Contemporary Issues in Urothelial Carcinoma of Upper Urinary Tract

Abstract

Upper urinary tract urothelial carcinoma (UTUC) is an uncommon malignancy involving the renal pelvis and ureter. Careful pathologic analysis plays a critical role in the diagnosis and clinical management of UTUC. In combination with clinical and radiologic evaluation, pathologic features can be used to stratify patients into low-risk and high-risk groups. This risk stratification can help clinicians select the optimal treatment for patients with UTUC, such as kidney-sparing (conservative) treatment, radical nephroureterectomy or ureterectomy, and perioperative systemic therapy. However, due to the technical difficulty of obtaining sufficient tissue from the upper urinary tract, it is often challenging for pathologists to accurately grade the tumor and assess tumor invasion in small biopsy specimens. Although the majority of UTUCs are pure urothelial carcinoma, a considerable subset of UTUCs show histologic subtypes or divergent differentiation. Recent studies have identified genetically distinct molecular subtypes of UTUC by examining DNA, RNA, and protein expression profiles. The prognosis of pT3 UTUC, particularly renal pelvic UC, remains controversial, and several studies have proposed subclassification of pT3 UTUC. Lynch syndrome is a significant risk factor for UTUC, and screening tests may be considered in young patients and those with familial histories of the disease. Despite significant progress in recent years, several issues remain to be addressed in the pathologic diagnosis, molecular classification, and treatment of UTUC.

Figure 1.

Gross specimens of radical nephroureterectomy show urothelial carcinoma in the renal pelvis (A) with invasion into the renal parenchyma and in the ureter (B).

Figure 2.

UTUC shows histological heterogeneity with mixed low-grade and high-grade components. (A) Low-power view of high-grade papillary UC of the renal pelvis (magnification ×5). (B) Low-grade (on the left) with adjacent high-grade (on the right) UC components. (C) Low-grade UC component in the same tumor. (D) High-grade UC component in the same tumor. (B, C, D: magnification ×100)

Figure 3.

UTUC with different histological subtypes and divergent differentiation. Here is an example of high grade UC of the renal pelvis (A, magnification ×5). This tumor has conventional high-grade UC mixed with sarcomatoid UC (B). Focal squamous (C) and glandular (D) features were also found in the same tumor. (B, C, D: magnification ×100)

Figure 4.

The muscular wall (muscularis) in the renal pelvis. (A) The muscularis is not well developed in the renal pelvis and can be thin or absent in some areas. (B) High-grade urothelial carcinoma involves the muscularis of renal pelvis and staged as pT2. (C) In minor renal calyx, the urothelium is immediately adjacent to the renal parenchyma without any subepithelial tissue or muscularis. (D) Any amount of invasive urothelial carcinoma in minor calyx is staged as pT3 disease. (A-D: magnification ×20)

Figure 5.

Urothelial carcinoma in situ involves the collecting ducts without definitive invasion of renal parenchyma (A, B), staged as pTis (not pT3). (C, D) High-grade urothelial carcinoma of the renal pelvis invades through muscularis into renal parenchyma, staged as pT3. (A: magnification ×20; C: magnification ×10; B &D: magnification ×100).

Figure 6.

High grade UTUC is incidentally identified in a radical nephrectomy specimen for renal cell carcinoma. (A) CT image demonstrates a 5.2 cm heterogeneous solid mass in the left kidney (Green arrow), and a subtle wall thickening (Red arrow) in the proximal left ureter with asymmetric ectasia of the upstream ureter and collecting system. (B) Renal mass shows clear cell renal cell carcinoma. (C, D) High grade urothelial carcinoma of the proximal ureter invades transmurally into periureteral fat. (B &C: magnification ×20; D: magnification ×100).