Journal of Pathology and Translational Medicine

Original Article

The proteomic landscape shows oncologic relevance in cystitis glandularis: Jun Yong Kim, Dohyun Han, Hyeyoon Kim, Minsun Jung, Han Suk Ryu; J Pathol Transl Med. 2023;57(1):67-74. Published online December 22, 2022; DOI: https://doi.org/10.4132/jptm.2022.10.24

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Background
The relationship between cystitis glandularis (CG) and bladder malignancy remains unclear.
Methods
We identified the oncologic significance of CG at the molecular level using liquid chromatography-tandem mass spectrometry-based proteomic analysis of 10 CG, 12 urothelial carcinoma (UC), and nine normal urothelium (NU) specimens. Differentially expressed proteins (DEPs) were identified based on an analysis of variance false discovery rate < 0.05, and their functional enrichment was analyzed using a network model, Gene Set Enrichment Analysis, and Gene Ontology annotation.
Results
We identified 9,890 proteins across all samples and 1,139 DEPs among the three entities. A substantial number of DEPs overlapped in CG/NU, distinct from UC. Interestingly, we found that a subset of DEP clusters (n = 53, 5%) was differentially expressed in NU but similarly between CG and UC. This “UC-like signature” was enriched for reactive oxygen species (ROS) and energy metabolism, growth and DNA repair, transport, motility, epithelial-mesenchymal transition, and cell survival. Using the top 10 shortlisted DEPs, including SOD2, PRKCD, CYCS, and HCLS1, we identified functional elements related to ROS metabolism, development, and transport using network analysis. The abundance of these four molecules in UC/CG than in NU was consistent with the oncologic functions in CG.
Conclusions
Using a proteomic approach, we identified a predominantly non-neoplastic landscape of CG, which was closer to NU than to UC. We also confirmed a small subset of common DEPs in UC and CG, suggesting that altered ROS metabolism might imply potential cancerous risks in CG.

Citations

Citations to this article as recorded by

Quantitative proteomics and immunohistochemistry uncover NT5DC2 as a diagnostic biomarker for papillary urothelial carcinoma
Jun Yong Kim, Jae Seok Lee, Dohyun Han, Ilias P. Nikas, Hyeyoon Kim, Minsun Jung, Han Suk Ryu
Heliyon.2024; 10(15): e35475. CrossRef
KRT18 as a Novel Biomarker of Urothelial Papilloma while Evaluating Low-Grade Papillary Urothelial Neoplasms: Bi-Center Analysis
Minsun Jung, Bohyun Kim, Jae Seok Lee, Jun Yong Kim, Dohyun Han, Kwangsoo Kim, Sunah Yang, Eun Na Kim, Hyeyooon Kim, Ilias P. Nikas, Sohyeon Yang, Kyung Chul Moon, Hyebin Lee, Han Suk Ryu
Pathobiology.2024; : 1. CrossRef

Case Study

Clinically undetected plasmacytoid urothelial carcinoma of the urinary bladder with non-mass-forming metastases in multiple organs: an autopsy case: Yuya Asano, Kosuke Miyai, Shinya Yoshimatsu, Makoto Sasaki, Katsunori Ikewaki, Susumu Matsukuma; J Pathol Transl Med. 2022;56(4):217-224. Published online May 3, 2022; DOI: https://doi.org/10.4132/jptm.2022.03.15

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Abstract PDF

This case report outlines a clinically undetected urinary bladder plasmacytoid urothelial carcinoma (PUC) with multiple metastases detected at autopsy. An 89-year-old man presented with edema in the lower limbs. Pleural fluid cytology revealed discohesive carcinomatous cells, although imaging studies failed to identify the primary site of tumor. The patient died of respiratory failure. Autopsy disclosed a prostate tumor and diffusely thickened urinary bladder and rectum without distinct tumorous lesions. Histologically, the tumor consisted of acinar-type prostate adenocarcinoma with no signs of metastasis. Additionally, small, plasmacytoid tumor cells were observed in the urinary bladder/rectum as isolated or small clustering fashions. These metastasized to the lungs, intestine, generalized lymph nodes in a non-mass-forming manner. Combined with immunohistochemical studies, these tumor cells were diagnosed PUC derived from the urinary bladder. Both clinicians and pathologists should recognize PUC as an aggressive histological variant, which can represent a rapid systemic progression without mass-forming lesions.

Citations

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Severe Rectal Stenosis as the First Clinical Appearance of a Metastasis Originating from the Bladder: A Case Report and Literature Review
Claudiu Daha, Eugen Brătucu, Ioan Burlănescu, Virgiliu-Mihail Prunoiu, Hortensia-Alina Moisă, Ștefania Ariana Neicu, Laurențiu Simion
Life.2025; 15(5): 682. CrossRef
Carcinomatous Meningitis and Hydrocephalus in Plasmacytoid Urothelial Carcinoma of the Urinary Bladder With Extremely Elevated CA19-9 Levels
Fumiaki Henmi, Kayako Ukai, Atsuhito Nakayama, Yutaka Takazawa, Yoshikazu Uesaka
Cureus.2024;[Epub] CrossRef
Current Advances in the Management of Nonurothelial Subtypes of Bladder Cancer
Evangelia Vlachou, Burles Avner Johnson, Ezra Baraban, Rosa Nadal, Jean Hoffman-Censits
American Society of Clinical Oncology Educational Book.2024;[Epub] CrossRef
Plasmacytoid urothelial carcinoma: a multidisciplinary approach to the diagnosis and management
Marcus Zorovich, Jude Khatib, Aysha Mubeen, Katie Gardner, Nayana Patel
Abdominal Radiology.2024;[Epub] CrossRef
Divergent Histology in Bladder Cancer: What We Need to Know?
Shashank Agrawal, Arun Ramdas Menon, Ginil Kumar Pooleri
UroCancer Clinics of India.2024; 2(2): 100. CrossRef

Original Articles

Differential Immunohistochemical Profiles for Distinguishing Prostate Carcinoma and Urothelial Carcinoma: Woo Jin Oh, Arthur Minwoo Chung, Jee Soon Kim, Ji Heun Han, Sung Hoo Hong, Ji Yeol Lee, Yeong Jin Choi; J Pathol Transl Med. 2016;50(5):345-354. Published online August 7, 2016; DOI: https://doi.org/10.4132/jptm.2016.06.14

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Abstract PDF

Background
The pathologic distinction between high-grade prostate adenocarcinoma (PAC) involving the urinary bladder and high-grade urothelial carcinoma (UC) infiltrating the prostate can be difficult. However, making this distinction is clinically important because of the different treatment modalities for these two entities.
Methods
A total of 249 patient cases (PAC, 111 cases; UC, 138 cases) collected between June 1995 and July 2009 at Seoul St. Mary’s Hospital were studied. An immunohistochemical evaluation of prostatic markers (prostate-specific antigen [PSA], prostate-specific membrane antigen [PSMA], prostate acid phosphatase [PAP], P501s, NKX3.1, and α-methylacyl coenzyme A racemase [AMACR]) and urothelial markers (CK34βE12, p63, thrombomodulin, S100P, and GATA binding protein 3 [GATA3]) was performed using tissue microarrays from each tumor.
Results
The sensitivities of prostatic markers in PAC were 100% for PSA, 83.8% for PSMA, 91.9% for PAP, 93.7% for P501s, 88.3% for NKX 3.1, and 66.7% for AMACR. However, the urothelial markers CK34βE12, p63, thrombomodulin, S100P, and GATA3 were also positive in 1.8%, 0%, 0%, 3.6%, and 0% of PAC, respectively. The sensitivities of urothelial markers in UC were 75.4% for CK34βE12, 73.9% for p63, 45.7% for thrombomodulin, 22.5% for S100P, and 84.8% for GATA3. Conversely, the prostatic markers PSA, PSMA, PAP, P501s, NKX3.1, and AMACR were also positive in 9.4%, 0.7%, 18.8%, 0.7%, 0%, and 8.7% of UCs, respectively.
Conclusions
Prostatic and urothelial markers, including PSA, NKX3.1, p63, thrombomodulin, and GATA3 are very useful for differentiating PAC from UC. The optimal combination of prostatic and urothelial markers could improve the ability to differentiate PAC from UC pathologically.

