Disclosure
Carcinoma of the buccal mucosa is relatively uncommon in North America, compared with other oral-cavity cancers such as carcinomas of the tongue or floor of the mouth. Squamous cell carcinoma is the most common pathology and most prevalent in those who use tobacco and/or alcohol. Problem: The oral cavity functions in speech, in the oral phase of swallowing, and in breathing. The buccal region is particularly important in the oral preparatory phase of swallowing because it prevents food from spilling into the lateral oral gutters or extraorally as the food bolus is being prepared. Both the cancer and its treatment may interfere with any of these functions. Buccal carcinoma has the propensity to become aggressive, with high rates of local recurrence. Early diagnosis of allows for surgery that is less extensive than that needed later and improves the prognosis. Frequency: In North America, buccal carcinoma accounts for only 5-10% of all cancers of the oral cavity. It occurs most often in the 7th or 8th decades, with the median age at diagnosis or 70 years. Buccal carcinoma occurs more commonly in men than woman, with a ratio of 3-4:1. An exception to this is noted in the Southern United States, where the incidence is highest among women because of their practice of snuff dipping. The incidence of buccal carcinoma is higher in Asia, particularly Southeast Asia, where it is the most common form of oral cavity cancer. In India, buccal carcinoma is the most common cancer in men and the third most common cancer in women. It tends to develop at an earlier age, with most cases occurring in those aged 40-70 years. The higher rate in Asia is believed to be due to the widespread practice of chewing betel nuts, a tobacco product that is placed along the buccal mucosa. Etiology: Tobacco and alcohol use are the main etiologic agents associated with the development of buccal carcinoma. In North America, a history of using tobacco, in the form of cigarettes or chewing tobacco, is documented in 70% of patients with buccal carcinoma. A dose-response relationship exists between tobacco exposure and the development of oral-cavity cancer. Betel nut and Paan are 2 forms of tobacco frequently used in Southeast Asia, particularly in India, where 98% of patients with buccal carcinoma have a history of using Betel nuts. A history of excessive alcohol use is less common in patients with buccal cancer compared with patients having carcinomas at other subsites of the oral cavity. Approximately 20-30% of patients with buccal carcinoma have a history of excessive alcohol use. Tobacco and alcohol have a well-recognized synergistic effect in the development of carcinoma. Other suspected but not confirmed etiologic agents include human papilloma virus (HPV subtype 16), poor oral hygiene, and chronic irritation. Premalignant conditions include submucosal fibrosis and lichen planus. The latter has a reported transformation rate of 0.5-3%, whereas the former has a malignant transformation rate of 0.5%. Clinical: Buccal carcinoma most commonly occurs as a slow-growing mass on the buccal mucosa. Pain occurs after ulcers develop and as the lesions enlarge. Oral intake may worsen the pain, leading to malnutrition and dehydration. Associated symptoms include bleeding, poor denture fit, facial weakness or sensory changes, dysphagia, odynophagia, and trismus. Small lesions tend to be asymptomatic, and dentists might notice them incidentally. The person often has a history of tobacco or alcohol use. A detailed medical history is important to determine the patient's candidacy for surgery or radiation therapy. A history of previous malignancies of the upper aerodigestive tract should be ascertained. Comprehensive examination of the head and neck should be conducted with a focus on the oral cavity. The ears should be examined in those with a history of otalgia, as a lack of evidence of ear disease suggests referred pain due to malignancy. The mucosa of all the subsites of the oral cavity and oropharynx should be examined systematically. Buccal carcinoma often arises in an area of leukoplakia, most commonly in the central portion of cheek. The etiology tends to affect the location of the carcinoma. For example, individuals who used chewing tobacco develop cancer in the lower sulcus of the buccal mucosa. The lesion often has 1 of 3 morphologic types: exophytic, ulceroinfiltrative, or verrucous. The exophytic type is the most common, appearing as a papillary mass that becomes ulcerated when large. The ulceroinfiltrative variety appears as an ulcer that penetrates deep into the underlying structures, with surrounding induration. Verrucous carcinomas are uncommon variants of oral-cavity carcinomas; among these, the buccal mucosa is the most common site. These lesions appear as papillary masses, and keratinization gives them a whitish appearance. Palpation is important to determine the depth of invasion. Mandibular or maxillary alveolar invasion should be noted on inspection and palpation. Dentition must also be assessed, especially if irradiation is part of the planned management. The larynx and hypopharynx should be assessed by means of examination with a mirror or flexible endoscopy to rule out a second primary tumor of the upper aerodigestive tract. Signs of advanced disease include bleeding, skin ulceration, facial swelling, neck mass, trismus, facial numbness, and paralysis of the facial musculature. The neck and parotid gland should be carefully examined for adenopathy. Diaz et al found that 27% of patients presented with clinically positive nodes. The risk of nodal disease at presentation increases with advanced-stage disease. In their meta-analysis of 4 studies with 223 cases of buccal carcinoma, Chhetri et al found that most presented with T2 or T3 disease (12% T1, 47% T2, 19% T3, 22% T4). The rate of nodal metastases at presentation was 40% for T2 disease and 52% for T3 disease.
