Update on Pathologic Conditions, Imaging Findings, Prevention, and Management of Human Papillomavirus-related Neoplasms.

Human papillomavirus (HPV) is the most common sexually transmitted infection that proliferates in the squamous epithelium and is the most common source of viral-related neoplasms. Low-risk subtypes (HPV-6 and -11) cause respiratory papillomas (laryngeal, tracheal, and bronchial) and condyloma acuminata of the penis, anus, and perineal region (anogenital warts). High-risk subtypes (HPV-16, -18, -31, and -33) are responsible for oropharyngeal squamous cell carcinoma (SCC) that involves the tongue base, tonsils, posterior pharyngeal wall, and larynx and malignancies of the anogenital region (cancers of the cervix, vagina, vulva, penis, and anal canal). Recent studies have increasingly shown a favorable treatment response and substantial differences in the overall prognosis associated with HPV-associated oropharyngeal cancers. Given this fact, oropharyngeal, cervical, and penile SCCs are classified as HPV-associated and HPV-independent cancers in the current World Health Organization classification. Imaging is essential in the early detection, diagnosis, and staging of HPV-associated cancers. Imaging also helps assess treatment response and postoperative complications and is used for long-term surveillance. HPV-associated oropharyngeal SCCs have well-defined borders and solid and cystic nodal metastases at imaging. Updated screening and vaccination guidelines are currently available that have great potential to decrease the overall disease burden and help control this worldwide public health concern. Novel therapeutic strategies, such as immunotherapies, are being explored, and imaging biomarkers that can predict treatment response and prognosis are being investigated; radiologists play a pivotal role in these efforts. ©RSNA, 2024 Supplemental material is available for this article.

Cross-Sectional Imaging Characteristics of Pancreatic Intraductal Oncocytic Papillary Neoplasms.

PURPOSE: Pancreatic intraductal oncocytic papillary neoplasms (IOPN) are rare precursors to pancreatic ductal adenocarcinoma. We report cross-sectional computed tomography and magnetic resonance imaging (where available) findings of pancreatic IOPNs. MATERIALS AND METHODS: Consecutive cases of pancreatic IOPNs identified on pathology between 2008 and 2020 at University of Pittsburgh and Johns Hopkins University were included in the study. Cross-sectional imaging of all patients was reviewed by two subspecialty trained abdominal radiologists. Patient demographics, cross-sectional imaging appearances and growth characteristics were evaluated. RESULTS: In this dual-center study, 14 patients with IOPNs were included. Median age was 64 years, and 64% were male. The median size of the lesions was 5.4 cm (range, 1.4-12.3 cm). All patients had either an enhancing mural nodule (93% of patients) and/or thick internal septations (29%). Thin/imperceptible outer wall was seen in 93%. Main duct was involved in 64% of the cases. Only 14% of the cases did not demonstrate abutment of the main duct. Histologic evaluation of surgical specimen showed high-grade dysplasia without invasive carcinoma in 57% and invasive carcinoma in 43% of cases. Lesions with invasive carcinoma were larger (7.1 cm vs 4.3 cm, P = 0.05) and tended to have larger mural nodule (3.7 cm vs 1.8 cm) compared with those without invasive carcinoma. CONCLUSION: Pancreatic IOPNs are rare cystic premalignant lesions, which among resected cases, are predominantly seen in middle aged men, are often large, have enhancing mural nodules and frequently harbor invasive carcinoma.

Intestinal and Multivisceral Transplantation: Complications.

Advancements in immunosuppression protocols, surgical techniques, and postoperative care in the last few decades have improved outcomes of intestinal transplant patients. Normal immediate postoperative imaging appearance can simulate pathology. Intestinal transplant recipients are prone for several postoperative complications due to the complex surgical technique, which involves multiple anastomoses, and immunogenic nature of the allograft intestine. Imaging plays a crucial role in detection of several major complications including infectious, immunologic, vascular, gastrointestinal, pancreaticobiliary, genitourinary, and neoplastic complications. The awareness of the posttransplant anatomy and normal imaging appearances helps radiologists anticipate and accurately detect posttransplant complications.