Citations

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Comparative histologic survey and transcriptomic investigation into canine prostate carcinoma
Nathan K. Hoggard, Said M. Elshafae, Nigel A. Daniels, Jonathan A. Young, Chris Premanandan, John B. Echols, Darshan S. Chandrashekar, Blake E. Hildreth, Michael C. Haffner, Thomas J. Rosol
Research in Veterinary Science.2026; 198: 105981. CrossRef
Impact of hormone sensitivity status on aberrant expression of CK7, CK20, CDX2, GATA3 and TTF1 in prostate cancer
Qing Yin Wang, Nazim Benzerdjeb, Samuel Jaquet, Andreea Stepanov, Mame-Kany Diop, Mirela Birlea, Fred Saad, Dominique Trudel
Human Pathology.2025; 163: 105877. CrossRef
Unusual Perineal Metastasis in a Case of Prostate Cancer on 68Ga-PSMA-11 PET/CT
Ritanshu Solanki, Bhagwant Rai Mittal, Rajender Kumar, Aravindh Sekar, Narender Kumar
Clinical Nuclear Medicine.2024; 49(2): e73. CrossRef
NKX3.1 Expression in Non-Prostatic Tumors and Characterizing its Expression in Esophageal/Gastroesophageal Adenocarcinoma
Ansa Mehreen, Kiran G. Manjee, Divyangi Paralkar, Gladell P. Paner, Thanh Lan
Advances in Anatomic Pathology.2024; 31(3): 202. CrossRef
Clinical Management of Intraductal Carcinoma of the Prostate
Gabriel Wasinger, Olivier Cussenot, Eva Compérat
Cancers.2024; 16(9): 1650. CrossRef
Adenocarcinomas of the Gynecologic Tract Involving the Urinary Bladder: A Series of 16 Cases Potentially Mimicking Urothelial Malignancy
Daniel H. Russell, Jonathan I. Epstein, Oleksandr N. Kryvenko, Matthew Schlumbrecht, Merce Jorda, Andre Pinto
Archives of Pathology & Laboratory Medicine.2024; 148(6): 705. CrossRef
Assessing the diagnostic impact of P63, PSA and BCL-2 proteins in premalignant and malignant prostate tissues
Aderonke C. Ogunlayi, Victor O. Ekundina, Adedapo O. Kehinde, Linus A. Enye, Adegoke O. Aremu
International Journal of Scientific Reports.2024; 10(6): 188. CrossRef
Concurrent occurrence of adenocarcinoma and urothelial carcinoma of the prostate gland: A case report
Jhe Yuan Hsu, Yi Sheng Lin, Li Hua Huang, Tang Yi Tsao, Chao Yu Hsu, Yen Chuan Ou, Min Che Tung
World Journal of Clinical Cases.2024; 12(26): 5952. CrossRef
Metastatic prostate cancer presenting as a posterior mediastinal mass: A rare presentation
Muhammad Haider, Arun Umesh Mahtani, Bachar Botrus, Foma Munoh Kenne, Madiha Fatima Master
Clinical Case Reports.2023;[Epub] CrossRef
Diagnostic and Prognostic Roles of GATA3 Immunohistochemistry in Urothelial Carcinoma
Daeseon Yoo, Kyueng-Whan Min, Jung-Soo Pyo, Nae Yu Kim
Medicina.2023; 59(8): 1452. CrossRef
Primary high-grade urothelial carcinoma of prostate with prostatic hyperplasia: a rare case report and review of the literature
Liang Liu, Fu-zhen Sun, Pan-ying Zhang, Yu Xiao, Xiao Yue, Dong-Ming Wang, Qiang Wang
The Aging Male.2023;[Epub] CrossRef
Expression of Gata Binding Protein 3 as a Prognostic Factor in Urogenital Lesions and Its Association With Morphology
T Govardhan, Debahuti Mohapatra, Sujata Naik, Prateek Das, Pranita Mohanty, Ankita Pal
Cureus.2023;[Epub] CrossRef
Histological and immunohistochemical investigation of canine prostate carcinoma with identification of common intraductal carcinoma component
Simone de Brot, Jennifer Lothion‐Roy, Llorenç Grau‐Roma, Emily White, Franco Guscetti, Mark A. Rubin, Nigel P. Mongan
Veterinary and Comparative Oncology.2022; 20(1): 38. CrossRef
Urothelial Carcinoma and Prostate-specific Membrane Antigen: Cellular, Imaging, and Prognostic Implications
Arsalan Tariq, Amy E. McCart Reed, Andrew Morton, Sima Porten, Ian Vela, Elizabeth D. Williams, John W. Yaxley, Peter C. Black, Matthew J. Roberts
European Urology Focus.2022; 8(5): 1256. CrossRef
Immunohistochemical Reactivity of Prostate-Specific Membrane Antigen in Salivary Gland Tumors
Haruto Nishida, Yoshihiko Kondo, Takahiro Kusaba, Hiroko Kadowaki, Tsutomu Daa
Head and Neck Pathology.2022; 16(2): 427. CrossRef
Weak NKX3.1 expression in a urothelial carcinoma: A diagnostic pitfall
Maryam Abdo, Robert Hoyt, Ashley Highfill, Daniel Mettman
Human Pathology Reports.2022; 27: 300599. CrossRef
Gene of the month: NKX3.1
Jon Griffin, Yuqing Chen, James W F Catto, Sherif El-Khamisy
Journal of Clinical Pathology.2022; 75(6): 361. CrossRef
Diagnostic Value of GATA3 and Uroplakin 3 in Differentiating Urothelial Carcinoma from Prostatic and Colorectal Carcinoma
Maha Salama, Dina A. Khairy
Open Access Macedonian Journal of Medical Sciences.2022; 10(A): 514. CrossRef
Diagnostic challenges for the distinction of high-grade prostatic adenocarcinoma and high-grade urothelial carcinoma of simultaneous occurrences - A literature review
Shreyas Bhushan Jayade, Manana Jikurashvili
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Cytomorphology, immunoprofile, and clinicopathologic correlation of metastatic prostatic carcinoma
Xiaoqi Lin, Qiuying Shi, Ximing J. Yang
Human Pathology.2022; 130: 36. CrossRef
Cutaneous Metastasis of Prostate Adenocarcinoma: A Rare Presentation of a Common Disease
Alexander Dills, Okechukwu Obi, Kevin Bustos, Jesse Jiang, Shweta Gupta
Journal of Investigative Medicine High Impact Case Reports.2021;[Epub] CrossRef
Mining The Cancer Genome Atlas gene expression data for lineage markers in distinguishing bladder urothelial carcinoma and prostate adenocarcinoma
Ewe Seng Ch’ng
Scientific Reports.2021;[Epub] CrossRef
Immunohistochemical analysis of thrombomodulin expression in myocardial tissue from autopsy cases of ischemic heart disease
Takeshi Kondo, Motonori Takahashi, Gentaro Yamasaki, Marie Sugimoto, Azumi Kuse, Mai Morichika, Kanako Nakagawa, Makoto Sakurada, Migiwa Asano, Yasuhiro Ueno
Legal Medicine.2021; 51: 101897. CrossRef
Application and Pitfalls of Immunohistochemistry in Diagnosis of Challenging Genitourinary Cases
Jenny Ross, Guangyuan Li, Ximing J. Yang
Archives of Pathology & Laboratory Medicine.2020; 144(3): 290. CrossRef
New Screening Test Improves Detection of Prostate Cancer Using Circulating Tumor Cells and Prostate-Specific Markers
Karin Ried, Tasnuva Tamanna, Sonja Matthews, Peter Eng, Avni Sali
Frontiers in Oncology.2020;[Epub] CrossRef
An Unlikely Culprit: Gastric Metastasis from Primary Prostatic Adenocarcinoma
Eric Omar Then, Spoorthi Nutakki, Andrew Ofosu, Saad Saleem, Vijay Gayam, Tagore Sunkara, Vinaya Gaduputi
Journal of Gastrointestinal Cancer.2020; 51(3): 1081. CrossRef
MRI of prostatic urethral mucinous urothelial carcinoma: Expanding the differential diagnosis for T2 hyperintense prostatic masses
Neel Patel, Bryan R. Foster, Elena K. Korngold, Kyle Jensen, Kevin R. Turner, Fergus V. Coakley
Clinical Imaging.2020; 68: 68. CrossRef
Morphological and Immunohistochemical Biomarkers in Distinguishing Prostate Carcinoma and Urothelial Carcinoma: A Comprehensive Review
Francesca Sanguedolce, Davide Russo, Vito Mancini, Oscar Selvaggio, Beppe Calò, Giuseppe Carrieri, Luigi Cormio
International Journal of Surgical Pathology.2019; 27(2): 120. CrossRef
A Case of Metastatic Prostate Cancer to the Urethra That Resolved After Androgen Deprivation Therapy
Darren J. Bryk, Kenneth W. Angermeier, Eric A. Klein
Urology.2019; 129: e4. CrossRef
The Homeodomain Transcription Factor NKX3.1 Modulates Bladder Outlet Obstruction Induced Fibrosis in Mice
Mehul S. Patel, Diana K. Bowen, Nicholas M. Tassone, Andrew D. Gould, Kirsten S. Kochan, Paula R. Firmiss, Natalie A. Kukulka, Megan Y. Devine, Belinda Li, Edward M. Gong, Robert W. Dettman
Frontiers in Pediatrics.2019;[Epub] CrossRef
Cancer of unknown primary: Ancillary testing of cytologic and small biopsy specimens in the era of targeted therapy
Morgan L. Cowan, Christopher J. VandenBussche
Cancer Cytopathology.2018; 126(S8): 724. CrossRef
Glandular Tumors of the Urachus and Urinary Bladder: A Practical Overview of a Broad Differential Diagnosis
Alexander S. Taylor, Rohit Mehra, Aaron M. Udager
Archives of Pathology & Laboratory Medicine.2018; 142(10): 1164. CrossRef
S100P as a Marker for Urothelial Histogenesis: A Critical Review and Comparison With Novel and Traditional Urothelial Immunohistochemical Markers
Moushumi Suryavanshi, Julian Sanz-Ortega, Deepika Sirohi, Mukul K. Divatia, Chisato Ohe, Claudia Zampini, Daniel Luthringer, Steven C. Smith, Mahul B. Amin
Advances in Anatomic Pathology.2017; 24(3): 151. CrossRef

