Intraductal Tubulopapillary Neoplasm Research Articles

A Review of Mucinous Cystic and Intraductal Neoplasms of the Pancreatobiliary Tract.

Although most pancreatic and bile duct neoplasms are solid, mucinous cystic neoplasms and intraductal neoplasms have been increasingly recognized even when clinically silent, thanks to the increased use of sensitive imaging techniques. Cystic and intraductal neoplasms of the pancreas are often resectable and curable and constitute about 5% of all pancreatic neoplasms. Owing to their preinvasive nature and different biology, recognition of these entities remains a major priority. Mucinous cystic neoplasms are histologically and clinically distinct from other cystic pancreatic neoplasms. Pancreatic intraductal neoplasms encompass 3 major entities: intraductal papillary mucinous neoplasm, intraductal oncocytic papillary neoplasm, and intraductal tubulopapillary neoplasm. Intraductal papillary neoplasms of bile ducts are also preinvasive mass-forming neoplasms with both similarities and differences with their pancreatic counterparts. All of these pancreatobiliary neoplasms have diverse and distinctive clinicopathologic, genetic, and prognostic variations. To review the clinical, pathologic, and molecular features of mucinous cystic and intraductal neoplasms of the pancreatobiliary tract. Literature review, diagnostic manuals, and guidelines. This review will briefly describe well-known clinical and pathologic features and will focus on selected recently described aspects of morphology, grading, classification, and genomic alterations of cystic and intraductal neoplasms of the pancreatobiliary tract.

Intraductal neoplasms of the pancreas

The latest WHO classification of tumors of the digestive system (2019) has introduced new concepts for the stratification of intraductal neoplasms of the pancreas, mostly based on molecular genetics and malignant potential. Among them, pancreatic intraepithelial neoplasias (PanINs) and intraductal papillary mucinous neoplasms (IPMN) are both precursors of pancreatic ductal adenocarcinoma, whereas intraductal oncocytic papillary neoplasms (IOPN) and intraductal tubulopapillary neoplasms (ITPN) are usually associated with less aggressive subtypes of pancreatic cancer and therefore have amuch better prognosis. Hence, it is of utmost importance to correctly classify these lesions and to distinguish them from each other as well as from other nonductal types of neoplasms, which can rarely display an intraductal growth, such as neuroendocrine tumors and acinar cell carcinomas. PanIN are microscopic lesions with limited clinical significance. In contrast, all other intraductal neoplasms can be identified as cystic processes and/or solid tumors by means of imaging, thereby setting an indication for apotential surgical resection. This review presents diagnostically relevant aspects of intraductal neoplasms of the pancreas, which are instrumental for the discussion within interdisciplinary tumor boards (resection vs. watch-and-wait strategies) as well as to determine the extent of resection intraoperatively.

Intestinal Autotransplantation and In-Situ Resection of Recurrent Pancreatic Head Intraductal Tubulopapillary Neoplasm with Portal Cavernoma: A Case Report

Intraductal tubulopapillary neoplasm (ITPN) is a new entity of a rare premalignant pancreatic neoplasia, and a radical curative resection is indicated. As with other tumors of the root of the mesentery, the proximity of the lesion to large splanchnic vessels, abdominal aorta, and inferior vena cava poses major risks of a massive hemorrhage and visceral ischemia using conventional surgical techniques. At times, these lesions are amenable for resection using novel techniques developed from organ transplantation. Multivisceral (allo-) transplantation should be considered when radical resection of a benign tumor is likely to compromise portal flow and possibly precipitate acute liver failure, but it may be associated with a long waitlist time and tumor progression. Autotransplantation offers a safe and curative resection of otherwise inoperable tumors in a bloodless field, an excellent exposure, and prevention of warm ischemic injury to the affected viscera, which are then autotransplanted. We describe the en bloc resection of a large and recurrent ITPN of the pancreas, distal stomach, proximal duodenum, transverse colon, superior mesenteric vein, and portal cavernoma, followed by intestinal autotransplantation. A complete tumor resection was achieved with negative margins, adequate cold preservation of the reimplanted intestine, and without significant hemorrhage. The patient was discharged from the hospital 10 days later. The histopathologic examination revealed free-margin resection of ITPN with an associated invasive carcinoma. The patient received adjuvant chemotherapy with folinic acid, fluorouracil, and oxaliplatin and remains disease-free 20 months after surgery. Autotransplantation offers curative resection of otherwise unresectable lesions of the root of the mesentery.

