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Malignant gastrointestinal neuroectodermal tumor (GNET) is an infrequent soft-tissue sarcoma, formerly referred to as clear-cell sarcoma-like gastrointestinal tumor (CCSLGT) and frequently reported in the literature as clear-cell sarcoma of the gastrointestinal tract (CCS-GI); it is characterized by an absence of melanocytic differentiation and the presence of nontumoral osteoclast-like giant cells (OLGCs). The current study reports a case of a 79 year old woman admitted to the emergency department (ED) with symptoms of constipation and intestinal obstruction; a mass was found within the ileal wall necessitating of surgical approach. Immunohistochemically, tumor cells surprisingly had the hallmark of GNETs. Unfamiliarity with tumors with the features of GNETs can easily lead to a misdiagnosis by surgical pathologist. Therefore, comprehensive evaluation, including morphology and additional studies, is required for an appropriated diagnosis. Furthermore, without a high index of suspicion, there is actually no consensus on staging or treatment.

Multifocal fibrosing thyroiditis (MFT) is an enigmatic entity, characterized by multiple fibrotic scar-like lesions with a paucicellular fibrotic center surrounded by a cellular peripheral area with reactive-appearing follicular cell atypia and variable chronic inflammation. Although poorly recognized and likely underreported in surgical pathology, the entity is considered rare with only 65 cases to date–including the current one reported to expand on the preoperative findings of this under-recognized entity. The average age of the patients is 46.8 years (range 15–71 years), 94% are female, with female to male ratio of 15:1. Individual MFT lesions typically have a superficial location. The average number of fibrotic lesions is 15.4 (range 2–51 per MFT case). Their average size is 3.1 mm (range 0.4–15.1). MFT is a disorder of diseased thyroids, typically found postoperatively in glands removed for other reasons, such as chronic lymphocytic/Hashimoto thyroiditis (32.3%), follicular nodular disease (nodular hyperplasia) (30.1%), hyperthyroidism/diffuse hyperplasia (Graves disease) (9.2%). Intriguing is the association with papillary thyroid carcinoma–present in 38.5% of MFT cases, and particularly with sub-centimetric and multifocal papillary thyroid carcinoma, with which MFT can be confused. Cases where MFT is the only thyroid pathology (7.7%) can be preoperatively mistaken for papillary thyroid carcinoma, due to worrisome ultrasound (US) and cytologic features, both of which are here documented for the first time as a component of this article. Wider recognition of MFT and of its cytologic and ultrasound features at preoperative evaluation may reduce unnecessary thyroidectomies.

Background Standard suction and slow-pull techniques have been utilized during endoscopic ultrasound-guided fine needle aspiration of pancreatic solid lesions, but the correct sampling technique remains unclear. New needles designed to obtain samples suitable for histological evaluation have become available. We performed a study comparing the two sampling methods during endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) in patients with pancreatic solid lesions. Methods We performed EUS-FNB with a 20 Gauge FNB needle using slow-pull or standard suction techniques in a prospective, randomized, multicenter study. The primary aim was bloodiness of the collected specimens. Secondary aims were technical success and performance of the two techniques. Results 110 patients were included (55 per group). No difference in blood contamination was observed (slow-pull 80% vs. suction 74%, p = 0.917). Technical success was 95% (96% vs. 94%, p = 0315). Sensitivity (96% vs. 93%), specificity (100% vs. 100%), positive likelihood ratio (NA), negative likelihood ratio (0.04 vs. 0.07), diagnostic accuracy (96 vs. 93%) did not differ between the two groups. Conclusion EUS-FNB with slow-pull and standard suction techniques are comparable in terms of blood contamination providing similar high diagnostic sensitivity and accuracy in pancreatic solid lesions. The use of the new generation FNB needle allows to reach such high level of diagnostic adequacy regardless of the technique utilized.

Endoscopic ultrasound-guided tissue acquisition (EUS-TA) of solid pancreatic tumors shows optimal specificity despite fair sensitivity, with an overall suboptimal diagnostic yield. We aim to quantify the adequacy and accuracy of EUS-TA and assess predictive factors for success, focusing on the presence and degree of specimen fibrosis. All consecutive EUS-TA procedures were retrieved, and the specimens were graded for sample adequacy and fibrosis. The results were evaluated according to patients’ and tumor characteristics and the EUS-TA technique. In total, 407 patients (59% male, 70 [63–77] year old) were included; sample adequacy and diagnostic accuracy were 90.2% and 94.7%, respectively. Fibrosis was significantly more represented in tumors located in the head/uncinate process (p = 0.001). Tumor location in the head/uncinate (OR 0.37 [0.14–0.99]), number of needle passes ≥ 3 (OR 4.53 [2.22–9.28]), and the use of cell block (OR 8.82 [3.23–23.8]) were independently related to adequacy. Severe fibrosis was independently related to false negative results (OR 8.37 [2.33–30.0]). Pancreatic tumors located in the head/uncinate process showed higher fibrosis, resulting in EUS-TA with lower sample adequacy and diagnostic accuracy. We maintain that three or more needle passes and cell block should be done to increase the diagnostic yield.

