Intraductal Papillary Mucinous Carcinoma Research Articles

Recurrent Invasive Intraductal Papillary Mucinous Carcinoma of the Pancreas Mimicking Pott Disease: Review of the Literature

Specific information regarding intraductal papillary mucinous neoplasm (IPMN) recurrence is limited because most series are small and the follow-up interval is short. We report an unusual case of cancer recurrence in an 86-year-old woman who had undergone a pancreaticoduodenectomy for a large IPMN in the head of the pancreas. Final pathological evaluation of the resected pancreas found a component of in situ and invasive ductal adenocarcinoma without lymph node involvement. The patient did not receive postoperative chemotherapy and was monitored with transaxial imaging at regular intervals. Nine years later, the patient developed a retroperitoneal psoas abscess that was misdiagnosed as tuberculous spondylitis (Pott disease) but was proven to be recurrent mucinous adenocarcinoma of pancreatic origin. In our review of published reports in patients who underwent resection of IPMN, we found a combined mean recurrence rate of approximately 20%.

Imaging Features of Large Intraductal Papillary Mucinous Carcinoma of the Pancreatic Tail

To the Editor:Pancreatic mucin-producing tumors, such as intraductal papillary mucinous tumor (IPMT) and mucinous cystic tumor (MCT),1,2 are good candidates for surgical resection because of their low-grade malignant potential. It is sometimes difficult to differentiate between IPMT and MCT on imagi

Pseudomyxoma Peritonei Caused by Acute Pancreatitis in Intraductal Papillary Mucinous Carcinoma of the Pancreas

Pseudomyxoma Peritonei Caused by Acute Pancreatitis in Intraductal Papillary Mucinous Carcinoma of the Pancreas

Advantage of pancreaticogastrostomy in detecting recurrent intraductal papillary mucinous carcinoma in the remnant pancreas: A case of successful re-resection after pancreaticoduodenectomy

Recently there has been an increase in the number of case reports detailing the recurrence of cancer in the pancreatic remnants following surgical resection of intraductal papillary mucinous carcinoma (IPMC) of the pancreas. A case is presented here to indicate the advantage of pancreaticogastrostomy (PG) in terms of postoperative follow-up after pancreaticoduodenectomy (PD) for IPMC. A 68-year-old man underwent PD for IPMC of the pancreatic head, and the cut margin of the pancreatic duct was diagnosed as having no cancer but moderately dysplastic epithelium by an intraoperative frozen section of histology. Thus, we decided to proceed with a PG rather than pancreaticojejunostomy (PJ) in order to facilitate easier postoperative examinations. Eight years and 6 months later, during a routine follow-up examination, duct dilation of the remnant pancreas was detected by magnetic resonance imaging (MRI). Upon examination by endoscopic gastroscopy, the anastomotic site was found to be covered with a large amount of mucin from which we easily obtained both cytologic and biopsied specimens, which subsequently proved positive for cancer. In line with our diagnosis of recurrent IPMC, the patient underwent a second surgery (resection of the remnant pancreas, total pancreatectomy) and postoperative histology confirmed that indeed the patient had experienced recurrent IPMC with no nodal involvement or invasion beyond the pancreatic confines. Based on this experience, we decided to recommend PG for all patients deemed to be at high risk for the recurrence of cancer in the pancreatic remnants following PD for IPMC of the pancreatic head.

