23 Squamous Cell Cancer of Retromolar Trigone
The retromolar trigone (RTM) is the mucosal space located between third molar of the mandible and maxillary tuberosity. Carcinomas of the RMT often remain asymptomatic for prolonged periods resulting in advanced clinical disease at presentation. Unfortunately, even early T stage disease (T1/T2) of the RMT can have a high local recurrence rate due to undetected extension to surrounding anatomic areas. Accurate diagnosis and staging require thorough clinical examination and appropriate imaging workup. Surgical therapy is the first line of management and can be technically challenging to resect and reconstruct.
The cancers of retromolar trigone (RMT) are prevalent in regions of the world where there is tobacco and/or betel nut use. Because of potential late presentation and under staging, they can have a poor clinical outcome.
23.2 Anatomic Considerations
The RMT is a triangular area of mucosa, overlying the mandibular ramus, immediately posterior to the 3rd molars (▶ Fig. 22.4). 1 The base of the triangle is posterior to the last mandibular molar and the apex is in continuity with the maxillary tuberosity behind the last upper molar. RMT is bounded laterally by the gingival buccal mucosa and medially by anterior tonsillar pillar (▶ Fig. 23.1). Pterygomandibular raphe (PMR), which is a central fibrous band extending from pterygoid hamulus superiorly to mylohyoid line inferiorly, lies under this triangular fold of mucosa (▶ Fig. 23.2). 1 PMR provides attachment to buccinators and superior constrictor muscles.
23.3 Clinical Presentation
The cancers involving this subsite of oral cavity are notorious for indolent growth and late presentation. Cancers of this area may present as isolated ulcerative or endophytic lesions and may present with involvement of adjacent structures, that is, buccal mucosa or tonsillar fossa. Patients often present with advanced stage disease presenting with trismus as an initial presenting symptom (▶ Fig. 23.3).
Due to proximity to the maxilla, mandible, and pterygomandibular raphe (PMR), the cancer of RMT has propensity for local invasion of these sites. Although superficial extension is not difficult to diagnose, the extent of involvement can be difficult to accurately discern. One or more adjacent subsites are involved in 73 to 84% of cases reported. 3 , 4 The most common sites of local involvement are reported to be the anterior tonsillar pillar (80%), the soft palate (59%), and the lower gum (37%). 5 , 6 The cancers of RMT are also known to have particular propensity toward bone involvement. The largest survey regarding bone invasion in RMT cancers was reported by Byers et al. 4 In a series of 110 patients with RMT involvement, they reported 14% incidence of histopathologic bone invasion. In another study examining all oral cancer sites, Gilbert et al 7 reported bone invasion in 3 out of 17 patients with RMT cancer. Brown et al 8 reported 75% incidence (9/12 cases) of bony involvement.
23.4 Epidemiology and Causes
Oral and pharyngeal cancers, together, constitute the sixth most common cancer in the world. There is wide geographical variation in the incidence of oral cancer, with the areas of South and Southeast Asia (India, Sri Lanka, Pakistan, and Taiwan), parts of Western (France) and Eastern Europe (Hungry, Slovenia, and Slovakia), parts of Latin America and the Caribbean (Puerto Rico, Brazil, and Uruguay), and Pacific regions (Papua New Guinea and Melanesia) characterized by higher incidence than the rest of the world. In countries like India, Sri Lanka, Pakistan, and Bangladesh, oral cancer is the most common cancer and constitutes 25% of all new cancers. 9 According to an estimate by American Cancer Society, there will be 51,540 new cases of oral cavity and pharyngeal cancer in United States in 2018. Approximately 10,030 will die of the disease in 2018. 10
Etiology of oral cancer including RMT is multifactorial. Cigarette smoking remains the most important risk factor for oral cavity cancer including RMT. Concomitant alcohol use has synergistic effect, further increasing the risk of oral cavity cancer by 10- to 15-fold. Regular alcohol consumption is associated with the increased risk of oral cancer including retromolar subsite of oral cavity. In this dose dependent association, people consuming 4-5 drinks daily are at two to three times higher risk of oral cancer than nondrinkers. 11