Despite the efforts made in the management of PDAC, the 5-year relative survival rate of pancreatic ductal adenocarcinoma (PDAC) still remains very low (10%). To date, precision oncology is far from being ready to be applied in cases of PDAC, although studies exploring the molecular and genetic alterations have been conducted, and the genomic landscape of PDAC has been characterized. This study aimed to apply a next-generation sequencing (NGS) laboratory-developed multigene panel to PDAC samples to find molecular alterations that could be associated with histopathological features and clinical outcomes. A total of 68 PDACs were characterized by using a laboratory-developed multigene NGS panel. KRAS and TP53 mutations were the more frequent alterations in 75.0% and 44.6% of cases, respectively. In the majority (58.7%) of specimens, more than one mutation was detected, mainly in KRAS and TP53 genes. KRAS mutation was significantly associated with a shorter time in tumor recurrence compared with KRAS wild-type tumors. Intriguingly, KRAS wild-type cases had a better short-term prognosis despite the lymph node status. In conclusion, our work highlights that the combination of KRAS mutation with the age of the patient and the lymph node status may help in predicting the outcome in PDAC patients.

Inflammatory pseudotumor of the liver (IPTL) is a rare benign lesion that can mimic hepatic malignant neoplasms. A 79-year-old woman, in follow-up care for a left breast cancer, was referred to our Ultrasound Diagnostic Centre for a hepatic mass of unknown nature, displayed on PET-CT, CT and Abdominal Ultrasonography (US). The patient presented with abdominal pain and low-grade fever, increased values of C-Reactive Protein (CRP) and gamma-glutamyl transpeptidase (γGT). Abdominal US confirmed the presence of a heterogeneous polycyclic mass 4.0 × 3.7 cm in size, sub-capsular, localized in the segment VI, isoechoic in arterial phase and hypoechoic in portal and late phase on contrast-enhanced ultrasound (CEUS). A liver biopsy revealed the presence of chronic inflammatory cells without evidence of malignancy. As the patient did not respond to medical therapy, she underwent hepatic segmentectomy and cholecystectomy. At histology, the specimen showed acute and chronic inflammation with xanthogranulomatous features.

Carcinoma of the ampulla of Vater is an uncommon neoplasm and represents 0.5% of all gastrointestinal malignancies, being less common than carcinoma of the pancreas and bile ducts. The most common ampullary tumor is the adenocarcinoma with tubular growth pattern. Signet ring cell carcinoma is extremely rare. In this article, we report a case of signet ring cell carcinoma of the ampulla of Vater showing focal neuroendocrine amphicrine differentiation and intestinal phenotype, which occurred in a 49-year-old male who is still alive 7 years after surgery, without evidence of recurrence. This long-term survival might be attributed not only to the early stage of the disease but also to the neuroendocrine differentiation and the absence of genetic alterations.

Background and Objective: EUS-guided fine-needle biopsy has become the standard for tissue sampling. A new 20G ProCore™ (PC) needle has been developed to overcome the limitations of tissue acquisition of the smaller needles (22G, 25G) and the rigidity of the larger one (19G). The aim of this study is to assess the performance of the 20G PC needle. Materials and Methods: Patients who underwent EUS-guided tissue acquisition with the 20G PC needle of pancreatic and extra-pancreatic mass lesions were retrospectively identified at three Italian centers (Bologna, Fermo, and Palermo). Diagnostic adequacy, accuracy, and tissue core acquisition were the outcome measures. All the cases were performed without rapid on-site evaluation. Results: A total of 384 patients with pancreatic (62.2%) and extra-pancreatic lesions were included in the study. For pancreatic lesions, adequacy, accuracy, sensitivity, and specificity were 92.4%, 91.5%, 90.8%, and 100%, respectively, with a number needed to misdiagnose (NNM) of 11.8. The tissue core was obtained in 72% of cases. Transduodenal approach was performed in 150 pancreatic lesions; adequacy, accuracy, and tissue core acquisition were 88.7%, 90%, and 66%, respectively (NNM 10). For extrapancreatic lesions, adequacy, accuracy, sensitivity, specificity, and tissue core sampling were 95.3%, 95.3%, 92.6%, 100%, and 84.5% (NNM 21.3). Conclusions: The 20G PC needle showed high diagnostic adequacy and accuracy, regardless the access route.

Background No study has compared the performance of light microscopy (LM) and whole slide imaging (WSI) for endoscopic ultrasound (EUS) histological acquired tissue samples from pancreatic solid lesions (PSLs). We evaluated the concordance between LM and WSI and the inter- and intra-observer agreements among pathologists on PSLs EUS acquired samples. Methods LM and WSI from 60 patients with PSLs were evaluated by five expert pathologists to define: diagnostic classification, presence of a core, number and percentage of lesional cells. Washout period between evaluations was 3 months. Time of the procedures was also assessed. Results Forty-eight cell-block and 12 biopsy samples were evaluated. A high concordance between LM and WSI was found. Inter- and intra-observer agreements for diagnostic classification were substantial and complete, respectively. For all the other parameters, the inter-observer agreement was usually higher for LM. For the intra-observer, a substantial agreement was reached regarding the presence of tissue core and the number and the percentage of malignant cells. Median time for performing LM was significantly shorter than for WSI (p Conclusions LM and WSI of cell-block and biopsy samples acquired by EUS in PSLs were highly concordant, with a substantial inter-observer and a complete intra-observer agreements regarding diagnostic classification.

