Implant Rehabilitation After a Partial Resection of the Mandible Resulting from Submandibular Gland Malignancy—A Case Report

Salivary gland malignancy makes up only 1% of all cancers in humans but can have quite debilitating consequences known to dental clinicians. Interestingly, the salivary glands give rise to no fewer than 30 histologically distinct benign and malignant tumors. Of all the salivary gland tumors, benign and malignant, 65%–80% occur in the parotid glands, 10% in the submandibular glands, and the remainder occur in the sublingual and minor salivary glands.¹  The adenoid cystic carcinoma (ACC) is a slow growing but aggressive malignant neoplasm occurring mostly in the submandibular gland and the minor salivary glands and may rarely occur in the parotid gland. ACC of the submandibular gland makes up only 5% of all salivary gland tumors.¹  This tumor is characterized by wide local infiltration, perineural spread, local recurrence, and potential metastatic spread to lung, bone, brain, and liver. Although the lesion may be seen in all age demographics, it is most commonly seen in patients between 50 and 60 years of age with no specific gender predilection.¹ 

Treatment of patients with this disease may undergo surgery alone, or surgery in conjunction with postoperative radiation therapy. In complex cases with regional spread of disease, partial mandibular resection with postoperative radiation therapy may be indicated. In these instances, dental rehabilitation is needed for improvement of function, comfort, and overall quality of life. In the treatment of maxillofacial prosthodontic cases, the use of dental implants can change an outcome from disappointment to success for the patient. The complicating factor for dental implant treatment in these cases is the bone health after therapeutic doses of ionizing radiation. The devastating results of osteoradionecrosis in the irradiated jaw are well known and must be avoided. This manuscript will present a case on adenoid cystic carcinoma of the submandibular gland, its treatment, and subsequent rehabilitation with a dental implant reconstruction.

A 57-year-old African-American female presented to the Post-Graduate Prosthodontics clinic at Nova Southeastern University College of Dental Medicine requesting mandibular oral rehabilitation. Her chief complaint was inability to eat, inability to open her mouth widely, and discomfort with her remaining mandibular teeth. The patient's medical history was significant for left adenoid cystic carcinoma of the submandibular gland as her initial primary tumor. When she reported multiple surgeries, including partial mandibular resection followed by radiation therapy, her full medical records were requested. Her complex history of this disease process follows and reinforces the insidiousness of an ACC tumor.

At age 24 the patient complained of a small left neck mass that was excised and diagnosed as ACC. Definitive treatment consisted of surgery alone and the patient had uneventful healing. A neck swelling occurred 10 years later at age 34 when tumor removal again was performed and verified as an ACC recurrence. Once again, the patient underwent surgical excision alone and had an uneventful healing period of approximately 13 years. At that point the patient was 47 years old and complained of pain in the left neck area. A positron emission tomography-computerized tomography scan revealed intermediate grade activity in the left submandibular region measuring 2.8 cm and suggestive of neoplasm. The patient underwent surgical intervention involving excision of the left neck recurrent tumor, hypoglossal nerve (cranial nerve XII) removal, parotid gland excision, left posterior mandibular resection, and suprahyoid neck dissection. Additionally, mandibular defect reconstruction with fixation bone plate, facial nerve reconstruction using a sural nerve graft, and skin graft closure was performed. Diagnosis of recurrent ACC was confirmed. Considering the patient's history, it was decided that postoperative radiation with concomitant chemotherapy was indicated. A radiation treatment plan was generated using RapidArc (Varian Medical Systems, Palo Alto, CA) intensity-modulated radiation therapy (IMRT) with 1800cGy fractions to a total dose of 5040cGy with a follow-up boost to 6480cGy over 33 fractions. Chemotherapy was also added to her treatment plan using single-agent cisplatin.

