A case report of carcinoma of the papilla of Vater associated with a hyperplasia-dysplasia-carcinoma sequence by pancreaticobiliary maljunction

Abstract

Background: Pancreaticobiliary maljunction (PBM) is a known risk factor for biliary tract cancer. However, its association with carcinoma of the papilla of Vater (PVca) remains unknown. We report a case with PVca that was thought to be caused by the hyperplasia-dysplasia-carcinoma sequence, which is considered a mechanism underlying PBM-induced biliary tract cancer.

Case presentation: A 70-year-old woman presented with white stool and had a history of cholecystectomy for the diagnosis of a non-dilated biliary tract with PBM. Esophagogastroduodenoscopy revealed a tumor in the papilla of Vater, and PVca was histologically proven by biopsy. We finally diagnosed her with PVca concurrent with non-biliary dilated PBM (cT1aN0M0, cStage IA, according to the Union for International Cancer Control, 8th edition), and subsequently performed subtotal stomach-preserving pancreaticoduodenectomy. Pathological findings of the resected specimen revealed no adenomas and dysplastic and hyperplastic mucosae in the common channel slightly upstream of the main tumor, suggesting a PBM related carcinogenic pathway with hyperplasia-dysplasia-carcinoma sequence. Immunostaining revealed positivity for CEA. CK7 positivity, CK20 negativity, and MUC2 negativity indicated that this PVca was of the pancreatobiliary type. Genetic mutations were exclusively detected in tumors and not in normal tissues, and bile ducts from formalin-fixed paraffin-embedded samples included mutated-ERBB2 (Mutant allele frequency, 81.95%). Moreover, of the cell-free deoxyribonucleic acid (cfDNA) extracted from liquid biopsy mutated-ERBB2 was considered the circulating-tumor deoxyribonucleic acid (ctDNA) of this tumor.

Conclusions: Herein, we report the first case of PVca with PBM potentially caused by a "hyperplasia-dysplasia-carcinoma sequence" detected using immunostaining and next-generation sequencing. Careful follow-up is required if pancreaticobiliary reflux persists, considering the possible development of PVca.

Keywords: Carcinoma of the papilla of Vater; Dysplasia; ERBB2; Formalin-fixed paraffin-embedded; Hyperplasia; Liquid biopsy; Next-generation sequencing; Pancreaticobiliary maljunction; cfDNA; ctDNA.

Fig. 1

Endoscopy and echography. (A) Esophagogastroduodenoscopy revealed a tumor of the papilla of Vater. (B, C) Endoscopic ultrasound and intraductal ultrasonography revealed that the tumor was located in the common channel and demonstrated no invasion of the duodenal muscular layer and pancreas. CBD, Common bile duct; MPD, Main pancreatic duct

Fig. 2

Abdominal enhanced computed tomography (CT). CT revealed a tumor in the duodenum, with a size of 14 × 14 mm (arrow). CBD, Common bile duct; MPD, Main pancreatic duct

Fig. 3

Magnetic resonance choledochopancreatography (MRCP). MRCP revealed dilatation of the extra/intrahepatic bile duct and main pancreatic duct, and the length of the common channel was 23 mm

Fig. 4

Morphological evaluation derived from pathological findings. No adenomas were observed, suggesting a hyperplasia–dysplasia–carcinoma sequence carcinogenic mechanism. No. 1: Main part of the carcinoma (C) in the common channel. No. 2: The depiction of front between hyperplasia (H) area, dysplasia (D) area, and carcinoma (C) area is observed in the common channel. No. 3: Hyperplasia (H) in the common bile duct. There was no evidence of increased nuclear-to-cytoplasmic ratio, increased nuclear chromatin and loss of nuclear polarity, or cell overlap. MP, Muscularis propria; Panc., Pancreas

Fig. 5

Immunohistological findings of the resected specimen. CEA was highly expressed at all sites of the hyperplasia, dysplasia, and carcinoma. COX-2, HER2, and IL-33 expression were positive in the carcinoma tissues