Diagnosis and Staging

Collecting duct renal cell carcinoma (RCC) is a very rare type of kidney cancer that occurs in less than 1% of all kidney cancers. Collecting duct tumors are different than other types of kidney cancers in that they are very aggressive and behave more similarly to bladder cancer.

Collecting duct tumors behave similarly to bladder cancer since both the bladder and collecting duct portion of the kidney share the same origin when the organs are formed in the body before birth. It is important that your cancer team works closely with expert pathologists who have experience in rare kidney cancers for accurate diagnosis. 

Collecting duct RCC is frequently diagnosed in younger patients and Black patients as well as men.

Currently, there are no known risk factors for developing collecting duct RCC.

Collecting duct RCC has many genetic mutations including genes such as NF2 and CDKN2A, which when mutated can lead to uncontrolled cell growth.

Due to the aggressive nature, collecting duct RCC can commonly spread to the lungs, liver, and bone.

The treatment of collecting duct RCC is largely different than clear cell RCC. Since the tumor behaves more similarly to bladder cancer, collecting duct tumors are treated similarly to bladder cancer with combination chemotherapy given IV. In contrast, clear cell RCC is typically treated with immunotherapy and/or pills  (VEGF inhibitors) that block the formation of blood vessels that nourish cancer cells. However, there is some data that collecting duct RCC may also respond to VEGF inhibitors as well.

Since collecting duct RCC is a very rare cancer, we do not have a lot of data on what is the best treatment approach. Also, these tumors have not received a lot of research focus in the past. Clinical trials represent a wonderful opportunity to help find new and better therapies for patients with collecting duct RCC and other rare kidney cancers. Participation in clinical trials for patients with rare kidney cancers is highly recommended. You can find a clinical trial using the KCA’s Clinical Trial Finder.

Renal medullary carcinoma (RMC) is a kidney cancer that was first described in 1995. RMC grows very fast and behaves very differently from the other kidney cancer subtypes. In the original study, half of the people diagnosed lived less than four months. Today, treatments have improved, and people can live about 18 months on average while up to 10% may be cured. Researchers are still working on better treatments.

The patient population affected by RMC is different than the typical kidney cancer patient. RMC mostly affects young Black people who have sickle cell trait, sickle cell disease, or other blood conditions that cause red blood cells to become sickle-shaped. About 1 in 14 African Americans have sickle cell trait, and only 1 in every 20,000 to 1 in 39,000 of individuals with the sickle cell trait will develop RMC. Overall, about 300 million people around the world have sickle cell trait. The number of people with this trait can vary from 7% in African Americans, 23.5% in some parts of Greece, 10% in parts of Turkey, up to 13% in central India, 20% in eastern Saudi Arabia, and 10%-40% across equatorial Africa. Among the Baamba tribe in Uganda, it can be as high as 45%. Most reports of RMC come from the United States or Europe. This may be because doctors in other places do not always recognize RMC, or because there are certain environmental or regional factors that could increase RMC risk in the United States and Europe. It is more common in men than in women, and about 70% of these tumors start in the right kidney. RMC is the third most common type of kidney cancer in children and young adults. Around half of people with RMC are 28 years old or younger, with some as young as 9. It is less common for people to be 35 or older when they get RMC.

The red blood cells of people with sickle cell disease turn into a sickle shape all over the body, causing many health problems that are not related to RMC. But for people with sickle cell trait, their red blood cells only become sickle-shaped in certain places, like in a part of the kidney called the “renal medulla.” When this happens, the red blood cells become sticky, stiff, and may block blood flow in the renal medulla. Scientists think this can sometimes damage a gene called INI1 (also known as SMARCB1) in kidney cells, which can lead to RMC. In rare cases, people who do not have any sickle cell conditions can also lose INI1 in the renal medulla, causing a type of RMC called “renal cell carcinoma, unclassified with medullary phenotype” (RCCU-MP).

Aside from having a sickle hemoglobinopathy, there are no known family or environmental risk factors that explain why some people get RMC and others do not. There is also no evidence that family members of someone with RMC have a higher chance of getting it. People with sickle hemoglobinopathies should pay close attention to possible RMC symptoms and see a doctor right away if they notice any. However, there is currently no known way to prevent RMC or test for it in people who do not have symptoms.

