Journal of Pathology and Translational Medicine

Original Article

Significance of tumor-associated neutrophils, lymphocytes, and neutrophil-to-lymphocyte ratio in non-invasive and invasive bladder urothelial carcinoma: Wael Abdo Hassan, Ahmed Kamal ElBanna, Noha Noufal, Mohamed El-Assmy, Hany Lotfy, Rehab Ibrahim Ali; J Pathol Transl Med. 2023;57(2):88-94. Published online January 10, 2023; DOI: https://doi.org/10.4132/jptm.2022.11.06

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Background
Tumor-infiltrating neutrophils and lymphocytes play essential roles in promoting or combating various neoplasms. This study aimed to investigate the association between tumor-infiltrating neutrophils and lymphocytes and the neutrophil-to-lymphocyte ratio in the progression of urothelial carcinoma.
Methods
A total of 106 patients diagnosed with urothelial carcinoma were was. Pathological examination for tumor grade and stage and for tumor-infiltrating neutrophils, both CD4 and CD8+ T lymphocytes, as well as the neutrophil- to-lymphocyte ratio were evaluated.
Results
The presence of neutrophils and the neutrophil-to-lymphocyte ratio correlated with high-grade urothelial neoplasms. In both low- and high-grade tumors, the lymphocytes increased during progression from a non-invasive neoplasm to an early-invasive neoplasm. CD8+ T lymphocytes increased in low-grade non–muscle-invasive tumors compared to non-invasive tumors. Additionally, there was a significant decrease in CD8+ T lymphocytes during progression to muscle-invasive tumors.
Conclusions
Our results suggest that tumor-infiltrating neutrophils and CD8+ T lymphocytes have a significant effect on tumor grade and progression.

Citations

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Immune cell networking in solid tumors: focus on macrophages and neutrophils
Irene Di Ceglie, Silvia Carnevale, Anna Rigatelli, Giovanna Grieco, Piera Molisso, Sebastien Jaillon
Frontiers in Immunology.2024;[Epub] CrossRef
Immunohistochemistry assessment of tissue neutrophil-to-lymphocyte ratio (tNLR) predicts outcomes in melanoma patients treated with anti-programmed cell death 1 therapy
Renan J. Teixeira, Vinícius G. de Souza, Bruna P. Sorroche, Victor G. Paes, Fabiana A. Zambuzi-Roberto, Caio A.D. Pereira, Vinicius L. Vazquez, Lidia M.R.B. Arantes
Melanoma Research.2024;[Epub] CrossRef
Association between alteration of neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, cancer antigen-125 and surgical outcomes in advanced stage ovarian cancer patient who received neoadjuvant chemotherapy
Ponganun Tuntinarawat, Ratnapat Tangmanomana, Thannaporn Kittisiam
Gynecologic Oncology Reports.2024; 52: 101347. CrossRef
Significant association between high neutrophil-lymphocyte ratio and poor prognosis in patients with hepatocellular carcinoma: a systematic review and meta-analysis
Chunhua Xu, Fenfang Wu, Lailing Du, Yeping Dong, Shan Lin
Frontiers in Immunology.2023;[Epub] CrossRef
Chitinase 3-like-1 Expression in the Microenvironment Is Associated with Neutrophil Infiltration in Bladder Cancer
Ling-Yi Xiao, Yu-Li Su, Shih-Yu Huang, Yi-Hua Chen, Po-Ren Hsueh
International Journal of Molecular Sciences.2023; 24(21): 15990. 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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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

Review

Distinctive morphological and molecular features of urothelial carcinoma with an inverted growth pattern: Francesca Sanguedolce, Beppe Calò, Marco Chirico, Ugo Falagario, Gian Maria Busetto, Magda Zanelli, Alessandra Bisagni, Maurizio Zizzo, Stefano Ascani, Giuseppe Carrieri, Luigi Cormio; J Pathol Transl Med. 2021;55(4):239-246. Published online June 14, 2021; DOI: https://doi.org/10.4132/jptm.2021.04.20

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Abstract PDF

Urothelial carcinoma with an inverted growth pattern (UC-IGP) is a peculiar entity within the spectrum of urothelial lesions. While efforts have been made over the last few decades to unravel its carcinogenesis and relationship with conventional urothelial carcinoma, the exact classification of inverted urothelial lesions is a matter of debate. The morphological features of UC-IGP pose several issues in differential diagnosis with other mostly benign lesions. Various techniques, including immunohistochemistry, UroVysion, and many molecular methods, have been employed to study the exact nature of this lesion. The aim of this review is to provide a comprehensive overview of the morphological and immunophenotypical aspects of UC-IGP. Moreover, we present and discuss the immunohistochemical and molecular markers involved in diagnosis and prognosis of UC-IGP lesions.

