On this page
Hereditary papillary RCC
HPRCC is an inherited disorder characterised by an increased lifetime risk of developing papillary renal cell carcinoma, a particular form of kidney cancer. It typically presents with multiple tumours in both kidneys and is caused by changes in the MET gene.
Available at Jeen Health
Clinical tests that include this
Overview
Hereditary Papillary Renal Cell Carcinoma (HPRCC) is a genetic condition that predisposes individuals to developing a specific type of kidney cancer called papillary renal cell carcinoma (PRCC). This condition is considered rare, meaning it affects a small number of people. Individuals with HPRCC typically develop multiple kidney tumours, often in both kidneys (bilateral), and these tumours can appear at various times throughout their life [PMID:31742490].
Unlike many cancers that occur sporadically (by chance), HPRCC is inherited within families, meaning it can be passed down from one generation to the next. Understanding this inheritance pattern is important for identifying individuals at risk and offering appropriate screening and management strategies.
Symptoms & clinical features
HPRCC itself does not typically cause symptoms in its early stages. The symptoms that may arise are usually related to the kidney tumours as they grow. These can include blood in the urine (haematuria), which may be visible or only detectable through laboratory tests. Other possible symptoms can include pain in the side or back, a lump in the abdomen, or unexplained weight loss.
It is important to remember that these symptoms are not exclusive to HPRCC and can be caused by many other conditions. If any of these symptoms are experienced, seeking medical advice from a GP is always recommended. For individuals with a family history of HPRCC, regular surveillance aims to detect tumours before symptoms appear.
Video: Is cancer in your genes?
Affected organs
The primary organ affected by HPRCC is the kidney. Specifically, the condition leads to the development of papillary renal cell carcinoma, which is a type of cancer originating from the cells lining the small tubes within the kidneys. In HPRCC, these tumours often present as multiple lesions and can affect both kidneys, distinguishing it from many sporadic cases of kidney cancer where a single tumour might develop in one kidney.
Risks & severity
Individuals with HPRCC have a significantly increased lifetime risk of developing papillary renal cell carcinoma. The exact percentage risk can vary, and not everyone with the genetic change will develop cancer, a concept known as reduced penetrance. Tumours associated with HPRCC can develop at different ages, but they typically become apparent in adulthood. The severity of HPRCC is largely dependent on the number, size, and aggressiveness of the kidney tumours that develop.
While papillary renal cell carcinomas can be aggressive, many tumours associated with HPRCC are Type 1 papillary RCCs, which are often less aggressive than other kidney cancer types [PMID:27878363]. However, regular monitoring is crucial to detect any tumours early, allowing for timely intervention and improving outcomes. The presence of multiple tumours and their potential to be bilateral can make management more complex.
Genetic causes
Hereditary Papillary Renal Cell Carcinoma is caused by pathogenic variants (genetic changes) in the MET gene [PMID:10729124]. The MET gene provides instructions for making the MET protein, which acts as a receptor on the surface of cells. This protein plays a vital role in cell growth, survival, and movement by receiving signals from outside the cell.
When a pathogenic variant occurs in the MET gene, it can lead to the MET protein being overactive or 'always on'. This uncontrolled signalling can promote the unregulated growth and division of cells, which is a hallmark of cancer development. These genetic changes are usually germline, meaning they are present in every cell of the body and can be passed on to future generations.
- MET MET proto-oncogene, receptor tyrosine kinaseThe MET gene provides instructions for making a protein involved in essential cellular processes, including cell growth, movement, and survival, acting as a proto-oncogene.
Inheritance pattern
HPRCC is inherited in an autosomal dominant pattern. This means that a person only needs to inherit one copy of the altered MET gene from one parent to be at an increased risk of developing the condition. Each child of an individual with HPRCC has a 50% (1 in 2) chance of inheriting the pathogenic variant, regardless of their sex. This inheritance pattern explains why the condition often appears in multiple generations within a family.
Each child has a 50% chance of inheriting the pathogenic variant, regardless of sex.
Diagnosis & testing
A diagnosis of HPRCC is typically suspected based on a personal or family history of papillary renal cell carcinoma, especially if multiple tumours or tumours in both kidneys are observed. The definitive diagnosis is confirmed through genetic testing, which looks for pathogenic variants in the MET gene. Genetic testing may be offered through the NHS Genomic Medicine Service (GMS) to individuals meeting specific criteria.
