ABSTRACT

Metastatic carcinoma to the ureter is very rare and was described to occur from breast, lung, stomach and prostate cancers. A 48 year old male was admitted with the complaint of gross hematuria. A suspicious mass in the middle part of the left ureter with hydroureteronephrosis was detected on Magnetic Resonance (MR) urography 3 months after the completion of postoperative chemotherapy. Histopathological evaluation of the ureter revealed adenocarcinoma with invasion into the muscularis and pT2. The tumor cells invaded through muscular layer to the lamina propria of the ureter. Biopsies under ureteroscopy are indispensable in the diagnosis of ureteral carcinoma.

Introduction

 Primary adenocarcinoma of the renal pelvis and ureter is an extremely rare tumor, representing less than one per cent of all renal tumors (1). Furthermore, metastatic carcinoma to the ureter is very rare and has been described to occur from breast, lung, stomach and prostate cancers (2). In most published cases the diagnosis was not made until postmortem examination or when gross metastases were present (3). This may be partly due to the asymptomatic nature of the majority of cases (4). Considering both early and late recurrences,distinguishing the metastatic lesion from primary carcinoma is crucial for both management and prognosis. Herein, late recurrence of sigmoid colon cancer presenting with ureteral solid mass is reported and discussed within current literature.

Case Report

 A 48 year old male was admitted with the complaint of gross hematuria. He had been operated 1 year ago for sigmoid colon adeno-carcinoma (T4, N2, M0, stage 2, Dukes B) in general surgery department followed by six cycles of adjuvant chemotherapy. The period after the completion of chemotherapy with follow-up colonoscopies and further investigations were uneventful until present day. Physical examination was unremarkable. Abdominal ultrasonography showed left hydroureteronephrozis. Ureteral suspicious mass in the middle part of the left ureter with hydroureteronephrosis was noted on MR urography 3 months after the completion of postoperative chemotherapy (Figure 1). There was no evidence of metastasis. Biopsies under ureteroscopy was performed. Histopathology revealed atypical epithelial cells with large vesicular nuclei and with prominent nucleoli. Central necrosis and high mitotic activity was also reported in tumour clusters. CK20 Immunohistochemistry (IHC) examination of tumour cells revealed diffuse and strong cytoplasmic staining pattern (Figure 2). Contrarily, there was no CK7 staining pattern observed in tumour cells (Figure 3). Also strong nuclear CDX2 immunoreactivity was found (5,6). These features were considered as strongly suggestive for ureteral metastasis of the colonic origin. Left nephroureterectomy was performed. The ureteric histology showed adenocarcinoma with invasion into the muscularis, pT2. The tumor cells invaded through muscular layer to the lamina propria of the ureter. Additional chemotherapy was planned but diffuse metastasis were seen and the patient died because of multiple organ failure in 3 months.

Discussion

Metastatic tumors of the ureter are very rare. The most common primary tumor sites may be kidney, stomach, prostate, breast, lung, and lymph nodes (7). Metastases from carcinoma of the colon are less frequently described and majority of the cases are found incidentally at autopsy (6). Clinical symptoms such as low backpain and renal colic may be due to obstruction of the upper urinary tract, or there may be anuria when there is bilateral involvement. In our case the first symptom was macroscopic hematuria. Hematuria is the most common presenting sign of primary adenocarcinoma of the renal pelvis and ureter, however it is infrequent in metastatic tumors since the mucosa of the urinary tract is rarely involved (8). Three types of metastatic ureteral involvement havebeen described 1- infiltration of the periureteral adventitial soft tissues with resultant compression of the ureteral wall; 2- transmural or a portion of the layers of the ureter with evidence of tumor cells in the muscular coat, perilymphatic components, or vascular components of the ureter; and 3- involvement of the local mucosa, with or without involvement of the muscularis of the ureter, and submucosal nodules (7). In our case the metastatic ureteral involvement was type 2. The clinical manifestations of the first two types of metastatic ureteral involvement may be stricture formation or even obstruction of the ureter, as occurred in our case.The third type of metastatic ureteral involvement may be manifested by filling defects within the lumen seen radiographically. With regard to the anatomy of the ureter, the periureteral adventitia has longitudinally running well-developed blood vessels, whereas the muscularis and mucosa of the ureter are supplied by fewer smaller perpendicularly arranged vessels. This is a possible reason, why hematogenous metastases more often occur in the periureteral adventitia with resultant compression of the ureter or stricture formation than in the muscularis or mucosal layer (6,7). Thus, the adventitial layer of the ureter is usually first involved and there is subsequent spread into the muscularis and lamina propria by direct extension or along vascular channels. Later, although rarely, attenuation or ulceration of the mucosa may ocur.

In our case MR urography revealed significant hydroureteronephrosis over the upper third of the right ureter. However, some ureteral abnormalities such as, inflammatory strictures or primary urothelial neoplasms may present with similar radiographic features. Pathologic confirmation is essential for the diagnosis of primary or metastatic malignancy. Unfortunately, it is difficult to obtain pathologic information in severely ill patients once they develop diffuse metastatic disease. Biopsies under ureteroscopy provides accurate diagnosis in most of cases just as our patient. In addition, ureteroscopy is a minimal invasive surgery and can be performed in local anesthesia. The diagnostic ureteroscopy has become a fundamental step in the preoperative evaluation of the ureteral tumors. Ureteroscopy allows to explore visually at least 95% of the upper urinary tract and to perform biopsies of the tumor (9).

The prognosis is poor for patients with ureteral metastasis; 75% of the patients die within 6 months after the onset of symptoms of ureteral blockage (10). This may emphasize the importance of early recognition of metastatic ureteral obstruction, especially in those patients without significant clinical symptoms or even after a good response to chemotherapy as occurred in our case. Early appropriate treatment and relief of ureteral obstruction may preserve renal function and increase the survival rate.

In conclusion, most cases are diagnosed from the resected specimen postoperatively. The treatment is nephro-ureterectomy. Although it is uncommon, the possibility of metastatic ureteral carcinoma should be considered as a differential diagnosis, especially in patients with a history of adenocarcinoma of the colon. Careful evaluation of patients with a thorough physical examination, appropriate imaging techniques and IHC is crucial for such complex cases. Biopsies under ureteroscopy is indispensable in the diagnosis of ureteral carcinoma.

Conflict of interest: The authors reported no conflict of interest related to this article.