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.

The literature is highly conflicting on hepatobiliary mucinous cystic neoplasms (MCNs), aka "hepatobiliary cystadenoma/cystadenocarcinoma," largely because ovarian stroma (OS) was not a requirement until WHO-2010 and is not widely applied even today. In this study, MCNs (with OS) accounted for 24 of 229 (11%) resected hepatic cysts in one institution. Eight of the 32 (25%) cysts that had been originally designated as hepatobiliary cystadenoma/cystadenocarcinoma at the time of diagnosis proved not to have an OS during this review and were thus re-classified as non-MCN. In total, 36 MCNs (with OS) were analyzed-24 from the institutional files and 12 consultation cases. All were women. Mean age was 51 (28 to 76 y). Mean size was 11 cm (5 to 23 cm). Most (91%) were intrahepatic and in the left lobe (72%). Preoperative imaging mentioned "neoplasm" in 14 (47%) and carcinoma was a differential in 6 (19%) but only 2 proved to have carcinoma. Microscopically, only 47% demonstrated diffuse OS (>75% of the cyst wall/lining); OS was often focal. The cyst lining was often composed of non-mucinous biliary epithelium, and this was predominant in 50% of the cases. Degenerative changes of variable amount were seen in most cases. In situ and invasive carcinoma was seen in only 2 cases (6%), both with small invasion (7 and 8 mm). Five cases had persistence/recurrence, 2 confirmed operatively (at 7 mo and 15 y). Of the 2 cases with carcinoma, one had "residual cyst or hematoma" by radiology at 4 months, and the other was without disease at 3 years. In conclusion, many cysts (25%) previously reported as hepatobiliary cystadenoma/cystadenocarcinoma are not MCNs. True MCNs are uncommon among resected hepatic cysts (11%), occur exclusively in females, are large, mostly intrahepatic and in the left lobe (72%). Invasive carcinomas are small and uncommon (6%) compared with their pancreatic counterpart (16%). Recurrences are not uncommon following incomplete excision.

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.

Diseases and tumors of the appendix vermiformis are very rare, except for acute appendicitis. This study aimed to examine rare findings in the histopathologic examinations of specimens of patients undergoing appendectomy due to the diagnosis of acute appendicitis. The files of 1970 patients undergoing appendectomy due to the diagnosis of acute appendicitis between March 2012 and March 2016 were retrospectively investigated. Rare findings were found in 59 (3 %) patients, and these were evaluated in detail. Patients' age, gender, pathology reports, and postoperation follow-ups were recorded. The rare histopathological findings of 59 patients were examined. Of these, 31 were female (52.5 %) and 28 were male (47.5 %). The average age was 33.1 ± 18.2 years. The unusual findings were as follows: 16 fibrous obliteration, 11 , 2 schistosomiasis, 3 appendiceal neuroma, 2 granulomatous appendicitis, 1 Crohn's disease, 3 chronic appendicitis, 1 endometriosis, 2 hyperplastic polyps, 9 mucinous cystadenoma (+mucocele), 8 carcinoid tumors, and 1 lymphoma. All of the malignant tumors were localized in the distal end of the appendix, and all of the patients were treated with appendectomy. Patients with parasitic diseases also underwent anthelmintic treatment, while chemotherapy was administered to the patient with lymphoma. All of the patients diagnosed with malignancy were alive reported no problems at their follow-ups. Although all of the appendectomy samples were normal macroscopically, data from this study suggest that all specimens should be sent for routine investigation.

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As the most common and most important cancer of the pancreas, with rapid mortality and now also as the third leading cause of cancer-related deaths in the United States, pancreatic ductal adenocarcinoma (PDAC) has become synonymous with "pancreas cancer". PDAC is also the prototype of the "pancreatobiliary-type" adenocarcinomas, along the biliary tract, ampullary and gallbladder cancers with the similar morphology and behavior. Recent molecular profiling studies have identified distinct subsets of PDAC, potentially with different behaviors and targetability. Moreover, while PDAC is by far the most common cancer of the pancreas, there are various other types that occur in this organ and are erroneously classified together with PDAC. Many of these have different molecular and biologic characteristics that warrant their management separately although they are also technically "pancreatic cancers". While some are closely related to PDAC and have as aggressive behavior (such as adenosquamous carcinomas which are recently recognized under "basal" like category in profiling studies, which are actually even worse prognostically than PDACs), in the meantime, others such as colloid carcinoma has a much better behavior than PDAC, and as a carcinoma with intestinal lineage (MUC2/CDX2) colloid carcinoma may require an entirely different treatment approach as well. Similarly, medullary carcinomas also appear to have different biology. Additionally, non-ductal cancers such as acinar, neuroendocrine, solid-pseudopapillary neoplasms and pancreatoblastoma have their respective clinicopathologic and molecular associations and warrant careful elimination in the management and study protocols. Another very problematic aspect in the classification of "pancreas cancer" is its delineation from the cancers of neighboring organs, in particular, ampullary/duodenal and common bile duct (CBD) cancers, for which recently more refined criteria have been provided. Additionally, the possibility of metastasis from another site and lymphomas also need to be considered. In summary, there is a whole host of cancers that occur in the pancreas that ought to be considered carefully before a case is classified as an ordinary "pancreas cancer" (PDAC).

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BACKGROUND: Pancreatoblastoma (PBL) is a rare malignant pancreatic tumor seen predominantly in childhood, and its cytologic diagnosis remains challenging. METHODS: Twelve fine-needle-aspirations from 11 adults were analyzed. RESULTS:In total, 6 men and 5 women (median age, 45 years; age range, 32-60 years) had tumors measuring a median 5.6 cm (range, 2.5-12 cm) located in the pancreatic head (n = 7) or tail (n = 4), including 3 with familial adenomatous polyposis (FAP)/ FAP-related syndromes and 4 with metastasis at diagnosis. The median follow-up was 39.8 months (range, 0.8-348 months), and 5 patients died of disease. The original cytology diagnoses were: PBL (n = 2), neuroendocrine neoplasm (n = 2), poorly differentiated neuroendocrine carcinoma (n = 2), well differentiated neuroendocrine tumor (n = 1), poorly differentiated carcinoma (n = 2), "positive for malignancy" (n = 1), acinar cell carcinoma (n = 1), and epithelioid neoplasm with endocrine and acinar differentiation versus PBL (n = 1). Universal cytopathologic findings included hypercellularity; 3-dimensional clusters; and single, monotonous, blast-like cells that were from 1.5 to 2.0 times the size of red blood cells with high nuclearto-cytoplasmic ratio, fine chromatin, small, distinct nucleoli, and a resemblance to well differentiated neuroendocrine tumor and poorly differentiated neuroendocrine carcinoma. Branching pseudopapillae (n = 7) and grooved nuclei (n = 3) raised the differential diagnosis of solid-pseudopapillary neoplasm, but with more atypia. Uncommon features included pleomorphism (n = 4) and numerous mitoses (n = 1). Squamoid morules were seen on smears (n = 5) or cell blocks (n = 6) in 70% of patients and were characterized by epithelioid cells with elongated, streaming nuclei, fine chromatin, absent nucleoli, and positive nuclear β-catenin (n = 6 of 8). The median Ki-67 index was 21% (range, 2%-70%), and neuroendocrine marker expression was common (100%), but acinar markers were variable (63%). CONCLUSIONS: A combination of cytologic findings in PBL, including a predominant population of primitive blast-like cells, subtle squamoid morules, frequent neuroendocrine and variable acinar phenotype, should facilitate accurate cytologic diagnosis and distinction from common mimics.