Basal cell carcinoma with progression to metastatic neuroendocrine carcinoma

Merkel cell carcinoma (MCC) or primary cutaneous neuroendocrine carcinoma is a malignant tumor considered to demonstrate differentiation towards Merkel cells that are present at the base of the epidermis or around the apical end of some hair follicles and are thought to play a yet uncertain role in sensory transduction. Here we present the case of a 54- year old female with a basal cell carcinoma (BCC) of the skin with neuroendocrine features (positivity for chromogranin) that has evolved during multiple recurrences and radiotherapy into a high-grade neuroendocrine carcinoma with morphological and immunohistochemical features of MCC (trabecular and nesting arrangement, positivity for chromogranin, cytokeratin 20, neuron specific enolase, and also neurosecretory granules on electron microscopy). The progression from a chromogranin positive basal cell carcinoma of the skin, to a high-grade neuroendocrine carcinoma demonstrates the potential for cross differentiation among skin tumors

Staging laparoscopy for proximal pancreatic cancer in a magnetic resonance imaging-driven practice: what's it worth?

AbstractBackgroundPreoperative imaging is often inadequate in excluding unresectable pancreatic cancer. Accordingly, many groups employ staging laparoscopy (SL), although none have evaluated SL after preoperative magnetic resonance imaging (MRI). We performed a retrospective, indirect cost-effectiveness analysis of SL after MRI for pancreatic head lesions.MethodsAll MRI scans administered for proximal pancreatic cancer between 2004 and 2008 were reviewed and the clinical course of each patient determined. We queried our billing database to render average total costs for all inpatients with proximal pancreatic cancer who underwent pancreaticoduodenectomy, palliative bypass or an endoscopic stenting procedure. We then performed an indirect evaluation of the cost of routine SL.ResultsThe average costs of hospitalization for patients undergoing pancreaticoduodenectomy, open palliative bypass and endoscopic palliation were: US$26122.43, US$21957.18 and US$11304.00, respectively. The calculated cost of SL without laparotomy was US$2966.25 or US$1538.61 prior to laparotomy. The calculated cost of treating unresectable disease by outpatient laparoscopy followed by endoscopy was US$5943.17. Routine SL would increase our costs by US$76967.46 (3.6%).ConclusionsStaging laparoscopy becomes cost-effective by diverting unresectable patients from operative to endoscopic palliation. Given the paucity of missed metastases on MRI, the yield of SL is marginal and its cost-effectiveness is poor. Future studies should address the utility of SL by both examining this issue prospectively and investigating the cost-effectiveness of endoscopic vs. surgical palliation in a manner that takes account of survival and quality of life data

Characterization of pancreatic lesions from MT-tgfα, Ela-myc and MT-tgfα/Ela-myc single and double transgenic mice

In order to identify good animal models for investigating therapeutic and preventive strategies for pancreatic cancer, we analyzed pancreatic lesions from several transgenic models and made a series of novel findings. Female MT-tgfα mice of the MT100 line developed pancreatic proliferation, acinar-ductal metaplasia, multilocular cystic neoplasms, ductal adenocarcinomas and prominent fibrosis, while the lesions in males were less severe. MT-tgfα-ES transgenic lines of both sexes developed slowly progressing lesions that were similar to what was seen in MT100 males. In both MT100 and MT-tgfα-ES lines, TGFα transgene was expressed mainly in proliferating ductal cells. Ela-myc transgenic mice with a mixed C57BL/6, SJL and FVB genetic background developed pancreatic tumors at 2–7 months of age, and half of the tumors were ductal adenocarcinomas, similar to what was reported originally by Sandgren et al [1]. However, in 20% of the mice, the tumors metastasized to the liver. MT100/Ela-myc and MT-tgfα-ES/Ela-myc double transgenic mice developed not only acinar carcinomas and mixed carcinomas as previously reported but also various ductal-originated lesions, including multilocular cystic neoplasms and ductal adenocarcinomas. The double transgenic tumors were more malignant and metastasized to the liver at a higher frequency (33%) compared with the Ela-myc tumors. Sequencing of the coding region of p16ink4, k-ras and Rb cDNA in small numbers of pancreatic tumors did not identify mutations. The short latency for tumor development, the variety of tumor morphology and the liver metastases seen in Ela-myc and MT-tgfα/Ela-myc mice make these animals good models for investigating new therapeutic and preventive strategies for pancreatic cancer

