Invasive carcinoma of the pancreas derived from intraductal papillary adenocarcinoma without mucin hypersecretion but with changes in the pancreatic duct on pancreatography

We present a case of invasive carcinoma of the pancreas derived from intraductal papillary adenocarcinoma without mucin hypersecretion in a 65-year-old man with a 45-year history of alcohol abuse and a 2-year follow-up of chronic pancreatitis. Two years previously, in May 1998, he was admitted for investigation of abdominal pain. Computed tomography (CT) showed diffuse dilation of the main pancreatic duct with atrophy of the pancreatic parenchyma. Endoscopic retrograde pancreatography (ERP) showed a diffusely dilated main pancreatic duct with irregular side branches in the head of the pancreas. Chronic alcoholic pancreatitis was diagnosed on the basis of the pancreatography findings. The patient was readmitted for investigation of progressive weight loss in August 2000. Serum CA19-9 levels were markedly elevated (750 U/ml) and CT showed enlargement of the head and body of the pancreas. ERP showed irregularity of the main pancreatic duct in the head of the pancreas, and the distal main pancreatic duct (which was dilated on initial ERP examination) was interrupted in the body of the pancreas. Suspected pancreatic carcinoma was diagnosed, and pylorus-preserving pancreatoduodenectomy was performed. Frozen section examination of the cut end of the pancreas revealed ductal carcinoma, and total pancreatoduodenectomy with portal vein resection was performed. Histologically, the resected tumor was diagnosed as an invasive carcinoma derived from intraductal papillary adenocarcinoma without mucin hypersecretion. We recommend observing changes in the pancreatic duct on pancreatography to diagnose invasive carcinoma of the pancreas derived from intraductal papillary adenocarcinoma in a resectable state. Received: February 6, 2002 / Accepted: June 10, 2002 Offprint requests to: S. Ariizumi     

Mixed acinar-endocrine carcinoma of the pancreas with intraductal growth into the main pancreatic duct: Report of a case

The patient was a 75-year-old asymptomatic man, in whom a tumor mass in the pancreatic tail had been found 6 months earlier. Computed tomography revealed a mass 7 cm in diameter, and an enhancement with contrast medium was observed at the periphery and partially inside the mass, but not in most parts of the tumor. Endoscopic retrograde cholangiopancreatography showed a filling defect in the main pancreatic duct. A distal pancreatectomy was performed because of the possibility of a malignant tumor. The tumor consisted of a lobular invasive growth component and a component with intraductal growth into the main pancreatic duct, and histologically the tumor cells had solid acinar to partially trabecular/tubular patterns. Trypsin (an acinic cell marker) expression was widely observed, followed by the expression of chromogranin A (an endocrine cell marker) in about 30% of the tumor cells. The tumor was diagnosed as mixed acinar-endocrine carcinoma according to the WHO classification.     

MRI-cholangiopancreatography characteristics of cystic pancreatic tumors

STUDY AIM: The purpose was to assess the value of MR cholangiopancreatography (MRCP) to evaluate the diagnosis and surgical resectability of pancreatic cystic tumors. PATIENTS AND METHODS: For MRCP, thick RARE and thin HASTE heavily T2-weighted sequences were performed with a 1.5 Tesla MR unit in 42 patients. Diffusion-weighted echo-planar sequences were performed in 16 patients. Surgical and histopathological correlation was obtained in 15 patients. RESULTS: MRCP detected all cystic lesions of the pancreas: 15 intraductal papillary mucinous tumors, 10 serous cystadenomas, 2 benign mucinous cystadenomas, 1 solid pseudopapillary tumor and 14 small cystic lesions (less than 2 cm) with no clinical signs. MRCP provided complete visualization of the pancreatic duct, showed excrescences within the dilated main or branch pancreatic ducts, identified microlacunar mixed and macrolacunar patterns, as well as septa, communications and stenosis, without contrast agent. MRCP did not characterize serous or mucinous cystic lesions. Specific diagnostic criteria of the various types of intraductal papillary mucinous tumors were noted (main duct, branch duct and combined types) and illustrated with the imaging findings necessary for accurate differential diagnosis. CONCLUSION: MRCP is a useful noninvasive and essential method in preoperative staging of cystic tumors of the pancreas; it is a reasonable alternative to endoscopic retrograde cholangiopancreatography and endosonography, as it provides the necessary information for treatment: surgical decision and/or follow-up.     