Systematic review of resectable intraductal tubulopapillary neoplasm with special reference to recurrence patterns.

Intraductal tubulopapillary neoplasm is a rare pancreatic tumor. The purpose of this study was to clarify the recurrence type and prognosis in recurrent cases after intraductal tubulopapillary neoplasm resection. PubMed was searched for previous reports on surgical resection of intraductal tubulopapillary neoplasm of the pancreas that were published from 2009 to July 2020. The clinical features obtained from these reports were summarized and analyzed. The clinicopathological data of 35 intraductal tubulopapillary neoplasm cases were obtained. Of these, 21 were males, and 14 were females, with an average age of 57.9years old. Invasive findings were observed in 21 of 35 patients (60%). Recurrence was observed in 11 of the 35 cases (31.4%), including remnant pancreatic recurrence in 6 cases (17.1%) and liver metastasis in 5 cases (14.3%). The tumor size was significantly larger in the liver metastasis group than in the remnant pancreas recurrence group (P = 0.04), and patients with liver metastases tended to have a poorer prognosis than those with remnant pancreas recurrence. The recurrence type of intraductal tubulopapillary neoplasm resection was mainly remnant pancreatic recurrence and liver metastasis recurrence. Total pancreatectomy for remnant pancreatic recurrence may be suitable because of its good prognosis.

Whole Exome Sequencing of Biliary Tubulopapillary Neoplasms Reveals Common Mutations in Chromatin Remodeling Genes.

Simple SummaryIntraductal tubulopapillary neoplasms (ITPN) have recently been described as rare precursor lesions of pancreatic ductal adenocarcinoma and cholangiocarcinoma. Despite a high number of associated invasive adenocarcinomas at the time of diagnosis, patients with ITPN tend to have a much better clinical outcome than those with classical pancreato-biliary adenocarcinoma. Furthermore, rare molecular studies of ITPN show an unexpected lack of hotspot mutations in common driver genes of pancreato-biliary adenocarcinoma, including KRAS. This article reports the first large comprehensive and comparative molecular study of pancreato-biliary ITPN. In the absence of KRAS mutations, we found a high genetic heterogeneity with enrichment in core signaling pathways, including putative actionable genomic targets in one-third of the cases. Whereas, pancreatic ITPN demonstrates a highly distinct genetic profile, differing from classical pancreatic carcinogenesis, biliary ITPN and classical cholangiocarcinoma share common alterations in key genes of the chromatin remodeling pathway, and therefore, appear more closely related than pancreatic ITPN and classical pancreatic ductal adenocarcinoma PDAC.The molecular carcinogenesis of intraductal tubulopapillary neoplasms (ITPN), recently described as rare neoplasms in the pancreato-biliary tract with a favorable prognosis despite a high incidence of associated pancreato-biliary adenocarcinoma, is still poorly understood. To identify driver genes, chromosomal gains and losses, mutational signatures, key signaling pathways, and potential therapeutic targets, the molecular profile of 11 biliary and 6 pancreatic ITPNs, associated with invasive adenocarcinoma in 14/17 cases, are studied by whole exome sequencing (WES). The WES of 17 ITPNs reveals common copy number variants (CNVs) broadly distributed across the genome, with recurrent chromosomal deletions primarily in 1p36 and 9p21 affecting the tumor suppressors CHD5 and CDKN2A, respectively, and gains in 1q affecting the prominent oncogene AKT3. The identified somatic nucleotide variants (SNVs) involve few core signaling pathways despite high genetic heterogeneity with diverse mutational spectra: Chromatin remodeling, the cell cycle, and DNA damage/repair. An OncoKB search identifies putative actionable genomic targets in 35% of the cases (6/17), including recurrent missense mutations of the FGFR2 gene in biliary ITPNs (2/11, 18%). Our results show that somatic SNV in classical cancer genes, typically associated with pancreato-biliary carcinogenesis, were absent (KRAS, IDH1/2, GNAS, and others) to rare (TP53 and SMAD4, 6%, respectively) in ITPNs. Mutational signature pattern analysis reveals a predominance of an age-related pattern. Our findings highlight that biliary ITPN and classical cholangiocarcinoma display commonalities, in particular mutations in genes of the chromatin remodeling pathway, and appear, therefore, more closely related than pancreatic ITPN and classical pancreatic ductal adenocarcinoma.

