Urinary IL-6 and IL-8 as predictive markers in bladder urothelial carcinoma: A pilot study.

BACKGROUND: Cytokines are known to be a key a factor in numerous malignancies and to exert an important regulatory role in the tumor microenvironment. Interest has grown in understanding how cytokines modulate the tumor microenvironment and which cytokines may serve as markers of the tumor process; however, a complete picture of the cytokine landscape in bladder cancer remains unclear. METHODS: Fresh urine specimens with sufficient volume were collected at random intervals. The urine concentrations of IL-8 (CXCL8), CCL18, and CXCL9 were determined using the standard commercially available enzyme immunoassay. The urine concentrations of IL-6 were determined using the high sensitivity enzyme immunoassay kit. Urinary cytokine concentrations were normalized with urinary creatinine concentrations. RESULTS: Significantly elevated concentrations of IL-6 and IL-8 were detected in the urine from patients with urothelial carcinoma on follow-up compared to patients with benign follow-up. The presence of both IL-6 and IL-8 in the urine samples from the high grade urothelial carcinoma (HGUC) cohort revealed a clear discrimination when compared to samples from patients with benign follow-up. The presence of the combination of both IL-6 and IL-8 had a sensitivity of 90.0% and a specificity of 81.25%. Similar data were obtained when receiver operating characteristic analysis was performed on both IL-6 and IL-8 concentrations in the urine from patients with HGUC vs. the hematuria cohort. CONCLUSIONS: The presence of IL-6 and IL-8 in urine specimens may have predictive value for urothelial carcinoma. However, a large longitudinal study is required to statistically eliminate confounding factors and support this theory.

Perceptions of Paris: an international survey in preparation for The Paris System for Reporting Urinary Cytology 2.0 (TPS 2.0).

INTRODUCTION: An international panel of experts in the field of urinary cytopathology conducted a survey, supported by the American Society of Cytopathology, to seek opinions, gather evidence, and identify practice patterns regarding urinary cytology before and after the introduction of The Paris System for Reporting Urinary Cytopathology (TPS). Results from this survey were utilized in the development of the second edition of TPS (TPS-2.0). MATERIALS AND METHODS: The study group, originally formed during the 2013 International Congress of Cytology, reconvened at the 2019 annual meeting of the American Society of Cytopathology. To prepare for the second edition of TPS, the group generated a survey that included 43 questions related to the taxonomy and practice of urinary cytology. RESULTS: A total of 523 participant responses were collected, and 451 from 54 countries passed a qualifying screen. Three hundred ninety-four participants provided information about their work settings. Eighty-two percent (218/266) of responding participants use TPS. One hundred sixty-eight people who responded on their urinary cytology atypia rates reported an average decrease from 21.6% to 16%. Over three fourths of participants felt that the same criteria should be used for upper and lower tract interpretations and for instrumented and voided samples. There were varied opinions on addressing atypical squamous cells and suggestions for an expanded discussion of the issue to be included in TPS 2.0. CONCLUSIONS: Results of the survey demonstrate strong support for TPS and show a decreased self-reported atypia rate in the laboratories using TPS. The majority of participants related that the criteria put forth for the reporting categories were user-friendly and applied with relative ease. The comment section of the survey included suggestions from the participants for further improvement of TPS. Results of this survey have been useful in fine-tuning and advancing TPS. They were considered along with recent literature to generate the second edition of TPS.

We'll always have Paris The Paris System for Reporting Urinary Cytology 2022.

Following the amazing acceptance of The Paris System for Reporting Urinary Cytology (TPS), the second edition (TPS 2.0) was inevitable. Based on new studies since the publication of the first edition, diagnostic criteria are refined, and pitfalls discussed. In addition to reinforcing the mandate that the focus of diagnostic urinary cytology is the detection of high-grade urothelial carcinoma, other issues are addressed. Low-grade lesions are included in the category of negative for high-grade urothelial cancer. The rationale for that decision is strongly supported by evidence from the authors' experiences as well as the recent literature. A new chapter on urine cytology of the upper tract, a rarely addressed topic, explores the challenges involved. Furthermore, the issue of cellular degeneration is discussed in the criteria of all diagnostic categories. Most importantly, data defining the risk of high-grade malignancy (ROHM) for each diagnostic category informs clinical management. The 65 authors are recognized authorities from 33 countries, attesting to the global impact of TPS 2.0.

Self-collected Papanicolaou tests in the United States market: more questions than answers.

