4 research outputs found
Biopsy in Renal Cell Carcinoma
Surveillance Epidemiology and End Results (SEER) estimates that 58,240 people will be diagnosed with cancer of the kidney and renal pelvis, while 13,040 will die in 2010. Renal cell cancer accounts for about two percent of all adult cancers. More than 80% of cancers of the kidney arise in the renal parenchyma, while the rest arise in the pelvis. Historically, renal cell carcinoma (RCC) has been treated with nephrectomy, often with no tissue diagnosis, because of the adverse effects and possibility of false negatives associated with renal mass biopsy. With the advancement of imaging modalities in the last decades, smaller tumors are now being discovered that pose therapeutic dilemmas that did not exist in the past. Growing numbers of studies are showing a substantial proportion of these masses is benign on nephrectomy pathology leading urologists to question the current paradigm and reconsider biopsy. Due to improved sampling techniques and advances in immunohistochemistry, recent studies have reported higher levels of sensitivity and specificity for biopsy than were previously reported in the literature. If biopsy could be proven to be dependable, options such as active surveillance and ablative therapies could provide physicians and patients with better choices if patients are not good surgical candidates.Master of Public Healt
Metachronous Bilateral Testicular Leydig-Like Tumors Leading to the Diagnosis of Congenital Adrenal Hyperplasia (Adrenogenital Syndrome)
A 33-year-old male with a history of left testis Leydig cell tumor (LCT), 3-month status after left radical orchiectomy, presented with a rapidly enlarging (0.6 cm to 3.7 cm) right testicular mass. He underwent a right radical orchiectomy, sections interpreted as showing a similar Leydig cell-like oncocytic proliferation, with a differential diagnosis including metachronous bilateral LCT and metachronous bilateral testicular tumors associated with congenital adrenal hyperplasia (a.k.a. “testicular adrenal rest tumors” (TARTs) and “testicular tumors of the adrenogenital syndrome” (TTAGS)). Additional workup demonstrated a markedly elevated serum adrenocorticotropic hormone (ACTH) and elevated adrenal precursor steroid levels. He was diagnosed with congenital adrenal hyperplasia, 3β-hydroxysteroid dehydrogenase deficiency (3BHSD) type, and started on treatment. Metachronous bilateral testicular masses in adults should prompt consideration of adult presentation of CAH. Since all untreated CAH patients are expected to have elevated serum ACTH, formal exclusion of CAH prior to surgical resection of a testicular Leydig-like proliferation could be accomplished by screening for elevated serum ACTH
Variants in GCNA, X-linked germ-cell genome integrity gene, identified in men with primary spermatogenic failure
Free PMC article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266742/pdf/nihms-1705620.pdfGEMINI Consortium: Donald F Conrad, Liina Nagirnaja, Kenneth I Aston, Douglas T Carrell, James M Hotaling, Timothy G Jenkins, Rob McLachlan, Moira K O'Bryan, Peter N Schlegel, Michael L Eisenberg, Jay I Sandlow, Emily S Jungheim, Kenan R Omurtag, Alexandra M Lopes, Susana Seixas, Filipa Carvalho, Susana Fernandes, Alberto Barros, João Gonçalves, Iris Caetano, Graça Pinto, Sónia Correia, Maris Laan, Margus Punab, Ewa Rajpert-De Meyts, Niels Jørgensen, Kristian Almstrup, Csilla G Krausz, Keith A Jarvi.Member of GEMINI Consortium: João Gonçalves (INSA), lista completa na pág 1179.Male infertility impacts millions of couples yet, the etiology of primary infertility remains largely unknown. A critical element of successful spermatogenesis is maintenance of genome integrity. Here, we present a genomic study of spermatogenic failure (SPGF). Our initial analysis (n=176) did not reveal known gene-candidates but identifed a potentially signifcant single-nucleotide variant (SNV) in X-linked germ-cell nuclear antigen (GCNA). Together with a larger follow-up study (n=2049), 7 likely clinically relevant GCNA variants were identifed. GCNA is critical for genome integrity in male meiosis and knockout models exhibit impaired spermatogenesis and infertility. Single-cell RNA-seq and immunohistochemistry confrm human GCNA expression from spermatogonia to elongated spermatids. Five identifed SNVs were located in key
functional regions, including N-terminal SUMO-interacting motif and C-terminal Spartan-like protease domain. Notably, variant p.Ala115ProfsTer7 results in an early frameshift, while Spartan-like domain missense variants p.Ser659Trp and p.Arg664Cys change conserved residues, likely afecting 3D structure. For variants within GCNA’s intrinsically disordered region, we performed computational modeling for consensus motifs. Two SNVs were predicted to impact the structure of these consensus motifs. All identifed variants have an extremely low minor allele frequency in the general population and 6 of 7 were not detected in>5000 biological fathers. Considering evidence from animal models, germ-cell-specifc expression, 3D modeling, and computational predictions for SNVs, we propose that identifed GCNA variants disrupt structure and function of the respective protein domains, ultimately arresting germ-cell division. To our knowledge, this is the frst study implicating GCNA, a key genome integrity factor, in human male infertility.This study was supported by The Eunice Kennedy Shriver
NICHD Grant HD080755 (ANY), the Magee-Womens Research
Institute University of Pittsburgh Start Up Fund (ANY), PA DoH
Grant SAP4100085736 (ANY), NIH P50 Specialized Center Grant
HD096723 (KO, ANY, DC, PNS, KH, and MBE), German Research
Foundation Clinical Research Unit ‘Male Germ Cells’ grant DFG
CRU326 (FT), National Science Centre in Poland, grants no.:
2017/26/D/NZ5/00789 (AM) and 2015/17/B/NZ2/01157; NCN
2020/37/B/NZ5/00549 (MK), Magee-Womens Research Institute
University of Pittsburgh, Faculty Fellowship Award and NICHD T32
HD087194 (JH), GM125812 (MB), GM127569 (MB, JLY, and ANY),
NIH R00H090289 (MABE), National Health and Medical Research
Council Project grant APP1120356 (MKOB, JAV, and DC), UUKi
Rutherford Fund Fellowship (BJH), Estonian Research Council, grants
IUT34-12 and PRG1021 (ML), and The Netherlands Organization
for Scientifc Research grant no.: 918-15-667 as well as an Investigator Award in Science from the Wellcome Trust grant no.: 209451 (JAV). Computational analysis was supported in part by the University
of Pittsburgh Center for Research Computing through the resources
provided.info:eu-repo/semantics/publishedVersio