Renal cell carcinoma uvula metastasis leading to airway compromise: an unusual site

Abstract

We present a case report of a gentleman presenting with a globular lesion arising from his uvula. Although elective admission was planned, he presented with airway compromise, and emergency excision was required. The patient had a background of metastatic clear cell renal carcinoma; histology confirmed the uvula lesion as a further secondary deposit. Renal cell carcinoma has a recognised metastatic propensity, but spread to the uvula is rare, with only two previously described cases in the literature. This case is notable for the unusual location of the metastasis, as well as the rapid progression of symptoms, which threatened the airway and necessitated urgent surgical intervention.

Background

Renal cell carcinoma (RCC) is the most common type of kidney cancer, and accounts for approximately 3% of adult malignancies.¹ There is a male preponderance (M:F=2:1), and it is most commonly diagnosed in the sixth decade. It is recognised to have a high potential for metastatic spread; commonly described sites include lung, bones, lymph nodes, liver and brain. Rarer locations have been noted in the literature, including inguinal lymph nodes, peritoneum and orbit.^2–4 Metastatic spread of RCC to the uvula has been reported on two occasions; in one case it was the presenting complaint,⁵ while the other case presented 3 years after initial diagnosis and had been preceded by metastatic spread to the nasal cavity and maxillary sinus.⁶

This case is notable for the unusual location of a secondary lesion and due to the rapid progression of the growth. While clinically the mass was suspicious for metastatic disease, radiological features reported by our most experienced head and neck radiologist suggested benign characteristics; surgical excision and histological examination were required to confirm the diagnosis.

Case presentation

A man in his 50s was referred to the Ears, Nose and throat (ENT) department with a 2-week history of sore throat and the sensation of a lump at the back of his throat. At initial presentation, he had no breathing difficulties, no dysphonia and no otalgia. Examination revealed a 4 cm slough covered globular lesion, arising from the posterior aspect of the uvula. Flexible nasal endoscopy demonstrated a normal hypopharynx and larynx.

The patient had been diagnosed with clear cell renal carcinoma the previous year; he had metastatic disease at the time of diagnosis, with bilateral lung metastases and skeletal metastases. He initially presented with a lytic lesion in his left hip; he sustained a pathological fracture and required a total hip replacement and radiotherapy. Palliative immunotherapy, consisting of ipilimumab and nivolumab, had been started 4 months prior to his presentation to the ENT department, and was ongoing at the time of presentation. Other significant medical issues included type two diabetes, ischaemic heart disease (for which he underwent cardiac stenting), hypertension and a 25 pack-year smoking history.

Investigations

Given this male’s significant oncological history, urgent imaging was requested. Ultrasound of the neck demonstrated no cervical lymphadenopathy. An MRI confirmed a polypoid tumour arising from the posterior aspect of the inferior tip of the uvula, measuring 25 mm sagittal diameter, 22.5 mm coronal diameter and 14.4 mm anterior–posterior (figures 1 and 2). The uvula itself was described as normal, as were the soft palate and tongue; there was no evidence of tumour extension. The diffusion characteristics of the lesion were described as benign, and suggestive of a benign polyp arising from the posterior uvula.

Figure 1.

MRI sagittal view (T2 weighted, contrast enhanced). Lesion marked by asterix.

Figure 2.

MRI axial view (T2, fat suppression (FSE), contrast enhanced). Lesion marked by asterix. FSE, fast spin echo sequence.

Differential diagnosis

Despite radiologically benign features, given the patient’s background (known metastatic disease, in addition to immunosuppressive treatment) and the appearance of the mass, clinical suspicion for malignancy was high. Metastatic spread of RCC was felt to be the most likely diagnosis, however the possibility of a new primary lesion of the uvula could not be excluded. Differential diagnosis included squamous cell carcinoma, lymphoma,^{7 8} benign polyp and oral squamous papilloma.⁹

Treatment

The patient was initially booked for an elective procedure, for excision of the lesion including uvulectomy. Unfortunately, he became increasingly symptomatic, experiencing dysphagia and breathing difficulties while lying flat at night. He presented acutely, with difficulty breathing; he was admitted and his procedure was performed as an emergency, due to concerns that further delay may risk airway compromise.

During the procedure, the lesion was excised with a clear margin and sent for histology (figure 3). This was followed by a uvulectomy, which was sent as a separate sample.

Figure 3.

Uvula lesion excised in toto. A well circumscribed, globular mass, measuring 30 mm × 30 mm once excised.

Outcome and follow-up

The patient experienced almost complete resolution of his symptoms following his procedure. There were no immediate postoperative concerns, and he was discharged the following day. He was reviewed 2 weeks later, and although he had a significant amount of postoperative pain, which is not unusual for this procedure, the operation site was healing well.

Histology results confirmed the mass as a metastatic deposit of clear cell renal carcinoma. The uvula itself did not contain any residual tumour, confirming complete excision. The patient was referred back to the oncology team for ongoing m0.18nt; a review 1 month following his procedure noted a mixed response to immunotherapy. He is to be continued on nivolumab and repeat imaging has been requested for 3 months’ time to monitor his progress.

