The modern face of esophageal candidiasis in an oncology center: Correlating clinical manifestations, endoscopic grade, and pathological data in 323 contemporary cancer patients.

OBJECTIVES: Clinical presentation and outcomes of esophageal candidiasis (EC) in cancer patients are scarcely studied in the azole era, as is the correlation between clinical, endoscopic, and histopathological EC manifestations. METHODS: We retrospectively reviewed the risk factors, clinical features, and outcomes of pathology-documented EC cases at MD Anderson Cancer Center. We further assessed associations between presence of symptoms, standardized 4-stage endoscopic grade (Kodsi classification), histopathological data, and fluconazole treatment failure. RESULTS: Among 323 cancer patients with EC, 89% had solid tumors, most commonly esophageal cancer (29%). Thirty-three percent of EC patients were asymptomatic. The proportion of symptomatic EC patients significantly increased with endoscopic grade (P=0.005). Among 202 patients receiving oral fluconazole, 27 (13%) had treatment failure. Underlying esophageal disease was the only independent predictor of fluconazole treatment failure (odds ratio: 3.88, P=0.005). Endoscopic grade correlated significantly with Candida organism burden (Correlation coefficient [ρ]=0.21, P<0.01) and neutrophilic inflammation (ρ=0.18, P<0.01). Candida invasion of the squamous mucosal layer was associated with treatment failure (P=0.049). CONCLUSIONS: EC was predominantly encountered in patients with solid tumors. One third of EC patients were asymptomatic, challenging traditional symptom-based diagnosis. Development of integrated clinicopathological scoring systems could further guide therapeutic management of cancer patients with EC.

High-dimensional deconstruction of pancreatic cancer identifies tumor microenvironmental and developmental stemness features that predict survival.

Numerous cell states are known to comprise the pancreatic ductal adenocarcinoma (PDAC) tumor microenvironment (TME). However, the developmental stemness and co-occurrence of these cell states remain poorly defined. Here, we performed single-cell RNA sequencing (scRNA-seq) on a cohort of treatment-naive PDAC time-of-diagnosis endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) samples (n = 25). We then combined these samples with surgical resection (n = 6) and publicly available samples to increase statistical power (n = 80). Following annotation into 25 distinct cell states, cells were scored for developmental stemness, and a customized version of the Ecotyper tool was used to identify communities of co-occurring cell states in bulk RNA-seq samples (n = 268). We discovered a tumor microenvironmental community comprised of aggressive basal-like malignant cells, tumor-promoting SPP1+ macrophages, and myofibroblastic cancer-associated fibroblasts associated with especially poor prognosis. We also found a developmental stemness continuum with implications for survival that is present in both malignant cells and cancer-associated fibroblasts (CAFs). We further demonstrated that high-dimensional analyses predictive of survival are feasible using standard-of-care, time-of-diagnosis EUS-FNB specimens. In summary, we identified tumor microenvironmental and developmental stemness characteristics from a high-dimensional gene expression analysis of PDAC using human tissue specimens, including time-of-diagnosis EUS-FNB samples. These reveal new connections between tumor microenvironmental composition, CAF and malignant cell stemness, and patient survival that could lead to better upfront risk stratification and more personalized upfront clinical decision-making.

Evolution of immune and stromal cell states and ecotypes during gastric adenocarcinoma progression.

Understanding tumor microenvironment (TME) reprogramming in gastric adenocarcinoma (GAC) progression may uncover novel therapeutic targets. Here, we performed single-cell profiling of precancerous lesions, localized and metastatic GACs, identifying alterations in TME cell states and compositions as GAC progresses. Abundant IgA+ plasma cells exist in the premalignant microenvironment, whereas immunosuppressive myeloid and stromal subsets dominate late-stage GACs. We identified six TME ecotypes (EC1-6). EC1 is exclusive to blood, while EC4, EC5, and EC2 are highly enriched in uninvolved tissues, premalignant lesions, and metastases, respectively. EC3 and EC6, two distinct ecotypes in primary GACs, associate with histopathological and genomic characteristics, and survival outcomes. Extensive stromal remodeling occurs in GAC progression. High SDC2 expression in cancer-associated fibroblasts (CAFs) is linked to aggressive phenotypes and poor survival, and SDC2 overexpression in CAFs contributes to tumor growth. Our study provides a high-resolution GAC TME atlas and underscores potential targets for further investigation.