Mesotheliomas and Benign Mesothelial Tumors: Update on Pathologic and Imaging Findings.

A diverse spectrum of benign entities and malignant neoplasms originate from the monotonous mesothelium that lines the serosal membranes of the pleural, pericardial, and peritoneal cavities. The mesothelium of myriad sites shows a common origin from the lateral plate mesoderm; primary mesothelial tumors thus demonstrate similar pathogenesis, imaging findings, and treatment options. Significant changes have been made in the 2021 World Health Organization (WHO) classification schemata of the pleural and pericardial tumors on the basis of recent advances in pathology and genetics. While malignant mesotheliomas are biologically aggressive malignancies that occur primarily in patients exposed to asbestos with attendant poor survival rates, well-differentiated papillary mesothelial tumors and adenomatoid tumors charter a benign clinical course with an excellent prognosis. Mesothelioma in situ is a newly characterized entity represented by recurrent unexplained pleural effusions without any identifiable mass at imaging or thoracoscopy. Immunohistochemical markers based on BAP1, MTAP, CDKN2A, and TRAF7 gene mutations help differentiate diffuse mesotheliomas from benign mesothelial proliferations and localized mesotheliomas. Cross-sectional imaging modalities, including US, CT, MRI, and fluorine 18-fluorodeoxyglucose (FDG) PET/CT, permit diagnosis and play a major role in staging and assessing surgical resectability. Imaging studies are invaluable in providing noninvasive and quantitative assessment of tumor response in patients with unresectable disease. Owing to significant overlap in patient characteristics and pathomorphology, accurate diagnosis based on advanced histopathology techniques and genetic abnormalities is imperative for optimal management and prognostication. While patients with nonepithelioid pleural mesotheliomas benefit from immunotherapy, novel targeted therapies for CDKN2A-, NF2-, and BAP1-altered mesotheliomas are under consideration. © RSNA, 2023 Quiz questions for this article are available through the Online Learning Center.

Morphomolecular Classification Update on Hepatocellular Adenoma, Hepatocellular Carcinoma, and Intrahepatic Cholangiocarcinoma.

Hepatocellular adenomas (HCAs), hepatocellular carcinomas (HCCs), and intrahepatic cholangiocarcinomas (iCCAs) are a highly heterogeneous group of liver tumors with diverse pathomolecular features and prognoses. High-throughput gene sequencing techniques have allowed discovery of distinct genetic and molecular underpinnings of these tumors and identified distinct subtypes that demonstrate varied clinicobiologic behaviors, imaging findings, and complications. The combination of histopathologic findings and molecular profiling form the basis for the morphomolecular classification of liver tumors. Distinct HCA subtypes with characteristic imaging findings and complications include HNF1A-inactivated, inflammatory, ß-catenin-activated, ß-catenin-activated inflammatory, and sonic hedgehog HCAs. HCCs can be grouped into proliferative and nonproliferative subtypes. Proliferative HCCs include macrotrabecular-massive, TP53-mutated, scirrhous, clear cell, fibrolamellar, and sarcomatoid HCCs and combined HCC-cholangiocarcinoma. Steatohepatitic and ß-catenin-mutated HCCs constitute the nonproliferative subtypes. iCCAs are classified as small-duct and large-duct types on the basis of the level of bile duct involvement, with significant differences in pathogenesis, molecular signatures, imaging findings, and biologic behaviors. Cross-sectional imaging modalities, including multiphase CT and multiparametric MRI, play an essential role in diagnosis, staging, treatment response assessment, and surveillance. Select imaging phenotypes can be correlated with genetic abnormalities, and identification of surrogate imaging markers may help avoid genetic testing. Improved understanding of morphomolecular features of liver tumors has opened new areas of research in the targeted therapeutics and management guidelines. The purpose of this article is to review imaging findings of select morphomolecular subtypes of HCAs, HCCs, and iCCAs and discuss therapeutic and prognostic implications. Online supplemental material is available for this article. ©RSNA, 2022.

