Large distal ureteric stone with high burden urothelial cancer of the entire ureter and renal pelvis: a dual pathology

Abstract

Upper-tract urothelial cancer comprises only 3% of all urothelial cancers. Risk factors include tobacco smoking, recurrent urinary infection, urolithiasis and analgesic abuse. Urolithiasis-induced chronic inflammation leads to urothelial proliferation and eventual malignant transformation. The most common association is reported with squamous cell cancer. A 54-year man under evaluation for right flank pain was diagnosed with a large distal ureteric stone and urothelial cancer of the entire right ureter and renal pelvis. The patient underwent right nephroureterectomy and stone retrieval, with urinary bladder cuff excision and pelvic lymph node dissection. On follow-up, the patient succumbed to disease recurrence with widespread metastasis. Urothelial cancer associated with stone disease is atypical. Long-standing inflammation causing metaplastic and dysplastic changes is a possible hypothesis. Careful assessment of the malignancy should be looked for in patients with long-standing obstruction due to stone disease.

Background

Upper-tract urothelial carcinoma is a tumour arising from the epithelium of renal calyces, pelvis and ureter. There are multiple risk factors described in literature for this cancer, which include smoking, occupational exposure to aromatic amines, analgesic abuse, Balkan nephropathy and chronic inflammatory diseases such as renal or ureteric stones. Stones are classically described with squamous cell carcinoma of the urinary tract. At times, malignancy is detected later in histopathology reports of kidney specimen operated for non-functional kidney secondary to ureteric stone disease. We present the case of a 54-year man with a distal ureteric stone managed initially with percutaneous nephrostomy. On further evaluation, the patient was diagnosed with extensive multifocal upper-tract urothelial cancer involving the renal pelvis and almost the whole of the ureter.

Case history

A 54-year-old man with no comorbidities presented with right flank pain of four months’ duration. The pain was a chronic, dull ache and radiated to the groin. He also complained of high-grade fever of five days’ duration. On evaluation, laboratory reports revealed haemoglobin 10.2g/dl, total leucocyte counts 14,200 cells/cumm, platelets counts 2.34 lacs/cumm, blood urea 34g/dl, serum creatinine 1.3mg/dl and serum electrolytes were within normal limits. Ultrasound of the abdomen showed right gross hydroureteronephrosis with a 4mm renal calculus and multiple large lower ureteric calculi. Urine analysis showed pH 7.1, 8–10 pus cells, 8–10 red blood cells and culture growing Gram-negative bacilli. A right percutaneous nephrostomy was placed under local anaesthesia.

The patient was referred to the urology clinic two days later with the percutaneous nephrostomy draining frank blood mixed with urine and output of 200ml/day. He was conscious, oriented and his vitals were stable. There was a haemoglobin drop of 1g/dl, and his renal and liver functions were within normal limits. Contrast-enhanced computed tomography (CT) of the chest and abdomen with CT urography showed a grossly hydronephrotic, non-excreting right kidney with a distended, tortuous ureter with multiple large distal ureteric calculi. The renal pelvis and the entire segment of the ureter showed enhancing soft-tissue masses proximal to the calculi (Figure 1). There were no enlarged regional lymph nodes or metastatic deposits and the left kidney was normal.

Figure 1 .

Contrast-enhanced computed tomography of the abdomen; axial cuts showing a grossly hydronephrotic right kidney with multifocal enhancing lesions in the renal pelvis and ureter and a large radiopaque calculus in the distal ureter

Urine for malignant cytology from the percutaneous nephrostomy showed atypical transitional cells suggestive of urothelial cancer. Right radical nephroureterectomy with bladder cuff excision was planned. Under general anaesthesia using a 26 French resectoscope and a 30-degree lens, the right ureteric orifice was cored with a Collins knife to the perivesicular fat. A right subcostal incision was made and the kidney was approached transperitoneally.

The renal parenchyma was thin and showed dilatation of the pelvicalyceal system with the percutaneous nephrostomy in place. The percutaneous nephrostomy entry into the kidney was secured with silk 2–0 sutures to prevent spillage. The ureter was dilated and tortuous. A single renal artery and vein were identified, ligated and cut. The kidney was dissected all round and part nephrectomy was completed. A Gibson incision was made to complete the nephroureterectomy, with excision of the bladder cuff, carefully dissecting along the common iliac vessels to prevent spillage. The obturator, external iliac and common iliac group of lymph node were removed. Haemostasis was achieved and a 24 French drain was placed and abdomen closed in layers.

