Neck lump with an unknown primary: what it means and how it is investigated

Macmillan Cancer Support explains that a primary cancer is where the cancer started, and a secondary cancer, also called a metastasis, forms when cancer cells spread to another part of the body through the blood or lymphatic system. In cancer of unknown primary (CUP), doctors have found a secondary cancer but have not yet found the primary cancer. A neck mass of unknown primary is a version of this in which the secondary cancer is in a lymph node in the neck.

Because the lymph nodes in the neck sit close to the ears, nose, throat and mouth, a neck node with cancer cells is assessed together with an examination of those areas. NICE's guideline on unknown primary notes the diagnosis is first assessed by looking for a primary site that will guide treatment, and for cancers such as lymphoma that can be treated regardless of primary site.

It matters to put this in proportion. Most neck lumps are not cancer. NICE CKS say that children are most likely to have a benign cause such as reactive cervical lymphadenopathy, that single neck lumps are often congenital or inflammatory, and that malignancy is rare, with lymphoma, thyroid cancer and soft tissue sarcoma most likely.

The first sign is usually the lump. NICE CKS say that persistent or rapidly growing neck masses, for example present for more than 6 weeks, are more likely to be malignant, that a lymph node larger than 3 cm may be indicative of malignancy, and that lymph node metastases tend to have a short history with progressive increase in size. They list red flag symptoms that suggest a local cancer of the upper airway or digestive tract.

• Difficulty swallowing or pain on swallowing.

• A cough, sore throat or persistent voice change or hoarseness.

• Pain in one ear, nasal obstruction or nosebleeds.

• Loose or misaligned teeth, or a sensation of a lump in the throat.

• Coughing up blood.

• Persistent fatigue, night sweats, unexplained fever or weight loss, which may suggest a blood cancer such as lymphoma.

The NHS says for swollen glands to see a GP if they are getting bigger or have not gone down within 1 week, feel hard or do not move when you press them, come with night sweats or a very high temperature, occur with no other signs of infection, or are just above or below the collarbone. It says to ask for an urgent GP appointment or call NHS 111 if you have swollen glands and are finding it very difficult to swallow or have difficulty breathing.

NICE CKS say signs of stridor, superior vena cava compression, or difficulty swallowing with aspiration require emergency admission, and NICE's suspected cancer guideline advises considering a suspected cancer pathway referral for oral cancer in people with a persistent and unexplained lump in the neck. Risk factors that raise suspicion include being over 40, smoking, heavy alcohol use, betel nut use, previous head and neck cancer or irradiation.

Assessment by the GP includes the history, risk factors and examination of the neck and of the ears, nose, throat and mouth, per NICE CKS. An urgent neck ultrasound may be arranged for a neck lump that is increasing in size. If cancer is suspected the person is referred to a specialist team; Macmillan notes the GP may refer directly to a malignancy of unknown origin (MUO) team, a CUP team or a rapid diagnostic centre.

NICE CG104 describes two phases. The first aims to identify a primary site, or a cancer that can be treated regardless of primary site such as lymphoma, melanoma, sarcoma or germ-cell tumours. For cervical lymphadenopathy with no primary found on ear, nose and throat panendoscopy, NICE advises PET-CT if radical treatment is an option. Macmillan lists the tests that may be used: blood tests, X-rays and scans, endoscopy, biopsy, and special tests on biopsy tissue such as immunohistochemistry, which look for proteins on cell surfaces, to give clues about where the cancer began.

Macmillan says doctors may stop looking for the primary if you are not well enough for tests or further results are unlikely to change treatment, and that tests such as gene expression profiling are not usually available on the NHS outside clinical trials. Waiting for results can be hard; Macmillan notes results may take from a few days to a couple of weeks.

NICE says every hospital with a cancer centre or unit should have a CUP team that, as a minimum, includes an oncologist, a palliative care physician and a CUP specialist nurse or key worker, and that each patient should have a named specialist nurse or key worker. A patient with suspected malignancy with no clear primary site should be assessed within 2 weeks of referral, and the CUP team remains involved until the person is referred to a site-specific consultant, referred for palliative care alone or found to have a non-malignant condition.

For a squamous cell carcinoma in the upper or mid neck nodes, NICE says referral is to a head and neck multidisciplinary team (MDT). Macmillan says that a team of specialists meets to discuss the best possible treatment, known as a multidisciplinary team (MDT) meeting.

Treatment depends on the cell type, the extent of spread and your general health, and is agreed by the MDT. NICE's guideline identifies neck presentations as one of the situations that may benefit from radical treatment, meaning treatment aimed at cure, and that is why the head and neck team is involved. Macmillan explains that in many cases of CUP the cancer is already advanced and not usually curable, and that the aim of treatment is then to control the cancer, help you live longer, treat symptoms and improve quality of life, so the likely aim will be explained to you.

After treatment you will have regular check-ups and may have follow-up scans. Macmillan says that if the aim was cure you may see your cancer doctor or specialist nurse every few months for up to two years, and that you should tell them about new symptoms between check-ups. Support is available from your specialist nurse and from cancer charities, and talking about how you feel is a valid part of care.