Urothelial Carcinoma Presentation

Urothelial Carcinoma Presentation

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Patient history
Past medical history is notable for hematuria, hypertension, non-insulin dependent diabetes mellitus, Warthin’s tumor of left parotid, pleomorphic adenoma of right parotid, tubular adenoma and adenomatous polyps of the colon, thyroid disorder, tonsillectomy, pilonidal cyst and arthritis.

Hospital course
A 79 year old male presented with gross hematuria and palpable right kidney hydronephrosis. Ureteroscopy found blockage of the right ureter by a mass and biopsy revealed features consistent with papillary urothelial carcinoma favoring high grade. A radical nephroureterectomy was performed.

Gross description
The right kidney and portion of ureter was surgically resected. Opening the ureter revealed two discrete tan-gray papillary lesions. One was 4.0 cm in length and 2.0 cm in open circumference and located 4.0 cm from the ureteropelvic junction and occluded the lumen. The other was 0.8 cm in length and 0.5 cm in open circumference, did not occlude the lumen and was located 2 cm from the ureteric margin. The remaining ureteric and renal pelvic mucosa was unremarkable. The kidney revealed markedly dilated renal pelvis and calyces.

Diagnosis
Microscopic examination of the larger occluding lesion is consistent with high grade papillary urothelial carcinoma which invades the muscularis propria (Fig. 1). The additional focus revealed high-grade papillary urothelial carcinoma with no invasion of the lamina propria or muscularis propria (Fig. 2). Also noted in random sampling of ureter and renal pelvic walls is focal urothelial carcinoma in situ (Fig. 3.)

Discussion
Urothelial carcinomas most commonly occur in the urinary bladder but can occur at any site which contains urothelium including the upper urinary tract from the ureteral orifice to the renal calyces. Cancers of the upper urinary tract account for 5-10% of all renal tumors and 5-7% of all urothelial tumors [1]. The types of urothelial tumors in the upper urinary tract mirror those that originate in the bladder. The four morphological patterns of growth include papilloma-papillary, invasive papillary, flat noninvasive carcinoma and flat invasive carcinoma [2]. Papillomas are benign, exophytic structures with finger-like papillae, central fibrovascular core with epithelium which resembles typical urothelium. Inverted papillomas can occur which are benign lesions, but extend into the lamina propria. Papillary urothelial neoplasms of low malignant potential (PUNLMPs) show thicker urothelium or diffuse nuclear enlargement with rare mitotic figures. Low grade papillary urothelial carcinomas are cohesive and maintain polarity with some nuclear atypia and infrequent mitotic figures. High grade papillary urothelial cancers have discohesive cells with large hyperchromatic nuclei, frank anaplasia and frequent mitotic figures.

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High grade tumors have a higher incidence of invasion and metastatic potential. Carcinoma in situ is defined as malignant cells confined to the epithelium. Although morphologically similar to bladder urothelial carcinomas, the tumor biology may differ between the two (3).

Urothelial carcinoma can have a common origin or develop as multiple foci throughout the urinary tract that have varying degrees of anaplasia and invasion. These tumors usually become clinically apparent when they fragment and cause hematuria or block the urinary outflow from the kidney and cause considerable pain. Most upper tract urothelial carcinomas occur in the renal pelvis and calyces but a 2012 study by Yafi et al suggested that tumor located in the ureter and multifocal tumors had a poorer prognosis than those present solely in the renal pelvis [4]. A concurrent bladder cancer is found in 17% of diagnosed upper tract urothelial carcinoma [5]. The current treatment of choice is radical nephroureterectomy with bladder cuff excision [6].

The incidence of upper urinary tract urothelial carcinomas in Western countries is 2.08 per 100,000 with a peak incidence occurring in the eighth decade of life [7]. Men are 3 times more likely to develop urothelial carcinoma than women [8] and smoking increases the likelihood as well. Although only 15-25% of bladder tumors are invasive at diagnosis, 60% of upper urinary tract tumors are invasive at diagnosis [9, 10].

The depth of invasion and pathologic stage are the most important prognostic indicators for upper urinary tract urothelial carcinomas [10, 11]. According to the College of Pathologists (CAP) [12], tumors of the upper urinary tract are staged as follows:
pT0: No evidence of primary tumor
pTa: Papillary noninvasive carcinoma
pTIS: Carcinoma in situ
pT1: Tumor invades lamina propria
pT2: Tumor invades muscularis propria
pT3: Tumor invades beyond muscularis into perinephric/periureteric fat or the renal parenchyma
pT4: Tumor invades adjacent organs, or through the kidney into the perinephric fat.
Prognosis drastically changes as a tumor advances to pT4. The 5 year survival rate for pTa/pTis is 100%, 91.7% for pT1, <50% for pT2/pT3 and <10% for pT4 [13, 14, 15].

Several situations exists which can create staging problems and include variable thickness of the lamina and muscularis propria in the ureter, renal pelvis and calyces, pagetoid cancer spread and determining the depth of invasion of inverted or endophytic papillary tumors [11]. Therefore, careful gross examination and understanding the microanatomy of the upper urinary tract are pivotal for accurate stage assessment.

In conclusion, proper staging of upper tract urothelial carcinomas begins at the gross bench with careful examination and keeping in mind the probability that these tumors can be multifocal. Adequate sampling of grossly observable lesions is crucial for proper staging as microscopic invasion can be quite variable. Also, it is important to adequately sample grossly uninvolved mucosa throughout the upper urinary tract as a wide-spectrum of dysplasia can be present. Only through proper preparation at the gross bench can the definitive stage assessment and best patient care be achieved.

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