The purpose of this study was to investigate histological findings at the puncture site on the pancreatic surface by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and to consider the ...potential and clinicopathological significances for microscopic needle tract seeding (NTS) on the pancreatic side. We evaluated 21 cases of pancreatic body or tail cancer for which both EUS-FNA and surgical resection had been performed. A single bleeding spot with shrinkage on the pancreatic anterior surface near the targeted tumor was regarded as the puncture site. The majority of cases showed flat shape and granulation tissue formation. Cancer cell clusters were present in 10 cases (48%), of which 7 cases were considered to potentially have microscopic NTS. There were no significant differences in clinicopathological and prognostic factors between the 7 NTS-positive and 14 NTS-negative cases. This study showed that microscopic NTS on the pancreatic side is not uncommon, although it may not indicate a significant increased risk of local recurrence or dissemination that directly affects the prognosis of patients.
Histopathological diagnosis of pancreatic ductal adenocarcinoma (PDAC) on endoscopic ultrasonography-guided fine-needle biopsy (EUS-FNB) specimens has become the mainstay of preoperative pathological ...diagnosis. However, on EUS-FNB specimens, accurate histopathological evaluation is difficult due to low specimen volume with isolated cancer cells and high contamination of blood, inflammatory and digestive tract cells. In this study, we performed annotations for training sets by expert pancreatic pathologists and trained a deep learning model to assess PDAC on EUS-FNB of the pancreas in histopathological whole-slide images. We obtained a high receiver operator curve area under the curve of 0.984, accuracy of 0.9417, sensitivity of 0.9302 and specificity of 0.9706. Our model was able to accurately detect difficult cases of isolated and low volume cancer cells. If adopted as a supportive system in routine diagnosis of pancreatic EUS-FNB specimens, our model has the potential to aid pathologists diagnose difficult cases.
Ki67 index is now an essential part of classification of pancreatic neuroendocrine tumors. However, its adaptation into daily practice has been fraught with challenges related to counting ...methodology. In this study, three reviewers used four counting methodologies to calculate Ki67 index in 68 well-differentiated pancreatic neuroendocrine tumors: (1) 'eye-ball' estimation, which has been advocated as reliable and is widely used; (2) automated counting by image analyzer; (3) manual eye-counting (eye under a microscope without a grid); and (4) manual count of camera-captured/printed image. Pearson's correlation (R) was used to measure pair-wise correlation among three reviewers using all four methodologies. Average level of agreement was calculated using mean of R values. The results showed that: (1) 'eye-balling' was least expensive and fastest (average time <1 min) but had poor reliability and reproducibility. (2) Automated count was the most expensive and least practical with major impact on turnaround time (limited by machine and personnel accessibility), and, more importantly, had inaccuracies in overcounting unwanted material. (3) Manual eye count had no additional cost, averaged 6 min, but proved impractical and poorly reproducible. (4) Camera-captured/printed image was most reliable, had highest reproducibility, but took longer than 'eye-balling'. In conclusion, based on its comparatively low cost/benefit ratio and reproducibility, camera-captured/printed image appears to be the most practical for calculating Ki67 index. Although automated counting is generally advertised as the gold standard for index calculation, in this study it was not as accurate or cost-effective as camera-captured/printed image and was highly operator-dependent. 'Eye-balling' produces highly inaccurate and unreliable results, and is not recommended for routine use.
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 chromatin reminiscent 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 is also 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.
Neuroendocrine neoplasms (NENs) are rare neoplasms that occur in various organs and present with diverse clinical manifestations. Pathological classification is important in the diagnosis of NENs. ...Treatment strategies must be selected according to the status of differentiation and malignancy by accurately determining whether the neoplasm is functioning or nonfunctioning, degree of disease progression, and presence of metastasis. The newly revised Clinical Practice Guidelines for Gastroenteropancreatic Neuroendocrine Neoplasms (GEP-NENs) comprises 5 chapters—diagnosis, pathology, surgical treatment, medical and multidisciplinary treatment, and multiple endocrine neoplasia type 1 (MEN1)/von Hippel–Lindau (VHL) disease—and includes 51 clinical questions and 19 columns. These guidelines aim to provide direction and practical clinical content for the management of GEP-NEN preferentially based on clinically useful reports. These revised guidelines also refer to the new concept of “neuroendocrine tumor” (NET) grade 3, which is based on the 2017 and 2019 WHO criteria; this includes health insurance coverage of somatostatin receptor scintigraphy for NEN, everolimus for lung and gastrointestinal NET, and lanreotide for GEP-NET. The guidelines also newly refer to the diagnosis, treatment, and surveillance of NEN associated with VHL disease and MEN1. The accuracy of these guidelines has been improved by examining and adopting new evidence obtained after the first edition was published.
Objective Both a percutaneous biopsy and endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) have been widely performed for liver tumors. However, no studies have compared these two biopsy ...methods. Method A retrospective study was conducted using medical records for patients who underwent a liver tumor biopsy from 2012 to 2019. The cases were classified into two groups for a comparison: an ultrasound-guided percutaneous biopsy group (percutaneous group) and an EUS-FNA group (EUS group). Results A total of 106 patients (47 in the percutaneous group and 59 in the EUS group) were included. The final diagnosis was malignant in 100 cases and benign in the remaining 6 cases. While the median lesion diameter was 62 mm in the percutaneous group, it was significantly smaller (34 mm) in the EUS group (p <0.01). The EUS group had more left lobe tumors than right lobe tumors. All cases of caudate lobe tumor (four cases) underwent EUS-FNA. The sensitivity, specificity, and accuracy of the procedure were 95%, 100%, and 96% in the percutaneous group and 100%, 100%, and 100% in the EUS group, respectively showing no significant difference. Adverse events were reported in 17% of the percutaneous group, which was significantly lower than in the EUS group (2%; p <0.01). Conclusion A percutaneous biopsy and EUS-FNA have equivalent diagnostic qualities for liver tumors, although EUS-FNA tends to be associated with fewer adverse events. A complete understanding of the characteristics of each procedure is essential when choosing the best biopsy method for each particular case.
