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Table of Contents
ORIGINAL ARTICLE
Year : 2021  |  Volume : 32  |  Issue : 4  |  Page : 151-156

Clinical features of patients with nonmalignant upper tract lesions mimicking urothelial cancer


Department of Urology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

Date of Submission02-Jan-2021
Date of Decision16-Mar-2021
Date of Acceptance01-Apr-2021
Date of Web Publication14-Dec-2021

Correspondence Address:
Dr. Ze-Hong Lu
Department of Urology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan
Taiwan
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/UROS.UROS_3_21

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  Abstract 


Purpose: The purpose is to evaluate the incidence and clinical features of patients who have undergone nephroureterectomy with nonmalignant upper tract lesions presumed to be urothelial carcinoma from images in Taiwan. Materials and Methods: Between October 2004 and October 2015, our institute had 350 patients who underwent retroperitoneoscopic nephroureterectomy for possible upper urinary tract urothelial carcinoma without a routine diagnostic ureteroscopy (URS) or ureteroscopic biopsy. Trauma, urolithiasis, or infection were excluded. We collected imaging findings; urine cytology results; renal function status; previous urothelial history; and the final pathology results. Twenty-three (6.6%) patients had nonmalignant benign lesions found from pathology. Results: The 23 patients comprised nine men and fourteen women. Most patients were middle-aged. Initial symptoms included gross hematuria, hydronephrosis, and flank pain. From self-voided urine cytology, the most common result was atypical cells. The number of patients was equal in the end-stage renal disease (ESRD) plus postkidney transplantation group and the non-ESRD group. In addition, we divided patients into two groups according to lesioned kidney function status: Nonfunctional kidney (NFK) or functional kidney (FK). The most common pathologic feature found in the NFK group was atrophic kidneys. On the other hand, the most common diagnosis in the FK group was pyelonephritis. Conclusion: Nonmalignant pathologic lesions were detected in 23 patients who had undergone retroperitoneoscopic nephroureterectomy without preoperative diagnostic URS for upper tract lesions. Self-voided urine cytology provided limited information for diagnosis in this group. For the almost 75% of patients with NFK, nephroureterectomy may be a feasible diagnostic and therapeutic method.

Keywords: Benign tumor, end-stage renal disease, mimicking, upper tract urothelial carcinoma, ureteroscopy biopsy


How to cite this article:
Lu ZH, Ou CH, Lin KC. Clinical features of patients with nonmalignant upper tract lesions mimicking urothelial cancer. Urol Sci 2021;32:151-6

How to cite this URL:
Lu ZH, Ou CH, Lin KC. Clinical features of patients with nonmalignant upper tract lesions mimicking urothelial cancer. Urol Sci [serial online] 2021 [cited 2022 May 21];32:151-6. Available from: https://www.e-urol-sci.com/text.asp?2021/32/4/151/332409




  Introduction Top


Prevalence rates of upper tract urothelial carcinoma (UTUC) and chronic kidney disease are high in Taiwan.[1],[2],[3],[4],[5] The relationship between urothelial carcinoma and renal insufficiency has previously been established.[2],[6] However, to the best of our knowledge, routine ureteroscopy (URS) or ureteroscopic biopsy may result in limited benefits for patients suspected with upper urinary tract lesions in imaging studies due to false-negative results and higher intravesical recurrence rate after ureteroscopic biopsy.[7],[8] In addition, in patients with end-stage renal disease (ESRD), performing ureteroscopies may be challenging, and endoscopic nephron-sparing management does not provide significant benefits. Guidelines of the European Association of Urology suggest performing URS or biopsy in cases where additional information will impact treatment decisions.[9],[10] For patients with nonfunctional kidneys, pathologic results of ureteroscopic biopsies may not change the surgical plan. Due to the high prevalence rate of UTUC and CKD in southern Taiwan, filling defects or tumor-like lesions in computed tomography (CT) scans is highly associated with malignancy. Even nonmalignancies are diagnosed using ureteroscopic biopsy; however, concerns on false-negative results exist.

In this study, we retrospectively reviewed the incidence and clinical features of patients who have undergone nephroureterectomy with nonmalignant upper tract lesions, which are presumed to be urothelial carcinoma, in our institute. Preoperative features of these patients were investigated, including imaging findings, urine cytology results, renal function status, and medical history.