Evaluation of Urine Cytology in Urothelial Carcinoma Patients: A Comparison of CellprepPlus® Liquid-Based Cytology and Conventional Smear: Seung-Myoung Son, Ji Hae Koo, Song-Yi Choi, Ho-Chang Lee, Yong-Moon Lee, Hyung Geun Song, Hae-Kyung Hwang, Hye-Suk Han, Seok-Joong Yun, Wun-Jae Kim, Eun-Joong Kim, Ok-Jun Lee; Korean J Pathol. 2012;46(1):68-74. Published online February 23, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.1.68

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Abstract PDF

Background

Urine cytology is an important test in the screening of urothlelial neoplasms. The conventional smear (CS) method of testing urine samples has a low sensitivity, approximately 50% result accuracy for detecting urothelial carcinomas, while liquid-based cytology (LBC) has much improved diagnostic accuracy, sensitivity, and specificity. The aim of this study was to compare the morphologic features and diagnostic efficacy of CellprepPlus® LBC with those of CS for urine cytology.

Methods

A total of 713 cases of urine specimens collected from November 2009 to September 2010 were included. All specimens were divided equally for the preparation of CellprepPlus® LBC and CS for each case.

Results

CellprepPlus® revealed more cellularity, a cleaner background and better cytomorphologic features, but it showed a less intact architectural pattern compared to that of CS. Of the 88 histologically confirmed cases, the diagnostic sensitivity for CellprepPlus® was 50% and higher than the 37.5% for CS. The specificity of both preparations was 100%.

Conclusions

The CellprepPlus® showed an improved quality of slides and provided better diagnostic accuracy, thus CellprepPlus® could be a first-line screening tool in urinary tract cytology.

Citations

Citations to this article as recorded by

A Study on the Workload of Cytotechnologists: Focus on Commercial Laboratories
Eun-Suk PARK
Korean Journal of Clinical Laboratory Science.2025; 57(2): 228. CrossRef
A Comparative Analysis of Diagnostic Performance and Cytomorphologic Features Between Newly Developed WellPrep® and SurePath™ in Serous Effusion Cytology
Ji Eun Choi, Min-Sun Jin, Da Sol Kim, Ilias P. Nikas, Han Suk Ryu
Journal of Cytology.2025; 42(3): 142. CrossRef
Advances in diagnostic liquid‐based cytology
Hideyuki Abe, Akihiko Kawahara, Jun Akiba, Rin Yamaguchi
Cytopathology.2024; 35(6): 682. CrossRef
Impact of implementing the first edition of the Paris system for reporting: A systematic review and meta‐analysis
Sahar J. Farahani, Joshua Li, Beatrice Minder, Philippe Vielh, Marija Glisic, Taulant Muka
Cytopathology.2024; 35(5): 616. CrossRef
Body fluids
Shyam H. Nemade, Meherbano M. Kamal
Indian Journal of Pathology and Microbiology.2023; 66(1): 75. CrossRef
Deep Learning-Based Screening of Urothelial Carcinoma in Whole Slide Images of Liquid-Based Cytology Urine Specimens
Masayuki Tsuneki, Makoto Abe, Fahdi Kanavati
Cancers.2022; 15(1): 226. CrossRef
Diagnostic efficacy of smear plus liquid-based cytology for EUS-FNA of solid pancreatic lesions
Masahiro Itonaga, Shin-Ichi Murata, Keiichi Hatamaru, Takashi Tamura, Junya Nuta, Yuki Kawaji, Takao Maekita, Mikitaka Iguchi, Jun Kato, Fumiyoshi Kojima, Hiroki Yamaue, Manabu Kawai, Ken-Ichi Okada, Seiko Hirono, Toshio Shimokawa, Kensuke Tanioka, Masayu
Medicine.2019; 98(19): e15575. CrossRef
Evaluation and application of Cellprep for cervical cytology
Rinko OZEKI, Keiichi IWAYA, Yuko UMAYAHARA, Yuka MORITA, Mie ARAI, Yukari TAKASUGI, Ryoko KIKUCHI, Kiyohiko MIYAKE, Atsuhiko SAKAMOTO, Masaru SAKAMOTO
The Journal of the Japanese Society of Clinical Cytology.2018; 57(3): 159. CrossRef
Quantitative Proteomic Analysis Identifies AHNAK (Neuroblast Differentiation-associated Protein AHNAK) as a Novel Candidate Biomarker for Bladder Urothelial Carcinoma Diagnosis by Liquid-based Cytology
Hyebin Lee, Kwangsoo Kim, Jongmin Woo, Joonho Park, Hyeyoon Kim, Kyung Eun Lee, Hyeyeon Kim, Youngsoo Kim, Kyung Chul Moon, Ji Young Kim, In Ae Park, Bo Bae Shim, Ji Hye Moon, Dohyun Han, Han Suk Ryu
Molecular & Cellular Proteomics.2018; 17(9): 1788. CrossRef
Reliability of Estrogen Receptor and Human Epidermal Growth Factor Receptor 2 Expression on Breast Cancer Cells Stored in Cellprep® Vials
Ayumi Ryu, Jyun-ichi Ashimura, Takahiro Nakayama, Yasuhiro Tamaki, Shin-ichi Nakatsuka, Yasuhiko Tomita
Acta Cytologica.2018; 62(5-6): 360. CrossRef
Current status of urine cytology: what should the urologist know?
Kristýna Pivovarčíková, Tomáš Pitra, Milan Hora, Marián Švajdler, Ondřej Hes
Czech Urology.2018; 22(4): 242. CrossRef
Morphologic Analysis of Cytomegalovirus Infected Cells in Bronchial Washing Cytology: Comparison of Liquid-Based Preparation and Conventional Smear
Jae Yeon Seok, Jungsuk An, Seung Yeon Ha, Dong Hae Chung, Sangho Lee, Hyunchul Kim
Journal of Pathology and Translational Medicine.2016; 50(2): 147. CrossRef
Romanowsky staining using liquid‐based cytology: A pilot study using Cytolyt®/HESPANDER® processing solution for ThinPrep® preparations
Yuichi Kinoshita, Takashi Yuri, Katsuhiko Yoshizawa, Kosho Takasu, Yuko Emoto, Airo Tsubura, Nobuaki Shikata
Diagnostic Cytopathology.2015; 43(12): 960. CrossRef
Diagnostic Value of Liquid-Based Cytology in Urothelial Carcinoma Diagnosis: A Systematic Review and Meta-Analysis
You Luo, Dong-Li She, Hu Xiong, Li Yang, Sheng-Jun Fu, Francisco X. Real
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Comparison of diagnostic accuracy between CellprepPlus® and ThinPrep® liquid‐based preparations in effusion cytology
Yong‐Moon Lee, Ji‐Yong Hwang, Seung‐Myoung Son, Song‐Yi Choi, Ho‐Chang Lee, Eun‐Joong Kim, Hye‐Suk Han, Jin young An, Joung‐Ho Han, Ok‐Jun Lee
Diagnostic Cytopathology.2014; 42(5): 384. CrossRef
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Carcinoma in situ of the urinary bladder in bladder washing cytology.: Doo Hyun Chung, In Ae Park, Eui Keun Ham; J Pathol Transl Med. 1991;2(1):51-55.