Complications developed after the patient had 18 radiation fractions. She complained of severe pain in the oral cavity and temporomandibular joint area, significant trismus, and exposed mandibular bone in the surgical site with purulent discharge. The patient was unable to eat due to generalized oral pain. The diagnosis at that point leading to the severe pain was a displaced mandibular fixation plate and neck scar contracture. A surgical revision was planned with removal of the failed fixation plate, reconstruction of the mandibular defect with a new fixation plate, and autogenous bone graft harvested from the ileum. Prophylactically, the patient underwent hyperbaric oxygen treatment in preparation for the surgical procedure.

The patient tolerated the revision surgery well and an uneventful postoperative course followed. It is unclear from the medical notes whether the patient completed her planned course of radiation treatments. Regardless, the patient experienced no subsequent tumor recurrence, successful mandibular fixation plate with autogenous bone graft, and alleviation of chronic pain. Seven years after the revision surgery, the patient presented for dental rehabilitation.

As mentioned already, the patient was 57 years when she presented for evaluation at the Post-Graduate Prosthodontics Clinic of Nova Southeastern University College of Dental Medicine. Clinical evaluation revealed an intact and healthy maxillary arch dentition and a discontinuity defect of the left posterior mandible (Figure 1). Radiographic survey (Figure 2) showed the reconstruction plate in place to rehabilitate a Class II Cantor and Curtis Classification defect.²  The patient exhibited loss of balance and symmetry of mandibular function with deviation toward the surgical site. The remaining mandibular teeth were #22–28 and #31. These teeth were mobile, carious, and far out of any functional occlusal relationship due to the mandibular deviation. The patient reported nonexisting masticatory function and limited oral opening. After careful consideration, we decided that to return the patient to a functional occlusion, we would need to set mandibular teeth in a relationship that would contribute to masticatory function considering the deviated jaw position. Our treatment plan, therefore, was placement of dental implants and fabrication of a removable bar/overdenture prosthesis in the mandibular arch. This plan would obviously involve surgical removal of the remaining teeth, placement of multiple dental implants, and subsequent rehabilitation. The complicating problem was that, in a review of her medical records, she received between 5000 cGy and 6000 cGy of therapeutic radiation. Considering this, we immediately requested the records from the radiation oncologist showing the intensity map of her IMRT treatment. After reviewing this and in consultation with the radiation oncologist, it was concluded that the entire anterior mandible and right body of the mandible were completely spared of any radiation exposure. Upon this verification, our treatment plan proceeded.

As a safety measure, we began the treatment plan with the extraction of tooth #31 and placement of 1 implant (3.6 mm × 11 mm) into the extraction site. We evaluated the subsequent healing to ensure that no complications of the healing process presented. When normal healing ensued, it was decided that we would continue with our plan. We then removed the remaining teeth and placed 3 additional implants in the anterior mandible finalizing positions of #22 (3.6 mm × 10 mm), 25 (3.6 mm × 10 mm), 27 (3.6 mm × 10 mm), and 31 (3.6 mm × 11 mm) (Figure 3). All implants were Astra EV (Dentsply, York, PA).

After an osseointegration period of 3 months, 1-mm cuff height, straight Uni abutments (Astra EV, Dentsply) were inserted and torqued to 25Ncm. Abutment-level impression was made and a soft-tissue moulage/ die-stone master cast was poured and articulated against the maxillary dentition. A 4-unit connecting bar with 3 sections of Hader bar was fabricated following the demands of the deviated jaw position that mandated that the bar in the posterior right quadrant was positioned lateral to the ridge to support the removable prosthesis to the occlusal position of the maxillary teeth (Figure 4). The connecting bar was tried and passive fit was verified. Long guide screws were substituted for fixation screws securing the connecting bar and a border-molded final impression was made in a custom tray using a polyvinyl siloxane heavy and light body impression material (Aquasil Ultra, Dentsply). The custom tray and border molded impression ensured adequate extension and excellent replication of the soft tissue areas. After setting of the impression material, guide screws were removed, and the tray was withdrawn with the connecting bar being incorporated in the impression. Abutment analogs were attached onto the connecting bar and master cast was poured in die stone. Chrome/cobalt framework was made with lingual major connector and meshwork to support the acrylic material. After articulation, denture teeth were set using 20° cuspal inclined acrylic teeth (IPN Portrait, Dentsply). After final try-in, the overdenture was processed and finished in the boil-out/flask conventional manner using denture acrylic (Lucitone 199, Dentsply) (Figures 5 and 6). After delivery, the patient was seen at a 3-month recall appointment and panoramic radiograph was taken to evaluate bone/implant healing which was satisfactory (Figure 7). The patient maintained adequate intercuspal relationship (Figure 8) and reported satisfactory masticatory efficiency and overall satisfaction. In fact, the patient reported that she was so satisfied with the mandibular rehabilitation, that she kept the prosthesis in place even during sleep since it stabilized her mandible for all-day and all-night comfort (Figure 9).