A case of intraductal tubulopapillary neoplasm of the pancreas in a branch duct: a rare case report and literature review

BackgroundIntraductal tubulopapillary neoplasm (ITPN) of the pancreas is a new disease concept defined by the World Health Organization in 2010. ITPN progresses with tubulopapillary growth in the pancreatic duct and is known to have a fair prognosis. Localization in the main pancreatic duct (MPD) is one characteristic. There are few case reports of ITPN in a branch of the pancreatic duct (BD).Case presentationWe encountered a case of ITPN localized in BD. An 85-year-old man was followed after colonic surgery for rectal carcinoma. An abdominal computed tomography scan revealed a cystic mass in the pancreatic head and further examination was done. A T2 weighted intension picture in magnetic resonance imaging showed a 20 mm cystic lesion with an internal mass of 15 mm. Duodenal papilla were slightly open and endoscopic retrograde pancreatography revealed mild and diffuse dilatation of the main pancreatic duct and mucin in the MPD. In consideration with the image examinations, we diagnosed the tumor as an intraductal papillary mucinous neoplasm with carcinoma because of its large mural nodule (> 10 mm in size) in a cyst. Consequently, a pancreaticoduodenectomy was performed. Macroscopically, a white solid tumor sized 2.5 × 1.8 × 1.0 was identified in the head of the pancreas. The cut surface of the resected pancreas showed a side-branch type intraductal tumor with tubulopapillary architecture without mucin secretion. Immunohistochemical staining was positive for MUC1, and negative for MUC2 and MUC5AC. The final diagnosis was determined to be pancreatic ITPN from BD. At the time of this report (48 months post-surgery), the patient remains disease-free without evidence of recurrence.ConclusionITPNs localized in BD are rare and diagnosis prior to surgery is difficult. In our case, the shape was round, not papillary, and with little fluid. These characteristics are different from a branch duct type IPMN and can be a clue to suspect ITPN in BD.

Cytologic Assessment of Cystic/Intraductal Lesions of the Pancreatobiliary Tract.

Because of new and improved imaging techniques, cystic/intraductal pancreatobiliary tract lesions are increasingly being discovered, and brushings or endoscopic ultrasound/computed tomography/magnetic resonance imaging-guided fine-needle aspiration biopsies from these lesions have become an integral part of pathologists' daily practice. Because patient management has become increasingly conservative, accurate preoperative diagnosis is critical. Cytologic distinction of low-risk (pseudocysts, serous cystadenoma, lymphoepithelial cysts, and squamoid cysts of the pancreatic duct) from high-risk pancreatic cysts (intraductal papillary mucinous neoplasm and mucinous cystic neoplasm) requires incorporation of clinical, radiologic, and cytologic findings, in conjunction with chemical and molecular analysis of cyst fluid. Cytopathologists must ensure appropriate specimen triage, along with cytologic interpretation, cyst classification, and even grading of some (mucinous) cysts. Epithelial atypia in mucinous cysts (intraductal papillary mucinous neoplasm and mucinous cystic neoplasm) has transitioned from a 3-tiered to a 2-tiered classification system, and intraductal oncocytic papillary neoplasms and intraductal tubulopapillary neoplasms have been separately reclassified because of their distinctive clinicopathologic characteristics. Because these lesions may be sampled on brushing or fine-needle aspiration biopsy, knowledge of their cytomorphology is critical. To use an integrated, multidisciplinary approach for the evaluation of cystic/intraductal pancreatobiliary tract lesions (incorporating clinical, radiologic, and cytologic findings with [chemical/molecular] cyst fluid analysis and ancillary stains) for definitive diagnosis and classification. Review of current literature on the cytopathology of cystic/intraductal pancreatobiliary tract lesions. Our knowledge/understanding of recent updates in cystic/intraductal pancreatobiliary lesions can ensure that cytopathologists appropriately triage specimens, judiciously use and interpret ancillary studies, and incorporate the studies into reporting.