The United States Food and Drug Administration held a public hearing in January 2018 to consider how it should evaluate a self-collection device for cervical cytology. Although no such device has been approved for use in the US market, the implications for patients and cytologists could be both sweeping and complex. Herein, the existing literature basis for self-collected Papanicolaou testing is reviewed, and some questions raised by this testing are considered. Questions include: what would be the value to patients; how effective could self-collected Papanicolaou tests be; how might ordering and collection work; what are the unique pre-analytic, analytic, and post-analytic challenges of self-collected Papanicolaou testing; and what effect might self-collection have on cervical cancer rates?

A 20-year and 46,000-specimen journey to Paris reveals the influence of reporting systems and passive peer feedback on pathologist practice patterns.

BACKGROUND: An important goal of The Paris System for Reporting Urinary Cytology (TPS) is to reduce unnecessary atypical diagnoses given to urinary tract cytology (UTC) specimens. Since implementation of TPS at the study institution in 2016, the institutional atypical rate has declined only slightly. The authors speculated that TPS might not have had an immediate impact because several faculty members were involved in TPS committees and because TPS contains elements that already had been integrated into institutional practice. To identify factors contributing to alterations in the institutional atypical rate, the authors examined their practice over the last 22 years. METHODS: UTC specimens submitted to the study laboratory between August 11, 1995, and August 10, 2017, were identified. Specimens were linked to the responsible pathologist, specimen diagnosis and type, association with high-grade urothelial carcinoma, and relevant cytomorphologic features. RESULTS: An increase in the institutional atypical rate occurred between 2002 and 2005. The atypical rate among individual pathologists also peaked during this same time. The increase coincided with an increase in the use of UTC and the arrival of a pathologist with a higher rate of atypical diagnoses. A substantial decrease in the institutional atypical rate occurred between 2005 and 2010 and coincided with the creation of the Johns Hopkins Hospital Template, the authors' first standardized reporting system for UTC specimens. CONCLUSIONS: The use of reporting systems (Johns Hopkins Hospital Template and TPS) has coincided with decreases in the institutional atypical rate at the study institution. An individual pathologist may influence the practice patterns of his or her colleagues, resulting in fluctuations in the institutional rate of atypia over time. Cancer Cytopathol 2018;126:381-9. © 2018 American Cancer Society.

When words matter: A "suspicious" urinary tract cytology diagnosis improves patient follow-up among nonurologists.

BACKGROUND: Urinary tract cytology (UTC) specimens diagnosed using high-risk indeterminate categories such as "atypical urothelial cells, cannot exclude high-grade urothelial carcinoma" (AUC-H) or "suspicious for high-grade urothelial carcinoma" (SHGUC) have a high rate of detection of high-grade urothelial carcinoma on subsequent biopsy. Although urologists are familiar with such terminology, it is unclear whether patients receive appropriate follow-up when UTC is ordered by nonurologists. In the current study, the authors investigated whether the use of AUC-H versus SHGUC altered patient management among nonurologists. METHODS: Specimens signed out as AUC-H or SHGUC were identified from the archives of the study institution, which included periods of time before the use of the standardized Johns Hopkins Hospital template, during use of the Johns Hopkins Hospital template, and after institution of The Paris System for Reporting Urinary Cytology. RESULTS: Approximately one-half of the specimens diagnosed as AUC-H were not investigated further when ordered by nonurologists. Patients with specimens diagnosed as AUC-H received fewer subsequent biopsies (14% vs 53%; P < .001) when the specimens were ordered by nonurologists versus urologists, despite having similar rates of high-grade urothelial carcinoma on follow-up biopsy (67% vs 66%). When specimens ordered by nonurologists were diagnosed as SHGUC, these patients received more follow-up (100%) compared with those whose specimens were diagnosed as AUC-H (44%; P < .001). Patients with specimens ordered by nonurologists also received more follow-up biopsies when these were diagnosed as suspicious (60%) compared with patients whose specimens were diagnosed as AUC-H (14%; P < .001). CONCLUSIONS: Use of the word "suspicious" for the high-risk indeterminate category results in greater follow-up among nonurologists ordering UTC specimens. Cancer Cytopathol 2018;126:282-8. © 2018 American Cancer Society.

Paris Interobserver Reproducibility Study (PIRST).