Standardization of MRI Screening and Reporting in Individuals With Elevated Risk of Pancreatic Ductal Adenocarcinoma: Consensus Statement of the PRECEDE Consortium.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies, with a dismal survival rate. Screening the general population for early detection of PDAC is not recommended, but because early detection improves survival, high-risk individuals, defined as those meeting criteria based on a family history of PDAC and/or the presence of known pathogenic germline variant genes with PDAC risk, are recommended to undergo screening with MRI and/or endoscopic ultrasound at regular intervals. The Pancreatic Cancer Early Detection (PRECEDE) Consortium was formed in 2018 and is composed of gastroenterologists, geneticists, pancreatic surgeons, radiologists, statisticians, and researchers from 40 sites in North America, Europe, and Asia. The overarching goal of the PRECEDE Consortium is to facilitate earlier diagnosis of PDAC for high-risk individuals to increase survival of the disease. A standardized MRI protocol and reporting template are needed to enhance the quality of screening examinations, improve consistency of clinical management, and facilitate multiinstitutional research. We present a consensus statement to standardize MRI screening and reporting for individuals with elevated risk of pancreatic cancer.

Gastrointestinal Manifestations of Immunodeficiency: Imaging Spectrum.

There is a wide spectrum of hereditary and acquired immunodeficiency disorders that are characterized by specific abnormalities involving a plethora of humoral, cellular, and phagocytic immunologic pathways. These include distinctive primary immunodeficiency syndromes due to characteristic genetic defects and secondary immunodeficiency syndromes, such as AIDS from HIV infection and therapy-related immunosuppression in patients with cancers or a solid organ or stem cell transplant. The gut mucosa and gut-associated lymphoid tissue (the largest lymphoid organ in the body), along with diverse commensal microbiota, play complex and critical roles in development and modulation of the immune system. Thus, myriad gastrointestinal (GI) symptoms are common in immunocompromised patients and may be due to inflammatory conditions (graft versus host disease, neutropenic enterocolitis, or HIV-related proctocolitis), opportunistic infections (viral, bacterial, fungal, or protozoal), or malignancies (Kaposi sarcoma, lymphoma, posttransplant lymphoproliferative disorder, or anal cancer). GI tract involvement in immunodeficient patients contributes to significant morbidity and mortality. Along with endoscopy and histopathologic evaluation, imaging plays an integral role in detection, localization, characterization, and distinction of GI tract manifestations of various immunodeficiency syndromes and their complications. Select disorders demonstrate characteristic findings at fluoroscopy, CT, US, and MRI that permit timely and accurate diagnosis. While neutropenic enterocolitis affects the terminal ileum and right colon and occurs in patients receiving chemotherapy for hematologic malignancies, Kaposi sarcoma commonly manifests as bull's-eye lesions in the stomach and duodenum. Imaging is invaluable in treatment follow-up and long-term surveillance as well. Online supplemental material is available for this article. ©RSNA, 2022.

Tumor Size Differences Between Preoperative Endoscopic Ultrasound and Postoperative Pathology for Neoadjuvant-Treated Pancreatic Ductal Adenocarcinoma Predict Patient Outcome.