Expression of CD117, CK17, CK20, MUC4, villin and mismatch repair deficiency in pancreatic intraductal papillary mucinous neoplasm

Among pancreatic intraductal papillary neoplasms, gastric, intestinal, and pancreatobiliary intraductal papillary mucinous neoplasm (IPMN), intraductal oncocytic papillary neoplasm (IOPN), and intraductal tubulopapillary neoplasm (ITPN) have been defined, differing regarding association with invasive carcinoma and prognosis. Immunohistochemistry (IHC) can help in the distinction of these neoplasms, but a proportion is unclassifiable using recommended markers. Hence, additional markers useful for the typing of pancreatic intraductal papillary neoplasms are needed. The reported frequencies of the different types of IPMNs in surgical series vary to some extent, and such data based on Danish patients are currently lacking. Besides, the role of mismatch repair (MMR) deficiency in these neoplasms has not been fully elucidated. We aimed to evaluate the frequency of different types of pancreatic intraductal papillary neoplasms in a Danish cohort. Furthermore, we aimed to examine the utility of CD117, CK17, CK20, MUC4, and villin as markers for their distinction, in addition to the recommended markers MUC1, MUC2, MUC5AC, MUC6 and CDX2, and to evaluate the frequency of MMR deficiency. We typed 40 consecutively resected pancreatic intraductal papillary neoplasms according to the WHO criteria from 2019. IHC for CD117, CDX2, CK17, CK20, MLH1, MSH2, MSH6, MUC1 (H23), MUC1 (Ma695), MUC2, MUC4, MUC5AC, MUC6, PMS2, and villin was performed and evaluated using a five-tiered semiquantitative scale. A subset of the tumours was examined with PCR for microsatellite instability (MSI). Most tumours were intestinal (40 %) and gastric (40 %) IPMNs, followed by pancreatobiliary (17 %) IPMNs and IOPN (3 %). All cases were MMR proficient. We found a higher expression of MUC4, CK20 and villin in intestinal compared to gastric IPMNs (p < 0.01, p < 0.001 and p < 0.001). MUC4 was more strongly expressed in intestinal compared to pancreatobiliary IPMNs, while the opposite was found for CK17 (p < 0.05 and p < 0.05). IOPN showed strong CD117 expression (score 4), while all gastric IPMNs were negative and 50 % and 29 % of intestinal and pancreatobiliary IPMNs only showed weak expression (score 1). Our data suggest that CK20, MUC4 and villin may aid in the identification of intestinal IPMNs, while CK17 and CD117 may aid in the identification of pancreatobiliary IPMNs and IOPN, in some cases. However, additional studies evaluating these markers in pancreatic intraductal papillary neoplasms are needed.

Preoperative diagnosis of multiple intraductal tubulopapillary neoplasms of the pancreas: dynamic imaging features from endoscopic ultrasound.

Preoperative diagnosis of multiple intraductal tubulopapillary neoplasms of the pancreas: dynamic imaging features from endoscopic ultrasound.

Intraductal tubulopapillary neoplasms with rupture of the distal main pancreatic duct: a case report

