A rare case of three different tumors in the same pancreatic specimen: a case report and brief review of the literature

Solid pseudopapillary tumors (SPT) of the pancreas are rare neoplasms mainly affecting young women. Pancreatic serous cystadenomas (SCAs) and pancreatic neuroendocrine tumors (PanNETs) account for about 2% of all pancreatic neoplasms. The combination of these three lesions, to our knowledge, has never been described in literature. Here we report a case of combined SPT, SCA and PanNET affecting a 33-year-old woman

Beyond Pancreatic Cyst Epithelium: Evidence of Ovarian-Like Stroma in EUS-Guided Through-the-Needle Micro-Forceps Biopsy Specimens

No abstract availabl

Over 700 Whipples for Pancreaticobiliary Malignancies: Postoperative Morbidity Is an Additional Negative Prognostic Factor for Distal Bile Duct Cancer

Background: Distal cholangiocarcinomas and pancreatic cancers both arise from pancreaticobiliary epithelium. Despite their common origin, there is a possible discrepancy in outcome. We analysed the surgical, pathological and survival outcome of resected distal cholangiocarcinoma compared with pancreatic cancer. Methods: All cases of resected distal cholangiocarcinoma and pancreatic cancer from 1998 to 2014 were extracted from our database. Outcomes were compared. Results: There were 54 (7.6%) cases of cholangiocarcinoma and 656 (92.4%) pancreatic cancer. Cholangiocarcinoma showed lower T and N stage, lymphatic and perineural invasion (p < 0.05), worse surgical outcome (p < 0.05) and less access to adjuvant therapy if compared with pancreatic cancer (72.7 vs. 83.1%, p = 0.05). Both showed a similar disease-specific survival (35 vs. 29 months, p = 0.3). Independent predictors of prognosis for pancreatic cancer were resection margin, grading, perineural invasion, T and N status, whereas for cholangiocarcinoma were grading and occurrence of POPF. Conclusion: Considering a large cohort of resected periampullary cancers, cholangiocarcinoma is extremely rare. An earlier diagnosis is associated with better pathological predictors of outcome but increased postoperative morbidity compared to pancreatic cancer, particularly POPF. Consequent decrease in the access to adjuvant therapy for complicated cholangiocarcinoma might explain why survival is as poor as for pancreatic cancer

Mixed adenoneuroendocrine carcinomas of the gastrointestinal tract: targeted next-generation sequencing suggests a monoclonal origin of the two components

Mixed adenoneuroendocrine carcinomas (MANECs) of the gastrointestinal tract are rare neoplasms characterized by coexisting exocrine and neuroendocrine neoplastic components. MANECs' histogenetic classification and molecular characterization remain unclear, significantly affecting the identification of innovative therapeutic options for these tumors

BRCA somatic and germline mutation detection in paraffin embedded ovarian cancers by next-generation sequencing

BRCA mutated ovarian cancers respond better to platinum-based therapy and to the recently approved PARP-inhibitors. There is the need for efficient and timely methods to detect both somatic and germline mutations using formalin-fixed paraffin-embedded (FFPE) tissues and commercially available technology. We used a commercial kit exploring all exons and 50bp exon-intron junctions of BRCA1 and BRCA2 genes, and semiconductor next-generation sequencing (NGS) on DNA from 47 FFPE samples of high-grade serous ovarian cancers. Pathogenic mutations were found in 13/47 (28%) cancers: eight in BRCA1 and five in BRCA2. All BRCA1 and two BRCA2 mutations were germline; three BRCA2 mutations were somatic. All mutations were confirmed by Sanger sequencing. To evaluate the performance of the NGS panel, we assessed its capability to detect the 6,953 variants described for BRCA1 and BRCA2 in ClinVar and COSMIC databases using callability analysis. 6,059 (87.1%) variants were identified automatically by the software; 829 (12.0%) required visual verification. The remaining 65 (0.9%) variants were uncallable, and would require 15 Sanger reactions to be resolved. Thus, the sensitivity of the NGS-panelwas 99.1%. In conclusion, NGS performed with a commercial kit is highly efficient for detection of germline and somatic mutations in BRCA genes using routine FFPE tissue

Radiofrequency ablation for locally advanced pancreatic cancer: SMAD4 analysis segregates a responsive subgroup of patients

