RARE DISEASE
Carcinoma of the ampulla of Vater
Carcinoma of the ampulla of Vater
Carcinoma of the ampulla of Vater
Synonyms: Ampullary carcinoma, Ampulloma
Synonyms: Ampullary carcinoma, Ampulloma
Synonyms: Ampullary carcinoma, Ampulloma
Drug discovery
0
drugs
With orphan designations
Overview
Carcinoma of the Ampulla of Vater (AVC) arises at the confluence of pancreaticobiliary and intestinal epithelia, often presenting with obstructive jaundice due to bile duct involvement. Histologically classified into intestinal, pancreatobiliary, or mixed subtypes, it exhibits molecular heterogeneity (e.g., KRAS, TP53, and ELF3 mutations). Surgical resection (Whipple procedure) is curative for localized disease, while adjuvant chemotherapy (gemcitabine/5-FU-based) is used for high-risk features. Metastatic disease employs platinum-based or XELOX regimens, with 5-year survival post-resection ranging 35–62% [1][4][5][7][8].
Therapies
Categories: rare gastroenterological diseases, rare neoplastic diseases
Research Papers
995 drug discovery papers about Carcinoma of the ampulla of Vater, with 3 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
995 drug discovery papers about Carcinoma of the ampulla of Vater, with 3 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-07-06 | Immunohistochemical profiling of ampullary carcinoma: Molecular subtypes, prognostic markers, and the role of Claudin-18.
Ampullary cancer is a rare malignancy, histologically divided into intestinal and pancreatobiliary subtypes based on histomorphological and immunophenotypic features as they arise from different epithelial origins and exhibit distinct biological behavior, treatment responses, and clinical outcomes. However, current histomorphological and immunohistochemical classification often remains ambiguous, complicating accurate subtype assignment to guide therapeutic approaches. In this retrospective study of 125 ampullary carcinoma cases, we performed immunohistochemical profiling using a panel of markers including CDX2, CK20, mucins (MUC1, MUC2, MUC5AC), and claudins (CLDN1-4, CLDN7, CLDN18) to refine subtype classification and identify prognostic biomarkers. Hierarchical clustering based on marker expression H-scores revealed two molecular subtypes corresponding to intestinal and pancreatobiliary differentiation. While CDX2 and CK20 are routinely used in combination for diagnosis, other markers, particularly CLDN3, CLDN7, and MUC5AC, demonstrated superior diagnostic and prognostic performance to CDX2. CK20, by contrast, remained a robust marker of intestinal differentiation and favorable outcome. Pancreatobiliary-type tumors exhibited elevated MUC1, MUC5AC, and CLDN18 expression, and were associated with advanced stage, invasive features, and significantly worse survival. Multivariate analysis showed high MUC5AC and apical MUC1 expression to be associated with adverse outcomes, whereas CLDN1, CLDN3 and CLDN4 expression were linked to improved survival. Membranous CLDN18 expression was more common in pancreatobiliary-type ampullary cancer, making it a potential therapeutic target. These findings underscore the diagnostic and prognostic value of multiplex immunohistochemical profiling. We propose retaining CK20 but replacing CDX2 with a more informative marker, namely CLDN3, to enhance classification and therapeutic stratification.
2026-07-02 | Squamous cell carcinoma of the ampulla of Vater: a rare case report and review of the literature
Introduction: Primary squamous cell carcinoma (SCC) of the ampulla of Vater is an exceptionally rare malignancy, with only a limited number of cases reported in the literature. Its pathogenesis, biological behavior, and optimal management remain poorly defined. Case presentation: We report the case of a 68-year-old man presenting with several weeks of atypical abdominal discomfort and cholestatic liver enzyme abnormalities. Upper gastrointestinal endoscopy revealed an ulcerated ampullary lesion, and biopsy confirmed moderately to poorly differentiated SCC. Cross-sectional imaging excluded metastatic disease. The patient underwent pylorus-preserving pancreaticoduodenectomy. Histopathological analysis confirmed primary SCC (pT2N0M0) with negative margins (R0 resection). Adjuvant chemotherapy with cisplatin and 5-fluorouracil was initiated 6 weeks postoperatively, with a planned duration of 6 months. The patient remains disease-free at 6-month follow-up. Discussion: Ampullary SCC is rare but not unique, with several cases reported. Surgical resection remains the cornerstone of treatment. Adjuvant therapy is extrapolated from other SCCs due to a lack of evidence. Prognosis appears variable, with better outcomes in node-negative disease. Conclusion: This case highlights the importance of accurate histopathological diagnosis and reinforces the role of radical surgical resection. Further case accumulation is required to define optimal management strategies.