BACKGROUND & AIMS: The assessment of therapeutic response after neoadjuvant treatment and pancreatectomy for pancreatic ductal adenocarcinoma (PDAC) has been an ongoing challenge. Several limitations have been encountered when employing current grading systems for residual tumor. Considering endoscopic ultrasound (EUS) represents a sensitive imaging technique for PDAC, differences in tumor size between preoperative EUS and postoperative pathology after neoadjuvant therapy were hypothesized to represent an improved marker of treatment response. METHODS: For 340 treatment-naïve and 365 neoadjuvant-treated PDACs, EUS and pathologic findings were analyzed and correlated with patient overall survival (OS). A separate group of 200 neoadjuvant-treated PDACs served as a validation cohort for further analysis. RESULTS: Among treatment-naïve PDACs, there was a moderate concordance between EUS imaging and postoperative pathology for tumor size (r = 0.726, P < .001) and AJCC 8th edition T-stage (r = 0.586, P < .001). In the setting of neoadjuvant therapy, a decrease in T-stage correlated with improved 3-year OS rates (50% vs 31%, P < .001). Through recursive partitioning, a cutoff of ≥47% tumor size reduction was also found to be associated with improved OS (67% vs 32%, P < .001). Improved OS using a ≥47% threshold was validated using a separate cohort of neoadjuvant-treated PDACs (72% vs 36%, P < .001). By multivariate analysis, a reduction in tumor size by ≥47% was an independent prognostic factor for improved OS (P = .007). CONCLUSIONS: The difference in tumor size between preoperative EUS imaging and postoperative pathology among neoadjuvant-treated PDAC patients is an important prognostic indicator and may guide subsequent chemotherapeutic management.

Significance of Uncinate Duct Dilatation in IPMNs: A New High-risk Criterion?

OBJECTIVE: To evaluate the significance of UDD in IPMNs. BACKGROUND: The uncinate process of the pancreas has an independent ductal drainage system. International consensus guidelines of IPMNs still consider it as a branch-duct, even though it is the main drainage system for the uncinate process. METHODS: A retrospective review of all surgically treated IPMNs at our institution after 2008 was performed. Preoperative radiological studies were reviewed by an abdominal radiologist who was blinded to the pathological results. In addition to the Fukuoka criteria, presence of UDD was recorded. Using multivariate analysis, the pathological significance of UDD in predicting advanced neoplasia [high grade dysplasia or invasive carcinoma (HGD/ IC)] was determined. RESULTS: Two hundred sixty patients were identified (mean age at diagnosis was 68 years and 49% were females): 122 (47%) had HGD/IC. UDD was noted in 59 (23%), of which 36 (61%) had HGD/IC (P < 0.003). On multivariate analysis, UDD was an independent predictor of HGD/IC (odds ratio = 2.99, P < 0.04). Subgroup analysis on patients with IPMNs confined to the dorsal portion of the gland (n = 161), also demonstrated UDD to be a significant predictor of HGD/IC in those remote lesions (odds ratio: 4.41, P = 0.039). CONCLUSIONS: This is the largest study to evaluate the significance of UDD in IPMNs and shows it to be a high-risk feature. This association persisted for remote IPMNs limited to the dorsal pancreas, suggesting UDD may be associated with an aggressive phenotype even in remote IPMN lesions.

Pancreatic-Portal Vein Fistula: a Rare Diagnosis with Wide-Ranging Complications-13-Year Experience of a Pancreas Center of Excellence.

PURPOSE: To determine factors affecting mortality, and long-term patency of portal vein, in patients with pancreatic-portal vein fistula (PPVF). METHODS: Consecutive cases of PPVF at the University of Pittsburgh Medical Center from 2008 to 2020 were retrospectively identified. Clinical history, imaging studies, management strategies, complications, and long-term outcomes were analyzed. RESULTS: Fourteen patients, representing the largest PPVF cohort reported to date (mean age 58.6 years, 64.3% women, median follow-up 10 months [1-98 months]) were identified. Underlying chronic pancreatitis was seen in 9 (64.3%) patients, while 5 (35.7%) developed PPVF with first attack of acute pancreatitis. PPVF involved proximal main portal vein (MPV) in 10 (78.6%) patients. Of the 5 patients (35.7%) who died, all had occlusive (n=4) or near-occlusive (n=1) PPVF-associated filling defect (FD) in the MPV. Conversely, 7 of 9 survivors (87.5%) had subocclusive FD and patent MPV. In patients with sepsis (n=5), 1 underwent surgical necrosectomy and survived, while 3 of 4 (75%) patients without debridement died. CONCLUSION: Occlusive/near-occlusive PPVF-associated MPV FD, and sepsis, are associated with high mortality rates, while subocclusive MPV FD is associated with survival and long-term MPV patency. PPVF is a potentially life-threatening, and possibly under-diagnosed, entity that warrants early clinical suspicion for timely diagnosis, to facilitate optimal management.

