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Cancer Imaging : the Official... Sep 2013Several uncommon primary pancreatic tumors, inflammatory conditions, metastasis to the pancreas and peripancreatic masses can mimic the appearance of pancreatic ductal... (Review)
Review
Several uncommon primary pancreatic tumors, inflammatory conditions, metastasis to the pancreas and peripancreatic masses can mimic the appearance of pancreatic ductal adenocarcinoma (PDA). Differentiation between these lesions and PDA can be challenging, due to the overlap in imaging features; however, familiarity with their typical imaging features and clinical presentation may be helpful in their differentiation, as in some cases, invasive diagnostic tests or unnecessary surgery can be avoided. The different pathologies that can mimic PDA include inflammatory conditions such as the various forms of pancreatitis (chronic-focal mass-forming, autoimmune and groove pancreatitis), pancreatic neuroendocrine tumors, solid pseudopapillary tumors, metastasis (solid non-lymphomatous and hematologic), congenital variants (annular pancreas), as well as peripancreatic lesions (accessory spleen, adrenal masses, duodenal masses, lymph nodes and vascular lesions), and certain rare pancreatic tumors (e.g., acinar cell tumors, solid serous tumors, hamartoma and solitary fibrous tumors). The clinical presentation and imaging features of the most commonly encountered mimics of PDA are discussed in this presentation with representative illustrations.
Topics: Adenocarcinoma; Carcinoma, Pancreatic Ductal; Diagnosis, Differential; Humans; Neoplasm Metastasis; Neuroendocrine Tumors; Pancreatic Neoplasms; Pancreatitis; Tomography, X-Ray Computed
PubMed: 24060833
DOI: 10.1102/1470-7330.2013.9012 -
Archives of Pathology & Laboratory... Jul 2015Many common diagnostic dilemmas are encountered in pancreatobiliary pathology, frequently resulting in uncertainty on behalf of the pathologist and referral for a second... (Review)
Review
CONTEXT
Many common diagnostic dilemmas are encountered in pancreatobiliary pathology, frequently resulting in uncertainty on behalf of the pathologist and referral for a second opinion.
OBJECTIVES
To review 4 common diagnostic dilemmas encountered in the practice of pancreatobiliary pathology: (1) pancreatic ductal adenocarcinoma versus chronic pancreatitis; (2) pancreatic ductal carcinoma versus adenocarcinomas arising in the ampulla and intrapancreatic common bile duct; (3) the distinction of uncommon intraductal neoplasms--intraductal oncocytic papillary neoplasm, intraductal tubulopapillary neoplasm, and intraductal acinar cell carcinoma; and (4) intrahepatic cholangiocarcinoma versus metastatic carcinoma.
DATA SOURCES
A review of pertinent literature, along with the authors' personal experience, based on institutional and consultation materials.
CONCLUSIONS
Important diagnostic features for a few challenging problems in pancreatobiliary pathology are reviewed. Careful study of the microscopic features along with awareness of differential diagnoses and diagnostic pitfalls generally allows distinction of these entities. We also highlight established and novel ancillary studies that help to arrive at an accurate diagnosis.
Topics: Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Carcinoma, Pancreatic Ductal; Cholangiocarcinoma; Diagnosis, Differential; Humans; Pancreatic Neoplasms; Pancreatitis, Chronic
PubMed: 26125425
DOI: 10.5858/arpa.2014-0205-RA -
Journal of Proteome Research Feb 2014Sensitive and specific biomarkers for pancreatic cancer are currently unavailable. The high mortality associated with adenocarcinoma of the pancreatic epithelium...
