MADSON QUEIROZ DE ALMEIDA
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/42 - Laboratório de Hormônios e Genética Molecular, Hospital das Clínicas, Faculdade de Medicina
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/42 - Laboratório de Hormônios e Genética Molecular, Hospital das Clínicas, Faculdade de Medicina
14 resultados
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- Cytoreductive Surgery of the Primary Tumor in Metastatic Adrenocortical Carcinoma: Impact on Patients' Survival(2022) SROUGI, Victor; BANCOS, Irina; DAHER, Marilyne; LEE, Jeffrey E.; GRAHAM, Paul H.; KARAM, Jose A.; HENRIQUEZ, Andres; MCKENZIE, Travis J.; SADA, Alaa; BOURDEAU, Isabelle; POIRIER, Jonathan; VAIDYA, Anand; ABBONDANZA, Tiffany; KIERNAN, Colleen M.; RAO, Sarika N.; HAMIDI, Oksana; SACHITHANANDAN, Nirupa; HOFF, Ana O.; CHAMBO, Jose L.; ALMEIDA, Madson Q.; HABRA, Mouhammed Amir; V, Maria C. B. FragosoContext The role of cytoreduction of adrenocortical carcinoma (ACC) remains poorly understood. Objective To analyze the impact of cytoreductive surgery of the primary tumor in patients with metastatic ACC. Design and Setting We performed a multicentric, retrospective paired cohort study comparing the overall survival (OS) in patients with metastatic ACC who were treated either with cytoreductive surgery (CR group) or without cytoreductive surgery (no-CR group) of the primary tumor. Data were retrieved from 9 referral centers in the American-Australian-Asian Adrenal Alliance collaborative research group. Patients Patients aged >= 18 years with metastatic ACC at initial presentation who were treated between January 1, 1995, and May 31, 2019. Intervention Performance (or not) of cytoreductive surgery of the primary tumor. Main outcome and measures A propensity score match was done using age and the number of organs with metastasis (<= 2 or >2). The main outcome was OS, determined from the date of diagnosis until death or until last follow-up for living patients. Results Of 339 patients pooled, 239 were paired and included: 128 in the CR group and 111 in the no-CR group. The mean follow-up was 67 months. Patients in the no-CR group had greater risk of death than did patients in the CR group (hazard ratio [HR] = 3.18; 95% CI, 2.34-4.32). Independent predictors of survival included age (HR = 1.02; 95% CI, 1.00-1.03), hormone excess (HR = 2.56; 95% CI, 1.66-3.92), and local metastasis therapy (HR = 0.41; 95% CI, 0.47-0.65). Conclusion Cytoreductive surgery of the primary tumor in patients with metastatic ACC is associated with prolonged survival.
- Internal validation and decision curve analysis of a preoperative nomogram predicting a postoperative complication in pheochromocytoma surgery: An international study(2020) PHILLIPS, John; BLOOM, Jonathan; YARLAGADDA, Vidhush; SCHULTZ, Luciana; GORDETSKY, Jennifer; TANNO, Fabio Y.; CHAMBO, Jose L.; ALMEIDA, Madson Q.; V, Maria C. B. Fragoso; SROUGI, Miguel; SROUGI, Victor; RAIS-BAHRAMI, SoroushObjectives To develop a preoperative nomogram that would predict the risk of a postoperative complication for pheochromocytoma patients undergoing adrenalectomy using an international database. Methods We retrospectively analyzed preoperative variables and postoperative outcomes in patients who underwent adrenalectomy for pheochromocytoma in three institutions from 2000 to 2017. Internal validation of a generated nomogram was carried out with receiver operating characteristics, calibration plots, and decision curve analyses. Results A total of 153 patients who had undergone 166 adrenalectomies were included in the study. Overall, post-adrenalectomy complications were seen in 30% of patients, whereas 9.6% of patients sustained a Clavien >= 3a complication. Independent predictors of a complication were a history of hypertension, body mass index, tumor size, and Charlson Comorbidity Index score. On internal validation, the multivariable model generated a nomogram that predicted a postoperative complication or clinically hemodynamic event with an area under the curve of 0.86, showed good calibration and had an overall net benefit. Conclusions An internally validated nomogram combining body mass index, Charlson Comorbidity Index score and tumor size can predict the probability of a post-adrenalectomy complication in those with and without hypertension. The model, the first of its kind in pheochromocytoma surgery, identifies patients at risk of a postoperative complication at the time of their presentation with pheochromocytoma.