Invasive ductal adenocarcinoma of the pancreas may originate from the larger pancreatic duct: a study of 13 tumors less than 2 cm in diameter

Background/Purpose We aimed to elucidate the origin/primary site of invasive ductal adenocarcinoma of the pancreas, based on the distribution of intraductal carcinoma components. These components were identified by a mural elastic fiber cuff. Methods Thirteen specimens from patients with invasive ductal adenocarcinoma (microscopically, less than 2 cm in diameter) of the pancreas were studied histopathologically. Variants of invasive ductal adenocarcinoma and intraductal papillary-mucinous carcinoma were excluded. Results Intraductal carcinoma components of invasive ductal adenocarcinoma were found in 12 of the specimens 13 (92%), and were observed within the tumor mass and/or on its boundary, or outside the tumor mass. Intraductal components were characterized by low papillary projections lacking a fibrovascular core, with/without surrounding tubular structures, or by irregular stratification and pleomorphism of the epithelial cells. Invasive components mostly showed a tubular pattern with desmoplasia. The distribution of the intraductal components in the 12 specimens was as follows: in 9 (75%), they were in both the main pancreatic duct and large branch ducts; and in 3, they were in the smaller branch ducts only. Conclusions Invasive ductal adenocarcinomas of the pancreas may originate most frequently from the main pancreatic duct or larger branch ducts, while the smaller ducts are less often the site of cancer origin.     

Pancreatobiliary fistula associated with an intraductal papillary-mucinous pancreatic neoplasm manifesting as obstructive jaundice: Report of a case

We report a pancreatobiliary fistula caused by an intraductal papillary-mucinous pancreatic neoplasm (IPMN), manifesting as obstructive jaundice. Computed tomography showed dilatation of the bile duct and main pancreatic duct, with multiple cystic masses in the head of the pancreas. Endoscopic retrograde pancreatocholangiography showed a patulous papilla with mucin secretion. Contrast enhancement outlined amorphous material obstructing the lower part of the common hepatic duct. Pancreatogram and magnetic resonance cholangiopancreatography showed diffuse dilatation of the main pancreatic duct and side branches without communication with the adjacent organs or duct. We performed pancreaticoduodenectomy for IPMN of the pancreatic head and a tumor-like lesion in the lower common bile duct (CBD). Macroscopically, impacted thick mucus protruded into the CBD from the pancreas via a pancreatobiliary fistula. Histologic examination revealed a pancreatobiliary fistula caused by intraductal papillary-mucinous carcinoma of the pancreas with mucin hypersecretion, an adenoma without interstitial infiltration, and isolated implantation of an IPMN in the bile duct mucosa around the fistula.     

A malignant nonfunctioning pancreatic endocrine tumor with a unique pattern of intraductal growth

The intraductal growth of nonfunctioning pancreatic endocrine tumors (NFPTs) is considered to be rare, and in our survey of the English-language literature, we found only three cases to have been described previously. We herein report the case of a 36-year-old man with a malignant NFPT that uniquely grew within the lumen of the main pancreatic duct (MPD) and completely obstructed the MPD, as shown by endoscopic retrograde pancreatography (ERP). Endoscopic ultrasonography clearly detected the tumor with intraductal growth. In addition, positron emission tomography (PET), using 18F-fluorodeoxyglucose (FDG) and computed tomography (CT) with the same scanner (FDG-PET/CT) showed enhanced uptake of FDG in the tumor. A pylorus-preserving pancreaticoduodenectomy and regional lymphadenectomy were performed under the preoperative diagnosis of an NFPT. Microscopically, positive immunoreactions for synaptophisin and vasoactive intestinal peptide indicated neuroendocrine differentiation of the tumor, while in addition, metastasis to a lymph node along the common hepatic artery was also observed. The patient has survived for 6 months after the surgery without any evidence of recurrence or metastasis. Both ERP and FDG-PET/CT were thus found to be useful for predicting the malignant potential of an NFPT in the preoperative diagnosis.     