Comparative Analyses of the Clinicopathologic Features of Short-Term and Long-Term Survivors of Patients with Pancreatic Ductal Adenocarcinoma Who Received Neoadjuvant Therapy and Pancreatoduodenectomy.

Neoadjuvant therapy (NAT) is increasingly used to treat patients with pancreatic ductal adenocarcinoma (PDAC). Patients with PDAC often show heterogenous responses to NAT with variable clinical outcomes, and the clinicopathologic parameters associated with these variable outcomes remain unclear. In this study, we systematically examined the clinicopathologic characteristics of 60 short-term survivors (overall survival < 15 months) and 149 long-term survivors (overall survival > 60 months) and compared them to 352 intermediate-term survivors (overall survival: 15-60 months) of PDAC who received NAT and pancreatoduodenectomy. We found that the short-term survivor group was associated with male gender (p = 0.03), tumor resectability prior to NAT (p = 0.04), poorly differentiated tumor histology (p = 0.006), more positive lymph nodes (p = 0.04), higher ypN stage (p = 0.002), and higher positive lymph node ratio (p = 0.03). The long-term survivor group had smaller tumor size (p = 0.001), lower ypT stage (p = 0.001), fewer positive lymph nodes (p < 0.001), lower ypN stage (p < 0.001), lower positive lymph node ratio (p < 0.001), lower rate of lymphovascular invasion (p = 0.001) and perineural invasion (p < 0.001), better tumor response grading (p < 0.001), and less frequent recurrence/metastasis (p < 0.001). The ypN stage is an independent predictor of both short-term and long-term survivors by multivariate logistic regression analyses. In addition, tumor differentiation was also an independent predictor for short-term survivors, and tumor response grading and perineural invasion were independent predictors for long-term survivors. Our results may help to plan and select post-operative adjuvant therapy for patients with PDAC who received NAT and pancreatoduodenectomy based on the pathologic data.

Tuberous sclerosis complex mutations in patients with pancreatic neuroendocrine tumors. Observations on phenotypic and treatment-related associations.

Pancreatic neuroendocrine tumors (PanNETs) in familial tuberous sclerosis (TSC1 and TSC2 mutations) have been known and studied. However, little is known about PanNET patients harboring the very rare (less than 2%) sporadic TSC mutations. Some renal tumors have been shown to harbor sporadic TSC mutations, with a distinctive morphological correlate. We hereby describe this rather unusual molecular alteration in well-differentiated pancreatic neuroendocrine tumors (WD PanNETs) with a focus on their morphology and treatment outcomes. Six cases of WD PanNETs harboring sporadic TSC mutations were identified retrospectively. H&E slides and corresponding immunostains were reviewed for all cases. Clinical, molecular, and radiological information was obtained using the electronic medical records. Cohort consisted of 4 males and 2 females. Median age at diagnosis was 50 years (range 33-74 years). Origin of neoplasm was the pancreas and, in all but one, patient had liver metastasis by the time of presentation. Six out of six cases demonstrated a unique tumor morphology, with ample eosinophilic cytoplasm. Tumors were arranged in sheets and nests; prominent cystic change was noted in one case. Two cases were additionally biopsied post-treatment with capecitabine and temozolomide, and showed even more abundant oncocytic cytoplasm, eccentric nuclei, and a prominent cherry red nucleolus, and were arranged in a cluster of 3-4 cells, separated by stromal cells. Every patient had a different TSC2 variant with no cases of TSC1 mutations. Other common variants included MEN1 (4/6), DAXX (2/6), and TP53 (2/6). Per the WH0 2019 classification, tumors were graded as NET-G3 (n = 3) and NET-G2 (n = 3). Ki-67 s ranged from 7.2 to 60. All cases had retained MMR protein expression. The majority of patients (4/6) have expired. Although they received multiple treatments, a consistent pattern observed in patients was marked radiologic response to chemotherapy with capecitabine and temozolomide (offered in 5/6 patients) with duration of responses reaching 11 months in the majority of cases, with one patient showing near complete pathologic response of localized disease. TSC2 mutations may confer distinctive appearance in WD PanNETs, reminiscent of their effects in renal tumors. Although not entirely specific, this distinct morphological pattern with abundant eosinophilic cytoplasm in WD PanNETs could be reflective of an associated TSC mutation, with suggestions of significant therapeutic response to a specific cytotoxic chemotherapy.

