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
981 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:
981 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.
2026-06-30 | Malignant epithelial states drive immune dysfunction in ampulla of Vater carcinoma.
Ampulla of Vater (AoV) carcinoma is a rare malignancy arising at the junction of intestinal and pancreatobiliary epithelium. Its heterogeneous clinical behavior and histological diversity have hindered therapeutic advances, and the cellular basis of this heterogeneity remains unclear. We aimed to construct a single-cell transcriptomic atlas of AoV carcinoma, with a focus on identifying epithelial subtypes and their interactions with the tumor microenvironment (TME). We performed single-cell RNA sequencing on eight primary AoV tumors and four matched normal tissues. Comprehensive clustering and transcriptomic analyses identified cell-type composition, epithelial heterogeneity, and tumor-immune interactions. Findings were validated using deconvolution of bulk RNA-seq data from 62 AoV carcinoma patients. Results Malignant epithelial cells were categorized into four distinct subtypes: Int-Wnt, PB-KRAS, Int-Hypoxia, and Cycling stage. PB-KRAS cells exhibited stem-like transcriptional programs and high genomic instability. Deconvolution analysis of bulk RNA-seq data from the independent AoV cohort revealed that enrichment of the PB-KRAS subtype correlated with tumor recurrence and poor survival. Our immune profiling analysis discovered a significant association between PB-KRAS subtype and GZMK+ CD8+ T cells, which are in a pre-dysfunctional state, alongside SPP1+ macrophages exhibiting immunosuppressive traits. Spatial transcriptome data further supports the immunosuppressive natures of TME around PB-KRAS subtype malignant epithelial cells in AoV carcinoma. Our study presents a single-cell atlas of AoV carcinoma, highlighting the molecular diversity of malignant epithelium and its association with the immune microenvironment. The PB-KRAS subtype emerges as a stem-like, immunosuppressive tumor state associated with poor prognosis, providing insights for future therapeutic targeting.
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.
2026-06-30 | Malignant epithelial states drive immune dysfunction in ampulla of Vater carcinoma.
Ampulla of Vater (AoV) carcinoma is a rare malignancy arising at the junction of intestinal and pancreatobiliary epithelium. Its heterogeneous clinical behavior and histological diversity have hindered therapeutic advances, and the cellular basis of this heterogeneity remains unclear. We aimed to construct a single-cell transcriptomic atlas of AoV carcinoma, with a focus on identifying epithelial subtypes and their interactions with the tumor microenvironment (TME). We performed single-cell RNA sequencing on eight primary AoV tumors and four matched normal tissues. Comprehensive clustering and transcriptomic analyses identified cell-type composition, epithelial heterogeneity, and tumor-immune interactions. Findings were validated using deconvolution of bulk RNA-seq data from 62 AoV carcinoma patients. Results Malignant epithelial cells were categorized into four distinct subtypes: Int-Wnt, PB-KRAS, Int-Hypoxia, and Cycling stage. PB-KRAS cells exhibited stem-like transcriptional programs and high genomic instability. Deconvolution analysis of bulk RNA-seq data from the independent AoV cohort revealed that enrichment of the PB-KRAS subtype correlated with tumor recurrence and poor survival. Our immune profiling analysis discovered a significant association between PB-KRAS subtype and GZMK+ CD8+ T cells, which are in a pre-dysfunctional state, alongside SPP1+ macrophages exhibiting immunosuppressive traits. Spatial transcriptome data further supports the immunosuppressive natures of TME around PB-KRAS subtype malignant epithelial cells in AoV carcinoma. Our study presents a single-cell atlas of AoV carcinoma, highlighting the molecular diversity of malignant epithelium and its association with the immune microenvironment. The PB-KRAS subtype emerges as a stem-like, immunosuppressive tumor state associated with poor prognosis, providing insights for future therapeutic targeting.
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