Referral to a clinical genetics service is often the pathway for individuals and families concerned about HPRCC. Genetic counsellors and clinical geneticists can assess family history, discuss the implications of genetic testing, and arrange appropriate tests. The relevant NHS National Genomic Test Directory code (R-code) for kidney cancer predisposition testing, which includes the MET gene, would be used for this purpose.
Management & lifestyle
Management for individuals with HPRCC focuses on surveillance to detect kidney tumours early and appropriate treatment if tumours develop. This typically involves regular imaging, such as MRI or ultrasound scans, of the kidneys to monitor for new or growing lesions. The frequency and type of surveillance are determined by a specialist team, taking into account individual risk factors and age.
If kidney tumours are found, treatment options are tailored to the individual and depend on the tumour's size, location, and type. These can include surgical removal of the tumour (nephrectomy) or, in some cases, active surveillance for very small, slow-growing tumours. Genetic counsellors and clinical genetics teams play a crucial role in providing support and information regarding the condition and its implications for family members. Management plans are always individualised and decided upon in consultation with healthcare professionals.
UK care pathway
In the UK, individuals suspected of having an inherited cancer predisposition syndrome like HPRCC are generally referred to a clinical genetics service. This service provides expert assessment, genetic counselling, and access to genetic testing through the NHS Genomic Medicine Service. If genetic testing confirms a diagnosis, the clinical genetics team works alongside other specialist teams, such as urology and oncology, to develop a comprehensive surveillance and management plan. This integrated approach ensures coordinated care in line with national guidelines.
Frequently asked questions
What does 'papillary' mean in the context of kidney cancer?
Papillary refers to a specific growth pattern of the cancer cells, where they form small, finger-like projections within the tumour. This is a common way to classify kidney cancers based on their appearance under a microscope.
If I have HPRCC, will I definitely get kidney cancer?
Not necessarily. Having a genetic change associated with HPRCC increases your risk, but it does not mean you will definitely develop kidney cancer. This concept is called 'reduced penetrance', meaning some people with the genetic change may never develop the condition. Regular surveillance helps to monitor for any changes.
How often will I need to be screened for kidney tumours?
The frequency of screening for kidney tumours will be decided by your specialist healthcare team. It typically involves regular imaging scans, such as MRI or ultrasound, but the exact schedule is tailored to your individual circumstances and risk factors.
Can HPRCC affect other organs besides the kidneys?
HPRCC primarily affects the kidneys, leading to papillary renal cell carcinoma. There is no strong evidence to suggest it significantly increases the risk of tumours in other organs, unlike some other inherited cancer syndromes that can affect multiple body systems.
What should I tell my family members if I am diagnosed with HPRCC?
It's important to inform your close relatives, such as parents, siblings, and children, about your diagnosis. Since HPRCC is inherited, they may also be at risk and could benefit from genetic counselling and testing. Your clinical genetics team can provide advice on how to share this information.
References
- Walker C. Molecular genetics of renal carcinogenesis. Toxicologic pathology. 1998. PMID: 9502393
- Wang MX, Diab M, Klekers AR. Hereditary Renal Cell Carcinoma: An Imaging Update. Magnetic resonance imaging clinics of North America. 2025. PMID: 42579732
- Van Poppel H, Nilsson S, Algaba F. Precancerous lesions in the kidney. Scandinavian journal of urology and nephrology. Supplementum. 2000. PMID: 11144893
- Randall JM, Millard F, Kurzrock R. Molecular aberrations, targeted therapy, and renal cell carcinoma: current state-of-the-art. Cancer metastasis reviews. 2014. PMID: 25365943
- Chan-Smutko G. Genetic testing by cancer site: urinary tract. Cancer journal (Sudbury, Mass.). 2012. PMID: 22846736
- Freifeld Y, Ananthakrishnan L, Margulis V. Imaging for Screening and Surveillance of Patients with Hereditary Forms of Renal Cell Carcinoma. Current urology reports. 2018. PMID: 30116909
- Takahashi M, Kahnoski R, Gross D. Familial adult renal neoplasia. Journal of medical genetics. 2002. PMID: 11826016
- García-Donas J, Hernando S, Romero N. Knowledge of hereditary renal cancer syndromes: a pending issue for oncologists. Anti-cancer drugs. 2011. PMID: 21173603