Head and neck metastases: case series

Précis: This case series highlights a range of head and neck metastases.

Abstract: Metastasis is the spread of primary cancer cells to another region in the body and the subsequent development of a metastatic malignant cancer. The most common oral metastases are primary breast, lung, bone and kidney cancers. Head and neck metastases have a very high mortality rate. This case series highlights some variable presentations of head and neck metastases. Each of the cases initially presented in a general dental setting. Both early diagnosis and correct management can improve outcomes for these patients, so it is important that dentists promptly recognise such clinical presentations.

Journal of the Irish Dental Association February/March 2022; 68 (1): 34-38

Introduction
Metastasis is the spread of primary cancer cells and the development of a cancer in a secondary, distant site within the body. The lymphatic or circulatory system facilitates this movement and an abundance of factors promote a successful secondary cancer colonisation.^1,2
Head and neck metastases are rare.³ They represent 1-3% of all oral malignant neoplasms, and peak prevalence is noted in the fourth to seventh decades.³ These patients have a high mortality rate with a poor life expectancy.² The most common primary cancers to metastasise to the head and neck include primary breast, lung, bone and kidney cancers. Breast cancer metastases are more common in women and lung metastases in males.^2,4-6 Pancreatic and hepatocellular cancers rarely metastasise to the head and neck.⁶ A metastatic tumour can sometimes lead to the diagnosis of the primary occult malignancy. This occurs in 20-35% of cases with oral metastases.^7-9 The majority of metastatic tumours in the oral cavity are of epithelial-derived tissue.^2,4,5,10 The predominant predilection for carcinomas has been well documented in comparison to sarcomas and other connective tissue tumours.⁴
Organ tropism is a term used to describe the site-specific predominance a primary cancer has for a secondary metastatic site. For example, this can be seen with breast, lung and prostate cancers, which have a tendency to metastasise to the mandible.^2,11 Some 70% of metastases in the oral cavity are located in the mandible, followed by the soft tissue, the attached gingivae and the tongue, respectively.¹² Oral metastases are twice as common in the mandible compared to the soft tissues.^2,8,13 Metastases to the salivary glands are very rare; however, the parotid gland is the most common salivary gland to be infiltrated.¹²

The metastatic process
The mechanism for metastatic movement and seeding of cancerous cells has been well documented in the literature. Hirshberg et al. (2014) documented that the development of a metastatic cancer is a regulated, controlled mechanism where it retains the cellular markers of the primary tumour in a distant site.² The ‘invasion-metastasis cascade’ describes the lifecycle of the circulating tumour cell (CTC) from the primary tumour, through a circulatory system in the body, and seeding in the secondary, distant site. This results in a metastatic colonisation and establishment of the neoplasm. ‘Tumour dormancy’ is a concept that describes the timeframe between the onset of the primary cancer and the subsequent development of the secondary metastatic cancer.² The metastatic process is both a host- and tumour-related process. There are two fundamental principles exhibited by a successful metastatic cancer: the ability to form its independent blood supply (angiogenesis); and, the destruction of host cells (apoptosis). Paget et al. were the first to describe the “seeds and soil” hypothesis, which remains the principal descriptor of distant tumour spread and invasion (Figure 1).¹

Clinical presentation of metastases in the head and neck
The presentation of an intra- or extra-oral metastasis can include intra- and extra-oral signs, symptoms and clinical findings, and predominantly has a sinister clinical appearance (Figures 2 and 3).³
Pain, swelling, paraesthesia and an exophytic mass are common soft tissue presentations of head and neck metastases.⁴ Pain was noted in 49% of cases in a study by D’Silva et al. (2006). Some 39% of patients did not have any symptoms on presentation.⁴

Radiographic signs of head and neck metastases
The orthopantomogram or intra-oral plain radiographic images are the first point of radiographic imaging. Further investigations, such as computed tomography (CT) and cone-beam computed tomography (CBCT), alongside a positron emission tomography (PET) scan, magnetic resonance imaging (MRI) and ultrasound for soft tissue enhancement,¹⁷ should be prescribed and interpreted in a hospital setting, and will often be discussed in a multidisciplinary team setting in conjunction with a precise history, clinical examination, special tests and photography. Sinister radiological findings include ill-defined or moth bony margins, atrophy of the lamina dura, and osteolytic and osteogenic defects, alongside relative anatomical size discrepancies.^11,18

CASE REPORT 1: soft tissue presentation

FIGURE 4: Initial presentation – an exophytic mass in the anterior maxillary alveolus, two months following the extraction of her upper left incisors and canine.

