Intraductal oncocytic papillary neoplasm arising in Peutz-Jeghers Syndrome bile duct: a unique case report

Abstract

Background: Peutz-Jeghers syndrome (PJS) is a rare, autosomal dominant disorder caused by germline mutations of STK11/LKB1, with an increased risk of tumors at multiple sites. Intraductal oncocytic papillary neoplasm (IOPN) is a unique subtype of intraductal papillary neoplasm of the bile duct (IPNB) defined by a premalignant neoplasm with intraductal papillary or villous growth of biliary-type epithelium. IOPN has a distinct mutation profile compared with both IPNB and intraductal papillary mucinous neoplasm (IPMN).

Case presentation: We herein describe the case of a 44-year-old woman who presented as polyps in the intestinal lumen of sigmoid colon and a 3.1 × 2.1 cm mass in the left lobe of liver. Gross feature revealed a cystic papillary mass and the neoplasm had a clear boundary with the surrounding liver tissue. Histology revealed complex papillary structures, a small amount of fine fibrovascular cores and immunohistochemistry showed extensive positive for MUC5AC, MUC6, CD117. Therefore, histological and immunohistochemical examination of the liver tumor suggested the diagnosis of IOPN. Next-generation sequencing (NGS) revealed other than STK11 germline mutation, the tumor also harbors GNAS somatic mutation at codon 478 and EGFR amplification.

Conclusion: To our knowledge, this is the first report of IOPN arising in PJS. This case enlarges the spectrum of PJS related tumors and genetic rearrangements in IOPN.

Keywords: EGFR; GNAS; Intraductal oncocytic papillary neoplasm; Peutz-Jeghers syndrome; STK11.

Fig. 1

Pelvic CT and Abdominal MRI from the case and gross features of the neoplasm. a Pelvic CT showed nodular soft tissue shadow in the intestinal lumen of sigmoid colon, surrounded by high-density contrast agent. Red arrow indicates designate polyps. b Abdominal MRI showed a round low-density mass in the left lobe of liver with a clear border. Red arrow indicates designate IOPN. c Macroscopically, the neoplasm had a clear boundary with the surrounding liver tissue. Red arrow indicates designate IOPN

Fig. 2

Histological and Immunohistochemical features of the neoplasm. a The bile duct wall and surrounding liver tissue were not invaded. (Scale bar = 1000 μm). b The neoplasm shows complex papillary structures, fine fibrovascular stalks. (Scale bar = 100 μm). c The tumor cells were abundant eosinophilic granular cytoplasm, round or oval nuclei, clear nucleoli. (Scale bar = 50 μm). d-h Tumor cells were positive for MUC5AC (d), MUC6 (e), CD117 (f), HepPar-1 (g) and the Ki-67 (h) index is relatively low. (All scale bars = 100 μm). i LKB1 staining was negative in the tumor cells. (Scale bar = 100 μm)

Fig. 3

Molecular profile of the IOPN described in this case. a-c Schematic illustration of STK11 (a) mutation, GNAS (b) mutation and EGFR (c) amplification. d The sequencing result showed STK11 c.924G > A (p.W308*), exon 8 in 57.39% of 1157 reads mutation. e The sequencing result showed GNAS c.1433G > A (p.R478H), exon 1 in 52.5% of 1784 reads mutation. f The sequencing result showed EGFR amplification was 3.69 folds. (Data presented as log2 fold change at the FDR < 0.05)