Background A hallmark of pancreatic ductal adenocarcinoma is the desmoplastic reaction, but its impact on the tumor behavior remains controversial. Our aim was to introduce a computer -aided method to precisely quantify the amount of pancreatic collagenic extra-cellular matrix, its spatial distribution pattern, and the degradation process. Methods A series of normal, inflammatory and neoplastic pancreatic ductal adenocarcinoma formalin-fixed and paraffin-embedded Sirius red stained sections were automatically digitized and analyzed using a computer-aided method. Results We found a progressive increase of pancreatic collagenic extra-cellular matrix from normal to the inflammatory and pancreatic ductal adenocarcinoma. The two-dimensional fractal dimension showed a significant difference in the collagenic extra-cellular matrix spatial complexity between normal versus inflammatory and pancreatic ductal adenocarcinoma. A significant difference when comparing the number of cycles necessary to degrade the pancreatic collagenic extra-cellular matrix in normal versus inflammatory and pancreatic ductal adenocarcinoma was also found. The difference between inflammatory and pancreatic ductal adenocarcinoma was also significant. Furthermore, the mean velocity of collagenic extra-cellular matrix degradation was found to be faster in inflammatory and pancreatic ductal adenocarcinoma than in normal. Conclusion These findings demonstrate that inflammatory and pancreatic ductal adenocarcinomas are characterized by an increased amount of pancreatic collagenic extra-cellular matrix and by changes in their spatial complexity and degradation. Our study defines new features about the pancreatic collagenic extra-cellular matrix, and represents a basis for further investigations into the clinical behavior of pancreatic ductal adenocarcinoma and the development of therapeutic strategies.

Context.—Integration of the analysis of genetic markers with endoscopic ultrasound–guided fine-needle aspiration and cytologic evaluation has increased the accuracy of the preoperative diagnosis of pancreatic lesions. The application of high-throughput gene panel analysis using next-generation sequencing platforms is now offering a great opportunity for further improvements.Objective.—To review the application of next-generation sequencing to the preoperative diagnosis of pancreatic lesions.Data Sources.—For data acquisition, a PubMed search using the terms next-generation sequencing, pancreas, pancreatic lesions, pancreatic tumors, and EUS-FNA was performed covering the years 2000–2017.Conclusions.—KRAS remains the gene most widely studied for preoperative single-gene tests. Next-generation sequencing reliably allows analysis of multiple gene markers starting from limited amounts of DNA. The study of multigene panels has become a very attractive option for the management and preoperative risk stratification of patients with pancreatic cancer.

Background Pancreatic adenocarcinoma (PDAC) is one of the deadliest human malignancies. Although surgery is currently the only effective treatment for PDAC, most patients survive less than 20 months after tumor resection. Objective The primary goal was to investigate alterations in KRAS, TP53, SMAD4 and CDKN2A/p16 in tumors from patients with exceptionally long survival after surgery. Methods Tumors from 15 patients with PDAC that survived more than 55 months after surgery ("LS") were analyzed for KRAS, TP53, IDH1, NRAS and BRAF using next-generation sequencing. SMAD4 and CDKN2A/p16 was tested using immunohistochemistry. MGMT promoter methylation was investigated. Results Tumors from "LS" have a lower prevalence of KRAS and TP53 mutations and had more frequently SMAD4 retained expression, if compared with that of patients died within 24 months from surgery. The survival of patients with wild-type KRAS and TP53 tumors was more than twice longer than that of patients bearing KRAS and TP53 mutations (90.2 vs. 41.1 months). Patients with KRAS wild-type tumors and that retained SMAD4 expression had a survival twice longer than cases with alterations in both genes (83.8 vs. 36.7 months). Eleven tumors (39.3%) showed MGMT methylation. Conclusions Our data indicate that absence of KRAS, TP53 and SMAD4 genetic alterations may identify a subset of pancreatic carcinomas with better outcome.

RECOMMENDATIONSFor routine EUS-guided sampling of solid masses and lymph nodes (LNs) ESGE recommends 25G or 22G needles (high quality evidence, strong recommendation); fine needle aspiration (FNA) and fine needle biopsy (FNB) needles are equally recommended (high quality evidence, strong recommendation).When the primary aim of sampling is to obtain a core tissue specimen, ESGE suggests using 19G FNA or FNB needles or 22G FNB needles (low quality evidence, weak recommendation).ESGE recommends using 10-mL syringe suction for EUS-guided sampling of solid masses and LNs with 25G or 22G FNA needles (high quality evidence, strong recommendation) and other types of needles (low quality evidence, weak recommendation). ESGE suggests neutralizing residual negative pressure in the needle before withdrawing the needle from the target lesion (moderate quality evidence, weak recommendation).ESGE does not recommend for or against using the needle stylet for EUS-guided sampling of solid masses and LNs with FNA needles (high quality evidence, strong recommendation) and suggests using the needle stylet for EUS-guided sampling with FNB needles (low quality evidence, weak recommendation).ESGE suggests fanning the needle throughout the lesion when sampling solid masses and LNs (moderate quality evidence, weak recommendation).ESGE equally recommends EUS-guided sampling with or without on-site cytologic evaluation (moderate quality evidence, strong recommendation). When on-site cytologic evaluation is unavailable, ESGE suggests performance of three to four needle passes with an FNA needle or two to three passes with an FNB needle (low quality evidence, weak recommendation).For diagnostic sampling of pancreatic cystic lesions without a solid component, ESGE suggests emptying the cyst with a single pass of a 22G or 19G needle (low quality evidence, weak recommendation). For pancreatic cystic lesions with a solid component, ESGE suggests sampling of the solid component using the same technique as in the case of other solid lesions (low quality evidence, weak recommendation).ESGE does not recommend antibiotic prophylaxis for EUS-guided sampling of solid masses or LNs (low quality evidence, strong recommendation), and suggests antibiotic prophylaxis with fluoroquinolones or beta-lactam antibiotics for EUS-guided sampling of cystic lesions (low quality evidence, weak recommendation). ESGE suggests that evaluation of tissue obtained by EUS-guided sampling should include histologic preparations (e. g., cell blocks and/or formalin-fixed and paraffin-embedded tissue fragments) and should not be limited to smear cytology (low quality evidence, weak recommendation).