Prognosticators for Patients with Pancreatic Ductal Adenocarcinoma Who Received Neoadjuvant FOLFIRINOX or Gemcitabine/Nab-Paclitaxel Therapy and Pancreatectomy.

Neoadjuvant FOLFIRINOX and gemcitabine/nab-paclitaxel (GemNP) therapies are increasingly used to treat patients with pancreatic ductal adenocarcinoma (PDAC). However, limited data are available on their clinicopathologic prognosticators. We examined the clinicopathologic factors and survival of 213 PDAC patients who received FOLFIRINOX with 71 patients who received GemNP. The FOLFIRINOX group was younger (p < 0.01) and had a higher rate of radiation (p = 0.049), higher rate of borderline resectable and locally advanced disease (p < 0.001), higher rate of Group 1 response (p = 0.045) and lower ypN stage (p = 0.03) than the GemNP group. Within FOLFIRINOX group, radiation was associated with decreased lymph node metastasis (p = 0.01) and lower ypN stage (p = 0.01). The tumor response group, ypT, ypN, LVI and PNI, correlated significantly with both DFS and OS (p < 0.05). Patients with the ypT0/T1a/T1b tumor had better DFS (p = 0.04) and OS (p = 0.03) than those with ypT1c tumor. In multivariate analysis, the tumor response group and ypN were independently prognostic factors for DFS and OS (p < 0.05). Our study demonstrated that the FOLFIRINOX group was younger and had a better pathologic response than the GemNP group and that the tumor response group, ypN, ypT, LVI and PNI, are significant prognostic factors for survival in these patients. Our results also suggest that the tumor size of 1.0 cm is a better cut off for ypT2. Our study highlights the importance of systemic pathologic examination and the reporting of post-treatment pancreatectomies.

Clinicopathologic characterization of hepatocellular adenomas in men: a multicenter experience.

Hepatocellular adenomas (HCAs) are benign liver neoplasms which most commonly present in women in their reproductive age. In men, they are rare and have a higher risk of malignant transformation to hepatocellular carcinoma (HCC). Here we present our multicenter experience with HCA in men in the United States. A total of 27 HCA cases were included, with a mean age of presentation of 37 years (range, 9-69 years) and a mean size of 6.8 cm (range, 0.9-18.5 cm). Based on the 2019 World Health Organization classification, the most common subtype identified was inflammatory HCA (IHCA; 10 cases, 37.0%) followed by unclassified HCA (UHCA; 7 cases, 25.9%), HNF1A-inactivated HCA (H-HCA; 6 cases, 22.2%), ß-catenin-activated IHCA (b-IHCA; 3 cases, 11.1%), and ß-catenin-activated HCA (b-HCA; 1 case, 3.7%). Six additional cases diagnosed as hepatocellular neoplasm of uncertain malignant potential (HUMP) were also included in the study. These cases presented in a mean age of 46 years (range, 17-64 years) and a size of 10.8 cm (range, 4.2-16.5 cm). We evaluated the significance of androgen receptor (AR) expression by immunohistochemistry (IHC); of the 16 cases with materials available, 8 were considered positive using the Allred score system (2 IHCA, 2 H-HCA, 1 UHCA, and 3 HUMP). Of the total cases, 12 were diagnosed on biopsies, for which follow-up information is available for 7, and none of them show evidence of malignant transformation. Of the 21 resection cases, a concomitant well-differentiated HCC within the same lesion was identified in 5 cases (23.8%), which were diagnosed as HCA (n = 4) or HUMP (n = 1). Overall, 15% of cases in our entire cohort of HCA and HUMP showed concomitant HCC, while none of the 7 biopsy cases showed any malignant transformation on follow-up (range, 22-160 months; mean, 61.8 months).