ACC is a rare cancer most often occurring in the salivary glands and can also arise in other locations such as breast, skin, respiratory system, and reproductive organs.³ 

Although certainly a malignant tumor, ACC typically has a deceptively benign histologic appearance. It is characterized by basaloid cells with small, angulated, and hyperchromatic nuclei and scant cytoplasm arranged into 3 prognostically significant patterns: cribriform, tubular, and solid, with cribriform being the most common.⁴  Some tumors undergo dedifferentiation into a high-grade form.⁵  ACC is characterized by an indolent but persistent course, with high rates of local-regional recurrence and distant metastasis that can develop even many years after initial treatment of the primary tumor. Distant metastasis is reported in up to 52% of ACC patients and can occur with or without local-regional recurrence. Although most patients with ACC are alive at 5 years, a majority of patients die from their disease 5 to 20 years after diagnosis. The long-term outcomes continue to be guarded, with an estimated 10-year overall survival of <70%. Therefore, understanding more about patient and tumor characteristics regarding prognosis is critical.⁴ 

Modern cancer research focuses heavily on genomics and cytogenetic studies. ACC suggests 2 different genetic events underlying the pathogenesis of this tumor. One event involves the generation of a fusion gene resulting from reciprocal translocation of the chromosome 6q terminal region with chromosome 9p, and the other event constitutes a loss of genetic material at the same location. The vast majority of ACC cases demonstrate an activation of oncogenic transcription factor MYB, together with fusion of transcription factor NFIB, and researchers are convinced that this fusion/translocation is a main oncogenic driver of this disease. A central issue, therefore, is whether the MYB-NFIB fusion gene represents a universal event necessary for the development of salivary ACC.^5,6 

A review of the anatomy of the submandibular gland is helpful to understand the pathology and subsequent treatment of ACC. The round, walnut-shaped submandibular gland is situated in the submandibular triangle, reaching anteriorly to the anterior belly of the digastric muscle and posteriorly to the stylomandibular ligament. It extends superiorly to the inferior border of the mandible and inferiorly to just above the mylohyoid muscle⁷  (Figure 10). The submandibular gland receives parasympathetic innervation from the superior salivatory nucleus via the chorda tympani, a branch of the facial nerve (CN VII), which runs with the lingual nerve, a branch of the mandibular division of the trigeminal nerve (CNV). The deep portion of the gland also lies in contact with the hypoglossal nerve, CN XII.⁷  The critical importance of the proximity of these neuroanatomical features results in a high incidence of gross or microscopic perineural involvement and spread of the ACC regionally and to the skull base.⁸ 

The treatment of ACC is primarily surgical, consisting of en bloc resection with or without a radical neck dissection. The combined-modality treatment consisting of surgery and postoperative radiotherapy has led to superior results compared to either modality alone.⁸  Unfortunately, when malignancies result in perineural invasion extending to the skull base and beyond, total removal of the ACC malignancy is often not possible and consequently, postsurgical radiotherapy is indicated.⁹  The local extension of cancer cells along nerves is an ominous clinical event that is associated with increased local recurrence and worsened survival. Perineural invasion is considered an exacerbating feature that can worsen the prognosis of patients with surgical close margins, and it has been associated with an increased risk of regional recurrence.^9,10 

Radiation therapy of the head and neck for management of malignancies typically involves IMRT). ACC tumors are relatively radioresistant and the usual therapeutic radiation dose is approximately 6000–6600 cGy. IMRT uses photon beams of varying intensities to precisely irradiate a tumor. The radiation intensity of each beam is controlled, and the beam shape changes throughout treatment. The goal of IMRT is to conform the radiation dose to the target and reduce exposure to healthy tissue. Patients are first imaged under fluoroscopy to ensure accurate isocenter placement, and a patient-specific mask is constructed for precise repeated radiation delivery (Figure 11). Computer software is employed to assist in treatment planning the radiation therapy¹⁰  (Figure 12).

