38.1 Introduction

Although squamous cell carcinoma and salivary gland carcinomas are by far more common tumors, other malignant tumors including melanoma, sarcomas, and lymphomas can also arise in the oral cavity. These tumors are rare and can often be mistaken for squamous cell carcinoma, so a proper pathologic diagnosis is critical. Most of these uncommon malignancies are treated with comprehensive surgical resection, except for lymphomas and some sarcomas.

38.2 Epidemiology

Given its rarity, epidemiologic data on oral mucosal melanoma (OMM) have been compiled primarily from small case series, database searches, and systematic reviews of the literature. Primary melanoma of the oral cavity is estimated to represent less than 1% of all melanoma cases ^{1 – 3} and 0.26% of oral cavity tumors. ⁴ It is more common in certain geographic areas and ethnic groups, with the highest incidence in Asia and lower incidence in North America and Europe. ^{4 – 6} OMM is usually noted in patients in their fourth to sixth decades of life and is exceedingly rare in younger patients. ^{3 , 5 – 7} The etiology of OMM is unclear. Some of these lesions arise de novo, but evolution of a benign pigmented lesion into a melanoma has also been reported. ^{3 , 4 , 8} No environmental risk factors have been identified, though OMM appears to be slightly more common in smokers. ^{3 , 7} A variety of genomic alterations have been identified in OMM including mutations in p53, p16, bcl-2, and NRAS. ^{3 , 7} The biology of mucosal melanoma is different in many ways from cutaneous melanoma. OMMs are more likely to have mutations in c-KIT and less likely to have mutations in BRAF. ^{3 , 6 , 7} There is no definite gender predominance, ^{1 , 2 , 5 , 6 , 8} though men with this disease appear more likely to develop distant metastases. ¹

The vast majority of patients will develop distant metastatic disease even when good local control is achieved, and the prognosis is poor. ^{4 , 6 , 7} The 5-year overall survival for OMM is approximately 20% ² with a range of 13 to 40% in the literature. ^{3 , 4 , 7} Age greater than 55 to 60 years; stage; thickness, ulceration, and mitotic rate of the tumor; positive surgical margins; and nonsurgical therapy are associated with worse survival in OMM. ^{1 – 3 , 5 , 7} As with other oral cavity lesions, lymphovascular and perineural invasions are also adverse prognostic features in OMM. ⁷

Sarcomas of the oral cavity are also relatively rare. Osteosarcoma and rhabdomyosarcoma are seen more frequently, but a number of sarcoma types have been reported to arise in the oral cavity, including Ewing’s sarcoma, angiosarcoma, granulocytic sarcoma, leiomyosarcoma, liposarcoma, myeloid sarcoma, malignant fibrous histiocytoma, fibrosarcoma, synovial sarcoma, spindle cell sarcoma, and malignant peripheral nerve sheath tumor. ^{9 – 21} These sarcomas can arise in the bone of the mandible/maxilla, temporomandibular joint, muscles, mucosa of the oral cavity, or salivary glands. ²² Osteosarcoma that arises de novo is most frequently seen in patients in their third or fourth decade of life. ²⁰ Rhabdomyosarcoma and Ewing’s sarcoma are more common in children or adolescents and rarely seen in adults. ^{11 , 23} Characteristics of several sarcoma types previously reported to arise in the oral cavity are listed in ▶ Table 38.1.

Prior radiation is one known risk factor for oral cavity sarcoma, most commonly osteosarcoma. The latency period between radiation and development of osteosarcoma of the mandible is usually 10 years or more. ^{20 , 24} Kaposi’s sarcoma may be noted in association with human immunodeficiency virus (HIV) infection, though cases in patients without HIV infection have also been reported. ^{25 – 28}

While extranodal lymphoma of the head and neck arises most commonly in the lymphoid tissue of Waldeyer’s ring, it can also arise in the oral cavity. Intraoral lymphomas are found in patients of all ages, ^{29 – 31} though the mean age was 71 years in one series. ³² There is no clear gender predominance. ^{30 , 32} Most are B cell lymphomas with aggressive clinical behavior, most commonly diffuse large B cell lymphoma (DLBCL). ³² A particularly aggressive subtype of DLBCL, plasmablastic lymphoma, is most often seen in patients with a history of HIV infection. ^{33 – 35} Burkitt’s lymphoma may also arise in the oral cavity in endemic areas of Africa or patients with HIV. ³² Less commonly, oral Hodgkin’s lymphoma, T cell or NK/T cell lymphomas may develop. ^{32 , 36 – 38} Patients with a history of Sjogren’s syndrome may also be at risk for development of oral cavity lymphomas, though these lesions usually arise in the major salivary glands. ³⁹ Sjogren’s-associated lymphoma is most commonly mucosa-associated lymphoid tissue (MALT) lymphoma, but this can transform into a more aggressive DLBCL. ³⁹ Given the lymphoma risk, a biopsy should be performed on any solid oral cavity or salivary gland mass in patients with a history of Sjogren’s syndrome. Finally, patients who have had bone marrow or solid organ transplants can, on rare occasion, develop posttransplant lymphoproliferative disease (PTLD) of the oral cavity. ⁴⁰

38.3 Clinical Presentation

As can be expected, mucosal melanoma of the oral cavity usually presents as a painless, pigmented lesion (▶ Fig. 37.5), though they do often ulcerate and bleed when more advanced. ^{2 , 3 , 5 , 7 , 8} The pigment may be black, brown, grey, red or purple, and in some cases the lesions are nonpigmented. ^{2 – 4} This may be related to lower levels of pigment production in melanocytes of oral mucosa versus melanocytes of the skin. ⁵ Similar to cutaneous melanomas, OMMs exhibit asymmetry, indistinct borders, and satellite lesions. ⁵ Because it causes few other symptoms, primary melanoma of the oral cavity often presents at advanced stage. ¹ The most common subsites of the oral cavity involved by OMM are the hard palate and gingiva, but other sites including the tongue, floor of mouth, and buccal mucosa may also be involved in rare cases. ^{1 – 6 , 8} Invasion of surrounding soft tissue and bony structures is also common. ³ Mucosal melanomas of the oral cavity are more likely to metastasize to the neck than melanomas of the paranasal sinuses, with rates of nodal metastasis estimated to be 25 to 43%. ^{3 , 8} Over half of OMM patients will have regional metastatic disease in the neck upon presentation, while distant metastases are not usually detected until later. ^{2 , 8} Common sites of distant metastasis include the lungs, brain, bone, and liver. ⁵

Sarcomas of the oral cavity are often rapidly growing lesions, though some may have more indolent behavior. ¹⁶ They often present as a painless mass or swelling. ^{14 , 15 , 17 , 20} Osteosarcomas may present as new mass in a prior radiation field and may be mistaken for osteoradionecrosis. ^{20 , 24 , 41} Other lesions may be mistaken for squamous cell carcinoma, which is far more common. Sarcomas involving the mandible or maxilla may present with loss or mobility of teeth. ²⁰

Extranodal lymphomas of the oral cavity often arise as a swelling or ulceration in the gingiva, spreading to the mandible, maxilla, or zygoma where they can cause pain and bony destruction, ^{29 – 32} as shown in ▶ Fig. 38.1. These lesions can progress rapidly. ²⁹ Lymphomas of the oral cavity are often solitary lesions with no involvement elsewhere; however, many patients will have other bony lesions or disseminated disease. ³¹