Liver pathology in retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations: vasculopathic disease beyond nodular regenerative hyperplasia.

Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is a rare autosomal dominant disease resulting from a frame-shift mutation in TREX1, an intracellular 3'-5' exonuclease 1. Hepatic findings include an elevated alkaline phosphatase (ALP) and nodular regenerative hyperplasia (NRH). Affected individuals typically succumb to brain lesions before clinically apparent hepatic manifestations; thus, little else is known about the hepatic pathology. Autopsy reports and a liver section from each (n = 11) of three unrelated kindreds with the most common mutation in TREX1 (V235Gfs∗6) were studied with standard and immunohistochemical stains. Cases were compared with "normal liver" controls from similar autopsy years. Cases consisted of six men and five women who died at a median age of 50 yr (range, 41-60 yr.). Seven had elevated ALP. Two had liver atrophy. Foci of NRH were variably detected in all. Inhomogeneous distribution of other findings included patternless parenchymal fibrous bands, approximation of vascular structures, and commonly, architectural changes of vascular structures. Only bile duct epithelia were unaffected. In addition, small trichrome-positive nodules were found along vein walls or isolated in the parenchyma. Rare foci of non-NRH hepatocytic nodules were noted in 3. Increased CD34 and altered α-SMA IHC expression were variably noted. Periportal ductules and perivenular K7 IHC expression were increased to unpredictable degrees. The extensive but inhomogeneous histopathologic findings in livers of autopsied patients with RVCL-S appear to involve hepatic vascular structures. These findings validate inclusion of vascular liver involvement beyond NRH in this complex hereditary disorder.

Integrated Genomic and Clinicopathologic Approach Distinguishes Pancreatic Grade 3 Neuroendocrine Tumor From Neuroendocrine Carcinoma and Identifies a Subset With Molecular Overlap.

Distinguishing grade 3 pancreatic neuroendocrine tumor (G3 PanNET) from neuroendocrine carcinoma (PanNEC) is a known diagnostic challenge, and accurate classification is critical because clinical behavior and therapies differ. Although current recommendations suggest that immunohistochemistry for p53, Rb, ATRX, and DAXX can distinguish most cases, some cases remain difficult to classify using this approach. In this study, we reviewed 47 high-grade neoplasms originally diagnosed as pancreatic neuroendocrine neoplasms. In addition to the currently recommended stains, we performed capture-based sequencing of approximately 500 cancer genes and immunohistochemistry for p16 and trypsin or chymotrypsin. Using an integrated molecular and clinicopathologic approach, 42 (89%) of 47 cases had a clear final diagnosis of either G3 PanNET (n = 17), PanNEC (n = 17), or mixed acinar-NEC (n = 8). The 17 G3 PanNETs demonstrated frequent alterations in MEN1 (71%), DAXX (47%), ATRX (24%), TSC2 (35%), SETD2 (42%), and CDKN2A (41%). Contrary to prior reports, TP53 alterations were also common in G3 PanNETs (35%) but were always mutually exclusive with CDKN2A alterations in this group. The 17 PanNECs demonstrated frequent alterations in TP53 (88%), cell cycle genes RB1 (47%), CCNE1/CCND1 (12%), CDKN2A (29%), and in KRAS (53%) and SMAD4 (41%); TP53 was coaltered with a cell cycle gene in 76% of PanNECs. Diffuse strong p16 staining was observed in 69% of PanNECs in contrast to 0% of G3 PanNETs. The 8 acinar-NECs had recurrent alterations in ATM (25%), APC (25%), and STK11 (25%). Five cases remained difficult to classify, 3 of which exhibited overlapping molecular features with alterations in MEN1 with or without ATRX, and RB1 with or without TP53, making it unclear whether to classify as PanNET or PanNEC. Our data demonstrate that molecular profiling and immunohistochemistry for p16 greatly improve the diagnostic accuracy of high-grade pancreatic neuroendocrine neoplasms and identify a subset of rare cases with overlapping features of both PanNET and PanNEC.