Differential diagnosis of pancreatic tumors using ultrasound contrast imaging

The development of equipment and contrast agents for ultrasound imaging has contributed to major breakthroughs in the diagnosis of pancreatic tumors. We aimed to determine the diagnostic effectiveness of contrast ultrasound with Levovist, using the Agent Detection Imaging (ADI) technique, in 50 patients with pancreatic tumors. We studied 50 cases of histologically proven pancreatic disease; 39 carcinomas, 2 endocrine tumors, 4 intraductal papillary mucinous carcinomas (IPMCs), and 5 cases of tumor-forming pancreatitis (TFP). Vascular and perfusion images of contrast-enhanced ultrasound (CE-US) were used for the evaluation of tumor vascularity and parenchymal perfusion of the tumor, respectively. The hemodynamics of the tumor, and the diagnostic capacity of CE-US were compared with those shown by computed tomography (CT). The histological diagnosis in all cases was made from either biopsy or surgical specimens. Thirty-four cases of pancreatic carcinoma (87%) showed a hypovascular and hypoperfusion pattern. The endocrine tumors showed a heterogeneous hypervascular and hyperperfusion pattern. All IPMC cases showed hypervascularity of the nodules inside the tumors. TFP showed an isovascular and homogeneous isoperfusion pattern. When tumors showing a hypovascular or hypoperfusion pattern on CE-US were diagnosed as carcinomas, 34 of the 39 carcinomas (87%) fit this criterion, with a 95% confidence interval (CI) of 73%-96%, whereas, on CT, 31 of the 39 were diagnosed as carcinoma; (sensitivity, 79%). The sensitivity and accuracy of CT were inferior to those of CE-US. Results of comparison between the CE-US findings and the histological diagnosis were as follows. The one papillary adenocarcinoma showed a hypervascular and hyperperfusion pattern; the 32 well or moderately differentiated adenocarcinomas showed a hypovascular and hypoperfusion pattern; and in the poorly differentiated adenocarcinomas, 2 cases of scirrhous type showed a hypovascular and hypoperfusion pattern, and the 4 cases of medullary type showed an isovascular and isoperfusion pattern. The differences in vascularity of pancreatic carcinomas depicted by CE-US were associated well with differences in histology. CE-US, by the ADI technique, is useful for the diagnosis of pancreatic tumors.

Intraductal Tubular Neoplasms of the Pancreas

Intraductal neoplasms of the pancreas are generally referred to as intraductal papillary mucin-producing neoplasms (IPMNs), according to the WHO classification system. Herein, we report that morphologic and immunohistochemical features of intraductal tubular carcinoma (ITC) are quite different from those of intraductal papillary mucinous carcinoma (IPMC). We analyzed histogenesis and differentiation of ITC by light microscopy and immunohistochemistry. Histologically, ITC was characterized as an intraductal nodular appearances with a monotonous tubular growth pattern without papillary projection. ITC showed de novo-like appearance without sequential progression usually observed in IPMC, suggesting that ITC is a homogeneous neoplasm. Cuboidal tumor cells in ITC resembled normal pancreatic duct epithelia, and the characteristic growth pattern of ITC replaced that of normal pancreatic duct epithelium. Immunohistochemically, ITC cells were positive for MUC-1 on the apical side of the cell membrane. In contrast to ITC cells, IPMC cells were negative for MUC-1, and ductal adenocarcinoma cells were strongly positive for MUC-1, as was the stroma around the cancer. The immunohistochemical staining pattern of DUPAN-2 resembled that of MUC-1. Interestingly, localization of MUC-1 and DUPAN-2 staining in ITC cells was similar to that in normal pancreatic ductules. ITC cells were negative for MUC-2 and MUC-5AC. In contrast, most IPMC cells were positive for MUC-2 and MUC-5AC. Based on our histologic and immunohistochemical findings, the intraductal pancreatic neoplasm (IPN) can be classified into 2 groups: IPN with gastrointestinal differentiation and IPN with pancreatic duct differentiation. Our present data indicated that ITC cells may arise directly from duct epithelia without progression and possessed pancreatic duct differentiation. On the basis of our data, we suggest that classification of pancreatic neoplasms in the WHO and The Armed Forces Institute of Pathology (AFIP) systems should be reconsidered.

