Metastatic tumors to the oral cavity are rare. When affecting the oral cavity, tumors may occur in the oral soft tissues or in the jawbones. Due to its rarity, the diagnosis of metastatic lesions is challenging for both the clinician and pathologist. Nonetheless, metastatic disease should be considered in the differential diagnosis of more common inflammatory and reactive lesions, particularly when the patient presents with a history of a previous malignancy [1].

Metastatic tumors to the oral region are seen in patients between the fifth and seventh decade, with a mean age of 54 years [7, 8]. In our series, 61% of the patients were males and 39% females. The mean age was 64.6 years, similar in both groups (66.2 years in males and 62 years in females), in agreement with other studies [5]. Hirschberg et al. [1] observed the mean age for males was 51.1 years and for females 47.1 years. Likewise, van der Waal et al. [2] found the overall median age was lower in women than in men (53 and 66 years of age, respectively). However, the lower mean age for females was likely due to a small sample size, rather than a true epidemiological difference [2].

The clinical presentation of the metastatic lesions differs between the various oral sites. In the jawbones, most patients complain of rapidly progressing swelling, pain and paresthesia. The early manifestation of the gingival metastases resembles a hyperplastic or reactive lesion [1]. In their study, D’Silva et al. [9] found that pain, paresthesia and swelling were the most common symptoms. In our series, swelling was the most common complaint, but paresthesia was not very frequent; this probably occurred because we included both soft and hard tissue metastastic lesions, whereas the other authors investigated only jaw metastasis. Importantly, paresthesia may be the first symptom of metastasis in 30% of patients and mental nerve paresthesia, known as “numb chin syndrome,” should raise clinical suspicion of malignancy. The phenomenon, which is a late event in the course of disease, probably occurs due to compression or invasion of the mental nerve by the tumor, base of skull involvement, or leptomeningeal spread [10]. Besides swelling and paresthesia, our patients also presented with pain, temporo-mandibular joint issues and dental-related (loose teeth, non-healing extraction sites) problems. Our results indicate metastatic lesions may present with a variety of symptoms, highlighting that dentists and other health professionals should maintain a high level of suspicion when examining and treating their patients.

The most common reported primary sites for oral metastases are the lung, kidney, liver and prostate for men; and breast, genital organs, kidney, and colorectum for females. These cancers are also the most prevalent in the general population [8]. Likewise, in our series, the lungs were the most common primary sites for males, corresponding to 36% of the cases. In females, the lungs and breast were responsible for 42% of primary tumors, each. Similarly, van der Waal et al. [2] found that the most common primary sites for oral metastatic disease were lung and breasts. It has been postulated that metastatic lesions involve more commonly the jaws (65–75%) than the oral soft tissues (25–35%) [11]. Similarly, in our series, 72% of the cases spread to the bones. Furthermore, a recent meta-analysis showed more published cases of jawbone metastases than oral soft tissue malignancies [1]. However, it should be noted that metastatic lesions in the oral soft tissues are easily recognized, in contrast to the jawbone, where a metastatic deposit may not be evident especially in a wide spread disease, in which the patient may succumb within several months [1].

An additional important feature of metastasis is that certain tumors preferentially spread to specific sites. For instance, 11% of the jaw metastases in men originate from the prostate, compared with 1.5% of soft tissues metastases. In women, 40% of jawbone metastases originate from the breast, compared with 25% of the soft tissues lesions. Other examples include metastatic lesions from the adrenal, thyroid, and eye, which metastasize to the jaws more commonly [1]. Such information is important during clinical work-up to determine which areas are at higher risk of developing metastatic lesions, in patients with a previous history of cancer. In our series, all breast cancer cases spread to the mandible, whereas 57% (4/7) of the lung primaries spread to bones.

Within the jaws, the most common location for bony metastasis is the mandible (80%), with the great majority occurring in the molar (55%) and premolar regions (38%) [5]. Our findings are in agreement with the literature, with most cases seen in the mandible. The condyle is said to be affected in about 3.5% of the cases [7], while in our series condylar metastasis represented 22% (4/18) of the cases. An explanation for this mandibular predilection may be related to the larger amount of hematopoietic tissue in the mandible, compared to the maxilla. Further, the vascular spaces in hematopoietic tissue are sinusoidal, allegedly allowing more easily penetration by tumor cells. In 5% of the cases, both the maxilla and mandible are affected [11], such as in one patient of our series.

In the oral soft tissues, the attached gingiva is the most common site for the metastatic colonization (57%), followed by the tongue (27%), tonsil (8%), palate, (4%), lip (3%), buccal mucosa (1%) and floor of mouth (<1%) [12]. A recent study analyzed 39 patients with gingival metastasis and found these lesions represented 67% of all soft tissue metastasis [6]. The reason for this distribution is not known, but inflammation may play a role in the attraction of metastatic cells towards the gingiva [12]. Indeed, chronic inflammation has been linked to various steps involved in tumorigenesis, including cellular transformation, promotion, survival, proliferation, invasion, angiogenesis, and metastasis. The rich capillary network of the chronically inflamed gingival tissue may also entrap malignant cells [13]. Further, the microenvironment present in the chronically inflamed gums, rich in cytokines and chemokines, may favor the progression of the metastatic cells [14, 15]. An intriguing finding is that gingival metastases have a predilection for the maxilla, whereas bone metastases tend to affect the mandible. However, the pathogenesis for such preference remains unclear [6].