Citations

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HER2 Expression in Bladder Cancer: A Focused View on Its Diagnostic, Prognostic, and Predictive Role
Francesca Sanguedolce, Magda Zanelli, Andrea Palicelli, Alessandra Bisagni, Maurizio Zizzo, Stefano Ascani, Maria Carmela Pedicillo, Angelo Cormio, Ugo Giovanni Falagario, Giuseppe Carrieri, Luigi Cormio
International Journal of Molecular Sciences.2023; 24(4): 3720. CrossRef
Proteomic-Based Machine Learning Analysis Reveals PYGB as a Novel Immunohistochemical Biomarker to Distinguish Inverted Urothelial Papilloma From Low-Grade Papillary Urothelial Carcinoma With Inverted Growth
Minsun Jung, Cheol Lee, Dohyun Han, Kwangsoo Kim, Sunah Yang, Ilias P. Nikas, Kyung Chul Moon, Hyeyoon Kim, Min Ji Song, Bohyun Kim, Hyebin Lee, Han Suk Ryu
Frontiers in Oncology.2022;[Epub] CrossRef

Case Study

Sarcomatoid urothelial carcinoma arising in the female urethral diverticulum: Heae Surng Park; J Pathol Transl Med. 2021;55(4):298-302. Published online June 1, 2021; DOI: https://doi.org/10.4132/jptm.2021.04.23

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Abstract PDF

A sarcomatoid variant of urothelial carcinoma in the female urethral diverticulum has not been reported previously. A 66-year-old woman suffering from dysuria presented with a huge urethral mass invading the urinary bladder and vagina. Histopathological examination of the resected specimen revealed predominantly undifferentiated pleomorphic sarcoma with sclerosis. Only a small portion of conventional urothelial carcinoma was identified around the urethral diverticulum, which contained glandular epithelium and villous adenoma. The patient showed rapid systemic recurrence and resistance to immune checkpoint inhibitor therapy despite high expression of programmed cell death ligand-1. We report the first case of urethral diverticular carcinoma with sarcomatoid features.

Citations

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Reprint of: Female Urethral Carcinoma: A contemporary review of the clinicopathologic features, with emphasis on the histo-anatomic landmarks and potential staging issues
Maria Sarah Lagarde-Lenon, Manju Aron
Human Pathology.2023; 133: 126. CrossRef
Female Urethral Diverticula: a Contemporary Narrative Review of Aetiology, Diagnosis, and Treatment
A. U. Nic an Ríogh, S. Monagas Arteaga, L. Tzelves, M. Karavitakis, A. K. Nambiar
Current Bladder Dysfunction Reports.2022; 17(4): 250. CrossRef
Female urethral carcinoma: a contemporary review of the clinicopathologic features, with emphasis on the histoanatomic landmarks and potential staging issues
Maria Sarah Lagarde-Lenon, Manju Aron
Human Pathology.2022; 129: 71. CrossRef

Review

Programmed cell death-ligand 1 assessment in urothelial carcinoma: prospect and limitation: Kyu Sang Lee, Gheeyoung Choe; J Pathol Transl Med. 2021;55(3):163-170. Published online April 7, 2021; DOI: https://doi.org/10.4132/jptm.2021.02.22

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Abstract PDF

Programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) inhibition has revolutionized the treatment paradigm of urothelial carcinoma (UC). Several PD-L1 assays are conducted to formulate appropriate treatment decisions for PD-1/PD-L1 target therapy in UC. However, each assay has its own specific requirement of antibody clones, staining platforms, scoring algorithms, and cutoffs for the determination of PD-L1 status. These prove to be challenging constraints to pathology laboratories and pathologists. Thus, the present article comprehensively demonstrates the scoring algorithm used and differences observed in each assay (22C3, SP142, and SP263). Interestingly, the SP142 score algorithm considers only immune cells and not tumor cells (TCs). It remains controversial whether SP142 expressed only in TCs truly accounts for a negative PD-L1 case. Moreover, the scoring algorithm of each assay is complex and divergent, which can result in inter-observer heterogeneity. In this regard, the development of artificial intelligence for providing assistance to pathologists in obtaining more accurate and objective results has been actively researched. To facilitate efficiency of PD-L1 testing, several previous studies attempted to integrate and harmonize each assay in UC. The performance comparison of the various PD-L1 assays demonstrated in previous studies was encouraging, the exceptional concordance rate reported between 22C3 and SP263. Although these two assays may be used interchangeably, a clinically validated algorithm for each agent must be applied.