BackgroundIntraductal tubulopapillary neoplasm (ITPN) is a rare and newly described entity defined as an intraductal, grossly visible, tubule-forming epithelial neoplasm with high-grade dysplasia and ductal differentiation without overt production of mucin. Because of its rarity, the clinical and molecular aspects of ITPN have not been fully investigated.Case presentationA 73-year-old woman presented to a local hospital with epigastric discomfort and pain. Abdominal multidetector-row computed tomography (MDCT) revealed a 2.5-cm hypovascular tumor in the pancreatic body with distal pancreatic duct dilatation and a slightly low-density area spreading over the ventral side of the pancreatic body. Endoscopic ultrasonography and fine-needle biopsy of the tumor revealed adenocarcinoma of the pancreas. She was referred to our hospital 2 months later. MDCT performed at our hospital showed no significant change in the tumor size or pancreatic duct dilatation. However, the low-density area at the ventral side of the pancreas had shrunk; therefore, this finding was considered to have been an inflammatory change. Under a preoperative diagnosis of resectable pancreatic ductal adenocarcinoma, distal pancreatectomy was performed. The final diagnosis was ITPN with associated invasive carcinoma. Macroscopically and microscopically, the main pancreatic duct (MPD) had ruptured at the distal side of the tumor, and the fistula connected the MPD and extrapancreatic scar tissue.ConclusionsITPN with rupture of the pancreatic duct is extremely rare. In the present case, a sudden increase in the pancreatic duct internal pressure or acute inflammation likely caused the rupture of the MPD.

Intracholecystic tubular non-mucinous neoplasm (ICTN) of the gallbladder: a clinicopathologically distinct, invasion-resistant entity.

Preinvasive tumor-forming gallbladder neoplasms that are composed of small, non-mucinous tubules with complex architecture remain a poorly characterized group. Here, we evaluated the clinicopathological characteristics of this entity. Twenty-eight examples were analyzed. Tumors were invariably pedunculated polyps with thin stalks, often presented as loosely attached intraluminal nodules, with cauliflower architecture (akin to cholesterol polyps) comprised of compact, back-to-back acinar-like, small tubular units with minimal/no cytoplasm showing variable complexity, creating a picture distinct from the other tubular type dysplasia in the gallbladder. Their limited stroma showed distinctive amorphous amyloid-like hyalinization (39%). While some had round nuclei with single prominent nucleoli, others exhibited slightly more elongated nuclei with washed out chromatinreminiscent of papillary thyroid carcinoma. Squamoid/meningothelial-like morules (71%) and subtle neuroendocrine cell clusters (39%) were frequent. The level of cytoarchitectural atypia qualified as high-grade dysplasia (HGD) in all cases, but none were invasive. The background mucosa showed no dysplasia, but cholesterolosis. The majority (n = 8/12) showed diffuse MUC6 expression and lacked MUC5AC expression. Based on these observations, 635 gallbladder carcinomas were re-analyzed for residual/adjacent lesions with entity-defining characteristics disclosed here, and none could be identified. Preinvasive tubular non-mucinous neoplasm of the gallbladder, which we propose to classify as intracholecystic tubular non-mucinous neoplasm, is a clinicopathologically discrete entity, which tends to occur in uninjured gallbladders and in association with cholesterol polyps. By being tubular, non-mucinous and MUC6-positive, it is akin to intraductal tubulopapillary neoplasms of pancreatobiliary tract, but it isalso different in many other aspects. Although their cytoarchitectural complexity warrants an HGD/carcinoma classification, they do not show invasion and their distinct characteristics warrant their separate classification.

Fine-needle-aspiration using forward-viewing echoendoscope for the recurrence of intraductal tubulopapillary neoplasm.

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Biliary intraductal tubule-forming neoplasm: a whole exome sequencing study of MUC5AC-positive and -negative cases.

