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Background Nephrogenic systemic fibrosis is a fibrosing disorder associated with exposure to gadolinium-based contrast agents in people with severely compromised renal function. Objective The purpose of this study was to determine the reported number of cases of nephrogenic systemic fibrosis in children using three distinct publicly available data sources. Materials and methods We conducted systematic searches of the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS), the International Center for Nephrogenic Systemic Fibrosis Research (ICNSFR) registry and published literature from January 1997 through September 2012. We contacted authors of individual published cases to obtain follow-up data. Data sets were cross-referenced to eliminate duplicate reporting. Results We identified 23 children with nephrogenic systemic fibrosis. Seventeen had documented exposure to gadolinium-based contrast agents. Six children had been reported in both the FAERS and the literature, four in the FAERS and the ICNSFR registry and five in all three data sources. Conclusion Nephrogenic systemic fibrosis has been rarely reported in children. Although rules related to confidentiality limit the ability to reconcile reports, active pharmaco-vigilance using RADAR (Research on Adverse Drug events And Reports) methodology helped in establishing the number of individual pediatric cases within the three major data sources.

Cite this article as: Edwards BJ, Laumann AE, Nardone B, Miller FH, Restaino J, Raisch DW, et al. Advancing pharmacovigilance through academic-legal collaboration: the case of gadolinium-based contrast agents and nephrogenic systemic fibrosis-a research on adverse drug events and reports (RADAR) report. Br J Radiol 2014;87:20140307. FULL PAPERAdvancing pharmacovigilance through academic-legal collaboration: the case of gadolinium-based contrast agents and nephrogenic systemic fibrosis-a research on adverse drug events and reports (RADAR) report Results: The FAERS encompassed the largest number (n 5 1395) of NSF reports. The ICNSFR contained the most complete (n 5 335, 100%) histopathological data. A total of 382 individual biopsy-proven, product-specific NSF cases were analysed from the legal data set. 76.2% (291/382) identified exposure to gadodiamide, of which 67.7% (197/291) were unconfounded. Additionally, 40.1% (153/382) of cases involved gadopentetate dimeglumine, of which 48.4% (74/153) were unconfounded, while gadoversetamide was identified in 7.3% (28/382) of which 28.6% (8/28) were unconfounded. Some cases involved gadobenate dimeglumine or gadoteridol, 5.8% (22/382), all of which were confounded. The mean number of exposures to gadolinium-based contrast agents (GBCAs) was gadodiamide (3), gadopentetate dimeglumine (5) and gadoversetamide (2). Of the 279 unconfounded cases, all involved a linear-structured GBCA. 205 (73.5%) were a non-ionic GBCA while 74 (26.5%) were an ionic GBCA. Conclusion: Clinical and legal databases exhibit unique characteristics that prove complementary in safety evaluations. Use of the legal data set allowed the identification of the most commonly implicated GBCA. Advances in knowledge: This article is the first to demonstrate explicitly the utility of a legal data set to pharmacovigilance research.

We confirmed that CD99 and CD10 are frequently expressed in AFX (65 and 85%, respectively) and that CD31 rarely stains positive (5%). The 50% positivity rate of D2-40, in contrast with published evidence for its absence in melanoma, suggests that D2-40 may be useful for distinguishing AFX from melanoma. Furthermore, because only one sample was positive for p75, we confirm that p75 is useful in differentiating AFX from spindle cell melanoma. We advocate adding p75 and D2-40 to assist in differentiating AFX from melanoma.

8563 Background: Melanoma is subdivided into molecular defined groups. One major subtype is characterized by a mutation in the BRAF gene. BRAF is less commonly mutated in acrolentiginous (ALM) and mucosal (MM) melanomas, instead these subtypes predominantly show aberrations in the KIT/CD117 gene. KIT aberrations predict the outcome of targeted therapies in ALM and MM patients, however the particular role of KIT expression in these melanoma subtypes remains controversial. To explore the relationship between KIT expression, mutation, and tumor stages, we investigated immunohistochemical KIT expression and mutation status in primary ALM/MM lesions and their metastases. We also compared the frequency of KIT mutations of MM in different anatomic locations. Methods: KIT immunoreactivity and mutation status was assessed in 41 ALM and 25 MM patients, using polyclonal rabbit anti-human KIT/CD117 antibody, and PCR was performed for KIT gene exons 9,11,13,17 and 18. Of these, 19 ALM and 15 MM patients had matched primary and metastatic lesions. Phosphorylated extracellular regulated kinase (P-ERK) was investigated in a subset of 8 ALM and 8 MM matched primary/metastatic pairs by immunohistochemistry. Results: Heterogeneous KIT immunoreactivity was observed in both primary and metastatic lesions. Mutations were present in four of 41 ALM (10%) and five of 25 MM (20%) patients. Only vulvar mucosal samples carried KIT mutations in contrast to sinonasal lesions (p= 0.0109). In KIT-mutated tumors, the mutations were present in KIT expressing as well as KIT negative cells, as shown by Laser Capture Microdissection (LCM). P-ERK expression was preferentially found in metastases. Conclusions: KIT expression is heterogeneous and shows no relationship with disease progression and mutation status, therefore KIT immunoreactivity is not a valuable marker for treatment decisions. In mucosal melanoma patients, KIT mutation frequency is significantly associated with anatomic location. Vulvar melanoma patients are prone to carry activating KIT mutations and thus may be more likely to benefit from KIT-targeted therapies than other subtypes. Therefore, especially vulvar melanoma patients should be screened for activating KIT mutations.