Magnetic Resonance Imaging of Liver Transplant.

MR imaging increasingly has been adopted for follow-up imaging post-liver transplantation and for diagnosis of its complications. These include vascular and biliary complications as well as post-transplant malignancies. Interpretation of postoperative MR imaging should take into account the surgical technique and expected post-transplant changes. Contrast-enhanced MR imaging has high sensitivity for identification of vascular complications. MR cholangiopancreatography on the other hand is the most accurate noninvasive method for evaluation of biliary complications.

Role of standardized reporting and novel imaging markers in chronic pancreatitis.

PURPOSE OF REVIEW: This article reviews recent efforts about standardized imaging features and reporting of chronic pancreatitis and recently published or ongoing imaging studies, which aim to establish novel imaging biomarkers for detection of parenchymal changes seen in chronic pancreatitis. RECENT FINDINGS: New novel MRI techniques are being developed to increase the diagnostic yield of chronic pancreatitis specifically in the early stage. T1 relaxation time, T1 signal intensity ratio and extracellular volume fraction offer potential advantages over conventional cross-sectional imaging, including simplicity of analysis and more objective interpretation of observations allowing population-based comparisons. In addition, standardized definitions and reporting guidelines for chronic pancreatitis based on available evidence and expert consensus have been proposed. These new imaging biomarkers and reporting guidelines are being validated for prognostic/therapeutic assessment of adult patients participating in longitudinal studies of The Consortium for the Study of Chronic Pancreatitis, Diabetes and Pancreatic Cancer. SUMMARY: New imaging biomarkers derived from novel MRI sequences promise a new chapter for diagnosis and severity assessment of chronic pancreatitis; a cross-sectional imaging-based diagnostic criteria for chronic pancreatitis combining ductal and parenchymal findings. Standardized imaging findings and reporting guidelines of chronic pancreatitis would enhance longitudinal assessment of disease severity in clinical trials and improve communication between radiologists and pancreatologists in clinical practice.

Pancreas in Hereditary Syndromes: Cross-sectional Imaging Spectrum.

A wide spectrum of hereditary syndromes predispose patients to distinct pancreatic abnormalities, including cystic lesions, recurrent pancreatitis, ductal adenocarcinoma, nonductal neoplasms, and parenchymal iron deposition. While pancreatic exocrine insufficiency and recurrent pancreatitis are common manifestations in cystic fibrosis and hereditary pancreatitis, pancreatic cysts are seen in von Hippel-Lindau disease, cystic fibrosis, autosomal dominant polycystic kidney disease, and McCune-Albright syndrome. Ductal adenocarcinoma can be seen in many syndromes, including Peutz-Jeghers syndrome, familial atypical multiple mole melanoma syndrome, Lynch syndrome, hereditary breast and ovarian cancer syndrome, Li-Fraumeni syndrome, and familial pancreatic cancer syndrome. Neuroendocrine tumors are commonly seen in multiple endocrine neoplasia type 1 syndrome and von Hippel-Lindau disease. Pancreatoblastoma is an essential component of Beckwith-Wiedemann syndrome. Primary hemochromatosis is characterized by pancreatic iron deposition. Pancreatic pathologic conditions associated with genetic syndromes exhibit characteristic imaging findings. Imaging plays a pivotal role in early detection of these conditions and can positively affect the clinical outcomes of those at risk for pancreatic malignancies. Awareness of the characteristic imaging features, imaging-based screening protocols, and surveillance guidelines is crucial for radiologists to guide appropriate patient management. ©RSNA, 2021.

