The thymus is a little-known organ in the body, but does some very important things. It is part of the lymphatic system, along with the tonsils, adenoids and spleen, and it’s also part of the endocrine system and contains neuroendocrine cells.
It sits just below the breast bone and whilst relatively large in infants through to puberty (where it can be up to 40 grammes), in adulthood, it starts to slowly shrink and in elderly adults has shrunk to weigh less than 5 grammes.
The thymus produces certain cells, which mature into T-cells (thymus-derived cells), which play a role in helping to destroy infected or cancerous cells. T-cells created by the thymus also help other organs in the immune system grow properly. As the thymus shrinks, other parts of the immune system take over its role.
Neuroendocrine Cancer of the Thymus is very rare – less than 5% of all chest based cancers: less than 0.5% of all Neuroendocrine Cancers.
There are 4 subtypes :
- Typical Carcinoid (TC) low grade neuroendocrine tumour (NET)
- Atypical Carcinoid (AC) mid-grade neuroendocrine tumour (NET)
- Small cell neuroendocrine carcinoma (NEC)
- Large cell neuroendocrine carcinoma (NEC)
Although Thymic Neuroendocrine Cancers can show slow-moderate growth (approximately 20%), the majority are NEC and therefore benefit from early diagnosis and intervention to either remove or try to control rapid growth rate.
Up to 20% may present with signs of Cushings syndrome : where your body makes too much cortisol hormone. Cortisol helps to regulate blood pressure, the immune system, balance the effect of insulin to keep blood sugar normal and helps the body to respond to stress.
It has been reported that 1 in 5 people with Thymic Neuroendocrine Cancers have an underlying, rare genetic condition (specifically, either Acromegaly or Multiple Endocrine Neoplasia 1 (MEN1).
Causes and potential risk factors
We do not know exactly what causes Neuroendocrine Cancer – however it is important to follow advice in leading a healthy lifestyle: eat healthily, exercise and avoid smoking and too much alcohol.
Most Neuroendocrine Cancers do not run in families; however, a number of rare conditions may increase the risk of them developing. Therefore, if other members of the family have been diagnosed with cancer, or have a known genetic condition, it is important that you tell your specialist team about not only your personal medical history, but also any family medical illnesses or conditions.
We recommend speaking to your GP, and specialist team, if you have a personal or family history of either Acromegaly and / or Multiple Endocrine Neoplasia 1. They may recommend referral for an NHS genetic test, if you have not already been tested, which will tell you if you have inherited one of these conditions.
Neuroendocrine Cancer of the Thymus is incredibly rare – and may not be associated with either of the above mentioned genetic conditions or family history.
Acromegaly is the name given to a condition caused by the body producing too much growth hormone (GH). The increased amount of GH also leads to increased formation of another hormone, insulin-like growth factor (IGF-1). These two hormones have a number of effects on the body including an increase in size of tissue or organs.
Further information about Acromegaly can be found at www.pituitary.org.uk
Multiple Endocrine Neoplasia Type 1 (MEN1) is a rare genetic condition (can be passed down in families) that may cause the development of growths (tumours), primarily within the pituitary, parathyroid and pancreatic glands, that may become Neuroendocrine Cancer.
Further information about MEN1 can be found at www.amend.org.uk
Symptoms that may or may not include Neuroendocrine Cancer associated syndromes
As with other Neuroendocrine Cancers, Neuroendocrine Cancer of the Thymus may not be associated with specific symptoms. Symptoms if they do occur may be more related to size and position.
Symptoms, if present, may therefore include:
- Shortness of breath
- A cough (which may bring up bloody sputum)
- Chest pain
- Hoarseness – voice may become breathy, raspy, strained, or there may be changes in volume (loudness) or pitch (how high or low the voice is)
- Trouble swallowing
- Loss of appetite and weight loss.
Neuroendocrine Cancer of the Thymus is rarely associated with a Neuroendocrine associated syndrome, such as Carcinoid Syndrome.
Although rare, other syndromes including Cushing’s syndrome, raised calcium levels (Hypercalcaemia) and SVCO (Superior Vena Cava Obstruction) have been reported and require urgent medical review.
SVCO may produce the following symptoms:
- Swelling & reddening of head, face or neck
- A bluish colour to the skin
and / or dizziness.
Further information about Neuroendocrine Cancer associated and Paraneoplastic Syndromes – including Oncological emergencies – can be found here.
Tests that may be used for the diagnosis and / or monitoring of Neuroendocrine Cancer of the Thymus
Bloods and / or urine:
Full blood count
Liver and kidney function
Gut hormone profile
Urinary or serum 5HiAA (serotonin).
NT-Pro-BNP – to check for evidence of Carcinoid Heart Disease
Clinical assessment for presence of Carcinoid Syndrome and/or other paraneoplastic syndromes – Cushings, SIADH, Hypoglycaemia and Hypercalcaemia
If MEN1 is suspected or known : calcium, PTH and consider genetic studies.