Intraductal papillary mucinous neoplasm of the pancreas with a bifid pancreatic duct

A bifid pancreatic duct presenting a major bifurcation in the main pancreatic duct is one of the anatomical variations of the pancreatic ducts. We encountered a 71-year-old female with a 5-cm-diameter branch duct intraductal papillary mucinous neoplasm of the pancreas in whom preoperative endoscopic retrograde pancreatography demonstrated an anomalous bifurcation of the main pancreatic duct at the body of the pancreas. We performed a distal pancreatectomy, instead of a middle pancreatectomy, with a cutting line at the downstream pancreas to the duct bifurcation point. Intraoperative ultrasonography was useful to confirm the exact location of the pancreatic duct bifurcation as well as the tumor extension. The procedure resulted in a favorable outcome without any postoperative complications. Although a bifid pancreatic duct is an unusual anomalous condition, this case should alert surgeons to be aware of such anatomical variants when performing pancreatic resection, otherwise, incurable pancreatic complications may occur postoperatively.     

Intraductal papillary-mucinous tumor of the pancreas head with complete absence of the ventral pancreatic duct of Wirsung

A case of intraductal papillary mucinous tumor of the pancreas with complete absence of the ventral pancreatic duct of Wirsung is presented. A 74-year-old Japanese man was admitted to our hospital because of elevated serum amylase concentration. Abdominal computed tomography (CT) scanning revealed diffuse dilatation of the main pancreatic duct and a diffuse and uncircumscribed area with heterogeneous density in the pancreas head. Endoscopic retrograde cholangiopancreatography revealed that the main pancreatic duct was connected with an accessory papilla and was diffusely dilated, without any irregularity of the duct wall being observed in the entire length of the duct. The common bile duct was detected only by cannulation through Vaters papilla, and no pancreatic duct or its communicating branch was found. Some branches, directed to the dorsal portion of the pancreas head, were found arising from the accessory pancreatic duct. Intraductal ultrasound examination performed through the accessory papilla and the common bile duct revealed a small tumor with a heterogeneous echo level in the pancreas head. From these findings, intraductal papillary-mucinous tumor (IPMT) occurring in the pancreas head was diagnosed, and pylorus-preserving pancreaticoduodenectomy was performed. The resected specimen revealed IPMT in the pancreas head. A roentgenographic study of the resected specimen revealed a defect caused by the tumor located in the pancreatic duct connected with the accessory papilla and showed that there was complete absence of the pancreatic duct connected with Vaters papilla. Surgical resection enabled us to completely analyze the duct system of pancreas divisum. Although it is not known whether there is a relationship between the pathogenesis of IPMT and embryological anomaly of the pancreatic duct system, this case may provide an insight into the pathogenesis of IPMT.     

保留十二指肠的胰头近全切除术治疗胰头部良性肿瘤

目的:探讨保留十二指肠的胰头近全切除术治疗胰头部良性肿瘤的价值。
方法:回顾性分析2004年1月—2009年12月4例施行保留十二指肠的胰头近全切除术患者的临床资料,均保留了胃肠道的完整性、肝外胆道、胆囊和Oddi括约肌的功能,仅在壶腹周围和胆管后方保留有少量胰腺组织。
结果:病理证实1例为导管内乳头状黏液瘤,1例为内分泌肿瘤,2例为实性假乳头状瘤。术后2例发生胰瘘,经过非手术治疗治愈。围手术期无死亡。随访8~20个月,均未发现复发征象。
结论:对于胰头部良性肿瘤,特别是摘除困难的,保留十二指肠的胰头近全切除术是合理的选择。

     

Multifocal intraductal papillary adenocarcinoma of the pancreas: Report of a case

This paper descibes a case of a mucin-producing tumor of the pancreas, histologically diagnosed as multifocal intraductal papillary adenocarcinoma. The patient had a markedly dilated main pancreatic duct, detected by ultrasound (US) and computed tomography (CT), and endoscopy showed a papillary tumor projecting from the patulous orifice of the enlarged papilla of Vater. Several biopsies taken from the tumor indicated a diagnosis of papillary adenocarcinoma. Total pancreatectomy was thus performed, revealing a multifocal papillary tumor growing along the main duct in the head, body, and tail of the pancreas. Microscopically, these multiple tumors were found to be mucin-producing papillary adenocarcinoma of the main and subsidiary pancreatic ducts with nodular and microfocal periductal invasion. The surgical treatment of multifocal tumors, may therefore necessitate total pancreatectomy to achieve curative resection, in some cases.     

