Renal Cell Carcinoma

Introduction

Renal cell carcinoma is the most common malignancy of the kidneys. The classic presentation is with the triad of haematuria, or blood in the urine, a palpable mass and flank pain
Advanced cancer characteristically extends into the lumen of the renal vein and into the inferior vena cava. This is known as ‘tumour thrombus’ which may cause a variety of strange symptoms including a varicocele.

Patient: Mr. John Smith

Age: 65

Sex: Male

Presenting Complaint:

Mr. Smith presents to the emergency department complaining of severe, tearing abdominal pain radiating to his lower back. He describes the pain as sudden in onset and progressively worsening over the past few hours. He denies any recent trauma but reports a history of hypertension and smoking for the past 30 years.

Clinical Assessment:

Upon examination, Mr. Smith appears pale and diaphoretic. His blood pressure is 160/100 mmHg, heart rate is 110 beats per minute, and respiratory rate is 22 breaths per minute. Abdominal examination reveals a pulsatile mass in the periumbilical region with tenderness on palpation. There are no signs of peritoneal irritation.

Diagnostic Workup:

Given the presentation suggestive of an abdominal aortic aneurysm, Mr. Smith undergoes urgent diagnostic imaging. A bedside ultrasound confirms the presence of a large abdominal aortic aneurysm measuring approximately 7 cm in diameter. Further imaging with a computed tomography (CT) scan of the abdomen confirms the diagnosis and provides detailed information about the extent and location of the aneurysm.

Its pathogenesis is mainly sporadic but there are rare familial forms, such as von Hippel–Lindau syndrome. Key risk factors include smoking, male sex, age over 55 years, obesity, hypertension, and hereditary familial syndromes.

Renal cell carcinoma can be classified into three main types: clear cell, papillary and chromophobe. Clear cell carcinoma is the most common form, accounting for 80% of cancers and originates in renal tubules. It is often associated with haemorrhage or necrosis. Papillary account for 10% of cancers. They are more commonly bilateral and have a better prognosis than clear cell carcinomas. Finally, chromophobe tumours account for 5% of cases and usually have a relatively indolent disease course.

Blood tests can help assess renal function, like UEC’s, assess prognosis, like lactate dehydrogenase and calcium levels, and detect paraneoplastic syndromes by checking haemoglobin in full blood counts.

Imaging can include ultrasound which can reliably distinguish simple benign cysts from solid masses most likely to be tumours and can demonstrate tumour thrombus in the inferior vena cava.

CT or MRI can be used to stage the disease by assessing invasion of perinephric tissues and by demonstrating regional lymph node involvement or metastases.

For biopsies, if imaging demonstrates a malignant renal mass with no metastatic disease evident, biopsy is not routinely indicated. On the other hand, if metastatic disease is found, biopsy of the most accessible metastatic lesion is performed to make the diagnosis.

The management of renal cell carcinoma is again dependent on the extent of disease. In general, surgery is the cornerstone for localised disease and may achieve cure. When possible, partial nephrectomy is preferred as it can facilitate preservation of as much renal function as possible. Three options for surgery techniques include open, laparoscopic or robotic-assisted laparoscopic nephrectomy.

For small renal masses or in older patients, less invasive options include active surveillance, cryotherapy, in which cell destruction is achieved by local freezing and radiofrequency ablation, which causes tumour death by coagulation from high-frequency current.

Therapeutic options for metastatic carcinoma include immunotherapy, using bevacizumab and interferon-α, and tyrosine kinase inhibitors, like sunitinib and radiotherapy which has a role in treating bone or brain metastases.

Interestingly, Chemotherapy has shown little efficacy in metastatic RCC probably due to the expression of the multidrug resistance protein 1 by tumour cells.

The clinical features of renal cell carcinoma are dependent on the extent of the disease, with ½ the number of cases being detected incidentally in asymptomatic patients. The classic triad of haematuria, flank pain, and abdominal mass is uncommon and indicative of aggressive advanced disease. Similarly, presentations with symptoms of metastatic disease such as respiratory symptoms or bone pain is rare.

Around 25% of RCCs will develop paraneoplastic syndromes. These are a group of disorders that occur when a cancer produces hormones itself or causes the production of antibodies that can act like hormones in an abnormal response to the cancer. One common example in RCC is polycythaemia, or lots of red blood cells, which is mediated by inappropriate erythropoietin production from the cancer. This can cause lots of clotting and erythromelalgia, which can make your hands pink with a burning sensation. Hypertension can also be caused by a similar mechanism where too much renin is produced.

As mentioned before advanced cases can cause a Tumour thrombus as they characteristically extend into the lumen of the renal vein. This can cause impairment and backup of the venous drainage of the pampiniform plexus in the spermatic cord, causing a varicocele. These are classically described as having the appearance of a bag of worms.

To remember some important facts, I think about renal cell carcinoma as a coloured disease. My mnemonic is that clear cells give you wine coloured wee, pink palms, and blue balls. This reminds me that clear cell carcinomas are the most common type, the tumour can cause haematuria, making your urine red, paraneoplastic syndromes can induce polycythaemia which can make your hands pink from erythromelalgia, finally, tumour invasion into the renal vein can cause a varicocele, giving the scrotum a bag of blue worms appearance.