch Repair Proteins in Gastric Mixed Neuroendocrine Non-Neuroendocrine Neoplasm: A Rare Case Report. Case Rep Oncol 2023; 16:1172-1182. [PMID: 37900850 PMCID: PMC10601832 DOI: 10.1159/000533707] [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: 07/25/2023] [Accepted: 08/16/2023] [Indexed: 10/31/2023] Open
Abstract
Mixed neuroendocrine non-neuroendocrine neoplasm (MiNEN) is a rare type of gastric carcinoma with controversial diagnosis and treatment. Recent data implies that deficiency mismatch repair proteins inducing microsatellite instability are considered one of the potential drivers of this disease. Hence, we report a stomach MiNEN with MMR protein loss. An admitted 60-year-old woman complained of epigastric pain. The pathological analysis of the gastro-endoscopic biopsy specimen revealed gastric adenocarcinoma. The radiological staging was cT3N1M0; therefore, she received D2 distal gastrectomy. Suspecting neuroendocrine component admix with adenocarcinoma part on the resected specimen microscopy, applying biomarkers including AE 1/3, synaptophysin, and chromogranin A to confirm the diagnosis of MiNEN. The neuroendocrine part was classified as neuroendocrine tumor grade 2 with Ki 67 at 16.5%. To further understand the molecular characterization of this disease, we evaluated mismatch protein expression by staining MLH1, MSH2, MSH6, and PMS2 antibodies. Interestingly, both components lost MLH1 and PMS2 proteins. Her radical surgery followed oxaliplatin/capecitabine adjuvant chemotherapy. The patient is still well after eight cycles of chemotherapy. dMMR gastric MiNENs and dMMR gastric cancer share many clinical and genetic characteristics. Further studies are necessary to survey the role of dMMR in the prognosis and treatment of this entity.
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Affiliation(s)
- Thi Hong Chuyen Nguyen
- Department of Oncology, Hue University of Medicine and Pharmacy, Hue University, Hue, Vietnam
| | - Bao Song Nguyen Tran
- Department of Histology, Embryology, Pathology, and Forensic Medicine, Hue University of Medicine and Pharmacy, Hue University, Hue, Vietnam
| | - Thanh Phuc Nguyen
- Department of Anatomy and Surgical Training, Hue University of Medicine and Pharmacy, Hue University, Hue, Vietnam
| | - Thi Minh Thi Ha
- Department of Medical Genetics, Hue University of Medicine and Pharmacy, Hue University, Hue, Vietnam
| | | | - Thu Giang Thi Nguyen
- Department of Oncology, Hue University of Medicine and Pharmacy, Hue University, Hue, Vietnam
| | - Huu Hoang
- Department of Oncology, Hue University of Medicine and Pharmacy, Hue University, Hue, Vietnam
| | - Thuan Dang Cong
- Department of Histology, Embryology, Pathology, and Forensic Medicine, Hue University of Medicine and Pharmacy, Hue University, Hue, Vietnam
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Keller HR, Senapathi SH, Morada A, Bertsch D, Cagir B. Survival in patients with neuroendocrine tumors of the colon, rectum and small intestine. Am J Surg 2023; 225:58-65. [PMID: 36216612 DOI: 10.1016/j.amjsurg.2022.09.053] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Revised: 09/25/2022] [Accepted: 09/28/2022] [Indexed: 12/30/2022]
Abstract
BACKGROUND Neuroendocrine neoplasms (NENs) of the colon, rectum and small intestine (SI) are increasing in incidence and prevalence. We evaluated the 5-year overall survival (OS), and cancer-specific survival (CSS). METHODS The Surveillance, Epidemiology, and End Results (SEER) 18 registry from 2000 to 2017 was accessed to identify patients with colonic, rectal, and SI NENs. RESULTS 46,665 patients were diagnosed with NENs of the colon (n = 10,518, 22.5%), rectum (18,063, 38.7%), and SI (18,084, 38.8%). By tumor site alone, patients with well-differentiated neuroendocrine tumors (NETs) of the rectum had improved 5-year OS (HR 0.72, 95% CI 0.68-0.77, p < 0.001). However, patients with rectal poorly-differentiated neuroendocrine carcinomas (NECs) who underwent oncologic resection had lower 5-year OS (35.1%) compared to colon (41.9%), and SI (72.5%). CONCLUSIONS Surgical resection may improve 5-year OS for NECs of the SI and colon, except in the rectum where survival was reduced. More frequent surveillance and timely initiation of systemic therapy should be considered for rectal NECs.
