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10. Proposal for a Novel Histological Scoring System as a Potential Grading Approach for Muscle-invasive Urothelial Bladder Cancer Correlating with Disease Aggressiveness and Patient Outcomes

Author

Eckstein, Markus, Matek, Christian, Wagner, Paul, Erber, Ramona, Büttner-Herold, Maike, Wild, Peter J., Taubert, Helge, Wach, Sven, Sikic, Danijel, Wullich, Bernd, Geppert, Carol I., Compérat, Eva M., Lopez-Beltran, Antonio, Montironi, Rodolfo, Cheng, Liang, van der Kwast, Theodorus, Colecchia, Maurizio, van Rhijn, Bas W.G., Amin, Mahul B., Netto, George J., Lehmann, Jan, Stöckle, Michael, Junker, Kerstin, Hartmann, Arndt, and Bertz, Simone

Published
2024
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12. International Opinions on Grading of Urothelial Carcinoma: A Survey Among European Association of Urology and International Society of Urological Pathology Members

Author

Irene J. Beijert, Liang Cheng, Fredrik Liedberg, Karin Plass, Sean R. Williamson, Paolo Gontero, Maria J. Ribal, Marko Babjuk, Peter C. Black, Ashish M. Kamat, Ferran Algaba, David M. Berman, Arndt Hartmann, Alexandra Masson-Lecomte, Morgan Rouprêt, Antonio Lopez-Beltran, Hemamali Samaratunga, Shahrokh F. Shariat, A. Hugh Mostafid, Murali Varma, Steven Shen, Maximilian Burger, Toyonori Tsuzuki, Joan Palou, Eva M. Compérat, Richard J. Sylvester, Theo H. van der Kwast, Bas W.G. van Rhijn, and Michelle R. Downes

Subjects
Bladder, Cancer, Grading, Survey, European Association of Urology, International Society of Urological Pathology, Diseases of the genitourinary system. Urology, RC870-923, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Background: Grade of non–muscle-invasive bladder cancer (NMIBC) is an important prognostic factor for progression. Currently, two World Health Organization (WHO) classification systems (WHO1973, categories: grade 1–3, and WHO2004 categories: papillary urothelial neoplasm of low malignant potential [PUNLMP], low-grade [LG], high-grade [HG] carcinoma) are used. Objective: To ask the European Association of Urology (EAU) and International Society of Urological Pathology (ISUP) members regarding their current practice and preferences of grading systems. Design, setting, and participants: A web-based, anonymous questionnaire with ten questions on grading of NMIBC was created. The members of EAU and ISUP were invited to complete an online survey by the end of 2021. Thirteen experts had previously answered the same questions. Outcome measurements and statistical analysis: The submitted answers from 214 ISUP members, 191 EAU members, and 13 experts were analyzed. Results and limitations: Currently, 53% use only the WHO2004 system and 40% use both systems. According to most respondents, PUNLMP is a rare diagnosis with management similar to Ta-LG carcinoma. The majority (72%) would consider reverting back to WHO1973 if grading criteria were more detailed. Separate reporting of WHO1973-G3 within WHO2004-HG would influence clinical decisions for Ta and/or T1 tumors according the majority (55%). Most respondents preferred a two-tier (41%) or a three-tier (41%) grading system. The current WHO2004 grading system is supported by a minority (20%), whereas nearly half (48%) supported a hybrid three- or four-tier grading system composed of both WHO1973 and WHO2004. The survey results of the experts were comparable with ISUP and EAU respondents. Conclusions: Both the WHO1973 and the WHO2004 grading system are still widely used. Even though opinions on the future of bladder cancer grading were strongly divided, there was limited support for WHO1973 and WHO2004 in their current formats, while the hybrid (three-tier) grading system with LG, HG-G2, and HG-G3 as categories could be considered the most promising alternative. Patient summary: Grading of non–muscle-invasive bladder cancer (NMIBC) is a matter of ongoing debate and lacks international consensus. We surveyed urologists and pathologists of European Association of Urology and International Society of Urological Pathology on their preferences regarding NMIBC grading to generate a multidisciplinary dialogue. Both the “old” World Health Organization (WHO) 1973 and the “new” WHO2004 grading schemes are still used widely. However, continuation of both the WHO1973 and the WHO2004 system showed limited support, while a hybrid grading system composed of both the WHO1973 and the WHO2004 classification system may be considered a promising alternative.

