What are the other Names for this Condition? (Also known as/Symptoms)

• Classic Renal Cell Carcinoma
• Clear Cell Carcinoma of Kidney
• Conventional Renal Cell Carcinoma

What is Clear Renal Cell Carcinoma? (Definition/Background Information)

• Clear Cell Renal Cell Carcinoma (CCRCC) is a type of renal cell carcinoma (kidney cancer) that develops from the renal cortex. It is a malignant tumor that develops due to an abnormality within the tissue lining in the tubules of the kidney
• About 65-70% of adult renal cancers are Clear Cell Renal Cell Carcinomas. The condition is more common in older men. The common risk factors for CCRCC include a family history of the condition (that may result in hereditary CCRCC), smoking, exposure to toxins, high blood pressure, and even obesity
• The exact cause of development of Clear Cell Renal Cell Carcinoma is presently unknown. Certain genetic mutations have been reported in these tumors. In most cases, a single tumor on one kidney is reported. Rarely, the tumors may be bilateral (involving both kidneys) and multifocal (tumor present in multiple foci within the same kidney)
• The typical signs and symptoms of Clear Cell Renal Cell Carcinoma include blood in urine, a lump on the side (abdomen), unexplained fever, flank pain, and inexplicable weight loss. CCRCC may give rise to complication such as metastasis (spreading) to other parts of the body
• The healthcare provider may diagnose the condition using blood tests and imaging studies as necessary. Genetic testing may be required, if hereditary Clear Cell Renal Cell Carcinoma is suspected
• The treatment options for Clear Cell Renal Cell Carcinoma include surgery, radiation therapy, chemotherapy, and targeted drug therapy. The prognosis of CCRCC depends on the type and size of tumor, whether it is localized in the kidney or has metastasized to other body regions (if the condition is in its early stage or advanced stage, at the time of diagnosis)
• Although inherited CCRCC might not be preventable, being aware of one’s family history and having regular check-ups might help in an early diagnosis. Moreover, leading a healthy lifestyle, managing an ideal body weight, controlling blood pressure, avoiding unnecessary medication, smoking cessation, and other such measures can help one reduce the risk for cancer formation

The main types of kidney cancers that arise from the renal cortex include:

• Clear Cell Renal Cell Carcinoma: This is also called Conventional Renal Cell Carcinoma. 65% of kidney cancers belong to this carcinoma type
• Papillary renal cell carcinoma: It is also known as chromophil renal cell carcinoma. They constitute 15% of kidney cancers. Some of these cancers can be seen in syndromes such as hereditary papillary renal cell carcinoma syndrome. A majority of individuals with this carcinoma type do not have a family history of kidney cancer
• Chromophobe renal cell carcinoma: They make up for 5% of the kidney cancers. Usually, it is a slower-growing cancer when compared to other kidney cancers
• Collecting duct carcinoma of kidney: They are rare and make up for approximately 1% of the kidney cancers. This cancer arises from the collecting ducts of the kidney

Who gets Clear Cell Renal Cell Carcinoma? (Age and Sex Distribution)

• Clear Cell Renal Cell Carcinoma is comparatively common, forming over two-thirds of all kidney cancer types
• CCRCC generally affects older individuals; the average age of diagnosis is between 60-64 years
• The condition is observed in both males and females. However, it is reportedly more common in men (2: 1 male-female ratio)
• The cancer is not specific to any particular ethnic or racial group; although, a greater number of cases are reported in African Americans than Caucasians

What are the Risk Factors for Clear Cell Renal Cell Carcinoma? (Predisposing Factors)

In a majority of individuals, no well-defined risk factors for Clear Cell Renal Cell Carcinoma have been identified. Some studies have shown that the following may predispose an individual to CCRCC or kidney cancer development:

• Family history of Clear Cell Renal Cell Carcinoma: If the cancer is present among close family members, then an increased risk for developing the same is noted. A positive family history of hereditary CCRCC also increases the risk in some individuals
• Obesity
• High blood pressure (hypertension)
• Smoking history
• Exposure to toxins, such as naphthylamine dye, asbestos, lead, polycyclic aromatic hydrocarbons, cadmium, and other chemical compounds
• Continuous use of certain medications such as non-steroidal anti-inflammatory drugs (NSAIDs)
• Long-term dialysis
• Family history of the following conditions:
  • Von Hippel-Lindau disorder
  • Tuberous sclerosis
  • Birt-Hogg-Dube syndrome
• Adult polycystic kidney disease

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your health care provider.

What are the Causes of Clear Cell Renal Cell Carcinoma? (Etiology)

Currently, scientists do not know the definitive factor(s) causing Clear Cell Renal Cell Carcinoma. However, numerous genetic mutations have been detected in CCRCC. Research is currently underway to well characterize these mutations.