Pancreatoblastoma: Cytologic and histologic analysis of 12 adult cases reveals helpful criteria in their diagnosis and distinction from common mimics

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152894/1/cncy22187_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152894/2/cncy22187.pd

Cytologic features and clinical implications of undifferentiated carcinoma with osteoclastic giant cells of the pancreas: An analysis of 15 cases

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137765/1/cncy21859.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137765/2/cncy21859_am.pd

Acinar Cell Cystadenoma (Acinar Cystic Transformation) of the Pancreas: the Radiologic-Pathologic Features

Acinar cystic transformation of the pancreas is also known as acinar cell cystadenoma (ACC), and this is an extremely rare benign lesion that was first described in April 2002. We report here on a case of a previously asymptomatic patient with pancreatic ACC and this was diagnosed by computed tomography (CT) and magnetic resonance imaging (MRI). To the best of our knowledge, there is no previous report concerning the CT or MRI features of ACC in the medical literature. We present here the CT, MRI and pathological findings of pancreatic ACC

Tris DBA palladium is highly effective against growth and metastasis of pancreatic cancer in an orthotopic model

Pancreatic carcinoma ranks among the most lethal of human cancers. Besides late detection, other factors contribute to its lethality, including a high degree of chemoresistance, invasion, and distant metastases. Currently, the mainstay of therapy involves resection of local disease in a minority of patients (Whipple procedure) and systemic gemcitabine. While systemic chemotherapy has some benefit, even with optimal treatment, the five year survival after diagnosis is dismal. Thus, treatment of pancreatic carcinoma remains a tremendous unmet need. The organometallic compound tris DBA palladium is a potent inhibitor of N-myristoyltransferase 1 (NMT1), an enzyme that catalyzes the transfer of myristate to protein substrates. This compound is highly effective in vivo against murine models of melanoma with both mutant and wild type b-RAF genotypes. Based upon the signaling similarities between melanoma and pancreatic carcinoma, we evaluated the efficacy of tris DBA palladium in vitro and in vivo against pancreatic carcinoma. We found that tris DBA palladium decreased proliferation and colony formation of pancreatic cancer cells in vitro. In an orthotopic mouse model, tris DBA palladium was highly active in inhibiting growth, ascites production, and distant metastases in vivo. Furthermore, tris DBA palladium impaired chemotaxis and inhibited cilia formation in Pan02 cells in a NMT1-dependent manner. We propose that NMT1 is a novel regulator of cilia formation and tris DBA palladium a novel inhibitor of cilia formation and metastasis in pancreatic cancer. Thus, further evaluation of tris DBA palladium for the treatment of pancreatic cancer is warranted

Surgical outcomes of gallbladder cancer:the OMEGA retrospective, multicentre, international cohort study