RMC is the only kidney cancer associated with sickle cell trait, sickle cell disease, or other blood conditions that cause red blood cells to become sickle-shaped. Even though all sickle blood conditions raise the risk of RMC, most people with RMC have sickle cell trait. Only a few have sickle cell disease or other sickle cell disorders like hemoglobin SC disease or sickle beta thalassemia. This could be because sickle cell trait is much more common than other sickle cell conditions. Pure thalassemias, such as alpha or beta thalassemia, are not linked to RMC. Early studies in people and animals suggest that high-intensity physical exercise in those with sickle cell trait may harm the kidneys and increase the risk of RMC.

All RMC tumors do not have a protein called INI1, also known as SMARCB1, hSNF5, or BAF47. This protein is often missing in other rare cancers, such as malignant rhabdoid tumors (MRT), atypical teratoid rhabdoid tumors (ATRT), and epithelioid sarcomas. INI1 normally acts as a “tumor suppressor,” meaning it helps protect cells from turning into cancer.

RMC most commonly spreads to the lymph nodes in more than 80% of cases. Other areas of the body RMC can spread to include the lungs (67% of cases), liver (27% of cases), and bone (25% of cases).

RMC is often treated with chemotherapy. Many treatments used for other kidney cancers do not work well against RMC. Many of the therapies developed for the most common kidney cancer, known as clear cell kidney cancer, do not work at all against RMC.  If a CT, MRI, or PET images show that RMC is only in the kidney and has not spread, doctors might remove the whole kidney and the cancer inside it. If the tumor is large (bigger than 4 cm), doctors may give chemotherapy first to shrink it and then do surgery later—even if the scans do not show any spread. This is because CT and MRI are not perfect and might miss very small tumors in the lymph nodes or other organs. Chemotherapy can help treat those tiny tumors before they grow. Other treatments might include radiation or other special therapies.

Exercise is good for your health, whether you have RMC or not, and even if you have sickle cell trait, sickle cell disease, or another hemoglobinopathy. Animal studies show that doing moderate-intensity exercise may lower the risk of RMC when compared to not exercising at all. However, some early studies suggest that doing long, very hard workouts may harm the kidneys of people with sickle cell trait and raise the risk of RMC. So, exercising at a moderate level may help everyone, but pushing yourself too hard might be harmful. This matches the advice from the Centers for Disease Control and Prevention about safe exercise for people with sickle cell trait. Following this advice helps athletes stay safe and get the benefits of exercise.

Moderate-intensity exercise is when your heart rate is between 50% and 70% of your maximum heart rate. To figure out your maximum heart rate, subtract your age from 220. For example, if you are 40, then your maximum heart rate is 180 beats per minute. During moderate-intensity exercise, your breathing speeds up, but you are not out of breath. You might start sweating after 5 to 10 minutes, and you can still talk but not sing.

High-intensity exercise is when your heart rate is 80% or more of your maximum. During high-intensity exercise, you breathe deeply and quickly, start sweating within a few minutes, and can only say a few words before you need to take a breath.

Exercise is not banned for people with sickle cell trait if it is done safely. Athletes and military recruits with sickle cell trait follow simple rules to avoid problems and do well without developing any issues. These rules include staying hydrated by drinking enough water, avoiding a lot of caffeine or stimulants, and not doing many hard, timed drills without enough rest—especially during the first two weeks of a new training session. You should also slow down if you are sick, rest between “sprints” or tough drills, and make sure to take breaks and drink fluids often.

The term unclassified RCC is used when the cancer does not fit into any of the other major renal cancer subtypes.  We are generally seeing that tumors with an unclassified designation behave more aggressively than typical clear cell or papillary renal cancers. 

In some studies, there is a higher percentage of females and African American patients with unclassified RCC when compared to “typical” renal cell carcinoma patients.

At this point we do not know of any specific risk factors, although, as mentioned above, there may be a higher risk of developing unclassified renal cell cancers in the African American population.

Several studies show that there is a higher incidence of NF2, SETD2, TP53, BAP1, KMT2C and MTOR mutations in unclassified renal cell carcinoma.

Unclassified RCC metastases are most common in the lung, lymph nodes, liver, and bone.

At this point in time, the recommended treatment for tumors with unclassified RCC would be a combination of a blood-vessel targeting agent, also referred to as a TKI, plus an immune stimulating agent.   

As we gain more knowledge about the different subtypes of renal cell carcinoma, the “unclassified” subtype will become less common.  Our goal is to be able to properly classify all renal cell carcinomas into groups where we have specific therapies.  We hope this category will eventually cease to exist!