Unexpected metastasis of intraductal papillary neoplasm of the bile duct without an invasive component to the brain and lungs: A case report

Abstract

Background: Despite an expanding number of studies on intraductal papillary neoplasm of the bile duct (IPNB), distant metastasis remains unexplained especially in cases of carcinoma in situ. In the present study, we report a rare and interesting case of IPNB without invasive components that later metastasized to lungs and brain.

Case summary: A 69-year-old male was referred to our hospital due to suspected cholangiocarcinoma. Laboratory tests on admission reported a mild elevation of alkaline phosphatase, γ-glutamyl transpeptidase, and total bilirubin in serum. Endoscopic retrograde cholangiography revealed a filling defect in the common bile duct (CBD) extending to the left hepatic duct. Peroral cholangioscopy delineated a tumor in the CBD that had a papillary pattern. Multidetector computed tomography and magnetic resonance cholangiopancreatography detected partial blockage ot interlude in the CBD leading to cholestasis without evidence of metastasis. Therefore, a diagnosis of IPNB cT1N0M0 was established. Left hepatectomy with bile duct reconstruction was performed. Pathological examination confirmed an intraepithelial neoplasia pattern without an invasive component and an R0 resection achievement. The patient was monitored carefully by regular examinations. However, at 32 mo after the operation, a 26 mm tumor in the lungs and a 12 mm lesion in the brain were detected following a suspicious elevated CA 19-9 level. Video-assisted thoracoscopic surgery of left upper lobectomy and stereotactic radiotherapy are indicated. In addition to histopathological results, a genomic profiling analysis using whole exome sequencing subsequently confirmed lung metastasis originating from bile duct cancer.

Conclusion: This case highlights the important role of genomic profiling analysis using whole exome sequencing in identifying the origin of metastasis in patients with IPNB.

Keywords: CA 19-9; Case report; Distant metastasis; Intraductal papillary neoplasm of the bile duct; Invasive component; Whole exome sequencing.

Figure 1

Peroral cholangioscopy findings: Biliary papillomatosis in the common bile duct.

Figure 2

Magnetic resonance imaging revealed extensively dilated bile ducts due to an intraluminal lesion located in the common bile duct.

Figure 3

Macroscopic findings showed a papillary tumor of the bile duct (arrowhead).

Figure 4

Microscopic findings of the bile duct tumor. A: The tumor showed the intraductal papillary proliferation of columnar cells with a high nuclear/cytoplasmic ratio; B: These neoplastic cells were entirely confined within the duct, and no invasion was identified (A: magnification × 20, B: magnification × 400); C-F: Immunohistological staining showed that the tumor cells were positive for CDX2, CK7, CK20, and Ki67.

Figure 5

Variation in the CA 19-9 level in correlation with clinical events. Time A (2015 December): Diagnosis of intraductal papillary neoplasm of the bile duct T1N0M0; Time B (2016 January): Good prognosis with satisfactory postoperative pathological findings, such as high-grade intraepithelial neoplasia pattern without an invasive component, R0 resection, no extended metastasis, lymph node (-) and ascites cytology (-); Time C (2018 September): Detection of suspected metastatic adenocarcinoma of bile duct origin with a 26 mm lung tumor, a 12 mm brain tumor and a 4-fold higher level of CA 19-9; Time D (2018 November): VATS lobectomy and SRT for brain tumor; and Time E (2019 January): Stable condition with normal level of CA 19-9.

Figure 6

Magnetic resonance imaging of a metastatic lung tumor in the left upper lobe (A) and suspected metastatic brain tumor on the right frontal lobe (B).

Figure 7

Macroscopic findings of lung-resected specimens.

Figure 8

Microscopic images of lung metastasis. A and B: Histologic appearance showed a well-demarcated nodule with marked necrosis in the center of the tumor (A: magnification × 20, B: magnification × 400). At high power magnification, there were eosinophilic, tall, columnar cells with nuclear pseudostratification. C-E: Immunohistological staining showed that the tumor cells were positive for CK7 (Panel C), CK20 (Panel D) and CDX2 (Panel E); F: Immunohistological staining showed that the tumor cells were negative for TTF-1.