Any lesion of the buccal mucosa that suggests malignancy should be studied at biopsy for definitive diagnosis. Once the diagnosis is established, treatment options include surgery, irradiation, or combined-modality treatment. The therapeutic modality depends on the stage of the tumor and on the patient's general health and desires. In North America, surgery with or without postoperative radiation therapy is the standard treatment, with primary radiation reserved for those patients who are poor candidates for surgery. Traditionally in India, irradiation has been the mainstay of primary treatment, with surgery followed with postoperative radiation therapy applied for advanced disease.
Relevant Anatomy: The American Joint Commission on Cancer defines the buccal mucosa as the membrane lining of the inner surface of the cheeks from the line of contact of the opposing lips anteriorly to the line of the pterygomandibular raphe (lateral to retromolar trigone) posteriorly. The medial boundary is the line of attachment of the buccal mucosa to the upper and lower alveolar ridges. The layers of the cheek from medial to lateral include the mucosa, pharyngobasilar fascia, buccinator muscle, buccinator fat pad, subcutaneous tissue and skin. Sensory innervation of the buccal mucosa and cheek skin is from the maxillary and mandibular branches of the trigeminal nerve. The buccinator muscle is innervated by the facial nerve. The parotid duct, also named the Stenson duct, pierces the buccinator muscle and buccal mucosa adjacent to the upper second molars. The region lacks anatomic barriers to prevent the spread of cancer. The only barrier is the buccinator muscle and its fascia. Buccal cancers can spread laterally outward through the skin of the cheek. Medially, the lesion may involve the alveoli, palate, tongue, and floor of the mouth. Posterior spread may involve the retromolar trigone mucosa, the ascending ramus of the mandible, and the masseter and pterygoid muscles. Anterior spread involves the oral commissure and lips. The primary-echelon lymphatics of the buccal mucosa drain to the facial nodes (prevascular and postvascular nodes) and submandibular nodes prior to draining to the upper jugular nodes (jugulodigastric nodes). The lymphatics may occasionally drain to the upper jugular nodes via the parotid nodes. Contraindications: Contraindications to surgery include poor medical status, a patient's refusal of surgery, unresectable disease (eg, skull-base fixation and carotid encasement), and the presence of distant metastases. Contraindications to radiation therapy include previous irradiation (relative contraindication) and collagen vascular disorders. Reluctance of the patient to undergo the dental intervention frequently required to prevent osteoradionecrosis is another relative contraindication for radiation therapy. |
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Lab Studies:
Imaging Studies:
Diagnostic Procedures:
Classic histologic features of squamous cell carcinoma include atypical epithelial cells infiltrating the basement membrane, with intercellular bridges and keratin formation depending on the degree of differentiation. Squamous cell carcinoma stains positive for keratin. Histologic features of verrucous carcinoma include papillary hyperplasia, hyperparakeratosis, and large bulbous frondlike rete ridges with a broad, pushing front. It is well differentiated, with rare mitoses. The tumor, metastases, and nodes (TMN) classification is an expression of the anatomic extent of a primary tumor (T), neck disease (N) and metastases (M). The stage grouping condenses the different TNM combinations into groups, with each stage being homogenous with respect to survival.