Background Cytologic diagnosis by endoscopic ultrasound-guided fine needle aspiration is associated with low sensitivity and adequacy. A newly designed endoscopic ultrasound-guided fine needle biopsy device, endowed with a side fenestration, is now available. Aims We carried out a study with the aim of evaluating the feasibility, safety, and diagnostic yield of the 22-gauge needle with side fenestration for endoscopic ultrasound fine needle aspiration and biopsy of pancreatic cystic lesions. Methods 58 patients with 60 pancreatic cystic lesions consecutively referred for endoscopic ultrasound guided-fine needle aspiration were enrolled in a prospective, dual centre study, and underwent fine needle aspiration and biopsy with the 22-gauge needle with side fenestration. Results Fine needle aspiration and biopsy was technically feasible in all cases. In 39/60 (65%) pancreatic cystic lesions, the specimens were adequate for cyto-histologic assessment. In lesions with solid components, and in malignant lesions, adequacy was 94.4% ( p = 0.0149) and 100% ( p = 0.0069), respectively. Samples were adequate for histologic evaluation in 18/39 (46.1%) cases. There were only 2 (3.3%) mild complications. Conclusions Fine needle aspiration and biopsy with the 22-gauge needle with side fenestration is feasible, and superior to conventional endoscopic ultrasound-guided fine needle aspiration cytology from cystic fluid, particularly in pancreatic cystic lesions with solid component or malignancy, with a higher diagnostic yield and with no increase in complication rate.

Background and Aims The recent development of microforceps for EUS through-the-needle biopsy (TTNB) sampling of the wall of pancreatic cystic lesions (PCLs) allows the collection of histologic specimens never handled and evaluated before by pathologists. We aimed to estimate the interobserver agreement among pathologists in evaluating such samples. Methods TTNB specimen slides from 40 PCLs with worrisome features were retrieved and independently evaluated for specimen adequacy, presence of lining epithelium, grade of epithelial dysplasia, presence of ovarian type stroma, and specific diagnosis by 6 expert pathologists from 6 different tertiary care centers. The Gwet's AC1 was used to assess interobserver agreement. Results An almost perfect agreement was observed for specimen adequacy (AC1, .82; 95% confidence interval [CI], .79-.98), presence of lesional epithelium (AC1, .90; 95% CI, .86-.92), epithelial dysplasia (AC1, .97; 95% CI, .95-.99), and ovarian-like stroma (AC1, .90; 95% CI, .86-.93). When considering all diagnoses separately, a moderate to substantial agreement was observed (AC1, .62; 95% CI, .57-.67), similarly to mucinous cysts versus serous adenoma versus other diagnoses (AC1, .65; 95% CI, .59-.70) and for mucinous cysts versus all other diagnoses (AC1,.74; 95% CI, .68-.84). The agreement for diagnosis of mucinous cystic neoplasm versus intraductal mucinous papillary neoplasm was almost perfect (AC1, .88; 95% CI, .81-.95). Conclusions Interobserver agreement between expert pathologists in the evaluation of TTNB samples from PCLs with worrisome features was close to perfection for all evaluated parameters, except definitive diagnosis. When mucinous cystic lesions were compared versus all other diagnoses, the agreement became substantial, thus indicating that TTNB specimens can provide important information for PCL management decisions.

Objectives: PEComas (perivascular epithelioid cell tumors) are a family of neoplastic lesions that share overlapping ultrastructure and morphological and immunohistochemical appearance and include angiomyolipoma, lymphangioleiomyomatosis, and clear cell “sugar” tumor of the lung, as well as similar tumors that occur in a variety of visceral, cutaneous, and soft tissue sites throughout the body. Methods: A 40-year-old woman came to medical attention because of epistaxis and because of unilateral nasal obstruction of 3 months' duration. Endoscopic examination revealed a well-demarcated exophytic lesion attached to the anterior portion of the middle turbinate. Results: The lesion was superficially located, and therefore amenable to complete surgical excision. Seven years after surgery, the patient is alive and well, without evidence of local recurrence or metastastic disease. Based on morphological and immunohistochemical appearance, a diagnosis of PEComa with worrisome histologic features was rendered. Conclusions: In the present study, we describe a PEComa that occurred in the nasal cavity and discuss the behavior of this entity. The importance of recognizing this disease will ensure its consideration in the differential diagnosis of tumors of the head that have similar morphological features. The histogenesis of PEComa still remains elusive, and collection of additional cases with a prolonged follow-up will be important in accurately determining the behavior of these distinctive tumors.