Biliary intraductal tubular neoplasms that are non-mucinous and negative for mucin 5AC (MUC5AC) are called intraductal tubulopapillary neoplasms (ITPNs). Intraductal tubular neoplasms with mucinous cytoplasm and MUC5AC positivity also occur and their nature remains unclear, although some pathologists may classify these as 'intraductal papillary neoplasms of the bile duct (IPNBs) of gastric type'. This study aimed to elucidate genetic features of biliary intraductal tubular neoplasms. Six resected cases of biliary intraductal neoplasm with>70% tubular configuration were characterised by clinicopathological examination and whole exome sequencing, and the findings obtained were compared between MUC5AC-negative (n=2) and -positive cases (n=4). The intraductal tumours consisted of the pancreatobiliary-type epithelium with high-grade dysplasia arranged in back-to-back tubules. Both of the two MUC5AC-negative cases were non-invasive neoplasms and developed in the liver, whereas all MUC5AC-positive cases had invasive carcinoma and were present in the intrahepatic (n=2), perihilar (n=1) and distal bile ducts (n=1). In an exome-sequencing study, MUC5AC-negative cases harboured mutations in CTNNB1, SF3B1, BAP1 and BRCA1 (one case each). KRAS mutations were observed in three of four MUC5AC-positive cases (75%) but none of the MUC5AC-negative neoplasms. Compared to published data, known driver genes of other intraductal neoplasms of the pancreatobiliary system (e.g. APC, CTNNB1, STK11, GNAS and PIK3CA) were wild-type in all but one MUC5AC-negative case with CTNNB1 mutation. Chromatin modifiers (ARID1A, BAP1 and KMT2C) were also altered in MUC5AC-positive cases, similar to usual cholangiocarcinomas. This exome-sequencing study suggested that MUC5AC-negative biliary ITPNs are genetically distinct from pancreatic ITPNs and IPNBs. They may also biologically differ from MUC5AC-positive tubular neoplasms despite morphological resemblance.

Not every cyst is an intraductal papillary mucosal neoplasm: a case of intraductal tubulopapillary neoplasm

Not every cyst is an intraductal papillary mucosal neoplasm: a case of intraductal tubulopapillary neoplasm

Intraductal Tubulopapillary Neoplasm of the Pancreas and Bile Duct: A Review.

Intraductal tubulopapillary neoplasms (ITPNs) of the pancreas and bile duct are contemporary entities. It is unclear on how to best manage patients with this diagnosis because little is known about its progression to cancer. This review provides an update on the current knowledge of ITPN of the pancreas and bile duct with an overview of clinical, radiological, histopathological, and molecular features, as well as the prognosis and management. Embase and Medline databases search were performed to identify studies that evaluated ITPN of the pancreas and bile duct. The infrequent exposure to this variant poses a diagnostic challenge. The diagnosis of ITPN is almost always made postoperatively because there are no characteristics on radiological studies to distinguish it from other cystic neoplasms of the pancreas. As ITPN has a favorable prognosis, it is crucial to establish an accurate diagnosis and differentiate it from other pancreatic and biliary variants. These neoplasms are considered to be precursor lesions to carcinomas, hence, surgery and close clinical surveillance are recommended. Further studies are essential to elucidate the natural history of ITPN, guide best treatment strategy and determine disease recurrence and survival.

Intraductal Tubulopapillary Neoplasm in the Branch Duct of the Pancreas That Shows Atypical Images

Intraductal Tubulopapillary Neoplasm in the Branch Duct of the Pancreas That Shows Atypical Images

Total pancreatectomy for multifocal pancreatic cancers

Presenter: Hiromichi Ito | Cancer Institute Hospital, Japanese Foundation for Cancer Research Background: It is not uncommon that intraductal neoplasm of the pancreas including intraductal papillary mucinous neoplasm (IPMN) and intraductal tubulopapillary neoplasm (ITPN) involves the entire pancreas, and total pancreatectomy is necessary for patients with such tumors to achieve cure.Herein, we illustrate the case of the patient with multifocal pancreatic cancers who underwent total pancreatectomy. The disease turned out to be derived from IPMN by histologic examination in the resected specimen. Methods: The patient was an 82-year-old woman who presented with epigastric pain and CT showed large pancreatic body mass. The staging work-up revealed at least 5 PET-avid lesions throughout the entire pancreas without extra-pancreatic metastasis, and EUS-FNA confirmed them as adenocarcinoma. Thus, total pancreatectomy was recommended. Results: Upon the exploration, there was no evidence of metastatic disease, and IOUS confirmed all pancreatic lesions identified by preoperative scans. Total pancreatectomy was completed uneventfully in 560 minutes with blood loss of 430 cc. Her postoperative course was uncomplicated. The pathology showed multifocal pancreatic cancers derived from IPMN. ITPN was ruled out by presence of MUC5AC expression on immunohistochemistry. Conclusion: The video described the technical detail of our total pancreatectomy and some useful tricks including SMA-first approach and left kidney mobilization to minimize blood loss and to maintain good exposure for dissection plane in the left side.