Integrated Pathologic Score Effectively Stratifies Patients With Pancreatic Ductal Adenocarcinoma Who Received Neoadjuvant Therapy and Pancreaticoduodenectomy.

Neoadjuvant therapy is increasingly used to treat patients with pancreatic ductal adenocarcinoma (PDAC). Pathologic parameters of treated PDAC, including tumor (ypT) and lymph node (ypN) stage, and tumor response grading (TRG) are important prognostic factors in this group of patients. To our knowledge, a multifactorial prognostic score combining pathologic features including ypT, ypN, and TRG in treated PDAC patients has not been reported. Our cohort consisted of 398 PDAC patients who received neoadjuvant therapy and underwent pancreaticoduodenectomy at our institution. All pancreaticoduodenectomy specimens were grossly and microscopically evaluated using a standard protocol. The integrated pathologic score (IPS) was calculated as the sum of the scores for ypT, ypN, and TRG according to either the MD Anderson grading system (IPSMDA) or the College of American Pathologists (CAP) grading system (IPSCAP). The IPSMDA and IPSCAP were correlated with clinicopathologic parameters and patient survival. Using either IPSMDA or IPSCAP, PDAC patients were stratified into 3 distinct prognostic groups for both disease-free survival (DFS) ( P <0.001) and overall survival (OS) ( P <0.001). The IPSMDA and IPSCAP correlated with tumor differentiation, margin status, the American Joint Committee on Cancer (AJCC) stage, and tumor recurrence ( P <0.05). In multivariate analysis, IPSMDA, IPSCAP, margin status, and tumor differentiation were independent prognostic factors for both DFS ( P <0.05) and OS ( P <0.05). However, patients with AJCC stage IB, IIA, or IIB disease had no significant difference in either DFS or OS ( P >0.05). The IPS appears to provide improved prognostic information compared with AJCC staging for preoperatively treated patients with PDAC.

Sequential histologic evolution of gallbladder inflammation in acute cholecystitis over the first 10 days after onset of symptoms.

BACKGROUND: The timing of cholecystectomy during acute cholecystitis (AC) is controversial, especially whether it is advisable to perform in patients with duration of symptoms between 3 and 10 days. The purpose of this study is to define clearly the sequential evolution of histological changes following symptoms onset to guide recommendations regarding timing of cholecystectomy. METHODS: We identified patients with AC (2005-2018) who had cholecystectomy within 10 days of symptom onset of a first attack of AC. Histologic features of gallbladder injury including cellular and exudative inflammatory response to injury were determined on blinded pathologic slides. RESULTS: One hundred and forty-nine patients were divided into three groups; early-who underwent cholecystectomy 1-3 days after symptom-onset, intermediate-4-6 days, and late-7-10 days. Key features of injury were necrosis and hemorrhage. A subgroup of patients in the early phase developed severe necrosis and hemorrhage of an extent associated with difficult cholecystectomy. Large spikes in extent of necrosis and hemorrhage occurred at 7-10 days. Major inflammatory responses to injury were eosinophilic and lymphocytic infiltration and early fibrosis. CONCLUSIONS: Severe necrosis may develop rapidly and be present in the early period after symptom onset of AC. Cholecystectomy may be reasonable in some patients but by day 7-10, severe necrosis and hemorrhage may be expected to be present in most patients.

Epithelial SOX9 drives progression and metastases of gastric adenocarcinoma by promoting immunosuppressive tumour microenvironment.