Medical therapy: Radiation therapy Radiation has a limited role as primary therapy in North America, but it is used as adjuvant postoperative therapy in advanced stage disease. Indications for radiation therapy in the postoperative setting include large or deeply invasive tumors, positive margins, multiple positive nodes, extracapsular spread of nodes, and vascular, neural or lymphatic invasion on pathology. Tumor thickness greater than 3-4 mm is an independent risk factor for local-regional recurrence; therefore, postoperative irradiation should be considered in these cases. For early-stage disease, local-regional control and survival rates for primary radiation therapy are comparable with those of surgery. In this select group of patients, irradiation can be offered as primary treatment, particularly for those who are poor surgical candidates. However, the results of using only radiation therapy in patients with advanced buccal carcinoma have been dismal. For advanced disease, local-regional control rates and survival are highest with combined surgery and postoperative radiation therapy. Radiotherapy should be given to 50-60 Gy and begin approximately 4-6 weeks after surgery. A dentist should be consulted before irradiation to many any carious teeth and minimize the risk osteoradionecrosis. Irradiation usually requires daily treatments for approximately 6-7 weeks. External-beam radiotherapy is the mainstay of treatment when this approach is used. Chemotherapy Chemotherapy may be indicated in the palliative setting. Minimal literature supports the use of chemotherapy as adjuvant therapy in the primary setting. Surgical therapy: Surgery is the preferred treatment for early and advanced buccal carcinoma in North America. Patients with advanced disease should receive postoperative radiation therapy. The surgical approach depends on the size of the tumor. Small lesions can be treated with a transoral wide local excision, whereas advanced lesions usually require excision via a cheek flap. Composite resection is indicated with mandibular invasion, and partial maxillectomy is used for superior alveolar ridge invasion. The tumor must be completely excised with clear margins because positive margins are associated with increased recurrence and decreased survival rates. Metastatic neck disease (N+ disease) requires either a modified radical neck dissection or radical neck dissection depending on the extent of disease. Management of the clinically negative neck is controversial. Diaz et al found a 26% rate of occult nodal metastases and noted that the regional recurrence rate decreased from 25% to 10% in those receiving neck prophylaxis. Mishra et al found that the recurrence rate in those having such prophylaxis was 29% versus 48% for those who did not. Most authors recommend neck treatment for tumors of T2 or worse. The goal of reconstruction is to prevent contracture in the buccal region that could interfere with function of the oral cavity. The type of reconstruction depends on the size of the surgical defect and on the tissue that needs to be replaced. The tissue defect may involve the mucosa, skin, bone, or any combination of these. Reconstructive options include primary closure; healing by secondary intention; split-thickness skin grafting; and use of local flaps, such as buccal fat-pad flaps, regional flaps (eg, pectoralis major or free tissue transfer with the radial forearm flap), or free fibula flap. Preoperative details: Written informed consent should be obtained after the patient is made aware of the risks and benefits of surgery. The patient should be counseled about the possible need for a tracheotomy, a nasogastric tube, or free tissue transfer for reconstruction. He or she should also be told that resection might be more extensive than the apparent size of the lesion to achieve clear margins. Before surgery, a radiation oncologist may be consulted in anticipation of postoperative therapy or as primary treatment for early carcinomas. A dentist might be consulted if postoperative therapy is required; for instance, extractions can be done at the time of surgery or arranged before or after surgery. An internal medicine specialist may be of help if the patient has medical comorbidities. Such medical consultation is also arranged to assess the risk of a general anesthetic and surgery and to optimize the patient's medical status prior to surgery. Lastly, an anesthesiologist should be consulted in any case involving multiple medical issues or any concern about maintaining the patient's airway. Intraoperative details: CT scans or MRIs should be reviewed before surgery and made available in the operating room. Small lesions may be excised with the patient under local anesthesia with sedation. However, most often general anesthesia is required. A detailed plan of securing the airway should be discussed with the anesthesiologist. For small lesions that are being treated with a transoral wide local excision, nasotracheal or orotracheal intubation may be performed. For advanced lesions, tracheotomy should be considered, especially if reconstruction is likely to cause intraoral swelling or bulk. The tracheotomy can usually be performed after the airway is secured with an endotracheal tube. If trismus is present, either tracheotomy under a local anesthetic or flexible fiberoptic intubation should be done. After the airway is secured and the patient anesthetized, the oral cavity and tumor is inspected to gauge the extent of resection and plan possible reconstruction. The