The genetic mutations include:

• Translocation between chromosome 3 and chromosome 1,2,4,6, or 8
• Xp11 translocations are usually seen in children with CCRCC; however, such mutations can also be infrequently observed in adults
• Chromosomal losses are noted in the following:
  • Chromosome 3 or 3p in 80-95% of the cases
  • Chromosome 14 or 14q in 40-60% of the cases
  • Chromosome 8 or 8q; chromosome 9 or 9q; and, chromosome 6 or 6q
• Gains in chromosome 5 or 5q are noted in 50-75% of the cases

What are the Signs and Symptoms of Clear Cell Renal Cell Carcinoma?

The signs and symptoms associated with Clear Cell Renal Cell Carcinoma may vary from one individual to another. Small tumors usually do not cause any significant symptoms; but occasionally may cause pain, if they compress the surrounding structures.

The signs and symptoms of CCRCC can include:

• Blood in urine; noted in 1 in 4 cases
• Fatigue due to anemia; noted in over half the cases
• Flank pain
• A visible lump may be seen on the side of the abdomen (if the tumor is large)
• Fluid accumulation in the lower legs (or pedal edema)
• Unexplained fever and night sweats
• Unexplained weight loss; noted in 1 in 4 cases
• Generalized weakness and pain in the body
• Increased blood pressure (hypertension)

Lab tests may reveal the following:

• Increased platelet count (thrombocytosis)
• Increased calcium in blood (hypercalcemia)
• Abnormal liver function tests
• Increased number of red blood cells (erythrocytosis) 

The signs and symptoms may also depend on the size of the kidney tumor.

How is Clear Cell Renal Cell Carcinoma Diagnosed?

Clear Cell Renal Cell Carcinoma does not cause significant signs or symptoms in many individuals. It is often diagnosed incidentally through imaging studies, when performed for some other condition. It is reported that nearly 60-80% of the tumors are discovered incidentally.

A physician might employ one or several of the following tools to arrive at a diagnosis of Clear Cell Renal Cell Carcinoma:

• Evaluation of the patient’s personal and family medical history
• A complete physical examination and assessment of the presenting signs and symptoms, if any
• Blood tests including albumin level, hematocrit, complete blood count (CBC), and serum calcium levels
• Urine analysis including urine albumin level
• Liver function tests
• Plain X-ray of the abdomen
• Ultrasound scan of the abdomen
• Computed tomography (CT) scans of the kidneys: CT scans with contrast of the affected region may show a well-defined mass, which may have calcifications
• Magnetic resonance imaging (MRI) and positron emission tomography (PET) scans may help differentiate between benign versus malignant tumors by detecting areas of metastasis (if any present)

Although the above modalities can be used to make an initial diagnosis, a tissue biopsy of the tumor may be required to make a definitive diagnosis to begin treatment of the condition.

• The tissue for diagnosis can be procured in multiple different ways, and they include:
  • Fine needle aspiration (FNA) biopsy of the tumor: An FNA biopsy may not be helpful, because one may not be able to visualize the different morphological areas of the tumor. Hence, FNA biopsies as diagnostic tools have certain limitations, and open surgical biopsies are preferred
  • Core biopsy of the tumor is often helpful
  • Open biopsy of the tumor
• A tissue biopsy of the tumor is performed and sent to a laboratory for a pathological examination. A pathologist examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis. Examination of the biopsy under a microscope by a pathologist is considered to be gold standard in arriving at a conclusive diagnosis
• Biopsy specimens are studied initially using Hematoxylin and Eosin staining. The pathologist then decides on additional studies depending on the clinical situation
• Sometimes, the pathologist may perform special studies, which may include immunohistochemical stains, molecular testing, and very rarely electron microscopic studies, to assist in the diagnosis
• The differential diagnosis for CCRCC may include:
  • Chromophobe eosinophilia variant RCC
  • Papillary RCC with focal clear cell change
  • Clear cell papillary RCC

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Clear Cell Renal Cell Carcinoma?

The possible complications associated with Clear Cell Renal Cell Carcinoma include:

• CCRCC can occur at multiple locations in one kidney, or it may involve both the kidneys
• Renal dysfunction due to large-sized tumors
• Metastasis: The cancer can spread to other areas of the body, such as to the lung, abdominal lymph nodes, bone, brain, and liver, and severely compromise their function
• Recurrence of the tumor following treatment
• Emotional and psychological stress due to cancer diagnosis
• Side effects due to cancer therapy; surgical complications from removal of tumor

How is Clear Cell Renal Cell Carcinoma Treated?