Citations

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Aspectos prácticos sobre la determinación de PD-L1 en el tratamiento de carcinoma urotelial. Consenso del grupo de uropatología de la SEAP
Antonio López-Beltrán, Pilar González-Peramato, Julián Sanz-Ortega, Juan Daniel Prieto Cuadra, Isabel Trias, Rafael J. Luque Barona, María Eugenia Semidey, Pablo Maroto, Ferran Algaba
Revista Española de Patología.2023; 56(4): 261. CrossRef
Systemic treatment of advanced and metastatic urothelial cancer: The landscape in Australia
Howard Gurney, Timothy D. Clay, Niara Oliveira, Shirley Wong, Ben Tran, Carole Harris
Asia-Pacific Journal of Clinical Oncology.2023; 19(6): 585. CrossRef
PD-L1 Testing in Urothelial Carcinoma: Analysis of a Series of 1401 Cases Using Both the 22C3 and SP142 Assays
Harriet Evans, Brendan O’Sullivan, Frances Hughes, Kathryn Charles, Lee Robertson, Philippe Taniere, Salvador Diaz-Cano
Pathology and Oncology Research.2022;[Epub] CrossRef
Insights on recent innovations in bladder cancer immunotherapy
Mohamed A. Abd El‐Salam, Claire E.P. Smith, Chong‐Xian Pan
Cancer Cytopathology.2022; 130(9): 667. CrossRef
What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 1: Focus on Immunohistochemical Results with Discussion of Pre-Analytical and Interpretation Variables
Andrea Palicelli, Martina Bonacini, Stefania Croci, Cristina Magi-Galluzzi, Sofia Cañete-Portillo, Alcides Chaux, Alessandra Bisagni, Eleonora Zanetti, Dario De Biase, Beatrice Melli, Francesca Sanguedolce, Moira Ragazzi, Maria Paola Bonasoni, Alessandra
Cells.2021; 10(11): 3166. CrossRef

Original Articles

Histologically confirmed distant metastatic urothelial carcinoma from the urinary bladder: a retrospective review of one institution’s 20-year experience: Youngeun Yoo, Junghye Lee, Heae Surng Park, Min-Sun Cho, Sun Hee Sung, Sanghui Park, Euno Choi; J Pathol Transl Med. 2021;55(2):94-101. Published online December 3, 2020; DOI: https://doi.org/10.4132/jptm.2020.10.19

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Abstract PDF

Background
Urothelial carcinoma (UC) accounts for roughly 90% of bladder cancer, and has a high propensity for diverse differentiation. Recently, certain histologic variants of UC have been recognized to be associated with unfavorable clinical outcomes. Several UC studies have also suggested that tumor budding is a poor prognostic marker. Distant metastasis of UC after radical cystectomy is not uncommon. However, these metastatic lesions are not routinely confirmed with histology.
Methods
We investigated the histopathologic features of 13 cases of UC with biopsy-proven distant metastases, with a special emphasis on histologic variants and tumor budding.
Results
Lymph nodes (6/13, 46%) were the most common metastatic sites, followed by the lung (4/13, 31%), liver (4/13, 31%), and the adrenal gland (2/13, 15%). The histologic variants including squamous (n=1), micropapillary (n=4), and plasmacytoid (n=1) variants in five cases of UC. Most histologic variants (4/5, 80%) of primary UCs appeared in the metastatic lesions. In contrast, high-grade tumor budding was detected in six cases (46%), including one case of non-muscle invasive UC. Our study demonstrates that histologic variants are not uncommonly detected in distant metastatic UCs. Most histologic variants seen in primary UCs persist in the distant metastatic lesions. In addition, high-grade tumor budding, which occurs frequently in primary tumors, may contribute to the development of distant metastasis.
Conclusions
Therefore, assessing the presence or absence of histologic variants and tumor budding in UCs of the urinary bladder, even in non-muscle invasive UCs, may be useful to predict distant metastasis.