If Acromegaly is suspected or known : IGF-1, GH and growth hormone-releasing hormone (GHRH)
Scans and other tests:
Contrast or High resolution CT chest
CT abdomen and pelvis – to exclude secondary disease / confirm Thymus as primary
Octreotide (SPECT) or Gallium-Dotatate PET/CT.
FDG-PET – if NEC or rapidly progressing disease is suspected or seen
Pathology (what can be seen through special tests under a microscope):
Differentiation and cellular morphology
The key aim of treatment, should be to help you have the best possible care and quality of life – by ensuring access to appropriate treatment, management of symptoms and addressing what’s most important to you
Treatment options will depend on the type, position and size of your cancer – and whether (and to where) it has spread.
It will also depend on whether you have any other health concerns and / or illnesses and your general health and fitness.
One or more of the approaches below may be suggested:
- Control of your disease, by slowing or stopping further growth and / or spread
- Palliation, or easing, of any symptoms you may be experiencing.
Monitoring through clinic review, bloods and scans, can be used to assess how well treatment is working or in periods between treatments (which may be months/years).
As not everyone will need to be on treatment – surveillance can be used to check your cancer and general health for any signs of change that may mean that a treatment might need to be considered. All treatments have possible side-effects, therefore, it is important to know when treatment may be helpful for you or not.
To remove, partially remove or bypass neuroendocrine cancer and / or secondary sites of disease (metastases).
Small Thymic Neuroendocrine Cancers may be removed using may be removed using video-assisted thoracic surgery (VATS) – larger tumours or those that may have spread to surrounding tissues and structures will require open surgery.
In open surgery, the cut is made either through the sternum (breastbone) – this is called a sternotomy OR through the chest wall – this is called a thoracotomy.
Removal of the Thymic gland is called a Thymectomy.
Chemotherapy and / or Radiotherapy:
May be given before surgery, if it is believed that this may help to control, or reduce size of ,the cancer, to improve surgical clearance of disease.
Somatostatin analogues (SSAs):
May be used to help regulate the secretion of hormones if abnormal levels are being produced. SSAs may also be used to slow down growth rate in low to moderate grade ‘well-differentiated’ neuroendocrine cancer (NET) : Typical or Atypical Carcinoid of the Thymus.
Can be given orally (in tablets) or Intravenously (through a vein) to slow tumour growth or try to reduce tumour size. This may be the first line therapy in high grade disease – particularly “poorly-differentiated’ NEC or in combination with other treatments. Chemotherapy may also be used to increase tumour cell sensitivity to radiation therapies or given after surgery.
Targeted Molecular Therapies:
Can be given orally (in tablets) or Intravenously (through a vein) to slow tumour growth or try to reduce tumour size.
Peptide receptor radionuclide therapy (PRRT):
May also be called Radioligand Therapy – uses targeted radiation to treat neuroendocrine cancer cells. Can be used in some patients who have had a ‘positive’ Octeotide or Gallium scan (‘receptor positive’ disease).
Is sometimes given after surgery to kill any cancer cells that might remain there. It may also be used for cancer that has spread beyond the primary site, in particular if disease has spread to the bones – here it is used to help control growth of any spread and alleviate bone pain
Through techniques such as embolisation or ablation – can be used to treat Neuroendocrine Cancer that may develop in the the liver and / or lung(s).
Clinical research and safe new treatment development is essential to provide best care for those with Neuroendocrine Cancer – we need to know that treatments not only work but work safely. There are several phases of trial therapy – further information can be found here.
Each trial will have specific criteria in regards to patient suitability – this can be discussed with your clinical team. You do not have take part in a trial – participation is voluntary.
Managing symptoms, including pain, is an important part of total care – and therefore occurs throughout care, not just at ‘end-of-life’. Symptom control or ‘palliation’ refers to what is used to alleviate or reduce the impact your cancer, other health issues and /or treatments may be having on you and your physical and mental health. It can include anything from simple medication and / or a combination of some of the treatments mentioned above to counselling and practical support.
There are expert agreed guidelines regarding how and when follow up should occur, however, in practice this varies and often with good reason. Follow up should be expert informed & evidence /research based but also tailored to you and what is appropriate for your best care.
There are no consensus guidelines for follow up for Thymic Neuroendocrine Cancer, however recommendations have been published:
- Given nature of disease and potential for recurrence – lifelong surveillance is recommended – starting with 3-6 monthly CT scan over the first 3 years following surgery.
- MRI and Functional imaging (with either Octreotide (SPECT) / Gallium-Dotatate PET/CT or FDG-PET) if recurrence is suspected.
Alongside diagnostic / pre-treatment biomarkers.
Follow up as per available guidelines – but should be guided by prognosis, expected treatment efficacy and treatment related toxicity. Your health, well-being, physical activity, informed choice and preference for ongoing care as well as aim of treatment should be reviewed and discussed to best plan care.