OBJECTIVE: Many cancers engage embryonic genes for rapid growth and evading the immune system. SOX9 has been upregulated in many tumours, yet the role of SOX9 in mediating immunosuppressive tumour microenvironment is unclear. Here, we aim to dissect the role of SOX9-mediated cancer stemness attributes and immunosuppressive microenvironment in advanced gastric adenocarcinoma (GAC) for novel therapeutic discoveries. METHODS: Bulk RNAseq/scRNA-seq, patient-derived cells/models and extensive functional studies were used to identify the expression and functions of SOX9 and its target genes in vitro and in vivo. Immune responses were studied in PBMCs or CD45+ immune cells cocultured with tumour cells with SOX9high or knockout and the KP-Luc2 syngeneic models were used for efficacy of combinations. RESULTS: SOX9 is one of the most upregulated SOX genes in GAC and highly expressed in primary and metastatic tissues and associated with poor prognosis. Depletion of SOX9 in patient-derived GAC cells significantly decreased cancer stemness attributes, tumour formation and metastases and consistently increased CD8+ T cell responses when cocultured with PBMCs/CD45+ cells from GAC patients. RNA sequencing identified the leukaemia inhibitory factor (LIF) as the top secreted molecule regulated by SOX9 in tumour cells and was enriched in malignant ascites and mediated SOX9-induced M2 macrophage repolarisation and inhibited T cell function. CONCLUSION: Epithelial SOX9 is critical in suppressing CD8+ T cell responses and modified macrophage function in GAC through the paracrine LIF factor. Cotargeting LIF/LIFR and CSF1R has great potential in targeting SOX9-mediated cancer stemness, T cell immunosuppression and metastases suggesting the novel combination therapy against advanced GAC.

Histopathological tumour response scoring in resected pancreatic cancer following neoadjuvant therapy: international interobserver study (ISGPP-1).

BACKGROUND: Most tumour response scoring systems for resected pancreatic cancer after neoadjuvant therapy score tumour regression. However, whether treatment-induced changes, including tumour regression, can be identified reliably on haematoxylin and eosin-stained slides remains unclear. Moreover, no large study of the interobserver agreement of current tumour response scoring systems for pancreatic cancer exists. This study aimed to investigate whether gastrointestinal/pancreatic pathologists can reliably identify treatment effect on tumour by histology, and to determine the interobserver agreement for current tumour response scoring systems. METHODS: Overall, 23 gastrointestinal/pancreatic pathologists reviewed digital haematoxylin and eosin-stained slides of pancreatic cancer or treated tumour bed. The accuracy in identifying the treatment effect was investigated in 60 patients (30 treatment-naive, 30 after neoadjuvant therapy (NAT)). The interobserver agreement for the College of American Pathologists (CAP) and MD Anderson Cancer Center (MDACC) tumour response scoring systems was assessed in 50 patients using intraclass correlation coefficients (ICCs). An ICC value below 0.50 indicated poor reliability, 0.50 or more and less than 0.75 indicated moderate reliability, 0.75 or more and below 0.90 indicated good reliability, and above 0.90 indicated excellent reliability. RESULTS: The sensitivity and specificity for identifying NAT effect were 76.2 and 49.0 per cent respectively. After NAT in 50 patients, ICC values for both tumour response scoring systems were moderate: 0.66 for CAP and 0.71 for MDACC. CONCLUSION: Identification of the effect of NAT in resected pancreatic cancer proved unreliable, and interobserver agreement for the current tumour response scoring systems was suboptimal. These findings support the recently published International Study Group of Pancreatic Pathologists recommendations to score residual tumour burden rather than tumour regression after NAT.

Preliminary experience with a new institutional tumor board dedicated to patients with neuroendocrine neoplasms.

PURPOSE: To determine the decision patterns of a neuroendocrine neoplasm (NEN) tumor board (TB) and the factors behind those. METHODS: We retrospectively reviewed all NEN-TB recommendations from 07/2018 to 12/2021 and recorded patient characteristics, TB outcomes and associations between them. RESULTS: A total of 652 patient entries were identified. Median age of participants was 61 years and an equal number of men and women were presented. Most patients (33.4%) had tumors originating in the small bowel with 16.8% of high grade and 25.9% of pancreatic origin. Imaging was reviewed 97.2% of the time, with most frequently reviewed modalities being PET (55.3%) and CT (44.3%). Imaging review determined that there was no disease progression 20.8% of the time and significant treatment changes were recommended in 36.1% of patients. Major pathology amendments occurred in 3.7% of cases and a clinical trial was identified in 2.6%. There was no association between patient or disease presentation with the tumor board outcomes. There was a slight decrease in number of patients discussed per session, from 10.0 to 8.2 (p < 0.001) when the TB transitioned to a virtual format during the COVID-19 pandemic but all other factors remained unchanged. CONCLUSION: NEN-TB relies heavily on image review, can impact significant treatment changes in patients with rare tumors like NENs, and was not affected by the switch to a virtual format. Finally, none of the examined factors were predictive of the tumor board recommendations.