Published
2023
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13. International Society of Urological Pathology (ISUP) Consensus Conference on Current Issues in Bladder Cancer. Working Group 2: Grading of Mixed Grade, Invasive Urothelial Carcinoma Including Histologic Subtypes and Divergent Differentiations, and Non-Urothelial Carcinomas

Author

Paner, Gladell P., Kamat, Ashish, Netto, George J., Samaratunga, Hemamali, Varma, Murali, Bubendorf, Lukas, van der Kwast, Theodorus H., Cheng, Liang, Adeniran, Adebowale, Al-Ahimadie, Hikmat, Algaba, Fernando, Bhattarai, Yves Allory Selina, Black, Peter, Berman, David, Bertz, Simone, Bubendorf, Lukas, Carlsen, Birgitte, Carvalho, Rita, Cheng, Liang, Chijioke, Obinna, Cho, Yong Mee, Comperat, Eva, di Cunha, Isabela, Dagher, Julien, de Cunha, Isabella, Delahunt, Brett, Downes, Michelle, Flaig, Thomas, Fleischmann, Achim, Florescu, Cosmin, Fontugne, Jacqueline, Genitsch, Vera, Gløersen, Guro Horni, von Gunten, Michael, Grobholz, Rainer, Hansel, Donna, Hartmann, Arndt, Hernandez, Loren Herrera, Hogland, Mattias, Huang, Jiaoti, Jensen, Brad, Iczkowski, Kenneth, Jimenez, Rafael, Jovanovic, Bojana, Kamat, Ashish, Koellermann, Jens, Levin, Trevor, Liedberg, Fredrik, Lopez-Beltran, Antonio, Loya, Anand C, Lyngra, Marianne, McHale, Teresa, Mokeddem, Khadidja, Netto, George, Nourieh, Maya, O’Rourke, Declan, Ostahi, Irina-Alexandra, Paner, Gladell, Picken, Maria M, Pineda, Flavia Guzman, Raspollini, Camelia Radulescu Maria, Reis, Henning, Ruoyu, Shi, Samaratunga, Hemamali, Semba, Remi, Shah, Nigam, Shen, Steven, Smith, Steven, Smith, Tovia, Srigley, John, Suzigan, Sueli, Swarbrick, Nicole, Szalay, Ildiko, Talleraas, Inger, Tille, Jean-Christophe, Toma, Marieta, Trias, Isabel, Tsuzuki, Toyonori, van der Kwast, Theodorus, van Rhijn, Bas, Varma, Murali, Verbeke, Sofie, Verma, Sangeeta, Vlajnic, Tatjana, Vlatkovic, Ljiljana, Warren, Anne, Warrick, Joshua, Williamson, Sean, Wobker, Sara, Woods, Clifton, Yang, Chen, and Yoon, Ghilsuk

Published
2024
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14. International Society of Urological Pathology Consensus Conference on Current Issues in Bladder Cancer. Working Group 4: Molecular Subtypes of Bladder Cancer—Principles of Classification and Emerging Clinical Utility

