AssessmentsRenal cell carcinoma
Renal cell carcinoma
USMLE® Step 1 style questions USMLE
USMLE® Step 2 style questions USMLE
A 19-year-old woman comes to the office because of a constant headache and decreased eyesight for 3 weeks. She also describes feeling weaker than normal, and difficulty walking. Family history includes renal cell carcinoma. Examination shows a wide-based, slow gait and decreased visual acuity. Fundoscopy shows a right sided retinal detachment. MRI is shown below. Which of the following is the most likely diagnosis?
Content Reviewers:Rishi Desai, MD, MPH
Renal cell carcinomas (or RCC’s) are the most common type of malignant kidney cancer in adults, generally affecting older men.
Unfortunately, RCC is often considered a “silent” cancer because symptoms don’t typically get noticed until the tumor has grown pretty large.
Renal cell carcinomas form from epithelial cells in the proximal convoluted tubule of the kidney; this is the section of the nephron that is usually located in the renal cortex—the outer rim of the kidney.
The most common type of renal cell carcinoma is composed of polygonal epithelial cells, which have funny angular shapes with at least four sides and are filled with clear cytoplasm full of carbohydrates and lipids. It’s those lipids that give the tumors their yellow color.
At a genetic level, renal cell carcinomas have been linked to mutations on the short arm of chromosome 3, or 3p. An easy way to remember this is that RCC has three letters and it’s linked to chromosome 3.
One of the main genes involved in renal cell carcinomas is the VHL gene, which codes for the von Hippel-Lindau tumor suppressor protein, or pVHL which is normally expressed in all tissues.
Mutations in pVHL can allow IGF-1, the type 1 insulin-like growth factor, pathway to go into overdrive. This does two things.
First, there is dysregulated cell growth, and second it upregulates specific transcription factors called hypoxia-inducible factors, which in turn help generate more vascular endothelial growth factor or VEGF, as well as VEGF receptor, leading to growth of new blood vessels, or angiogenesis. Dysregulated cellular growth and angiogenesis are a recipe for tumor formation.
Renal cell carcinomas can arise sporadically or they can be a part of an inherited syndrome. Sporadic tumors are usually solitary tumors in the upper pole of the kidney, and most often happen among older men that smoke cigarettes.
Inherited syndromes, like von Hippel-Lindau disease, can also give rise to renal cell carcinomas, and in this situation the tumors typically affect younger men and women and often involve both kidneys.
Von Hippel Lindau disease is a rare autosomal dominant disorder characterized by a mutation in a tumor suppressor gene which leads to the formation of cysts and benign tumors in various parts of the body like the eye and central nervous system.
The number one cause of death in patients with von Hippel-Lindau disease, though, is the development of renal cell carcinomas.
Individuals with renal cell carcinoma typically have one or more of the following symptoms: hematuria, or red blood cells in the urine, which is most common, a palpable mass in the abdomen or lower back, and pain in the flank or near the hip bone.
Since the cancer causes a state of chronic inflammation, other classic symptoms include fever and weight loss.
Renal cell carcinoma is also frequently responsible for causing various paraneoplastic syndromes, which is where the tumor cells generate a hormone that causes it’s own set of symptoms.
For example, these tumors can release the hormone erythropoietin which increases the production of new red blood cells, and this can lead to polycythemia or too many red blood cells, which can cause the blood to start sludging or slow down its normal flow.