Discussion

Nearly a quarter of RCC patients present with metastases, while a further 50% will go on to develop secondary deposits during the disease course.¹⁰ The tendency of RCC to metastasise is attributed to its vascularity. Survival is dependent on staging at diagnosis; those presenting with metastatic disease have a 12% 5-year survival rate.¹¹ While the lungs, liver, brain, bones and lymph nodes are the most common sites, spread to more unusual locations has been described.¹² Secondary spread of RCC to the head and neck region is rare and is typically associated with a poor prognosis.¹³ The tongue has been noted to be the most common site of metastatic spread of RCC within the oral cavity.¹⁴ To our knowledge, spread to the uvula has been reported on two occasions prior to this case. The first case was described in 1973; the uvula lesion led to the patient’s initial presentation and subsequent diagnosis of RCC.⁵ In contrast, the second case described presented 3 years after initial diagnosis. The patient had undergone several surgeries, including right nephrectomy, Whipple’s procedure for pancreatic metastases and endoscopic sinus surgery for metastases to her left ethmoid sinus and nasal cavity. She presented a year later with vague nasal symptoms, and while an MRI did not detect the tumour, a 2 mm uvula mass was identified on examination of the oropharynx.⁶ The tumour described in the current case was considerably larger, thereby accounting for the more clearly defined symptomology. In keeping with our current case, complete surgical excision was the treatment of choice.

Metastatic disease accounts for only 1% of all malignant oral cavity lesions,¹⁴ and therefore, it is important to obtain histological confirmation of the diagnosis, as this dictates treatment options and prognosis. Secondary spread to the head and neck region is typically as a result of seeding from other metastatic deposits, the most common site being the lungs. RCC favours haematogenous spread, and in the case of head and neck metastasis, the likely route is from lung deposits, via the axial skeleton to the head and neck region. The oral soft tissues have a rich capillary network, and the uneven basement membrane of proliferating capillaries may allow malignant cells to penetrate the tissues more easily.¹⁵

Given the proportion of RCC patients that have secondary disease at the time of presentation, it is not uncommon for the discovery of metastatic lesions to initiate further investigation and eventual diagnosis, as was the case described Lansigan et al.⁵ Being readily visible, and with the potential for even small masses to cause troublesome symptoms, patients will usually present promptly with lesions of the uvula. The uvula metastases described by Khade and Devarakonda,⁶ and in the current case, were discovered in patients that already had wide-spread metastasis. This is in keeping with the theory of spread described above, in which metastases in the head and neck are most commonly seeded from deposits in the lung. The rapid growth of the lesion described in this case, may be in part attributed to the vascularity of the uvula.

As previously noted, survival prognosis in patients with renal cell metastases to the head and neck region is poor; treatment options include surgical excision and radiotherapy to aid symptom management. In the case described, surgical excision was both diagnostic and provided full symptomatic relief. It is interesting to note the rapid progression of symptoms in this case: the patient was asymptomatic at an oncology review 1 month prior to his initial ENT presentation, yet within 2 weeks of that review he had developed swallowing and breathing difficulties, necessitating urgent removal of the mass.

Surgical excision of metastatic RCC lesions has been supported for local control of the tumour and symptom management.¹⁰ Non operative modalities have not been shown to significantly improve survival in metastatic RCC, although immunotherapy with interleukins or interferon has demonstrated some improvement.¹⁶ While the benefits of metastectomy have been widely discussed, desirable excision margins have not, although clearly the aim is to achieve a negative margin. A margin of at least 10 mm has been suggested for the excision of liver secondary deposits, although there is evidence to support narrower margins when this is not achievable.¹⁷ When deciding whether surgical intervention is appropriate for RCC metastases, the disease course to date, the location of the secondary deposit and the potential surgical morbidity must be considered. For patients with multiple metastases, systemic therapy is the recommended initially.¹⁸ Given the acute, airway threatening presentation of the current case, surgical excision was unavoidable, but regardless, the location of the metastasis offered easy surgical access with low risk of morbidity, and effective symptom relief. The tumour was excised in toto, and negative margins were achieved.

Patient’s perspective.

The main thing I would say was the speed, it was incredible how quickly it grew – this thing was going to grow another head! The original surgery date was obviously not going to be something that I would make. In a 2-week period, it had grown from a little spot and it blossomed to the point I couldn’t breathe. It was a difficult thing to deal with, with all the other things going on with my treatment, as I couldn’t sleep—I was struggling to breathe at night and having to physically dislodge the mass to breathe again. I had quite a tortuous year, waiting 6 weeks in hospital for my hip replacement. I think a sense of urgency in the future would be useful—it didn’t seem anybody wanted to deal with the thing that was choking me because of politics and COVID-19. I wouldn’t wish it on anybody. Seeing how quickly it grew, it makes you think, if that can grow in 3 weeks, what can happen in the 3 months between my scans. It makes me nervous.

Learning points.

• Renal cell carcinoma (RCC) has a high metastatic potential.

• Metastatic spread of RCC to the head and neck region is uncommon.

• Metastases account for a very small proportion of malignant lesions in the oral cavity.

• Histological confirmation is instrumental to treatment planning.

• Treatment options for metastatic RCC include surgery and radiotherapy, with the primary aim of localised disease control. The patient’s overall performance status, the site of the metastasis and the potential of treatment related morbidity, is used to guide decision making.

Ethics statements

Patient consent for publication

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