- Email: [email protected]
Chromophobe Tumors
Urological Survey Urological Oncology: Adrenal, Renal, Ureteral and Retroperitoneal Tumors Re: Prospective Evaluation of 99mTc-Sestamibi SPECT/CT for the Diagnosis of Renal Oncocytomas and Hybrid Oncocytic/Chromophobe Tumors M. A. Gorin, S. P. Rowe, A. S. Baras, L. B. Solnes, M. W. Ball, P. M. Pierorazio, C. P. Pavlovich, J. I. Epstein, M. S. Javadi and M. E. Allaf James Buchanan Brady Urological Institute, Department of Urology, Russell H. Morgan Department of Radiology and Radiological Science, and Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland Eur Urol 2016; 69: 413e416. doi: 10.1016/j.eururo.2015.08.056
Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/26386607 Editorial Comment: For decades diagnostic imaging of renal tumors has roughly relied on crosssectional imaging and magnetic resonance imaging. An enhancing renal mass was considered suspicious for cancer and accordingly a treatment plan was devised. Once considered unuseful, nuclear imaging is now emerging as a means to differentiate clear cell renal cell carcinoma (RCC) from other subtypes, or as in this preliminary report as a possible way to differentiate benign lesions and those with low agressiveness, eg oncocytomas, chromophobe RCCs and hybrid oncocytic chromophobe tumors (HOCTs) from other RCCs. In this study 50 patients with a solid cT1 renal mass underwent imaging with 99mtechnetiumsestamibi single photon emission computerized tomography before surgical resection. Two nuclear medicine specialists blinded for pathology reports reviewed the preoperative scans and quantified maximum uptake of radiotracer in normal renal parenchyma and tumor. Relative radiotracer uptake was calculated as the ratio of tumor/parenchyma uptake, and the mean across 4 reads was calculated for each tumor. Two blinded pathologists reviewed the cases collaboratively and the consensual diagnosis served as the standard for comparison of the index test. Sestamibi correctly identified 5 of 6 oncocytomas and the 2 HOCTs for an overall sensitivity of 87.5% and specificity of 95.2% for diagnosis of oncocytoma/HOCT. Still 50% of chromophobe RCC and 1 of 8 oncocytoma plus HOCT cases were false-positive. This study is simple and well designed, and the methodology is adequate for the purposes of a diagnostic series. With caution ascribed to a preliminary report with as yet insufficient data to establish definitive conclusions, the idea is novel and if confirmed in a wide sample will signify an important advance in noninvasive diagnostic methods when RCC is suspected. M. Pilar Laguna, MD, PhD
Suggested Reading Halverson SJ, Kunju LP, Bhalla R et al: Accuracy of determining small renal mass management with risk stratified biopsies: confirmation by final pathology. J Urol 2013; 189: 441. Ginzburg S, Uzzo R, Al-Saleem T et al: Coexisting hybrid malignancy in a solitary sporadic solid benign renal mass: implications for treating patients following renal biopsy. J Urol 2014; 191: 296.
0022-5347/16/1956-1718/0 THE JOURNAL OF UROLOGY® Ó 2016 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
1718
j
www.jurology.com
AND
RESEARCH, INC.
http://dx.doi.org/10.1016/j.juro.2016.03.028 Vol. 195, 1718-1722, June 2016 Printed in U.S.A.
ADRENAL, RENAL, URETERAL AND RETROPERITONEAL TUMORS
Re: Genomic Characterization of Upper Tract Urothelial Carcinoma J. P. Sfakianos, E. K. Cha, G. Iyer, S. N. Scott, E. C. Zabor, R. H. Shah, Q. Ren, A. Bagrodia, P. H. Kim, A. A. Hakimi, I. Ostrovnaya, R. Ramirez, A. J. Hanrahan, N. B. Desai, A. Sun, P. Pinciroli, J. E. Rosenberg, G. Dalbagni, N. Schultz, D. F. Bajorin, V. E. Reuter, M. F. Berger, B. H. Bochner, H. A. Al-Ahmadie, D. B. Solit and J. A. Coleman Urology Service, Department of Surgery, Genitourinary Oncology Service, Department of Medicine, Department of Pathology, Computational Oncology Service, Department of Epidemiology and Biostatistics, Human Oncology and Pathogenesis Program, and Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, Department of Urology, Icahn School of Medicine at Mount Sinai and Weill Medical College of Cornell University, New York, New York, and Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy Eur Urol 2015; 68: 970e977. doi: 10.1016/j.eururo.2015.07.039
Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/26278805 Editorial Comment: Despite originating from the same cell lining, a different genotype between upper tract urothelial carcinoma (UTUC) and urothelial carcinoma of the bladder (UCB) has been advanced. Using next generation DNA sequencing (MSK-IMPACT assay), the authors describe co-mutations and copy number alterations of 300 genes in 83 UTUCs and 102 primary high risk UCBs. When comparing the 59 high grade UTUCs and 102 UCBs, a similar spectrum of genetic alterations was found. However, when adjusted for tumor stage, significant differences in the prevalence of somatic alterations were noted for HRAS and CDKN2B (more frequent in UTUC) and TP53, ARID1A and RB1 (more frequent in UCB). When high and low grade UTUCs were compared, activating mutations in FGFR3 were found in almost all low grade UTUCs. High grade UTUCs exhibited mutually exclusive mutation patterns in FGFR3, HRAS and TP53. Furthermore, some of these mutations were associated with grade (eg TP53 was more frequent in high grade) and others with tumor stage (eg FGFR3 was more frequent in pTa2). Consistent with findings in UCB, frequent mutations of chromatin modifying genes were found in all UTUCs. The greater frequency in low grade disease suggests that these genes may have a role in the pathogenesis of UTUC. Overall these findings seem to support the theory that low grade UTUC may evolve into high grade disease by acquisition of additional genetic or epigenetic alterations through time. However, in the accompanying editorial Matin and McConkey offer an alternative explanation.1 Based on the similar number of UTUCs that contained activating FGFR3 mutations in this study (35%) compared to FGFR3 mutations in the TCGA (The Cancer Genome Atlas) cluster I papillary luminal UCB (37.5%), the authors hypothesize that UTUC may be predominantly “luminal” by analogy with what occurs in invasive UCB. M. Pilar Laguna, MD, PhD
1. Matin SF and McConkey DJ: Bridging the gap in upper tract urothelial carcinoma. Eur Urol 2015; 68: 978.
Suggested Reading Catto JW, Yates DR, Rehman I et al: Behavior of urothelial carcinoma with respect to anatomical location. J Urol 2007; 177: 1715. Munoz JJ and Ellison LM: Upper tract urothelial neoplasms: incidence and survival during the last 2 decades. J Urol 2000; 164: 1523. Krabbe LM, Bagrodia A, Haddad AQ et al: Multi-institutional validation of the predictive value of Ki-67 in patients with high grade urothelial carcinoma of the upper tract. J Urol 2015; 193: 1486. Meiron M, Chamie K, Lerner SP et al: Mitogel: optimizing drug delivery to the upper urinary tractda preclinical evaluation. J Urol, suppl., 2014; 191: e914. Green DA, Rink M, Xylinas E et al: Urothelial carcinoma of the bladder and the upper tract: disparate twins. J Urol 2013; 189: 1214. Krabbe LM, Lotan Y, Bagrodia A et al: Prospective comparison of molecular signatures in urothelial cancer of the bladder and the upper urinary tractdis there evidence for discordant biology? J Urol 2014; 191: 926. Gayed BA, Seideman C and Lotan Y: Cost-effectiveness of fluorescence in situ hybridization in patients with atypical cytology for the detection of urothelial carcinoma. J Urol 2013; 190: 1181.
1719
Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/26386607 Editorial Comment: For decades diagnostic imaging of renal tumors has roughly relied on crosssectional imaging and magnetic resonance imaging. An enhancing renal mass was considered suspicious for cancer and accordingly a treatment plan was devised. Once considered unuseful, nuclear imaging is now emerging as a means to differentiate clear cell renal cell carcinoma (RCC) from other subtypes, or as in this preliminary report as a possible way to differentiate benign lesions and those with low agressiveness, eg oncocytomas, chromophobe RCCs and hybrid oncocytic chromophobe tumors (HOCTs) from other RCCs. In this study 50 patients with a solid cT1 renal mass underwent imaging with 99mtechnetiumsestamibi single photon emission computerized tomography before surgical resection. Two nuclear medicine specialists blinded for pathology reports reviewed the preoperative scans and quantified maximum uptake of radiotracer in normal renal parenchyma and tumor. Relative radiotracer uptake was calculated as the ratio of tumor/parenchyma uptake, and the mean across 4 reads was calculated for each tumor. Two blinded pathologists reviewed the cases collaboratively and the consensual diagnosis served as the standard for comparison of the index test. Sestamibi correctly identified 5 of 6 oncocytomas and the 2 HOCTs for an overall sensitivity of 87.5% and specificity of 95.2% for diagnosis of oncocytoma/HOCT. Still 50% of chromophobe RCC and 1 of 8 oncocytoma plus HOCT cases were false-positive. This study is simple and well designed, and the methodology is adequate for the purposes of a diagnostic series. With caution ascribed to a preliminary report with as yet insufficient data to establish definitive conclusions, the idea is novel and if confirmed in a wide sample will signify an important advance in noninvasive diagnostic methods when RCC is suspected. M. Pilar Laguna, MD, PhD
Suggested Reading Halverson SJ, Kunju LP, Bhalla R et al: Accuracy of determining small renal mass management with risk stratified biopsies: confirmation by final pathology. J Urol 2013; 189: 441. Ginzburg S, Uzzo R, Al-Saleem T et al: Coexisting hybrid malignancy in a solitary sporadic solid benign renal mass: implications for treating patients following renal biopsy. J Urol 2014; 191: 296.