  Materials and Methods Top


This study was approved by the institutional review board of National Cheng Kung University Hospital (ER-99-237). From October 2004 to October 2015, 350 patients with suspected upper urinary tract urothelial carcinoma underwent retroperitoneoscopic nephroureterectomy and bladder cuff resection at our institution, a tertiary center in southern Taiwan. All patients' consent has been obtained.

All surgeries were conducted by one urologist (CHO). In this study, inclusion criteria were suspected with upper urinary tract malignancy due to (1) suspected upper tract tumor from an imaging study; (2) unexplained hydronephrosis in patients with ESRD; (3) unexplained hematuria in patients with ESRD without bladder tumors; and (4) unexplained hematuria or hydronephrosis of patients with a history of urothelial carcinoma of the opposite upper tract or bladder. Patients who had suspicious benign lesions, such as renal staghorn stone, pyelonephrosis, or trauma, were excluded from this study. All patients provided a detailed medical history and underwent biochemistry tests, voided urine cytology, and imaging studies, including CT, sonography, intravenous urography, or retrograde pyelography.

Patient characteristics including age, gender, comorbidities, body mass index (BMI), initial presentation, laterality, renal function, and prior or concurrent urothelial cancer were also retrospectively recorded. All patients underwent a cystoscopy preoperatively to rule out concurrent concomitant bladder tumors. Diagnostic URS or ureteroscopic biopsies are not performed routinely at our institute. Additionally, performing semi-rigid URS in patients with ESRD may be challenging, and the procedure may result in unnecessary complications. According to EAU Guidelines on Urothelial Carcinomas of the Upper Urinary Tracts, diagnostic URS and biopsies should be performed in cases where additional information will impact treatment decisions. For patients with NFK, results of diagnostic URS may not change the final decision for nephroureterectomy.

Patients were divided into two groups based on whether the targeted lesion was found in a functional kidney (FK) or NFK. NFK status covers the kidney of patients with ESRD, the native kidney of a patient at postkidney transplantation, or a patient kidney with a thin renal cortex, as determined from imaging studies. Clinical features and pathologic diagnoses were analyzed between FK and NFK groups.


  Results Top


A total of 23 patients were included in this study, comprising 9 male and 14 female patients. All patient characteristics are listed in [Table 1]. The percentage of nonmalignant upper tract lesions mimicking urothelial cancer was 6%. Patients' age ranged from 35 to 83 (mean, 60.6) years, and the mean BMI was 23.7. Possible initial presentations included gross hematuria, hydronephrosis, or flank pain. For laterality, lesions slightly more commonly occur on the right than on the left side. The number of patients with ESRD plus the number of patients on postkidney transplant was almost equal to the number of patients without ESRD. We also evaluated the targeted (lesioned) kidney status using medical history, laboratory data, and clinical images. We defined all patients with ESRD, postkidney transplant, and atrophic kidney (defined by thinning cortex, visible in images) as the NFK group, whereas the remaining patients were defined as the FK group [Table 2]. Urine cytology and pathology results are also listed in [Table 2].
Table 1: Patients characteristics

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Table 2: Demographic and clinical feature

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The most common finding of voided urine cytology was atypical cells; however, data were not available from 52% of patients due to anuria or missing data. Nearly 41% of patients in the NFK group had a concomitant urothelial carcinoma history, including opposite upper tract and bladder. Conversely, no concomitant urothelial carcinoma history was found among patients in the FK group. Based on pathological results, the most common finding in the NFK group was atrophic kidney. In the FK group, half of the patients had pyelonephritis. From preoperative CT scans, soft tissue lesions over the upper urinary tract mimicking UTUC were found in some patients, in both NFK and FK groups. In [Figure 1], a CT scan of a 78-year-old man in the NFK group shows gross hematuria and left lower calyx tumor; however, his pathological results showed low-grade dysplasia. Another patient in the NFK group was a 62-year-old woman with a presumed gross hematuria and right ureteropelvic junction tumor who had a final pathology report suggesting an atrophic kidney.
Figure 1: Clinical image of nonfunctional kidney group Representive image of upper urinary tract lesions mimicking urothelial carcinoma in nonfunctional kidney group. Red circles point out lesion location of two nonfunctional kidney group patients. (a) Case number 23: 78-year-old male with gross hematuria had left lower calyx tumor from computed tomography scan results, but pathology is low-grade dysplasia. (b) Case number 5: 62-year-old female presenting gross hematuria had right ureteropelvic junction tumor, and pathology is atrophic kidney