Sensitive and specific biomarkers for pancreatic cancer are currently unavailable. The high mortality associated with adenocarcinoma of the pancreatic epithelium justifies the broadest possible search for new biomarkers that can facilitate early detection or monitor treatment efficacy. Protein glycosylation is altered in many cancers, leading many to propose that glycoproteomic changes may provide suitable biomarkers. In order to assess this possibility for pancreatic cancer, we have performed an in-depth LC-MS/MS analysis of the proteome and MS(n)-based characterization of the N-linked glycome of a small set of pancreatic ductal fluid obtained from normal, pancreatitis, intraductal papillary mucinous neoplasm (IPMN), and pancreatic adenocarcinoma patients. Our results identify a set of seven proteins that were consistently increased in cancer ductal fluid compared to normal (AMYP, PRSS1, GP2-1, CCDC132, REG1A, REG1B, and REG3A) and one protein that was consistently decreased (LIPR2). These proteins are all directly or indirectly associated with the secretory pathway in normal pancreatic cells. Validation of these changes in abundance by Western blotting revealed increased REG protein glycoform diversity in cancer. Characterization of the total N-linked glycome of normal, IPMN, and adenocarcinoma ductal fluid clustered samples into three discrete groups based on the prevalence of six dominant glycans. Within each group, the profiles of less prevalent glycans were able to distinguish normal from cancer on this small set of samples. Our results emphasize that individual variation in protein glycosylation must be considered when assessing the value of a glycoproteomic marker, but also indicate that glycosylation diversity across human subjects can be reduced to simpler clusters of individuals whose N-linked glycans share structural features.
Topics: Adenocarcinoma; Body Fluids; Carbohydrate Metabolism; Carcinoma, Pancreatic Ductal; Chromatography, Reverse-Phase; Glycomics; Humans; Pancreas; Pancreatitis-Associated Proteins; Proteome; Tandem Mass Spectrometry
PubMed: 24328148
DOI: 10.1021/pr400422g -
Cell Death & Disease Jul 2023Heparanase 2 (Hpa2, HPSE2) is a close homolog of heparanase. Hpa2, however, lacks intrinsic heparan sulfate (HS)-degrading activity, the hallmark of heparanase enzymatic...
Heparanase 2 (Hpa2, HPSE2) is a close homolog of heparanase. Hpa2, however, lacks intrinsic heparan sulfate (HS)-degrading activity, the hallmark of heparanase enzymatic activity. Mutations of HPSE2 were identified in patients diagnosed with urofacial syndrome (UFS), a rare genetic disorder that exhibits abnormal facial expression and bladder voiding dysfunction, leading to renal damage and eventually renal failure. In order to reveal the role of HPSE2 in tissue homeostasis, we established a conditional Hpa2-KO mouse. Interestingly, the lack of Hpa2 was associated with a marked decrease in the expression of key pancreatic transcription factors such as PTF1, GATA6, and Mist1. This was associated with a two-fold decrease in pancreas weight, increased pancreatic inflammation, and profound morphological alterations of the pancreas. These include massive accumulation of fat cells, possibly a result of acinar-to-adipocyte transdifferentiation (AAT), as well as acinar-to-ductal metaplasia (ADM), both considered to be pro-tumorigenic. Furthermore, exposing Hpa2-KO but not wild-type mice to a carcinogen (AOM) and pancreatic inflammation (cerulein) resulted in the formation of pancreatic intraepithelial neoplasia (PanIN), lesions that are considered to be precursors of invasive ductal adenocarcinoma of the pancreas (PDAC). These results strongly support the notion that Hpa2 functions as a tumor suppressor. Moreover, Hpa2 is shown here for the first time to play a critical role in the exocrine aspect of the pancreas.