neck should also be examined with the patient in a relaxed state. Panendoscopy may be performed if not previously done. The patient is appropriately prepared and draped. His or her eyes are protected, and a Foley catheter is inserted for long procedures. Cases involving a free flap may require placement of a radial artery line and central line with monitoring of central venous pressure. Preoperative antibiotics should cover the flora of the upper aerodigestive tract. For long surgeries, prophylaxis against deep venous thrombosis with either subcutaneous heparin or pneumatic compression garments should be used. Early-stage lesions Small, easily accessible lesions of the buccal mucosa (stage T1) can usually be managed with a wide local excision via a transoral approach. The carcinoma can be excised with a scalpel, an electrocautery device, or a laser. Use of a general anesthetic, muscle paralysis, and a bite block or side-biting mouth gag can aid in achieving exposure. Adequate margins of at least 1 cm should be obtained around the tumor. The depth of resection depends on the depth of tumoral invasion, which is determined by means of constant inspection and palpation during the resection. The orientation of the specimen is marked, and margins are sent for frozen section to confirm complete resection. Deep margins must also be sent for frozen section. Small defects can be closed primarily or allowed to heal by secondary intention. A split-thickness skin graft is also an option for reconstruction; however, with large grafts, resulting contraction can interfere with function of the oral cavity. A graft obtained from the buccal fat pad, whereby the buccal fat is brought out to fill the defect, can also be an effective means of reconstructing a small-to-moderate defect. Advanced-stage lesions These lesions are best approached with a cheek flap and lower lip split, which provides excellent exposure of the tumor to ensure adequate resection. With mandibular invasion, composite resection can be done through a midline lip-splitting incision and segmental or rim resection in continuity with the buccal cancer. Free flap reconstruction with either a radial forearm flap or an anterolateral thigh flap is preferred for any mucosal defect of significant size with or without an associated skin defect. These flaps provide adequate tissue that is pliable and easily conformed to the defect, with minimal contracture. An external skin defect may be closed with a portion of the flap or with a cheek advancement flap. Bone and mucosal defects can be reconstructed with a free fibula flap. Management of the Stensen duct If the parotid duct is not grossly infiltrated by tumor but within the field of resection, it should be identified during resection and repositioned if possible after the procedure. The duct may be repositioned more posteriorly or incorporated into the reconstruction, whereby it is either brought out through the flap or at the junction of the flap and mucosa. A margin of the duct should be sampled and sent for analysis if there is any concern about tumor involvement. If relocation is not possible, the duct should be ligated to prevent salivary leakage. This procedure causes initial parotid swelling with eventual atrophy of the parotid gland. Parotidectomy is usually unnecessary unless the proximal margins of the parotid duct are positive for carcinoma or unless the branches of the facial nerve branches need to be identified and preserved. If the duct or its papillae are grossly involved, tumor margins of the proximal aspect of the resected duct should be sent for frozen section. Diaz et al did not find any association among locoregional recurrence, survival, or proximity of the tumor to the Stensen duct. Neck dissection The N+ neck is managed with either modified radical or radical neck dissection. For the N0 neck, selective neck dissection at level I to level IV should be performed for a carcinoma of stage T2 or worse. If suspicious nodes are encountered during dissection, they should be sent for frozen section; the procedure should be changed to a more extensive neck dissection if the results are positive. The prevascular and postvascular (facial) lymph nodes should be removed in the neck dissection. These nodes are intimately associated with the facial artery and the marginal mandibular branch of the facial nerve. The nerve must be identified and carefully dissected away from the region of the nodes to be removed. Postoperative details: Vigilant mouth care is necessary in the postoperative period. Consultation with a speech therapist should be arranged for patients who have had extensive resection and reconstruction. Consultation with a radiation oncologist should be arranged for those in whom irradiation is indicated. For advanced disease (stage 3 or 4) postoperative radiotherapy is recommended. Follow-up care: Initial follow-up involves postoperative wound management. Follow-up is then scheduled as follows: every 1-3 months for the first year, every 2-4 months for the second year, every 3-6 months for the third year, then yearly after the fourth year. Chest radiography should be performed on a yearly basis, as should thyroid function tests if the neck has been irradiated. Patients should be instructed to seek immediate care if they develop pain or have any concern of recurrence. Patients should also be encouraged to stop smoking and drinking alcohol. Routine dental follow-up is necessary in patients with dentition who received radiation as part of their treatment.