Pancreatic metastases are rare. The role of surgery is poorly defined, and data on long-term survival are lacking.Data from patients with pancreatic metastases observed in our division from 2003 to 2008 were retrospectively analyzed. In addition, the recent English medical literature was reviewed regarding series of patients with pancreatic secondary tumors.Data from 234 patients including 9 consecutive patients observed in our division were retrieved. Metastasis from renal cell carcinoma accounted for 67.9% of all cases. Factors predictive of worse survival, as determined by multivariate analysis, were symptoms at diagnosis, synchronous tumors, radical-intent surgery not performed, and pathologic diagnosis of the primary tumor. Compared with pancreatic metastases from renal cell cancer, metastases from melanoma (P0.001) and lung cancer (P = 0.002) were associated with worse survival. The differences in survival of patients with renal cell cancer metastases and those with breast cancer, colorectal, or sarcoma metastases did not reach statistical significance.There may be a subset of patients with pancreatic metastases who are able to benefit from surgery with respect to improved long-term survival. Symptoms at diagnosis, presentation with primary tumor, surgical resection, and pathologic diagnosis seem to be important prognostic factors.

The first case of well-differentiated intrahepatic cholangiocarcinoma with remarkable follicular architecture resembling a follicular neoplasm of thyroid is described in a 52-year-old man. The follicles contained homogenous eosinophilic material akin to colloid and were lined by benign-looking cuboidal cells. Immunohistochemically, thyroid transcription factor-1 (TTF-1) and thyroglobulin were negative and the patient had no evidence of a previous or concomitant thyroid tumour. This case can be added to the list of extrathyroid primary tumours that resemble thyroid neoplasms.

AIM: To summarize the current knowledge about the potential relationship between hepatitis C virus (HCV) infection and the risk of several extra-liver cancers. METHODS: We performed a systematic review of the literature, according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) Statement. We extracted the pertinent articles, published in MEDLINE and the Cochrane Library, using the following search terms: neoplasm/cancer/malignancy/tumor/carcinoma/adeno-carcinoma and non-Hodgkin lymphomas, kidney/renal-, cholangio-, pancreatic-, thyroid-, breast-,oral-, skin-, prostate-, lung-, colon-, stomach-, haematologic. Case series, case-series with control-group, case-control, cohort-studies as well as meta-analyses, written in English were collected. Some of the main characteristics of retrieved trials, which were designed to investigate the prevalence of HCV infection in each type of the above-mentioned human malignancies were summarised. A main table was defined and included a short description in the text for each of these tumours, whether at least five studies about a specific neoplasm, meeting inclusion criteria, were available in literature. According to these criteria, we created the following sections and the corresponding tables and we indicated the number of included or excluded articles, as well as of meta-analyses and reviews: (1) HCV and haematopoietic malignancies; (2) HCV and cholangiocarcinoma; (3) HCV and pancreatic cancer; (4) HCV and breast cancer; (5) HCV and kidney cancer; (6) HCV and skin or oral cancer; and (7) HCV and thyroid cancer. RESULTS: According to available data, a clear correlation between regions of HCV prevalence and risk of extra-liver cancers has emerged only for a very small group of types and histological subtypes of malignancies. In particular, HCV infection has been associated with: (1) a higher incidence of some B-cell Non-Hodgkin-Lymphoma types, in countries, where an elevated prevalence of this pathogen is detectable, accounting to a percentage of about 10%; (2) an increased risk of intra-hepatic cholangiocarcinoma; and (3) a correlation between HCV prevalence and pancreatic cancer (PAC) incidence. CONCLUSION: To date no definitive conclusions may be obtained from the analysis of relationship between HCV and extra-hepatic cancers. Further studies, recruiting an adequate number of patients are required to confirm or deny this association.

Five cases of mucoepidermoid carcinoma (MEC) of the breast are reported. All patients were women ranging in age from 29 years to 80 years. As histological grading is one of the most important prognostic factors in breast invasive carcinomas, MEC was graded using the Auclair et al. [1] grading system specific for MEC of salivary glands and the Elston and Ellis [4] grading method, a widely employed grading system in breast cancer. It was found that the two different grading systems appear to be interchangeable in assessing the grade of MEC of the breast. Accordingly, three cases were regarded low grade (G. 1), one intermediate (G. 2) and one high grade (G. 3). The cases were studied with immunohistochemistry and were found to have the same keratin pattern shown by their salivary gland counterpart. It was found that there are more similarities than differences between MEC of the breast and of salivary glands.

Background Pancreatic mucinous cystic lesions might develop malignancy if untreated, or could harbor malignancy at the time of the diagnosis. Many reports stated that cyst fluid carcinoembryonic antigen is an accurate diagnostic marker of pancreatic mucinous cysts. Methods A man with a incidental pancretic cystic lesion of 35 mm in diameter was admitted to our Department. CT and EUS did not reveal solid components, main duct was not dilated and cyst fluid CEA was very high (1445 ng/ml). Results The patient underwent a pancreatoduodenectomy and the surgical specimen showed a pseudocyst with columnar mucinous epithelium, consistent with low-grade PanIN. Conclusions Is it possible that the mucinous epithelium of panIN was responsible for the unexpectedly high CEA value?Clinicians should be aware of the usefulness of the CEA level in cystic fluid but even a very high CEA value should not be considered by itself to be evidence of a mucinous lesion.

