Metastatic urothelial carcinoma presenting as acute cholecystitis.

Metastatic involvement of the gallbladder is uncommon. We report a case of an 84-year-old male who presented with acute cholecystitis secondary to metastatic urothelial carcinoma (UC). An 84-year-old man presented with right upper quadrant pain and a positive Murphy's sign on the background of known metastatic UC. He was diagnosed with acute cholecystitis and underwent laparoscopic cholecystectomy. His postoperative period was complicated by a cardiac event, and he died 2 days later. Histology of the gallbladder revealed extensive infiltration by nested malignant epithelioid proliferation, consistent with UC. This case demonstrates that although uncommon, UC may metastasize to unusual sites, including the gallbladder. This serves as a reminder for surgeons to consider metastatic disease as a cause for acute cholecystitis.

INTRODUCTION

Urothelial carcinoma (UC) is one of the common cancers in Australia, affecting about 1 in 70 people over the age of 85.[1] In 2017, an estimated 2995 new cases of bladder cancer were diagnosed in Australia and approximately 1172 of deaths will be attributed to bladder cancer.[2] Metastatic disease to the gallbladder is an uncommon occurrence, and patients rarely present with symptoms to the emergency department.[3] While the common sites of metastases of UC have been well-outlined in contemporary literature,[4] rare sites of metastatic deposits have been reported scarcely.[3567] To date, only one case of metastatic UC mimicking acute surgical issues have been reported.[35] Our case report is the second in the world.

CASE REPORT

An 84-year-old male was diagnosed with pT3N2M0 UC in 2014, with primary in the renal pelvis with associated para-aortic lymphadenopathy. His medical history was significant for atrial fibrillation requiring rivaroxaban, sick sinus syndrome requiring a permanent pacemaker, hypertension, dyslipidemia, benign prostate hyperplasia, vertigo, diverticulosis, and glaucoma.

A few months following the diagnosis of UC, the patient underwent left nephroureterectomy and retroperitoneal lymph node dissection of which 20/20 lymph nodes were positive. Repeated resection for local recurrence in November 2014 showed noninvasive high-grade papillary UC. He subsequently completed a course of adjuvant carboplatin and gemcitabine therapy in 2015. A repeat staging computerized tomography (CT) in May 2016 revealed stable disease with no further metastasis. He underwent a surveillance cystoscopy in June 2016, which revealed vesical carcinoma in situ, and he was commenced on intravesical mitomycin postresection. Further surveillance CT in October 2016 showed new and progressive lytic lesions in his cervical and thoracic vertebrae, and he underwent palliative radiotherapy and additional four cycles of carboplatin/gemcitabine. Restaging CT post-chemotherapy revealed stable disease in February 2017; however, there was progressive disease on surveillance scans in August with enlargement of vertebral sclerotic deposits. Fortunately, he was asymptomatic from his disease progression.

In September 2017, he presented to the emergency department with intermittent right upper quadrant pain for the last 6 weeks, associated with lethargy, anorexia, and malaise. He was hemodynamically stable and afebrile. Physical examination revealed signs of cholecystitis. Biochemically, his liver function test was deranged and obstructive (ALP: 439 U/L, GGT: 436 U/L, AST: 64 U/L, ALT: 36 U/L, bilirubin: 24 umol/L). Ultrasonographic assessment revealed thickened gallbladder wall (5.3 mm) and multiple mobile stones. The common bile duct diameter was 7.7 mm and he was probe tender. He was admitted and treated with broad-spectrum antibiotics.

After failing to improve on intravenous antibiotics, a decision was made to perform a laparoscopic cholecystectomy. Intraoperative findings noted significant free fluid in the upper abdomen as well as an inflamed gallbladder. Operative cholangiogram was attempted but could not be performed due to a narrow cystic duct. A Jackson–Pratt drain was left in the subhepatic space.

On postoperative day 1, 700 ml of bile-stained fluid was observed in the drain tube. It was hypothesized that he had a probable cystic duct leak. A few hours later, he had a cardiac arrest and received approximately 20 min of cardiopulmonary resuscitation with three cardioversions as along with 2 mg of IV adrenaline and 300 mg IV amiodarone. Electrocardiogram (ECG) showed a new left bundle branch block, suggestive of acute myocardial infarction. After discussion with his family and given the clinic and premorbid context, support was withdrawn and he died a short while after.

On histopathology, the gallbladder specimen measured 60 mm × 40 mm × 20 mm and contained multiple black gall stones. Mild thickening of the wall was noted; however, no discrete lesions were seen macroscopically. Microscopic examination revealed extensive infiltration by a nested malignant epithelioid proliferation [Figure 1]. There was widespread lymphatic and vascular involvement present in both small and large vessels, many of which were plugged by the tumor [Figure 2]. The tumor extended through the full thickness of the wall [Figure 3]. On cytological examination, the peritoneal fluid was positive for malignancy.

Figure 1

Reactive gallbladder mucosa at the bottom of photograph. At the top of the photograph, nests and sheets of invasive urothelial carcinoma with comedo necrosis can be seen within the muscularis (H and E, ×40)

Figure 2

Nests of tumor in lymphatics (H and E, ×200)

Figure 3

Reactive gallbladder epithelium at the bottom left of photograph with nests of infiltrative urothelial carcinoma, extending into the gallbladder epithelium (H and E, ×200)

DISCUSSION

Diagnosis of bladder cancer is associated with a predicted expected relative 5-year survival rate of 53.5% in the general population; 55.5% in men and 46.1% in women.[1]

Bladder cancer rarely metastasizes to distant sites but has been documented in 4% of patients.[3] Most commonly, bladder cancers metastasize to lymph nodes, bone, lung, liver, and peritoneum.[5] Distant metastases of UC to the biliary tree are extremely uncommon and have only been reported twice in literature.[46] Other more common carcinomas that have the propensity to metastasize to the biliary tree include melanoma, renal cell carcinoma, and breast cancers.[5] Even so, metastases to the gallbladder are often asymptomatic and only detected at autopsy. When symptomatic, it may be associated with right upper quadrant pain mimicking acute cholecystitis and deranged liver function tests.

This case demonstrates that although uncommon, UC may metastasize to unusual sites including the gallbladder. In this setting, despite the prolonged prodrome, patients can still present with symptoms mimicking that of acute cholecystitis.

Comparing the two other known cases of metastatic disease mimicking acute cholecystitis, Ogu et al.[6] described a similar case in a patient with metastatic UC masquerading as acute cholecystitis. In the case described by Ogu et al., the patient had an acute presentation, i.e., 3–4 days, and underwent an uncomplicated laparoscopic cholecystectomy, which he fully recovered from. The other published case of metastatic disease mimicking acute cholecystitis was reported by Hong et al.,[7] which details the clinical course of a patient with recurrence of choledochal cyst presenting as acute cholecystitis. In that case, the patient underwent a pylorus sparring pancreaticoduodenectomy and made a full recovery.[7]

CONCLUSION

The case presented above is unique due to the rarity of mention in literature. A literature review revealed only two cases that included metastatic UC as the cause of acute surgical issues in the biliary tree. The symptomatology that mimicked acute cholecystitis with associated obstructive picture on liver function tests itself adds to the rare clinical picture.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.