Maxfacts

Metastases in the head and neck region can be to regional lymph nodes, bones or extranodal. They may be part of a primary tumour process, a manifestation of recurrence of a primary head and neck cancer which has been treated, or a manifestation of a distant primary tumour. The investigation and management of each is very different.

We start with a description of the challenges in accurately diagnosing recurrence and metastases of head and neck cancer after initial treatment by surgery and/or radiotherapy.

Next, we discuss briefly head and neck metastases arising from other, distant solid tumours and how maxillofacial surgery is engaged in the management of such conditions (with some similarities to the various support tasks that oral & maxillofacial surgery has in the treatment of haematological malignancies).

About 30 to 40 percent of head and neck malignancies are initially diagnosed when local / regional lymph nodes are already involved in some way, with micro- or macro-metastases manifest as part of a primary tumour process. Accordingly, these local and regional aspects of disease and the corresponding staging are also discussed on our pages on the initial diagnosis, assessment and treatment of, in particular, oral malignancies. That situation has similarities both with the situation after recurrence and/or the later discovery of metastases, as well as significant differences with regard to diagnosis and treatment options. Below we discuss head & neck malignancies in the context of tumour recurrence and associated metastasis.

Diagnostic (imaging) challenges after previous treatment for head & neck cancer

Most head and neck tumour recurrences and/or metastasis occur within two years of initial treatment. Ongoing close monitoring is therefore important after initial treatment, as well as self-observation by patients and prompt reporting of any newly developing symptoms (such as pain, dysphagia, weight loss, neck lumps or earache). Medical examination and the usual range of imaging modalities - ultrasound, X-ray, CT and MRI scans - are the main monitoring tools.

This is the reason behind specialist clinical follow up (as opposed to expecting a non-specialist to manage follow up in the early post-treatment years). The first two years are also the time when most patients have to deal with the most distressing consequences of treatment and a regular association with those who conducted the treatment is of obvious value.

Specialist clinical examination has to be coupled with specialist radiological investigations and their interpretation by those with particular expertise in this area. Evaluation of imaging results in these circumstances is challenging because of effects of previous treatment (major surgery and reconstruction and/or radiotherapy) leading to tissue changes that can make detection of local recurrence and/or locoregional metastasis difficult. In these circumstances all imaging modalities and biopsies carry a risk of false positives or false negatives. The tissue conditions following radiotherapy, after initial swelling and inflammation, are a particular form of extensive fibrosis with thickening affecting all layers and compartments of soft tissues, including fatty and muscle tissues, and oedema. Major ablative and reconstructive surgery, in particular previous neck dissection leads not only to neck asymmetry but longer term also causes fibrosis. All of these tissue changes following major surgery and/or radiotherapy change over extended periods of time and at all stages make it difficult to distinguish tumour recurrence from tissue changes caused by previous treatment(s). For example, shortly after surgery fluid collections or haematoma may appear like residual tumour. Later in the process, the disruption of muscles and nerves by free flaps leads to changes in muscle and fat tissue that are noticeable in MRI and CT scans and require careful interpretation of results. Late effects of fibrosis may resemble or obscure recurring malignancy.

In practice this means that a complete history of the nature of previous treatment(s) and imaging results is an important part of the diagnostic interpretation. Typically, more than one imaging modality will be necessary to reduce uncertainty, and possibly some less standard imaging methods may be helpful, for example diffusion-weighted MRI in addition to the more commonly used MRI sequences. PET scans can be useful to detect or exclude distant metastases as well as persistent or recurring disease from about 10 weeks after initial treatment (to avoid false positives). It is commonly assumed that a PET/CT scan with only positive results for the neck but nowhere else is a good indication for the absence of distant metastasis. Biopsies are likely to be necessary and it may be necessary to opt for local examination and/or biopsy under general anaesthesia in order to obtain accurate identification of location and extent of any recurrence and/or locoregional metastases. Even with such invasive exploration by biopsy under general anaesthesia, a significant percentage of false negatives has been reported in the literature.

Obtaining as much information as accurately as possible is key to being able to determine the best possible treatment options by trying to find answers to some questions such as

• is the tumour / metastasis operable and with what intent;
• what salvage options exist;
• what functional deficiencies would result;
• can the sensitivity of the tumour / metastases to radio-, chemo-, or immunotherapy be predicted;
• are there any signs of distant metastases;
• are there any serious co-morbidities;
• do the tumour / metastases affect vital structures such as the carotid artery (artery in the neck), pre-vertebral muscles, or the brachial plexus;
• are the jugular veins (veins in the neck) viable (more for venous drainage of a flap than a necessity, sacrifice of a unilateral jugular vein is not a major problem);
• what information is obtained from histology / cytology about the nature (microscopic and genetic) of the tumour / metastases.

Head and neck metastases from other distant solid tumours

The majority of cervical (neck) metastatic lymph nodes originate from head and neck malignancies. However, other distant solid tumours can deposit metastases to the lymph nodes in the neck, usually by lymphatic spread although rarely haematogenous spread can result in deposits in the bone of the jaws or cervical spine.

