Jakobiec FA, Borkar DS, Stagner AM, Lee NG.
Intraocular Teratoid Medulloepithelioma Presenting With a Completely Rhabdomyosarcomatous Distant Metastasis. JAMA Ophthalmol 2016;134(8):919-923.
AbstractImportance: Medulloepithelioma is the second most common primary neuroepithelial tumor of the eye. The full range of its morphologic expressions and appearances in metastases have not been fully explored. Observations: A patient in her 50s with glaucoma for decades had undergone multiple filtering surgical procedures, including the placement of a glaucoma drainage device. A paraspinal mass was discovered, and tumor and bone marrow biopsies disclosed rhabdomyosarcoma. This led to the discovery of a multicystic intraocular tumor. A metastatic rhabdomyosarcoma to the eye was considered unlikely because, to our knowledge, this event had never been reported. An enucleation was performed, and an intraocular tumor composed almost entirely of rhabdomyoblasts (desmin- and myogenin-positive) was discovered along with rare clusters of persistent neuroepithelial cells. Conclusions and Relevance: To our knowledge, this is the first case of a medulloepithelioma in which teratoid rhabdomyoblasts effaced all but trace amounts of neuroepithelium and generated a distant metastasis entirely composed of rhabdomyoblasts. The prolonged history and filtering procedures probably led to these 2 phenomena.
Joshi AD, Andersson C, Buch S, Stender S, Noordam R, Weng L-C, Weeke PE, Auer PL, Boehm B, Chen C, Choi H, Curhan G, Denny JC, De Vivo I, Eicher JD, Ellinghaus D, Folsom AR, Fuchs C, Gala M, Haessler J, Hofman A, Hu F, Hunter DJ, Janssen HLA, Kang JH, Kooperberg C, Kraft P, Kratzer W, Lieb W, Lutsey PL, Darwish Murad S, Nordestgaard BG, Pasquale LR, Reiner AP, Ridker PM, Rimm E, Rose LM, Shaffer CM, Schafmayer C, Tamimi RM, Uitterlinden AG, Völker U, Völzke H, Wakabayashi Y, Wiggs JL, Zhu J, Roden DM, Stricker BH, Tang W, Teumer A, Hampe J, Tybjærg-Hansen A, Chasman DI, Chan AT, Johnson AD.
Four Susceptibility Loci for Gallstone Disease Identified in a Meta-analysis of Genome-Wide Association Studies. Gastroenterology 2016;151(2):351-363.e28.
AbstractBACKGROUND & AIMS: A genome-wide association study (GWAS) of 280 cases identified the hepatic cholesterol transporter ABCG8 as a locus associated with risk for gallstone disease, but findings have not been reported from any other GWAS of this phenotype. We performed a large-scale, meta-analysis of GWASs of individuals of European ancestry with available prior genotype data, to identify additional genetic risk factors for gallstone disease. METHODS: We obtained per-allele odds ratio (OR) and standard error estimates using age- and sex-adjusted logistic regression models within each of the 10 discovery studies (8720 cases and 55,152 controls). We performed an inverse variance weighted, fixed-effects meta-analysis of study-specific estimates to identify single-nucleotide polymorphisms that were associated independently with gallstone disease. Associations were replicated in 6489 cases and 62,797 controls. RESULTS: We observed independent associations for 2 single-nucleotide polymorphisms at the ABCG8 locus: rs11887534 (OR, 1.69; 95% confidence interval [CI], 1.54-1.86; P = 2.44 × 10(-60)) and rs4245791 (OR, 1.27; P = 1.90 × 10(-34)). We also identified and/or replicated associations for rs9843304 in TM4SF4 (OR, 1.12; 95% CI, 1.08-1.16; P = 6.09 × 10(-11)), rs2547231 in SULT2A1 (encodes a sulfoconjugation enzyme that acts on hydroxysteroids and cholesterol-derived sterol bile acids) (OR, 1.17; 95% CI, 1.12-1.21; P = 2.24 × 10(-10)), rs1260326 in glucokinase regulatory protein (OR, 1.12; 95% CI, 1.07-1.17; P = 2.55 × 10(-10)), and rs6471717 near CYP7A1 (encodes an enzyme that catalyzes conversion of cholesterol to primary bile acids) (OR, 1.11; 95% CI, 1.08-1.15; P = 8.84 × 10(-9)). Among individuals of African American and Hispanic American ancestry, rs11887534 and rs4245791 were associated positively with gallstone disease risk, whereas the association for the rs1260326 variant was inverse. CONCLUSIONS: In this large-scale GWAS of gallstone disease, we identified 4 loci in genes that have putative functions in cholesterol metabolism and transport, and sulfonylation of bile acids or hydroxysteroids.