Tumors of the ampulla-pancreatobiliary tract are encountered increasingly; however, their staging can be highly challenging due to lack of familiarity. In this review article, the various issues ...encountered in staging of these tumors at the pathologic level are evaluated and possible solutions for daily practice as well as potential improvements for future staging protocols are discussed. While N-stage parameters have now been well established (the number of lymph nodes required in pancreatoduodenectomies is 12), the T-staging has several issues: for the pancreas, the discovery of small cancers arising in intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs) necessitates the creation of substages of T1 (as T1a, b, and c); lack of proper definition of “peripancreatic soft tissue” and “common bile duct involvement” (as to which part is meant) makes T3 highly subjective. Increasing resectability of main vessels (portal vein) brings the need to redefine a “T” for such cases. For the ampulla, due to factors like anatomic complexity of the region and the under-appreciation of three-dimensional spread of the tumors in this area (in particular, the frequent extension into periduodenal soft tissues and duodenal serosa, which are not addressed in the current system and which require specific grossing approaches to document), the current T-staging lacks reproducibility and clinical relevance, and therefore, major revisions are needed. Recently proposed refined definition and site-specific subclassification of ampullary tumors highlight the areas for improvement. For the extrahepatic bile ducts, the staging schemes that use the depth of invasion may be more practical to circumvent the inconsistencies in the histologic layering of the ducts; better definition of terms like “periductal spread” is needed. For the gallbladder, since many gallbladder cancers are “unapparent” (found in clinically and grossly unsuspected cholecystectomies), establishing proper grossing protocols and adequate sampling are crucial. Since the gallbladder does not have the distinct layering of the other gastrointestinal organs, the definitions of Tis/T1a/T1b lack practicality, and therefore, “early gallbladder carcinoma” category proposed in high-risk regions may have to be recognized instead. Involvement of the Rokitansky–Aschoff sinuses should be a part of the evaluation and management of these early gallbladder cancers; for advanced cancers, documentation of hepatic versus serosal involvement is necessary. In summary, T-staging of ampulla-pancreatobiliary tract tumors has many challenges. Proper grossing and appreciation of histo-anatomic subtleties of this region are crucial in addressing these issues and achieving more applicable and clinically relevant staging systems in the future.
Objective Clinical practice guidelines in Japan recommend surgery for all nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs), regardless of their size or associated symptoms. Because ...pancreatic resection is highly invasive, follow-up for small NF-PNETs is often chosen in clinical practice. However, the natural history of NF-PNET remains poorly understood. We aimed to examine the natural history of pathologically confirmed NF-PNET. Methods This single-center retrospective case series investigated NF-PNETs that were pathologically diagnosed using endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) at our hospital between 2014 and 2018. Patients who were followed up without treatment due to their general condition or their wish were included in the study. Patients' background characteristics, imaging findings, pathological findings, and long-term prognoses were investigated using medical records. Results Overall, 26 patients were diagnosed with NF-PNET by EUS-FNA during the observation period. Of these, 9 patients (3 men and 6 women; median age: 64 years old) were followed up without treatment. All of these patients were asymptomatic, and localization was noticed in 3 cases in the head, body, and tail (1 each), with a median size of 12 (range: 4-18) mm. Neuroendocrine tumor (Grade 1 G1) was pathologically diagnosed in all patients with EUS-FNA. The median observation period was 63 (range: 26-90) months. Tumor growth and distant metastasis were not observed in any of the nine patients who remained asymptomatic. Conclusion Follow-up is a feasible option for asymptomatic NF-PNET ≤20 mm in size with a pathological grade of G1.
Acinar cell carcinoma of the pancreas is a rare tumor with a poor prognosis. Compared to pancreatic ductal adenocarcinoma, its molecular features are poorly known. We studied a total of 11 acinar ...cell carcinomas, including 3 by exome and 4 by target sequencing. Exome sequencing revealed 65 nonsynonymous mutations and 22 indels with a mutation rate of 3.4 mutations/Mb per tumor, on average. By accounting for not only somatic but also germline mutations with loss of the wild-type allele, we identified recurrent mutations of BRCA2 and FAT genes. BRCA2 showed somatic or germline premature termination mutations, with loss of the wild-type allele in 3 of 7 tumors. FAT1, FAT3, and FAT4 showed somatic or germline missense mutations in 4 of 7 tumors. The germline FAT mutations were with loss of the wild-type allele. Loss of BRCA2 expression was observed in 5 of 11 tumors. One patient with a BRCA2-mutated tumor experienced complete remission of liver metastasis following cisplatinum chemotherapy. In conclusion, acinar cell carcinomas show a distinct mutation pattern and often harbor somatic or germline mutations of BRCA2 and FAT genes. This result may warrant assessment of BRCA2 abrogation in patients with the carcinoma to determine their sensitivity to chemotherapy.
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