Radiation therapy Complications of radiation therapy for buccal carcinoma are similar to those of irradiation to any site of the head and neck. Complications are best described as early/acute or late. Early or acute complications are as follows: (1) Xerostomia may occur and be temporary or permanent. (2) Mucositis can lead to malnutrition. Appropriate pain control can aid in oral intake to maintain adequate nutrition. If malnutrition occurs, supplemental nutrition with feeding through a nasogastric or gastric tube should be considered. (3) Dysgeusia usually improves as the mucositis improves. (4) Skin reaction may be observed. (5) Wound breakdown can occur. Late complications include xerostomia, soft tissue fibrosis, osteoradionecrosis, spinal cord myelitis, radiation-induced malignancy, and hypothyroidism. Surgery Surgical complications may be related to the general anesthetic or the surgical procedure. Surgical complications can be categorized as intraoperative or postoperative; the latter can be subcategorized as early or late. Intraoperative complications include dental injury; bleeding that may require blood transfusion; injury to the facial, hypoglossal, accessory, vagus, or phrenic nerve; and chyle leak. Early postoperative complications include medical complications, cardiopulmonary complications, wound complications, hematoma or seroma, wound infection and/or dehiscence, salivary fistula or sialocele, flap failure, sialadenitis, and airway obstruction. Late postoperative complications include scarring (hypertrophic or keloid), poor speech and swallowing, and trismus (if scar contracture develops).
Recurrence About 90% of recurrences occur within the first 1.5 years after treatment. Local recurrence is more common than regional recurrence. There is marked heterogeneity in the reported recurrence rates in the literature due to the small number of patients in each series and the differences in the stage of tumor and the treatment studied. Reported local recurrence rates are 12-100%. In the largest published series to date, Diaz et al reported a 23% local recurrence rate and a regional recurrence rate of 11%. Although the rates vary between studies, general similarities are observed among the factors that predict recurrence. Increased depth of invasion or tumor thickness increases the risk of locoregional recurrence. Lesions deeper than 3-4 mm are associated with a recurrence rate higher than that of tumors less than 3 mm deep. In a multivariate analysis, depth was independent risk factor and a better predictor for local recurrence than T stage, which was a poor predictor of depth. Therefore, the depth of the tumor on pathology should be considered an independent risk factor for locoregional recurrence and must be taken into account when deciding on further management such as postoperative radiation or neck management. Other factors that increase locoregional recurrence include positive surgical margins, tumor size, and clinical stage. Survival Survival rates vary among studies. The overall reported 5-year survival rates for buccal carcinoma are between 49% and 68%. Advanced-stage diseases have higher survival rates with combined-modality therapy (surgery with postoperative radiation). Factors that decrease survival include advanced stage of disease, nodal metastases at presentation, extracapsular nodal spread, and recurrence. Nodal disease decreases survival by 50%, as it does with other cancers of the oral cavity. Distant metastases are uncommon in buccal carcinoma. Most studies have shown low rates of distant metastases, with reports of 0-3%. When distant metastases do occur, they most commonly involve lung and bone. The incidence of a second primary lesion is similar to that of other subsites in the oral cavity, with a reported rate of 29-37%, of which more than 90% occur in the upper aerodigestive tract.
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