Bladder-to-bladder metastasis: gallbladder cancer metastasising to the urinary bladder

Abstract

We report a 48-year-old fit and healthy woman who was incidentally diagnosed to have adenocarcinoma of gallbladder after laparoscopic cholecystectomy. Subsequent imaging showed no evidence of regional or distant spread. She was scheduled for elective laparotomy and resection of gallbladder bed, but during laparotomy frozen section analysis of an incidentally discovered peritoneal deposit confirmed metastasis, so the procedure was abandoned. Thereafter, she received cisplatin and gemcitabine chemotherapy. However, surveillance computed tomography incidentally noted a urinary bladder mass which had not been present before. Transurethral resection of the bladder lesion revealed moderately differentiated adenocarcinoma of urinary bladder. The appearance and immunoprofile of the lesion confirmed metastasis from the primary gallbladder cancer, which has not been documented in the literature to the best of our knowledge. Her disease progressed and she is being challenged with gemcitabine and carboplatin as second-line palliative chemotherapy. She is still alive two years after the initial diagnosis.

Background

Gallbladder cancer is an aggressive and rare malignancy that mainly occurs in elderly people.¹ Common sites of metastatic spread from gallbladder cancer are liver, lymph nodes, lung and bone.² Metastatic involvement of urinary bladder from gallbladder primary has not been documented to our best possible knowledge. We report a case of incidentally diagnosed advanced gallbladder cancer that subsequently developed metastasis to urinary bladder confirmed on transurethral resection of the bladder tumour (TURBT).

Case history

A 48-year old woman with intermittent biliary colic and ultrasound showing a 2cm gallbladder stone with a gallbladder wall thickness of 8mm underwent elective laparoscopic cholecystectomy. The gallbladder histology showed moderate and focal poorly differentiated invasive adenocarcinoma with tumour lying less than 1mm from the liver bed margin with no cystic duct involvement or lymphovascular invasion (Figure 1). Surgical stage was at least pT2, as serosal involvement could not be excluded.

Figure 1 .

Moderate and focal poorly differentiated invasive adenocarcinoma of the gallbladder; (a) magnification ×100; (b) magnification ×200

Subsequently, computed tomography (CT) of the chest, abdomen and pelvis and magnetic resonance imaging (MRI) of the liver showed no evidence of local spread or distant metastasis of the cancer. Tumour markers such as carbohydrate antigen 19–9 and carcinoembryonic antigen were within normal limits. She was then scheduled for elective laparotomy and resection of the gallbladder bed. During laparotomy, frozen section analysis of an incidentally discovered peritoneal deposit over the greater omentum confirmed metastasis, so the procedure was abandoned. Intraoperative examination did not show any other deposit in rest of the abdomen and pelvis. A vaginal examination performed at the same time was normal.

After that, the patient received eight cycles of first-line palliative cisplatin and gemcitabine chemotherapy. However, follow-up CT six months later, while the patient was on chemotherapy, revealed a 2cm well-defined hyperdense nodularity in the right posterosuperior aspect of the urinary bladder (Figure 2a) which had increased to 3cm on repeat scan (Figure 2b). There was no evidence of lymph node enlargement or involvement of other organs. She had no history of haematuria, dysuria or any other lower urinary tract symptoms.

Figure 2 .

(a) Coronal view of computed tomography (CT) performed six months after initial diagnosis while the patient was on chemotherapy, showing an around 2cm well-defined hyperdense nodularity in the right posterosuperior aspect of the urinary bladder. (b) Coronal view of the repeat CT scan performed at the end of chemotherapy, showing the urinary bladder nodule has increased from 2cm to 3cm in size

Her case was discussed in the urology cancer meeting and she underwent TURBT under general anaesthesia. A solid lesion of about 3cm was found in the right side of the bladder dome (Figure 3) which correlated with the CT finding. Both ureteric orifices and rest of the bladder mucosa were normal. Macroscopic tumour clearance was achieved and the specimen was sent for histological examination.

Figure 3 .

