Pseudointraductal papillary mucinous neoplasia caused by microscopic periductal endocrine tumors of the pancreas: a report of 3 cases
ABSTRACT Intraductal papillary mucinous neoplasms constitute histologically distinctive pancreatic tumors characterized by cystically dilated pancreatic ducts lined by papillary epithelium, often with extensive mucin production. With increasing awareness of and vigilance for these tumors, there has been a surge in the incidence of intraductal papillary mucinous neoplasms in the last few decades. However, resections of presumed intraductal papillary mucinous neoplasms sometimes reveal other types of cystic lesions. Here we describe 3 cases of small, incidentally identified pancreatic endocrine tumors that focally compressed the main pancreatic duct and presented clinically, radiologically, and grossly as intraductal papillary mucinous neoplasm. The histology of the dilated ducts in all cases lacked convincing features of intraductal papillary mucinous neoplasm, prompting more careful examination of the specimens and eventual identification of small well-differentiated endocrine neoplasms. The constellation of findings represented by pancreatic endocrine neoplasm-associated duct stricture and dilatation can mimic intraductal papillary mucinous neoplasm clinically and pathologically. Awareness of this phenomenon can potentially avoid misdiagnosis of intraductal papillary mucinous neoplasm in such cases.
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ABSTRACT: There are three types of pancreatic neoplasms that predominantly have an intraductal growth pattern: the common, usually cystic, intraductal papillary mucinous neoplasms (IPMNs), the rare usually solid intraductal tubulopapillary neoplasms (ITPNs) and the rare intraductal tubular pyloric gland type adenoma. In addition to these three tumor types, pancreatic neoplasms with a usually solid growth pattern such as acinar cell carcinomas, neuroendocrine tumors and undifferentiated carcinomas, may present, though very rarely, as predominantly intraductally growing neoplasms. IPMNs can be subclassified into main duct and branch duct tumors, into low- and high-grade dysplasia groups, and into tumors with intestinal, pancreatobiliary, oncocytic or gastric cellular differentiation. The intestinal, pancreatobiliary and oncocytic type IPMNs occur predominantly in the main duct of the head of the pancreas and more commonly progress to invasive adenocarcinomas. The gastric type IPMNs are frequently multifocal, occur predominantly in the branch ducts of the uncinate process and have a low risk of progressing to invasive carcinoma. The prognosis for patients with an IPMN depends largely on the subtype and the presence and the stage of an invasive carcinoma. ITPNs are nodular tumors, often in the pancreatic head and composed of densely packed tubular glands. Molecular genetics reveal KRAS, GNAS and RNF43 as the most frequently mutated genes in IPMNs, while ITPNs show wild type KRAS. Recent progress in genetic sequencing of pancreatic neoplasms and the identification of specific genetic mutations, also holds promise for the future development of novel gene based diagnostic tests in intraductal neoplasms of the pancreas that might even been used in preoperative conditions.Seminars in Diagnostic Pathology 09/2014; 31(6). DOI:10.1053/j.semdp.2014.08.005 · 1.80 Impact Factor
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ABSTRACT: In the past decade, the clinico-pathologic characteristics of neuroendocrine tumors (NETs) in the pancreas have been further elucidated. Previously termed "islet cell tumors/carcinomas" or "endocrine neoplasms", they are now called pancreatic NETs (PanNETs). They occur in relatively younger patients and may arise anywhere in the pancreas. Some are associated with von Hippel-Lindau, MEN1, and other syndromes. It is now widely recognized that, with the exception of tumorlets (minute incipient neoplasms) that occur in some syndromes like MEN1, all PanNETs are malignant, albeit low-grade, and although they have a protracted clinical course and overall 10-year survival of 60-70 %, even low-stage and low-grade examples may recur and/or metastasize on long-term follow-up. Per recent consensus guidelines adopted by both European and North American NET Societies (ENETS and NANETs) and WHO-2010, PanNETs are now graded and staged separately, unlike previous classification schemes that used a combination of grade, stage, and adjunct prognosticators in an attempt to define "benign behavior" or "malignant" categories. For staging, the ENETs proposal may be more applicable than CAP/AJCC, which is based on the staging of exocrine tumors. Current grading of PanNETs is based on mitotic activity and ki-67 index. Other promising prognosticators such as