Topics: Mice; Animals; Pancreas; Acinar Cells; Pancreatic Neoplasms; Pancreatitis; Cell Differentiation; Inflammation; Carcinoma, Pancreatic Ductal
PubMed: 37491420
DOI: 10.1038/s41419-023-05990-y -
Theranostics 2021Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal types of cancer due to the relatively late diagnosis and the limited therapeutic options. Current... (Review)
Review
Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal types of cancer due to the relatively late diagnosis and the limited therapeutic options. Current treatment regimens mainly comprise the cytotoxic agents gemcitabine and FOLFIRINOX. These compounds have shown limited efficacy and severe side effects, highlighting the necessity for earlier detection and the development of more effective, and better-tolerated treatments. Although targeted therapies are promising for the treatment of several types of cancer, identification of suitable targets for early diagnosis and targeted therapy of PDAC is challenging. Interestingly, several transmembrane proteins are overexpressed in PDAC cells that show low expression in healthy pancreas and may therefore serve as potential targets for treatment and/or diagnostic purposes. In this review we describe the 11 most promising transmembrane proteins, carefully selected after a thorough literature search. Favorable features and potential applications of each target, as well as the results of the preclinical and clinical studies conducted in the past ten years, are discussed in detail.
Topics: Biomarkers, Tumor; Carcinoma, Pancreatic Ductal; Computational Biology; Humans; Membrane Proteins; Molecular Targeted Therapy; Pancreas; Pancreatic Ducts; Pancreatic Neoplasms
PubMed: 34522225
DOI: 10.7150/thno.60350 -
Archives of Pathology & Laboratory... Mar 2022Pancreatic cystic lesions are increasingly diagnosed. Among other criteria, they are often distinguished in mucinous versus nonmucinous cysts. Mucinous pancreatic cystic...
CONTEXT.—
Pancreatic cystic lesions are increasingly diagnosed. Among other criteria, they are often distinguished in mucinous versus nonmucinous cysts. Mucinous pancreatic cystic lesions have received increasing attention, especially those known as precursors of pancreatic ductal adenocarcinoma. However, the group of nonmucinous cystic lesions of the pancreas includes numerous entities that may pose a diagnostic challenge. Their accurate diagnosis and classification are crucial for adequate patient management.
OBJECTIVE.—
To review the spectrum of nonmucinous cystic lesions of the pancreas, taking into consideration their epidemiology and typical clinical context, their characteristic gross morphology and histomorphology, as well as their immunohistochemical and molecular profile.
DATA SOURCES.—
Literature was searched and reviewed with MEDLINE via PubMed. Macroscopic and microscopic images were obtained from the archives of the Institute of Pathology, Heinrich Heine University and University Hospital of Duesseldorf, Germany.
CONCLUSIONS.—
Nonmucinous cysts of the pancreas comprise numerous, mostly rare entities displaying different biological behaviors. The most frequent are serous cystic neoplasms, solid-pseudopapillary neoplasms, cystic neuroendocrine tumors, and pancreatitis-associated pseudocysts. Accurate diagnosis can be achieved if characteristic clinical context, histomorphology, and immunoprofile are taken into account.
Topics: Carcinoma, Pancreatic Ductal; Humans; Pancreas; Pancreatic Cyst; Pancreatic Ducts; Pancreatic Neoplasms
PubMed: 33503226
DOI: 10.5858/arpa.2020-0446-RA -
Clinical Cancer Research : An Official... Apr 2017The "hallmarks" of pancreatic ductal adenocarcinoma (PDAC) include proliferative, invasive, and metastatic tumor cells and an associated dense desmoplasia comprised of... (Review)
Review
The "hallmarks" of pancreatic ductal adenocarcinoma (PDAC) include proliferative, invasive, and metastatic tumor cells and an associated dense desmoplasia comprised of fibroblasts, pancreatic stellate cells, extracellular matrix, and immune cells. The oncogenically activated pancreatic epithelium and its associated stroma are obligatorily interdependent, with the resulting inflammatory and immunosuppressive microenvironment contributing greatly to the evolution and maintenance of PDAC. The peculiar pancreas-specific tumor phenotype is a consequence of oncogenes hacking the resident pancreas regenerative program, a tissue-specific repair mechanism regulated by discrete super enhancer networks. Defined as genomic regions containing clusters of multiple enhancers, super enhancers play pivotal roles in cell/tissue specification, identity, and maintenance. Hence, interfering with such super enhancer-driven repair networks should exert a disproportionately disruptive effect on tumor versus normal pancreatic tissue. Novel drugs that directly or indirectly inhibit processes regulating epigenetic status and integrity, including those driven by histone deacetylases, histone methyltransferase and hydroxylases, DNA methyltransferases, various metabolic enzymes, and bromodomain and extraterminal motif proteins, have shown the feasibility of disrupting super enhancer-dependent transcription in treating multiple tumor types, including PDAC. The idea that pancreatic adenocarcinomas rely on embedded super enhancer transcriptional mechanisms suggests a vulnerability that can be potentially targeted as novel therapies for this intractable disease.