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As shown in [Figure 2], we list all patients in the FK group. First, a 56-year-old man presented with gross hematuria, and images suggested a right renal pelvis tumor. Pathology showed a benign fibroepithelial polyp. Another 37-year-old man suffering from gross hematuria had a right renal pelvis-filling defect identified through CT urography, and the pathology showed pyelonephritis. An 83-year-old man with gross hematuria and left ureteropelvic junction tumor detected on the CT scan had a final pathological report of inverted papilloma. Another FK-group patient, a 67-year-old woman with repeated pyelonephritis, had ill-defined hypoenhanced infiltrative lesions at the middle portion of her right kidney; however, her final pathology showed no malignancy and she was diagnosed with chronic pyelonephritis. An 80-year-old woman had a right renal pelvis-filling defect determined from CT urography and hematuria; however, her pathological test showed a xanthogranulomatous inflammation. Finally, a 56-year-old woman with hematuria and atypical cells on urine cytology underwent a CT scan revealing right hydronephrosis and ureteral wall thickening. The final pathology was pyelonephritis.
Figure 2: Clinical images and specimen gross pictures of upper urinary tract lesions mimicking urothelial carcinoma in functional kidney. Lesions location are marked. (a) Case number 12: 56-year-old male with gross hematuria and right renal pelvis tumor, and pathology is benign fibroepithelial polyp. (b) Case number 15: 37-year-old male suffered from gross hematuria, right renal pelvis filling defect from computed tomography urography, and pathology shows pyelonephritis. (c) Case number 10: 83-year-old male suffered from gross hematuria for 2 months, and left ureteropelvic junction tumor was detected, and pathology is inverted papilloma. Gross picture of specimen is nonavailable. (d) Case number 22: 67-year-old female had repeated pyelonephritis, and had ill-defined hypoenhanced infiltrative lesions at middle portion of the right kidney. Pathology is chronic pyelonephritis. (e) Case number 20: 80-year-old female with right renal pelvis filling defect from computed tomography urography and hematuria, but pathology is xanthogranulomatous inflammation. (f) Case number 16: 56-year-old female with hematuria and atypical cell from urine cytology. Computed tomography reveals right hydronephrosis and ureteral wall thickening. The final pathology is pyelonephritis

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  Discussion Top


According to data from the Health Promotion Administration of the Ministry of Health and Welfare in Taiwan, UTUC is the 16th leading malignancy in men and 14th in women based on incidence in 2015. In addition, it is the 16th cause of cancer-specific death based on the highest rate in men and 14th in women. The incidence rate of UTUC was higher in Taiwan than that in other countries.[5] Additionally, the incidence rate of UTUC is higher in southern Taiwan than that in northern Taiwan and is more common in women than in men, which differs from that of other countries.[11],[12] Besides, UTUC is highly associated with renal insufficiency.[4],[5] High arsenic levels in drinking water are also positively associated with the incidence of ESRD in Taiwan.[13] In our study, half of the patients had ESRD or were on postkidney transplantation.

The incidence rate of patients with nonmalignant upper urinary tract lesions mimicking urothelial cancer was 6.6%, compared with previous studies, i.e., 2.9%.[14] However, the sample size of the study was small, which may result in selection bias.

For urothelial carcinomas of the upper urinary tract, nephroureterectomy is the curative treatment. Prior to nephroureterectomy, imaging studies including intravenous urography, retrograde pyelography, and CT urography or diagnostic URS were considered part of clinical surveys. According to the EAU Guidelines on urothelial carcinomas of the upper urinary tract, diagnostic URS and biopsies should be performed in patients where additional information will impact treatment decisions.[9],[10] For those who have upper urinary tract tumors based on imaging results, URS or biopsy may not change the treatment plan considering the risk of false-negative results, especially in the NFK group.

