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Hereditary papillary thyroid carcinoma
This condition is characterised by an inherited predisposition to a specific type of thyroid cancer. It typically affects adults, and early detection and surveillance are important for managing risks.
Overview
Hereditary papillary thyroid carcinoma (HPTC) is a rare inherited disorder that makes individuals more likely to develop papillary thyroid cancer. Papillary thyroid cancer is the most common form of thyroid cancer, originating in the follicular cells of the thyroid gland. While most cases of papillary thyroid cancer occur sporadically, meaning they are not inherited, HPTC accounts for a small proportion of these cancers [PMID:33676228].
The thyroid gland, located at the front of the neck, plays a vital role in producing hormones that regulate metabolism, heart rate, and body temperature. In HPTC, the cells within the thyroid gland have an increased tendency to grow abnormally, leading to the formation of cancerous tumours. Understanding the hereditary nature of this condition helps in identifying at-risk family members for appropriate screening and management.
Symptoms & clinical features
Individuals with HPTC typically do not show any symptoms unless a thyroid tumour develops. When a papillary thyroid cancer forms, symptoms may include a lump or swelling in the neck, which might be visible or felt during a self-examination or medical check-up. Other potential symptoms can include difficulty swallowing, hoarseness, or pain in the neck that may extend to the ears.
these symptoms are not unique to HPTC and can be caused by many other, often non-cancerous, thyroid conditions. Therefore, any new or concerning neck symptoms should be evaluated by a healthcare professional. In families with HPTC, regular screening is often recommended to detect any changes early, before symptoms become noticeable [PMID:33676228].
Video: Is cancer in your genes?
Affected organs
Hereditary papillary thyroid carcinoma primarily affects the thyroid gland. This butterfly-shaped gland, situated at the base of the neck, is the main organ involved in the development of cancer in individuals with HPTC. While the condition specifically predisposes to papillary thyroid cancer, some studies suggest a possible, though less common, association with other cancers, such as those of the kidney or breast, in certain families [PMID:24072213]. However, the primary focus of surveillance and management for HPTC remains the thyroid gland.
Risks & severity
HPTC significantly increases an individual's lifetime risk of developing papillary thyroid cancer compared to the general population. The age of onset for thyroid cancer in individuals with HPTC can vary, but it often occurs earlier than in sporadic cases of papillary thyroid cancer. The severity of thyroid cancer can range widely, from small, slow-growing tumours that are easily treatable to more aggressive forms.
Individuals with HPTC may also have a higher chance of developing multifocal tumours (multiple tumours within the thyroid gland) or having cancer spread to nearby lymph nodes. However, with appropriate surveillance and early intervention, the prognosis for papillary thyroid cancer is generally very good. The exact prevalence of HPTC is not well established, but it is considered a rare condition.
Genetic causes
While HPTC is recognised as an inherited condition, specific causative genes are not consistently identified across all affected families. Unlike some other hereditary cancer syndromes where a single gene is clearly implicated, HPTC often involves a more complex genetic picture. Research suggests that genetic changes, often in genes that regulate cell growth and development, contribute to the increased risk of papillary thyroid cancer.
In some families, specific gene variants have been identified that appear to increase susceptibility, but these are not universally found in all cases of HPTC. This suggests that the condition may be genetically heterogeneous, meaning different genetic changes can lead to the same clinical presentation. Ongoing research aims to identify these underlying genetic factors more precisely, which could lead to improved diagnostic tools and targeted therapies.
Inheritance pattern
Hereditary papillary thyroid carcinoma is inherited in an autosomal dominant pattern. This means that an individual only needs to inherit one copy of an altered gene from one parent to have an increased risk of developing the condition. If a parent has HPTC, there is a 50% chance that each of their children will inherit the genetic predisposition.
Autosomal dominant inheritance affects males and females equally. Family members who inherit the genetic change may not all develop cancer, or they may develop it at different ages and with varying severity, a concept known as variable penetrance. Genetic counselling is highly recommended for families affected by HPTC to understand the inheritance patterns and implications for relatives.
Each child has a 50% chance of inheriting the pathogenic variant, regardless of sex.
Diagnosis & testing
The diagnosis of HPTC is typically suspected when multiple family members develop papillary thyroid cancer, especially at a younger age or with multifocal tumours. A definitive diagnosis relies on a combination of clinical assessment and genetic testing. However, given that specific causative genes are not always identified, the diagnosis can sometimes be based on strong family history alone.
In the UK, individuals with a suspected hereditary cancer predisposition, such as HPTC, would typically be referred to a clinical genetics service. Genetic testing for inherited cancer syndromes often falls under specific NHS Genomic Medicine Service R-codes. If a genetic cause is identified in a family member, predictive genetic testing can then be offered to at-risk relatives to determine their genetic status.
Management & lifestyle
Management for individuals with HPTC focuses on early detection of thyroid cancer and appropriate treatment, tailored to the individual's risk and clinical findings. Regular surveillance often includes physical examinations of the neck, blood tests to check thyroid hormone levels, and ultrasound scans of the thyroid gland to look for any suspicious nodules. The frequency and type of surveillance will be determined by a specialist team, usually an endocrinologist or an endocrine surgeon.
If thyroid cancer is detected, treatment typically involves surgical removal of the thyroid gland (thyroidectomy), often followed by radioactive iodine therapy to destroy any remaining thyroid cells or cancer cells. Following treatment, lifelong monitoring with thyroid hormone replacement therapy is usually required. Management plans are developed in accordance with NHS guidelines, aiming to provide comprehensive and individualised care. Genetic counsellors can also help families understand their risk and navigate management options.
UK care pathway
In the UK, individuals suspected of having hereditary papillary thyroid carcinoma would typically be referred to a Clinical Genetics service within the NHS Genomic Medicine Service (GMS). This pathway allows for comprehensive evaluation, including detailed family history assessment and discussion of genetic testing options. Genetic counsellors play a key role in explaining the implications of genetic conditions and supporting individuals and families through the diagnostic process. Genetic testing for inherited cancer predispositions is performed through the NHS GMS, often guided by specific PanelApp R-codes.
Frequently asked questions
What is the chance of my children inheriting HPTC if I have it?
Hereditary papillary thyroid carcinoma is inherited in an autosomal dominant manner. This means there is a 50% chance for each child to inherit the genetic predisposition if one parent has the condition.
Do I need genetic testing if I have family members with HPTC?
If you have a strong family history of papillary thyroid cancer, particularly with features suggestive of HPTC, it is advisable to discuss this with your GP, who may refer you to a Clinical Genetics service. They can assess your personal and family history and discuss whether genetic testing is appropriate for you.
What kind of surveillance will I need if I am at risk for HPTC?
Surveillance for individuals at risk of HPTC typically involves regular physical examinations of the neck, blood tests to check thyroid function, and ultrasound scans of the thyroid gland. The exact schedule and type of surveillance will be determined by your specialist team.
Does HPTC mean I will definitely get thyroid cancer?
No, inheriting the genetic predisposition for HPTC means you have an increased lifetime risk of developing papillary thyroid cancer, but it does not mean you will definitely get it. The condition can have variable penetrance, meaning not everyone with the genetic change will develop cancer.
Is HPTC related to other types of cancer?
HPTC primarily increases the risk of papillary thyroid cancer. Some research suggests a possible, though less common, association with other cancers in certain families, such as kidney or breast cancer. However, the main focus for HPTC is the thyroid gland.
References
- Sarquis M, Moraes DC, Bastos-Rodrigues L. Germline Mutations in Familial Papillary Thyroid Cancer. Endocrine pathology. 2020. PMID: 32034658