- Comparison of Pheochromocytoma-Specific Morbidity and Mortality Among Adults With Bilateral Pheochromocytomas Undergoing Total Adrenalectomy vs Cortical-Sparing Adrenalectomy(2019) NEUMANN, Hartmut P. H.; TSOY, Uliana; BANCOS, Irina; AMODRU, Vincent; WALZ, Martin K.; TIROSH, Amit; KAUR, Ravinder Jeet; MCKENZIE, Travis; QI, Xiaoping; BANDGAR, Tushar; PETROV, Roman; YUKINA, Marina Y.; ROSLYAKOVA, Anna; HORST-SCHRIVERS, Anouk N. A. van der; BERENDS, Annika M. A.; HOFF, Ana O.; CASTRONEVES, Luciana Audi; FERRARA, Alfonso Massimiliano; RIZZATI, Silvia; MIAN, Caterina; DVORAKOVA, Sarka; HASSE-LAZAR, Kornelia; KVACHENYUK, Andrey; PECZKOWSKA, Mariola; LOLI, Paola; ERENLER, Feyza; KRAUSS, Tobias; ALMEIDA, Madson Q.; LIU, Longfei; ZHU, Feizhou; RECASENS, Monica; WOHLLK, Nelson; CORSSMIT, Eleonora P. M.; SHAFIGULLINA, Zulfiya; CALISSENDORFF, Jan; GROZINSKY-GLASBERG, Simona; KUNAVISARUT, Tada; SCHALIN-JANTTI, Camilla; CASTINETTI, Frederic; VLCEK, Petr; BELTSEVICH, Dmitry; I, Viacheslav Egorov; SCHIAVI, Francesca; LINKS, Thera P.; LECHAN, Ronald M.; BAUSCH, Birke; YOUNG JR., William F.; ENG, Charis; JAISWAL, Sanjeet Kumar; ZSCHIEDRICH, Stefan; V, Maria C. B. Fragoso; PEREIRA, Maria A. A.; LI, Minghao; COSTA, Josefina Biarnes; JUHLIN, Carl Christofer; GROSS, David; VIOLANTE, Alice H. D.; KOCJAN, Tomaz; NGEOW, Joanne; YOEL, Uri; FRAENKEL, Merav; SIMSIR, Ilgin Yildirim; UGURLU, M. Umit; ZIAGAKI, Athanasia; DIAZ, Luis Robles; KUDLAI, Inna Stepanovna; GIMM, Oliver; SCHERBAUM, Christina Rebecca; ABEBE-CAMPINO, Gadi; BARBON, Giovanni; TASCHIN, Elisa; MALINOC, Angelica; KHUDIAKOVA, Natalia Valeryevna; V, Nikita Ivanov; PFEIFER, Marija; ZOVATO, Stefania; PLOECKINGER, Ursula; MAKAY, Ozer; GRINEVA, Elena; JARZAB, Barbara; JANUSZEWICZ, Andrzej; SHAH, Nalini; SEUFERT, Jochen; OPOCHER, Giuseppe; LARSSON, CatharinaIMPORTANCE Large studies investigating long-term outcomes of patients with bilateral pheochromocytomas treated with either total or cortical-sparing adrenalectomies are needed to inform clinical management. OBJECTIVE To determine the association of total vs cortical-sparing adrenalectomy with pheochromocytoma-specific mortality, the burden of primary adrenal insufficiency after bilateral adrenalectomy, and the risk of pheochromocytoma recurrence. DESIGN, SETTING, AND PARTICIPANTS This cohort study used data from a multicenter consortium-based registry for 625 patients treated for bilateral pheochromocytomas between 1950 and 2018. Data were analyzed from September 1, 2018, to June 1, 2019. EXPOSURES Total or cortical-sparing adrenalectomy. MAIN OUTCOMES AND MEASURES Primary adrenal insufficiency, recurrent pheochromocytoma, and mortality. RESULTS Of 625 patients (300 [48%] female) with a median (interquartile range [IQR]) age of 30 (22-40) years at diagnosis, 401 (64%) were diagnosed with synchronous bilateral pheochromocytomas and 224 (36%) were diagnosed with metachronous pheochromocytomas (median [IQR] interval to second adrenalectomy, 6 [1-13] years). In 505 of 526 tested patients (96%), germline