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Affiliation(s)
- Hilary R Keller
- Department of Surgery, Guthrie Robert Packer Hospital, Sayre, PA, 18840, USA
| | - Sri H Senapathi
- Department of Surgery, Guthrie Robert Packer Hospital, Sayre, PA, 18840, USA
| | - Anthony Morada
- Department of Surgery, Guthrie Robert Packer Hospital, Sayre, PA, 18840, USA
| | - David Bertsch
- Department of Surgery, Guthrie Robert Packer Hospital, Sayre, PA, 18840, USA
| | - Burt Cagir
- Department of Surgery, Guthrie Robert Packer Hospital, Sayre, PA, 18840, USA.
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Wu H, Yu Z, Liu Y, Guo L, Teng L, Guo L, Liang L, Wang J, Gao J, Li R, Yang L, Nie X, Su D, Liang Z. Genomic characterization reveals distinct mutation landscapes and therapeutic implications in neuroendocrine carcinomas of the gastrointestinal tract. Cancer Commun (Lond) 2022; 42:1367-1386. [PMID: 36264285 PMCID: PMC9759768 DOI: 10.1002/cac2.12372] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Revised: 06/24/2022] [Accepted: 10/08/2022] [Indexed: 01/25/2023] Open
Abstract
BACKGROUND Neuroendocrine carcinomas of the gastrointestinal tract (GI-NECs) remain a disease of grim prognosis with limited therapeutic options. Their molecular characteristics are still undefined. This study aimed to explore the underlying genetic basis and heterogeneity of GI-NECs. METHODS Comprehensive genomic analysis using whole-exome sequencing was performed on 143 formalin-fixed, paraffin-embedded samples of surgically resected GI-NEC with a thorough histological evaluation. Mutational signatures, somatic mutations, and copy number aberrations were analyzed and compared across anatomic locations and histological subtypes. Survival analysis was conducted to identify the independent factors. RESULTS In total, 143 GI-NECs were examined: the stomach, 87 cases (60.8%); the esophagus, 29 cases (20.3%); the colorectum, 20 cases (14.0%); and the small intestine, 7 cases (4.9%). Eighty-three (58.0%) and 60 (42.0%) cases were subclassified into small cell and large cell subtypes, respectively. GI-NECs showed distinct genetic alterations from their lung counterparts and non-neuroendocrine carcinomas in the same locations. Obvious heterogeneity of mutational signatures, somatic mutations, and copy number variations was revealed across anatomic locations rather than histological subtypes. Except for tumor protein p53 (TP53) and retinoblastoma 1 (RB1), the most frequently mutated genes in the stomach, esophagus, colorectum, and small intestine were low-density lipoprotein receptor-related protein 1B (LRP1B), notch receptor 1 (NOTCH1), adenomatosis polyposis coli (APC), catenin beta 1 (CTNNB1), respectively. Mutations in the WNT-β-catenin, NOTCH and erythroblastic leukemia viral oncogene B (ERBB) pathways were prevalently identified in gastric, esophageal, and colorectal NECs, respectively. Importantly, 104 (72.7%) GI-NECs harbored putative clinically relevant alterations, and non-gastric location and RB1 bi-allelic inactivation with copy number alterations were identified as two independent poor prognostic factors. Furthermore, we found that tumor cells in GI-NECs first gain clonal mutations in TP53, RB1, NOTCH1 and APC, followed by subsequent whole-genome doubling (WGD) and post-WGD clonal mutations in LRP1B, CUB and Sushi multiple domains 3 (CSMD3), FAT tumor suppressor homolog 4 (FAT4) and erb-b2 receptor tyrosine kinase 4 (ERBB4), and finally develop subclonal mutations. CONCLUSIONS GI-NECs harbor distinct genomic landscapes and demonstrate significant genetic heterogeneity across different anatomic locations. Moreover, potentially actionable alterations and prognostic factors were revealed for GI-NECs.
