MPCC was first reported by Chou et al. [9] in 1976; thereafter, the disease concept has been described by Nagino et al. [1]. MPCC is not a pathological but a clinical disease entity characterized by mucin-hypersecretion, although its extent has not been standardized. Several investigators verified that MPCC histologically exhibits an intraductal papillary proliferation along with delicate fibrovascular cores; heterogenous atypia of the tumour cells; and frequent flat intraepithelial lesion around the primary tumour [10, 11]. These features suggest that MPCC is an overlapping disease category with intraductal papillary neoplasm of the bile duct (IPNB) [10, 12–14]. In this report, we used the term MPCC in the historical sense for the detection of the disease. Alternative terminology of IPNB was also possible in this patient, although the definition of IPNB has not been consistent.
Yang et al. [6] showed that the extent of mucin-secretion bears no relationship to the atypia of the tumour cells; some mucin-producing tumours are pathologically diagnosed as adenoma. Onoe et al. [15] also reported that pathologically malignant potentials representing size, tumour depth, or nodal status were comparable between papillary cholangiocarcinomas with mucin-secretion and those without. These observations fail to confirm specific pathological features and, in turn, suggest a morphological variation in MPCC. In fact, Yeh et al. [16] retrospectively analyzed cholangiographic findings in 13 patients with histologically proven MPCC, of which 8 patients had a finding of mucobilia without gross tumour. Surprisingly, one-third of patients with MPCC had occult (radiologically invisible) tumours. Overall, the following three clinical lessons should be considered: first, mucobilia is a sentinel sign of MPCC; second, MPCC exhibits a variety of morphologies; and third, gross neoplasia is unrecognized more frequently than expected. Thus, we should revise our diagnostic strategy to be applicable to patients with a sole sign of mucobilia (occult MPCC).
MPCC exhibits two representative morphologies: ductectatic type and cystic type. The former is defined as a papillary tumour in the dilated intrahepatic bile duct branch that shows disproportional enlargement, and the latter is defined as a papillary tumour within a large liver cyst that communicates with the biliary system [4]. Notably, saturating mucus usually fills not only the diseased cyst but also the communication; therefore, conventional cholangiography has limited value unless specific preparations are performed [17]. In contrast, the presence of mucin never impairs MDCT images, allowing dilated bile ducts to be easily evaluated by multidirectional reconstructions and by paging view on electronic medical records systems. Therefore, MDCT is an important alternative to cholangiography, particularly in occult MPCC.
In the present case, we hypothesized that the occult MPCC was associated with any of the liver cysts (a variation of cystic type MPCC). As the communication between the S1 cyst and the hepatic duct was clearly demonstrated on CT images, the S1 cyst was specified as the target region. Additionally, biopsy samples from the bile duct were all negative for cancer, indicating that the tumour was confined to the cyst and the communication. Based on this limited information, we planned left hepatectomy, caudate lobectomy, and extrahepatic bile duct resection to maximize the chance of R0 resection.
The clinical impact of the remnant carcinoma in situ at the ductal remains a matter of debate; however, our recent study clearly demonstrates the growing nature of the foci, the risk of local disease relapse, and a deteriorating impact on postoperative survival [18]. These biological behaviours, however, are observed only in patients with early stage cholangiocarcinoma. In another words, ductal margin status is a sole prognostic factor in an early stage of the disease (occult MPCC) [19]. The diagnostic utility of the peroral cholangioscopy (POCS) tool has been reported [5, 20, 21]. POCS provides an accurate diagnostic yield regarding intraepithelial neoplasia in the large bile duct. In this study, we unfortunately did not perform POCS, mainly due to the endoscopists’ preference.