Author

Warrick, Joshua I., Al-Ahmadie, Hikmat, Berman, David M., Black, Peter C., Flaig, Thomas W., Höglund, Mattias, Bubendorf, Lukas, van der Kwast, Theodorus H., Cheng, Liang, Adeniran, Adebowale, Al-Ahimadie, Hikmat, Algaba, Fernando, Allory, Yves, Bhattarai, Selina, Black, Peter, Berman, David, Bertz, Simone, Bubendorf, Lukas, Carlsen, Birgitte, Carvalho, Rita, Cheng, Liang, Chijioke, Obinna, Cho, Yong Mee, Comperat, Eva, di Cunha, Isabela, Dagher, Julien, de Cunha, Isabella, Delahunt, Brett, Downes, Michelle, Flaig, Thomas, Fleischmann, Achim, Florescu, Cosmin, Fontugne, Jacqueline, Genitsch, Vera, Gløersen, Guro Horni, von Gunten, Michael, Grobholz, Rainer, HanselArndt Hartmann, Donna, Hernandez, Loren Herrera, Hogland, Mattias, Huang, Jiaoti, Jensen, Brad, Iczkowski, Kenneth, Jimenez, Rafael, Jovanovic, Bojana, Kamat, Ashish, Koellermann, Jens, Levin, Trevor, Liedberg, Fredrik, Lopez-Beltran, Antonio, Loya, Anand C, Lyngra, Marianne, McHale, Teresa, Mokeddem, Khadidja, Netto, George, Nourieh, Maya, O’Rourke, Declan, Ostahi, Irina-Alexandra, Paner, Gladell, Picken, Maria M, Pineda, Flavia Guzman, Raspollini, Camelia Radulescu Maria, Reis, Henning, Ruoyu, Shi, Samaratunga, Hemamali, Semba, Remi, Shah, Nigam, Shen, Steven, Smith, Steven, Smith, Tovia, Srigley, John, Suzigan, Sueli, Swarbrick, Nicole, Szalay, Ildiko, Talleraas, Inger, Tille, Jean-Christophe, Toma, Marieta, Trias, Isabel, Tsuzuki, Toyonori, van der Kwast, Theodorus, van Rhijn, Bas, Varma, Murali, Verbeke, Sofie, Verma, Sangeeta, Vlajnic, Tatjana, Vlatkovic, Ljiljana, Warren, Anne, Warrick, Joshua, Williamson, Sean, Wobker, Sara, Woods, Clifton, Yang, Chen, and Yoon, Ghilsuk

Published
2024
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17. International Opinions on Grading of Urothelial Carcinoma: A Survey Among European Association of Urology and International Society of Urological Pathology Members

Author

Beijert, Irene J., Cheng, Liang, Liedberg, Fredrik, Plass, Karin, Williamson, Sean R., Gontero, Paolo, Ribal, Maria J., Babjuk, Marko, Black, Peter C., Kamat, Ashish M., Algaba, Ferran, Berman, David M., Hartmann, Arndt, Masson-Lecomte, Alexandra, Rouprêt, Morgan, Lopez-Beltran, Antonio, Samaratunga, Hemamali, Shariat, Shahrokh F., Mostafid, A. Hugh, Varma, Murali, Shen, Steven, Burger, Maximilian, Tsuzuki, Toyonori, Palou, Joan, Compérat, Eva M., Sylvester, Richard J., van der Kwast, Theo H., van Rhijn, Bas W.G., and Downes, Michelle R.

Published
2023
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18. Frequent Telomerase Reverse Transcriptase (TERT) Promoter and Fibroblast Growth Factor Receptor 3 (FGFR3) Mutations Support the Precursor Nature of Papillary Urothelial Hyperplasia of the Urinary Bladder

Author

Cheng, Liang, Lopez-Beltran, Antonio, Wang, Mingsheng, Whaley, Rumeal D., De Souza, Andre, Au, Sammy, Ge, Rongbin, Cimadamore, Alessia, Amin, Ali, Golijanin, Borivoj, MacLennan, Gregory T., Osunkoya, Adeboye O., Montironi, Rodolfo, and Zhang, Shaobo

Published
2023
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19. International Society of Urological Pathology Consensus Conference on Current Issues in Bladder Cancer. Working Group 4: Molecular Subtypes of Bladder Cancer—Principles of Classification and Emerging Clinical Utility