OBJECTIVES: In concert with the 2015 publication of The Paris System for Urinary Cytopathology (TPS), a Web-based interobserver study, co-sponsored by the American Society of Cytopathology (ASC) and International Academy of Cytology (IAC), was performed to determine diagnostic agreement among volunteer participants and with the TPS author consensus. MATERIAL AND METHODS: Participants at various levels of training and certification were recruited through national and international cytopathology professional societies. Although the survey was open to all comers, potential participants were screened by two basic cytopathology questions. Information was collected on the level of training, practice patterns, and experience. Study participants evaluated 85 images (previously unpublished) chosen from the TPS atlas. These images spanned all diagnostic categories. RESULTS: Of the 1993 attempts to access the survey, 1313 participants correctly answered the qualifying questions and were included in the survey. Respondents were concentrated in the United States, although many participants came from other countries. The majority of respondents were board-certified in anatomic pathology with cytopathology certification. A smaller number were cytotechnologists. Board-certified cytopathologists and specialist cytotechnologists outperformed other certifications. Practice type (academics versus non-academic), and country (US versus international) were not major factors in concordance. Diagnostic categories with the best agreement were Negative for High-Grade Urothelial Carcinoma (NHGUC; 71%), Low-Grade Urothelial Neoplasm (LGUN; 62%), and High-Grade Urothelial Carcinoma (HGUC; 57%). Indeterminate categories showed low concordance. CONCLUSIONS: The NHGUC, LGUN, and HGUC were most correlated with diagnostic agreement among observers. This study can serve as a baseline for future comparisons.

Performance of ovarian cyst fluid fine-needle aspiration cytology.

BACKGROUND: Although ovarian fine-needle aspiration (FNA) cytology is not commonly used as a primary modality of diagnosis for patients with ovarian lesions, many ovarian cysts are aspirated intraoperatively and occasionally for diagnostic purposes. Therefore, the ability to interpret these specimens remains critical. Previous studies have suggested a high specificity but low sensitivity as a limitation. The objective of the current study was to further explore the use and performance of ovarian cyst FNA for diagnosing malignancy at the study institution. METHODS: The electronic database was searched from 1998 through 2016 for ovarian cyst fluid cytology specimens; any concurrent or follow-up surgical pathology; and clinical information including patient age, radiology findings, and procedure type. Test performance was calculated using the surgical pathology diagnosis as the gold standard. RESULTS: A total of 459 ovarian cyst FNA specimens had the following diagnoses: 416 (90.6%) were diagnosed as benign, 32 (7.0%) as atypical, 4 (0.9%) as suspicious, and 7 (1.5%) as malignant. Overall, 300 specimens (65.4%) had a corresponding surgical pathology specimen. On follow-up, the rate of malignancy (including borderline neoplasms) for benign FNA was 10 of 264 specimens (3.8%), that for atypical FNA was 0 of 24 specimens (0%), that for suspicious FNA was 5 of 5 specimens (100%), and that for malignant FNA was 7 of 7 specimens (100%). Test sensitivity was 54.0% and test specificity was 100%. The positive predictive value was 1.00 and the negative predictive value was 0.97, with a disease (malignancy) prevalence of 7.33%. CONCLUSIONS: Ovarian cyst fluid cytology is highly specific and moderately sensitive for the detection of ovarian malignancies. A negative FNA is reassuring for patients with a low pretest probability of malignancy. Cancer Cytopathol 2018;126:112-21. © 2017 American Cancer Society.

Urinary tract washing specimens containing atypical urothelial tissue fragments are significantly associated with urothelial neoplasia.

BACKGROUND: We previously found that the presence of atypical urothelial tissue fragments (AUTF) was associated with an increased risk of high-grade urothelial carcinoma (HGUC) but not low-grade urothelial neoplasia (LGUN) in voided urine (VU) specimens. However, we subsequently found that patients with LGUN were more likely to have cytologic atypia in urinary washing (UW) specimens, suggesting that cytologic atypia found in UW specimens might be associated with both LGUN and HGUC. In this study, we retrospectively examined UW specimens containing AUTF to determine whether they were associated with HGUC, LGUN, or both HGUC and LGUN. METHODS: 1173 UW specimens and any follow up biopsies were identified over a 10-year period and the presence of AUTF was recorded based on the original clinical diagnosis. RESULTS: The presence of AUTF in UW specimens was significantly associated with high-risk indeterminate diagnosis or definitive diagnosis of HGUC (P < .001). In addition, AUTF specimens were significantly associated with a neoplastic diagnosis of low-grade urothelial carcinoma (LGUC) or HGUC on subsequent biopsies when compared to specimens lacking AUTF (P = .047). The overall rate of CIS/HGUC in specimens with AUTF was 33.0 vs. 13.5% for specimens without AUTF (P = .051). CONCLUSIONS: Urothelial tissue fragments (UTF) found in UW specimens should be examined for the presence of cytomorphological atypia, as the presence of AUTF almost triples the risk of HGUC. As opposed to what has been found in VU specimens, AUTF in UW specimens is also associated with an increased risk of LGUN.

