From Volume 41, Issue 3, April 2014 | Pages 230-235
Metastatic involvement of the jawbones is uncommon, particularly in the maxilla. Case reports of such metastases from renal cell primaries are few, making a consensus on treatment difficult to establish. We present a case of metastatic involvement of the maxilla two years following a nephrectomy for renal cell carcinoma. The case exemplifies the broad range of symptoms attributable to metastases in the maxilla and the management dilemmas.
Maxillary swellings may be caused by a variety of aetiologies, however, metastatic involvement of the maxilla remains uncommon, with metastases accounting for only 1–3% of all malignant neoplasms in the oral region.1,2 Identification of metastases by adequate histology is essential in determining further treatment as, in around 30% of cases, the oral lesion is the first sign of disease.3 This puts an onus of responsibility on primary dental care practitioners to recognize key clinical and radiographic features and have a low threshold of suspicion for presentation that might suggest such pathology.
A 65-year-old man presented to his general dental practitioner with a large palatal swelling measuring approximately 2 cm by 2.5 cm and confined to the right side of the hard palate. On examination, the swelling appeared firm on palpation, painless and pulsatile, with normal overlying oral mucosa. In association with this, the patient had begun to develop mobility of adjacent teeth in the upper right quadrant over the preceding weeks. Clinical examination revealed increased mobility of UR6, UR5, UR4 and UR3, despite there being no mobility of the dentition in any other quadrant. An orthopantomogram (OPT) was taken (Figure 1) which revealed a uniform enlargement of the right maxillary sinus with evidence of significant alveolar resorption in comparison to the contralateral side. There was accompanying evidence of root resorption of the adjacent teeth with no signs of displacement.
The patient was referred to an oral and maxillofacial surgery department, where further questioning revealed several months' history of nasal obstruction, recurrent epistaxes, unilateral hearing loss and an uncomfortable sensation around the right eye. On examination, the patient's right eye was found to be proptosed and the globe displaced superiorly. Flexible nasoendoscopy was performed which revealed a large, pulsatile swelling on the right side of the hard palate with no further extension into the nasopharynx and normal appearances of the pharynx and laryngeal inlet.
Past medical history of note included ischaemic heart disease and a T1N0M0 renal cell carcinoma, which had been treated by a right radical nephrectomy two years previously, with no adjuvant treatment in accordance with recommendations for the treatment of localized disease.4
A computed tomography (CT) scan was requested, which showed a large soft tissue mass in the right maxillary sinus extending into the ethmoidal sinuses posteriorly and the floor of the orbit superiorly (Figure 2).
Given the pulsatile nature of the swelling, differential diagnoses at this stage included intra-osseus haemangioma, nasopharyngeal angiofibroma, haemangiopericytoma and haemangioendothelioma. Malignant variants, such as angiosarcoma, were also considered, as was the possibility of secondary metastases from the preceding renal cell carcinoma. An opinion was sought from the interventional radiology team regarding the need for embolization prior to biopsy of the lesion. This was felt to be unwarranted and biopsy revealed features consistent with a metastasis from a renal cell carcinoma primary of a clear cell variety.
Treatment options of surgery (hemimaxillectomy), chemotherapy and radiotherapy were discussed with the patient. Two months subsequent to the initial presentation, the patient completed a course of chemo-radiotherapy. The clinical response to interferon and sorafenib was limited and had to be discontinued owing to unacceptable side-effects. Continued growth of the tumour was noted on a follow-up CT scan at six months and the patient was started on sunitinib, which was well tolerated (the mode of action of both sorafenib and sunitinib will be discussed later in the text). The lesion appeared stable with no further growth at a subsequent CT scan at one year. Maxillary artery embolization was successfully carried out at 18 months to help control symptoms, mainly epistaxis and bleeding from the palatal mass (Figures 3 and 4).