Multimodality imaging studies of intraductal tubulopapillary neoplasms of the pancreas.

We aimed to investigate multimodality imaging findings of intraductal tubulopapillary neoplasms (ITPN) of the pancreas. This study was approved by the institutional review board with waived informed consent. A total of eight patients were histopathologically diagnosed with pancreatic ITPN in a single institution over a 6-year period. The imaging findings of dynamic contrast-enhanced computed tomography (CT), magnetic resonance cholangiopancreatography (MRCP), endoscopic ultrasonography (EUS), and positron emission tomography-computed tomography (PET-CT) were reviewed and correlated with clinicopathologic findings. Histopathologically, an invasive carcinoma component was found in 5 of 8 patients (62.5%). The median diameter of the lesions and the main pancreatic ducts were larger in ITPN with invasive carcinoma (19 mm, 13.3-98.0 mm and 13 mm, 5.9-16.3 mm, respectively) than in ITPN without invasive carcinoma (13 mm, 12.7-18.5 mm and 6 mm, 5.6-6.1 mm, respectively), but not significantly (lesions, P = 0.229 and main pancreatic ducts, P = 0.143). Pancreatolithiasis accompanied invasive carcinoma in 3 of 5 patients (60%). Intraductal solid tumors were demonstrated on CT (5/8, 62.5%), MRCP (5/7, 71.4%), and EUS (7/7, 100%). In addition, various imaging findings mimicking chronic autoimmune pancreatitis or pancreatic ductal adenocarcinoma were found in 3 patients (37.5%) on multimodality imaging. The lesion multiplicity and synchronous or metachronous biliary cancer occurred in 3 patients (37.5%), respectively. Patients with associated invasive carcinoma from pancreatic ITPN may have presented a trend toward larger tumor size and dilated pancreatic duct with pancreatoliths, but the difference was not statistically significant. Further studies with a larger number of patients are needed to provide better insight into these findings. Pancreatic ITPN can show various atypical imaging findings as well as typical intraductal solid tumor on multimodality imaging. The presence of lesion multiplicity and synchronous or metachronous biliary cancer can be helpful for assisting with the diagnosis of pancreatic ITPN.

Anatomical, histomorphological and molecular classification of cholangiocarcinoma.

Cholangiocarcinoma constitutes a heterogeneous group of malignancies that can emerge at any point of the biliary tree. Cholangiocarcinoma is classified into intrahepatic, perihilar and distal based on its anatomical location. Histologically, conventional perihilar/distal cholangiocarcinomas are mucin-producing adenocarcinomas or papillary tumours; intrahepatic cholangiocarcinomas are more heterogeneous and can be sub-classified according to the level or size of the displayed bile duct. Cholangiocarcinoma develops through multistep carcinogenesis and is preceded by dysplastic and in situ lesions. Definition and clinical significance of precursor lesions, including biliary intraepithelial neoplasia, intraductal papillary neoplasms of the bile duct, intraductal tubulopapillary neoplasms and mucinous cystic neoplasm, are discussed in this review. A main challenge in diagnosing cholangiocarcinoma is the fact that tumour tissue for histological examination is difficult to obtain. Thus, a major clinical obstacle is the establishment of the correct diagnosis at a tumour stage that is amenable to surgery which still represents the only curable therapeutic option. Current standards, methodology and criteria for diagnosis are discussed. Cholangiocarcinoma represents a heterogeneous tumour with regard to molecular alterations. In intrahepatic subtype, mainly two distinctive morpho-molecular groups can currently be discriminated. Large-duct type intrahepatic cholangiocarcinoma shows a high mutation frequency of oncogenes and tumour suppressor genes, such as KRAS and TP53 while Isocitrate Dehydrogenase 1/2 mutations and Fibroblast Growth Factor Receptor 2-fusions are typically seen in small-duct type tumours. It is most important to ensure the separation of the given anatomical subtypes and to search for distinct subgroups within the subtypes on a molecular and morphological basis.

AB057. P-25. Clinicopathologic features of intraductal tubulopapillary neoplasms of the bile duct

AB057. P-25. Clinicopathologic features of intraductal tubulopapillary neoplasms of the bile duct