mutationswere detected in the genes RET (282 patients [54%]), VHL (184 patients [35%]), and other genes (39 patients [7%]). Of 849 adrenalectomies performed in 625 patients, 324 (52%) were planned as cortical sparing and were successful in 248 of 324 patients (76.5%). Primary adrenal insufficiency occurred in all patients treated with total adrenalectomy but only in 23.5% of patients treated with attempted cortical-sparing adrenalectomy. A third of patients with adrenal insufficiency developed complications, such as adrenal crisis or iatrogenic Cushing syndrome. Of 377 patients who became steroid dependent, 67 (18%) developed at least 1 adrenal crisis and 50 (13%) developed iatrogenic Cushing syndrome during median (IQR) follow-up of 8 (3-25) years. Two patients developed recurrent pheochromocytoma in the adrenal bed despite total adrenalectomy. In contrast, 33 patients (13%) treated with successful cortical-sparing adrenalectomy developed another pheochromocytoma within the remnant adrenal after a median (IQR) of 8 (4-13) years, all of which were successfully treated with another surgery. Cortical-sparing surgery was not associated with survival. Overall survivalwas associated with comorbidities unrelated to pheochromocytoma: of 63 patients who died, only 3 (5%) died of metastatic pheochromocytoma. CONCLUSIONS AND RELEVANCE Patients undergoing cortical-sparing adrenalectomy did not demonstrate decreased survival, despite development of recurrent pheochromocytoma in 13%. Cortical-sparing adrenalectomy should be considered in all patients with hereditary pheochromocytoma.
- XAF1 as a modifier of p53 function and cancer susceptibility(2020) PINTO, Emilia M.; FIGUEIREDO, Bonald C.; CHEN, Wenan; GALVAO, Henrique C. R.; FORMIGA, Maria Nirvana; V, Maria Candida B. Fragoso; ASHTON-PROLLA, Patricia; RIBEIRO, Enilze M. S. F.; FELIX, Gabriela; COSTA, Tatiana E. B.; SAVAGE, Sharon A.; YEAGER, Meredith; I, Edenir Palmero; VOLC, Sahlua; SALVADOR, Hector; FUSTER-SOLER, Jose Luis; LAVARINO, Cinzia; CHANTADA, Guillermo; VAUR, Dominique; ODONE-FILHO, Vicente; BRUGIERES, Laurence; ELSE, Tobias; STOFFEL, Elena M.; MAXWELL, Kara N.; ACHATZ, Maria Isabel; KOWALSKI, Luis; ANDRADE, Kelvin C. de; PAPPO, Alberto; LETOUZE, Eric; LATRONICO, Ana Claudia; MENDONCA, Berenice B.; ALMEIDA, Madson Q.; BRONDANI, Vania B.; BITTAR, Camila M.; SOARES, Emerson W. S.; MATHIAS, Carolina; RAMOS, Cintia R. N.; MACHADO, Moara; ZHOU, Weiyin; JONES, Kristine; VOGT, Aurelie; KLINCHA, Payal P.; SANTIAGO, Karina M.; KOMECHEN, Heloisa; PARAIZO, Mariana M.; PARISE, Ivy Z. S.; V, Kayla Hamilton; WANG, Jinling; RAMPERSAUD, Evadnie; CLAY, Michael R.; MURPHY, Andrew J.; LALLI, Enzo; NICHOLS, Kim E.; RIBEIRO, Raul C.; RODRIGUEZ-GALINDO, Carlos; KORBONITS, Marta; ZHANG, Jinghui; THOMAS, Mark G.; CONNELLY, Jon P.; PRUETT-MILLER, Shondra; DIEKMANN, Yoan; NEALE, Geoffrey; WU, Gang; ZAMBETTI, Gerard P.Cancer risk is highly variable in carriers of the common TP53-R337H founder allele, possibly due to the influence of modifier genes. Whole-genome