Non-muscle invasive transitional cell carcinoma of the distal ureter and bladder with lung metastasis: A case report and literature review

Abstract

INTRODUCTION

Non-muscle invasive transtitional cell carcinoma (TCC) with metastases is exceedingly rare.

PRESENTATION OF CASE

We report the case of a 78-year old man with an incidental finding of a non-muscle invasive TCC of the left distal ureter during treatment for Duke's B Colon cancer. Following laparoscopic nephro-ureterectomy (LNU) he had two further superficial recurrences in the bladder over a 14-month period which underwent transurethral resection (TUR). On surveillance imaging for his colorectal cancer follow-up a lung nodule was detected and video-assisted thoracic surgical (VATS) resection of the lesion showed it to be TCC in origin. He was referred to oncology for chemotherapy and remains clinically well.

DISCUSSION

A Literature search found only three other such cases and the ureteric TCC is the most likely source of the metastasis.

CONCLUSION

This occurrence is exceedingly rare.

1. Introduction

Non-muscle invasive TCC with metastases is exceedingly rare. In the bladder superficial TCC can be confined to the mucosa and is staged Ta, or show invasion into the lamina propria, stage T1. The presence of lympho-vascular invasion is seen as a poor prognostic indicator and is more commonly associated with muscle invasive disease (stages T2, T3, T4) via which metastatic disease is able to occur. This is why metastases in non-muscle invasive disease without any evidence of lympho-vascular invasion is so rare, yet we report a case of this very same occurrence.

2. Presentation of case

A 78-year old gentleman presented to casualty four years ago under the general surgeons with a perforated caecal tumour for which he had an emergency right hemi-colectomy. The histology was Duke's B, T4 N0 M0 adenocarcinoma of the caecum. Post-operative CT scan revealed an incidental finding of marked left hydronephrosis and hydroureter and no lung metastasis (Fig. 1) and a CT urogram confirmed the presence of a filling defect in the left distal ureter (Fig. 2). After 8 weeks of convalescence and adjuvant chemotherapy following his bowel surgery he had a cystoscopy which did not show any intravesical abnormalities but on diagnostic ureteroscopy there was a papillary lesion in the left distal ureter. A biopsy was taken and the histology was Grade 2, Ta papillary TCC. Four weeks later he underwent a left LNU and endoscopic resection of the left ureteric orifice and the histology confirmed Grade 2, pTa papillary TCC. The histology report specifically mentions the absence of infiltration of underlying connective tissue or muscle wall and there was no evidence of carcinoma in situ (CIS). The distal ureteric margin and left ureteric orifice specimens were microscopically clear of tumour. He was discharged home four days later and a cystogram two weeks post-operatively showed no evidence of leak.

Fig. 1.

Initial CT thorax.

Fig. 2.

CT urogram demonstrating filling defect in left distal ureter.

This gentleman was now in a programme of regular endoscopic surveillance and his first check four months after his LNU revealed superficial-looking papillary tumour at the bladder neck and left lateral wall. These were resected and he had one dose of intravesical Mitomycin C (MMC) post-op. The histology again confirmed Grade 2, pTa papillary TCC of the bladder. Further check cystoscopy at fourteen months again showed recurrence at the bladder neck and prostatic urethra. These were resected showing further Grade 2, pTa papillary TCC so he had a six-week course of intravesical MMC. He has not had any further recurrences to date.

Meanwhile, this patient was still undergoing regular GI follow-up with cross-sectional imaging and 3 years following his right hemi-colectomy his CT scan showed an 8.5 mm nodule in the left apex of the lung suspicious for a possible pulmonary metastasis. Referral to the respiratory multi-disciplinary team advised a repeat CT scan in 4 months and this showed the nodule had increased in size to 10.5 mm (Fig. 3) and likely to be a pulmonary metastasis. He underwent video-assisted thoracic surgical (VATS) resection of this apical lung nodule to determine the tumour primary and this confirmed TCC. He has been referred to oncology for a full course of chemotherapy and remains without recurrence of his caecal adenocarcinoma.