Islet neogenesis is stimulated by brief occlusion of the main pancreatic duct.

OBJECTIVE: Current models of islet neogenesis either cause substantial pancreatic damage or continuously stimulate the pancreas, making these models unsuitable for the study of early events that occur in the neogenic process. We aimed to develop a method where the initial events that culminate in increased pancreatic endocrine mass can be studied. DESIGN AND METHODS: Ten 12-week-old female Wistar rats were subjected to a midline laparotomy, the pancreas was isolated and the main pancreatic duct was occluded for 60 seconds. The pancreas was released and carefully relocated within the abdomen. Ten age-, strain- and sex-matched control rats were subjected to a sham operation. The animals were killed 56 days post occlusion, and the pancreata excised and fixed for histological analysis. Body, pancreatic and hepatic weights were noted at termination and serum was taken for analysis. The endocrine-to-exocrine ratio was calculated and the number of endocrine cells in each islet from the sectioned pancreata was counted. RESULTS: Occlusion of the main pancreatic duct for 60 seconds results in an increase in endocrine mass by 80% 56 days post occlusion. This constitutes an increase in endocrine units (1-6 cells), and in small (7-30 cells), medium (31-60 cells) and large (> 60 cells) islets by 85%, 96%, 95% and 71% respectively. CONCLUSION: Brief occlusion of the main pancreatic duct results in an increase in pancreatic endocrine mass. An increase in endocrine units and small islets is indicative of islet neogenesis. Therefore, owing to the briefness of the stimulation, this model can therefore be used to study the initial events that occur during the neogenic process.     

Experimental study of pancreatic duct adenocarcinoma in dog

It may be useful to study the incipient phase and growth behavior of pancreatic cancer if experimental pancreatic carcinoma can be produced in dogs. Twelve mongrel dogs were used. Pancreatography was done every month. N-nitrosobis (2-oxopropyl) amine (BOP) was administered through the drainage tube inserted into the dorsal pancreatic duct in 4 dogs. Macroscopically, atrophy of the pancreas was recognized, but microscopically, no tumors were observed. BOP was injected intraperitoneally in 2 dogs. No tumors were found, and the hepatic necrosis was detected in one dog. N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) was administered into the dorsal pancreatic duct in 2 dogs. Macroscopically, atrophy of the pancreas was recognized, but microscopically, no tumors were observed. ENNG was administered through the drainage tube inserted into the tail portion in 4 dogs. In one dog received a total dose of 595mg of ENNG, duct obstruction was detected by pancreatography and duct adenocarcinoma microscopically was found. Papillary hyperplasia of the epithelium of pancreatic duct was observed in all others. Pancreatic duct adenocarcinoma and papillary hyperplasia were successfully produced in dogs by intraductal administration of ENNG through the pancreatic tail portion. This method seems to be useful for producing experimental pancreatic cancer.     

Intraductal tubular adenoma, pyloric type, of the pancreas: additional observations on a new type of pancreatic neoplasm

Three cases of a distinctive intraductal tubular adenoma, pyloric type, of the main pancreatic duct are reported. The patients, two women and a man, whose ages ranged from 63 to 70 years, complained of abdominal pain attributed to chronic pancreatitis in two patients. The patient with the largest tumor also had symptoms of gastric outlet obstruction. The tumors, two of which arose in the head and one in the tail of the pancreas, led to occlusion and cystic dilatation of the main pancreatic duct. Two adenomas were sessile and one was attached to the wall of the pancreatic duct by a thin fibrous stalk. Microscopically, they were composed of lobules of closely packed tubular glands similar to pyloric glands. In one tumor, nearly all glands were lined by columnar mucin-secreting cells with abundant clear cytoplasm and basally oriented nuclei. In addition to pyloric glands, two adenomas contained glands lined by cells with little or no mucin as well as by pink oncocytic cells. Focal intestinal differentiation was identified in one tumor. Both intracellular and extracellular mucin was detected with the mucicarmine, periodic acid-Schiff, and alcian blue stains. All three adenomas were CK7 positive and CK20 negative. Focal carcinoembryonic antigen linear reactivity along the apical cytoplasm was seen in many cells, but few cells expressed cytoplasmic carcinoembryonic antigen. All three adenomas showed low proliferative activity as measured by the MIB-1 labeling index. The three adenomas were p53 negative and showed loss of DPC4 expression. No endocrine cells were identified in any of the tumors. All patients are alive and symptom free from 4 months to 5 years following surgical treatment.     

