The first case of oral cavity mucosal melanoma was described in 1859 by Weber. The tumor was found in the palate, which remains the most common location for this malignancy to date followed by the guns [60–64]. Since the original description primary oral mucosal melanoma (OMM) represents a small percentage of tumors unlike their cutaneous counterparts and is a highly aggressive tumor. OMM represent approximately 0.2–8 % of all melanomas in the USA and Europe, but it appears this incidence differs with geographic location. In regard to oral cavity tumors, OMM represent approximately 0.26 % demonstrating the rarity of this entity [65, 66]. There is a higher male-to-female predilection (2.1–1) for OMM, and the median age of presentation is reported 20 years later than cutaneous melanoma with a mean age in the mid-50s [66–69]. The etiology of OMM remains unknown. In the 2010 American Joint Commission of Cancer staging system, mucosal melanoma of the head and neck was added as an entity with staging starting at T3 (Table 14.1).

Mucosal melanoma of the lip specifically is even rarer entity with only few cases or series found in the literature [65, 70, 71]. In all series and case reports, the theme appears similar, late diagnosis advanced disease at time of presentation and poor prognosis [70–72]. Nodal involvement appears to consistently influence survival as does misdiagnosis that leads to inadequate treatment and multiple recurrences [73]. Radiographic surveillance of the head and neck with CT or MRI should be included in the work-up with particular attention to invasion or the underlying bone of the maxilla or the mandible (Fig. 14.3). Surveillance for distant metastasis should also be included in the initial work-up especially in advanced cases. Surgery is the treatment of choice for these malignancies. Aggressive wide local excision is the treatment of choice for lip tumors similar to the recommendations for the oral cavity OMM. The need for neck dissection should be considered based on the clinical and radiographic findings. Recurrences could be treated with additional surgery. Strong consideration should be given to chemotherapy with high doses of IL-2 or newer options such as vemurafenib and ipilimumab in the presence of distant metastasis for eligible patients as they appear to be the only potential chance for cure [74–77]. Retrospective studies on patients with mucosal melanomas have shown an improvement in local control with adjunct radiotherapy compared to surgery alone, but the impact to long-term survival remains unknown [78]. Unfortunately patients with mucosal melanoma develop distant metastasis and have poor prognosis despite adequate surgical resection especially when advanced stage disease is present (Fig. 14.4a, b).

Mesenchymal origin malignant tumors are overall rare entities in the head and neck with aggressive behavior and generally poor prognosis. Only few cases from various entities are reported in the lips. The types of mesenchymal tumors reported throughout the literature include descriptions of round cell, spindle cell, and mixed cell sarcomas in addition to more specific lymphangiosarcomas or neurogenic sarcomas [79–83]. Only few cases from various entities are reported specifically in the lips. For example, out of 136 dermatofibrosarcoma protuberans, a slow-growing but locally aggressive skin malignancy – that can be found in the head and neck in 12–15 % of the time – only one case was found in the lips [84]. In the oldest case series of sarcomas found in the lips reported in 1934 by Cholnocky, 20 tumors were located specifically in the lips, and the author added another four cases all located in the vermillion border. It is thus difficult based on the available literature to draw conclusions on incidence gender predilection and provide treatment recommendations for such entities. Generally speaking surgical resection with wide tumor-free margins is the generally accepted approach. Each case though requires careful review of pathology to determine the exact entity on hand and tailor treatment appropriately.