Topics: Adenocarcinoma; Carcinoma, Pancreatic Ductal; Cell Transformation, Neoplastic; Enhancer Elements, Genetic; Humans; Molecular Targeted Therapy; Pancreas; Pancreatic Stellate Cells; Tumor Microenvironment
PubMed: 28373363
DOI: 10.1158/1078-0432.CCR-16-3275 -
The Turkish Journal of Gastroenterology... Oct 2023Pancreatic and ampullary adenocarcinoma (AAC) are quite resistant to chemotherapy with high metastasis potential. Our study aimed to interpret high-mobility group A...
BACKGROUND/AIMS
Pancreatic and ampullary adenocarcinoma (AAC) are quite resistant to chemotherapy with high metastasis potential. Our study aimed to interpret high-mobility group A protein 2 (HMGA2) expression in benign and precursor pancreatic lesions and pancreatic and ampullary carcinoma and to evaluate its relationship with epithelial-mesenchymal transition (EMT) and clinicopathological parameters.
MATERIALS AND METHODS
In this study, normal-appearing pancreas, chronic pancreatitis (CP), low- (L) and high (H)-grade pancreatic intraepithelial neoplasia (PanIN), pancreatic ductal adenocarcinoma (PDAC), and AAC were evaluated with the immunohistochemical marker of HMGA2. Vimentin and E-cadherin immunohistochemical stains were applied in PDAC and AAC.
RESULTS
The HMGA2 expression was not detected in normal-appearing pancreas, CP, and L-PanIN. A statistically significant expression was observed in PDAC and H-PanIN (P < .001). A statistically significant correlation was found between loss of membranous E-cadherin expression and vimentin positivity and HMGA2 expression (P > .05). The HMGA2 expression was observed to increase the risk of diseaserelated death and decrease overall survival (OS) in AAC and the neoplasia group (P = .002 and P = .016, respectively). There was no significant difference in OS and risk of death in PDAC (P > .05) with respect to HMGA2 positivity.
CONCLUSION
High-mobility group A protein 2 is a helpful immunohistochemical marker in differentiating CP from PDAC. It also plays a role in EMT and may serve as a potential new prognostic agent and therapeutic target in tumors of the periampullary region, especially AAC.
Topics: Humans; Ampulla of Vater; Vimentin; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Adenocarcinoma; Common Bile Duct Neoplasms; Duodenal Neoplasms; Pancreatitis, Chronic; Cadherins
PubMed: 37787719
DOI: 10.5152/tjg.2023.22881 -
Medicine Jul 2017Functional and morphological evolution of remnant pancreas after resection for pancreatic adenocarcinoma is investigated.The medical records of 45 patients who had...