Citations

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Do Histology and Primary Tumor Location Influence Metastatic Patterns in Bladder Cancer?
Hyung Kyu Park
Current Oncology.2023; 30(10): 9078. CrossRef

Double cocktail immunostains with high molecular weight cytokeratin and GATA-3: useful stain to discriminate in situ involvement of prostatic ducts or acini from stromal invasion by urothelial carcinoma in the prostate: Junghye Lee, Youngeun Yoo, Sanghui Park, Min-Sun Cho, Sun Hee Sung, Jae Y. Ro; J Pathol Transl Med. 2020;54(2):146-153. Published online February 10, 2020; DOI: https://doi.org/10.4132/jptm.2019.11.12

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Abstract PDF

Background
Distinguishing prostatic stromal invasion (PSI) by urothelial carcinoma (UC) from in situ UC involving prostatic ducts or acini with no stromal invasion (in situ involvement) may be challenging on hematoxylin and eosin stained sections. However, the distinction between them is important because cases with PSI show worse prognosis. This study was performed to assess the utility of double cocktail immunostains with high molecular weight cytokeratin (HMWCK) and GATA-3 to discriminate PSI by UC from in situ UC involvement of prostatic ducts or acini in the prostate.
Methods
Among 117 radical cystoprostatectomy specimens for bladder UCs, 25 cases showed secondary involvement of bladder UC in prostatic ducts/acini only or associated stromal invasion and of these 25 cases, seven cases revealed equivocal PSI. In these seven cases with equivocal PSI, HMWCK, and GATA-3 double immunohistochemical stains were performed to identify whether this cocktail stain is useful to identify the stromal invasion.
Results
In all cases, basal cells of prostate glands showed strong cytoplasmic staining for HMWCK and UC cells showed strong nuclear staining for GATA-3. In cases with stromal invasion of UC, GATA-3-positive tumor cells in the prostatic stroma without surrounding HMWCK-positive basal cells were highlighted and easily recognized. Among seven equivocal cases, two cases showed PSI and five in situ UC in the prostate. In two cases, the original diagnoses were revised.
Conclusions
Our study suggested that HMWCK and GATA-3 double stains could be utilized as an adjunct method in the distinction between PSI by UC from in situ UC involving prostatic ducts or acini.

Citations

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Aberrant expression of GATA3 in metastatic adenocarcinoma of the prostate: an important pitfall
João Lobo, Nazario P Tenace, Sofia Cañete‐Portillo, Isa Carneiro, Rui Henrique, Roberta Lucianò, Lara R Harik, Cristina Magi‐Galluzzi
Histopathology.2024; 84(3): 507. CrossRef
Utility of D2-40, Cytokeratin 5/6, and High–Molecular-weight Cytokeratin (Clone 34βE12) in Distinguishing Intraductal Spread of Urothelial Carcinoma From Prostatic Stromal Invasion
Oleksii A. Iakymenko, Laurence M. Briski, Katiana S. Delma, Merce Jorda, Oleksandr N. Kryvenko
American Journal of Surgical Pathology.2022; 46(4): 454. CrossRef

Comparison of the FDA and ASCO/CAP Criteria for HER2 Immunohistochemistry in Upper Urinary Tract Urothelial Carcinoma: Gilhyang Kim, Yul Ri Chung, Bohyun Kim, Boram Song, Kyung Chul Moon; J Pathol Transl Med. 2016;50(6):436-441. Published online October 10, 2016; DOI: https://doi.org/10.4132/jptm.2016.07.12

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Abstract PDF

Background
Human epidermal growth factor receptor 2 (HER2) is one of the known oncogenes in urothelial carcinoma. However, the association between HER2 and the prognosis of upper urinary tract urothelial carcinoma (UUTUC) has not yet been fully clarified. The aim of this study was to evaluate HER2 expression using the United States Food and Drug Administration (FDA) criteria and American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) criteria and compare their prognostic significance in UUTUC.
Methods
HER2 expression was evaluated in 144 cases of UUTUC by immunohistochemistry (IHC) using tissue microarrays. We separately analyzed HER2 expression using the FDA and ASCO/CAP criteria. The IHC results were categorized into low (0, 1+) and high (2+, 3+) groups.
Results
Using the FDA criteria, 94 cases were negative, 38 cases were 1+, nine cases were 2+, and three cases were 3+. Using the ASCO/CAP criteria, 94 cases were negative, 34 cases were 1+, 13 cases were 2+, and three cases were 3+. Four cases showing 2+ according to the ASCO/CAP criteria were reclassified as 1+ by the FDA criteria. High HER2 expression by both the FDA criteria and ASCO/CAP criteria was significantly associated with International Society of Urological Pathology high grade (p = .001 and p < .001). The high HER2 expression group classified with the FDA criteria showed significantly shorter cancer-specific survival (p = .004), but the HER2 high and low expression groups classified with the ASCO/CAP criteria did not show significant differences (p = .161) in cancer-specific survival.
Conclusions
HER2 high expression groups were significantly associated with shorter cancer-specific survival, and our study revealed that the FDA criteria are more suitable for determining HER2 expression in UUTUC.