2026-07-01 | Transcriptomic-based molecular classification of ampullary adenocarcinoma.
Ampullary adenocarcinoma (AMPAC) is a rare and heterogeneous malignancy with markedly variable clinical outcomes, underscoring the urgent need for molecularly informed classification and personalized therapeutic strategies. Current AMPAC classification relies primarily on morphological and immunohistochemical criteria, which lack prognostic accuracy and fail to capture the underlying molecular and tumor microenvironment heterogeneity. In this study, we integrated bulk RNA sequencing, single-cell RNA sequencing (scRNA-seq), and clinicopathological data to elucidate the molecular architecture of AMPAC and introduced a transcriptomic-based molecular classification (AMS). The AMS categorized patients into two molecular subtypes: mesenchymal AMPAC (AMS-M) and classical AMPAC (AMS-C). The AMS-M demonstrated increased epithelial-mesenchymal transition (EMT) and stromal activation, correlating with basal-like subtypes associated with unfavorable prognosis. In contrast, AMS-C tumors exhibited metabolic and differentiation programs with relatively preserved immune infiltration. Importantly, we identified MUC16 as a pivotal biomarker specifically overexpressed in AMS-M tumors. MUC16 knockout markedly reversed EMT, attenuated invasive and migratory capacities, and restored chemosensitivity in both cell lines and their xenograft models. Collectively, our findings establish AMS as a prognostically and therapeutically informative molecular classification framework for AMPAC, unveil the critical role of the tumor microenvironment in AMPAC heterogeneity, and provide a translational foundation for precision oncology in this rare tumor.
2026-06-26 | Exploring the Role of MET Gene as a Potential Biomarker and Therapeutic Target in Ampullary Cancer.
The incidence of Ampullary carcinoma (AC) has dramatically increased. Nearly 50% of patients develop recurrence indicating need for additional prognostic markers and treatment options. Emerging evidence suggests that Mesenchymal Epithelial Transition (MET) genes play a role in tumorigenesis and can be a useful therapeutic target, however, its role in AC remains unexplored. This study investigated the methylation status using methylation specific PCR, mRNA expression using quantitative PCR and protein expression using Immunohistochemistry of the MET proto-oncogene in 61 surgically resected AC specimens and further examined its co-expression with HER2. Our findings revealed MET promoter hypomethylation (68.85%), increased expression of MET at mRNA (67.21%) and protein level (54%) in ACs patients. Significant correlation was observed between both hypomethylation and increased mRNA expression (P=0.026; P<0.000), and MET mRNA and protein expression (P=0.037). Further, MET expression was notably higher in early stage (P=0.003) and Intestinal-type (84.21%) than Pancreatobiliary type (PB-type) (61.76%) (P=0.199). Additionally, co-expression of MET and HER2 receptors occurred in a significant subset of cases in AC suggesting receptor tyrosine kinase convergence (P=0.014). In silico analysis of the GSE60979, dataset corroborated these findings, showing increased MET and ERBB2 (HER2) expression in tumor samples compared to normal tissues. At a median follow-up of 34 months the mean survival of AC patient was 37.3±2.5 months. These findings demonstrate that MET dysregulation is a recurrent molecular event in ampullary carcinoma and support further investigation of MET and HER2 co-expression as a basis for future mechanistic and therapeutic studies.
2026-06-24 | A Case of Unresectable Ampulla of Vater Carcinoma Successfully Treated with Conversion Surgery Following Sequential Systemic Chemotherapy Including Durvalumab.
The criteria for indications and postoperative treatment strategies for conversion surgery in patients with unresectable ampulla of Vater carcinoma with distant metastasis have not been clarified. We present an unusual case of a patient with initially unresectable ampulla of Vater carcinoma with multiple liver metastases who underwent conversion surgery after treatment with durvalumab and gemcitabine plus cisplatin. A 69-year-old male was found to have ampulla of Vater carcinoma with multiple liver metastases. A diagnosis of unresectable ampulla of Vater carcinoma was made, and the treatment plan was chemotherapy. After 12 cycles of gemcitabine, cisplatin, and S-1, the tumor did not shrink. Six cycles of gemcitabine, cisplatin, and durvalumab were then administered. The metastases were obscured on imaging; however, micrometastases were observed on the liver surface by staging laparoscopy. Six additional cycles of gemcitabine, cisplatin, and durvalumab were administered, and the disappearance of metastases was confirmed by staging laparoscopy. The patient then underwent conversion surgery with subtotal gastric-preserving pancreaticoduodenectomy. Pathology revealed a complete response, and radical resection was successfully performed. Immunostaining of tissue collected during endoscopic ultrasound-guided acquisition revealed less than 1% expression of programmed death ligand-1. Sequential systemic chemotherapy including durvalumab is suggested as a useful future treatment option and may contribute to conversion surgery for unresectable ampulla of Vater carcinoma.