Early detection of small pancreatic cancer is important because expected survival is markedly better for tumors ≤2 cm. A new endoscopic ultrasound-(EUS) guided biopsy needle with side fenestration has been recently developed to enable fine-needle biopsy (FNB) under EUS guidance. The aim of this study was to evaluate the outcome of EUS–FNB using a 22-gauge ProCore needle in solid pancreatic lesions ≤2 cm, in terms of diagnostic accuracy and yield. From January 2011 to December 2012, all consecutive EUS-guided tissue sampling of small pancreatic lesions (≤2 cm) were performed using 22-gauge ProCore needles; the data of these patients were analyzed retrospectively. Sixty-eight patients with a mean age of 65.7 years were included. The mean lesion size was 16.5 mm (range 5–20). None of the patients developed complications. On pathological examination, the tissue retrieved was judged adequate in 58 out of 68 cases (85.3 %) and the presence of a tissue core was recorded in 36 out of 68 cases (52.9 %). The overall sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 80, 100, 100, 40, and 82 %, respectively. Our results suggested that EUS–FNB of small pancreatic lesions using a 22-gauge ProCore needle is effective and safe, and supports our hypothesis that EUS–FNB is highly useful in establishing the nature of small pancreatic lesions.

Merkel cell carcinoma of the parotid gland associated with Warthin tumour: report of two cases Aims: Two cases of Merkel cell carcinoma occurring simultaneously and in close association with a Warthin tumour of the parotid gland are reported Methods and results: The patients were a 65-year-old man and a 70-year-old man, respectively. The Merkel cell carcinoma component was immunoreactive for chromogranin and keratin 20 and contained neuroendocrine-type granules at the ultrastructural level. Conclusions: The histogenesis of this heretofore undescribed combination is discussed.

A case of uterine leiomyoma with skeletal muscle differentiation is described. The patient is a 40-year-old woman who underwent abdominal hysterectomy and left salpingo-oophorectomy for fibroids. Evidence of skeletal muscle differentiation was evident at light and electron microscopy in one out of three "ordinary" leiomyomas. This was also shown by positive immunoreactions with antiskeletal muscle actin and myoglobin antisera. To our knowledge, this is the second case reported of the occurrence of skeletal muscle differentiation within a uterine leiomyoma and highlights the divergent differentiating potential of smooth muscle cells.

A case of extra-abdominal fibromatosis (EF) of the orbit is described in a 35-year-old man presenting with progressive exophthalmos, right ptosis and diplopia. MRI showed an orbital mass of intermediate signal in T1-weighted images (WI) and low signal in T2WI, which enhanced non-homogeneously after contrast injection. The histological diagnosis of EF was made and the lesion was surgically removed. No recurrence occurred in 40 months of follow-up.

Aim of the present review is to summarize the current knowledge about the potential relationship between miRNAs and hepatitis B virus (HBV)-hepatitis C virus (HCV) related liver diseases. A systematic computer-based search of published articles, according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis Statement, was performed to identify relevant studies on usefulness of serum/plasma/urine miRNAs, as noninvasive biomarkers for early detection of HBV and HCV-induced hepatocellular carcinoma (HCC) development, as well as for its prognostic evaluation. The used Medical Subject Headings terms and keywords were: “HBV”, “HCV”, “hepatocellular carcinoma”, “microRNAs”, “miRNAs”, “diagnosis”, “prognosis”, “therapy”, “treatment”. Some serum/plasma miRNAs, including miR-21, miR-122, mi-125a/b, miR-199a/b, miR-221, miR-222, miR-223, miR-224 might serve as biomarkers for early diagnosis/prognosis of HCC, but, to date, not definitive results or well-defined panels of miRNAs have been obtained. More well-designed studies, focusing on populations of different geographical areas and involving larger series of patients, should be carried out to improve our knowledge on the potential role of miRNAs for HCC early detection and prognosis.

Neuroendocrine gastroenteropancreatic tumors constitute a heterogeneous group of neoplasms, with the primary tumors being located in the gastric mucosa, pancreas, and small and large intestine. The development of a second primary malignancy in patients with these tumors is a well-described phenomenon, and the reported incidence ranges from 12% to 46%. The most common site of associated noncarcinoid malignancies is the gastrointestinal tract, which involves from 30% to 60% of the tumors. We report a case of concurrent colon carcinoma and two neuroendocrine tumors of the duodenum.

Background The difference in the diagnostic accuracy of 22- versus 25-gauge needles in EUS-FNA is not clear. Aims To compare the rates of technical success, diagnostic accuracy and complications of EUS-FNA performed with 22-gauge and 25-gauge needles on the same solid pancreatic mass. Methods All patients with solid pancreatic masses evaluated from September 2007 to December 2008 were enrolled and underwent EUS-FNA with both 22- and 25-gauge needles with randomisation of needle sequence. The accuracy of the EUS-FNA was determined by comparing the cytological results with the final surgical pathological diagnoses or with the results of a clinical follow-up. A cytological score with different qualitative parameters was created, and a comparison between these parameters was carried out for each needle. Results Fifty patients with 50 pancreatic masses were recruited. Technical success was 100% and no complications occurred. Diagnostic accuracy was 94% and 86% for the 25- and 22-gauge needles, respectively. Analysis of the cytological score showed a tendency towards the 25-gauge needle, although the difference was not statistically significant. Conclusions EUS-FNA performed with 22- or 25-gauge needles had the same diagnostic accuracy. Our study results confirm a significant trend towards a better cytological diagnosis for the 25-gauge needle.

