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The Pathology of the Urothelium

Smith, Tim MD

doi: 10.1097/PCR.0000000000000162

From the Anatomic Pathology, Medical University of South Carolina, Charleston, SC.

Reprints: Tim Smith, MD, Anatomic Pathology, Medical University of South Carolina, 171 Ashley Ave, MSC 908, Charleston, SC 29425. E-mail:

The author has no funding or conflicts to declare.



Lining the renal pelvis, ureters, bladder, and part of the urethra is an epithelium that in the past has been called “transitional” because it appears to some observers midway between stratified squamous and columnar epithelium. Today, the name “urothelium” is considered more appropriate for pathologists’ use. The urothelium covers the surfaces of all tubular organs that transmit urine. The urothelium is constantly bathed in any carcinogens secreted into the urine, and resulting neoplasms have a surprising morphological variety of invasive and noninvasive malignancies. This issue of AJSP: Reviews and Reports concerns the complex spectrum of neoplasms of the urothelium and the natural reflection of that complexity in the molecular pathways.

In the first 2 reviews Drs Udager and Smith cover the classification, grading, and variants of urothelial neoplasia through the history of evolutions of the World Health Organization system (1973, 1998, and 2016). The significant and often problematic variants of urothelial carcinoma are described. After explaining the historical changes, they describe the criteria for diagnosis and staging of invasion in the urinary tract. Pathologic staging is synonymous with the decision of level of invasion, based on the small bits of cauterized bladder often received in daily practice. The staging decision can be decidedly difficult and is critically important for patient care. A patient given a diagnosis of stage T2 is very likely to be treated with radical cystectomy, which is a life-altering event. Cautery artifact and necrosis can make the choice between T1 and T2 frustrating and exasperating. The authors provide important tips and clues for that decision. Next, Dr Spruill provides a case report of urethral carcinoma and reviews important variants. Primary carcinoma of the urethra, not extending from the bladder, is very rare and infrequently considered. All of the problematic variants of malignancies of the bladder also occur in the urethra. The next topic covered is the nightmarish separation of neoplasms with sarcomatoid architecture. They appear infrequently in the urothelial tract, and Dr Bruner describes a case and provides clues used to separate spindled carcinoma from true sarcomas and reactive processes.

Urine cytology is a frequently used clinical laboratory test. Past criteria for reactive, atypical, and malignant cells have been operationally difficult from a consistency standpoint. The new Paris classification system for urine cytology is described by Dr Lindsey using a case-based approach. The Paris system emphasizes identification of the high-grade lesions. In the last review, Drs Allison and Baras provide an explanation of the molecular features of urothelial carcinoma. There is now evidence for differences between noninvasive papillary urothelial carcinoma and invasive carcinoma. The differences are distinctive and stimulate support for origin of malignancy and for therapeutic regimens.

These articles were designed to provide pathologists with valuable information about the entities discussed, as well as clues for their diagnosis. We also hope that the illustrations are found to be memorable and useful.

© 2016 Lippincott Williams & Wilkins, Inc.