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Abstract PDF: The diagnosis of carcinoma in situ of urinary bladder is difficult in that the symptoms and cystoscopic findings are nonspecific. The cytology of urine could be helpful for diagnosis of carcinoma in situ of urinary bladder. We present a case of bladder washing cytology of carcinoma in situ. A 54 year old man presented with dysuria for 1 year. Cystoscopic findings revealed multifocal reddish trabeculated lesions. The bladder washing cytology revealed rather uniform tumor cells which were singly scattered or forming syncytium in the clean background. The nuclei were round to oval with inconspicious nucleoli. The cystoscopic biopsy revealed typical histologic features of carcinoma in situ of urinary bladder.

The Expression Pattern of Annexin A1 in Urinary Bladder Urothelial Carcinoma and Its Clinicopathologic Significance.: Hojung Lee, Seung Kyu Choi, Young Ok Hong, Won Mi Lee, Sook Kyung Ko, Eun Kyung Kim, Jong Eun Joo; Korean J Pathol. 2011;45(1):62-68.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.1.62

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Abstract PDF: BACKGROUND
Annexin A1 (ANXA1) is known to be involved in the progression and differentiation of various tumors. However, its significance and role in bladder carcinogenesis has not been fully elucidated. To determine the role ANXA1 plays in urothelial carcinoma (UC), we investigated the expression of ANXA1 protein in normal urothelial tissue, carcinoma in situ (CIS), and UC of the urinary bladder.
METHODS
Protein expression level of ANXA1 and its subcellular localization were analyzed in 88 cases of UCs and corresponding 24 normal tissues and 24 CISs by immunohistochemistry.
RESULTS
ANXA1 was significantly down-regulated at all subcellular localization in CIS and in the cytoplasm and membrane of cells of UC, compared to normal tissues. No significant correlation between ANXA1 expression level and tumor depth (pT), growth pattern, and recurrence was found. However, cytoplasmic and membranous ANXA1 were significantly up-regulated in high grade than in low grade UC (p=0.02 in cytoplasm and p=0.03 in membrane).
CONCLUSIONS
These results suggest that ANXA1 dysregulation is involved in urothelial carcinogenesis and ANXA1 is potentially a marker for the pathologic differentiation of UC.

Case Reports

Primary Malignant Melanoma of the Urinary Bladder: A Case Report.: Sung Hak Lee, Eun Deok Chang, Eun Jung Lee, Chang Suk Kang; Korean J Pathol. 2010;44(2):216-219.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.2.216

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Abstract PDF: Primary malignant melanoma in the bladder is very rare, with only 18 cases having been currently reported. A 65-year-old male patient presented with a 5-month history of gross hematuria. On ultrasonography, an 8.1 x 6.1 cm mass was revealed on the bladder wall. A partial cystectomy was performed. Microscopically, the tumor was composed of atypical, pigmented melanocytes that were positive for S-100 protein and they were negative for human melanoma black-45. Although he underwent supportive therapy, an 8.7 x 5.9 cm mass occupying the prevesical space was noted on a follow-up computed tomography scan 4 months later. Two nodules of the left lower lung and multiple enlarged lymph nodes in the left external iliac chain were also revealed. The patient declined any further treatment. The histogenesis of primary bladder melanoma is uncertain, but an origin from neural crest cells has been proposed. The prognosis for patients with this tumor is still poor despite the availability of several therapeutic options.

Solitary Fibrous Tumor of the Urinary Bladder: A Case Report.: Jong Sil Lee, Jeong Seok Hwa, Gyung Hyuck Ko, Jeong Hee Lee, Hwal Woong Kim; Korean J Pathol. 2004;38(2):129-131.

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Abstract PDF: Solitary fibrous tumor (SFT) most commonly affects the pleura and these tumors have been recently reported to be found in unusual locations. We describe here a solitary fibrous tumor of the urinary bladder that was removed from a 79-year-old man having a history of gross hematuria and dysuria. Transabdominal ultrasonography showed a huge soft tissue mass in the urinary bladder. The cut surface of the tumor showed a grayish-white, hemorrhagic and gelatinous appearance. Necrosis was not found. Microscopically, the tumor showed a proliferation of spindle or ovoid cells that were intervened by a collagenous stroma. A variety of growth patterns was identified but the so-called patternless pattern was the predominant one. The spindle cells had almost no mitotic figures, and there was very little or no nuclear atypia. Immunohistochemical stains showed a strong reactivity for CD34 and a focal reactivity for bcl-2. The ultrastructure of the tumor cells showed mesenchymal-myofibroblastic traits.

Collision Tumor Composed of Papillary Transitional Cell Carcinoma, and Osteosarcoma in Urinary Bladder: A cases report.: Nam Hoon Cho, Chanil Park; Korean J Pathol. 1995;29(3):374-377.

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Abstract PDF: This is to report a case of collision tumor of the urinary bladder, which was composed of papillary transitional cell carcinoma(PTCC) and osteosarcoma. Grossly the tumor was located at left antero-lateral wall and was a fungating, gray yellow, bony hard mass with papillary configuration of the luminal surface. Histologically the tumor was composed of PTCC confined to the mucosa and sarcomatous component not intermixed with the overlying PTCC. The sarcomatous area had features of classic osteosarcoma with anaplastic tumor cells and haphazardly arranged osteoid matrix, and was positive for osteonectin but entirely negative for cytokeratin or epithelial membrane antigen. Ultrastructural study demonstrated the tumor cells to be osteoblast which had rich rERs and a few lipid vesicles in plump cytoplasm without any evidence of epithelial ongin. The case is thought to be an example of collision tumor because there was no evidence of transition between PTCC and osteosarcoma.

Urinary Cytologic Findings of Plasmacytoid Transitional Cell Carcinoma of the Urinary Bladder: A Case Report .: Mi Ok Park, Yong Jin Kim, Jae Bok Park; J Pathol Transl Med. 1999;10(1):67-71.