Groove pancreatitis has a spectrum of severity and can be managed conservatively.

BACKGROUND & AIMS: The natural history of groove pancreatitis is incompletely characterized. Published literature suggests a high rate of surgery. We describe the short- and long-term outcomes in a cohort of patients with groove pancreatitis treated at our institution. METHODS: Medical records of patients hospitalized in the University of Pittsburgh Medical Center system from 2000 to 2014 and diagnosed with groove pancreatitis based on imaging were retrospectively reviewed. Clinical presentation and outcomes during index admission and follow-up were recorded. RESULTS: Forty-eight patients with groove pancreatitis were identified (mean age 53.2 years, 79% male). Seventy-one percent were alcohol abusers and an equal number were cigarette smokers. Prior histories of acute and chronic pancreatitis were noted in 30 (62.5%) and 21 (43.8%), respectively. Forty-four (91.7%) met criteria for acute pancreatitis during their index admission. Alcohol was the most common etiology (68.8%). No patient experienced organ failure. The most frequent imaging findings were fat stranding in the groove (83.3%), duodenal wall thickening (52.1%), and soft tissue mass/thickening in the groove (50%). Over a mean follow-up of 5.0 years, seven (14.6%) required a pancreas-related surgery. Patients had a high burden of pancreatitis-related readmissions (68.8%, 69.4/100 patient-years). Incident diabetes and chronic pancreatitis were diagnosed in 5 (13.9% of patients at risk) and 8 (29.6% of patients at risk) respectively. CONCLUSIONS: Groove pancreatitis has a wide spectrum of severity; most patients have mild disease. These patients have a high burden of readmissions and progression to chronic pancreatitis. A small minority requires surgical intervention.

Imaging-Based Subtypes of Pancreatic Ductal Adenocarcinoma Exhibit Differential Growth and Metabolic Patterns in the Pre-Diagnostic Period: Implications for Early Detection.

BACKGROUND: Previously, we characterized subtypes of pancreatic ductal adenocarcinoma (PDAC) on computed-tomography (CT) scans, whereby conspicuous (high delta) PDAC tumors are more likely to have aggressive biology and poorer clinical outcomes compared to inconspicuous (low delta) tumors. Here, we hypothesized that these imaging-based subtypes would exhibit different growth-rates and distinctive metabolic effects in the period prior to PDAC diagnosis. MATERIALS AND METHODS: Retrospectively, we evaluated 55 patients who developed PDAC as a second primary cancer and underwent serial pre-diagnostic (T0) and diagnostic (T1) CT-scans. We scored the PDAC tumors into high and low delta on T1 and, serially, obtained the biaxial measurements of the pancreatic lesions (T0-T1). We used the Gompertz-function to model the growth-kinetics and estimate the tumor growth-rate constant (α) which was used for tumor binary classification, followed by cross-validation of the classifier accuracy. We used maximum-likelihood estimation to estimate initiation-time from a single cell (10-6 mm3) to a 10 mm3 tumor mass. Finally, we serially quantified the subcutaneous-abdominal-fat (SAF), visceral-abdominal-fat (VAF), and muscles volumes (cm3) on CT-scans, and recorded the change in blood glucose (BG) levels. T-test, likelihood-ratio, Cox proportional-hazards, and Kaplan-Meier were used for statistical analysis and p-value <0.05 was considered significant. RESULTS: Compared to high delta tumors, low delta tumors had significantly slower average growth-rate constants (0.024 month-1 vs. 0.088 month-1, p<0.0001) and longer average initiation-times (14 years vs. 5 years, p<0.0001). α demonstrated high accuracy (area under the curve (AUC)=0.85) in classifying the tumors into high and low delta, with an optimal cut-off of 0.034 month-1. Leave-one-out-cross-validation showed 80% accuracy in predicting the delta-class (AUC=0.84). High delta tumors exhibited accelerated SAF, VAF, and muscle wasting (p <0.001), and BG disturbance (p<0.01) compared to low delta tumors. Patients with low delta tumors had better PDAC-specific progression-free survival (log-rank, p<0.0001), earlier stage tumors (p=0.005), and higher likelihood to receive resection after PDAC diagnosis (p=0.008), compared to those with high delta tumors. CONCLUSION: Imaging-based subtypes of PDAC exhibit distinct growth, metabolic, and clinical profiles during the pre-diagnostic period. Our results suggest that heterogeneous disease biology may be an important consideration in early detection strategies for PDAC.