Fig. 3.

CT thorax showing left apical lung metastasis.

3. Discussion

An extensive pubmed literature search yielded eight cases of metastatic superficial bladder cancer and of these, three reported lung metastasis. Hirayama et al.¹ reported the case of a 66-year old woman with a history of low-grade superficial bladder tumours who presented with a coin-sized lesion in the right lung. Thoracoscopic partial pneumonectomy revealed metastatic TCC and recurrent bladder tumours were found in the bladder on cystoscopic follow-up. Dougherty et al.² reported on a case series of two patients with low grade non-muscle invasive TCC of the bladder and pulmonary metastases. The first case described a 78-year old male with recurrent superficial low grade TCC after failed bacille Calmette Guerin (BCG) therapy who went on to develop lung metastases 10 years from his initial diagnosis of bladder cancer. This was confirmed histologically following right middle lobectomy 3 years after carboplatin-based chemotherapy gave only a partial response the growth of the metastases. The second case was that of a 61-year old male investigated for a lung lesion 8 years after left nephroureterectomy for low grade superficial TCC in his ureter and renal pelvis. This was followed by recurrent low grade superficial bladder tumours in the intervening years. Right lower lobectomy confirmed the diagnosis of metastatic TCC and the patient went on to receive adjuvant carboplatin-based chemotherapy as well.

Other sites of metastasis from non-invasive bladder cancer include the ovary³ in a 60-year old woman with an abdominal mass who had a Grade 3 TCC metastasis on her left ovary 4 years after initial TUR resection for Grade 2 superficial TCC of the bladder. She later progressed and developed pelvic metastases and died. The only other case with a distant site of metastasis from non-muscle invasive TCC bladder was published by Shikishima et al. in 1989.⁴ In this case a 74-year old man presented with a 2-week history of red eye and diplopia 3 years after undergoing TUR for Grade 2 superficial TCC of the bladder. A trans-septal anterior orbitotomy revealed nests of carcinomatous cells confirmed histologically as TCC. More regional sites of non-muscle invasive TCC bladder metastases include the uterine corpus of a 78-year old woman who had TUR of a bladder tumour for Grade 3, pT1 disease 2 years earlier,⁵ and vaginal implantation of Grade 2 non-muscle invasive TCC in an 82-year old woman 10 years after TUR of the same histological lesion from the bladder. Interestingly, the authors proposed that vaginal implantation of TCC may have occurred via irrigation fluid during TUR or from patient's urine.

The interesting question in this case is what is the likely source of the metastasis – ureter or bladder? Our opinion is that the ureter is the more likely primary for the metastasis as the papillary tumour was more extensive and had been present for longer compared to the very superficial-looking bladder tumour picked up at the first check flexible cystoscopy. Histologically, there is also the possibility that muscle invasion was missed on analysis of the nephroureteric tissue.

4. Conclusion

Our case highlights a rare incidence of distant metastatic non-muscle invasive bladder cancer in an elderly man. Using the European Organisation for Research and Treatment of Cancer (EORTC) risk stratification tables⁶ his probability of recurrence at 1 and 5 years was intermediate at 38.0% and 62.0%, respectively. The probability of progression at 1 and 5 years (i.e. to muscle-invasive disease) also fell in the intermediate category at only 1.0% and 6.0%, respectively. His progression was detected at 3 years which further highlights how unlikely the progression to metastatic disease was. Cross-sectional imaging of the thorax is not routinely used in our urology department for follow-up of non-muscle invasive TCC, therefore, had this patient not been having such surveillance as part of his colorectal follow-up his lung metastasis would likely not have been found until he became symptomatic with chest symptoms or indeed metastatic disease elsewhere.

Conflict of interest statement

None.

Funding

None.

Ethical approval

Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

Author contributions

Initially, TF Chen had identified this case. Both N Nkwam and TF Chen reviewed the patient in clinical setting and discussed literature review, and Nkwam performed literature search. After getting guidance from Chen for the write-up, Nkwam sourced case notes and wrote case report. Finally, Chen obtained consent from the patient for publication.