Upper urinary tract washings outperform voided urine specimens to detect upper tract high-grade urothelial carcinoma.

BACKGROUND: Cytological examination of voided urine (VU) can reliably diagnose high-grade urothelial carcinoma (HGUC) of the lower urinary tract, but its value in the diagnosis of upper tract HGUC (UTHGUC) is less well-established. To clarify the utility of VU in the setting of UTHGUC, we examined urinary specimens from patients with UTHGUC on follow-up surgical pathology. METHODS: 52 VU specimens (47 patients) with subsequent biopsy-proven UTHGUC were identified over a 12-year period; 32 had a corresponding upper tract urinary washing (UW) specimen. Patients with concurrent bladder HGUC were excluded. The diagnoses of VU specimens were tabulated and compared to those of UW specimens. RESULTS: Three UW specimens had a less severe diagnosis, 8 had the same diagnosis, and 21 had a more severe diagnosis than the corresponding VU specimen from the same patient. Significantly more UW specimens demonstrated high-risk features as compared with VU specimens (P = .003). In specimens with atypia, a definitive diagnosis of HGUC was made significantly more often on UW vs. VU specimens (P = .003). CONCLUSIONS: Among patients with confirmed UTHGUC, 50% of preceding VU specimens demonstrated high-grade features compared to almost 90% of UW specimens. Though VU cytology shows atypia in the majority of cases, it performs inferiorly to UW for the detection of UTHGUC. Diagn. Cytopathol. 2017;45:700-704. © 2017 Wiley Periodicals, Inc.

Improved risk stratification for patients with high-grade urothelial carcinoma following application of the Paris System for Reporting Urinary Cytology.

BACKGROUND: The Paris System for Reporting Urinary Cytology (TPS) requires 4 cytomorphologic criteria for a definitive diagnosis of high-grade urothelial carcinoma (HGUC) in urinary tract cytology (UTC) specimens: an elevated nuclear-to-cytoplasmic (N/C) ratio (at or above 0.7), markedly atypical nuclear borders, moderate to severe hyperchromasia, and coarse chromatin. However, malignant UTC specimens often contain degenerative changes, and this limits the number of malignant cells meeting all 4 TPS cytomorphologic criteria. METHODS: One hundred twelve UTC specimens from patients with a subsequent diagnosis of HGUC were reviewed and reclassified according to TPS criteria. The presence of TPS cytomorphologic criteria for HGUC in each specimen was recorded, as was the proportion of atypical cells meeting all 4 criteria. RESULTS: The number of specimens definitively diagnosed as HGUC did not significantly change upon reclassification. However, approximately 40% of indeterminate specimens (21 of 51) were reclassified into a higher risk category. The most restrictive cytomorphologic criterion was an N/C ratio of 0.7 or higher (seen in 78% of specimens), and approximately half of specimens containing all 4 cytomorphologic criteria did not meet TPS's numerical criterion for HGUC (at least 5 malignant cells). In the majority of specimens qualifying for HGUC by TPS standards, only a small fraction of atypical cells (10%-20%) met all the criteria. CONCLUSIONS: When applied to malignant UTC specimens, TPS criteria improved specimen risk stratification by upgrading approximately 40% of indeterminate specimens into higher risk categories while not significantly changing the frequency of HGUC diagnoses. Cancer Cytopathol 2017;125:427-34. © 2017 American Cancer Society.

Fine-needle aspiration of metastatic melanoma presenting as bilateral breast cysts.

Melanoma is the second most common non-hematopoietic malignancy after carcinomas to metastasize to the breast and often appears as a well-circumscribed, dense nodule on imaging. Although metastatic lesions presenting as bilateral cysts have been reported, this presentation is not common and may mimic benign breast cysts. We present a challenging case of metastatic melanoma presenting as bilateral breast cysts with spindled cytomorphology in a patient with a history of mammary carcinoma. Discordance between the spindled cytomorphology and the morphology of the core biopsy, which was similar to the patient's primary breast cancer, allowed for entertainment of other tumors and disease processes. Confirmatory immunostaining of the cytology material with HMB-45 was important to establish the diagnosis of metastatic melanoma. Diagn. Cytopathol. 2017;45:446-451. © 2017 Wiley Periodicals, Inc.