Endoscopic view of the bladder at the time of transurethral resection of the bladder tumour showing a solid lesion of around 3cm in the in the right side of the bladder dome

Histology report showed moderately differentiated adenocarcinoma of urinary bladder with extensive stromal invasion (Figures 4 and 5). There was no muscle coat in the specimen. The urothelium was intact without any atypical features. The tumour marked with CK7, CK19 and CDX2. It was negative for TTF1, PAX8, CEA, CK20, GATA3, p63, WT1 and 34BE12 (Figure 6). The appearance and immunoprofile were in keeping with a metastasis from the primary gallbladder cancer. The slides of the original gallbladder specimen were also reviewed and the morphology was found to be similar to the urinary bladder tumour, although the bladder tumour lacked the prominent fibrotic stroma of the gallbladder. In this clinical setting, the urinary bladder tumour is best described as a metastasis.

Figure 4 .

Low power image of the urinary bladder tumour showing evidence of adenocarcinoma and inflamed stroma with intact urothelium

Figure 5 .

Moderately differentiated adenocarcinoma of urinary bladder with extensive stromal invasion. The appearance and immunoprofile are in keeping with a metastasis from the primary in the gallbladder; (a) magnification ×100; (b) magnification ×200

Figure 6 .

Image of the GATA3 stain on the bladder which marks urothelial nuclei, as well as some T lymphocytes, brown, but the adenocarcinoma cells are negative.

She subsequently developed metastasis to porta hepatis, resulting in obstructive jaundice, and required a biliary stent. The urinary bladder metastasis also progressed further. She has now been challenged with gemcitabine and carboplatin as second-line palliative chemotherapy. She is still alive two years after initial diagnosis.

Discussion

Adenocarcinoma of gallbladder is an aggressive malignancy which is more common in elderly people.¹ It is at least twice as common in female patients than male. The cancer is generally asymptomatic during initial stage and may be detected incidentally after cholecystectomy. However, most of the patients are diagnosed at advanced stage and thus prognosis is usually poor, with reported five-year survival of around 5%.¹

Our patient was relatively young, in her late forties; although it was diagnosed incidentally after cholecystectomy, the disease was quite advanced with peritoneal metastasis. Gallbladder cancer can spread directly to liver, bile duct, duodenum, pancreas, peritoneum, hepatic flexure of the colon and right kidney.² Lymphatic spread can occur to the adjacent lymph nodes.² It can spread distally through the blood route to liver, lung and bone.² Rare metastases to adrenal glands, spleen, brain, breast, thyroid, heart, uterus and ovaries have also been described.³ However, as far as we are concerned, distant metastasis from gallbladder cancer to urinary bladder has not been reported in the past.

Our patient developed urinary bladder mass around six months after initial diagnosis and subsequent resection revealed metastatic adenocarcinoma of the urinary bladder from the gallbladder primary. The mechanism of metastasis is unclear; but the probable explanation could be spread via the transperitoneal route to urinary bladder serosa with subsequent tumour infiltration in to the bladder wall. Secondary bladder tumours are commonly solitary and 54% of them are located in the bladder neck or trigone.⁴ However, in this case, the metastatic deposit was in the posterosuperior aspect of the urinary bladder.

Gemcitabine and cisplatin combination therapy is generally considered as the first-line chemotherapy in patients with metastatic gallbladder cancer. In a study by Sakamoto and colleagues, 18 patients with unresectable and metastatic biliary tract cancer were treated with gemcitabine and cisplatin combination therapy. The reported response rate was 11.1% and the disease control rate was 66.7%.⁵ However, there are no studies about therapeutic strategies and outcomes of urinary bladder metastases from gallbladder cancer because of its rarity. Tumour debulking through TURBT followed by chemotherapy could provide some benefits. However, overall prognosis seems to be poor.

Conclusion

Very rarely gallbladder cancer can spread to the urinary bladder. Although extremely rare, clinicians should consider the possibility of metastasis to urinary bladder while performing TURBT in a patient with history of gallbladder cancer, and the patient should be counselled appropriately before surgery. Moreover, gallbladder cancer patients should be enquired about haematuria and pelvic imaging should be included in postoperative surveillance.