necrosis, CK19, c-kit, and others are still under investigation. It has also been recognized that PanNETs have a rather wide morphologic repertoire including oncocytic, pleomorphic, ductulo-insular, sclerosing, and lipid-rich variants. Most PanNETs are diagnosed by fine needle aspiration biopsy, in which single, monotonous plasmacytoid cells with fair amounts of cytoplasm and distinctive neuroendocrine chromatin are diagnostic. Molecular alterations of PanNETs are also very different than that of ductal or acinar tumors. Loss of expression of DAXX and ATRX proteins has been recently identified in 45 %. Along with these improvements, several controversies remain, including grading, value of current cutoff ranges, and the best methods for counting ki-67 index (manual count by computer-captured image may be the most practical for the time being). More important is the controversial use of the term "carcinoma", which was previously employed in WHO-2004 only for invasive and metastatic cases but has now been made synonymous with grade 3 group of tumors. It is becoming clear that grade 3 group comprises two distinct categories: (1) differentiated but proliferatively more active tumors which typically have ki-67 indices in the 20-50 % range and (2) true poorly differentiated NE carcinomas as defined in the lung, with ki-67 typically >50 %. Further studies are needed to address these controversial aspects of PanNETs.Endocrine Pathology 01/2014; 25(1). DOI:10.1007/s12022-013-9295-2 · 1.64 Impact Factor
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ABSTRACT: Pancreaticoduodenectomy (PD) specimens present a challenge for surgical pathologists because of the relative rarity of these specimens, combined with the anatomic complexity. Here, we describe our experience on the orientation, dissection, and sampling of PD specimens for a more practical and accurate evaluation of pancreatic, distal common bile duct (CBD), and ampullary tumors. For orientation of PDs, identification of the "trapezoid," created by the vascular bed at the center, the pancreatic neck margin on the left, and the uncinate margin on the right, is of outmost importance in finding all the pertinent margins of the specimen including the CBD, which is located at the upper right edge of this trapezoid. After orientation, all the margins can be sampled. We submit the uncinate margin entirely as a perpendicular inked margin because this adipose tissue-rich area often reveals subtle satellite carcinomas that are grossly invisible, and, with this approach, the number of R1 resections has doubled in our experience. Then, to ensure proper identification of all lymph nodes (LNs), we utilize the orange-peeling approach, in which the soft tissue surrounding the pancreatic head is shaved off in 7 arbitrarily defined regions, which also serve as shaved samples of the so-called "peripancreatic soft tissue" that defines pT3 in the current American Joint Committee on Cancer TNM. With this approach, our LN count increased from 6 to 14 and LN positivity rate from 50% to 73%. In addition, in 90% of pancreatic ductal adenocarcinomas there are grossly undetected microfoci of carcinoma. For determination of the primary site and the extent of the tumor, we believe bisectioning of the pancreatic head, instead of axial (transverse) slicing, is the most revealing approach. In addition, documentation of the findings in the duodenal surface of the ampulla is crucial for ampullary carcinomas and their recent site-specific categorization into 4 categories. Therefore, we probe both the CBD and the pancreatic duct from distal to the ampulla and cut the pancreatic head to the ampulla at a plane that goes through both ducts. Then, we sample the bisected pancreatic head depending on the findings of the case. For example, for proper staging of ampullary carcinomas, it is imperative to take the sections perpendicular to the duodenal serosa at the "groove" area, as ampullary carcinomas often extend to this region. Amputative (axial) sectioning of the ampulla, although good for documentation of the peri-Oddi spread of the intra-ampullary tumors, unfortunately disallows documentation of mucosal spread of the papilla of Vater tumors (those arising from the edge of the ampulla, where the ducts transition to duodenal mucosa and extending) into the neighboring duodenum. Axial sectioning also often fails to document tumor spread to the "groove" area. In conclusion, knowledge of the gross characteristics of the anatomic hallmarks is essential for proper dissection of PD specimens. The approach described above allows practical and accurate documentation and staging of pancreas, distal CBD, and ampullary cancers.The American journal of surgical pathology 01/2014; 38(4). DOI:10.1097/PAS.0000000000000165 · 4.59 Impact Factor