Pathology of Upper Tract Urothelial Carcinoma with Emphasis on Staging

Abstract

The first two authors contributed equally to this work Classification of upper tract urothelial preneoplastic and neoplastic lesions mirrors that of the urinary bladder, with aU lesions of the bladder urothelium being possible in the upper tract and vice versa. There are three major groups of non-invasive urothelial neoplasms: flat, papillary, and inverted. These three groups share a similar morphological spectrum of intraurothelial changes, ranging from hyperplasia to dysplasia to carcinoma in situ. However, they differ in terms of architectural growth pattern compared to the surrounding non-neoplastic mucosal surface. Infiltrating urothelial carcinoma is defined as a urothelial tumor that invades beyond the basement membrane. Unlike in non-invasive papillary urothelial neoplasms (pTa), the role of histologic grade in pTl and higher stage tumors has been suggested to be of only relative importance. The vast majority of tumors of the upper urinary tract are urothelial carcinoma. More commonly seen, however, are foci ofsquamous differentiation and, less frequently, glandular differentiation. Pure urothelial carcinomas also display a wide range of variant morphologies, and recognition of these morphologies is important for diagnosis, classification, and prognosis.The pathology ofupper tract urothelial carcinoma (UTUC) is considered to be the same as that of urothelial carcinoma of the bladder (UCB) (1-3). While this assumption seems reasonable given that the histologic features of UTUC and UCB are microscopically identical, a growing body of evidence has begun to suggest that differences between these two cancers do exist (4). Nevertheless, studies specific to the pathology of UTUC remain rare and much of what is known about UTUC is derived from studies on UCB. CLASSIFICATION AND GRADINGUreteroscopic evaluation with biopsy is currently the gold standard for diagnosing tumors of the upper

Identification of Significant Prognostic Tissue Markers Associated with Survival in Upper Urinary Tract Urothelial Carcinoma Patients Treated with Radical Nephroureterectomy: A Retrospective Immunohistochemical Analysis Using Tissue Microarray

“…More prognostic factors including postoperative pathologic stage, grade, lymph node invasion, lymphovascular invasion, and tumor location have been identified for UTUC than for bladder cancer. Meanwhile, the presence of previous bladder cancer history distinguished UTUC from bladder cancer [4,5,10,14,17,29].…”

“…Recent studies with TMA of RNU specimens have attempted to define more stratified and precise classification methods based on tissue and genetic markers similar to other cancers [10,21]. Immunohistochemistry using TMA was widely used to better predict the therapeutic outcome of surgical and systemic medical interventions [9].…”

“…All samples were transitional cell carcinoma specimens and reviewed blindly, retrospectively, and pathologically by an uropathologist (W.S.P.) with 15 years of experience in accordance with the 2009 tumor, node, and metastasis (TNM) classification for UTUC and the 2004 World Health Organization (WHO)/ International Society of Urologic Pathologists (ISUP) consensus classification [10].…”

“…Tissue microarray (TMA) of surgical specimens, and the expression of immunohistochemical tissue markers, may provide important clues to better understand the pathogenetic characteristics of UTUC and identify universal prognostic markers, which will aid in estimating more precise prognoses of UTUC after surgery. Therefore, in this study, 27 potential urothelial carcinoma-related tissue markers from previous urothelial carcinoma-related tissue studies and National Cancer Center bladder cancer panel [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] were applied immunohistochemically (IHC) to the TMA of specimens from patients with UTUC who underwent RNU, in order to identify any significant prognostic tissue markers of survival, including intravesical recurrence-free survival (IVRFS), disease-free survival (DFS), and overall survival (OS).…”

High grade infiltrative adenocarcinomas of renal cell origin: New insights into classification, morphology, and molecular pathogenesis

“…Considering the broad differential diagnosis upon encountering a high grade, poorly differentiated adenocarcinoma in the kidney, we cannot over‐emphasize exclusion of both (i) urothelial carcinoma of the upper tract, which may show extensive glandular and other variant differentiation, and (ii) metastatic carcinoma of various primary sites. With regards to the question of urothelial carcinoma of the upper tract, correlation with risk factors, any urine cytologic findings, any history of urothelial carcinoma elsewhere in the urinary tract, and any potential stigmata of Lynch syndrome is essential in workup, as is careful gross dissection including generous sampling of the pelvicalyceal mucosa for any nephrectomy with an infiltrative carcinoma .…”