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A systematic review and meta-analysis for human epidermal growth factor receptor 2 on upper tract urothelial carcinoma patients
Jianjun Ye, Xinyang Liao, Yu Qiu, Qiang Wei, Yige Bao
Tumori Journal.2024; 110(1): 25. CrossRef
ERBB2 Amplification as a Predictive and Prognostic Biomarker in Upper Tract Urothelial Carcinoma
Annette Zimpfer, Said Kdimati, Melanie Mosig, Henrik Rudolf, Heike Zettl, Andreas Erbersdobler, Oliver W. Hakenberg, Matthias Maruschke, Björn Schneider
Cancers.2023; 15(9): 2414. CrossRef
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Hiroshi Fukushima, Baris Turkbey, Peter A. Pinto, Aki Furusawa, Peter L. Choyke, Hisataka Kobayashi
Cancers.2022; 14(12): 2996. CrossRef
Assessment of HER2 Protein Overexpression and Gene Amplification in Renal Collecting Duct Carcinoma: Therapeutic Implication
Manuela Costantini, Carla Azzurra Amoreo, Liborio Torregrossa, Greta Alì, Enrico Munari, Carmen Jeronimo, Rui Henrique, Sara Petronilho, Umberto Capitanio, Roberta Lucianò, Nazareno Suardi, Maria Teresa Landi, Umberto Anceschi, Aldo Brassetti, Vito Michel
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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.

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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

Parafibromin Staining Characteristics in Urothelial Carcinomas and Relationship with Prognostic Parameters: Serap Karaarslan, Banu Yaman, Hakan Ozturk, Banu Sarsik Kumbaraci; J Pathol Transl Med. 2015;49(5):389-395. Published online September 15, 2015; DOI: https://doi.org/10.4132/jptm.2015.08.10

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Abstract PDF

Background
Parafibromin is a recently defined tumor suppressor gene. The aim of our study was to determine the relationships of parafibromin expression in urothelial carcinomas (UCs) with prognostic parameters and to evaluate the use of parafibromin as a potential marker of UC. Methods: Parafibromin expression was assessed in 49 UC specimens using immunohistochemistry. The correlations between parafibromin expression and clinical and pathologic parameters were investigated. Results: Of the patients, 42 (85.7%) were male, and the mean age was 69.6 ± 8.2 years (range, 54 to 88 years). Morphologically, the UCs were divided into two groups: papillary (n = 27) and non-papillary (n = 22). There were seven low-grade (14.3%) and 42 high-grade (85.7%) tumors. Parafibromin was negative in 13 tumors (26.5%), partially positive in 19 tumors (38.8%), and positive in 17 tumors (34.7%). Parafibromin expression was more negative in UCs from upper urinary locations (n=17) and with muscularis propria invasion (n=28), which was statistically significant (p = .009 and p = .007, respectively). There was no statistically significant relationship between parafibromin expression and gender, age, tumor grade, survival, or disease-free survival. Conclusions: We found that UC cases with parafibromin positivity had less of a tendency to show muscularis propria invasion and were more commonly located in the lower urinary system. These results need to be confirmed with studies based on larger case series.