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Abstract PDF: We report a case of 53-year-old man with plasmacytoid transitional cell carcinoma of the urinary bladder, which may be confused with plasmacytoma. The patient initially presented with gross hematuria and dysuria for two months. Cystoscopy and radiologic studies revealed multiple intraluminal protruding masses on the urinary bladder invading perivesical fat tissue. After urinary cytologic examination and cystoscopic biopsy, radical cystectomy and pelvic lymph node dissections were done. Urine cytology showed single cells and poorly cohesive cells with round eccentric nuclei, bi-or multi-nucleation, indistinct nucleoli, coarse chromatin, and abundant basophilic cytoplasm within relatively clear background. The cytologic findings of tumor cells were similar to the plasma cells seen in plasmacytoma. The tumor of the bladder was composed of discohesive, individual cancer cells with diffuse pattern that simulated lymphoma or plasmacytoma. Immunohistochemical and electron microscopic studies clearly established the epithelial nature of the neoplasm. Recognition of this plasmacytoid type of transitional cell carcinoma of the urinary bladder can avoid the misdiagnosis.

Urachal Adenocarcinoma with a Concomitant Urachal Remnant: A Case Report.: Tae Hoon Kim, Mee Joo, Min Kyung Kim, Hanseong Kim, Je G Chi, Jae Y Ro; Korean J Pathol. 2004;38(4):280-283.

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Abstract PDF: Urachal adenocarcinoma is a rare tumor, and it has similarities with nonurachal adenocarcinoma; therefore, it is sometimes difficult to make a diagnosis. We present a typical case of urachal adenocarcinoma that had all the diagnostic criteria including the presence of an urachal remnant. A 65-year-old woman presented with complaints of a painless gross hematuria. Pelvic CT and cystoscopy showed an intraluminal protruding mass centered in the bladder wall. When diagnosed as adenocarcinoma with a signet ring cell component being noted by frozen biopsy, partial cystectomy with resection of the median umbilical ligament and peritoneum was carried out for a suspected urachal adenocarcinoma. The tumor morphology showed as typical mucinous adenocarcinoma. Characteristic tubular structures showing the typical histology of an urachal remnant was found in the perivesical fat. On immunohistochemical staining, the urachal adenocarcinoma showed a pattern similar to colonic adenocarcinoma, while the urachal remnant showed strong positivity for CK7 and Chromogranin A.

Radiation-Induced Epithelial Proliferation Mimicking Invasive Carcinoma of the Urinary Bladder: A Report of 2 Cases.: Ok Jun Lee, Kyu Rae Kim, Dae Woon Eom, Hyun Jung Kim, Na Hye Myong, Jae Y Ro; Korean J Pathol. 2004;38(5):341-344.

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Abstract PDF: Radiation-induced epithelial proliferation in the urinary bladder mimicking urothelial carcinoma has received only a little attention in the literature. Herein, we describe two cases of radiation-induced epithelial proliferative changes, which mimicked invasive urothelial carcinoma. Cystoscopy revealed bullous or edematous mucosal changes with multiple hemorrhagic foci. Microscopically, we observed inverted epithelial proliferation, forming nests and cords extending into the lamina propria. The epithelial cells in these nests and cords exhibited enlarged, hyperchromatic and pleomorphic nuclei, closely mimicking the infiltrative growth of urothelial carcinoma. However, the presence of radiation-induced changes was validated by the observation of abundant vacuolated cytoplasm, normal or slightly increased nuclear to cytoplasmic ratios, the absence of mitotic activity, dilated blood vessels containing frequent fibrin thrombi, scattered atypical fibroblasts, and the patients' previous history of radiation treatment. Radiation-induced changes should be always included in differential diagnoses of proliferative epithelial lesions in the urinary bladder and a pertinent clinical history of radiotherapy should be searched.

Original Article

Immunohistochemical Study for p53 and hsc70 in Transitional Cell Carcinoma of the Urinary Bladder: Correlation with Histologic Grade, Clinical Stage and DNA Ploidy Pattern.: Hyuni Cho, Sung Jin Cho, Han Kyeom Kim, Yang Seok Chae; Korean J Pathol. 1995;29(6):766-775.

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Abstract PDF: Transitional cell carcinoma of the urinary bladder is the most common cancer of the genitourinary tract in Korea and its prognosis is determined by the histologic grade and clinical stage present at initial diagnosis. Recently, an extensive search for a more objective and reproducible method to evaluate the proliferation activity of cancer cells has been done. The p53 gene is located on the short arm of the chromosome 17 and acts as a cancer suppressor gene. Mutant p53 gene induces malignant transformation. Recent studies reveal that the level of mutant p53 protein is elevated in some human tumor and many diverse transformed cell lines. Heat shock proteins(HSPs) are present constitutively in normal cells, where they play an important role in normal cell metabolism. In mammalian cells, they are induced by a variety of physical and chemical stimuli. A protein that belongs to the hsp70 family, called hsc70, is only slightly heat inducible and is found at a higher level in growing cells than in the resting cells. The mutant p53 protein binds with hsc70 and the p53-hsc70 complex has functional significance in the transforming capacity of the mutant p53. We investigated the correlation between the p53 and hsc70 by immunohistochemical methods and with better defined prognostic indicators such as histologic grade, clinical stage, and DNA ploidy pattern in 42 transitional cell carcinomas of the urinary bladder. The results are summarized as follows. p53 expression rate was higher in the DNA aneuploid group than in the DNA diploid group(p=0.061), but there was no significant difference in the histologic grade(p=0.861) or clinical stage(p=0.154). The higher the hsc70 expression rate was, the poorer the tumor differentiation(p=0.000) and the deeper the invasion(p=0.001). The aneuploid group showed a higher hsc70 expression rate than the diploid group(p=0.017). 27 of 42(64.3%) carcinomas showed positivity of both p53 and hsc70. Though statistically insignificant, their correlation showed a relatively low correlation coefficient (P=0.059). In conclusion, we suspect that p53 and hsc70 are closely correlated to each other by comparing the results of this immunohistochemical study, and hsc70 will be a useful prognostic marker in transitional cell carcinomas of the urinary bladder after sufficient follow up studies are performed.

Case Reports

Cytologic Findings of Primary Small Cell Carcinoma of the Urinary Bladder: A case report.: Mi Seon Kwon, Geung Hwan Ahn, Jin Haeng Chung, Seung Sook Lee, Jae Soo Koh; J Pathol Transl Med. 2001;12(2):121-126.

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Abstract PDF: Primary small cell carcinoma of the urinary bladder is a rare malignant tumor. A more rapidly fatal course may be seen in advanced stages of small cell carcinoma as compared to similar stages of urothelial carcinoma. It is very important to recognize this distinct form of bladder cancer by urinary cytology. The differential diagnosis of small cell carcinoma of the urinary bladder includes metastatic small cell carcinoma, urothelial carcinoma, and primary or secondary malignant lymphoma. This article highlights the urinary cytologic diagnosis of a case of primary small cell carcinoma. A 59-year-old male presented with gross hematuria for five months. Urinary cytology showed high cellularity consisting of tiny monotonous tumor cells in the necrotic background. The tumor cells occurred predominantly singly, but a few in clusters. The cytoplasm was so scanty that only a very narrow rim of it was seen. The nuclei were oval or round and had finely stippled chromatin. Rarely, the nuclei contain visible nucleoli. Frequently cell molding was noted in clusters. Many single cells demonstrated nuclear pyknosis or karyorrhexis. The histologic findings of transurethral resection and partial cystectomy specimen were those of small cell carcinoma. Cytologic distinction may be very difficult but careful attention to clinical features and cellualr details can classify these neoplasms correctly.

Florid von Brunn Nests of the Urinary Bladder: A Case Report.: Han Seong Kim, Ji Eun Kwak, Sang Hwa Shim, Mee Joo, Sun Hee Chang, Je G Chi, In Rae Cho; Korean J Pathol. 2008;42(3):169-171.

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Abstract PDF: Among benign proliferations of the urinary bladder, von Brunn nests and cystitis cystica et glandularis are common. Sometimes florid proliferation of von Brunn nests makes an intravesical mass, which mimics tumorous lesions. We report here on a case of florid von Brunn nests, occurred in the 34-year-old man with hematuria. Radiological and cystoscopic examinations reveal a polypoid-papillary lesion and transurethral resection was then performed. Pathologically, prominent proliferations of urothelial cell nests were found deep in the lamina propria. Neither significant cytologic atypia nor muscle invasion was noted. Florid von Brunn nests should be considered both clinically and pathologically in the differential diagnosis of a intravesical mass.