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Affiliation(s)
- Huanwen Wu
- Department of PathologyState Key Laboratory of Complex Severe and Rare DiseasesMolecular Pathology Research CenterPeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100730P. R. China
| | - Zicheng Yu
- Geneplus‐BeijingBeijing102200P. R. China
| | - Yueping Liu
- Department of PathologyThe Fourth Hospital of Hebei Medical UniversityShijiazhuangHebei050011P. R. China
| | - Lei Guo
- Department of PathologyCancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100021P. R. China
| | - Lianghong Teng
- Department of PathologyXuanwu HospitalCapital Medical UniversityBeijing100053P. R. China
| | - Lingchuan Guo
- Department of PathologyThe First Affiliated Hospital of Soochow UniversitySuzhouJiangsu215000P. R. China
| | - Li Liang
- Department of PathologySouthern Medical UniversityGuangzhouGuangdong510515P. R. China
| | - Jing Wang
- Department of PathologyState Key Laboratory of Complex Severe and Rare DiseasesMolecular Pathology Research CenterPeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100730P. R. China
| | - Jie Gao
- Department of PathologyState Key Laboratory of Complex Severe and Rare DiseasesMolecular Pathology Research CenterPeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100730P. R. China
| | - Ruiyu Li
- Department of PathologyState Key Laboratory of Complex Severe and Rare DiseasesMolecular Pathology Research CenterPeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100730P. R. China
| | - Ling Yang
- Geneplus‐BeijingBeijing102200P. R. China
| | - Xiu Nie
- Department of PathologyUnion HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei430022P. R. China
| | - Dan Su
- Department of PathologyThe Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)Institute of Basic Medicine and Cancer (IBMC)Chinese Academy of SciencesHangzhouZhejiang310022P. R. China
| | - Zhiyong Liang
- Department of PathologyState Key Laboratory of Complex Severe and Rare DiseasesMolecular Pathology Research CenterPeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100730P. R. China
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From morphology to molecular targets—the pathologist’s view in diagnosing gastroenteropancreatic neuroendocrine neoplasms. MEMO - MAGAZINE OF EUROPEAN MEDICAL ONCOLOGY 2022. [DOI: 10.1007/s12254-022-00850-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
SummaryIn the last decade, a number of genetic alterations in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) have been identified. In addition, differences in tumor morphology as well as proliferation index (Ki-67) or number of mitoses have led to changes in the classification of these neoplasms. According to the new World Health Organization (WHO) classification, GEP-NENs are now divided into two genetically and prognostically different categories: (i) well-differentiated neuroendocrine tumors (NET) subdivided into low (G1), intermediate (2) and high (G3) grade tumors, and (ii) poorly differentiated neuroendocrine carcinomas (NEC). In addition, a group of mixed neuroendocrine–non-neuroendocrine neoplasms (MiNEN) has been defined. This review focuses on the clinical, morphological, immunohistochemical and molecular findings of the GEP-NENs and their key diagnostic features that can help the pathologist to differentiate between tumors in this heterogeneous group. In challenging cases, additional immunohistochemical and/or molecular analysis can be helpful to determine the correct diagnosis and proper treatment for the patient.