sequencing identified a variant in the tumor suppressor XAF1 (E134*/Glu134Ter/rs146752602) in a subset of R337H carriers. Haplotype-defining variants were verified in 203 patients with cancer, 582 relatives, and 42,438 newborns. The compound mutant haplotype was enriched in patients with cancer, conferring risk for sarcoma (P = 0.003) and subsequent malignancies (P = 0.006). Functional analyses demonstrated that wild-type XAF1 enhances transactivation of wild-type and hypomorphic TP53 variants, whereas XAF1-E134* is markedly attenuated in this activity. We propose that cosegregation of XAF1-E134* and TP53-R337H mutations leads to a more aggressive cancer phenotype than TP53-R337H alone, with implications for genetic counseling and clinical management of hypomorphic TP53 mutant carriers.
- Phosphodiesterase 2A and 3B variants are associated with primary aldosteronism(2021) RASSI-CRUZ, Marcela; MARIA, Andrea G.; FAUCZ, Fabio R.; LONDON, Edra; VILELA, Leticia A. P.; SANTANA, Lucas S.; BENEDETTI, Anna Flavia F.; GOLDBAUM, Tatiana S.; TANNO, Fabio Y.; SROUGI, Vitor; CHAMBO, Jose L.; PEREIRA, Maria Adelaide A.; CAVALCANTE, Aline C. B. S.; CARNEVALE, Francisco C.; PILAN, Bruna; BORTOLOTTO, Luiz A.; DRAGER, Luciano F.; LERARIO, Antonio M.; LATRONICO, Ana Claudia; V, Maria Candida B. Fragoso; MENDONCA, Berenice B.; ZERBINI, Maria Claudia N.; STRATAKIS, Constantine A.; ALMEIDA, Madson Q.Familial primary aldosteronism (PA) is rare and mostly diagnosed in early-onset hypertension (HT). However, 'sporadic' bilateral adrenal hyperplasia (BAH) is the most frequent cause of PA and remains without genetic etiology in most cases. Our aim was to investigate new genetic defects associated with BAH and PA. We performed whole-exome sequencing (paired blood and adrenal tissue) in six patients with PA caused by BAH that underwent unilateral adrenalectomy. Additionally, we conducted functional studies in adrenal hyperplastic tissue and transfected cells to confirm the pathogenicity of the identified genetic variants. Rare germline variants in phosphodiesterase 2A (PDE2A) and 3B (PDE3B) genes were identified in three patients. The PDE2A heterozygous variant (p.Ile629Val) was identified in a patient with BAH and early-onset HT at 13 years of age. Two PDE3B heterozygous variants (p.Arg217Gln and p.Gly392Val) were identified in patients with BAH and HT diagnosed at 18 and 33 years of age, respectively. A strong PDE2A staining was found in all cases of BAH in zona glomerulosa and/or micronodules (that were also positive for CYP11B2). PKA activity in frozen tissue was significantly higher in BAH from patients harboring PDE2A and PDE3B variants. PDE2A and PDE3B variants significantly reduced protein expression in mutant transfected cells compared to WT. Interestingly, PDE2A and PDE3B variants increased SGK1 and SCNN1G/ENaCg at mRNA or protein levels. In conclusion, PDE2A and PDE3B variants were associated with PA caused by BAH. These novel genetic findings expand the spectrum of gene tic etiologies of PA.
