Late onset metastasis from renal cell carcinoma masquerading as a gallbladder polyp

Abstract

Renal cell carcinoma (RCC) accounts for approximately 3% of all adult malignancies. A third of people with RCC have metastatic lesions when diagnosed, and another third develop metachronous metastasis during follow-up or after surgical treatment. We report a case of gallbladder metastasis from clear-cell RCC in a 71-year-old woman 13 years after RCC of her right kidney. Preoperative imaging studies showed a suspicious, progressively enlarged gallbladder polyp. The patient underwent open cholecystectomy and lymph node dissection along the hepatoduodenal ligament. The pathology report was compatible with metastatic disease from the kidney that was previously resected. Gallbladder metastasis can occur from RCC several years after initial management. Physicians should be aware of this rare pathology, and intensive follow-up is essential after surgery for RCC.

Introduction

Renal cell carcinoma (RCC) accounts for approximately 3% of all adult malignancies. The highest incidence is in western countries.¹ RCC accounts for 90% of all kidney malignancies, and the clear-cell type represents about 70% of all RCC.² A third of people with RCC have metastatic lesions when diagnosed, and another third develop metachronous metastasis during follow-up or after surgical treatment. The most common metastatic sites are the lungs, liver, brain, adrenal glands and lymph nodes.³ Gallbladder and cystic duct metastases have also been reported.

We report a case of gallbladder metastasis from clear-cell RCC in a 71-year-old woman 13 years following RCC of her right kidney.

Case history

A 71-year-old woman was referred to our department with a progressively enlarged gallbladder mass (0.3–1.8cm) found 6 months earlier on her annual ultrasound check-up (Fig 1). She underwent right nephrectomy for a pT2 RCC in 2006 and abdominoperineal resection for a pT3N0 low rectal adenocarcinoma in 2008. Clinical examination did not reveal any pathological findings. Laboratory examinations were all within normal values.

Figure 1.

Abdominal ultrasound revealed a 1.8cm gallbladder polypoid-like lesion

We ordered upper abdominal magnetic resonance imaging and magnetic resonance cholangiopancreatography. A solid gallbladder polyp (maximum diameter 2.4cm) was identified. Post-gadolinium images demonstrated enhancement of the mass, with high suspicion for malignancy (Fig 2). No pathological nodes were noticed.

Figure 2.

Upper abdominal magnetic resonance imaging revealed a solid gallbladder polyp 2.4cm in maximum diameter

The patient was offered exploratory laparotomy. Open cholecystectomy was carried out and intraoperative frozen section of the specimen was ordered. Frozen section examination pointed towards the malignant nature of the tumour, and hence excision of the liver bed. Following this, lymphadenectomy of the hepatoduodenal ligament was performed. The postoperative course was uneventful, and the patient was discharged in good condition five days later.

Pathological assessment of the specimen showed the polypoid tumour consisted of neoplastic tissue with extensive ulceration and necrosis. The neoplastic cells were large, with abundant clear cytoplasm and small, hyperchromatic nuclei. They were arranged in nests and islets, with no invasion of the cyst wall (Fig 3). The neoplastic cells were positive for CD10 (Fig 4), CAIX (Fig 5) and PAX8 (Fig 6), with no expression of CK, inhibin, HMB45 or napsin. These findings were compatible with clear-cell RCC. Resection margins of the specimen were negative, and all the extracted lymph nodes were negative for metastasis. Taking into account the patient’s medical history, it was obvious that this gallbladder polypoid mass was metastatic disease arising from RCC.

Figure 3.

Solid nests of large, clear neoplastic cells (H+E, ×100)

Figure 4.

Membrane staining for CD10 in neoplastic cells (×200)

Figure 5.

Intense membrane staining for CAIX in neoplastic cells (×100)

Figure 6.

Neoplastic cells with intense nuclear staining for PAX8 (×100)

The woman remains in good overall condition, with no signs of recurrence six months postoperatively.

Discussion

RCC is one of the most lethal tumours of the urological system. It has a 1.5:1 predominance in men over women and an increasing prevalence due to several factors, such as smoking, obesity, hypertension and having a first-degree relative with RCC.¹ RCC has a highly metastatic rate that reaches one-third of patients at the time of diagnosis.⁴ The behaviour of metastatic RCC is often unpredictable. The rich vascular proliferation noticed in RCC is thought to be the reason for the multiple synchronous or metachronous metastatic lesion sites that have been reported, which are (by frequency) the lungs, liver, brain, adrenal glands and lymph nodes.³ Most patients appear with a metastatic lesion in the first examination. The 5-year survival reaches up to 59% in the published literature. Disease-free interval and single-site metastasis are prognosis factors.⁴

Gallbladder tumours are usually adenocarcinomas with a polypoid mass appearance. Metastases are rare; the main cause is malignant melanoma, followed by carcinomas of the digestive system, such as stomach tumours.⁵ The gallbladder is not among the usual sites of RCC metastasis: fewer than 65 relevant cases have been reported, and it is present in less than 0.6% of autopsies.⁴ Metastasis often occurs metachronously, with a median interval of four years after nephrectomy.³ The development of RCC metastasis is thought to be via the invaded blood vessels, by systemic dissemination of the disease rather than contiguity, as its occurrence happens late.⁵

Patients are usually asymptomatic. Diagnosis is usually made accidentally at follow-up imaging. In clinical examination, the symptoms noticed are abdominal pain, nausea, vomiting, and signs of acute cholecystitis and pancreatitis. Rarely, other clinical features are found from the physical examination.⁵

Computed tomography is the radiological method most commonly used for diagnosis, staging and planning the therapeutic strategy. The challenge is to differentiate the primary gallbladder carcinoma from the RCC metastasis. In this case, a combination of biopsy and immunohistochemistry methods are needed. Endoscopic ultrasonography may reveal a well-circumscribed, oval, low-echoic mass suggesting the presence of a tumour in the gallbladder. Biopsy using a peroral cholangioscope can be attempted to establish a pathological diagnosis. Use of endoscopic ultrasonography-guided fine-needle aspiration remains controversial, due to the risk of bile leakage and tumour bleeding and seeding.² Histopathological findings may demonstrate a solid metastatic tumour of clear-cell RCC in the gallbladder, with alveolar architecture of cells with a clear or eosinophilic cytoplasm, separated by a delicate branching network of vascular tissue. A normal epithelium may remain in some parts of the tumour surface.² Immunohistochemistry is essential to confirm the diagnosis, as increased levels of CEA and CK7, moderate CK10 levels, and high vimentin levels are found in gallbladder metastases.⁵

Surgical treatment is required for the management of gallbladder metastasis from RCC. An R0 resection cholecystectomy can be performed as the metastasis is generally developed within the gallbladder mucosa. From the published literature, it is well established that more than half of patients are alive with no evidence of recurrent disease after cholecystectomy, despite the short follow-up period.⁴ Adjuvant therapies following cholecystectomy, including chemotherapy, radiotherapy and immunotherapy, have been proposed, but there is no consensus regarding their roles.

Conclusions

Gallbladder metastasis can occur from RCC years after initial management. In most cases, diagnosis is made accidentally during follow-up examination, with imaging studies showing a polypoid-like gallbladder mass. Preoperative biopsy and immunohistochemistry methods can be useful to confirm the diagnosis. Surgical treatment is indicated for the treatment of gallbladder metastasis with R0 resection cholecystectomy, as the metastasis is generally developed within the gallbladder mucosa. The role of adjuvant therapies remains debatable. Physicians should be aware of this rare pathology, and intensive follow-up is essential after surgery for RCC. Further studies are needed to better elucidate our results.