The Clinical and Pathologic Features of Intracholecystic Papillary-Tubular Neoplasms of the Gallbladder.

Intracholecystic papillary-tubular neoplasm denotes a discrete mucosal-based neoplastic proliferation into the gallbladder lumen. It is diagnosed incidentally during cholecystectomy or radiologically during a workup for abdominal pain. The majority of polypoid lesions in the gallbladder are non-neoplastic; therefore, pathologic examination is the gold standard to establish this diagnosis. Intracholecystic papillary-tubular neoplasm is considered as premalignant, although associated invasive carcinomas may be present in the specimen. Invasive carcinoma arising from intracholecystic papillary-tubular neoplasm have a better prognosis than de novo gallbladder carcinomas. The pathology of intracholecystic papillary-tubular neoplasm, including the challenges involved in the diagnosis of this entity, is discussed.

Imaging Features of Premalignant Biliary Lesions and Predisposing Conditions with Pathologic Correlation.

Biliary malignancies include those arising from the intrahepatic and extrahepatic bile ducts as well as the gallbladder and hepatopancreatic ampulla of Vater. The majority of intrahepatic and extrahepatic malignancies are cholangiocarcinomas (CCAs). They arise owing to a complex interplay between the patient-specific genetic background and multiple risk factors and may occur in the liver (intrahepatic CCA), hilum (perihilar CCA), or extrahepatic bile ducts (distal CCA). Biliary-type adenocarcinoma constitutes the most common histologic type of ampullary and gallbladder malignancies. Its prognosis is poor and surgical resection is considered curative, so early detection is key, with multimodality imaging playing a central role in making the diagnosis. There are several risk factors for biliary malignancy as well as predisposing conditions that increase the risk; this review highlights the pertinent imaging features of these entities with histopathologic correlation. The predisposing factors are broken down into three major categories: (a) congenital malformations such as choledochal cyst and pancreaticobiliary maljunction; (b) infectious or inflammatory conditions such as parasitic infections, hepatolithiasis, primary sclerosing cholangitis, and porcelain gallbladder; and (c) preinvasive epithelial neoplasms such as biliary intraepithelial neoplasm, intraductal papillary neoplasm of the bile duct, intra-ampullary papillary tubular neoplasm, and intracholecystic papillary neoplasm of the gallbladder. Recognizing the baseline features of these premalignant biliary entities and changes in their appearance over time that indicate the advent of malignancy in high-risk patients can lead to early diagnosis and potentially curative management. An invited commentary by Volpacchio is available online. Online supplemental material is available for this article. ©RSNA, 2022.

Clinical classification of symptomatic heterotopic pancreas of the stomach and duodenum: A case series and systematic literature review.