Betel nut chewing is one of key factors causing the increase in the incidence of retromolar cancers in Southeast Asia. International Agency for Research on Cancer classifies betel quid as oral carcinogen with evidence of dose-response relationship. 12 About 600 million people are exposed to the habit of betel nut chewing making it the fourth most-consumed drug after nicotine, ethanol, and caffeine. 13
Parker et al reported higher incidence of oral and pharyngeal cancer in the area of the world with high prevalence of betel-quid chewing. 14 According to a study by Yeole et al in 2001, oral cancers among Parsi subgroup of population in Mumbai, India was significantly lower than non-Parsi population. Parsis are known to be nonsmoker and also avoid chewing betel quid due to religious reasons, although both of these addictions are very common in Mumbai, India. They reported that, in 1995, annual age-adjusted incidence rates (per 100,000) of cancers at several sites were lower among Parsi men than among the male population of Mumbai as a whole: tongue and mouth, 4.5 versus 11.9; pharynx, 2.6 versus 10.6; esophagus, 2.6 versus 8.7; stomach, 2.8 versus 6.6; larynx, 2.2 versus 7.2; and lung, 4.2 versus 12.6. 15
Betel nut quid is known to induce fibroblast dysfunction and fibrosis causing a premalignant condition called submucosal fibrosis. 13 Oral submucosal fibrosis (OSF) is characterized by hypovascularity of mucosa leading to blanching, staining, and trismus. The fibroblast dysfunction and fibrosis are caused by the main constituents of betel nut quid, i.e., arecoline and copper. Paymaster 16 described slow growth of squamous cell carcinoma (SCC) in one-third of the patients with OSF. Malignant transformation rate of OSF has been reported to be in the range of 7-13%. On long-term follow-up, studies have reported a transformation rate of 7.6% over a period of 17 years. 17 Pindborg et al 18 and Murti et al 19 in two separate studies reported malignant transformation of OSF in oral cancer in 4.5% of their study populations.
Deficiencies in non-starchy vegetables, fruits, and foods containing carotenoids has been reported to be associated with oral cancer. 11 Role of various micronutrients is not very clear. It has been theorized that plant-based foods contain substances with antioxidant and anticarcinogenic properties. These nutrients could play an important role in amending the carcinogenic effects of tobacco smoke, alcohol consumption, and betel quid chewing.
Most cancers arising in retromolar area are SCCs. The lesions could be ulcerative, exophytic, or infiltrative in nature. A thorough history and physical examination is crucial for initial diagnosis and staging. Cancers of RMT have a very complex spatial relationship with surrounding structures. They can spread in several directions through direct extension as well as can involve the mandibular bone or have a perineural extension via the inferior alveolar nerve. Although the presence of trismus may raise the suspicion of pterygoid muscle involvement, it may be due to the inflammation of pterygoid musculature. It is important to assess the space from where the pathology has originated, tumor size, and if there is trans-spatial extension or invasion of deep structures. History and physical examination should evaluate the factors such as lifestyle habits (including alcohol consumption, smoking, and use of drugs), comorbid conditions (including nutritional status, chronic obstructive lung disease, and liver function), and a detailed family history. All of these factors may affect the management of primary disease.
23.5.1 Clinical Examination
Detailed clinical examination performed in an upright position is a vital part of the management of retromolar cancers. This should not only involve inspection, but also palpation of the mucosa and underlying soft tissue. It is the practice of our institute to evaluate all new cancer patients with flexible fiberoptic laryngoscope and document the examination as videos. This allows for adequate assessment of various subsites of the head and neck that are not easily evaluated by direct visualization.
It is often difficult to diagnose cortical bone and periosteal invasion based on clinical examination. Due to apposition of mucosal surfaces in oral cavity and oropharynx, early stage small lesions can be missed or its true depth may not be accurately delineated. It is extremely important for any imaging study to evaluate the local as well as regional/distal extent of the tumors for appropriate surgical or nonsurgical management.