Author

Warrick, Joshua I., Al-Ahmadie, Hikmat, Berman, David M., Black, Peter C., Flaig, Thomas W., Höglund, Mattias, Bubendorf, Lukas, van der Kwast, Theodorus H., Cheng, Liang, Adeniran, Adebowale, Al-Ahimadie, Hikmat, Algaba, Fernando, Allory, Yves, Bhattarai, Selina, Black, Peter, Berman, David, Bertz, Simone, Bubendorf, Lukas, Carlsen, Birgitte, Carvalho, Rita, Cheng, Liang, Chijioke, Obinna, Cho, Yong Mee, Comperat, Eva, di Cunha, Isabela, Dagher, Julien, de Cunha, Isabella, Delahunt, Brett, Downes, Michelle, Flaig, Thomas, Fleischmann, Achim, Florescu, Cosmin, Fontugne, Jacqueline, Genitsch, Vera, Gløersen, Guro Horni, von Gunten, Michael, Grobholz, Rainer, HanselArndt Hartmann, Donna, Hernandez, Loren Herrera, Hogland, Mattias, Huang, Jiaoti, Jensen, Brad, Iczkowski, Kenneth, Jimenez, Rafael, Jovanovic, Bojana, Kamat, Ashish, Koellermann, Jens, Levin, Trevor, Liedberg, Fredrik, Lopez-Beltran, Antonio, Loya, Anand C, Lyngra, Marianne, McHale, Teresa, Mokeddem, Khadidja, Netto, George, Nourieh, Maya, O’Rourke, Declan, Ostahi, Irina-Alexandra, Paner, Gladell, Picken, Maria M, Pineda, Flavia Guzman, Raspollini, Camelia Radulescu Maria, Reis, Henning, Ruoyu, Shi, Samaratunga, Hemamali, Semba, Remi, Shah, Nigam, Shen, Steven, Smith, Steven, Smith, Tovia, Srigley, John, Suzigan, Sueli, Swarbrick, Nicole, Szalay, Ildiko, Talleraas, Inger, Tille, Jean-Christophe, Toma, Marieta, Trias, Isabel, Tsuzuki, Toyonori, van der Kwast, Theodorus, van Rhijn, Bas, Varma, Murali, Verbeke, Sofie, Verma, Sangeeta, Vlajnic, Tatjana, Vlatkovic, Ljiljana, Warren, Anne, Warrick, Joshua, Williamson, Sean, Wobker, Sara, Woods, Clifton, Yang, Chen, and Yoon, Ghilsuk

Published
2023
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23. Flower lose, a cell fitness marker, predicts COVID‐19 prognosis

Author

Michail Yekelchyk, Esha Madan, Jochen Wilhelm, Kirsty R Short, António M Palma, Linbu Liao, Denise Camacho, Everlyne Nkadori, Michael T Winters, Emily S Rice, Inês Rolim, Raquel Cruz‐Duarte, Christopher J Pelham, Masaki Nagane, Kartik Gupta, Sahil Chaudhary, Thomas Braun, Raghavendra Pillappa, Mark S Parker, Thomas Menter, Matthias Matter, Jasmin Dionne Haslbauer, Markus Tolnay, Kornelia D Galior, Kristina A Matkwoskyj, Stephanie M McGregor, Laura K Muller, Emad A Rakha, Antonio Lopez‐Beltran, Ronny Drapkin, Maximilian Ackermann, Paul B Fisher, Steven R Grossman, Andrew K Godwin, Arutha Kulasinghe, Ivan Martinez, Clay B Marsh, Benjamin Tang, Max S Wicha, Kyoung Jae Won, Alexandar Tzankov, Eduardo Moreno, and Rajan Gogna

Subjects
biomarker, cell fitness, COVID‐19, flower, prognosis, Medicine (General), R5-920, Genetics, QH426-470
Abstract

Abstract Risk stratification of COVID‐19 patients is essential for pandemic management. Changes in the cell fitness marker, hFwe‐Lose, can precede the host immune response to infection, potentially making such a biomarker an earlier triage tool. Here, we evaluate whether hFwe‐Lose gene expression can outperform conventional methods in predicting outcomes (e.g., death and hospitalization) in COVID‐19 patients. We performed a post‐mortem examination of infected lung tissue in deceased COVID‐19 patients to determine hFwe‐Lose’s biological role in acute lung injury. We then performed an observational study (n = 283) to evaluate whether hFwe‐Lose expression (in nasopharyngeal samples) could accurately predict hospitalization or death in COVID‐19 patients. In COVID‐19 patients with acute lung injury, hFwe‐Lose is highly expressed in the lower respiratory tract and is co‐localized to areas of cell death. In patients presenting in the early phase of COVID‐19 illness, hFwe‐Lose expression accurately predicts subsequent hospitalization or death with positive predictive values of 87.8–100% and a negative predictive value of 64.1–93.2%. hFwe‐Lose outperforms conventional inflammatory biomarkers and patient age and comorbidities, with an area under the receiver operating characteristic curve (AUROC) 0.93–0.97 in predicting hospitalization/death. Specifically, this is significantly higher than the prognostic value of combining biomarkers (serum ferritin, D‐dimer, C‐reactive protein, and neutrophil–lymphocyte ratio), patient age and comorbidities (AUROC of 0.67–0.92). The cell fitness marker, hFwe‐Lose, accurately predicts outcomes in COVID‐19 patients. This finding demonstrates how tissue fitness pathways dictate the response to infection and disease and their utility in managing the current COVID‐19 pandemic.

