The Paris system for reporting urinary cytology: An updated review
image: Superficial urothelial (umbrella) cells have one or multiple nuclei with finely granular chromatin and conspicuous nucleoli, abundant cytoplasm, and low N/C ratios (a and b). For bladder washing specimens, urothelial cells may be arranged in papillary-like fragments without a fibrovascular core, but with small round or oval nuclei that contains finely granular chromatin, moderate cytoplasm, and low N/C ratios (<0.5) (c). Benign squamous cells are large polygonal cells with abundant dense cytoplasm, small round nuclei that contain finely granular chromatin or dark chromatin, and low N/C ratios (d). Degenerated urothelial cells present with shrunken (condensed), dark nuclei with mildly irregular nuclear borders, granular cytoplasm, and eosinophilic and/or cyanophilic intracytoplasmic inclusions (Melamed-Wolinska bodies) (e). Flat sheet of urothelial cells with low N/C ratios, scant-to-moderate cytoplasm, and small round nuclei that contain finely granular chromatin. Umbrella cells are present on the outer surface (f). Atypical urothelial tissue fragment (AUTF). Clusters of urothelial cells with nuclear overlapping: some had N/C ratios of ≥0.5, and slightly enlarged nuclei with nuclear membrane irregularity and finely granular chromatin (g). Low-grade papillary urothelial carcinoma. Three-dimensional clusters of innocuous urothelial cells with round nuclei, finely granular chromatin and inconspicuous nucleoli, low N/C ratios, and a surrounding fibrovascular core (h). Urolithiasis: clusters of urothelial cells with reactive changes, finely granular chromatin, conspicuous nucleoli, smooth nuclear contours, and low N/C ratios (i). Magnification: ×600.
Credit: Xiaoqi Lin, Fei Chen
The Paris System for Reporting Urinary Cytology (TPS), first introduced in 2016, was established to provide a standardized, evidence-based reporting system for urine specimens. Its primary aim is to reduce unnecessary indeterminate diagnoses while maintaining high efficacy in detecting high-grade urothelial carcinoma (HGUC). With six diagnostic categories, TPS outlines diagnostic criteria, estimated risk of malignancy, and management recommendations. In 2022, TPS 2.0 was introduced, incorporating new data to refine diagnostic categories, update risk assessments, and enhance molecular testing protocols. This review provides an updated summary of TPS 2.0, addressing diagnostic pitfalls and discussing relevant molecular tests.
Pathogenesis of Urothelial Carcinoma
TPS 2.0 incorporates insights from the Cancer Genome Atlas, detailing the molecular pathways involved in urothelial carcinoma. Genomic alterations such as FGFR and RAS are frequently observed in low-grade papillary carcinoma, while FGFR and TP53 alterations are common in HGUC. TP53 and RB pathways are particularly prevalent in carcinoma in situ. In muscle-invasive HGUC, significant genomic alterations involve the RTK/RAS/PI3K pathway, FGFR3, ERBB2 enrichment, histone modification, the SWI/SNF complex, and the TP53/RB pathway.
Adequacy of Urine Specimens
Adequacy criteria for urine specimens in TPS 2.0 are stringent. Voided urine specimens should have more than 25-30 ml, while instrumented urine samples require more than 20 urothelial cells per 10 high-power fields (HPFs). Cases with 10-20 cells per 10 HPFs are considered satisfactory but limited by low cellularity, and those with fewer than 10 cells per 10 HPFs are unsatisfactory. The category "less-than-optimal adequacy" addresses specimens meeting most criteria but falling short in urothelial cellularity.
Negative for High-Grade Urothelial Carcinoma (NHGUC)
NHGUC, accounting for 90.5% of voided urine specimens, indicates an adequate specimen lacking cytomorphologic findings of HGUC. Diagnostic criteria include benign urothelial cells classified into superficial, intermediate, and deep types. Superficial urothelial cells are large with low nuclear/cytoplasmic (N/C) ratios, while deep cells are small with high N/C ratios and scant cytoplasm.
Atypical Urothelial Cells (AUC)
AUC encompasses specimens where urothelial cells exhibit atypia insufficient for a definitive HGUC diagnosis. Criteria include nuclear enlargement, hyperchromasia, and irregular nuclear membranes. Issues unresolved by TPS 1.0, such as atypical squamous cells, are addressed, recommending not categorizing them as atypical urothelial cells.
Suspicious for High-Grade Urothelial Carcinoma (SHGUC)
SHGUC is used for cases with abnormal urothelial cells that do not meet the threshold for definitive HGUC diagnosis. Diagnostic criteria include an increased N/C ratio due to nuclear enlargement and features like moderate-to-severe hyperchromasia, irregular clumpy chromatin, and irregular nuclear membranes.
High-Grade Urothelial Carcinoma (HGUC)
The primary aim of TPS is to ensure high positive predictive value for HGUC, which accounts for 1.9% of voided urine specimens. Diagnostic criteria require at least 5-10 malignant cells for lower tract specimens and 10 or more cells for upper tract specimens, with an N/C ratio of 0.7 or higher due to nuclear enlargement.
Cytopathology of the Upper Urinary Tract
TPS 2.0 includes criteria for diagnosing upper tract urothelial carcinoma (UTUC), which is less common but significant. Proper specimen collection and preparation are crucial, with ancillary testing like UroVysion FISH and other biomarkers playing a supportive role.
Non-Urothelial Malignancies (NUM) and Miscellaneous Lesions
TPS 2.0 also covers primary epithelial malignancies and other non-urothelial tumors that may be encountered in urinary cytology. These include various carcinoma subtypes and rare lesions, highlighting the need for precise ancillary testing and clinical correlation.
Ancillary Studies in Urinary Cytology
Molecular tests such as UroVysion FISH and other liquid-based biomarkers are emphasized in TPS 2.0. Next-generation sequencing technology offers additional diagnostic precision, aiding in the accurate identification of urothelial and non-urothelial malignancies.
Clinical Management Recommendations
TPS 2.0 provides detailed management guidelines for each diagnostic category. These include handling unsatisfactory specimens, managing NHGUC, addressing AUC, and providing protocols for SHGUC and HGUC cases. The management of low-grade urothelial neoplasms and non-urothelial tumors is also discussed.
Conclusions
TPS 2.0 represents a significant advancement in the standardized reporting of urinary cytology, integrating new molecular insights and refining diagnostic criteria to improve the accuracy and clinical utility of urine cytology in detecting urothelial carcinoma and other malignancies.
Full text
https://www.xiahepublishing.com/2771-165X/JCTP-2022-00035
The study was recently published in the Journal of Clinical and Translational Pathology.
Journal of Clinical and Translational Pathology (JCTP) is the official scientific journal of the Chinese American Pathologists Association (CAPA). It publishes high quality peer-reviewed original research, reviews, perspectives, commentaries, and letters that are pertinent to clinical and translational pathology, including but not limited to anatomic pathology and clinical pathology. Basic scientific research on pathogenesis of diseases as well as application of pathology-related diagnostic techniques or methodologies also fit the scope of the JCTP.
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