What Is Renal Medullary Carcinoma?

Overview

Renal medullary carcinoma, also referred to as RMC, is a rare cancer of the kidney. It predominantly affects young people of African ethnicity who have sickle cell disease, carry the sickle cell trait, or other sickle haemoglobinopathies¹ (other inherited disorders that result in the abnormal production or structure of the haemoglobin, also known as red blood cells)²

RMC is a devastating condition both for the affected individuals as well as for their families. Therefore, to better understand this disorder, this article will encompass a thorough explanation of RMC, providing information and sources of support for those affected.

The kidney

Before delving into the details of renal medullary carcinoma, it is essential to understand the basic anatomy and function of the kidney.

The kidneys are two-bean-shaped organs situated just below the ribcage on either side of the spine. Their function is to filter the blood, removing emoving waste materials and excess water producing  urine.³

The kidney is comprised of two main regions: the renal cortex, which is the outer layer, and the renal medulla, which is the inner part and where RMC originates.⁴

Background of Renal Medullary Carcinoma

Originally described in 1995, renal medullary carcinoma is one of the most aggressive kidney cancers. 

Although there is no current exact and unanimous understanding and explanation as to why RMC develops, it is evident that almost all patients have a blood disorder that causes the red blood cells to change shape from round discs to sickle shapes. Other than this trait (sickle haemoglobinopathy), there is no known other genetic predisposition that explains the incidence of RMC. There is no current evidence that suggests that family members of RMC-affected individuals also have an increased risk of developing the condition, meaning that it is unlikely to be  hereditary.

As a result of the ambiguity surrounding renal medullary carcinoma, at the moment, there are no known effective strategies to screen for RMC in asymptomatic individuals. However, whatis known is that all RMC tumours lack a protein called INI1, also commonly known as SMARCB1, hSNF5 or BAF47. The protein INI1 acts as a tumour suppressor, which typically protects cells from becoming cancerous.

Moreover, as red blood cells have a sickle shape they become sticky, rigid and prone to blocking the blood supply of the renal medulla. Due to this process, it is believed that it may provoke the damage of the INI1 gene within the renal medulla, leading to the subsequent development of renal medullary carcinoma. However, occasionally, the INI1 gene may be lost in the renal medullary cells even if the individual does not have any sickle haemoglobinopathies. This is known as a subtype of RMC provisionally called renal cell carcinoma unclassified with the medullary phenotype (RCCU-MP).¹

In addition, other than the risk posed by having sickle haemoglobinopathies for the development of this condition, in light of recent evidence, it is also suggested that high-intensity exercise may be associated with RMC in individuals with sickle cells.⁵ This is because high-intensity exercise can cause dehydration, low oxygenation and overheating that occasionally lead to serious complications in people with sickle cell trait, including damaging the kidneys in ways that may increase the risk for RMC.

Symptoms and early signs

With a mean age of presentation being around 20 years, with an age range between 11 and 39 (6), the most common symptom of renal medullary carcinoma is blood in the urine (haematuria). It is also frequent for individuals to experience pain in their flank (area between the hips and the ribcage) around the kidney area. Furthermore, although less common, individuals may also feel a lump or fullness in their abdomen, typically on the right side. Other common symptoms include unintentional weight loss,  fevers and night sweats.¹ Due to the aggressive nature of RMC, some people have signs of metastatic disease when they are diagnosed that cancer cells have spread to other parts of the body, such as the lungs or bones.⁷

Diagnosis

Early diagnosis and treatment provide the best chance for affected individuals, but as RMC does not cause symptoms until it is advanced, early diagnosis and treatment are difficult to provide.

To diagnose RMC, a combination of medical tests and techniques are used; these include:

• Ultrasound: for individuals with sickle cell trait or other sickle haemoglobinopathies who develop signs or symptoms such as blood in the urine. During the ultrasound, a mass can sometimes be seen in the kidney. Computing tomography (CT) scan or magnetic resonance imaging (MRI): More detailed images of a kidney mass, which helps doctors who may need to perform a biopsy of the mass.
• Biopsy: The method to obtain a biopsy involves the use of a needle that is passed through the skin to take a tiny sample of tumor tissue. The biopsy of the kidney tissue or other areas where the cancer may have spread is then looked at under the microscope to confirm the diagnosis.
• Immunohistology: This method will assess the tissue for the presence or absence of INI1, a tumour suppressor protein that normally protects cells from turning into cancerous ones, commonly absent in rare cancers such as renal medullary carcinoma.

Treatment options 

To provide treatment for renal medullary carcinoma, a team of specialists is required to work collaboratively to address all the symptoms. This may include:

• Oncologists who are cancer-treating doctors; 
• Urologists who are doctors who conduct surgery on  the kidneys;
• Radiation oncologists who are specialists that use ionizing radiation to treat cancer;
• Interventional radiologists who use minimally invasive, image-guided techniques  to diagnose and treat cancer;
• Psychosocial support for the affected individual and their families
• Other healthcare professionals.

Regarding the therapeutic procedures and interventions, these may vary depending on factors such as disease stage, the size of the tumour, the presence or absence of certain symptoms, whether the disease has spread (metastasized) to other areas of the body, the individual’s age, and general health. Decisions concerning the use of surgery, radiation, and specific drug treatments should be made by physicians taking into consideration the individual characteristics of the patient. The most common course of treatment for RMC is chemotherapy unless the cancer is solely located in the kidney and surgical removal is possible. In addition, a recent study suggested that surgical and oncological management may include cisplatin-based chemotherapy, followed by nephrectomy (surgery to remove the kidney) with retroperitoneal lymphadenectomy (removing lymph nodes at the back of the abdomen and continued adjuvant chemotherapy. This has been shown to result in survival of 37 months,⁸ 24 more months,¹ than the other treatments currently available. However,  this treatment is still in clinical trials. However, it provides an optimistic outlook for future treatments. Ongoing research is developing new treatments to improve the prognosis for people with RMC.

Prognosis 

Renal medullary carcinoma has an extremely poor prognosis, with a mean survival time of less than a year. Unfortunately, neither chemotherapy nor radiation therapy has been found to be particularly efficacious.⁹

However, researchers are continuously investigating RMC to discover new information to improve our understanding and to develop new treatments to improve the prognosis of the affected individuals.

Conclusion

In conclusion, renal medullary carcinoma is a rare and devastating kidney cancer that primarily affects young individuals of African descent who carry sickle cell traits or other sickle hemoglobinopathies. Understanding the basics of RMC, from its causes and symptoms to diagnosis and treatment, can make a significant difference in the lives of those affected. By increasing awareness and understanding of this rare cancer, we can contribute to a more compassionate and informed approach to supporting those affected by RMC and working toward a brighter future.

Nevertheless, despite ongoing research and promising developments, the prognosis for RMC remains grim, with a mean survival time of less than a year due to the aggressive nature of the cancer and the difficulty in finding effective treatments. However, the medical community continues to explore new avenues for understanding RMC and developing improved treatments to offer hope and better quality of life to those affected. 

FAQs

What is stage 4 renal medullary carcinoma?

Stage 4 renal cell carcinoma is a form of aggressive kidney cancer where the cancer cells have spread beyond the kidneys into other organs and tissues in the body.¹⁰

How long does it take for renal cell carcinoma to spread?

This is widely variable, but if left untreated RMC can quickly spread to the lymph nodes or other organs, even in those patients who initially have RMC contained within the kidney. RMC most commonly spreads to the lymph nodes (85% of patients), lungs (46%), liver (15%), and bone (15%), but rarely spreads to the brain.¹