none 21 Pancreatic adenocarcinoma (PAC) is a very aggressive cancer with a poor prognosis. To date, the causes and pathogenetic mechanisms involved in the development of this malignancy remain largely unknown. Therefore, additional studies are required to improve our knowledge of the events that occur during the process of pancreatic carcinogenesis. The purpose of this article is to describe the most recent evidence, concerning the possible risk factors and mechanisms that may contribute to determine the development of PAC, as well as models, such as the tensegrity model, that may explain this complex process. Available studies suggest that approximately 15-20% of human malignancies are somehow associated with chronic infection. Some epidemiological research has shown that some infectious agents represent risk factors for PAC. In particular, several reports showed that the infection caused by some micro-organisms, including helicobacter pylori and some bacterial species of oral microbiota, as well as by viral agents, such as human immunodeficiency virus (HIV), and hepatitis B (HBV) and C (HCV) viruses, is associated with an increased probability of developing PAC. For the first time, observational studies and meta-analyses have suggested that HBV and HCV, two hepatotropic viruses with oncogenic properties, may be also risk factors for PAC. However, the small number of available reports, nearly all performed in Asian populations, limits their validity to these ethnic groups. Therefore, additional studies focusing on populations of different geographical areas and enrolling larger series of patients are required to confirm this association. Furthermore, an accurate description and a better understanding of the events and of the pathogenetic mechanisms involved in the process of pancreatic carcinogenesis, as proposed by the tensegrity model, might be a useful approach to effectively deal with this pathology. Sirio Fiorino;Letizia Bacchi-Reggiani;Laura Pontoriero;Claudio Gallo;Elisabetta Chili;Michele Masetti;Nicola Zanini;Anna Grondona;Tania Silvestri;Gaia Deleonardi;Elisabetta Magrini;Roberto Motta;Adele Fornelli;Arrigo Bondi;Dario De Biase;Paola Baccarini;Giovanni Tallini;Antonio Tropeano;Andrea Cuppini;Gastone Castellani;Elio Jovine Sirio Fiorino;Letizia Bacchi-Reggiani;Laura Pontoriero;Claudio Gallo;Elisabetta Chili;Michele Masetti;Nicola Zanini;Anna Grondona;Tania Silvestri;Gaia Deleonardi;Elisabetta Magrini;Roberto Motta;Adele Fornelli;Arrigo Bondi;Dario De Biase;Paola Baccarini;Giovanni Tallini;Antonio Tropeano;Andrea Cuppini;Gastone Castellani;Elio Jovine

EUS to exclude, detect and stage ampullary lesions and perform biopsy or FNA. EUS excluded suspected malignant disease in 43% of cases. Mo1477 FISH Analysis of Aspirates Increases the Sensitivity of EUS-Guided FNA for the Diagnosis of Pancreatic Adenocarcinoma Jose-Guillermo De La Mora-Levy*, Juan O. Campuzano, Judith Cruz-Velazquez, Octavio Alonso, Julio Sanchez Del Monte, Sergio R. Sobrino-Cossio, Angelica Hernandez-Guerrero Gastroenterology, National Cancer Institute, Mexico City, Mexico; Cytogenetics, National Cancer Institute, Mexico City, Mexico Background: The sensitivity of EUS-guided cytology for the diagnosis of pancreatic adenocarcinoma is between 70 & O90%; among the identified factors that predict a positive result, the presence of a cytopathologist, number and passes and posible the type of needle have been identified as helpful. Aim: To study if the addition of FISH to cytology increases the sensitivity of EUS-guided FNA. Material & Methods: Consecutive patients with a pancreatic mass, sent for EUS-guided FNA to our Unit. An Olympus GF-UCT 160 echoendoscope and 22 gauge needles (EchoTip , Cook Medical), were used. Between 1-4 passes (median: 2) were performed for preparation of slides and cell block; 1 random slide was used for FISH analysis, which was performed using a commercially available kit (Urovision ). NO cytopathologist was present during the procedure. A total of 112 patients was calculated as the number needed to demonstrate at least a 10% increase in sensitivity, assuming an average of 80% sensitivity. A positive result was considered when either cytopathology or FISH alone or both were positive. Diagnostic values were calculated for Cytology, FISH and the combination; increase in sensitivity was the main variable. Inadequate specimens were purposely not included. The gold standard was considered to be: the surgical specimen, or a combination of CA 19-9 values, appropriate clinical and imaging picture plus compatible outcome on follow-up (FU). The study was approved by the IRB of our Institution. Results: A total of 105 patients were included; 16 were excluded for various reasons and analysis was performed on 89 patients. 49 were female, with a median age of 58 years (37-84); median FU was 4 months (1-12). Diagnostic values are shown in Table 1: A 13% increase in sensitivity was found, even when the calculated number was not reached. Conclusion: The addition of FISH analysis to EUS-guided FNA increases the sensitivity and positive results in patients with pancreatic adenocarcinoma. FISH could be used routinely, specially in settings without an onsite cytopathologist and with relatively few needle passes.