Published
2021
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24. Digital Biopsy with Fluorescence Confocal Microscope for Effective Real-time Diagnosis of Prostate Cancer: A Prospective, Comparative Study

Author

Rocco, Bernardo, Sighinolfi, Maria Chiara, Sandri, Marco, Spandri, Valentina, Cimadamore, Alessia, Volavsek, Metka, Mazzucchelli, Roberta, Lopez-Beltran, Antonio, Eissa, Ahmed, Bertoni, Laura, Azzoni, Paola, Reggiani Bonetti, Luca, Maiorana, Antonino, Puliatti, Stefano, Micali, Salvatore, Paterlini, Maurizio, Iseppi, Andrea, Rocco, Francesco, Pellacani, Giovanni, Chester, Johanna, Bianchi, Giampaolo, and Montironi, Rodolfo

Published
2021
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29. Buprenorphine is a weak dopamine releaser relative to heroin, but its pretreatment attenuates heroin‐evoked dopamine release in rats

Author

Dominic P. Isaacs, Ryan P. Leman, Thomas J. Everett, Hendrick Lopez‐Beltran, Lindsey R. Hamilton, and Erik B. Oleson

Subjects
addiction, agonist therapy, dopamine, opioid, substitution therapy, voltammetry, Therapeutics. Pharmacology, RM1-950, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Abstract Aims The United States of America is currently in an opioid epidemic. Heroin remains the most lethal opioid option with its death rate increasing by over 500% in the last decade. The rewarding and reinforcing effects of heroin are thought to be mediated by its ability to increase dopamine concentration in the nucleus accumbens shell. By activating Gi/o‐coupled μ‐opioid receptors, opioids are thought to indirectly excite midbrain dopamine neurons by removing an inhibitory GABAergic tone. The partial μ‐opioid receptor agonist buprenorphine is a substitution‐based therapy for heroin dependence that is thought to produce a steady‐state level of μ‐opioid receptor activation. But it remains unclear how buprenorphine alters dopamine release relative to heroin and how buprenorphine alters the dopamine‐releasing effects of heroin. Because buprenorphine is a partial agonist at the μ‐opioid receptor and heroin is a full agonist, we predicted that buprenorphine would function as a weak dopamine releaser relative to heroin, while functioning as a competitive antagonist if administered in advance of heroin. Methods We performed fast‐scan cyclic voltammetry in awake and behaving rats to measure how heroin, buprenorphine HCl, and their combination affect transient dopamine release events in the nucleus accumbens shell. We also performed a complimentary pharmacokinetic analysis comparing opioid plasma levels at time points correlated to our neurochemical findings. Results Both buprenorphine and heroin produced changes in the frequency of transient dopamine release events, although the effect of buprenorphine was weak and only observed at a low dose. In comparison with vehicle, the frequency of dopamine release events maximally increased by ~25% following buprenorphine treatment and by ~60% following heroin treatment. Distinct neuropharmacological effects were observed in the high‐dose range. The frequency of dopamine release events increased linearly with heroin dose but biphasically with buprenorphine dose. We also found that buprenorphine pretreatment occluded the dopamine‐releasing effects of heroin, but plasma levels of buprenorphine had returned to baseline at this time point. Conclusion These findings support the notion that low‐dose buprenorphine is a weak dopamine releaser relative to heroin and that buprenorphine pretreatment can block the dopamine‐releasing effects of heroin. The finding that high‐dose buprenorphine fails to increase dopamine release might explain its relatively low abuse potential among opioid‐dependent populations. Because high‐dose buprenorphine decreased dopamine release before occluding heroin‐evoked dopamine release, and buprenorphine was no longer detected in plasma, we conclude that the mechanisms through which buprenorphine blocks heroin‐evoked dopamine release involve multifaceted pharmacokinetic and pharmacodynamic interactions.