Background: Gallbladder cancer (GBC) is rare but aggressive. The extent of surgical intervention for different GBC stages is non-uniform, ranging from cholecystectomy alone to extended resections including major hepatectomy, resection of adjacent organs and routine extrahepatic bile duct resection (EBDR). Robust evidence here is lacking, however, and survival benefit poorly defined. This study assesses factors associated with recurrence-free survival (RFS), overall survival (OS) and morbidity and mortality following GBC surgery in high income countries (HIC) and low and middle income countries (LMIC). Methods: The multicentre, retrospective Operative Management of Gallbladder Cancer (OMEGA) cohort study included all patients who underwent GBC resection across 133 centres between 1st January 2010 and 31st December 2020. Regression analyses assessed factors associated with OS, RFS and morbidity. Findings: On multivariable analysis of all 3676 patients, wedge resection and segment IVb/V resection failed to improve RFS (HR 1.04 [0.84–1.29], p = 0.711 and HR 1.18 [0.95–1.46], p = 0.13 respectively) or OS (HR 0.96 [0.79–1.17], p = 0.67 and HR 1.48 [1.16–1.88], p = 0.49 respectively), while major hepatectomy was associated with worse RFS (HR 1.33 [1.02–1.74], p = 0.037) and OS (HR 1.26 [1.03–1.53], p = 0.022). Furthermore, EBDR (OR 2.86 [2.3–3.52], p &lt; 0.0010), resection of additional organs (OR 2.22 [1.62–3.02], p &lt; 0.0010) and major hepatectomy (OR 3.81 [2.55–5.73], p &lt; 0.0010) were all associated with increased morbidity and mortality. Compared to LMIC, patients in HIC were associated with poorer RFS (HR 1.18 [1.02–1.37], p = 0.031) but not OS (HR 1.05 [0.91–1.22], p = 0.48). Adjuvant and neoadjuvant treatments were infrequently used. Interpretation: In this large, multicentre analysis of GBC surgical outcomes, liver resection was not conclusively associated with improved survival, and extended resections were associated with greater morbidity and mortality without oncological benefit. Aggressive upfront resections do not benefit higher stage GBC, and international collaborations are needed to develop evidence-based neoadjuvant and adjuvant treatment strategies to minimise surgical morbidity and prioritise prognostic benefit. Funding:Cambridge Hepatopancreatobiliary Department Research Fund.</p

Genomic characterization of malignant progression in neoplastic pancreatic cysts

Intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs) are non-invasive neoplasms that are often observed in association with invasive pancreatic cancers, but their origins and evolutionary relationships are poorly understood. In this study, we analyze 148 samples from IPMNs, MCNs, and small associated invasive carcinomas from 18 patients using whole exome or targeted sequencing. Using evolutionary analyses, we establish that both IPMNs and MCNs are direct precursors to pancreatic cancer. Mutations in SMAD4 and TGFBR2 are frequently restricted to invasive carcinoma, while RNF43 alterations are largely in non-invasive lesions. Genomic analyses suggest an average window of over three years between the development of high-grade dysplasia and pancreatic cancer. Taken together, these data establish non-invasive IPMNs and MCNs as origins of invasive pancreatic cancer, identifying potential drivers of invasion, highlighting the complex clonal dynamics prior to malignant transformation, and providing opportunities for early detection and intervention

Gallbladder reporting and data system (GB-RADS) for risk stratification of gallbladder wall thickening on ultrasonography:an international expert consensus

The Gallbladder Reporting and Data System (GB-RADS) ultrasound (US) risk stratification is proposed to improve consistency in US interpretations, reporting, and assessment of risk of malignancy in gallbladder wall thickening in non-acute setting. It was developed based on a systematic review of the literature and the consensus of an international multidisciplinary committee comprising expert radiologists, gastroenterologists, gastrointestinal surgeons, surgical oncologists, medical oncologists, and pathologists using modified Delphi method. For risk stratification, the GB-RADS system recommends six categories (GB-RADS 0–5) of gallbladder wall thickening with gradually increasing risk of malignancy. GB-RADS is based on gallbladder wall features on US including symmetry and extent (focal vs. circumferential) of involvement, layered appearance, intramural features (including intramural cysts and echogenic foci), and interface with the liver. GB-RADS represents the first collaborative effort at risk stratifying the gallbladder wall thickening. This concept is in line with the other US-based risk stratification systems which have been shown to increase the accuracy of detection of malignant lesions and improve management. Graphical abstract: [Figure not available: see fulltext.]