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Papillary Urothelial Carcinoma

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1: Papillary Urothelial Carcinoma – Gross morphology


	Comments: This radical cysectomy specimen shows multifocal papillary tumors with delicate fronds. Microscopically, it was grade 2 papillary urothelial carcinoma (WHO Classification, 1973) with muscularis propria invasion.

2: Papillary Urothelial Carcinoma – Gross morphology


	Comments: Another radical cystectomy specimen showing multifocal papillary urothelial carcinoma.

3: Papillary Urothelial Carcinoma, Grade 1 (WHO Classification, 1973)


	Comments: These papillary tumors show an orderly proliferation with 6 or more layers of urothelium lining the fibrovascular cores. There is no alteration of cellular polarity, little or no cytologic atypia, and infrequent mitoses which, if present, are usually basally located.

4: Papillary Urothelial Carcinoma, Grade 1 (WHO Classification, 1973)


	Comments: Higher magnification view demonstrates lack of significant cytologic atypia. More than 8-10 layers of urothelium line a delicate fibrovascular core.

5: Papillary Urothelial Carcinoma, Grade 1 (WHO Classification, 1973)


	Comments: Another look at grade 1 papillary urothelial carcinoma. These patients are at risk of developing recurrent tumors which may be of higher grade. This entity is considered synonymous with papillary urothelial neoplasm of low malignant potential in the 1998 WHO/ISUP Classification of papillary urothelial neoplasms.

6: Papillary Urothelial Carcinoma, Grade 2 (WHO Classification, 1973)


	Comments: These tumors show more architectural disorder and nuclear atypia than Grade 1 tumors. The nuclear size, shape, polarity, and chromatin show greater variability. Mitoses are still infrequent.

7: Papillary Urothelial Carcinoma, Grade 2 (WHO Classification, 1973)


	Comments: As compared to Grade 1 tumors, this example of Grade 2 tumor shows slightly more architectural and cytologic disorganization while retaining features such as nuclear polarity. Umbrella cells can still be seen.

8: Papillary Urothelial Carcinoma, Grade 2 (WHO Classification, 1973)


	Comments: Another example of Grade 2 papillary urothelial carcinoma.

9: Papillary Urothelial Carcinoma, Grade 3 (WHO Classification, 1973)


	Comments: These tumors display total architectural disorganization and significant cytologic atypia of urothelium. There is loss of nuclear polarity; considerable variation in nuclear size, shape, and chromatin content; mitoses are frequent and may be abnormal. Umbrella cells are usually absent.

10: Papillary Urothelial Carcinoma, Grade 3 (WHO Classification, 1973)


	Comments: The nuclei in this Grade 3 tumor are significantly enlarged and show variably increased chromatin content.

11: Papillary Urothelial Carcinoma, Grade 3 (WHO Classification, 1973)


	Comments: The cells in this Grade 3 tumor have voluminous cytoplasm. The nuclei are enlarged and vesicular and have prominent nucleoli.

12: Papillary Urothelial Carcinoma, Grade 3 (WHO Classification, 1973)


	Comments: Same case as previous image. Pleomorphic nuclei with prominent nucleoli, frequent abnormal mitoses, and loss of cellular polarity and organization are prominently displayed here.

13: Papillary Urothelial Carcinoma, Grade 3 (WHO Classification, 1973)


	Comments: High-grade papillary urothelial carcinoma frequently display abundant apoptotic cells as seen in this case.

14: Papillary Urothelial Carcinoma, Grade 3 (WHO Classification, 1973)


	Comments: This high-grade tumor shows little or no resemblance to urothelial cells. The exact histogenesis of high-grade urothelial tumors may be difficult to ascertain in metastatic sites. Clinical information may be of tremendous value in such cases.

15: Papillary Urothelial Carcinoma, Grade 2, with focal lamina propria invasion


	Comments: The base of the tumor shows small isolated tumor cell nests which are beginning to infiltrate into the lamina propria. No other focus of invasion was seen in this transurethral resection specimen.

16: Papillary Urothelial Carcinoma, Grade 2, with focal lamina propria invasion


	Comments: Higher magnification view of the preceding slide. There is little cytologic atypia. Grade 2 morphology was present elsewhere in the tumor (urothelial tumors are graded according to the worst [highest] grade present. There is some resemblance to nested variant of urothelial carcinoma.

17: Papillary Urothelial Carcinoma, Grade 3, with lamina propria invasion


	Comments: At the base of the tumor, small nests of tumor cells are seen infiltrating the lamina propria. Muscularis propria was present and free of tumor. The tumor cells display considerable nuclear pleomorphism.

18: Papillary Urothelial Carcinoma, Grade 3, with muscularis propria invasion

Comments: One of the most challenging tasks faced by pathologist reading bladder biopsies/transurethral resections is the correct identification of muscularis propria invasion. It is critical to not confuse thin, delicate, discontinuous fascicles of muscularis mucosae for muscularis propria since patient with muscularis propria invasion may be offered cystectomy. Muscularis propria has thick fascicles as seen here.

19: Papillary Urothelial Carcinoma, Grade 2-3


	Comments: Note the abrupt transition from Grade 2 to Grade 3 morphology in this papillary urothelial carcinoma.

20: Urothelial Carcinoma : Vascular invasion


	Comments: The tumor cell clusters conform to the shape of the vessel. Immunostain for CD31 confirmed the presence of an endothelial lining around the space. Vascular invasion should be distinguished from shrinkage artifact which would have no endothelial lining, blood, or lymphocytes.

21: Urothelial Carcinoma with Glandular Metaplasia


	Comments: Presence of focal or even extensive malignant squamous and/or glandular epithelium (seen here) is not uncommon in typical urothelial carcinoma.

22: Urothelial Carcinoma involving Ureter


	Comments: A nephroureterectomy specimen showing bulbous expansion of proximal ureter near the renal pelvis caused by papillary urothelial carcinoma. (Photo: Courtesy of Dr. Gary Bokinsky, Virginia Urology Center, Richmond, VA).

23: Urothelial Carcinoma involving Ureter


	Comments: The expanded portion of the ureter has been opened longitudinally revealing an exophytic mass blocking its lumen. Microscopically, it was a non-invasive grade 2 papillary urothelial carcinoma. (Photo: Courtesy of Dr. Gary Bokinsky, Virginia Urology Center, Richmond, VA).

24: Urothelial Carcinoma involving Ureter


	Comments: A low-power scan of glass slide from another case demonstrating non-invasive papillary urothelial carcinoma filling up the lumen of the ureter.