KOC (K Homology Domain Containing Protein Overexpressed in Cancer)

KOC (K homology domain containing protein overexpressed in cancer) is a novel oncofetal RNA-binding protein highly expressed in pancreatic carcinomas. Recently, Corixa Corporation developed a monoclonal antibody specific for KOC that can be used with standard immunohistochemical techniques. The purposes of this study were 1) to assess KOC mRNA expression in pancreatic carcinoma, 2) to determine the pattern of KOC immunoexpression among benign, borderline, and malignant pancreatic epithelial lesions, and 3) to evaluate the utility of the KOC antibody in distinguishing between these entities. mRNA was isolated from fresh pancreatic tissues (19 carcinomas, 2 normal pancreas, 1 chronic pancreatitis) and amplified using standard RT-PCR techniques. Fifteen of 19 (79%) carcinomas overexpressed KOC mRNA relative to non-neoplastic tissue samples and expression increased progressively with tumor stage: the mean copy number of KOC mRNA transcripts was 1.5, 11.1, 31, and 28 for stage I, II, III, and IV carcinomas, respectively, compared with 0.9 and 1 for normal pancreatic tissue and chronic pancreatitis, respectively. Immunostains using the KOC antibody were performed on 50 surgical resection specimens (38 invasive adenocarcinomas, 3 intraductal papillary-mucinous neoplasms, 2 mucinous cystic neoplasms, 7 chronic pancreatitis). KOC staining was present in 37 of 38 (97%) carcinomas: the staining reaction was moderate or strong in 36 of 38 (94%) and present in >50% of the tumor cells in 35 of 38 (92%) cases. Severe dysplasia of the ductal epithelium, present in 19 foci of intraductal papillary mucinous carcinoma, mucinous cystadenocarcinoma, and grade 3 pancreatic intraepithelial neoplasia (PanIN3) showed strong or moderate staining in 15 (79%) cases, whereas foci of mild and moderate dysplasia (intraductal papillary-mucinous neoplasms and mucinous cystic neoplasms with adenoma and/or moderate dysplasia, PanIN1, and PanIN2) were uniformly negative for this marker in 25 and 22 cases, respectively. In the normal pancreas, weak background staining of acini was present in 12 of 50 (24%) cases but was easily distinguishable from the type of staining identified in neoplastic epithelium, and benign ducts and ductules were negative in all cases. Four of 38 (11%) foci of chronic pancreatitis, present in the 7 resections performed for chronic pancreatitis as well as 31 foci of peritumoral chronic pancreatitis, showed weak staining in <10% of the ductules. We conclude that KOC is a sensitive and specific marker for carcinomas and high-grade dysplastic lesions of the pancreatic ductal epithelium. Therefore, immunostains directed against KOC may be of diagnostic utility in the evaluation of pancreatic lesions, particularly when biopsy material is limited.

A case of invasive adenocarcinoma derived from intraductal papillary-mucinous carcinoma showing high MUC 1 expression in non-invasive component: Possible relationship between MUC 1 expression and tumor invasion

A case of invasive adenocarcinoma derived from intraductal papillary-mucinous carcinoma showing high MUC 1 expression in non-invasive component: Possible relationship between MUC 1 expression and tumor invasion

In situ and invasive adenocarcinomas of the gallbladder extending into or arising from Rokitansky-Aschoff sinuses: a clinicopathologic study of 49 cases.