Computed tomography (CT) and magnetic resonance imaging (MRI) scans are complementary in the evaluation of retromolar cancers. CT is considered to be a good first-line imaging test to assess the extent of RMT lesion. On contrast enhanced CT, the lesion appears as enhancing mass in the area of RMT. It is difficult to pick up small lesions due to opposition of mucosal surfaces. “Puffed-cheek” technique is reported to be helpful in the detection of small doubtful lesions. Erdogan et al 20 evaluated 11 patients in a prospective study to compare the effectiveness of conventional CT and puffed-cheek CT in detecting the presence and extent of oral malignant tumors. They reported that the puffed-cheek CTs provided additional information about the true size and extent of the tumor than the conventional CT. Puffed-cheek maneuver is easily taught and is easy to comply with. Initially, the patients were asked to hold breath while puffing their cheeks. But it was also possible to puff out the cheeks and continue breathing quietly further improving the compliance as well as quality of the study.
Bone windows of CT scan can be used to evaluate the erosion of cortical bone adjacent to the tumor. These windows may also be able to show findings suggestive of aggressive periosteal reaction, pathological fractures, and abnormal attenuation in bone marrow. Lane et al 21 reviewed the records of patients with biopsy proven retromolar cancer. They compared the preoperative CT findings with histopathologic findings during surgery. They reported that preoperative CT scan failed to detect bone invasion in 27% of the patients. In the study, the sensitivity of CT for bone involvement in RMT was reported to be 50%, with a negative predictive value of 61.1%. The positive predictive value was reported to be 91.1%. The inaccuracy of CT scan in detecting bone involvement is significant in treatment planning. Arya et al 22 investigated the accuracy of 16 section multidetector computed tomography (MDCT) in assessing mandibular invasion in RMT cancers. MDCT involves replacing the linear array of detector elements used on typical conventical and helical CT scanners with two-dimensional array of detector elements. This permits acquisition of multiple slices simultaneously and with increased speed. They reported sensitivity, specificity, and accuracy of 16 section MDCT for mandibular, cortical, and marrow invasion as 94, 90, and 91.8% and 83, 92, and 89%, respectively. The accuracy for detection of inferior alveolar canal invasion was reported to be 100%.
Crecco et al 23 evaluated the diagnostic accuracy of magnetic resonance images to find out both the T stage and establish the spatial relationship between the tumors and surrounding structures in RMT area. In this study, preoperative MRI staging data correlated with pathology in 19 of 22 patients with overall accuracy of 86%. MRI is able to provide exact T staging of tumors due to better soft tissue contrast. MRI images are also less affected by dental amalgam compared to CT and have high sensitivity for marrow infiltration and perineural spread.
Vidiri et al 24 retrospectively compared the diagnostic accuracy of MRI and MDCT. Thirty-six surgical patients with histologically proven SCC of oral cavity who performed both a preoperative MRI and MDCT were retrospectively analyzed. Although, MRI showed higher sensitivity compared to MDCT, findings were not statistically significant. Wiener et al 25 retrospectively reviewed 52 patients with histologically proven primary SCC of oral cavity who underwent both 16-slice MDCT and MRI. Results of radiological assessment were correlated with the intraoperative and histopathological findings. They reported MRI to be better for T staging compared to MSCT due to underestimation of tumor size by MSCT.
Advantages of preoperative MDCT are ability to use multiplanar reformatting at a faster speed of scanning and better patient compliance. When used optimally, it also has high accuracy in detecting mandibular invasion. MRI images are less likely to be degraded by dental amalgam, have more accurate T staging, and have high sensitivity for marrow infiltration and perineural spread. Genden et al 26 recommended a panoramic radiograph and CT scan for all patients presenting with a tumor of RMT. In patients with trismus, extensive soft tissue involvement, and/or change of sensation including pain, MRI scanning was recommended.