- Targeted Assessment of G0S2 Methylation Identifies a Rapidly Recurrent, Routinely Fatal Molecular Subtype of Adrenocortical Carcinoma(2019) MOHAN, Dipika R.; LERARIO, Antonio Marcondes; ELSE, Tobias; MUKHERJEE, Bhramar; ALMEIDA, Madson Q.; VINCE, Michelle; REGE, Juilee; MARIANI, Beatriz M. P.; ZERBINI, Maria Claudia N.; MENDONCA, Berenice B.; LATRONICO, Ana Claudia; MARIE, Suely K. N.; RAINEY, William E.; GIORDANO, Thomas J.; V, Maria Candida B. Fragoso; HAMMER, Gary D.Purpose: Adrenocortical carcinoma (ACC) is a rare, aggressive malignancy with few therapies; however, patients with locoregional disease have variable outcomes. The Cancer Genome Atlas project on ACC (ACC-TCGA) identified that cancers of patients with homogeneously rapidly recurrent or fatal disease bear a unique CpG island hypermethylation phenotype, ""CIMP-high."" We sought to identify a biomarker that faithfully captures this subgroup. Experimental Design: We analyzed ACC-TCGA data to characterize differentially regulated biological processes, and identify a biomarker that is methylated and silenced exclusively in CIMP-high ACC. In an independent cohort of 114 adrenocortical tumors (80 treatment-naive primary ACC, 22 adrenocortical adenomas, and 12 non-naive/nonprimary ACC), we evaluated biomarker methylation by a restriction digest/qPCR-based approach, validated by targeted bisulfite sequencing. We evaluated expression of this biomarker and additional prognostic markers by qPCR. Results: We show that CIMP-high ACC is characterized by upregulation of cell cycle andDNAdamage response programs, and identify that hypermethylation and silencing of G0S2 distinguishes this subgroup. We confirmed G0S2 hypermethylation and silencing is exclusive to 40% of ACC, and independently predicts shorter disease- free and overall survival (median 14 and 17 months, respectively). Finally, G0S2 methylation combined with validated molecular markers (BUB1B-PINK1) stratifies ACC into three groups, with uniformly favorable, intermediate, and uniformly dismal outcomes. Conclusions: G0S2 hypermethylation is a hallmark of rapidly recurrent or fatal ACC, amenable to targeted assessment using routine molecular diagnostics. Assessing G0S2 methylation is straightforward, feasible for clinical decision-making, and will enable the direction of efficacious adjuvant therapies for patients with aggressive ACC.