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Yao J, Bergsland E, Aggarwal R, Aparicio A, Beltran H, Crabtree JS, Hann CL, Ibrahim T, Byers LA, Sasano H, Umejiego J, Pavel M. DLL3 as an Emerging Target for the Treatment of Neuroendocrine Neoplasms. Oncologist 2022; 27:940-951. [PMID: 35983951 PMCID: PMC9632312 DOI: 10.1093/oncolo/oyac161] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Accepted: 07/01/2022] [Indexed: 01/05/2023] Open
Abstract
INTRODUCTION Neuroendocrine neoplasms (NEN) are heterogeneous malignancies that can arise at almost any anatomical site and are classified as biologically distinct well-differentiated neuroendocrine tumors (NET) and poorly differentiated neuroendocrine carcinomas (NEC). Current systemic therapies for advanced disease, including targeted therapies, chemotherapy, and immunotherapy, are associated with limited duration of response. New therapeutic targets are needed. One promising target is delta-like ligand 3 (DLL3), an inhibitory ligand of the Notch receptor whose overexpression on the surface of NEN is associated with tumorigenesis. METHODS This article is a narrative review that highlights the role of DLL3 in NEN progression and prognosis, the potential for therapeutic targeting of DLL3, and ongoing studies of DLL3-targeting therapies. Classification, incidence, pathogenesis, and current management of NEN are reviewed to provide biological context and illustrate the unmet clinical needs. DISCUSSION DLL3 is overexpressed in many NENs, implicated in tumor progression, and is typically associated with poor clinical outcomes, particularly in patients with NEC. Targeted therapies using DLL3 as a homing beacon for cytotoxic activity mediated via several different mechanisms (eg, antibody-drug conjugates, T-cell engager molecules, CAR-Ts) have shown promising clinical activity in small-cell lung cancer (SCLC). DLL3 may be a clinically actionable target across NEN. CONCLUSIONS Current treatment options for NEN do not provide sustained responses. DLL3 is expressed on the cell surface of many NEN types and is associated with poor clinical outcomes. Initial clinical studies targeting DLL3 therapeutically in SCLC have been promising, and additional studies are expanding this approach to the broader group of NEN.
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Affiliation(s)
- James Yao
- Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Emily Bergsland
- Department of Medicine, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA
| | - Rahul Aggarwal
- Department of Medicine, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA
| | - Ana Aparicio
- The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Himisha Beltran
- Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Judy S Crabtree
- Department of Genetics, Louisiana State University Health Sciences Center, New Orleans, LA, USA
| | - Christine L Hann
- Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Toni Ibrahim
- Osteoncology, Bone and Soft Tissue Sarcomas and Innovative Therapies Unit, IRCSS Istituto Ortopedico Rizzoli, Bologna, Italy
| | - Lauren A Byers
- Thoracic Head and Neck Medical Oncology, MD Anderson Cancer Center, Houston, TX, USA
| | - Hironobu Sasano
- Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | | | - Marianne Pavel
- Department of Medicine 1, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany
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Ikeda M, Miura S, Kume K, Kikuta K, Hamada S, Takikawa T, Nakagawa K, Unno M, Furukawa T, Masamune A. Pancreatic mixed acinar-neuroendocrine carcinoma in a patient with a germline BRCA2 mutation: a case report. Clin J Gastroenterol 2022; 15:999-1005. [PMID: 35819745 DOI: 10.1007/s12328-022-01668-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Accepted: 06/20/2022] [Indexed: 11/28/2022]
Abstract
Loss of function in the BRCA2 gene exacerbates ovarian, breast, and pancreatic ductal cancer risk. Despite being implicated in the pancreatic ductal epithelium carcinogenesis, the involvement of a germline BRCA2 mutation in acinar and endocrine cells is less reported. A 45-year-old woman with a history of breast cancer was referred to our hospital for a detailed examination of epigastric pain. Her father had pancreatic cancer, and her paternal aunt had a history of breast cancer. Contrast-enhanced computed tomography revealed a round tumor with a contrast effect in the pancreatic head. The patient underwent pancreaticoduodenectomy, and postoperative pathology and genetic testing revealed amphicrine-type mixed acinar-neuroendocrine carcinoma with a germline BRCA2 mutation. Recent studies have reported the BRCA2 mutation in genome sequencing of pancreatic acinar cell carcinoma and neuroendocrine tumor; perhaps, genetic testing for the BRCA2 mutation is feasible for patients with mixed neuroendocrine-non-neuroendocrine neoplasm.