Tumours of the maxilla tend more often to be malignant than benign. Furthermore, malignant lesions tend most commonly to be primary tumours, the most frequent of these being squamous cell carcinomas, with others including pleomorphic adenomas, mucoepidermoid carcinomas, lymphomas and rhabdomyosarcomas.1,5 Pulsatility may be one indicator of renal cell carcinoma metastases as a differential diagnosis, with other possible sources of pulsatile metastases to the maxilla including thyroid and choriocarcinoma.6
A number of histopathological subtypes have been identified of renal cell carcinomas, with subtypes including clear cell, papillary, chromophobe and collecting duct on haematoxylin and eosin staining, with clear cell carcinomas having poorer prognosis, even after stratifying for stage and nuclear grade.7 Clear cell carcinomas classically demonstrate cells with small nuclei and abundant cytoplasm set in delicate vasculature. Whilst histological diagnosis is usually possible by light microscopy alone, immunomarkers have been highlighted in helping to make the diagnosis in equivocal cases in recent literature.8 All subtypes have the potential to demonstrate sarcomatoid differentiation, a particular growth pattern suggesting an aggressive disease course.9
Metastatic involvement of the maxillary sinus from renal cell carcinomas has been documented elsewhere in the literature but remains uncommon in clinical practice.10,11,12,13 Clinical features may vary from proptosis and recurrent epistaxes, as in the case presented here, to paralysis of the abducens nerve.11,12 Surgery remains one option but palliative treatments, such as interferon therapy and embolization, remain tried and tested methods. Ord et al reported two cases of embolization for renal cell carcinoma metastases to the maxilla and point out that this may be utilized as either palliative treatment or pre-operatively pending surgical resection.6
Developments have been made in the field of targeted therapies for the treatment of renal cell carcinoma metastases and featured in the case presented here. Sorafenib is an inhibitor of VEGFR-2, VEGFR-3, PDGFRβ, RAF-1, c-Kit and RET that has shown equivalent efficacy when compared with interferon-α in a phase II trial in terms of progression-free survival (PFS). Sunitinib is an inhibitor of c-Kit and Flt-3 tyrosine kinases which has been shown to yield improved PFS when compared with interferon-α in randomized controlled trials. (Table 1 gives a brief explanation of the growth factor receptors and tyrosine kinase receptors highlighted in this paragraph.)14
| Receptor | Summary of Action | Clinical Associations |
|---|---|---|
| c-Kit/CD117 | Codes for a membrane tyrosine kinase receptor which has stem cell factor or mast cell growth factor as its ligand | Piebaldism, gastro-intestinal stromal tumours (GISTs), breast cancer, colorectal cancer (CRC), small cell lung cancer (SCLC), seminoma, melanoma, ovarian cancer, prostate cancer, leukaemias, salivary gland adenoid cystic carcinoma |
| RET | A tyrosine kinase receptor | Medullary thyroid carcinoma, parathyroid hyperplasia, phaeochromocytoma, multiple endocrine neoplasia types IIA and IIB |
| RAF-1 | A family of protein-serine/threonine kinases that participate in the RAS-RAF-MEK-ERK signal transduction cascade | Malignant melanoma, thyroid cancers, colorectal carcinoma, ovarian carcinoma, juvenile myelomonocytic leukaemia |
| VEGFR-2 and -3 | Tyrosine kinase receptors for vascular endothelial growth factor (VEGF) responsible for angiogenesis and lymphangiogenesis | Role in angiogenesis of a wide range of solid tumours including: colorectal carcinoma; non-small cell lung cancer and small cell lung cancer; breast carcinoma and prostate carcinoma; as well as benign conditions such as wet macular degeneration |
| PDGFRβ | Tyrosine kinase receptor for platelet derived growth factor family | Myeloproliferative disorders, chronic myeloid leukaemia, acute myeloid leukaemia |
| Flt-3 | Tyrosine kinase receptor that regulates haematopoiesis | Acute myeloid leukaemia, acute lymphoblastic leukaemia |
It is important to recognize in clinical practice that metastatic involvement may occur many years after nephrectomy, and should always be included in the differential diagnosis of growths in the paranasal sinuses in a patient with a known history of renal cell carcinoma.11
Primary dental care practitioners are uniquely placed to recognize the initial presentation of metastatic involvement of the maxillary antrum. There should be a low threshold of suspicion when the periodontal health of a single quadrant is out of keeping with the remainder of the mouth. Other associated features in the history and examination, such as pulsatile swelling, recurrent epistaxes, nasal obstruction, proptosis, cranial nerve involvement and hearing deficits should be sought and referral for further investigation and management made in a timely manner.