Once head and neck malignancies can be excluded as the origin for these, a search for a primary tumour in some other distant location is warranted unless the distant tumour of origin is already known. The neck is usually investigated by MRI scans with PET/CT for the rest of the body as primary radiological investigations. Careful clinical examination is usually assisted by flexible nasendoscopy to confirm no occult head and neck primary tumour is present. Ultrasound imaging and/or biopsy may follow.

If no primary can be identified, the term most frequently applied to the disease is carcinoma of unknown primary (CUP). CUP, if the histopathology is commensurate with a malignancy which could arise in the head & neck region and no other primary is identified, is then treated on the basis that the cancer has started in some undetectable location (or possibly regressed) in the oropharyngeal mucosa. Treatment is then combined surgery to remove the residual disease and any seeding created by the biopsy process by way of an extended, modified radical neck dissection with total mucosal irradiation afterwards. This is very much a ‘blunderbuss technique’ with severe, often devastating, post-treatment adverse effects, so every effort is made to identify a specific primary site.

Malignancies of lung, stomach, oesophagus, breast, prostate, cervix, testis and kidney have all been reported as the primary source of neck metastases. Sometimes a neck lump is the first detected sign of such malignancies. For most of these primary tumours, the occurrence of neck metastases is associated with a poor prognosis. By definition the metastasis is beyond the first echelon of lymphatic drainage. Biopsy confirmation of the pathology of the metastasis coupled with appropriate staging of the primary tumour is essential as in some instances treatment with curative intent is appropriate (for example testicular cancer). In other instances aggressive treatment would be completely inappropriate.

Neck dissection for isolated metastatic deposits of some of these primary tumours has been shown to be beneficial (oesophagus, testis) if the intention of treatment is clearly defined. In some other cases neck dissection may not extend the life span, but may help to improve quality of life by better management of dysfunction caused by local bulky or fungating (ulcerating) metastatic tumours. This, and rarely resection of an extranodal or bony deposit with limited reconstruction, is sometimes termed ‘curative surgery with palliative intent’. That is; the same surgery that would be performed if the primary tumour was local in order to attempt cure is performed at the site of the metastatic deposit but is performed with the intention of improving symptoms even though cure is impossible.

Beyond that, the role of maxillofacial surgery is essentially in establishing a diagnosis. If the primary site is outwith the head and neck region, the relevant site-specific multidisciplinary oncology team guides treatment. Treatment of metastatic melanoma with immunotherapy agents would be an example of a multidisciplinary approach.

Recurrence of, and metastases from, primary head and neck tumours

Above we describe in some detail the difficulties of obtaining reliable diagnostic information when monitoring the situation after treatment for a primary head and neck malignancy. Having all this information is key when tumour recurrence and/or locoregional metastases require decisions about the most suitable treatment option(s) and whether these should be considered with curative or palliative intent.

In turn, these decisions can only be made with confidence if sufficient information about the biology and microenvironment of a tumour (in addition to other patient factors) is known. Taken together, all these different diagnostic pieces form parts of a large information-jigsaw puzzle in the attempt to characterise specific properties of a tumour.

This is becoming increasingly important as progress in understanding tumour biology and genetics is rapid. In the future, knowing as much as possible about the characteristics of a tumour will become increasingly relevant to enable more specific treatment modalities.

For example, if the initial treatment modality was radiotherapy, the primary tumour may have had intrinsic or acquired resistance to high-energy irradiation, some malignant stem cells with intrinsic insensitivity to radio- or chemotherapy may have survived. Some malignant cell lines, over courses of chemotherapy acquire improved ability for cell DNA repair and thus become insensitive to chemotherapy with drugs such as cisplatin that harm cell lines by causing damage to DNA. Over time and over previous treatment, surviving tumour cell lines will have undergone further mutations, resulting in changed tumour characteristics. This includes activation of the various mechanisms by which tumour cells become mobile, travel by lymphatic and/or haematogenous routes, and are able to settle and start new growth / metastasis in other parts of the body.

Predicting a logical anatomical progression of metastasis is often possible before treatment of a primary tumour (with the exception of some malignancies behaving in unusual fashion, for example adenoid cystic or salivary duct malignancies). Once treatment for a primary tumour has been undertaken, especially if it involves neck surgery and/or radiotherapy, this orderly spread pattern of metastases according to type, stage and exact location of the primary tumour, gravity, and local & regional haematogenous and lymphatic networks, is no longer followed. This evolution of behaviour adds to the diagnostic challenges, and the resulting difficulties to select the most suitable treatment modalities for recurrence of and/or metastases from head & neck malignancies.

Nevertheless, some trends exist. Common sites for distant metastasis from head and neck malignancies are the lungs and spine (both near well vascularised zones, so lymphatic spread to axilla and lungs makes sense as does haematogenous spread to the spine), followed by the liver.

Few specific treatments of distant metastasis from head and neck malignancy currently exist. The most pertinent is localised radiotherapy to spinal metastasis of oral or oro-pharyngeal squamous cell carcinoma. This is indicated and effective for pain and is one of the few times when emergency radiotherapy is administered. This is when signs and symptoms of spinal cord compression are present in conjunction with a spinal bony metastasis. Despite what has been said above, in these rare cases symptomatic relief almost always occurs.