BACKGROUND: Heterotopic pancreas (HP) is an aberrant anatomic malformation that occurs most commonly in the upper gastrointestinal tract. While the majority of heterotopic pancreatic lesions are asymptomatic, many manifest severe clinical symptoms which require surgical or endoscopic intervention. Understanding of the clinical manifestations and symptoms of HP is limited due to the lack of large volume studies in the literature. The purpose of this study is to review symptomatic cases at a single center and compare these to a systematic review of the literature in order to characterize common clinical manifestations and treatment of this disease. AIM: To classify the common clinical manifestations of heterotopic pancreas. METHODS: A retrospective review was conducted of pathologic samples containing heterotopic pancreas from 2000-2018. Review was limited to HP of the upper gastrointestinal tract due to the frequency of presentation in this location. Symptomatic patients were identified from review of the medical records and clinical symptoms were tabulated. These were compared to a systematic review of the literature utilizing PubMed and Embase searches for papers pertaining to heterotopic pancreas. Publications describing symptomatic presentation of HP were selected for review. Information including demographics, symptoms, presentation and treatment were compiled and analyzed. RESULTS: Twenty-nine patient were identified with HP at a single center, with six of these identified has having clinical symptoms. Clinical manifestations included, gastrointestinal bleeding, gastric ulceration with/without perforation, pancreatitis, and gastric outlet obstruction. Systemic review of the literature yielded 232 publications detailing symptomatic cases with only 20 studies describing ten or more patients. Single and multi-patient studies were combined to form a cohort of 934 symptomatic patients. The majority of patients presented with abdominal pain (67%) combined with one of the following clinical categories: (1) Dyspepsia, (n = 445, 48%); (2) Pancreatitis (n = 260, 28%); (3) Gastrointestinal bleeding (n = 80, 9%); and (4) Gastric outlet obstruction (n = 80, 9%). The majority of cases (n = 832, 90%) underwent surgical or endoscopic resection with 85% reporting resolution or improvement in their symptoms. CONCLUSION: Heterotopic pancreas can cause significant clinical symptoms in the upper gastrointestinal tract. Better understanding and classification of this disease may result in more accurate identification and treatment of this malformation.

Pancreatic neuroendocrine neoplasms: a 2022 update for radiologists.

Pancreatic neuroendocrine neoplasms (PaNENs) are a unique group of pancreatic neoplasms with a wide range of clinical presentations and behaviors. Given their heterogeneous appearance and increasing detection on cross-sectional imaging, it is essential that radiologists understand the variable presentation and distinctions PaNENs display compared to other pancreatic neoplasms. Additionally, some of these neoplasms may be hormonally functional, and it is imperative that radiologists be aware of the common clinical presentations of hormonally active PaNENs. Knowledge of PaNEN pathology and treatments may influence which imaging modality is optimal for each patient. Each imaging modality used for PaNENs has distinct advantages and disadvantages, particularly in different treatment settings. Thus, the focus of this manuscript is to provide an update for the radiologist on PaNEN pathology, imaging, and treatments.

Qualitative imaging features of pancreatic neuroendocrine neoplasms predict histopathologic characteristics including tumor grade and patient outcome.

OBJECTIVES: To identify PanNEN imaging features associated with tumor grade and aggressive histopathological features. METHODS: Associations between histopathological and imaging features of resected PanNEN were retrospectively tested. Histopathologic features included WHO grade, lymphovascular invasion (LVI), growth pattern (infiltrative, circumscribed), and intratumoral fibrosis (mature, immature). Imaging features included size, degree/uniformity of enhancement, progressive enhancement, contour, infiltrative appearance (infiltrativeim), calcifications, cystic components, tumor thrombus, vascular occlusion (VO), duct dilatation, and atrophy. Multinomial logistic regression analyses evaluated the magnitude of associations. Association of variables with outcome was assessed using Cox-proportional hazards regression. RESULTS: 133 patients were included. 3 imaging features (infiltrativeim, ill-defined contour [contourill], and VO) were associated with all histopathologic parameters and poor outcome. Increase in grade increased odds of contourill by 15.6 times (p = 0.0001, 95% CI 3.8-64.4). PanNEN with VO were 51.1 times (p = 0.0002, 6.5-398.6) more likely to demonstrate LVI. For PanNEN with contourill, infiltrative growth pattern was 51.3 times (p < 0.0001, 9.1-288.4), and fibrosis was 14 times (p = 0.0065, 2.1-93.7) more likely. Contourill was associated with decreased recurrence-free survival (p = 0.0003, HR 18.29, 3.83-87.3) and VO (p = 0.0004, HR6.08, 2.22-16.68) with decreased overall survival. CONCLUSIONS: Infiltrativeim, contourill, and VO on imaging are associated with higher grade/histopathological parameters linked to tumor aggression, and poor outcome.