2026-07-06 | Immunohistochemical profiling of ampullary carcinoma: Molecular subtypes, prognostic markers, and the role of Claudin-18.
Ampullary cancer is a rare malignancy, histologically divided into intestinal and pancreatobiliary subtypes based on histomorphological and immunophenotypic features as they arise from different epithelial origins and exhibit distinct biological behavior, treatment responses, and clinical outcomes. However, current histomorphological and immunohistochemical classification often remains ambiguous, complicating accurate subtype assignment to guide therapeutic approaches. In this retrospective study of 125 ampullary carcinoma cases, we performed immunohistochemical profiling using a panel of markers including CDX2, CK20, mucins (MUC1, MUC2, MUC5AC), and claudins (CLDN1-4, CLDN7, CLDN18) to refine subtype classification and identify prognostic biomarkers. Hierarchical clustering based on marker expression H-scores revealed two molecular subtypes corresponding to intestinal and pancreatobiliary differentiation. While CDX2 and CK20 are routinely used in combination for diagnosis, other markers, particularly CLDN3, CLDN7, and MUC5AC, demonstrated superior diagnostic and prognostic performance to CDX2. CK20, by contrast, remained a robust marker of intestinal differentiation and favorable outcome. Pancreatobiliary-type tumors exhibited elevated MUC1, MUC5AC, and CLDN18 expression, and were associated with advanced stage, invasive features, and significantly worse survival. Multivariate analysis showed high MUC5AC and apical MUC1 expression to be associated with adverse outcomes, whereas CLDN1, CLDN3 and CLDN4 expression were linked to improved survival. Membranous CLDN18 expression was more common in pancreatobiliary-type ampullary cancer, making it a potential therapeutic target. These findings underscore the diagnostic and prognostic value of multiplex immunohistochemical profiling. We propose retaining CK20 but replacing CDX2 with a more informative marker, namely CLDN3, to enhance classification and therapeutic stratification.
2026-07-02 | Squamous cell carcinoma of the ampulla of Vater: a rare case report and review of the literature
Introduction: Primary squamous cell carcinoma (SCC) of the ampulla of Vater is an exceptionally rare malignancy, with only a limited number of cases reported in the literature. Its pathogenesis, biological behavior, and optimal management remain poorly defined. Case presentation: We report the case of a 68-year-old man presenting with several weeks of atypical abdominal discomfort and cholestatic liver enzyme abnormalities. Upper gastrointestinal endoscopy revealed an ulcerated ampullary lesion, and biopsy confirmed moderately to poorly differentiated SCC. Cross-sectional imaging excluded metastatic disease. The patient underwent pylorus-preserving pancreaticoduodenectomy. Histopathological analysis confirmed primary SCC (pT2N0M0) with negative margins (R0 resection). Adjuvant chemotherapy with cisplatin and 5-fluorouracil was initiated 6 weeks postoperatively, with a planned duration of 6 months. The patient remains disease-free at 6-month follow-up. Discussion: Ampullary SCC is rare but not unique, with several cases reported. Surgical resection remains the cornerstone of treatment. Adjuvant therapy is extrapolated from other SCCs due to a lack of evidence. Prognosis appears variable, with better outcomes in node-negative disease. Conclusion: This case highlights the importance of accurate histopathological diagnosis and reinforces the role of radical surgical resection. Further case accumulation is required to define optimal management strategies.
2026-07-01 | Transcriptomic-based molecular classification of ampullary adenocarcinoma.