The treatment of Clear Cell Renal Cell Carcinoma may depend upon a consideration of the following set of factors:

• The stage of the cancer
• Size and location of the tumor
• Severity of the signs and symptoms
• Age and overall health status of the individual
• The treatment preferences of the individual

The treatment measures for Clear Cell Renal Cell Carcinoma may include the following:

• Surgery:
  • In a majority of individuals, surgical resection of the tumor with clear margins may result in a cure, especially if the tumor is confined to the kidneys. In some cases, due to location of the tumor, a complete surgical removal may be difficult
  • Several different surgical procedures may be available, such as partial/radical nephrectomy or laparoscopic surgery, depending on the type, size, and location of the tumor
  • Post-operative care is important: One must maintain minimum activity levels until the surgical wound heals
• Radiation therapy:
  • Radiotherapy can be used as primary therapy in situations where the tumor cannot be removed completely, or when the tumor reappears (recurrent Clear Cell Renal Cell Carcinoma) after surgery
  • Radiotherapy can also be used as an additional therapy after surgery, if there is a possibility of tumor recurrence, or if there are inadequate margins following surgery (possibility of residual tumor being left behind)
• Chemotherapy can be used for treating Clear Cell Renal Cell Carcinoma under the following circumstances:
  • The tumor cannot be removed completely (incomplete surgical resection)
  • Tumors that recur after surgery (recurrent CCRCC)
  • Tumors that have spread to distant parts of the body (metastatic CCRCC)
• Immunotherapy: A patient’s immune system is activated to combat the cancer in this kind of therapy.
• Targeted drug therapy: This kind of drug treatment targets and kills cancer cells specifically, avoiding harm to the surrounding normal/healthy cells
• Arterial embolization of Clear Cell Renal Cell Carcinoma is a possible treatment option. Here the blood supply to the tumor is blocked resulting in tumor death

A long-term follow-up is required, because recurrence of the tumor at the site of surgery or metastasis in distant sites have been reported many years after surgery, even with relatively ‘benign-appearing’ tumors.

How can Clear Cell Renal Cell Carcinoma be Prevented?

• Current medical research has not established a method of preventing Clear Cell Renal Cell Carcinoma formation
• Regular health check-ups might help those individuals with a family history of the condition and help diagnose CCRCC early
• Regular medical screening at periodic intervals with blood tests, radiological scans, and physical examinations for those who have already endured the tumor are helpful

In general, preventive methods for Clear Cell Renal Cell Carcinoma include reducing the contributory risk factors such as:

• Smoking
• Unhealthy diet and lifestyle
• Obesity
• Exposure to toxins
• Use of unnecessary medication

What is the Prognosis of Clear Cell Renal Cell Carcinoma? (Outcomes/Resolutions)

The prognosis of Clear Cell Renal Cell Carcinoma depends on the size and number of tumors, their localization (whether confined to the kidneys), and spread to near and distant sites.

• Surgical resectability of the tumor: The most reliable prognostic factor of Clear Cell Renal Cell Carcinoma is dependent on whether the tumor can be completely removed through surgery with free margins or not (whether any traces of the tumor remain in adjoining tissue)
• The prognosis of CCRCC also depends upon a set of several factors, which include:
  • Stage of tumor: With lower-stage tumors, when the tumor is confined to the site of origin, the prognosis is usually excellent with appropriate therapy. In higher-stage tumors, such as tumors with metastasis, the prognosis is poor
  • Overall health of the individual: Individuals with overall excellent health have better prognosis compared to those with poorer health
  • Age of the individual: Older individuals generally have poorer prognosis than younger individuals
  • Whether the tumor is occurring for the first time or is a recurrent tumor. Recurring tumors have worse prognosis compared to tumors that do not recur
  • Response to treatment. Tumors that respond to treatment have better prognosis compared to tumors that do not respond to treatment
• When Clear Cell Renal Cell Carcinoma is diagnosed in the early stages, the possibility of survival increases, and the prognosis is generally considered good with treatment
• In cases where both kidneys are affected, the prognosis is not projected to be favorable. Additionally, if the cancer has spread to other parts of the body, such as to the liver, lungs, or bone, prolonged survival following diagnosis and treatment is generally limited
• Overall, the prognosis of Clear Cell Renal Cell Carcinoma type is generally worse than papillary renal cell carcinoma and other subtypes

As with any malignant conditions, it is important to have regular follow-up appointments with a healthcare provider to monitor for any returning tumors.

Additional and Relevant Useful Information for Clear Cell Renal Cell Carcinoma:

• Clear Cell Renal Cell Carcinoma used to be formerly known as Hypernephroma. The term is not currently in use

The following article link will help you understand other cancers and benign tumors:

http://www.dovemed.com/diseases-conditions/cancer/