Partial pancreatic head resection for intraductal papillary mucinous carcinoma originating in a branch of the duct of santorini

We report partial pancreatic head resection of intraductal papillary mucinous carcinoma originating in a branch of the duct of Santorini. The tumor was located in the ventral part of pancreatic head at a distance from the Wirsung duct. Magnetic resonance cholangiopancreatography accurately showed the communication between the duct of Santorini and the cystic tumor, and was useful for determining the part of the pancreas to be resected. Both the duct of Wirsung and the duct of Santorini were preserved. Partial pancreatic head resection would play an important role in surgical management of low-grade malignant neoplasm.     

Intraductal tubular adenoma of the pancreas, pyloric gland type: a clinicopathologic and immunohistochemical study of 6 cases

The intraductal tubular adenoma (ITA), pyloric gland type, of the pancreas is an uncommon benign tumor, akin to the pyloric gland type adenoma of the gallbladder. We report 6 cases of ITA of the pancreas: 3 male and 3 female aged 50 to 79 years (mean, 63.5 years; median, 65 years); all were examined clinicopathologically. Four patients showed no symptoms, but appetite loss and/or general fatigue presented in two. Grossly, all tumors formed a localized polypoid mass protruding into the lumen of the dilated pancreatic duct. Five of the six tumors were found within the main duct, and the other arose within the branch duct of the pancreas. Microscopically, the tumors were composed of closely packed tubular glands resembling pyloric type glands. They were lined by columnar or cuboidal epithelial cells with foci of mild to moderate dysplastic change. In 2 cases, the adjacent pancreas showed foci of intraductal papillary-mucinous adenoma. Histochemically, the tumors largely showed neutral mucin with a lesser amount of acidic mucin made up mainly of sialomucin. Endocrine cells were found in five tumors. Immunohistochemically, all tumors were labeled with M-GGMC-1 and MUC6, whereas MUC1 and MUC2 stains were negative. Pepsinogen II was positive in 5 tumors; thus, the results displayed a pattern of differentiation similar to those of ordinary gastric pyloric or metaplastic pyloric glands. DPC4 expression was maintained in all tumors and p53-positive nuclei were hardly encountered. All patients are alive with no evidence of disease 3 to 10.5 years after surgical resection.     

Two cases of pancreatic serous cystadenoma

Two cases of operated pancreatic serous cystadenoma were reported with radiological findings. A 67-year-old man was admitted to our hospital complaining of pain in the left upper quadrant. Ultrasonography revealed a mass having a mixed hypoechoic and echogenic pattern at the body of the pancreas. Computed tomography showed a honeycomb appearance. Angiogram showed hypervascularity and ERCP finding showed narrowing of the main pancreatic duct at the body of the pancreas. A 73-year-old man was detected incidentally to have a low density mass with central satellite appearance by computed tomography at the tail of the pancreas during the examination for the renal tumor. The mass showed hypervascularity and A-V shunt angiographically and narrowing of the main pancreatic duct at the tail of the pancreas by ERCP. Both patients underwent distal pancreatectomy. Histopathological findings showed microcystic pattern with single lining epithelial cells which were low cuboidal or flattened and contained intracytoplasmic glycogen.     

Clinicopathological studies on pancreatic carcinoma in totally pancreatectomized cases--with special reference to its intrapancreatic development and the pancreatogram

Histological examination and pancreatography were performed on 31 totally pancreatectomized cases of pancreatic ductal carcinoma, which was divided into four types according to its growth pattern in the pancreas. Pancreatograms of the resected specimens were also classified according to histological findings. Pancreatic carcinoma of Type I (20 cases) was diffusely infiltrating carcinoma with scirrhous stroma which was particularly present between the lobules. The pancreatogram of this type showed constriction of the main pancreatic duct accompanied by dilatation of the distal pancreatic duct. Carcinoma of Type II (6 cases) was diffusely developing in or around the dilated main pancreatic duct or its branches. The pancreatogram of Type II demonstrated the irregularly dilated main pancreatic duct with absence of its branches. Type III (4 cases) was the localized carcinoma with medullary structure. The pancreatogram showed replacement and dilatation of pancreatic ducts without marked stenosis of the main pancreatic duct. Type IV (1 case) was intraductal protruding carcinoma which showed polypoid shadow defects in remarkably dilated pancreatic ducts. The results suggested that a total pancreatectomy should be applied mainly for pancreatic carcinomas of Type II.     