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Affiliation(s)
- Mio Ikeda
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Shin Miura
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
| | - Kiyoshi Kume
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Kazuhiro Kikuta
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Shin Hamada
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Tetsuya Takikawa
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Kei Nakagawa
- Division of Surgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Michiaki Unno
- Division of Surgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Toru Furukawa
- Division of Investigative Pathology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Atsushi Masamune
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
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Zavrtanik H, Luzar B, Tomažič A. Intra-ampullary papillary-tubular neoplasm combined with ampullary neuroendocrine carcinoma: A case report. World J Clin Cases 2022; 10:8045-8053. [PMID: 36158500 PMCID: PMC9372858 DOI: 10.12998/wjcc.v10.i22.8045] [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: 03/21/2022] [Revised: 05/03/2022] [Accepted: 06/26/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The ampulla of Vater is an anatomically and histologically complex region giving rise to a heterogenous group of tumors. This is, to the best of our knowledge, the first case of intra-ampullary papillary-tubular neoplasm combined with ampullary neuroendocrine carcinoma reported in the literature.
CASE SUMMARY A 61-year-old woman presented to the emergency department for evaluation of painless jaundice. Contrast-enhanced computed tomography (CT) of the abdomen and chest showed a periampullary tumor mass measuring 15 mm × 12 mm × 14 mm, with no evidence of locoregional and distant metastases, for which she underwent pancreatoduodenectomy. Histopathologic examination of a resected specimen revealed an intra-ampullary papillary tubular neoplasm with high-grade dysplasia in combination with poorly differentiated grade 3 neuroendocrine carcinoma with a mitotic count of more than 20 mitoses per 10 high power fields and Ki-67 index of 100%. No positive lymph nodes were identified. Her postoperative course was uneventful. Postoperatively, she remained under close surveillance. Multiple liver metastases were observed on follow-up CT 8 mo after the surgery, so systemic therapy with cisplatin and etoposide was initiated.
CONCLUSION The simultaneous occurrence of neuroendocrine and non-neuroendocrine tumors in the ampulla of Vater is rare and the pathogenesis of such tumors is largely unknown. Due to unpredictable clinical behavior and lack of solid evidence on optimal treatment strategy, close patient surveillance is advised after radical resection of the primary tumor.
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Affiliation(s)
- Hana Zavrtanik
- Department of Abdominal Surgery, University Medical Centre Ljubljana, Ljubljana 1000, Slovenia
| | - Boštjan Luzar
- Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana 1000, Slovenia
| | - Aleš Tomažič
- Department of Abdominal Surgery, University Medical Centre Ljubljana, Ljubljana 1000, Slovenia
- Faculty of Medicine, University of Ljubljana, Ljubljana 1000, Slovenia
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Ren X, Jiang H, Sun K, Qin X, Qu Y, Xia T, Chen Y. Mixed neuroendocrine-non-neuroendocrine neoplasm of the gallbladder: case report and literature review. Diagn Pathol 2022; 17:51. [PMID: 35715834 PMCID: PMC9206291 DOI: 10.1186/s13000-022-01231-6] [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: 11/11/2021] [Accepted: 05/18/2022] [Indexed: 11/30/2022] Open
Abstract
Background Mixed neuroendocrine–non-neuroendocrine neoplasms (MiNENs) of the gallbladder are rare malignancies. Here we presented two cases and reviewed the related literature. Case presentation Our two patients were postoperatively diagnosed with gallbladder MiNENs, which pathologically consisted of a large cell neuroendocrine carcinoma and papillary adenocarcinoma. After cholecystectomy, one patient had a survival time of 30 months, while the other remained alive through 12 months of follow-up. In the literature, a total of 72 cases of gallbladder MiNENs were identified, and with our two patients included, we calculated a male-to-female ratio of 0.22 and a mean age of 64.5 years for the 74 reported cases. About one-half of these patients were found to have gallstones and presented with abdominal pain or discomfort in a relatively early stage. The preoperative diagnosis of these 74 cases mainly relied on abdominal ultrasound, contrast-enhanced computed tomography (CT) scanning, and magnetic resonance imaging or positron emission tomography/CT. However, the final diagnosis was established based upon the pathological evidence and expression of synaptophysin (Syn) and/or chromogranin A identified by immunohistochemical staining or neurosecretory granules detected by electron microscopy. Fifty-eight patients (78.4%) underwent various operations including simple cholecystectomy (n = 14), en bloc cholecystectomy (n = 9), standard or non-standard radical cholecystectomy (n = 25), or extended radical cholecystectomy (n = 6). The mean size of the resected gallbladder masses was 50.8 ± 36.1 mm (n = 63) with regional lymph node metastasis in 37 patients (52.1%), liver invasion or staging greater than T3 in 33 patients (45.8%), and hepatic metastasis in 26 patients (35.1%). The postoperative median survival time was 36 ± 11.42 months (95% confidence interval, 13.62 to 58.38 months). The log-rank analysis did not find that postoperative adjuvant chemotherapy contributed to a longer survival time relative to that among the patients who did not receive chemotherapy (numbers of patients, 15 versus 43; survival times, 36 months versus 30 months, p > 0.05). Conclusions Our two cases and the cases in the literature suggest that MiNENs of the gallbladder predominantly occur in women; are associated with early lymph node metastasis, local hepatic invasion, and hepatic metastasis; and can be managed by various surgeries as well as chemotherapy combined with somatostatin analogs.