s / Pancreatology 13 (2013) S2–S98 S81 OR body mass index OR lean tissue loss OR fat free mass). Relevant Abstracts were read, eligible articles retrieved and a manual search of the bibliographies performed. The «related article» function in PubMed was used to identify missed studies. English language relevant clinical studies of any level of evidence were included. Unpublished data, Abstract or duplicate publications were excluded. Results: Two articles were found of 343 articles and related research. Two retrospective trials included 152 patients with inoperable pancreatic adenocarcinoma. The prevalence of sarcopenia was 62(56%) and 26(63%) patients. All had advanced cancer and underwent chemotherapy/chemoradiation. Sarcopenia was assessed by means of CT-scan skeletal muscle calculation. Sarcopenia alone was not significantly associated with poor survival. In multivariate analysis sarcopenic obesity but not sarcopenia alone was associated with significantly lower survival. Conclusion: The systematic review showed the lack of data about sarcopenia impact on survival in patients with pancreatic cancer. It justifies the need of further research. PII-96 Abstract id: 85. Liver resection for metastatic periampullary cancer: Is it (sometimes) worthwile? Nicola Zanini , Raffaele Lombardi , Luca Valeriani , Dario de Biase , Francesco Cinquantini , Adele Fornelli , Michele Masetti , Elio Jovine . Dept of Surgery, Maggiore Hospital, Bologna, Italy Dept of Clinical Nutrition, Maggiore Hospital, Bologna, Italy University of Bologna, Bologna, Italy Dept of Radiology, Maggiore Hospital, Bologna, Italy Dept of Pathology, Maggiore Hospital, Bologna, Italy Introduction: Surgery is generally not indicated for metastatic periampullary adenocarcinoma because it does not appear to improve survival. Aims: Is metastastic periampullary cancer an absolute contraindication to surgery? Could someone benefit from liver resection? Patients & methods: Our prospectively collected database (20032012) lists 21 patients who underwent liver resection for metastases from periampullary adenocarcinoma. Resection was offered to young patients who were fit for surgery and had few synchronous or metachronous metastases. Potential prognostic factors were taken into consideration to design a score that was applied to the study population to predict survival. Results: Ductal carcinoma was the primary tumor in 15 patients; the remaining patients had ampullary carcinoma or distal bile duct carcinoma. One right hepatectomy, 2 bisegmentectomies and 18 atypical resections were performed. Simultaneous liver and pancreatic resection did not significantly improve postoperative morbidity and mortality compared to standard pancreatic resection. The median overall survival from liver resection (OS) of patients with synchronous and metachronous disease was 11.4 months (95% CI: 6.0-16.9) and 28.5 months (95% CI: 1.7-55.2), respectively (p1⁄40.12). The proposed score was able to divide the subjects into three classes of prognosis, inwhich the estimated OS was significantly different. Conclusion: Surgery for liver metastases from periampullary tumors is controversial. It is not suggested for most patients, and death may occur even earlier compared to palliative cure. However, a small group of highly select patients could benefit from surgery. PII-97 Abstract id: 109. MMP9 and S100A9 expression in peripheral blood mononuclear cells (PBMC) are correlated with PDAC and with PDAC-associated diabetes mellitus Stefania Moz , Dania Bozzato , Carlo Federico Zambon , Paola Fogar , Michela Pelloso , Anna Caterina Milanetto , Andrea Padoan , Filippo Navaglia , Eliana Greco , Claudio Pasquali , Mario Plebani , Daniela Basso . Department of Medicine DIMED,University of Padova., Italy Department of Surgical, Oncological and Gastroenterological Sciences DISCOG; University of Padova, Italy Introduction: Tumor-stroma-endocrine interactions favour pancreatic adenocarcinoma (PDAC) growth/progression and PDAC-associated diabetes mellitus (DM). S100A8/A9 and the matrix methalloproteinases (MMPs) 8 and 9 are overexpressed in PDAC stroma. Aims: To verify whether S100A8, S100A9, MMP8 and MMP9 mRNA in PBMC is useful for diagnosing and staging PDAC and/or for detecting PDACassociated DM. To study the impact of S100A8/A9 and of PDAC-associated growth factors and cytokines on MMPs expression. Patients & methods: S100A8, S100A9, MMP8 e MMP9 mRNA were quantified by qRT-PCR in 62 PDAC, 37 chronic pancreatitis, 23 pancreatobiliary tract tumors (PBT) and 30 healthy controls (HC). PBMC (blood donors) were treated with insulin, EGF, TGFb1, S100A8/A9 before MMP8 and MMP9 mRNA analysis. Results:MMP8 andMMP9 were higher in PDAC and in PBT than in HC (Kruskal-Wallis Test: p

Thirty cases of ductal carcinoma in situ (DCIS) of the breast, showing histological microcalcifications, were studied to clarify their mechanism of formation. Undecalcified sections revealed three types of calcium precipitates: type I and II granular calcifications (GCs) and laminar calcifications (LCs). In type I GCs the core on which the calcium had deposited was constituted mainly by nuclear debris. Type II GCs were predominantly composed by mucosubstances. LCs were the result of calcium deposits on mucoid or proteinaceous material, arranged in concentric lamellae. LCs and type II GCs were mainly present in well and intermediately differentiated DCIS. Type I GCs were observed in only DCIS with necrosis, frequently being present in intermediately and poorly differentiated DCIS.