Pathomorphologic study of undifferentiated carcinoma in seven cases: relationship between tumor and pancreatic duct epithelium

Background/purpose  By the time undifferentiated carcinoma is detected, it has formed a large mass, and it is reportedly difficult to pathologically observe its relationship with the pancreatic duct. In this study, we examined the pancreatic ducts of seven patients of surgical samples, and pathomorphologically investigated the relationship between the adenocarcinomatous and sarcomatous components and the pattern of tumor extension. In addition, we evaluated the usefulness of pancreatic juice cytology by comparison with the findings of the main pancreatic duct (MPD). Methods  Seven primary undifferentiated carcinomas of the pancreas (from three male and four female patients with a mean age of 59 years) were analyzed. Histopathological evaluation was based on the WHO diagnostic criteria. Pancreatic juice cytology was performed and evaluated in two patients. Results  All the undifferentiated carcinomas contained adenocarcinomatous and sarcomatous components, and two had a distinct glandular structure. However, we could not pathomorphologically confirm the continuity of the adenomatous with the sarcomatous components in any of the patients. Three undifferentiated carcinomas contained osteoclast-like giant cells. Pathological observation of the tumor and MPD was possible in three of the seven undifferentiated carcinomas. PanIN-3 was observed in the MPD of three patients, suggesting extension into the MPD. In one of these three, the tumor presented intraductal growth in the MPD, and preoperative pancreatic juice cytology revealed atypical cells with osteoclast-like giant cells. In the remaining two, the tumor extraductally compressed the MPD upward. Conclusions  Undifferentiated carcinoma showed two patterns of cancer extension: (1) invasion and expansive growth during the sarcomatous transformation of adenocarcinoma, and (2) intraductal extension. In addition, some undifferentiated carcinomas showed extension in the MPD. Of note, postoperative pancreatic juice cytology may be useful for the diagnosis.     

A Resected Case of Intraductal Tubulopapillary Neoplasm of the Pancreas: Report of a Case

The patient was a 61-year-old male who was referred to our hospital after dilatation of the main pancreatic duct was detected by screening ultrasonography. Computed tomography revealed a protruding lesion measuring 15 mm in diameter within the main pancreatic duct in the head of the pancreas, and magnetic resonance cholangiopancreatography revealed interruption of the duct at the tumor site. We performed pancreaticoduodenectomy under a suspected diagnosis of invasive ductal carcinoma. Gross examination of the resected specimen showed that the tumor invaginated into the main pancreatic duct, and no mucin was found. Histological examination revealed proliferation of high-grade dysplastic cells in a tubulopapillary growth pattern. Immunohistochemically, cytokeratin 7 expression was detected, but not trypsin expression. Based on these morphological features, we diagnosed the tumor as intraductal tubulopapillary neoplasm (ITPN). We report the case with bibliographic consideration, together with a review of intraductal neoplasms of the pancreas encountered at our institution.Key words: Intraductal tubulopapillary neoplasm (ITPN), Intraductal neoplasms of the pancreas, PancreaticoduodenectomyIntraductal tubulopapillary neoplasms (ITPN) were first reported in 2009 by Yamaguchi et al¹ and were adopted by the WHO classification revised in 2010, as a subclass of intraductal neoplasms of the pancreas, along with intraductal papillary mucinous neoplasm (IPMN). Intraductal tubulopapillary neoplasms are rare, accounting for less than 1% of all pancreatic exocrine neoplasms, and are considered to have a better prognosis than conventional pancreatic cancer.¹ Clinicopathologically, ITPNs have features distinct from those of other intraductal neoplasms of the pancreas. Here, we report on a case of ITPN encountered by us who was treated by resection, along with some bibliographic consideration, as well as present a comprehensive review of intraductal neoplasms of the pancreas encountered at our hospital.