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Affiliation(s)
- Xu Ren
- Digestive Hospital of Heilongjiang Provincial Hospital Affiliated to Harbin University of Technology, No. 405, Guogeli Street, Harbin, 150001, Heilongjiang, China.
| | - Hong Jiang
- Department of Pathology, Heilongjiang Provincial Hospital Affiliated to Harbin University of Technology, Harbin, 150001, Heilongjiang Province, China
| | - Kan Sun
- Department of General Surgery, Heilongjiang Provincial Hospital Affiliated to Harbin University of Technology, Harbin, 150001, Heilongjiang Province, China
| | - Xufu Qin
- Department of Gastroenterology, Heilongjiang Provincial Hospital Affiliated to Harbin University of Technology, Harbin, 150001, Heilongjiang Province, China
| | - Yongping Qu
- Digestive Endoscopy Center, Heilongjiang Provincial Hospital of Harbin Institute of Technology, Harbin, 150001, Heilongjiang Province, China
| | - Tian Xia
- Digestive Hospital of Heilongjiang Provincial Hospital Affiliated to Harbin University of Technology, No. 405, Guogeli Street, Harbin, 150001, Heilongjiang, China
| | - Yan Chen
- Hospital Information Center of Heilongjiang Province Affiliated to Harbin Institute of Technology, Harbin, 150001, Heilongjiang Province, China
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Toor D, Loree JM, Gao ZH, Wang G, Zhou C. Mixed neuroendocrine-non-neuroendocrine neoplasms of the digestive system: A mini-review. World J Gastroenterol 2022; 28:2076-2087. [PMID: 35664032 PMCID: PMC9134131 DOI: 10.3748/wjg.v28.i19.2076] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Revised: 03/25/2022] [Accepted: 04/28/2022] [Indexed: 02/06/2023] Open
Abstract
Mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) are rare mixed tumors containing both neuroendocrine (NE) and non-NE components. Each component must occupy at least 30% of the tumor volume by definition. Recent molecular evidence suggests MiNENs are clonal neoplasms and potentially harbor targetable mutations similar to conventional carcinomas. There have been multiple changes in the nomenclature and classification of MiNENs which has created some confusion among pathologists on how to integrate the contributions of each component in a MiNEN, an issue which in turn has resulted in confusion in communication with front-line treating oncologists. This mini review summarizes our current understanding of MiNENs and outline diagnosis, prognosis, and management of these neoplasms. The authors emphasize the importance of treating the most aggressive component of the tumor regardless of its percentage volume.
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Affiliation(s)
- Deepak Toor
- Department of Pathology and Laboratory Medicine, BC Cancer, Vancouver V5Z 1H5, Canada
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver V5Z 1H5, Canada
| | | | - Zu-Hua Gao
- Department of Pathology and Laboratory Medicine, BC Cancer, Vancouver V5Z 1H5, Canada
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver V5Z 1H5, Canada
| | - Gang Wang
- Department of Pathology and Laboratory Medicine, BC Cancer, Vancouver V5Z 1H5, Canada
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver V5Z 1H5, Canada
| | - Chen Zhou
- Department of Pathology and Laboratory Medicine, BC Cancer, Vancouver V5Z 1H5, Canada
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver V5Z 1H5, Canada
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