Urinary Cytologic Findings of Small Cell Neuroendocrine Carcinoma: A Case Report.: Dong Hoon Kim, Dong Wook Kang, Kyung Hee Kim, Ju Heon Kim, Mee Ja Park; J Pathol Transl Med. 2002;13(2):78-83.

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Abstract PDF: We report the cytologic features of a case of primary small cell carcinoma of the urinary bladder with high grade transitional cell and signet ring cell carcinomatous components. A 64-year-old male presented with gross hematuria for one week. Computed tomography revealed an ill-defined mass in the left lateral wall of the urinary bladder. Urinary cytology showed hypercellularity with predominantly isolated single cells and clustered cells. They have scanty cytoplasm and naked hyperchromatic nuclei with finely granular nuclear chromatin and rare nucleoli. The tumor cells occurred predominantly singe cells, but a few in clusters. Nuclear molding was prominent. No glandular formation or nesting was noted. The second tumor cells had high nuclear/cytoplasmic ratio, irregular nuclear membrane, and coarse granular chromatin. The background was inflamed and necrotic. The histologic findings of transurethral resection were mainly composed of small cell carcinoma, and partly transitional cell and signet ring cell carcinomatous components. Small cell neuroendocrine carcinoma have distinctive cytologic features to make a proper diagnosis.

Leiomyoma of the Urinary Bladder.: Kye Weon Kwon, Hee Jung Ahn, Yoon Jung Choi, Young Kwon Hong, Jae Seop Shin; Korean J Pathol. 1997;31(12):1320-1323.

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Abstract PDF: Leiomyoma is commonly found in the female genital tract, but occurrence in the urinary bladder is very rare with only 235 cases reported in the literature. These tumors have been classified as intravesical (63%), intramural (7%) and extravesical (30%) depending on the direction of the growth. We report a case of intravesical leiomyoma of the urinary bladder in a 36 year-old woman who exhibited dysuria and urinary retention. The gross and microscopical findings of leiomyoma of the bladder are similar to those of the uterus. Immunohistochemical stains for estrogen receptor (ER) and progesterone receptor (PR) revealed diffuse nuclear staining in smooth muscle cells, supporting the hypothesis of hormonal influence in tumorigenesis.

A Case of Inflammatory Pseudotumor of the Urinary Biadder.: Hye Rim Park, Min Chul Lee, Nack Kyu Choi, Young Euy Park; Korean J Pathol. 1991;25(3):256-262.

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Abstract PDF: Inflammatory pseudotumor of the urinary bladder is a proliferative spindle cell lesion that microscopically may suggest a sarcoma but that are benign without a recent history of an operation. The first such case was reported by Roth, in 1980, and thereafter about seven more cases were reported in medical literatures. We reported a case of inflammatory pseudotumor of the urinary bladder mimicking leiomyosarcoma. Patient was a 36-year-old woman with complaint of painless total and gross hematuria for 3 weeks. Partial cystectomy specimen showed a well-demarcated nodular mass of yellow white color, involving the submucosal and muscular layers. Microscopic examination revealed proliferating bundles of spindle cells interspersed with infiltration of many inflammatory cells including eosinophils. Spindle cells were positive for vimentin on immunohistochemistry and corresponding to myofibroblasts on the electron microscopic examination.

Original Articles

Inflammatory Pseudotumor of the Urinary Bladder: An Immunohistochemical and Ultrastructural Study.: Seung Sam Paik, Joo Seob Keum, Moon Hyang Park, Jung Dal Park; Korean J Pathol. 1996;30(5):447-452.

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Abstract PDF: Inflammatory pseudotumor of the urinary bladder is an unusual, benign mesenchymal proliferative lesion of the submucosal stroma easily mistaken for a malignant neoplasm clinically and histologically. We present a case and describe the clinical presentation and radiologic, histologic, histochemical, immunohistochemical, and ultrastructural findings. A 23-year old patient presented with sudden onset of gross painless hematuria for 3 months. There was no previous instrumentation or surgery involving the genitourinary tract. Cystoscopy revealed a large polypoid and ulcerated bladder mass. The lesion consisted of plump spindle shaped, fibroblast-like cells embedded in a myxoid stroma. Mitotic figures were negligible and the lesion showed encroachment on the superficial muscle bundles. The spindle cells were immunoreactive for vimentin and muscle specific actin. Immunohistochemical and ultrastructural findings revealed the fibroblastic-myofibroblastic nature of this lesion. Complete surgical excision by partial cystectomy was successful in eradicating the lesion. The findings are described with a discussion of the pathogenesis and review of the literature.

New Techniques for the Detection of the Malignant Cells in Urine Cytology.: Gyungyub Gong; J Pathol Transl Med. 2006;17(1):18-26.

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Abstract PDF: Transitional cell carcinoma of the urinary bladder is common in the genitourinary tract. The gold standard for the diagnosis of bladder cancer has been cystoscopy, along with urine cytology. Cystoscopy is an invasive and relatively expensive technique. By comparison, urine cytology is easy to perform and specific for a diagnosis of bladder cancer, although less sensitive, especially in low-grade tumors. For this reason, there has been a need for superior noninvasive technology to increase our confidence in being able to detect bladder cancer. There are many reports of the various urinary tests that are available to facilitate the diagnosis. In this article, I reviewed the literature on urinary markers and tests that may be clinically useful, including fluorescence in situ hybridization, uCyt+/Immunocyte, the BTA(R) test, the NMP 22TM, the FDP(R) test, the telomerase activity test, the HA and HAse tests, and flow cytometry. Most of these tests have a higher sensitivity and specificity than cytology. However, urine cytology has the highest specificity, especially in individuals with a high-grade tumor. We conclude that no urinary markers or tests can replace the role of cystoscopy along with cytology in the diagnosis of transitional cell carcinoma of the bladder. However, some markers could be used adjunctively to increase the diagnostic accuracy during screening or during the postoperative follow-up examination of patients with bladder cancer.

Prognostic Value of the PCNA Index in Transitional Cell Carcinoma of the Urinary Bladder.: Sang Yeop Yi, Young Nyun Park, Chan Il Park; Korean J Pathol. 1994;28(3):282-287.

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Abstract: It is well known that histologic grade and tumor stage are important prognostic factors, and that the monoclonal antibody to proliferating cell nuclear antigen(PCNA) can recognize S-phase cells. The PCNA index of 53 transitional cell carcinomas(TCCs) of the urinary bladder was studied to evaluate its prognostic validity. The PCNA indices of TCCs ranged from 38 to 92, whih were quite different from that of normal transitional epithelium(9.4). The PCNA indices were significantly higher in tumors of the higher histologic grade and/or tumor stage(correlation coefficient 0.64 and 0.43; P=0.00). The PCNA index was particularly valuable in discriminating the superficial TCCs from the deeply invasive TCCs(67.1+/-15.46 and 79.9+/-9.70; P=0.000). Among TCCs of the same tumor stage, the histologic grade affected the PCNA index. However, TCCs of the same histologic grade revealed similar PCNA indices regardless of tumor stage. These results indicate that the PCNA index is an objective and reliable prognostic factor in TCCs, which is superior to the conventional histologic grade.

Case Reports

Micropapillary Variant of Urothelial Carcinoma of the Urinary Bladder: Report of a Case with Cytologic Diagnosis in Urine Specimen.: Young Seok Lee, Hyunjoo Lee, Jung Woo Choi, Bongkyung Shin, Hankyem Kim, Insun Kim, Aeree Kim; J Pathol Transl Med. 2006;17(1):46-50.