We report 49 cases of gallbladder carcinomas that extended into or originated from Rokitansky-Aschoff sinuses (RAS), all of which were resected by laparoscopic cholecystectomy. Twenty-one tumors were in situ carcinomas that extended along RAS; six in situ carcinomas arose in adenomyomatous hyperplasia and 22 were invasive adenocarcinomas with extension into RAS. Thirty-seven patients were women and 12 men. Forty patients had cholelithiasis. The age of the patients ranged from 55 to 84 years (mean 67 years). All in situ carcinomas were incidental microscopic findings in gallbladders removed for cholelithiasis and/or cholecystitis. No patient with in situ carcinoma died as a result of the tumor, including two with in situ carcinoma that originated in adenomyomatous hyperplasia and showed microinvasion. In contrast, of 15 patients with invasive well to moderately differentiated adenocarcinoma extending into RAS and invading the muscle layer or subserosal connective tissue, 8 died 2 to 4 years after surgery. Seven patients survived 1 to 8 years after cholecystectomy. Useful clues to separate RAS with in situ carcinoma from tubular neoplastic invasive glands were the following: connection of the epithelial invaginations to the surface epithelium, recognition of normal biliary epithelium admixed with neoplastic epithelium, presence of inspissated bile in long dilated spaces, and lack of invasion to the smooth muscle bundles. In situ carcinoma spreading along RAS consisted of long tubular often dilated structures extending through the intermuscular connective tissue, whereas neoplastic glands were usually small or of medium size that invaded smooth muscle bundles or intermuscular connective tissue. Perineural invasion was seen only in invasive glands located in the subserosal connective tissue. Two cases of in situ carcinoma that arose in adenomyomatous hyperplasia and three invasive adenocarcinomas that were composed predominantly of tall columnar mucin containing cells similar to gastric foveolar cells with varying degrees of atypia and cells with biliary phenotype bear some resemblance to intraductal papillary mucinous carcinoma of the pancreas or to mucinous cystic pancreatic neoplasm. Metaplastic pyloric glands often seen in the muscle layer and subserosal connective tissue maintain their lobular pattern and should not be confused with invasive glands. Our findings indicate that distinction of in situ carcinoma spreading into RAS from tubular neoplastic glands of invasive adenocarcinomas is crucial to determine prognosis in this group of patients with gallbladder carcinoma.

Marker profile of pancreatic intraepithelial neoplasia (PanIN) in intraductal papillary mucinous neoplasms of the pancreas: by-standers or forerunners?

Anti-tumor immunity changes over the course of tumor progression; it is not clear how or when the developing tumor overcomes immune surveillance. Intraductal papillary mucinous neoplasm (IPMN) is an intraepithelial precursor lesion of pancreatic cancer that progresses from adenoma to carcinoma. We investigated when and how the human anti-tumor immune reaction changes during pancreatic tumor development.Using immunohistochemical analysis of cells isolated from patients with IPMN, the numbers of tumor-infiltrating lymphocytes and dendritic cells and the maturation state of dendritic cells in the regional lymph nodes were investigated during tumor progression. Gene expression profiles were compared among epithelial neoplastic cells at each stage of tumor development. Biological functions of the selected gene products were analyzed using syngeneic mouse models.The anti-tumor immune reaction changed from an immune response to immune tolerance between the stages of intraductal papillary mucinous adenoma (IPMA) and intraductal papillary mucinous carcinoma (IPMC). Chemokine (C-X-C motif) ligand 17 (CXCL17) and intercellular adhesion molecule 2 (ICAM2) were involved in immune surveillance during tumor development—their expression levels were up-regulated exclusively in IPMA and disappeared from IPMC. CXCL17 and ICAM2 induced infiltration and accumulation of the tumor epithelial layer by immature myeloid dendritic cells. This was followed by a cellular immune reaction and ICAM2 simultaneously promoted the susceptibility of the tumor cells to cytotoxic T-cell−mediated cytolysis. These processes had a synergistic effect to increase the anti-tumor immune response.Immune surveillance occurs during the early intraepithelial stages of human pancreatic carcinogenesis and is mediated by expression of CXCL17 and ICAM2.

A case of intraductal papillary-mucinous carcinoma diagnosed by arterial flows revealed with endoscopic color Doppler ultrasonography

A case of intraductal papillary-mucinous carcinoma diagnosed by arterial flows revealed with endoscopic color Doppler ultrasonography

Pancreatic Mucinous Noncystic (Colloid) Carcinomas and Intraductal Papillary Mucinous Carcinomas Are Usually Microsatellite Stable