Decoding Genes: Current Update on Radiogenomics of Select Abdominal Malignancies.

Technologic advances in chromosomal analysis and DNA sequencing have enabled genome-wide analysis of cancer cells, yielding considerable data on the genetic basis of malignancies. Evolving knowledge of tumor genetics and oncologic pathways has led to a better understanding of histopathologic features, tumor classification, tumor biologic characteristics, and imaging findings and discovery of targeted therapeutic agents. Radiogenomics is a rapidly evolving field of imaging research aimed at correlating imaging features with gene mutations and gene expression patterns, and it may provide surrogate imaging biomarkers that may supplant genetic tests and be used to predict treatment response and prognosis and guide personalized treatment options. Multidetector CT, multiparametric MRI, and PET with use of multiple radiotracers are some of the imaging techniques commonly used to assess radiogenomic associations. Select abdominal malignancies demonstrate characteristic imaging features that correspond to gene mutations. Recent advances have enabled us to understand the genetics of steatotic and nonsteatotic hepatocellular adenomas, a plethora of morphologic-molecular subtypes of hepatic malignancies, a variety of clear cell and non-clear cell renal cell carcinomas, a myriad of hereditary and sporadic exocrine and neuroendocrine tumors of the pancreas, and the development of targeted therapeutic agents for gastrointestinal stromal tumors based on characteristic KIT gene mutations. Mutations associated with aggressive phenotypes of these malignancies can sometimes be predicted on the basis of their imaging characteristics. Radiologists should be familiar with the genetics and pathogenesis of common cancers that have associated imaging biomarkers, which can help them be integral members of the cancer management team and guide clinicians and pathologists. Online supplemental material is available for this article. ©RSNA, 2020 See discussion on this article by Luna (pp 1627-1630).

Pancreatic Neuroendocrine Neoplasms: 2020 Update on Pathologic and Imaging Findings and Classification.

Pancreatic neuroendocrine neoplasms (panNENs) are heterogeneous neoplasms with neuroendocrine differentiation that show characteristic clinical, histomorphologic, and prognostic features; genetic alterations; and biologic behavior. Up to 10% of panNENs develop in patients with syndromes that predispose them to cancer, such as multiple endocrine neoplasia type 1, von Hippel-Lindau disease, tuberous sclerosis complex, neurofibromatosis type 1, and glucagon cell adenomatosis. PanNENs are classified as either functioning tumors, which manifest early because of clinical symptoms related to increased hormone production, or nonfunctioning tumors, which often manifest late because of mass effect. PanNENs are histopathologically classified as well-differentiated pancreatic neuroendocrine tumors (panNETs) or poorly differentiated pancreatic neuroendocrine carcinomas (panNECs) according to the 2010 World Health Organization (WHO) classification system. Recent advances in cytogenetics and molecular biology have shown substantial heterogeneity in panNECs, and a new tumor subtype, well-differentiated, high-grade panNET, has been introduced. High-grade panNETs and panNECs are two distinct entities with different pathogenesis, clinical features, imaging findings, treatment options, and prognoses. The 2017 WHO classification system and the eighth edition of the American Joint Committee on Cancer staging system include substantial changes. Multidetector CT, MRI, and endoscopic US help in anatomic localization of the primary tumor, local-regional spread, and metastases. Somatostatin receptor scintigraphy and fluorine 18-fluorodeoxyglucose PET/CT are helpful for functional and metabolic assessment. Knowledge of recent updates in the pathogenesis, classification, and staging of panNENs and familiarity with their imaging findings allow optimal patient treatment. ©RSNA, 2020.

