Hereditary papillary renal cell carcinomacancer arising from tissues that line organs (HPRCC) is a rare genetic condition that increases the riskthe possibility that something bad will happen of developing a specific type of kidneya pair of bean-shaped organs in the abdomen that are responsible for filtering excess water and waste products from the blood and converting them into urine to be removed from the body cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs known as papillary renal cell carcinoma. It is caused by a mutation of the mesenchymal-epithelial transition factor (MET) gene, which is a tumoura tissue mass that forms from groups of unhealthy cells suppressor gene found on chromosome seven.
Familial cancer syndromes, also known as hereditary cancer syndromes, are rare conditions that cause an increased risk of cancer as the result of inherited genetic mutations in certain cancer-related genes. They can affect both adults and children, however they generally develop in people at a younger age than normal. While familial cancer syndromes are not classified as cancer, they are equally as severe and can be life-threatening as they are associated with the development of various tumours throughout the body. Having a familial cancer syndrome does not guarantee the development of cancer, however the risk of developing cancer is higher than those who do not have a familial cancer syndrome.
HPRCC syndrome tends to affect the sexes equally, and is generally diagnosed around the age of 40. However, anyone can develop this disease.
HPRCC Related Tumours
HPRCC causes the development of papillary renal cell carcinoma, which is a common type of kidney cancer. Unlike sporadic (random) kidney cancers, HPRCC tumours are generally bilateralaffecting both sides (i.e. affect both kidneys) and multifocal (has more than one tumour presenting on each kidney).
The kidneys are a pair of bean-shaped organs that sit in the middle of your back on each side of your spine. It is responsible for filtering excess water and waste products from the bloodthe red bodily fluid that transports oxygen and other nutrients around the body, and converting them into urine to be removed from the body. The kidneys also produce and secrete certain hormones that regulate blood pressure and initiate the production of red blood cellsthe basic structural and functional unit of all living things.
Papillary renal cell carcinoma (PRCC) is the second most common type of renal cell carcinoma, and is characterised by renal cells arranged in finger-like structures. There are two types of PRCC, which are classified by growth rate. Type I PRCC is more common in patients with HPRC, and tends to grow slowly. Type II is less common, tends to be more aggressive and grows quicker.
For more information on kidney cancer (RCC), please refer to the Rare Cancers Australia Kidney Cancer (Renal Cell Carcinoma (RCC)) page.
Treatment
As PRCC is the only malignancy thus far that is associated with this disease, HPRC is staged and graded in the same way.
If PRCC is detected, it will be staged and graded based on size, metastasiswhen the cancer has spread to other parts of the body, also known as mets, and how the cancer cells look under the microscope. Stagingthe process of determining how big the cancer is, where it started and if it has spread to other areas and grading helps your doctors determine the best treatment for you.
Cancers can be staged using the TNM staging system:
- T (tumour) indicates the size and depth of the tumour.
- N (nodea small lump or mass of tissue in your body) indicates whether the cancer has spread to nearby lymph nodessmall bean-shaped structures that filters harmful substances from lymph fluid.
- M (metastasis) indicates whether the cancer has spread to other parts of the body.
This system can also be used in combination with a numerical value, from stage 0-IV:
- Stage 0: this stage describes cancer cells in the place of origin (or ‘in situ’) that have not spread to nearby tissuea group of cells that work together to perform a function.
- Stage I: cancer cells have begun to spread to nearby tissue. It is not deeply embedded into nearby tissue and had not spread to lymph nodes. This stage is also known as early-stage cancer.
- Stage II: cancer cells have grown deeper into nearby tissue. Lymph nodes may or may not be affected. This is also known as localisedaffecting only one area of body cancer.
- Stage III: the cancer has become larger and has grown deeper into nearby tissue. Lymph nodes are generally affected at this stage. This is also known as localised cancer.
- Stage IV: the cancer has spread to other tissues and organs in the body. This is also known as advancedat a late stage, far along or metastatic cancer.
Cancers can also be graded based on the rate of growth and how likely they are to spread:
- Gradea description of how abnormal cancer cells and tissue look under a microscope when compared to healthy cells I: cancer cells present as slightly abnormal and are usually slow growing. This is also known as a low-grade tumour.
- Grade II: cancer cells present as abnormal and grow faster than grade-I tumours. This is also known as an intermediate-grade tumour.
