This is defined by the presence of keratinization and⁄or intercellular bridges as classic morphological features. Squamous cells are intermixed with malignant cells exhibiting classic features of HGUC. The squamous cells display hyperchromatic and spindle-shaped nuclei with clumped chromatin. The cytoplasm is dense, keratinized, and orangeophilic. Keratin flakes and necrosis are frequently observed in the background (Figs. 6.9 and 6.10) [21–23]. Diagnosis of squamous carcinoma of the urinary tract can only be determined by extensive examination of biopsy or cystectomy tissue.

Glandular differentiation is defined as the presence of true glandular formation within groups of tumor cells. Glandular cells are intermixed with malignant cells exhibiting classic features of HGUC (Figs. 6.11 and 6.12). Diagnosis of adenocarcinoma of the urinary tract can only be determined by extensive examination of biopsy or cystectomy tissue.

HGUC is diagnosed on the basis of the following criteria according to The Paris System consensus (see Explanatory Note):

The percentage of urinary cytology cases reported as “positive for malignancy” is relatively low and would be expected to vary based on the clinical and demographic characteristics (risk) of the population, and the practice habits of physicians who are ordering urinary cytology evaluations. Therefore, laboratories may have quite different rates of cases interpreted as “positive for malignancy”. It is also noteworthy that patients with cytologic results of “positive for malignancy” and “suspicious for malignancy” are often managed similarly. Thus many studies appropriately combine these two categories when evaluating the diagnostic accuracy of urinary cytology.

In Dr. Papanicolaou’s initial publication demonstrating the feasibility of using urinary cytology to detect bladder cancer, 27 of 83 cases, or 33 % were reported as positive for neoplasm [24]. Undoubtedly this cohort of patients was a selected and high-risk population. More contemporary, larger studies from laboratories have reported much lower rates of malignancy that have ranged from 1.7 to 5.8 % of all urinary cytology cases [25–27]. These studies also confirmed that bladder washings and upper urinary tract specimens tend to have a higher percentage of malignant cases as compared to voided urine specimens.

The Paris System working group also made an international outreach attempt to further ascertain the rate of malignancy in various academic and nonacademic practice settings. The data from this study are included in Table 6.1. The cytopathology laboratories contributing these data included both academic and nonacademic practices, and provided data for the year 2013. The rate of malignancy or cases identified as “positive for malignancy” ranged from 1.0 to 6.3 %. In addition, cases that were suspicious for malignancy showed a range of 0.2 to 5.4 %. This again, demonstrates a low number of cases being finalized as equivocal, in most clinical laboratories. The cases that were designated as “Negative for malignancy” ranged from 64.8 to 96.1 %, which demonstrates that the majority of the samples reviewed are benign.