- High Prevalence of Alterations in DNA Mismatch Repair Genes of Lynch Syndrome in Pediatric Patients with Adrenocortical Tumors Carrying a Germline Mutation on TP53(2020) BRONDANI, Vania Balderrama; MONTENEGRO, Luciana; LACOMBE, Amanda Meneses Ferreira; MAGALHAES, Breno Marchiori; NISHI, Mirian Yumie; FUNARI, Mariana Ferreira de Assis; NARCIZO, Amanda de Moraes; CARDOSO, Lais Cavalca; SIQUEIRA, Sheila Aparecida Coelho; ZERBINI, Maria Claudia Nogueira; DENES, Francisco Tibor; LATRONICO, Ana Claudia; MENDONCA, Berenice Bilharinho; ALMEIDA, Madson Queiroz; LERARIO, Antonio Marcondes; SOARES, Ibere Cauduro; FRAGOSO, Maria Candida Barisson VillaresAdrenocortical cancer is a rare malignant neoplasm associated with a dismal prognosis. Identification of the molecular pathways involved in adrenal tumorigenesis is essential for a better understanding of the disease mechanism and improvement of its treatment. The aim of this study is to define the prevalence of alterations in DNA mismatch repair (MMR) genes in Lynch syndrome among pediatric patients with adrenocortical neoplasia from southern Brazil, where the prevalence of a specific TP53 germline mutation (p.Arg337His) is quite high. Thirty-six pediatric patients were retrospectively evaluated. Immunohistochemistry (IHC) for theMMR enzymes MLH1, MSH2, MSH6, and PMS2, as well as next-generation sequencing (NGS) were performed. For IHC, 36 pediatric tumors were tested. In all of them, the expression of all evaluated MMR proteins was well-preserved. For NGS, 35 patients with pediatric tumor were tested. Three patients (8.57%) with the TP53 p.Arg337His germline mutation presented pathogenic and likely pathogenic variants in the MMR genes (two in MLH1 and one in MSH6). The prevalence of alteredMMR genes among pediatric patients was elevated (8.57%) and higher than in colorectal and endometrial cancer cohorts. Pediatric patients with adrenocortical tumors should, thus, be strongly considered as at genetic risk for Lynch syndrome.
- Embryonic stem cell factor FOXD3 (Genesis) defects in gastrointestinal stromal tumors(2023) FAUCZ, Fabio R.; HORVATH, Anelia D.; ASSIE, Guillaume; ALMEIDA, Madson Q.; SZAREK, Eva; BOIKOS, Sosipatros; ANGELOUSI, Anna; LEVY, Isaac; MARIA, Andrea G.; CHITNIS, Ajay; ANTONESCU, Cristina R.; CLAUS, Rainer; BERTHERAT, Jerome; PLASS, Christoph; ENG, Charis; STRATAKIS, Constantine A.Gastrointestinal stromal tumors (GISTs) are mesenchymal neoplasms, believed to originate from the interstitial cells of Cajal (ICC), often caused by overexpression of tyrosine kinase receptors (TKR) KIT or PDGFRA. Here, we present evidence that the embryonic stem cell factor FOXD3, first identified as 'Genesis' and involved in both gastrointestinal and neural crest cell development, is implicated in GIST pathogenesis; its involvement is investigated both in vitro and in zebrafish and a mouse model of FOXD3 deficiency. Samples from a total of 58 patients with wild-type GISTs were used for molecular analyses, including Sanger sequencing, comparative genomic hybridization, and methylation analysis. Immunohistochemistry and western blot evaluation were used to assess FOXD3 expression. Additionally, we conducted in vitro functional studies in tissue samples and in transfected cells to confirm the pathogenicity of the identified genetic variants. Germline partially inactivating FOXD3 sequence variants (p.R54H and p.Ala88_Gly91del) were found in patients with isolated GISTs. Chromosome 1p loss was the most frequent chromosomal abnormality identified in tumors. In vitro experiments demonstrate the impairment of FOXD3 in the presence of those variants. Animal studies showed disruption of the GI neural network and changes in the number and distribution in the ICC. FOXD3 suppresses KIT expression in human cells; its inactivation led to an increase in ICC in zebrafish, as well as mice, providing evidence for a functional link between FOXD3 defects and KIT overexpression leading to GIST formation.