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Abstract PDF: A micropapillary variant of urothelial carcinoma (MPC) is a distinct entity with an aggressive clinical course. It has a micropapillary configuration resembling that of ovarian papillary serous carcinoma. Its cytologic features have rarely been reported. We report a case of MPC detected by urine cytology. A woman aged 93 years presented with a chief complaint of macroscopic hematuria. Cytology of her voided urine showed clusters of malignant cells in a micropapillary configuration. Each tumor cell had a vacuolated cytoplasm, a high nuclear:cytoplasmic ratio, and irregular hyperchromatic nuclei. An ureteroscopic examination revealed exophytic sessile papillary masses extending from the left lateral wall to the anterolateral wall of the urinary bladder. A transurethral resection of the tumor was carried out. The tumor was characterized by delicate papillae with a thin, well-developed fibrovascular stromal core and numerous secondary micropapillae lined with small cuboidal cells containing uniform low- to intermediate-grade nuclei and occasional intracytoplasmic mucinous inclusions. These tumor cells infiltrated the muscle layers of the bladder, and lymphatic tumor emboli were frequently seen. Recognizing that the presence of MPC components in urinary cytology is important for distinguishing this lesion from low-grade papillary lesions and high-grade urothelial carcinomas can result in early detection and earlier treatment for an improved treatment outcome.

Cytologic Findings of a Plasmacytoid Variant of Urothelial Carcinoma of the Urinary Bladder in Voided Urine.: Soo Jin Jung, Joo Yeon Song, Hye Kyoung Yoon, Sung Hyup Choi; J Pathol Transl Med. 2006;17(1):51-55.

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Abstract PDF: The plasmacytoid variant is an extremely rare form of urothelial carcinoma in which the malignant cells resemble those of plasmacytoma. We report the cytologic features of 3 cases of this disorder. All 3 patients were male and presented with painless macroscopic hematuria. The voided urine cytology revealed a few scattered clusters of tumor cells in a bloody background. Each tumor cell had an abundant amount of cytoplasm that was clear or densely stained and characterized by eccentrically located nuclei. A histological examination of tissue obtained from a radical cystectomy confirmed the cytologic diagnosis in each 3 case, revealing a diffusely infiltrating tumor composed of round, noncohesive tumor cells demonstrating a high nuclear grade. These cells had infiltrated the tunica propria in 2 cases, but were limited to the submucosa in 1 case. The tumor cells were plasmacytoid in appearance, each demonstrating an eccentric nucleus and dense cytoplasm, as seen in the cytologic findings. All of the tumors were immunoreactive for pancytokeratin, CK7, CK20; negative for epithelial membrane antigen (EMA), leukocyte common antigen (LCA), kappa, lambda, and CD79a. Thus, it is important to consider the plasmacytoid variant of urothelial carcinoma in addition to plasmacytoma or lymphoma as a diagnosis when encountering plasmacytoid tumor cells in a voided urine sample.

Paraganglioma of the Urinary Bladder: A case report.: H K Lee, K M Lee, D K Chung; Korean J Pathol. 1988;22(2):164-168.

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Abstract PDF: We herein report a case of paraganglioma arising from the urinary bladder in a 67-year-old woman. Her chief complaint was gross hematuria. However, she didn't manifest any other catecholamine-associated symptoms such as hypertension, palpitation and micturitional attack. Grossly, the tumor revealed bilobular external appearance with foci of ulceration and hemorrhage. The cut surface showed pinkish yellow homogeneous soft tissue. Microscopically, the tumor was composed of polygonal cells with basophilic granular plump cytocopic study, numerous membrane-bound electron dense granules were noted in the cytoplasm.

Original Articles

Expression of p27Kip1 Protein in Carcinoma of the Urinary Bladder.: Ki Kwon Kim, Jung Ran Kim; Korean J Pathol. 2000;34(5):341-348.

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Abstract PDF: The cyclin-dependent kinase (cdk) inhibitor p27Kip1 gene is a powerful molecular determinant of cell cycle progression. Loss of expression of p27Kip1 has recently been shown to be predictive of disease progression in several human malignancies. The prognostic value and expression of p27Kip1 have been incompletely studied in bladder cancer. In this study, we investigated the relationship between p27Kip1 protein expression and clinicopathologic parameters in 50 cases of carcinoma of the urinary bladder by conducting immunohistochemical analysis and DNA flow-cytometry. Malignant bladder tissue demonstrated a heterogeneous pattern of p27Kip1 immunoreactivity. In addition, there was progressive loss of expression with increasing tumor grade. The expression of p27Kip1 protein was unrelated to stage, DNA ploidy and S phase fraction (SPF). SPF was unrelated with tumor grade and DNA ploidy. The results indicate that p27Kip1 is frequently expressed in well differentiated transitional cell carcinomas of the urinary bladder but less often expressed in muscle-invasive transitional cell carcinomas. The expression of p27Kip1 and its prevalence in low-grade tumors may reflect growth regulatory influences and potential inhibiting action in tumor progression and novel predictive markers of the biological potential of bladder tumors.

Correlation between Histopathologic Grade, Stage, and Degree of EGFR Expression in Transitional Cell Carcinoma of the Urinary Bladder.: Hyeon Ok Kim, Hwa Sun Lee, Kang Suek Suh; Korean J Pathol. 1996;30(9):784-791.

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Abstract PDF: This study was performed to estimate the correlation between the histopathological grade and the clinical stage, which are known as important prognostic factors, and EGFR expression status in 57 cases of transitional cell carcinoma of the urinary bladder. There was a significant correlation between the histopathological grade and clinical stage of transitional cell carcinoma of the urinary bladder and between expression grades of EGFR and histopathological grades, or clinical stages of transitional cell carcinoma of the urinary bladder. Therefore, the presence of a high intensity of EGFR staining in the transitional cell carcinoma of the urinary bladder was associated with poor differentiation and invasion. On the basis of the above results, it was suggested that the degree of EGFR expression is one of the objective and reliable prognostic factors in transitional cell carcinoma of the urinary bladder.

Clinicopathologic Analysis of the Micropapillary Variant of Urothelial Carcinoma in Urinary.: Kyungji Lee, Ahwon Lee, Yeong Jin Choi, Kyo Young Lee, Chang Suk Kang, Sang In Shim; Korean J Pathol. 2006;40(4):263-268.

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Abstract PDF: BACKGROUND
Micropapillary urothelial carcinoma of urinary bladder is a rare and aggressive subtype of urothelial carcinoma (UC).
METHODS
AND RESULTS: Seven UCs with a micropapillary component (MPC) were identified by reviewing 135 cystectomy specimens of UC (5.2% in incidence). MPC was associated with conventional UC in 6 cases and the plasmacytoid variant of UC in 1 case. Lymph node metastasis, that characteristically contained MPC was present in 60% (3 out of 5 cases of regional lymph node dissection). Three patients with extensive MPC showed laminar propria invasion (pT1; 33%) and perivesical fat invasion (pT3; 67%). Two out of 3 patients with extensive MPC showed distant metastasis into the colon after cystectomy. The colonic lesions showed exclusively micropapillary differentiation. Four patients with focal or moderate MPC (pT2, 25%; pT3, 75%) were alive without disease at the time of writing this article. All 3 cases with extensive MPC had surface and/or invasive MPC on the prior TURB specimen. Immunohistochemically, the tumor cells were positive for cytokeratin 7, cytokeratin 20, EMA and E-cadherin and tissue retraction spaces that simulate lymphatic spaces were negative for CD34 in all 7 cases.
CONCLUSIONS
This study suggests that the micropapillary growth pattern in UC is a manifestation of aggressive behavior and UC with MPC must be included as part of the differential diagnosis when dealing with a metastatic lesion with a micropaillary structure.

Expression of Survivin, HSP90, Bcl-2 and Bax Proteins in N-butyl-N-(4-hydroxybutyl)nitrosamine-induced Rat Bladder Carcinogenesis.: Sang Dae Lee, Sung Woong Park, Soon Auck Hong, Gui Young Kwon, Tae Jin Lee; Korean J Pathol. 2006;40(5):333-338.

