Index case of synovial metastasis in a patient with transitional cell carcinoma of the bladder

Background

Bladder cancer is the most common malignancy identified in the urinary tract, and approximately 90% of all bladder cancers are histologically transitional cell (urothelial) carcinomas in the western world.1 Squamous cell carcinoma of the bladder is highly prevalent in East Africa and the Middle East, secondary to schistosomiasis infection.2 3 Risk factors for developing the condition include tobacco consumption and occupational carcinogenic exposures. Patients often present with macroscopic haematuria and diagnosis is facilitated by cystoscopy examination as well as transurethral resection of bladder tumour, followed by cytological or histopathological confirmation.4 Transitional cell carcinoma carries substantial morbidity and mortality; and the frequent sites of metastasis reported include lung, liver, bone, peritoneum and lymph nodes.5

Synovial metastasis is a rare entity and the number of cases reported in the literature is scarce. It often has a monoarthritic presentation and approximately 50 cases have been reported to our knowledge, lung cancer being the most common primary malignancy.6–11 We present the first reported case of synovial metastasis of the knee joint in a patient with transitional cell carcinoma of the bladder.

Case presentation

A 67-year-old man was diagnosed with grade 2 T2N0M0 muscle-invasive transitional cell carcinoma of the bladder in January 2014 due to a 1-month history of macroscopic haematuria.

An initial multidisciplinary team (MDT) management plan was made to initiate neoadjuvant chemotherapy, radiotherapy followed by surgery. He received external beam radiotherapy and neoadjuvant chemotherapy with one cycle of a combination of cisplatin and gemcitabine.

His cancer treatment was unfortunately complicated by an ST-elevation myocardial infarction in April 2014 for which he was treated with cardiac stenting to his left-anterior descending artery. He received further radical radiotherapy to his bladder with carbogen and nicotinamide which was completed in July 2014. As a consequence of his cardiac history, he developed severe left ventricular impairment as well as a subsequent left ventricular thrombus, for which he was warfarinised and an elective implanted cardiac defibrillator (ICD) was inserted in July 2015. These comorbidities made him a poor candidate for definitive surgical treatment (salvage cystectomy).

In February 2017, he was found to have a 14 mm left pulmonary nodule which was surgically resected in May 2017. Histopathological findings were consistent with urothelial metastasis. A follow-up positron emission tomography-CT scan in June 2017 showed no active metastatic disease and as per the recommendations of the urology MDT, he was placed on a surveillance cystoscopy programme.

In summary, the patient’s medical history included bladder cancer with lung metastasis, myocardial infarction causing severe left ventricular impairment requiring an ICD and left ventricular thrombus.

His medication history included warfarin 5 mg once daily, lansoprazole 30 mg once daily, aspirin 75 mg once daily, bisoprolol 5 mg once daily, losartan 50 mg once daily, spironolactone 12.5 mg once daily and atorvastatin 40 mg once daily. He had no significant family history and was a previously socially independent and active man who frequently enjoyed playing golf and badminton. He was a non-smoker and had moderate alcohol consumption (<14 units/week).

Investigations

In July 2017, the patient presented to his general practitioner with left knee pain and swelling for 4 months. He described a dull ache and swelling in his left knee with a dragging sensation, waking him up at night on a regular basis.

On gross inspection of the left knee: there was visible unilateral knee joint swelling and left-sided quadriceps wasting (3 cm less in diameter compared with the right quadriceps). There was no evidence of scars, bruising, abnormal patellar position, valgus or varus deformities as well as lateral extension or flexion abnormalities. On palpation, there was tenderness in the suprapatellar region of the left knee associated with a moderate suprapatellar joint effusion elicited by a positive patellar tap test. No tenderness was elicited on palpation of the medial and lateral joint lines, tibial tuberosity or head of the fibula. No masses were palpable in the popliteal fossa and there was no difference in temperature between both knees on gross palpation. There was a reduction in active left knee flexion (120°) due to pain, however, a full range of motion in passive left knee flexion (140°). The active and passive extensions had a full range of motion (180°). Anterior drawer test, posterior drawer test, varus and valgus stress tests were unremarkable. No abnormalities were noted on the examination of the right knee.

A plain radiograph of the left knee was performed (figure 1), which demonstrated no evidence of joint effusion, minor loss of joint space in both the lateral and medial tibiofemoral joints as well as minimal osteophytic lipping.

A CT scan of the left knee was organised for further detailed evaluation (figure 2), which depicted a permeative, granular appearance of the bones at the left knee with erosive changes. This was reported as a non-specific finding for which the differential diagnosis would include a primary bone lymphoma, metastatic deposits or chronic infection. There was also a moderate-sized suprapatellar pouch joint effusion and aspiration of this region was suggested for definitive diagnostic confirmation.

One week later, he had an ultrasound-guided aspiration of his left knee suprapatellar effusion with local anaesthetic (figure 3). A moderate-sized effusion was visualised along with synovial thickening associated with minimal Doppler signals on ultrasound. A total of 40 mL of thick, straw-coloured fluid was aspirated and sent to the laboratory for microscopy, culture and sensitivity, acid-fast bacilli as well as cytological analyses.

Microscopy, culture and acid-fast bacilli analyses were negative and exhibited no growth of organisms. Cytological evaluation of the aspirate showed three-dimensional clusters of atypical epithelial cells, scattered within a haemorrhagic background along with synovial cells. Immunocytochemistry with cytokeratin epithelial markers, including broad spectrum anti-keratin antibody (MNF116) and Cytokeratin 5/6 (CK5/6), highlighted the presence of epithelial cells. By correlating these findings with the clinical history, it was evident that these atypical cells were malignant and had a urothelial origin (figure 4).

Treatment

Treatment aims were to reduce pain and improve function in the affected knee. The patient was treated with palliative external beam radiotherapy to the left knee and received a total of two single doses of 8 Gy radiation therapy. He was also initiated on pembrolizumab (anti-programmed cell death protein-1 (anti-PD-1) monoclonal therapy) at a dose of 200 mg three times per week as an intravenous infusion in view of his metastatic disease. For the treatment of bone pain, he was prescribed zoledronic acid 4 mg infusion three times per week.

Outcome and follow-up

Unfortunately, the patient passed away in January 2018 due to the progression of his disease, approximately 6 months after being diagnosed with synovial metastasis.