The Paris System for Reporting Urinary Cytology: The Quest to Develop a Standardized Terminology.

The main purpose of urine cytology is to detect high-grade urothelial carcinoma (HGUC). With this principle in mind, The Paris System (TPS) Working Group, composed of cytopathologists, surgical pathologists, and urologists, has proposed and published a standardized reporting system that includes specific diagnostic categories and cytomorphologic criteria for the reliable diagnosis of HGUC. This paper outlines the essential elements of TPS and the process that led to the formation and rationale of the reporting system. The Paris System Working Group, organized at the 2013 International Congress of Cytology, conceived a standardized platform on which to base cytologic interpretation of urine samples. The widespread dissemination of this approach to cytologic examination and reporting of urologic samples and the scheme's universal acceptance by pathologists and urologists is critical for its success. For urologists, understanding the diagnostic criteria, their clinical implications, and the limitations of TPS is essential if they are to utilize urine cytology and noninvasive ancillary tests in a thoughtful and practical manner. This is the first international/inclusive attempt at standardizing urinary cytology. The success of TPS will depend on the pathology and urology communities working collectively to improve this seminal paradigm shift, and optimize the impact on patient care.

The Paris System for Reporting Urinary Cytology: The Quest to Develop a Standardized Terminology.

The main purpose of urine cytology is to detect high-grade urothelial carcinoma. With this principle in mind, The Paris System (TPS) Working Group, composed of cytopathologists, surgical pathologists, and urologists, has proposed and published a standardized reporting system that includes specific diagnostic categories and cytomorphologic criteria for the reliable diagnosis of high-grade urothelial carcinoma. This paper outlines the essential elements of TPS and the process that led to the formation and rationale of the reporting system. TPS Working Group, organized at the 2013 International Congress of Cytology, conceived a standardized platform on which to base cytologic interpretation of urine samples. The widespread dissemination of this approach to cytologic examination and reporting of urologic samples and the scheme's universal acceptance by pathologists and urologists is critical for its success. For urologists, understanding the diagnostic criteria, their clinical implications, and limitations of TPS is essential if they are to utilize urine cytology and noninvasive ancillary tests in a thoughtful and practical manner. This is the first international/inclusive attempt at standardizing urinary cytology. The success of TPS will depend on the pathology and urology communities working collectively to improve this seminal paradigm shift, and optimize the impact on patient care.

Should the BK polyomavirus cytopathic effect be best classified as atypical or benign in urine cytology specimens?

BACKGROUND: According to The Paris System for Reporting Urinary Cytology (TPS), the category of atypical urothelial cells (AUC) should not be applied to specimens in which cellular changes can be entirely attributed to the polyoma (BK) virus cytopathic effect (CPE). Until recently, cases with BK CPE at The Johns Hopkins Hospital were categorized as atypical urothelial cells of uncertain significance (AUC-US), which is equivalent to the TPS AUC category. This study was performed to determine how significantly the rate of AUC-US specimens would decrease if specimens with only BK CPE were classified as benign. METHODS: Two reviewers and 1 adjudicator re-evaluated urinary tract specimens to determine whether sufficient cytological atypia justified an AUC-US diagnosis independent of the presence of BK CPE. For patients with surgical follow-up, the rate of high-grade urothelial carcinoma (HGUC) on tissue biopsy was tracked over a 5-year period. RESULTS: The reclassification rate of AUC-US cases with BK CPE as benign was 62.6%. The rate of subsequent HGUC was 6.0% for cases reclassified as benign and 10.0% for cases still classified as AUC-US. These rates were not significantly elevated in comparison with control cohorts among all-comers. However, for patients without a history of HGUC, the rate of HGUC on follow-up was significantly elevated in comparison with the rate for a benign control cohort and was similar to the rate for the AUC-US control cohort. CONCLUSIONS: Reclassification as benign would have decreased the rate of AUC-US from 24.8% to 20.7% during the study year. However, the high rate of subsequent HGUC among nonsurveillance patients suggests that the reclassification of specimens with BK CPE in these patients may be inappropriate. Cancer Cytopathol 2016;124:436-42. © 2016 American Cancer Society.

The cytomorphological features of low-grade urothelial neoplasms vary by specimen type.