Citations

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The roles of the tumor suppressor parafibromin in cancer
Hua-chuan Zheng, Hang Xue, Cong-yu Zhang
Frontiers in Cell and Developmental Biology.2022;[Epub] CrossRef
Prognostic role of parafibromin staining and CDC73 mutation in patients with parathyroid carcinoma: A systematic review and meta‐analysis based on individual patient data
Ruizhe Zhu, Zixing Wang, Ya Hu
Clinical Endocrinology.2020; 92(4): 295. CrossRef
The in vitro and in vivo effects of nuclear and cytosolic parafibromin expression on the aggressive phenotypes of colorectal cancer cells: a search of potential gene therapy target
Hua-chuan Zheng, Jia-jie Liu, Jing Li, Ji-cheng Wu, Lei Yang, Gui-feng Zhao, Xin Zhao, Hua-mao Jiang, Ke-qiang Huang, Zhi-jie Li
Oncotarget.2017; 8(14): 23603. CrossRef
The clinicopathological and prognostic significances of CDC73 expression in cancers: a bioinformatics analysis
Hua-Chuan Zheng, Bao-Cheng Gong, Shuang Zhao
Oncotarget.2017; 8(56): 95270. CrossRef
Significance of Parafibromin Expression in Laryngeal Squamous Cell Carcinomas
Inju Cho, Mija Lee, Sharon Lim, Ran Hong
Journal of Pathology and Translational Medicine.2016; 50(4): 264. CrossRef

Cytological Findings of the Micropapillary Variant of Urothelial Carcinoma: A Comparison with Typical High-Grade Urothelial Carcinoma: Kyu-Ho Kim, Chang-Hwan Choi, Jee-Young Han, Lucia Kim, Suk-Jin Choi, In-Suh Park, Joon-Mee Kim, Young-Chae Chu; Korean J Pathol. 2013;47(4):365-371. Published online August 26, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.4.365

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Abstract PDF

Background

Micropapillary variant of urothelial carcinoma (MPUC) showed distinct pathologic features and aggressive behavior. The cytologic findings of MPUC are still indistinct. In this study, we evaluated the cytological findings of MPUC compared with those of high-grade urothelial carcinoma (HGUC).

Methods

The voided urine cytology of 8 cases of MPUC and 8 cases of HGUC was reviewed. Following cytological parameters were evaluated: cellularity, background, number of small, tight papillary clusters, small acinar structure, scattered single cells, cytoplasmic features, nuclear-to-cytoplasmic ratio, nuclear pleomorphism, nuclear membrane irregularity, hyperchromasia, chromatin pattern and nucleoli.

Results

Compared to that of HGUC, cytology of MPUC showed large numbers of small, tight papillary clusters, small acinar structure, few numbers of single cells, and hyperchromatic nuclei. Other parameters were similar between the two groups; both groups showed similar cellularity, dense or vacuolated cytoplasm, moderate to severe nuclear pleomorphism, irregular nuclear membrane, coarse granular chromatin, and small and prominent nucleoli.

Conclusions

The urine cytology of MPUCs showed smaller and tighter papillary cell clusters, more small acinar structures, fewer numbers of scattered single cells, and more hyperchromatic nuclei than that of HGUC. These features can help to distinguish MPUC and HGUC and offer an early cytological diagnosis of MPUC.

Citations

Citations to this article as recorded by

Cytologic features of micropapillary variant urothelial carcinoma in urinary tract cytology: Case series and review of literature
Nancy Y. Greenland, Yue Peng, Poonam Vohra, Z. Laura Tabatabai
Diagnostic Cytopathology.2022;[Epub] CrossRef
Cyto-histo correlations of plasmacytoid and micropapillary variants of high-grade urothelial carcinoma: do they fit well in The Paris System for reporting urinary cytology?
Liye Suo, Ivonne Vega, Michael Thrall
Journal of the American Society of Cytopathology.2021; 10(1): 20. CrossRef
A case report of urothelial carcinoma with combined micropapillary and plasmacytoid morphology in the urinary bladder
Sanghui Park, Min‐Sun Cho, Kwang Hyun Kim
Diagnostic Cytopathology.2016; 44(2): 124. CrossRef
Two cases with the micropapillary variant of urothelial carcinoma of the urinary bladder
Akiko KAGOTANI, Mitsuaki ISHIDA, Muneo IWAI, Nozomi IWAMOTO, Nozomi KASUGA, Yuji HAYASHI, Yoshimitsu MIYAHIRA, Ryoji KUSHIMA
The Journal of the Japanese Society of Clinical Cytology.2016; 55(3): 165. CrossRef

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.