Pancreatic mucinous noncystic (colloid) carcinomas (MNCC) differ from the usual ductal adenocarcinomas in their mucin expression profile and share with many extrapancreatic mucinous carcinomas the expression of MUC2. Because mucinous carcinomas are frequently associated with mutations of the DNA mismatch repair genes, causing them to exhibit the so-called mutator phenotype, we decided to investigate whether MNCCs of the pancreas are characterized by microsatellite instability (MSI). Twelve carcinomas with a mucinous phenotype (8 mucinous noncystic carcinomas, 3 intraductal papillary-mucinous carcinomas with an invasive muconodular component, and 1 ductal adenocarcinoma with an extensive mucinous noncystic component) and 11 ductal adenocarcinomas were immunostained with monoclonal antibodies to the mismatch repair gene products hMLH1, hMSH2, and hMSH6. For MSI analysis, DNA was isolated from microdissected tissue, and five primary microsatellites (BAT 25, BAT 26, D5S346, D17S250, and D2S123) were analyzed. MSI was diagnosed in case a novel allele was found, compared with the normal tissue. The criterion for LOH was a 75% signal reduction. All carcinomas tested exhibited nuclear expression of mismatch repair gene products, except for one MNCC that also showed MSI at the molecular level. The data suggest that pancreatic carcinomas with a mucinous phenotype (MUC2+/MUC1−) do not appear to normally exhibit mutations in the mismatch repair genes and therefore differ in their carcinogenesis from those in other organs.

A case of intraductal papillary-mucinous carcinoma without mucin-hypersecretion of the pancreas

A case of intraductal papillary-mucinous carcinoma without mucin-hypersecretion of the pancreas

Genetic alterations in adenoma-carcinoma sequencing of intraductal papillary-mucinous neoplasm of the pancreas

We investigated the adenoma-carcinoma sequence in intraductal papillary-mucinous neoplasm from the aspect of genetic changes. The formalin-fixed paraffin-embedded tumors and surrounding normal pancreatic tissues from patients with 16 intraductal papillary-mucinous adenoma of the pancreas (IPMA) and 10 intraductal papillary-mucinous carcinoma of the pancreas (IPMC) were provided for DNA extraction after microdissection. SSCP-DNA sequencing analysis demonstrated K-ras mutations at codon 12 in 75% of IPMA and 70% of IPMC, while those at codon 13 were observed neither in IPMA nor IPMC. There were no characteristic K-ras mutation types in IPMA and IPMC and no significant differences in incidence of K-ras mutations between the two categories. The frequencies of p53 mutations analyzed by SSCP-DNA sequencing were not high in IPMA (18.8%) and IPMC (30%), showing no significant difference between them. LOHs of APC in IPMA and IPMC were infrequent (6.3 and 20%, respectively) and showed no significant difference in incidence between the two categories. The LOH frequencies of DCC in IPMA and IPMC were 31.3 and 40%, respectively, and were not statistically different from each other. Taken together, genetic changes such as K-ras, p53, APC and DCC mutations may not be associated with adenoma-carcinoma sequence in intraductal papillary-mucinous neoplasm of pancreas.

Very low incidence of microsatellite instability in intraductal papillary-mucinous neoplasm of the pancreas.

Intraductal papillary-mucinous carcinoma (IPMC) of the pancreas, a new entity of pancreatic cancer with a favorable prognosis, has shown a gradual increase in the number of reported cases. Patients with high-frequency microsatellite instability (MSI-H) tumors have been shown to survive longer than those with low-frequency MSI (MSI-L) or microsatellite stable (MSS) tumors in colorectal and gastric cancer. We investigated whether MSI-H in patients with IPMC can contribute to a good prognosis. The formalin-fixed paraffin-embedded tumors and surrounding normal pancreatic tissues from 10 patients with IPMCs and 16 with intraductal papillary-mucinous adenomas (IPMAs) were provided for DNA extraction after microdissection. Polymerase chain reaction (PCR) was carried out using 8 microsatellite primer marker sets. The mixed PCR samples were analyzed using a genetic analyzer. MSI-H was determined by assessment of microsatellite variations in 3 or more of the 8 tested markers. Immunohistochemical staining of the MSI-responsible proteins hMLH1 and hMSH2 was conducted for both the IPMC and IPMA samples. Ten percent of IPMC harbored MSI-H tumors, whereas no MSI-H tumors were detected in the IPMAs. Thirty percent of IPMC tumors and 25% of IPMA tumors showed MSI-L. All IPMCs and IPMAs showed normal expression of both hMLH1 and hMSH2. MSI-H and loss of hMLH1 and hMSH2 are very rare events in both IPMCs and IPMAs. We conclude that a good prognosis for patients with IPMC is not associated with MSI-H.