BACKGROUND: Urinary tract (UT) cytology has been used successfully to diagnose high-grade urothelial carcinoma but is reported to have poor sensitivity for low-grade urothelial neoplasms (LGUNs). However, the literature has shown that LGUN may be associated with atypical findings in UT specimens. The authors determined which features were most commonly observed, and whether the method of specimen procurement had an effect. METHODS: A total of 326 specimens were identified over an 8-year period. One hundred fifty-three specimens were reviewed and graded for cellularity, number of tissue fragments (TFs), degeneration, inflammation, hyperchromasia, nuclear pleomorphism, nuclear border irregularity, nuclear size, cytoplasmic tails, nuclear eccentricity, and high-grade features. RESULTS: Of the 153 specimens, 86 specimens (56.2%) demonstrated cellular atypia; of those, 51.2% were voided urine (VU) and 31.4% were UT washing (UW) specimens. The majority of specimens had many cells (46.5%), many single cells (44.2%), few to moderate TFs (46.5% and 27.9%, respectively), mild hyperchromasia (52.3%), mild nuclear pleomorphism (51.2%), mild nuclear border irregularity (60.5%), cytoplasmic tails (51.2%), and few to moderate eccentric nuclei (37.2% and 36.1%, respectively). The presence of TFs, cytoplasmic tails, and eccentric and enlarged nuclei were significantly more common in UW versus VU specimens (P = .036, .012, .014, and .027, respectively) and in UW versus benign UW controls (P = .001, .002, .002, and .003, respectively). CONCLUSIONS: Approximately 50% of UT specimens with LGUN on follow-up demonstrated atypical features. Based on comparison with benign UW controls, TFs, cytoplasmic tails, nuclear eccentricity, and enlarged nuclei were more pronounced in neoplastic UW than VU specimens, suggesting that the method of urine specimen procurement affects the presence of certain low-grade features. Cancer Cytopathol 2016;124:552-64. © 2016 American Cancer Society.

The Paris System for Reporting Urinary Cytology: the quest to develop a standardized terminology.

The main purpose of urine cytology is to detect high-grade urothelial carcinoma (HGUC). With this principle in mind, The Paris System (TPS) Working Group, composed of cytopathologists, surgical pathologists, and urologists, has proposed and published a standardized reporting system that includes specific diagnostic categories and cytomorphologic criteria for the reliable diagnosis of HGUC. This paper outlines the essential elements of TPS and the process that led to the formation and rationale of the reporting system. The Paris System Working Group, organized at the 2013 International Congress of Cytology, conceived a standardized platform on which to base cytologic interpretation of urine samples. The widespread dissemination of this approach to cytologic examination and reporting of urologic samples and the scheme's universal acceptance by pathologists and urologists is critical for its success. For urologists, understanding the diagnostic criteria, their clinical implications, and the limitations of TPS is essential if they are to utilize urine cytology and noninvasive ancillary tests in a thoughtful and practical manner. This is the first international/inclusive attempt at standardizing urinary cytology. The success of TPS will depend on the pathology and urology communities working collectively to improve this seminal paradigm shift, and optimize the impact on patient care.

Adequacy in voided urine cytology specimens: The role of volume and a repeat void upon predictive values for high-grade urothelial carcinoma.

BACKGROUND: Adequacy assessment is one of the most controversial and overlooked components in the daily practice of cytopathology, because it is generally determined from limited samples. Because voided urine varies widely in terms of its volume and cellularity, there is little consensus about the proper role for these variables in assessing specimen adequacy. In this study, the authors explored the role of volume in voided urine specimens to determine whether it plays a role in determining adequacy for the detection of high-grade urothelial carcinoma. METHODS: Voided urine specimens received at the authors' laboratory over the 9.5 years since the introduction of the Johns Hopkins Template for Reporting Urinary Cytopathology were analyzed for correlations between volume, specimen adequacy, and the diagnosis of high-grade malignancy. The same data set also was queried to determine whether a patient who provided a voided low-volume specimen could yield a higher volume specimen and thereby increase adequacy. RESULTS: In total, 15,731 voided urine specimens with a cumulative volume of 891 liters originating from 8594 individual patients were analyzed. Specimen adequacy increased linearly for each increment of volume submitted to the laboratory up to 30 mL, after which the correlation was nonlinear. Low-volume specimens below this cutoff also had lower fractions of specimens that were diagnosed as malignant or suspicious. CONCLUSIONS: Volume is an important component in the evaluation of adequacy for voided urine cytology specimens.