What are Kidney Cancer Subtypes?

By Chris -

Kidney cancer is a type of cancer that begins in the cells of the kidneys, which are two vital organs responsible for filtering blood and producing urine. The disease is not a single entity but consists of various subtypes, each with distinct characteristics, behaviors, and treatment responses. While all forms of kidney cancer originate in the kidney, the differences in cell types and genetic mutations lead to diverse subtypes, each with its own challenges and treatment options.

What are Kidney Cancer Subtypes?
Kidney cancer encompasses a diverse group of subtypes, each with distinct characteristics, genetic mutations, and treatment responses. Clear cell renal cell carcinoma is the most common subtype, but other subtypes such as papillary renal cell carcinoma, chromophobe renal cell carcinoma, and transitional cell carcinoma also contribute to the complexity of the disease. Rare subtypes, including Wilms tumor, renal sarcoma, collecting duct carcinoma, and medullary carcinoma, present unique challenges in diagnosis and treatment. Image Credit: Deka Saputra via Canva.com

The most common subtype of kidney cancer is renal cell carcinoma, which accounts for the majority of cases. However, there are several other subtypes, including transitional cell carcinoma, Wilms tumor, and renal sarcoma. Each subtype arises from different types of cells within the kidney and behaves differently in terms of growth, spread, and response to treatment. A detailed examination of the major subtypes can help in understanding the complexity of kidney cancer.

Clear Cell Renal Cell Carcinoma

Clear cell renal cell carcinoma is the most common subtype of kidney cancer, making up about 70 to 80 percent of all cases. This subtype derives its name from the clear appearance of the cancer cells when viewed under a microscope. The clear appearance results from the accumulation of lipids and glycogen in the cells.

The development of clear cell renal cell carcinoma is often linked to mutations in the von Hippel-Lindau (VHL) gene. The VHL gene plays a critical role in regulating cell growth and preventing the formation of tumors. When mutations occur in this gene, cells can grow uncontrollably, leading to the formation of cancerous tumors. In hereditary cases, individuals with von Hippel-Lindau syndrome have a higher risk of developing this subtype.

Treatment options for clear cell renal cell carcinoma typically include targeted therapies that inhibit angiogenesis, the process by which tumors form new blood vessels. Drugs such as sunitinib (Sutent), pazopanib (Votrient), and cabozantinib (Cabometyx) are commonly used to block the vascular endothelial growth factor (VEGF) pathway. Immunotherapy agents like nivolumab (Opdivo) and pembrolizumab (Keytruda) have also shown effectiveness in treating advanced cases.

Papillary Renal Cell Carcinoma

Papillary renal cell carcinoma is the second most common subtype, accounting for about 10 to 15 percent of kidney cancer cases. These types differ in their genetic mutations, histological appearance, and clinical behavior. Papillary renal cell carcinoma is often associated with mutations in the MET gene, which encodes a receptor tyrosine kinase involved in cell growth and differentiation. They also may be linked to hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome, caused by mutations in the fumarate hydratase (FH) gene.

Treatment for papillary renal cell carcinoma varies depending on the stage and type. Targeted therapies that inhibit the MET pathway, such as crizotinib (Xalkori) and cabozantinib (Cabometyx), have shown promise in clinical trials. Immunotherapy and surgery remain important components of treatment for localized and advanced cases.

Chromophobe Renal Cell Carcinoma

Chromophobe renal cell carcinoma is a rare subtype, accounting for approximately 5 percent of kidney cancer cases. It arises from the intercalated cells of the kidney’s collecting ducts. Under the microscope, chromophobe renal cell carcinoma cells appear pale and have distinctive cell borders.

Unlike clear cell and papillary renal cell carcinoma, chromophobe renal cell carcinoma is not typically associated with VHL or MET gene mutations. Instead, it may involve alterations in other genes such as TP53 and PTEN. Chromophobe renal cell carcinoma generally has a better prognosis compared to other subtypes, as it tends to grow more slowly and is less likely to spread to other parts of the body.

Treatment primarily involves surgical removal of the tumor through partial or radical nephrectomy. In cases where the cancer has spread, targeted therapies and immunotherapy may be considered, although their efficacy in this subtype is less well established compared to clear cell renal cell carcinoma.

Transitional Cell Carcinoma

Transitional cell carcinoma, also known as urothelial carcinoma, arises in the lining of the renal pelvis, the part of the kidney that collects urine and channels it to the bladder. This subtype is distinct from renal cell carcinoma and closely resembles bladder cancer in terms of its origin and behavior.