Surgical management of intraductal papillary mucinous tumor of the pancreas

Background. Intraductal papillary mucinous tumor (IPMT) is a type of pancreatic cystic neoplasm. IPMT consists of intraductal papillary mucinous adenoma (benign IPMT) and intraductal papillary mucinous carcinoma (malignant IPMT). Preoperative diagnosis of malignancy is difficult; the invasiveness and metastatic character are not well known. The purpose of the study was to evaluate the optimal diagnostic and therapeutic strategy of IPMT. Methods. Medical charts of 38 patients with final diagnosis of IPMT in Kyoto University Hospital were retrospectively reviewed. Preoperative imaging, mode of operation, and clinical and histopathologic findings were analyzed. Results. In 38 IPMTs, imaging of localization was correct in 82% by computed tomography, 90% by ultrasonography, 70% by endoscopic retrograde cholangiopancreatography, 100% by magnetic resonance cholangiopancreatography, and 100% by endoscopic ultrasonography. Evaluation of malignancy by endoscopic ultrasonography resulted in sensitivity and specificity of 81% and 78%, respectively. Pylorus-preserving pancreaticoduodenectomy was preferably performed in 20 of 38 patients with IPMT. Twenty-two patients had histologically malignant disease. Half of them had an invasive component in the adjacent stroma. One case of malignant IPMT showed lymph node metastasis, and the patient had no recurrence after pancreaticoduodenectomy with regional lymphadenectomy. No case was diagnosed as margin positive; however, 27% showed a dysplasia with atypia in the epithelial cells of the cut edge of the pancreas. One patient with negative atypia at the cut edge of the pancreas developed a recurrent tumor in the remnant pancreas. Conclusions. The preoperative diagnosis of malignancy is difficult, and 50% of malignant IPMT showed an invasive component. Thus, radical resection of the pancreas with regional lymph node dissection should be the choice of treatment. Lymph node metastasis and intraductal distant invasion should be carefully managed in the surgical treatment of these lesions. (Surgery 2002;132:80-5.)

Expression of cyclooxygenase-2 and vascular endothelial growth factor in pancreatic tumors

Cyclooxygenase (COX)-2 and vascular endothelial growth factor (VEGF) have been reported to be significantly related to carcinogenesis or progression of various cancers. However, there has been no report on the relation between COX-2 and VEGF overexpression in pancreatic tumors. We investigated the overexpression of COX-2 and VEGF immunohistochemically in intraductal papillary-mucinous tumors (IPMT) and invasive ductal carcinoma (IDC) and examined the relationship with clinicopathological factors and the correlation between these immunoactivities in IPMT and IDC. In IPMT, the positive rates of COX-2 overexpression were 0% in 10 areas of hyperplasia, 54.5% of adenoma, 83.3% of intraductal areas of adenocarcinoma, and 66.7% of invasive areas of adenocarcinoma. On the contrary, 47.8% of IDC were positive for COX-2 overexpression. The positive rates of VEGF in IPMT were 10% in areas of hyperplasia, 54.5% of adenoma, 66.7% of intraductal areas of adenocarcinoma and 66.7% of invasive areas of adenocarcinoma. However, in IDC it was 47.8%. Only lymph node metastasis correlated significantly with VEGF overexpression (p=0.04), while the other factors had no significant relationships with either COX-2 or VEGF overexpression. There was a statistically significant correlation between COX-2 and VEGF overexpression in IPMT (p<0.001), in 5 patients with adenoma of which both COX-2 and VEGF were stained in almost exactly the same locations. On the contrary, COX-2 and VEGF overexpression had no statistically significant relationship in IDC. In conclusion, we demonstrate evidence of COX-2 and VEGF overexpression in human pancreatic tumors. Chemoprevention via the suppression of angiogenesis by means of COX-2 inhibitor may be more effective in IPMT than in IDC, because of the strong correlation of both factors especially in IPMT.

Aberrant p16(INK4A) and DPC4/Smad4 expression in intraductal papillary mucinous tumours of the pancreas is associated with invasive ductal adenocarcinoma.

