Metastatic ameloblastoma refers to a lesion that metastasizes to a distant organ but the histology of both primary and metastatic tissues is benign [11]. It is an infrequent entity, accounting for approximately 2% of ameloblastoma cases [12]. The commonly reported site for metastasis includes the lungs, cervical lymphnodes, diaphragm, liver, brain and bone [5]. The lung is the most common site for metastasis, and in approximately 80% of the cases, the primary site is the mandible [4]. The case which has been presented here is considered rare not only because of being metastatic ameloblastoma but also due to the fact that maxilla was the primary site.
The mechanism by which a histologically benign-looking lesion spreads to a distant organ is unclear [13]. Proposed mechanisms of metastatic spread include hematogenous and lymphatic routes and aspiration of tumour cells from the primary oral lesion [4, 13, 14]. Another possible mode of metastasis is tumour implantation during surgical procedures [8]. In the current case reported, direct implantation of tumour cells in the lung and aspiration from the endotracheal tube during previous surgery (hemimaxillectomy) cannot be ruled out.
Metastatic ameloblastoma may occur at any age, ranging between 5 and 94 years [13, 15]. However, the 3rd decade of life seems to be the most affected age group [8, 10, 12, 16, 17]. The number of years between the diagnosis of the primary tumour and metastases varies between 0 and 15 years [15]. In the case presented here, the patient presented with a primary tumour at the age of 17 years, and at the age of 24 years, he developed metastasis. This falls within the same range of time as documented in the literature.
Our patient did not have any signs or symptoms that could raise suspicious of lung metastasis, unlike in case reported by Rabo et al. [8] in which the patient had intermittent, non-radiating, sharp and piercing upper back pains. It was the clinical behaviour of the tumour (i.e. painful, bleeding and highly invasive) that did not match with histological diagnosis of ameloblastoma that led to further workup including a chest x-ray and CT scan. These investigations led to the identification of a lesion on the chest raising suspicion of metastasis that was later confirmed by cytology. The diagnosis of metastatic ameloblastoma is almost always made retrospectively after metastasis has occurred and not otherwise [14]. It is difficult to predict which cases would metastasize and which would not, and this is among the challenges in managing these lesions.
Histopathologically, it is difficult to differentiate between metastatic ameloblastoma and non-metastatic ameloblastoma, however, there are specific markers that show strong positivity in metastatic ameloblastoma [4, 18, 19]. Immunohistochemical markers that are strongly positive in ameloblastoma but not in metastatic ameloblastoma include extracellular-signal-regulated kinase 5 (ERK-5) and KRSA, whereas, N-terminus-truncated p73 isoform (∆Np73) was reported to be found in 100% of metastatic ameloblastomas [19]. In the current reported cases, however, these investigations could not be carried out due to reasons such as unavailability of reagents for carrying such investigations and the cost of acquiring these reagents. Immunohistochemistry for Ki 67 was done, however, it does not specifically point out to metastatic ameloblastoma but rather indicates local invasiveness and recurrences of ameloblastoma, thereby its prognosis [20, 21].
There is no therapeutic gold standard for treating metastasizing ameloblastoma due to the small number of cases reported [18]. Radical surgery remains the mainstay of therapy, while the role of chemo- and radiotherapy still is yet to be defined [10, 18]. In some cases, surgery has been successfully combined with additive and adjuvant radiotherapy [10]. Radiotherapy has been recommended for inoperable metastatic deposits, but because the response is unpredictable, it is used only for palliative care [8]. In the case reported herein, surgery could not be done as the tumour had already extended to the cranium, thus palliative chemo-radiotherapy was chosen, which, however, showed no significant benefit. Since surgery was not done, the prognosis was expected to be poor, as it has been reported that with adequate resection and radiotherapy, the median survival is 6 years compared to 2 years when resection is not done [17].
There may be a role for routine annual chest x-rays when assessing patients with ameloblastomas [22], however, in our case, this could not be done as the patient did not turn up for follow-up clinics after the first surgery, and only came back with a huge tumour 6 years later. Delay in seeking health care and failure to attend the follow-up clinics is attributed mainly to financial difficulties that most of the patients in developing countries face [23].