PURPOSE: SMAD4 mutational status correlates with pancreatic ductal adenocarcinoma (PDAC) failure pattern. We investigated in a subset of locally advanced patients submitted to radiofrequency ablation (RFA) whether the assessment of SMAD4 status is a useful way to select the patients. METHODS: Clinical, radiological, and follow-up details of patients submitted to RFA for locally advanced pancreatic cancer (LAPC), in whom cytohistological material was available at our institution, were retrospectively retrieved. SMAD4 expression was evaluated by immunohistochemistry (IHC) and considered "negative" or "positive." The survival analysis was conducted using Kaplan-Meier and Cox proportional hazards models. RESULTS: The study population consisted of 30 patients. Thirteen patients (43.3%) received RFA upfront, whereas 17 (56.7%) after induction treatments. SMAD4 was mutant in 18 out of 30 patients (60%). The overall estimated post-RFA disease-specific survival (DSS) was 15 months (95% CI 11.64-18.35). The estimated post-RFA DSS of patients with wild-type and mutant SMAD4 was 22 and 12 months, respectively (log-rank p < 0.05). At the multivariate analysis, SMAD4 was the only independent predictor of survival (p = 0.05). The pattern of failure was not associated with SMAD4 status (p = 0.4). CONCLUSIONS: Within patients undergoing RFA for LAPC, SMAD4 analysis could segregate a subgroup of subjects with improved survival, who likely benefited from tumor ablation

Comparison of imaging-based and pathological dimensions in pancreatic neuroendocrine tumors

AIMTo establish the ability of magnetic resonance (MR) and computer tomography (CT) to predict pathologic dimensions of pancreatic neuroendocrine tumors (PanNET) in a caseload of a tertiary referral center.METHODSPatients submitted to surgery for PanNET at the Surgical Unit of the Pancreas Institute with at least 1 preoperative imaging examination (MR or CT scan) from January 2005 to December 2015 were included and data retrospectively collected. Exclusion criteria were: multifocal lesions, genetic syndromes, microadenomas or mixed tumors, metastatic disease and neoadjuvant therapy. Bland-Altman (BA) and Mountain-Plot (MP) statistics were used to compare size measured by each modality with the pathology size. Passing-Bablok (PB) regression analysis was used to check the agreement between MR and CT.RESULTSOur study population consisted of 292 patients. Seventy-nine (27.1%) were functioning PanNET. The mean biases were 0.17 +/- 7.99 mm, 1 +/- 8.51 mm and 0.23 +/- 9 mm, 1.2 +/- 9.8 mm for MR and CT, considering the overall population and the subgroup of non-functioning-PanNET, respectively. Limits of agreement (LOA) included the vast majority of observations, indicating a good agreement between imaging and pathology. The MP further confirmed this finding and showed that the two methods are unbiased with respect to each other. Considering = 2 cm non-functioning-PanNET, no statistical significance was found in the size estimation rate of MR and CT (P = 0.433). PBR analysis did not reveal significant differences between MR, CT and pathology.CONCLUSIONMR and CT scan are accurate and interchangeable imaging techniques in predicting pathologic dimensions of PanNET

MAP Kinase inhibition reshapes tumour microenvironment of mouse pancreatic cancer by depleting anti-inflammatory macrophages

Pancreatic ductal adenocarcinoma (PDAC) is a pancreatic disease with the lowest survival rate of all cancers. The current therapeutic strategies provide only marginal increase in patients\u2019 survival. It has been recently demonstrated that the tumor microenvironment (TME) plays a major role in the resistance to therapy. Four subtypes of PDAC have been defined based on mRNA profiling of primary tumors. Of these, two (Immunogenic and Squamous) possess high expression of immune-related transcripts, including a macrophage transcriptional signature that indicates worse patients\u2019 survival. Despite important phenotypic differences, all subtypes present activating mutations of KRAS. Activated KRAS engages the MAP Kinase pathway, which has been the index oncogenic signaling towards which many compounds have been developed and tested for the treatment of KRAS-driven cancers. We showed that transcriptional signatures of downstream Ras signaling (MAP kinase) are enriched in human PDAC subtypes dominated by immune-related transcripts (Immunogenic and Squamous). We found that increased MAP kinase transcriptional output is observed in biologically-aggressive PDAC subtypes (Squamous/Basal-like). We used preclinical models of PDAC to demonstrate that MEK inhibition promoted tumor infiltration by leukocytes. Integrative mRNA expression and immunophenotypic analyses showed that MEKi relieved immunosuppression in the TME by reducing the number of anti-inflammatory M2 macrophages and favored infiltration of CD8 positive T cells. The same MEKi-induced M2 depletion was also observed in PDAC tissues from an independent isografts as well as in a genetically-engineered mouse model (GEMM) of PDAC. We showed that depletion of M2 macrophages is seen early during the course of the in vivo treatment, and it is likely due to increased drug sensitivity of M2 macrophages compared to the other macrophage phenotypes. In addition, MEKi induces a \u201cswitch away\u201d from the Squamous/Basal-like subtype and a significant deregulation of a \u201csquamous\u201d gene program. Taken together, our data show that MEKi influences the TME in PDAC by depleting M2 macrophages and favoring infiltration of T cells. As tumor-associated macrophages have been reported to impair chemotherapy efficacy in PDAC, MEKi-induced depletion of M2 macrophages could be exploited to increase treatment efficacy in PDAC