Besides, in our NFK group, performing semi-rigid diagnostic URS or biopsies was relatively difficult and can result in severe ureteral injuries in patients with a severe ureteral stricture. Furthermore, nonmalignant results of URS biopsies of those lesions could be false negatives.[15] Although CT scans and URS are important diagnostic tools for UTUC, both cannot achieve 100% accuracy.[16] Endoscopic management for UTUC may result in underestimating the disease aggressiveness.[17] The possibility of carcinoma in situ (CIS) in the upper urinary tract also results in undertreatment of endo-urology procedures. Besides, concurrent CIS with upper tract papillary tumor cannot be detected by images. Thus, nephroureterectomy will still be offered as a treatment option.

Almost three-quarters of our study population were in the NFK group. In addition, 41% of patients in the NFK group had concomitant urothelial carcinoma histories. For these patients, performing nephroureterectomy as soon as possible could prevent delayed malignancy diagnoses. Furthermore, nephroureterectomy has been reported to increase the 5-year survival in patients on dialysis with upper urinary tract urothelial carcinoma.[18]

In the FK group, six patients were included. The most common pathological result was pyelonephritis. No patients in this group had a history of urothelial carcinoma. [Figure 2] shows representative CT images of all patients in the FK group. All patients had suspicious upper tract urothelial lesions found during imaging. Benign tumors in the bladder mimicking papillary urothelial neoplasia had been reported.[19] Whether diagnostic URS should be performed before nephroureterectomy or not remains to be clinically elucidated. A higher intravesical recurrence rate was observed after URS prior to nephroureterectomy, especially for renal pelvic lesions.[20] False negatives showing nonmalignant biopsy results will still be considered in clinical settings[17] if the image reveals highly suspicious tumor lesions.

The prevalence rate of UTUC is also relatively high in southern Taiwan.[12] Therefore, identifying patients who should receive diagnostic URS prior to nephroureterectomy is currently challenging. Discussing the treatment options along with possible risks and benefits with the patient and family is suggested.

In addition, case 22, a 67-year-old woman who suffered from flank pain, was suspected with malignancy according to self-voided urine cytology results, but the pathology revealed pyelonephritis. During follow-up, no any evidence of urothelial malignancy had been found in this patient. This is a limitation of self-voided urine cytology.

Currently, flexible URS, also known as retrograde intrarenal surgery (RIRS), has been increasingly known to provide another way to evaluate renal pelvis and renal calyces that cannot be managed using semi-rigid URS. Besides, tumor ablation by laser can also be performed through RIRS for renal pelvis tumor, which cannot be performed with semi-rigid URS. However, the accessibility and price of RIRS remain an obstacle in daily practice. Besides, the diameter of flexible ureteroscopes is larger than semi-rigid ones, and thereby, performing flexible URS is difficult in the NFK group, especially in those with ureteral stricture.

This study has several limitations. Due to the nature of retrospective studies, the protocol of prescribing diagnostic URS cannot be established. The final decision of nephroureterectomy could be affected by the doctor's suggestion, patient's condition, and family's preferences. Any of these may lead to a selection bias in patients receiving a nephroureterectomy without URS. Second, in Taiwan, flexible URS is still costlier and less accessible than semi-rigid URS. However, reaching renal pelvic lesions can be very difficult with semi-rigid URS, which could lead to policy changes for targeting those lesions. It may be helpful if the flexible and semi-rigid ureteroscope have smaller diameters, lower prices, and greater durability. Third, in Taiwan, where the prevalence of ESRD and UTUC is high, urologists may have a more aggressive attitude about nephroureterectomy to prevent missing diagnoses because the situation is different than in other countries.


  Conclusions Top


Twenty-three (6.6%) patients had nonmalignant upper tract lesions mimicking urothelial cancer and underwent retroperitoneoscopic nephroureterectomy. Self-voided urine cytology provided limited information in this population. Diagnostic URS prior to nephroureterectomy may not change the final decision due to false-negative concerns in patients who had a filling defect or tumor-like lesions in CT scans. Besides, for renal pelvic lesions or atrophic urinary tract in the NFK group, performing semi-rigid URS is challenging and can bring unnecessary complications. The risk and benefit of diagnostic URS should be both considered and discussed for those patients. With the improvement of urological endoscopy, those difficulties and challenges may be conquered in the future.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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