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Abstract PDF: BACKGROUND
Survivin belongs to the inhibitor of apoptosis family, and it has recently been found to be expressed in most solid tumors. Therefore, its expression is suggested to have prognostic significance. However, no data are available concerning the significance of survivin for the carcinogenesis of bladder cancer.
METHODS
In order to induce urothelial tumor in the rat urinary bladder, 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was administered to male Sprague-Dawley rats for 30 weeks. We used immunohistochemistry to investigate the expressions of survivin, HSP90, Bcl-2 and Bax in rat bladder carcinogenesis.
RESULTS
Urothelial cell hyperplasia, papilloma, non-invasive urothelial carcinoma and invasive urothelial carcinoma appeared at 5, 10, 20 and 30 weeks, respectively. The expressions of survivin and HSP90 increased sequentially from normal mucosa, hyperplasia, papilloma, non-invasive urothelial carcinoma to invasive urothelial carcinoma. The expressions of Bcl-2 and Bax did not increase, however the number of cases with more than 1 of Bcl-2/Bax expression ratio increased sequentially during the progression of urothelial lesion. The expression of survivin showed a statistically significant correlation with the expression of HSP90 and the Bcl-2/Bax expression ratio.
CONCLUSIONS
Our findings suggest that survivin may be involved in the carcinogenesis of rat bladder and its expression is correlated with the expression of HSP90 and the Bcl-2/Bax expression ratio.

The Study of Histopathologic Grade, PCNA and AgNORs Staining in the Recurrent Urinary Bladder Cancer.: Soo Yeon Cho, Woon Sub Han; Korean J Pathol. 1994;28(6):643-650.

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Abstract PDF: The prognosis of transitional cell carcinoma(TCC) of the urinary bladder is related to histopathologic parameters, among which the clinical stage and histopathologic grade are most important prognostic determiantors. Recently the immunohistochemical assessment of proliferating cell nuclear antigen(PCNA) and nucleolar organizer region number(AgNORs) can obtain the PCNA, and AgNORs stainings were studied in 55 the sequential biopsies of 22 recurrent TCCs of the urinary bladder. 6 cases showed the increased changes of grade, of which 5 cases was independently to the change of grade. The AgNORs in 18 cases showed increase in 10 cases. The comparison between PCNA count and AgNORs score according to grade was performed in the changes between grade II and III, both PCNA count and AgNORs score were increased with in crease of grade. However, The change of the PCNA count was stastically significant, but not AgNORs score.

Expression of Cyclins (D1, A, E, and B1) in N-butyl-N-(4-hydroxybutyl)nitrosamine-induced Rat Bladder Carcinogenesis.: Gui Young Kwon, Eon Sub Park, Sung Geun Bong, Tae Jin Lee, Mi Kyung Kim, Jae Hyung Yoo, Kye Yong Song; Korean J Pathol. 2003;37(4):255-262.

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Abstract PDF: BACKGROUND
Cell cycle deregulation plays a major role in chemical multistage carcinogenesis.Therefore, the evaluation of cell cycle proteins is important.
METHODS
In order to induce carcinogenesis in the rat urinary bladder, 0.05% N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)was administered to male Sprague-Dawley rats for 30 weeks. Expressions of cyclin D1, A, E, and B1 were examined by immunohistochemical stainings.
RESULTS
Urothelial cell hyperplasia appeared at 5 weeks, followed by papilloma at 10 weeks. Superficial carcinoma was observed at 20 weeks, and invasive carcinoma developed in 40% (4/10) of the rats at 30 weeks. Expressions of cyclin D1 and A increased sequentially from normal mucosa throughhyperplasia, papilloma, and carcinoma (p<0.01). Expressions of cyclin D1, B1 and cyclin Ewere higher in invasive carcinomas than in superficial carcinomas (p<0.01). In contrast, therewas no significant difference in the expression of cyclin B1 between hyperplasia, papillomaand superficial carcinoma.
CONCLUSIONS
The present results indicate the important roles of cyclin D1 and A in the development of BBN-induced urothelial carcinoma of rats. Aberrantexpression of cyclin B1 and E may contribute to the progression from superficial to invasivebladder cancer rather than tumorigenesis.

Case Reports

Adenocarcinoma of Urinary Bladder: 2 cases report.: Ki Kwon Kim, Eunk Sook Chang, Chai Hong Chung; Korean J Pathol. 1988;22(4):456-461.

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Abstract PDF: Two cases of adenocarcinoma of the urinary bladder with clinical and pathological features, and brief review of the literatureare presented. Case 1: The patient, a 52 year-old man, was admitted to this hospital because of intermittent painless total gross hematuria for 15 years. Cystoscopy was done, and showing a cauliflower mass with broad based diffuse infiltrating lesion at the right anten or portion of bladder. TUR-B was performed. Microscopically, the lesion consisted of colonic metaplastic epithelium with atypical glands and cystic dilatation and adenocarcinoma. Case 2: The patient, a 52-year-old woman, was admitted to this hospital because of total painless gorss hematuria for 1 year. Cystoscopy was done showing a sessile diffuse mass with ulceration on the dome area. Total cystectomy was performed. Grossly, the tumor showed an ulcerative tumor mass with elevated nodular margin at the dome of the bladder. Microscopically, the lesion consisted of anaplastic glands with back to back arrangement and branching glands through the entire thickness of the bladder wall.

The Intestinal Type of Florid Cystitis Glandularis Mimics Bladder Tumor: A Case Report.: Young Soo Song, Ki Seok Jang, Si Hyong Jang, Kyueng Whan Min, Woong Na, Soon Young Song, Hong Sang Moon, Tchun Yong Lee, Seung Sam Paik; Korean J Pathol. 2007;41(2):116-118.

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Abstract PDF: Cystitis glandularis is a benign metaplastic proliferative lesion of the urinary bladder which usually occurs in the setting of chronic irritation and infection or in some cases as a congenital process. Sometimes it presents as a tumor mass-like florid lesion, grossly mimicking malignancy. We report a case of 59-year-old man with multiple mass lesions around the trigone and the neck portion, which suggested the possibility of malignancy in clinical and radiological evaluations. Final diagnosis was confirmed by transurethral resection. The surface urothelial lining was intact. The submucosa showed von Brunn's nests, cystitis glandularis and cystitis cystica in the edematous lamina propria. There were numerous glands lined by tall columnar, mucin producing epithelium without atypia, conforming to the appearance of the intestinal variant of cystitis glandularis. The cystitis glandularis may mimic a neoplasm on gross evaluation. The intestinal variant of cystitis glandularis is particularly likely to be problematic when florid.

Original Article

Cyclin D1 Protein Expression is Inversely Correlated with p53 Protein in Primary and Recurrent Transitional Cell Carcinoma of the Urinary Bladder.: Min Jin Lee, Sun Hee Sung, Woon Sup Han; Korean J Pathol. 2000;34(12):1009-1015.

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Abstract PDF: Transitional cell carcinoma of the urinary bladder is the most common cancer of the urinary tract and is characterized by frequent recurrence. Like the other malignant tumor, the genetic alterations leading to neoplastic transformation of the urothelium are related with the activation of oncogenes and loss of functional tumor suppressor genes. Cyclin D1 is a putative protooncogene as cell cycle regulator essential for G1 phase progression and is frequently overexpressed in several human tumor. In this study we performed immunohistochemical stainings of cyclin D1 and p53 in both primary and recurrent transitional cell carcinomas of urinary bladder from 56 patients including 20 cases of recurrent tumor, and compared their results with histopathologic features. The results were as follows. Cyclin D1 immunoreactivity was found in 10 of 10 cases (100%) of grade 1, 25 of 41 (61%) cases of grade 2, and 11 of 25 (44%) cases of grade 3 transitional cell carcinomas. p53 immunoreactivity was found in 40% of grade 1, 63% of grade 2, and 87% of grade 3 lesions. Cyclin D1 expression was significantly higher in Ta and T1 lesions than T2 to T4 by pathologic tumor stage. Conversely p53 immunoreactivity was increased in proportion to the T classification. Cyclin D1 was de creased in recurrent transitional cell carcinomas, compared with primary transitional cell carcinomas. However, there was no statistical significance. In conclusion, cyclin D1 immunoreactivity is associated with low histologic grade and low tumor stage. And there is inverse relationship between the cyclin D1 and p53 overexpression.

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