A 69-year-old female presented to the Cork University Dental School and Hospital following urgent referral by her general dental practitioner (GDP) with regard to non-healing extraction sockets in the upper left quadrant. Her medical history included hypertension. She reported she was a non-smoker with low alcohol consumption. On initial presentation, clinicians noted an exophytic mass in the anterior maxillary alveolus, two months following the extraction of her upper left incisors and canine. There was no pain or paraesthesia on presentation. The mass was firm, fixed, pedunculated, and bled on probing. There was no fluctuance noted (Figure 4).
Routine blood tests, an urgent biopsy of the exophytic mass and histopathological examination were performed. The patient was also being investigated for lung cancer by her medical team; she was experiencing pain in her right shoulder radiating to her right arm. All haematological parameters were within normal limits. Histopathology results revealed a poorly differentiated non-small-cell carcinoma with morphological features of a metastatic adenocarcinoma of the lung. The patient was placed on a palliative chemotherapy treatment regimen (carboplatin and VP16) for the primary adenocarcinoma of the lung and the oral metastatic non-small-cell carcinoma.

CASE REPORT 2: hard tissue presentation

FIGURE 5: Intraoral view – soft tissue mass in the left retro-molar region measuring 15mm 10mm – smooth, firm, dome-shaped swelling.

A 58-year-old male was referred by his dentist with a left-sided solid mass in the mandible. The patient stated that he had been experiencing submandibular swelling for one month. Two days before the appointment he heard a ‘snap’ in his left jaw. He was previously diagnosed with stage IV moderately differentiated rectal adenocarcinoma. Treatment included both chemotherapy and radiation therapy for his rectal cancer. He was an ex-smoker and consumed 10 units of alcohol per week. On examination, a soft tissue mass was detected in the left retro-molar region measuring 15mm × 10mm. There was a smooth, firm, dome-shaped swelling. (Figure 5). OPG showed a pathological, left-sided mandibular body fracture. An associated radiolucency is seen in the body of the mandible (Figure 6).

FIGURE 6: OPG showing a pathological, left-sided mandibular body fracture.
An associated radiolucency is seen in the body of the mandible.

An incisional biopsy of the intra-oral swelling was performed under local anaesthetic. Histopathology reported a metastatic, moderately differentiated adenocarcinoma, involving bone and sub-epithelial corium, consistent with metastasis from a large bowel primary cancer. The mandibular fracture was treated conservatively, which included a soft diet, analgesics and antibiotics. He was referred for radiotherapy by his oncology team. We removed the remaining two upper left premolar and molar teeth prior to commencing radiotherapy for the oral metastasis. The cancer was terminal and he subsequently passed away.

CASE REPORT 3: extra-oral presentation

FIGURE 7: Clinical examination
revealed an enlarged left parotid
gland, in particular fullness under the
left earlobe

A 72-year-old male presented to Prince Charles Hospital, Merthyr Tydfil, Wales, with a left-sided parotid swelling and associated ipsilateral cervical lymphadenopathy. The previous medical history included four cerebrovascular accidents (CVAs) since 2015, right-sided arm and leg weakness, ischaemic heart disease, pericarditis, and a previous pulmonary embolism. He did not declare any smoking habits or alcohol intake. Clinical examination revealed an enlarged left parotid gland, in particular fullness under the left earlobe (Figure 7). The was also a 7mm brown patch on the left helical, which was examined using a dermatoscope (Figure 8). The findings were indicative of a malignant melanoma. There was no family history of melanomas and the patient did not declare any other dermatological involvement.

FIGURE 8: 7mm brown patch on the
left helical.

Radiographic analysis included CT head, thorax, and pelvis, which detected a 3cm mass in the left parotid. An ultrasound-guided core biopsy was performed of the left parotid gland and an excisional biopsy was performed of the brown patch on the left ear. The histopathological findings confirmed a malignant melanoma on the left ear. This confirmed a pT2a superficial spreading malignant melanoma with Breslow thickness of 1.9mm.
A metastatic malignant melanoma was confirmed in the left parotid gland. The histological picture was described as an infiltration of pleomorphic plasmacytoid cells with occasional ‘cherry red’ nucleoli. The level four lymph nodes were reactive in nature and showed no evidence of atypia or malignancy material. Due to medical comorbidities, the patient is under palliative chemotherapy treatment for his metastatic melanoma of the left parotid.