Functional and morphological evolution of remnant pancreas after resection for pancreatic adenocarcinoma is investigated.The medical records of 45 patients who had undergone radical resection for pancreatic adenocarcinoma from March 2010 to September 2013 were reviewed retrospectively. There were 34 patients in the pancreaticoduodenectomy (PD) group and 10 patients in the distal pancreatectomy (DP) group. One patient received total pancreatectomy. The endocrine function was measured using the glucose tolerance index (GTI), which was derived by dividing daily maximum serum glucose fluctuation by daily minimum glucose. Remnant pancreas volume (RPV) was estimated by considering pancreas body and tail as a column, and head as an ellipsoid, respectively. The pancreatic atrophic index (PAI) was defined as the ratio of pancreatic duct width to total pancreas width. Representative indices of each patient were compared before and after resection up to 2 years postoperatively.The area under receiver operating characteristic curve of GTI for diagnosing DM was 0.823 (95% confidence interval, 0.699-0.948, P < .001). Overall, GTI increased on postoperative day 1 (POD#1, mean ± standard deviation, 1.79 ± 1.40 vs preoperative, 1.02 ± 1.41; P = .001), and then decreased by day 7 (0.89 ± 1.16 vs POD#1, P < .001). In the PD group, the GTI on POD#14 became lower than preoperative (0.51 ± 0.38 vs 0.96 ± 1.37; P = .03). PAI in the PD group was significantly lower at 1 month postoperatively (0.22 ± 0.12 vs preoperative, 0.38 ± 0.18; P < .001). In the PD group, RPV was significantly lower at 1 month postoperatively (25.3 ± 18.3 cm vs preoperative, 32.4 ± 20.1 cm; P = .02), due to the resolution of pancreatic duct dilatation. RPV of the DP group showed no significant change. GTI was negatively related to RPV preoperatively (r = -0.317, P = .04), but this correlation disappeared postoperatively (r = -0.044, P = .62).Pancreatic endocrine functional deterioration in pancreatic adenocarcinoma patients may in part be due to pancreatic duct obstruction and dilatation caused by the tumor. After resection, this proportion of endocrine insufficiency is corrected.
Topics: Adenocarcinoma; Aged; Aged, 80 and over; Area Under Curve; Blood Glucose; Female; Follow-Up Studies; Humans; Male; Middle Aged; Organ Size; Pancreas; Pancreatectomy; Pancreatic Neoplasms; Pancreaticoduodenectomy; Postoperative Period; ROC Curve; Retrospective Studies; Treatment Outcome
PubMed: 28700497
DOI: 10.1097/MD.0000000000007495 -
World Journal of Gastroenterology Sep 2013To distinguish acinar cell carcinoma (ACC) from pancreatic adenocarcinoma (AC) by comparing their computed tomography findings. (Comparative Study)
Comparative Study
AIM
To distinguish acinar cell carcinoma (ACC) from pancreatic adenocarcinoma (AC) by comparing their computed tomography findings.
METHODS
Patients with ACC and AC were identified on the basis of results obtained using surgically resected pancreatectomy specimens. The preoperative computer tomographic images of 6 acinar cell carcinoma patients and 67 pancreatic adenocarcinoma patients in 4 phases (non-contrast, arterial, portal venous, and delayed phase) were compared. The scan delay times were 40, 70, and 120 s for each contrast-enhanced phase. The visual pattern, tomographic attenuation value, and time attenuation curve were assessed and compared between AC and ACC cases using the χ² test, Wilcoxon signed-rank test, and Mann Whitney U test.
RESULTS
The adenocarcinomas tended to be hypodense in all 4 phases. The acinar cell carcinomas also tended to be hypodense in the 3 contrast-enhanced phases, although their computed tomographic attenuation values were higher. Further, 5 of the 6 acinar cell carcinomas (83%) were isodense in the non-contrast phase. The time attenuation curve of the adenocarcinomas showed a gradual increase through the 4 phases, and all adenocarcinomas showed peak enhancement during the delayed phase. The time attenuation curve of the acinar cell carcinomas showed peak enhancement during the portal venous phase in 4 cases and during the arterial phase in 2 cases. None of the 6 acinar cell carcinomas showed peak enhancement during the delayed phase.
CONCLUSION
The tumor density in the non-contrast phase and time attenuation curve pattern clearly differ between acinar cell carcinomas and adenocarcinomas, and multidetector-row computed tomography can thus distinguish these tumors.
Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Carcinoma, Acinar Cell; Diagnosis, Differential; Female; Humans; Male; Middle Aged; Multidetector Computed Tomography; Pancreas; Pancreatic Neoplasms; Retrospective Studies
PubMed: 24039366
DOI: 10.3748/wjg.v19.i34.5713