Published
2020
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37. Do Female Motives for Enrolling Vary According to STEM Profile?

Author

Olmedo-Torre, Noelia, Sanchez Carracedo, Fermin, Salan Ballesteros, M. Nuria, Lopez, David, Perez-Poch, Antoni, and Lopez-Beltran, Mireia

Abstract

Contribution: Stereotypes and immediate environment are the reasons for low enrollment of women in STEM studies. Background: The low number of women in STEM degree courses has been the subject of much research, which has found that the lack of female enrollment is not evenly distributed across all STEM studies. In some areas, such as computing, communications, and electrical and electronic engineering (CCEEE), not only has the number of women not increased, it has even fallen. Research Questions: Is there a stereotype for women taking STEM studies? Is this stereotype different between women taking CCEEE and non-CCEEE degrees? What are the main reasons that lead women to enroll in STEM studies? Methodology: A survey was sent to 3699 female students and STEM graduates belonging to the authors' university in six schools with a lowest level of enrollment, and 1060 replies were received. A qualitative study based on data analysis triangulation was performed. Findings: The women surveyed consider social stereotypes (31.47%) and the immediate environment (14.5%) as the main reasons for the low enrollment of women in STEM studies. Surprisingly, the third reason (11.03%) is that women do not like engineering. New knowledge concerning what motivates female students to enroll in STEM studies, what stereotypes they must struggle against, and the existence of possible differences between CCEEE and STEM but non-CCEEE female students could help policy makers and academia to improve female enrollment in STEM and, in particular, in CCEEE studies.

Published
2018
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38. Flower lose, a cell fitness marker, predicts COVID‐19 prognosis

Author

Yekelchyk, Michail, Madan, Esha, Wilhelm, Jochen, Short, Kirsty R, Palma, António M, Liao, Linbu, Camacho, Denise, Nkadori, Everlyne, Winters, Michael T, Rice, Emily S, Rolim, Inês, Cruz‐Duarte, Raquel, Pelham, Christopher J, Nagane, Masaki, Gupta, Kartik, Chaudhary, Sahil, Braun, Thomas, Pillappa, Raghavendra, Parker, Mark S, Menter, Thomas, Matter, Matthias, Haslbauer, Jasmin Dionne, Tolnay, Markus, Galior, Kornelia D, Matkwoskyj, Kristina A, McGregor, Stephanie M, Muller, Laura K, Rakha, Emad A, Lopez‐Beltran, Antonio, Drapkin, Ronny, Ackermann, Maximilian, Fisher, Paul B, Grossman, Steven R, Godwin, Andrew K, Kulasinghe, Arutha, Martinez, Ivan, Marsh, Clay B, Tang, Benjamin, Wicha, Max S, Won, Kyoung Jae, Tzankov, Alexandar, Moreno, Eduardo, and Gogna, Rajan

Published
2021
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41. Paratesticular well-differentiated liposarcoma initially diagnosed as fibrous pseudotumour

Author

Svitlana Y Bachurska, Petar A Antonov, Ivan Y Dechev, and Antonio Lopez-Beltran

Subjects
fibrous pseudotumour, liposarcoma, paratesticular, Pathology, RB1-214, Microbiology, QR1-502
Abstract

Paratesticular tumours are relatively rare and mostly of the mesenchymal origin. Due to its rarity, general surgical pathologists might have limited experience on the diagnostic entities and relevant differential diagnoses related to mesenchymal paratesticular tumours. This may likely cause diagnostic difficulties in a daily pathology practice. Paratesticular liposarcoma is a highly heterogeneous tumour and may be misdiagnosed as a benign fibromatous lesion. Herein we present a case of well-differentiated paratesticular liposarcoma of the sclerosing type initially diagnosed as a fibrous pseudotumour. Main differential diagnostic considerations are highlighted.