Intraductal papillary mucinous tumours (IPMT) of the pancreas constitute a unique pathological entity with an overall incidence of associated invasive malignancy of 20%. The malignant potential of an individual IPMT cannot be accurately predicted. Preoperative estimation of the risk of associated invasive malignancy with IPMT would be of significant clinical benefit. As aberrations in cell cycle regulatory genes are associated with the progression of precursor pancreatic ductal lesions to invasive adenocarcinoma, we examined expression of key cell cycle regulatory genes in the cyclin D1/retinoblastoma pathway and the transforming growth factor beta/Smad4 signalling pathway in a cohort of patients with surgically resected IPMT. Sections of formalin fixed paraffin embedded pancreatic tissue from a cohort of 18 patients with IPMT were examined using immunohistochemistry for protein expression of cell cycle regulatory genes p16(INK4A), p21(CIP1), p27(KIP1), cyclin D1, pRb, and p53, as well as the cell signalling molecule Smad4. A comparison of expression levels was made between adenoma/borderline IPMT (10 patients) and intraductal papillary mucinous carcinoma (IPMC) (eight patients, four of whom harboured invasive carcinoma). Statistical analysis was performed using the chi(2) and Fisher's exact tests. Aberrant expression of the proteins examined increased in frequency from adenoma/borderline IPMT to IPMC. Specifically, there was a significantly greater incidence of loss of p16(INK4A) expression in IPMC: 8/8 lesions (100%) compared with 1/10 (10%) adenoma/borderline IPMT (p<0.001). Similarly, loss of Smad4 expression was associated with IPMC: 3/8 (38%) versus adenoma/borderline IPMT 0/10 (p<0.03). Loss of Smad4 expression within the IPMT was the best marker for the presence of invasive carcinoma (p<0.001). These data indicate that loss of p16(INK4A) and Smad4 expression occur more frequently in IPMC alone, or with associated invasive carcinoma, compared with adenoma/borderline IPMT. Aberrant protein expression of these cell cycle regulatory genes in IPMT and pancreatic intraepithelial neoplasia in the current model of pancreatic cancer progression suggest similarities in their development and may also represent the subsequent risk of invasive carcinoma.

A Case with Long-term survival after undergoing total pancreatectomy for intraductal papillary-mucinous carcinoma

A Case with Long-term survival after undergoing total pancreatectomy for intraductal papillary-mucinous carcinoma

Noninvasive and minimally invasive papillary carcinomas of the extrahepatic bile ducts.

Adenocarcinomas of the extrahepatic bile ducts (EBD) are uncommon neoplasms that are morphologically heterogenous and associated with a poor prognosis. Papillary carcinomas of the EBD, however, appear to follow a much less aggressive clinical course. The authors reviewed the clinical records of nine patients with papillary carcinoma of the EBD, analyzed the microscopic features, and selected immunohistochemical reactivity (p53 and MIB-1) that might correlate with patient survival. Six patients were male and three were female, with a mean age of 65 years (range, 48-83 years). The clinical presentation of disease in these patients was similar to that reported for conventional adenocarcinoma of EBD. According to their cell phenotypes, these papillary carcinomas were classified as biliary type (7 cases) and intestinal type (2 cases). Most were located in the common bile duct and were well differentiated (7 cases). Five showed minimal expansile invasion into the ductal wall and four were noninvasive. Five patients were treated with a Whipple operation, three underwent segmental resections, and one underwent a left hepatic lobectomy. One patient died of unrelated causes 16 years after a Whipple operation, and another died of postoperative complications. The remaining 7 patients are alive and disease free 1-13 years after surgery. Noninvasive and minimally invasive papillary carcinomas of the EBD are associated with excellent long term prognosis regardless of their cytologic features or their immunohistochemical reactivity to p53 and MIB-1. These tumors should be distinguished from biliary papillomatosis, intraductal papillary mucinous carcinomas of the pancreas extending into the bile ducts, papillary adenomas, and papillary hyperplasia.