0022-5347/16/1956-1718/0 THE JOURNAL OF UROLOGY® Ó 2016 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
1718
j
www.jurology.com
AND
RESEARCH, INC.
http://dx.doi.org/10.1016/j.juro.2016.03.028 Vol. 195, 1718-1722, June 2016 Printed in U.S.A.
ADRENAL, RENAL, URETERAL AND RETROPERITONEAL TUMORS
Re: Genomic Characterization of Upper Tract Urothelial Carcinoma J. P. Sfakianos, E. K. Cha, G. Iyer, S. N. Scott, E. C. Zabor, R. H. Shah, Q. Ren, A. Bagrodia, P. H. Kim, A. A. Hakimi, I. Ostrovnaya, R. Ramirez, A. J. Hanrahan, N. B. Desai, A. Sun, P. Pinciroli, J. E. Rosenberg, G. Dalbagni, N. Schultz, D. F. Bajorin, V. E. Reuter, M. F. Berger, B. H. Bochner, H. A. Al-Ahmadie, D. B. Solit and J. A. Coleman Urology Service, Department of Surgery, Genitourinary Oncology Service, Department of Medicine, Department of Pathology, Computational Oncology Service, Department of Epidemiology and Biostatistics, Human Oncology and Pathogenesis Program, and Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, Department of Urology, Icahn School of Medicine at Mount Sinai and Weill Medical College of Cornell University, New York, New York, and Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy Eur Urol 2015; 68: 970e977. doi: 10.1016/j.eururo.2015.07.039
Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/26278805 Editorial Comment: Despite originating from the same cell lining, a different genotype between upper tract urothelial carcinoma (UTUC) and urothelial carcinoma of the bladder (UCB) has been advanced. Using next generation DNA sequencing (MSK-IMPACT assay), the authors describe co-mutations and copy number alterations of 300 genes in 83 UTUCs and 102 primary high risk UCBs. When comparing the 59 high grade UTUCs and 102 UCBs, a similar spectrum of genetic alterations was found. However, when adjusted for tumor stage, significant differences in the prevalence of somatic alterations were noted for HRAS and CDKN2B (more frequent in UTUC) and TP53, ARID1A and RB1 (more frequent in UCB). When high and low grade UTUCs were compared, activating mutations in FGFR3 were found in almost all low grade UTUCs. High grade UTUCs exhibited mutually exclusive mutation patterns in FGFR3, HRAS and TP53. Furthermore, some of these mutations were associated with grade (eg TP53 was more frequent in high grade) and others with tumor stage (eg FGFR3 was more frequent in pTa2). Consistent with findings in UCB, frequent mutations of chromatin modifying genes were found in all UTUCs. The greater frequency in low grade disease suggests that these genes may have a role in the pathogenesis of UTUC. Overall these findings seem to support the theory that low grade UTUC may evolve into high grade disease by acquisition of additional genetic or epigenetic alterations through time. However, in the accompanying editorial Matin and McConkey offer an alternative explanation.1 Based on the similar number of UTUCs that contained activating FGFR3 mutations in this study (35%) compared to FGFR3 mutations in the TCGA (The Cancer Genome Atlas) cluster I papillary luminal UCB (37.5%), the authors hypothesize that UTUC may be predominantly “luminal” by analogy with what occurs in invasive UCB. M. Pilar Laguna, MD, PhD
1. Matin SF and McConkey DJ: Bridging the gap in upper tract urothelial carcinoma. Eur Urol 2015; 68: 978.
Suggested Reading Catto JW, Yates DR, Rehman I et al: Behavior of urothelial carcinoma with respect to anatomical location. J Urol 2007; 177: 1715. Munoz JJ and Ellison LM: Upper tract urothelial neoplasms: incidence and survival during the last 2 decades. J Urol 2000; 164: 1523. Krabbe LM, Bagrodia A, Haddad AQ et al: Multi-institutional validation of the predictive value of Ki-67 in patients with high grade urothelial carcinoma of the upper tract. J Urol 2015; 193: 1486. Meiron M, Chamie K, Lerner SP et al: Mitogel: optimizing drug delivery to the upper urinary tractda preclinical evaluation. J Urol, suppl., 2014; 191: e914. Green DA, Rink M, Xylinas E et al: Urothelial carcinoma of the bladder and the upper tract: disparate twins. J Urol 2013; 189: 1214. Krabbe LM, Lotan Y, Bagrodia A et al: Prospective comparison of molecular signatures in urothelial cancer of the bladder and the upper urinary tractdis there evidence for discordant biology? J Urol 2014; 191: 926. Gayed BA, Seideman C and Lotan Y: Cost-effectiveness of fluorescence in situ hybridization in patients with atypical cytology for the detection of urothelial carcinoma. J Urol 2013; 190: 1181.
1719