Ampullary adenocarcinoma (AMPAC) is a rare and heterogeneous malignancy with markedly variable clinical outcomes, underscoring the urgent need for molecularly informed classification and personalized therapeutic strategies. Current AMPAC classification relies primarily on morphological and immunohistochemical criteria, which lack prognostic accuracy and fail to capture the underlying molecular and tumor microenvironment heterogeneity. In this study, we integrated bulk RNA sequencing, single-cell RNA sequencing (scRNA-seq), and clinicopathological data to elucidate the molecular architecture of AMPAC and introduced a transcriptomic-based molecular classification (AMS). The AMS categorized patients into two molecular subtypes: mesenchymal AMPAC (AMS-M) and classical AMPAC (AMS-C). The AMS-M demonstrated increased epithelial-mesenchymal transition (EMT) and stromal activation, correlating with basal-like subtypes associated with unfavorable prognosis. In contrast, AMS-C tumors exhibited metabolic and differentiation programs with relatively preserved immune infiltration. Importantly, we identified MUC16 as a pivotal biomarker specifically overexpressed in AMS-M tumors. MUC16 knockout markedly reversed EMT, attenuated invasive and migratory capacities, and restored chemosensitivity in both cell lines and their xenograft models. Collectively, our findings establish AMS as a prognostically and therapeutically informative molecular classification framework for AMPAC, unveil the critical role of the tumor microenvironment in AMPAC heterogeneity, and provide a translational foundation for precision oncology in this rare tumor.
2026-06-26 | Exploring the Role of MET Gene as a Potential Biomarker and Therapeutic Target in Ampullary Cancer.
The incidence of Ampullary carcinoma (AC) has dramatically increased. Nearly 50% of patients develop recurrence indicating need for additional prognostic markers and treatment options. Emerging evidence suggests that Mesenchymal Epithelial Transition (MET) genes play a role in tumorigenesis and can be a useful therapeutic target, however, its role in AC remains unexplored. This study investigated the methylation status using methylation specific PCR, mRNA expression using quantitative PCR and protein expression using Immunohistochemistry of the MET proto-oncogene in 61 surgically resected AC specimens and further examined its co-expression with HER2. Our findings revealed MET promoter hypomethylation (68.85%), increased expression of MET at mRNA (67.21%) and protein level (54%) in ACs patients. Significant correlation was observed between both hypomethylation and increased mRNA expression (P=0.026; P<0.000), and MET mRNA and protein expression (P=0.037). Further, MET expression was notably higher in early stage (P=0.003) and Intestinal-type (84.21%) than Pancreatobiliary type (PB-type) (61.76%) (P=0.199). Additionally, co-expression of MET and HER2 receptors occurred in a significant subset of cases in AC suggesting receptor tyrosine kinase convergence (P=0.014). In silico analysis of the GSE60979, dataset corroborated these findings, showing increased MET and ERBB2 (HER2) expression in tumor samples compared to normal tissues. At a median follow-up of 34 months the mean survival of AC patient was 37.3±2.5 months. These findings demonstrate that MET dysregulation is a recurrent molecular event in ampullary carcinoma and support further investigation of MET and HER2 co-expression as a basis for future mechanistic and therapeutic studies.
2026-06-24 | A Case of Unresectable Ampulla of Vater Carcinoma Successfully Treated with Conversion Surgery Following Sequential Systemic Chemotherapy Including Durvalumab.
The criteria for indications and postoperative treatment strategies for conversion surgery in patients with unresectable ampulla of Vater carcinoma with distant metastasis have not been clarified. We present an unusual case of a patient with initially unresectable ampulla of Vater carcinoma with multiple liver metastases who underwent conversion surgery after treatment with durvalumab and gemcitabine plus cisplatin. A 69-year-old male was found to have ampulla of Vater carcinoma with multiple liver metastases. A diagnosis of unresectable ampulla of Vater carcinoma was made, and the treatment plan was chemotherapy. After 12 cycles of gemcitabine, cisplatin, and S-1, the tumor did not shrink. Six cycles of gemcitabine, cisplatin, and durvalumab were then administered. The metastases were obscured on imaging; however, micrometastases were observed on the liver surface by staging laparoscopy. Six additional cycles of gemcitabine, cisplatin, and durvalumab were administered, and the disappearance of metastases was confirmed by staging laparoscopy. The patient then underwent conversion surgery with subtotal gastric-preserving pancreaticoduodenectomy. Pathology revealed a complete response, and radical resection was successfully performed. Immunostaining of tissue collected during endoscopic ultrasound-guided acquisition revealed less than 1% expression of programmed death ligand-1. Sequential systemic chemotherapy including durvalumab is suggested as a useful future treatment option and may contribute to conversion surgery for unresectable ampulla of Vater carcinoma.
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