Published
2020
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42. Small-cell Carcinomas of the Urinary Bladder and Prostate: TERT Promoter Mutation Status Differentiates Sites of Malignancy and Provides Evidence of Common Clonality Between Small-cell Carcinoma of the Urinary Bladder and Urothelial Carcinoma

Author

Priemer, David S., Wang, Mingsheng, Zhang, Shaobo, Lopez-Beltran, Antonio, Kouba, Erik, Montironi, Rodolfo, Davidson, Darrell D., MacLennan, Gregory T., Wang, Lisha, Osunkoya, Adeboye O., Deng, Youping, Emerson, Robert E., and Cheng, Liang

Published
2018
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43. Primary mucinous adenocarcinoma of the urethra: A clinicopathological analysis of 35 cases.

Author

Ge, Rongbin, Zhang, Jing, Lu, Min, Shi, Yuchuan, Yan, Shi, Xue, Zixuan, Wang, Zongwei, Lopez‐Beltran, Antonio, and Cheng, Liang

Subjects
MUCINOUS adenocarcinoma, URETHRA, CLINICAL pathology, MICROSCOPY, BRAF genes, MOLECULAR weights
Abstract

Aim: Primary mucinous adenocarcinoma of the urethra represents an extremely rare entity. We sought to characterise further these tumours' clinicopathological, immunohistochemical and molecular features. Methods and results: Thirty‐five cases were identified, occurring in 18 males and 17 females. The mean age at diagnosis was 65 years (28–89 years). The main presentation symptoms were haematuria and urinary outlet obstruction. Microscopic analysis revealed that all 35 tumours have stromal dissection by mucin. Ten tumours showed villoglandular dysplasia, nine showed mucinous metaplasia, two showed adenocarcinoma in situ and four showed signet ring cell features. All tumours were immunopositive for CEA, while immunonegative for nuclear β‐catenin; 19 of 23 (83%) expressed high molecular weight cytokeratin; 19 of 33 (58%) CK7; 28 of 34 (82%) CK20; 32 of 35 (91%) CDX2; 22 of 27 (81%) cadherin‐17 (CDH‐17); 26 of 29 (90%) SATB2; and one of 31 (3%) GATA3. Mismatch repair gene products, including MLH1, PMS2, MSH2 and MSH6, were immunopositive, suggesting the MSI‐low genotype of mucinous adenocarcinoma of the urethra. BRAF V600E and ALK rearrangements were not detected. During the mean follow‐up of 20 months, nine patients either developed distant metastasis or succumbed to the illness. Conclusion: Our study, encompassing the most extensive series of 35 cases of primary mucinous adenocarcinoma of the urethra, provides crucial insights into its precise diagnosis, management and potential targeted treatments. We found a greater CDX2, SATB2 and CDH17 sensitivity in these urethral tumours for the first time, to our knowledge. We identified characteristics such as an MSI‐low profile, non‐V600E BRAF mutations and an absence of ALK rearrangements. [ABSTRACT FROM AUTHOR]

Published
2024
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44. Contemporary grading of prostate cancer: 2017 update for pathologists and clinicians

Author

Silvia Gasparrini, Alessia Cimadamore, Marina Scarpelli, Francesco Massari, Andrea Doria, Roberta Mazzucchelli, Liang Cheng, Antonio Lopez-Beltran, and Rodolfo Montironi

Subjects
Gleason grading, Gleason system, prognostic grade grouping, prostate cancer, tertiary pattern, Diseases of the genitourinary system. Urology, RC870-923
Abstract

The Gleason grading system for prostate cancer (PCa) was developed in the 1960s by DF Gleason. Due to changes in PCa detection and treatment, the application of the Gleason grading system has changed considerably in pathology routine practice. Two consensus conferences were held in 2005 and in 2014 to update PCa Gleason grading. This review provides a summary of the changes in the grading of PCa from the original Gleason grading system to the prognostic grade grouping, as well as a discussion of the clinical significance of the percentage of Gleason patterns 4 and 5.

Published
2019
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