- Grade III: cancer cells present as very abnormal and grow quickly. This is also known as a high-grade tumour.
Once your tumour has been staged and graded, your doctor may recommend genetic testinga procedure that analyses DNA to identify changes in genes, chromosomes and proteins, which can be used to analyse tumour DNA to help determine which treatment has the greatest chance of success, which analyses your tumour DNA and can help determine which treatment has the greatest chance of success. They will then discuss the most appropriate treatment option for you.
Treatment is dependent on several factors, including location, stage of disease and overall health.
Treatment options for patients with HPRCC may include:
- Surgerytreatment involving removal of cancerous tissue and/or tumours and a margin of healthy tissue around it to reduce recurrence, potentially including:
-
- Nephrectomycomplete or partial removal of affected kidney(s).
-
- Lymphadenectomysurgical removal of lymph node(s).
- Radiation therapya treatment that uses controlled doses of radiation to damage or kill cancer cells, potentially including stereotactic body radiation therapy (SBRT).
- Cryotherapythe process of freezing off cancerous tumours and/or lesions using liquid nitrogen.
- Targeted therapymedication that targets specific molecular features of cancer cells.
- Immunotherapya treatment that uses a person's immune system to fight cancer.
- Ablation therapya minimally invasive procedure that uses extremely high or low temperatures to destroy (ablate) abnormal tissue and/or cancer cells.
- Watch and waitthe close monitoring of a cancer without giving treatment until symptoms appear or worsen.
- Clinical trialsresearch studies performed to test new treatments, tests or procedures and evaluate their effectiveness on various diseases.
- Palliative carea variety of practices and exercises used to provide pain relief and improve quality of life without curing the disease.
Cancer Screening
Once a diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results of HPRCC has been confirmed, implementing a targeted screeningtesting for cancer or conditions that can lead to cancer before symptoms appear, also known as cancer screening plan becomes essential due to the increased risk of developing certain cancers. The content of this plan will vary from person to person based on the genetic mutation involved, your family’s history of cancer and the types of cancers that may be present. It will also outline the routine tests you should have and how regularly you should have them.
Screening options for HPRCC may evolve as new technologies are developed and our understanding of the condition grows. It is essential to discuss your individual circumstances with your healthcare team to determine the most appropriate screening plan for you.
Risk factors
HPRCC is caused by a genetic mutation of the mesenchymal-epithelial transition factor (MET) gene, which is a type of tumour suppressor gene. It is an autosomal dominant disease, which means that you have a 50% chance of developing the condition if one of your parents carries the mutation.
Symptoms
Early stage HPRCC may appear symptomatic. As the tumour(s) progress, some of the following symptoms may appear:
- Blood in the urine.
- Pain/dull ache in the side or lower back.
- Unexplained weight loss.
- Fatiguea state of extreme tiredness or exhaustion, can be physical or mental.
- Fever.
- A lump in the kidney region.
Not everyone with the symptoms above will have cancer, but see your general practitioner (GP) if you are concerned.
Diagnosis
If your doctor suspects you have tumours associated with HPRCC, they may order some of the following tests to confirm the diagnosis and refer you to a specialist for treatment. The tests required for diagnosis will often vary based on the symptoms present, and where the tumour(s) are suspected to be located.
- Physical examinationan examination of your current symptoms, affected area(s) and overall medical history.
- Genetic testing.
- Blood teststesting done to measure the levels of certain substances in the blood.
- Urine teststesting done to measure the levels of certain substances in the urine.
- Imagingtests that create detailed images of areas inside the body tests, potentially including:
-
- MRI (magnetic resonance imaging)a type of medical imaging that uses radiowaves, a strong magnet and computer technology to create detailed images of the body.
-
- CT (computed tomography) scana type of medical imaging that uses x-rays and computer technology to create detailed images of the body.
-
- Ultrasounda type of medical imaging that uses soundwaves to create detailed images of the body .
- Exploratory procedures, potentially including:
-
- Cystoscopyan examination of the bladder and urethra with a small, flexible instrument known as a cystoscope (examination of the bladdera hollow, muscular sac in the pelvis that stores urine).
-
- Ureteroscopyexamination of the bladder and ureters using a small, flexible instrument called a ureteroscope .
- Biopsyremoval of a section of tissue to analyse for cancer cells.