- Progression to Adrenocortical Tumorigenesis in Mice and Humans through Insulin-Like Growth Factor 2 and beta-Catenin(2012) HEATON, Joanne H.; WOOD, Michelle A.; KIM, Alex C.; LIMA, Lorena O.; BARLASKAR, Ferdous M.; ALMEIDA, Madson Q.; FRAGOSO, Maria C. B. V.; KUICK, Rork; LERARIO, Antonio M.; SIMON, Derek P.; SOARES, Ibere C.; STARNES, Elisabeth; THOMAS, Dafydd G.; LATRONICO, Ana C.; GIORDANO, Thomas J.; HAMMER, Gary D.Dysregulation of the WNT and insulin-like growth factor 2 (IGF2) signaling pathways has been implicated in sporadic and syndromic forms of adrenocortical carcinoma (ACC). Abnormal beta-catenin staining and CTNNB1 mutations are reported to be common in both adrenocortical adenoma and ACC, whereas elevated IGF2 expression is associated primarily with ACC. To better understand the contribution of these pathways in the tumorigenesis of ACC, we examined clinicopathological and molecular data and used mouse models. Evaluation of adrenal tumors from 118 adult patients demonstrated an increase in CTNNB1 mutations and abnormal beta-catenin accumulation in both adrenocortical adenoma and ACC. In ACC, these features were adversely associated with survival. Mice with stabilized beta-catenin exhibited a temporal progression of increased adrenocortical hyperplasia, with subsequent microscopic and macroscopic adenoma formation. Elevated Igf2 expression alone did not cause hyperplasia. With the combination of stabilized beta-catenin and elevated Igf2 expression, adrenal glands were larger, displayed earlier onset of hyperplasia, and developed more frequent macroscopic adenomas (as well as one carcinoma). Our results are consistent with a model in which dysregulation of one pathway may result in adrenal hyperplasia, but accumulation of a second or multiple alterations is necessary for tumorigenesis. (Ant J Pathol 2012, 181:1017-1033; http://dx.doi.org/10.1016/j.ajpath.2012.05.026)
- Presentation, Management, and Outcomes of Urinary Bladder Paraganglioma: Results From a Multicenter Study(2022) YU, Kai; EBBEHOJ, Andreas Ladefoged; OBEID, Hiba; VAIDYA, Anand; ELSE, Tobias; WACHTEL, Heather; MAIN, Ailsa Maria; SONDERGAARD, Esben; CHRISTENSEN, Louise Lehmann; JUHLIN, C. Christofer; CALISSENDORFF, Jan; COHEN, Debbie L.; BENNETT, Bonita; ANDERSEN, Marianne Skovsager; LARSSON, Catharina; ALMEIDA, Madson Q.; FISHBEIN, Lauren; BOORJIAN, Stephen A.; YOUNG JR., William F.; BANCOS, IrinaContext Urinary bladder paraganglioma (UBPGL) is rare. Objective We aimed to characterize the presentation and outcomes of patients diagnosed with UBPGL. Methods We conducted a multicenter study of consecutive patients with pathologically confirmed UBPGL evaluated between 1971 and 2021. Outcomes included repeat bladder surgery, metastases, and disease-specific mortality. Results Patients (n=110 total; n=56 [51%] women) were diagnosed with UBPGL at a median age of 50 years (interquartile range [IQR], 36-61 years). Median tumor size was 2 cm (IQR, 1-4 cm). UBPGL was diagnosed prior to biopsy in only 37 (34%), and only 69 (63%) patients had evaluation for catecholamine excess. In addition to the initial bladder surgery, 26 (25%) required multiple therapies, including repeat surgery in 10 (9%). Synchronous metastases were present in 9 (8%) patients, and 24 (22%) other patients with UBPGL developed metachronous metastases at a median of 4 years (IQR, 2-10 years) after the initial diagnosis. Development of metachronous metastases was associated with younger age (hazard ratio [HR] 0.97; 95% CI, 0.94-0.99), UBPGL size (HR 1.69; 95% CI, 1.31-2.17), and a higher degree of catecholamine excess (HR 5.48; 95% CI, 1.40-21.39). Disease-specific mortality was higher in patients with synchronous metastases (HR 20.80; 95% CI, 1.30-332.91). Choice of initial surgery, genetic association, sex, or presence of muscular involvement on pathology were not associated with development of metastases or mortality. Conclusions Only a minority of patients were diagnosed before biopsy/surgery, reflecting need for better diagnostic strategies. All patients with UBPGL should have lifelong monitoring for development of recurrence and metastases.