Accuracy of grading of urothelial carcinoma on urine cytology: an analysis of interobserver and intraobserver agreement

Abstract

Background: Urine samples of known urothelial carcinoma were independently graded by 3 pathologists with (MS, MR) and without (AO) fellowship training in cytopathology using a modified version of the 2004 2-tiered World Health Organization classification system. By measuring interobserver and intraobserver agreement among pathologists, compared with the gold standard of biopsy/resection, specimen accuracy and reproducibility of grading in urine was determined.

Methods: 44 urine cytology samples were graded as low or high-grade by 3 pathologists with a 2-3 week interval between grading. Pathologists were blinded to their and others' grades and histologic diagnoses. Coefficient kappa was used to measure interobserver and intraobserver agreement among pathologists. Accuracy was measured by percentage agreement with the biopsy/resection separately for each pathologist, and for all pathologists and occasions combined.

Results: The overall accuracy was 77% (95% C.I., 72%-82%). Pathologist AO was significantly more accurate than MR on occasion 1 (p = 0.006) and 2 (p = 0.039). No other significant differences were found among the observers. Interobserver agreement using coefficient kappa was unacceptably low, with all but one of the kappa value being less than 0.40, the cutoff for a "fair" degree of agreement. Intraobserver agreement, as measured by coefficient kappa, was adequate.

Conclusions: Our study underscores the lack of precision and subjective nature of grading urothelial carcinoma on urine samples. There was poor inter- and intraobserver agreement among pathologists despite fellowship training in cytopathology. Clinicians and cytopathologists should be mindful of this pitfall and avoid grading urothelial carcinoma on urine samples, especially since grading may impact patient management.

Keywords: Urothelial carcinoma; accuracy of grading; urine cytology.

Figure 1

Low grade urothelial carcinoma. A. Papillary cluster of malignant cells with high nuclear to cytoplasmic ratio (Papanicolaou stain, magnification x 400). B. Three-dimensional cluster of malignant cells with nuclear pleomorphism, hyperchromasia and irregular nuclear borders (Papanicolaou stain, magnification x 200).

Figure 2

Low grade urothelial carcinoma. Urinesample contains papillary cluster of cells with a suggestionof a central fibrovascular core (Papanicolaoustain, magnification x 200).

Figure 3

High grade urothelial carcinoma. Note numerous large single malignant cells with high nuclear to cytoplasmicratio, coarse chromatin, irregular nuclear borders, single cell necrosis and background necrosis (Papanicolaoustain, magnification x 400).

Figure 4

Case of urothelial carcinoma showing mixed low and high grade features. Note tight clusters of malignant hyperchromatic low grade tumor cell clusters with dense cytoplasm and irregular nuclear borders (in A and B), and rare, isolated clusters of high grade malignant cells (in C and D) (Papanicolaou stain, magnification x 200).