Prognostic Significance of Methylation Profiles in Urothelial Carcinomas of the Bladder.: Hee Jung Park, Eui Jin Lee, Sang Yun Ha, Ghee Young Kwon, Young Lyun Oh, Kyoung Mee Kim, Dae Shick Kim, Seongil Seo, Hyun Moo Lee, Han Yong Choi; Korean J Pathol. 2010;44(6):623-630.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.6.623

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Abstract PDF

BACKGROUND
Study on epigenetics of urothelial carcinomas has expanded and allowed better understanding of their correlation with clinicopathologic features. The aim of this study was to determine reliable predictive epigenetic markers for patients with urothelial carcinoma of urinary bladder.
METHODS
In 64 urothelial carcinomas of the urinary bladder, methylationspecific polymerase chain reaction with RAS association domain family 1A (RASSF1A), adenomatous polyposis coli (APC), death-associated protein-kinase (DAPK), runt-related transcription factor 3 (RUNX3), p14, p16 and MGMT was performed and correlated the results with p53 mutations, DNA ploidy, clinicopathologic parameters and recurrences.
RESULTS
Hypermethyation of RASSF1A, APC, DAPK, RUNX3, p14, p16 and MGMT promoters was observed in 35 (54.7%), 29 (45.3%), 18 (28.1%), 18 (28.1%), 9 (14.1%), 2 (3.1%), and 6 (9.4%) cases, respectively. Hypermethylation of RUNX3 and APC was significantly associated with high histologic grades and aneuploidy. Methylation of DAPK was significantly associated with muscle invasion. Methylation of DAPK and RUNX3 genes was significantly associated with recurrence. In survival analyses, methylation of RUNX3 gene and methylation-high (methylation at two or more loci) phenotype was significantly associated with poor recurrence-free survival.
CONCLUSIONS
Methylation of RUNX3 gene and methylation-high phenotype are significant indicator of recurrence.

Citations

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DAPK Promoter Methylation and Bladder Cancer Risk: A Systematic Review and Meta-Analysis
Lihe Dai, Chong Ma, Zhensheng Zhang, Shuxiong Zeng, Anwei Liu, Shijie Tang, Qian Ren, Yinghao Sun, Chuanliang Xu, Shengtao Zhou
PLOS ONE.2016; 11(12): e0167228. CrossRef

Detecting Malignant Urothelial Cells by Morphometric Analysis of ThinPrep(R) Liquid-based Urine Cytology Specimens.: Bong Kyung Shin, Young Suk Lee, Hoiseon Jeong, Sang Ho Lee, Hyunchul Kim, Aree Kim, Insun Kim, Han Kyeom Kim; Korean J Cytopathol. 2008;19(2):136-143.; DOI: https://doi.org/10.3338/kjc.2008.19.2.136

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Abstract PDF

Urothelial carcinoma accounts for 90% of all the cases of bladder cancer. Although many cases can be easily managed by local excision, urothelial carcinoma rather frequently recurs, tends to progress to muscle invasion, and requires regular follow-ups. Urine cytology is a main approach for the follow-up of bladder tumors. It is noninvasive, but it has low sensitivity of around 50% with using the conventional cytospin preparation. Liquid-based cytology (LBC) has been developed as a replacement for the conventional technique. We compared the cytomorphometric parameters of ThinPrep(R) and cytospin preparation urine cytology to see whether there are definite differences between the two methods and which technique allows malignant cells to be more effectively discriminated from benign cells. The nuclear-to-cytoplasmic ratio value, as measured by digital image analysis, was efficient for differentiating malignant and benign urothelial cells, and this was irrespective of the preparation method and the tumor grade. Neither the ThinPrep(R) nor the conventional preparation cytology was definitely superior for distinguishing malignant cells from benign cells by cytomorphometric analysis of the adequately preserved cells. However, the ThinPrep(R) preparation showed significant advantages when considering the better preservation and cellularity with a clear background.

Citations

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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
A Comparison Between ThinPrep Monolayer and Cytospin Cytology for the Detection of Bladder Cancer
Ji Yong Kim, Hyung Jin Kim
Korean Journal of Urology.2014; 55(6): 390. CrossRef
Cytological and Morphometric Study of Urinary Epithelial Cells with Histopathological Correlation
Asim Kumar Manna, Manisha Sarkar, Ujjal Bandyopadhyay, Srabani Chakrabarti, Swapan Pathak, Diptendra Kumar Sarkar
Indian Journal of Surgery.2014; 76(1): 26. 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 Journal of Pathology.2012; 46(1): 68. CrossRef

Case Report

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; Korean J Cytopathol. 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.

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