Risk factors for transitional cell carcinoma include smoking and long-term exposure to certain chemicals. It is more likely to present with symptoms such as blood in the urine and urinary obstruction.

Treatment options for transitional cell carcinoma typically include surgery, chemotherapy, and immunotherapy. Since this subtype behaves similarly to bladder cancer, systemic chemotherapy regimens used for bladder cancer, such as cisplatin-based combinations, are often employed.

Wilms Tumor

Wilms tumor is a rare type of kidney cancer that primarily affects children. It is most commonly diagnosed in children under the age of five and is one of the most common cancers in pediatric populations. Wilms tumor arises from immature kidney cells and may be associated with genetic syndromes such as WAGR syndrome and Beckwith-Wiedemann syndrome.

The treatment of Wilms tumor involves a combination of surgery, chemotherapy, and, in some cases, radiation therapy. The prognosis for Wilms tumor is generally favorable, with high survival rates when treated promptly and appropriately.

Renal Sarcoma

Renal sarcoma is an extremely rare subtype of kidney cancer that originates in the connective tissues of the kidney. It accounts for less than 1 percent of all kidney cancer cases. Renal sarcomas are aggressive tumors that are more likely to spread to distant organs and have a poorer prognosis compared to other subtypes.

Surgery is the primary treatment for renal sarcoma, often followed by chemotherapy and radiation therapy. Due to its rarity, treatment approaches are largely based on case reports and small clinical studies.

Collecting Duct Carcinoma

Collecting duct carcinoma is a rare and aggressive subtype of kidney cancer that arises from the ducts that collect urine in the kidney. It is often diagnosed at an advanced stage and has a poor prognosis. Collecting duct carcinoma may be associated with mutations in the SMARCB1 gene.

Treatment options are limited, and there is no established standard of care. Surgery, chemotherapy, and experimental therapies may be used to manage the disease. Due to its aggressive nature, clinical trials are often recommended for patients with collecting duct carcinoma.

Medullary Carcinoma

Medullary carcinoma is an extremely rare subtype of kidney cancer that primarily affects young individuals, particularly those with sickle cell trait. It is considered a highly aggressive cancer with a poor prognosis.

Treatment for medullary carcinoma typically involves a combination of surgery, chemotherapy, and immunotherapy. However, due to its rarity, there is limited data on the effectiveness of various treatment approaches. Clinical trials may offer additional options for patients with this subtype.

Unclassified Renal Cell Carcinoma

In some cases, kidney cancer does not fit neatly into any of the established subtypes and is classified as unclassified renal cell carcinoma. This category includes tumors with unusual or mixed features that do not correspond to the typical subtypes.

Treatment for unclassified renal cell carcinoma depends on the specific characteristics of the tumor. Surgery remains the primary treatment, and targeted therapies or immunotherapy may be considered based on the tumor’s behavior and genetic profile.

Conclusion

Kidney cancer encompasses a diverse group of subtypes, each with distinct characteristics, genetic mutations, and treatment responses. Clear cell renal cell carcinoma is the most common subtype, but other subtypes such as papillary renal cell carcinoma, chromophobe renal cell carcinoma, and transitional cell carcinoma also contribute to the complexity of the disease. Rare subtypes, including Wilms tumor, renal sarcoma, collecting duct carcinoma, and medullary carcinoma, present unique challenges in diagnosis and treatment.

Advances in molecular research have improved our understanding of the genetic basis of these subtypes, leading to the development of targeted therapies and personalized treatment approaches. Early detection and accurate classification of kidney cancer subtypes are essential for optimizing treatment outcomes and improving survival rates. Ongoing research and clinical trials continue to offer hope for better therapies and management strategies for patients with kidney cancer.

References

  1. Capitanio U, Montorsi F. Renal cancer. Lancet. 2016;387(10021):894-906. https://doi.org/10.1016/S0140-6736(15)00046-X
  2. Jonasch E, Gao J, Rathmell WK. Renal cell carcinoma. BMJ. 2014;349:g4797. https://doi.org/10.1136/bmj.g4797
  3. Linehan WM, Ricketts CJ. The metabolic basis of kidney cancer. Semin Cancer Biol. 2013;23(1):46-55. https://doi.org/10.1016/j.semcancer.2012.06.002

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