The postoperative period was uneventful and the drain was removed on postoperative day 3. The patient was discharged on day 5 in a stable condition.

The gross specimen showed a renal pelvis and almost the entire length of ureter involved with multifocal papillary tumours and large multiple distal ureteric calculi (Figure 2). Histopathology showed high-grade urothelial cancer involving the pelvicalyceal system and ureter, with infiltration into the renal parenchyma and the muscular layer of the ureter (Figure 3). The resection margins and lymph nodes were free of tumour. The patient was counselled and advised for gemcitabine/cisplatin-based chemotherapy in view of the locally advanced disease. He was unfortunately lost to follow-up and returned one year later with a poor appetite, significant weight loss and swelling in the lower abdomen. On evaluation, contrast-enhanced CT of the chest and abdomen showed a large enhancing mass occupying the whole pelvis with multiple metastatic deposits in the right lung suggestive of disease recurrence. The patient died in hospital.

Figure 2 .

Gross specimen of nephroureterectomy showing (a) dilated tortuous ureter, and (b) cut specimen showing large ureteric calculi and multiple papillary growth along the entire length of ureter and renal pelvis

Figure 3 .

Histopathology slides (eosin and haematoxylin stain) showing tumour cells arising from the transitional cell lining of the ureter (a, low-power view 10× magnification; b, high-power view 20× magnification)

Discussion

Upper-tract urothelial carcinoma is a tumour arising from the epithelium of the renal calyces, pelvis and ureter. It is rare compared with urinary bladder cancer and is usually more advanced at the time of diagnosis. Multifocality is seen in 6–38% of cases.¹ The renal pelvis is most common site of upper-tract urothelial carcinoma, followed by the distal and proximal ureter. Multiple risk factors are described in literature, include smoking, occupational exposure to aromatic amines, analgesic abuse, Balkan nephropathy and chronic inflammatory diseases such as urolithiasis. Prognostic factors include tumour stage, tumour grade, lymph vascular invasion, lymph nodes involvement and multifocality.² Calculi are classically described with squamous cell carcinoma of urinary tract.

Symptoms related to stone disease may camouflage the symptoms of malignancy. At times, patients with a non-functional kidney secondary to stone disease are found to have malignancy on histopathology of a kidney specimen. Yeh et al reported 51% malignancy (24/47) in nephrectomy specimens taken of a non-functional kidney due to varied pathology.³ Only seven of these patients had preoperative imaging suggestive of malignancy. Urothelial cancer (17/24) was the most common, followed by renal cell cancer, squamous cell cancer and epidermoid cancer.³

One possible hypothesis for this rare association is stones, which induce morphological changes in the urinary epithelium, chronic mechanical irritation and recurrent infections leading to dysplasia. Another hypothesis is stasis caused by complete blockage of urine by stones leading to dysplastic changes. A major hindrance in the diagnosis of such cases is the presence of non-specific symptoms. The index patient presented with flank pain that was thought to be due to ureteric calculi with a non-functional grossly hydronephrotic kidney. CT showed multiple large distal ureteric calculi with a grossly dilated renal pelvis and a tortuous ureter. Echogenic contents in the ureter and renal pelvis were misinterpreted initially as infective in nature and correlated with fever and increased leucocyte counts. A percutaneous nephrostomy was placed with no suspicion of urothelial cancer.

Upper-tract urothelial carcinoma is classically hyperattenuating to urine (5–30 HU) but less attenuating to other filling defects such as clots or stones on CT. Features suggestive of malignancy are pelvicalyceal irregularities, focal or diffuse mural thickening, polypoidal-enhancing lesions with infiltration into the renal parenchyma or surrounding structures. Multiphasic CT with urography is the diagnostic imaging of choice for upper-tract urothelial carcinoma.⁴ Urologists and radiologists should be cautious when reporting doubtful findings and always consider malignancy as one of the differential diagnoses in such cases.

Radical nephroureterectomy is considered the standard of care for high-grade upper-tract urothelial carcinoma, although minimally invasive techniques have also been used in some clinical settings. We decided to proceed with radical nephroureterectomy with bladder cuff excision and lymph node dissection because of the already extensive disease and non-functional kidney due to ureteric calculi. The histopathology report confirmed a high-grade urothelial carcinoma. Unfortunately, this patient was lost to follow-up and presented a year later with widespread metastases and died during his second hospital stay.