Discussion
Metastases of the head and neck are rare. Currently, lung cancer remains the most prevalent primary tumour to metastasise to the head and neck.^7,13 Murillo et al. (2013) documented the frequency of lung (25%), kidney (15%), bone (10%), breast (9%) and liver (8%) cancers that metastasise to the oral cavity.¹³ Hepatocellular cancer metastasises in 50% of cases; however, only 1% of cases were reported in the oral cavity.¹⁹ A metastatic deposit is a prognostic factor for the overall survival of a cancer patient. Metastases are indicative of high mortality rates.²⁰
D’Silva et al. noted that 83.5% of metastases were present in the mandible compared the maxilla⁴ (significant to a P value less than 0.0002). The majority of patients were in their sixth and seventh decades. Other authors have noted an earlier prevalence, in the fifth and sixth decades.¹³ Some 23% of cases examined by Hirshberg et al. (2014) did not have a previous primary cancer diagnosis.^2,19 This figure coincides with the majority of the literature, which reports undiagnosed primary malignant cancers in 23-35% of cases.^7-9

Prognosis and mortality
There is an overall poor prognosis for these patients, irrespective of the primary origin.⁸ Palliative care has been the principal treatment modality for patients with oral metastases.^2,7,8,13 Another aspect of metastatic cancer is the timing between the diagnosis of a primary tumour and the metastasis. One study of 673 metastatic tumours to the oral cavity reported that the average time between the diagnosis of the primary tumour and the secondary tumour diagnosis was 40 months.²¹ After the diagnosis of the metastatic tumour, the average survival rate was seven months. This can limit a treatment plan to a palliative approach.⁸

Advice for the GDP
As part of a dental examination, dentists must be vigilant and screen for oral cancer (Table 1). The most common intra-oral presentations of squamous cell carcinoma are usually swelling and ulceration with raised rolled edges. The intra-oral swelling in case report 2 did not have these features. The features were more consistent with an adenocarcinoma. Dentists should be aware that oral cancer can have varying presentations. Cancer patients are living longer with their malignancy. It is imperative to obtain the correct information about a patient’s cancer history. Dental check-ups should include examination of the cervical lymph nodes, as cancer survivors are at a higher risk of developing a metastasis.^14,22,23

Guidance for the referral of an urgent suspected cancer
‘Suspected cancer: recognition and referral’ is guidance published by the National Institute for Health and Care Excellence (NICE) in the UK in 2015.²⁴ It helps practitioners to decide the most suitable management for a patient with a suspect oral cancer. Urgent referrals are warranted for ulcers of unknown aetiology persisting longer than three weeks, and swellings in the head or neck. Lumps on the lip or in the mouth, and erythematous patches present for greater than three weeks, which have been assessed by a dentist, must also be sent to a specialist centre with a two-week wait protocol.

Conclusion
The presentation of head and neck metastases is rare. No one sign or symptom is indicative of a metastatic deposit; however, the clinical indicators in this case series should help dentists during routine examination. The high mortality and morbidity rates associated with metastatic cases demands a high level of vigilant and clinical awareness in order to appropriately manage the case.

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Harriet Byrne
BA BDentSc (Hons) MFDS Dip
PCD RCSI PgCert (ClinEd)
Oral and Maxillofacial Department,
St James’s Hospital, Dublin

Jonathan Hulbert
MBChB BDS (Hons) FRCS (OMFS)
Maxillofacial surgeon,
Prince Charles Hospital,
Merthyr Tydfil, Wales

Kaumal Baig BDS
(NUI) MFD (RCSI) DipPCD (RCSI)
PgCert (Anatomy) PgCert (ClinEd)
Oral Surgery Department,
Cork University Dental School and Hospital,
Wilton, Cork

Paul Brady B
DS PhD MFDS FFDRCSI
MScConSed PGCert-TLHE
Oral surgeon,
Oral Surgery Department,
Cork University Dental School and Hospital,
Wilton, Cork

Catherine Gallagher
MB FDSRCS FFDRCSI (OS)
PCME PCSPM
Oral surgeon,
Oral Surgery Department,
Cork University Dental School and Hospital,
Wilton, Cork

Corresponding author: Harriet Byrne, Oral and Maxillofacial Department,
St James’s Hospital, Dublin Hbyrne@stjames.ie