Hereditary and Sporadic Pancreatic Ductal Adenocarcinoma: Current Update on Genetics and Imaging.

Pancreatic ductal adenocarcinoma (PDAC) is a genetically heterogeneous, biologically aggressive malignancy with a uniformly poor prognosis. While most pancreatic cancers arise sporadically, a small subset of PDACs develop in patients with hereditary and familial predisposition. Detailed studies of the rare hereditary syndromes have led to identification of specific genetic abnormalities that contribute to malignancy. For example, germline mutations involving BRCA1, BRCA2, PRSS1, and mismatch repair genes predispose patients to PDAC. While patients with Lynch syndrome develop a rare "medullary" variant of adenocarcinoma, intraductal papillary mucinous tumors are observed in patients with McCune-Albright syndrome. It is now well established that PDACs originate via a multistep progression from microscopic and macroscopic precursors due to cumulative genetic abnormalities. Improved knowledge of tumor genetics and oncologic pathways has contributed to a better understanding of tumor biology with attendant implications on diagnosis, management, and prognosis. In this article, the genetic landscape of PDAC and its precursors will be described, the hereditary syndromes that predispose to PDAC will be reviewed, and the current role of imaging in screening and staging assessment, as well as the potential role of molecular tumor-targeted imaging for evaluation of patients with PDAC and its precursors, will be discussed. Keywords: Abdomen/GI, Genetic Defects, Oncology, Pancreas Supplemental material is available for this article. © RSNA, 2020.

Integrating next-generation sequencing to endoscopic retrograde cholangiopancreatography (ERCP)-obtained biliary specimens improves the detection and management of patients with malignant bile duct strictures.

OBJECTIVE: Despite improvements in imaging, serum CA19-9 and pathological evaluation, differentiating between benign and malignant bile duct strictures remains a diagnostic conundrum. Recent developments in next-generation sequencing (NGS) have opened new opportunities for early detection and management of cancers but, to date, have not been rigorously applied to biliary specimens. DESIGN: We prospectively evaluated a 28-gene NGS panel (BiliSeq) using endoscopic retrograde cholangiopancreatography-obtained biliary specimens from patients with bile duct strictures. The diagnostic performance of serum CA19-9, pathological evaluation and BiliSeq was assessed on 252 patients (57 trainings and 195 validations) with 346 biliary specimens. RESULTS: The sensitivity and specificity of BiliSeq for malignant strictures was 73% and 100%, respectively. In comparison, an elevated serum CA19-9 and pathological evaluation had sensitivities of 76% and 48%, and specificities of 69% and 99%, respectively. The combination of BiliSeq and pathological evaluation increased the sensitivity to 83% and maintained a specificity of 99%. BiliSeq improved the sensitivity of pathological evaluation for malignancy from 35% to 77% for biliary brushings and from 52% to 83% for biliary biopsies. Among patients with primary sclerosing cholangitis (PSC), BiliSeq had an 83% sensitivity as compared with pathological evaluation with an 8% sensitivity. Therapeutically relevant genomic alterations were identified in 20 (8%) patients. Two patients with ERBB2-amplified cholangiocarcinoma received a trastuzumab-based regimen and had measurable clinicoradiographic response. CONCLUSIONS: The combination of BiliSeq and pathological evaluation of biliary specimens increased the detection of malignant strictures, particularly in patients with PSC. Additionally, BiliSeq identified alterations that may stratify patients for specific anticancer therapies.