Undifferentiated carcinomas with osteoclastic giant cells of the pancreas (OGC) are rare tumors. The current impression in the literature is that they are highly aggressive tumors similar in prognosis to ductal adenocarcinomas. In this study, the clinicopathologic characteristics of 38 resected OGCs were investigated and contrasted with 725 resected pancreatic ductal adenocarcinomas without osteoclastic cells (PDCs). The frequency among systematically reviewed pancreatic cancers was 1.4%. OGCs showed a slight female predominance (62.9%, vs 51.4% in PDCs). The mean age was 57.9 years (vs 65.0). The mean size of invasive cancer was 5.3 cm (vs 3.2). They were characterized by nodular, pushing-border growth, and 8 arose in tumoral intraepithelial neoplasms [4 in mucinous cystic neoplasms (MCN), 4 in intraductal papillary mucinous neoplasms (IPMN) type lesions] and 23 (61%) also showed prominent intraductal/intracystic growth. Twenty nine (76%) had an invasive ductal/tubular adenocarcinoma component. Osteoid was seen in 12. Despite of their larger size, perineural invasion and nodal metastasis were uncommon (31.6 and 22.6%, vs 85.5 and 64.0% respectively). Immunohistochemistry performed on 24 cases revealed that osteoclastic cells expressed the histiocytic marker CD68, and background spindle cells and pleomorphic/giant carcinoma cells often showed p53 and often lacked cytokeratin. Survival of OGCs was significantly better than that of PDCs (5-year, 59.1 vs 15.7%, respectively, p=0.0009). In conclusion, pancreatic OGCs present with larger tumor size and in slightly younger patients than PDC, 21% arise in MCN/IPMN, and 61% show intraductal/intracystic polypoid growth. OGCs have a significantly better prognosis than is currently believed in the literature.

Objective Appendiceal mucinous neoplasms (AMNs) are a rare and heterogeneous disease for which clinical management is challenging. We aim to review the literature regarding modalities of treatment to guide the management of AMNs. Methods and Review Criteria We conducted a PubMed search in February 2016 for English‐language publications, using the terms “appendiceal,” “appendix,” “carcinoma,” “cancer,” “mucinous,” “treatment,” “genes,” “target,” “genomic,” and terms listed in the articles' subheadings. Published reports and abstracts from the American Society of Clinical Oncology meetings were also searched. Results In this review, we summarize current data and controversies in AMN classification, clinical presentation, molecular alterations, treatment outcomes with regard to cytoreductive surgery, hyperthermic intraperitoneal chemotherapy (HIPEC), and the role of systemic chemotherapy. Conclusion Appendiceal mucinous neoplasms are a heterogeneous group of tumors with a rising incidence. Treatment is based on stage and histology. Low‐grade tumors are treated surgically with resection of the primary site in early stage disease, or peritoneal debulking and HIPEC in patients with advanced stage disease. Treatment of high‐grade tumors requires further prospective trials, and options include debulking surgery and HIPEC with or without preoperative chemotherapy. Trials evaluating novel therapies based on the molecular profiling of AMN tumors are needed to evaluate therapeutic options in patients who are not surgical candidates. Implications for Practice This review provides a reference to guide gastroenterologists, pathologists, surgeons, and oncologists in the management of appendiceal mucinous neoplasms (AMNs), a rare and heterogeneous disease with no consensus on histologic classification or guidelines for treatment algorithms. This review summarizes all AMN classifications and proposes a treatment algorithm based on stage and histology of disease.

The regulation of metastatic organotropism in pancreatic ductal a denocarcinoma (PDAC) remains poorly understood. We demonstrate, using multiple mouse models, that liver and lung metastatic organotropism is dependent upon p120catenin (p120ctn)-mediated epithelial identity. Mono-allelic p120ctn loss accelerates Kras-driven pancreatic cancer formation and liver metastasis. Importantly, one p120ctn allele is sufficient for E-CADHERIN-mediated cell adhesion. By contrast, cells with bi-allelic p120ctn loss demonstrate marked lung organotropism; however, rescue with p120ctn isoform 1A restores liver metastasis. In a p120ctn-independent PDAC model, mosaic loss of E-CADHERIN expression reveals selective pressure for E-CADHERIN-positive liver metastasis and E-CADHERIN-negative lung metastasis. Furthermore, human PDAC and liver metastases support the premise that liver metastases exhibit predominantly epithelial characteristics. RNA-seq demonstrates differential induction of pathways associated with metastasis and epithelial-to-mesenchymal transition in p120ctn-deficient versus p120ctn-wild-type cells. Taken together, P120CTN and E-CADHERIN mediated epithelial plasticity is an addition to the conceptual framework underlying metastatic organotropism in pancreatic cancer.

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Diagnosing malignancy in bile duct brushings is highly challenging. Seven reviewers of variable backgrounds and levels of participation in bile duct brushing sign out blindly reviewed 60 specimens (30 malignant with histologic confirmation and 30 benign (15 stented) with resection or ≥18 months of uneventful follow-up), testing the utility of 14 malignant characteristics. Eleven characteristics were statistically significantly associated with malignancy including 3-dimensional clusters (63% in malignant vs 3% in benign, odds ratio 50, P=0.0003), pleomorphism (62 vs 3, odds ratio 48, P=0.0004), 2-cell population (60% vs 3, odds ratio 44, P=0.0005), chromatin pattern (hypo/hyperchromasia) changes (70% vs 7%, odds ratio 33, P<0.0001), high nuclear-to-cytoplasmic ratio (48 vs 3%, odds ratio 27, P=0.0023), cytoplasmic vacuoles (43 vs 3%, odds ratio 22, P=0.0042), nuclear irregularity (70 vs 10%, odds ratio 21, P<0.0001), cellular discohesion (38 vs 3%, odds ratio 18, P=0.0082), hypercellularity (23% vs 0), nuclear molding (20% vs 0) and prominent nucleoli (21% vs 0). Necrosis and infiltrating inflammation were not helpful in identifying malignancy ('neutrophil cannibalism' was noted in 43% malignant); 21/30 (70%) malignant brushings had ≥3 malignant characteristics, while 23 (77%) benign brushings had none. Of 20 brushings with ≥4 characteristics, 1(5%) proved benign and showed detachment atypia, a close malignant mimicker in brushings. Identification of 3 characteristics maximized the combined sensitivity (70%), specificity (97%) and accuracy (83%), but sensitivity dropped as number of characteristics increased. Identification of 3/11 characteristics (3-dimensional clusters, pleomorphism, high nuclear-to-cytoplasmic ratio, nuclear irregularity, hypercellularity, discohesion, chromatin changes, vacuoles, prominent nucleoli, molding and 2-cell population) improves pathologists' overall performance greatly.