Radiation treatment to the head and neck area is of great concern to the dental clinician. Although radiation is a critical therapeutic regimen for patients with malignant disease, side effects such as skin irritation, xerostomia, mucositis, and osteoradionecrosis can result. These side effects may have devastating dental complications resulting in significant quality-of-life issues. Xerostomia is the most prominent complication of head and neck carcinoma due to disruption in salivary volume, consistency, and pH.¹¹  When salivary volume decreases, consistency becomes thick, and pH becomes increasingly acidic.

Osteoradionecrosis (ORN) is a complication of radiation therapy where jawbone becomes necrotic and may protrude through the soft tissues of the mouth. This disease process may occur spontaneously or may result from a traumatic injury and may manifest years after the original radiation exposure. Oral surgical procedures performed in irradiated bone can cause ORN and be quite difficult to manage due to poor osseous healing characteristics. Radiation therapy causes DNA damage resulting in cell death. While death of cancer cells is obviously the goal, normal tissues suffer cell death as well. A cumulative damage of normal tissue by radiation creates a disturbance in cell metabolism and homeostasis. Radiation also causes injury to endothelial cells of the bony vasculature creating a hypovascular environment leading to hypoxic tissues, which behave like chronic nonhealing wounds.¹³ It should be noted that since osteoradionecrosis is quite dependent on hypoxic conditions, it is more commonly seen in the mandible due to a blood supply that is less robust than that of the maxilla. One of the therapeutic modalities used to prevent this problem is hyperbaric oxygen therapy prior to oral surgical procedures. This approach drives extra amounts of oxygen to the tissues in an effort to preclude hypoxic conditions.¹² 

Based on all the aforementioned information, the patient who undergoes salivary gland removal followed by IMRT radiation treatment presents complex considerations when presenting for dental care. First, the absence of one of the major salivary glands may certainly result in xerostomia and the importance of adequate salivary flow cannot be overemphasized. Adequate salivary flow is essential for its buffering capacity, soft tissue lubrication, and antimicrobial and digestive functions. Xerostomia is a major contributor to rampant dental caries and salivary gland removal can be a significant problem for a patient's dental health. Second, any oral surgical intervention in an irradiated site may result in areas of necrotic, nonhealing bone from osteoradionecrosis requiring specialized management. These facts underscore the importance of a thorough medical history and the gathering of all pertinent data prior to instituting dental treatment. If a patient reports a history of salivary gland removal with subsequent irradiation with 5000–6000 cGy of radiotherapy, it is essential that the clinician obtains an intensity map of the radiation fields to which the patient was subjected. The importance of this map can guide the dental clinician to see danger areas of the jaw that should be avoided and view those areas in which a normal response to surgical procedures can be expected (Figure 3). As can be seen in Figure 3, (which is an illustration of a typical radiation intensity map but is not the patient in this case report); the intensity map shows the isocenter received a maximum radiation dose and peripheral areas received sequentially lesser doses. Tissue outside of the most peripheral band would be spared any radiation exposure and therefore would not be expected to exhibit adverse radiation effects. Careful evaluation of a patient's intensity map of radiation fields can guide the clinician in performing safe surgical procedures and dictate the need for hyperbaric oxygen therapy.

Dental treatment planning of the patient who has undergone submandibular gland tumor excision in conjunction with hemimandibulectomy and postoperative radiation therapy to the jaw has multiple unique considerations. Typically, when mandibular resection is performed, deviation toward the affected side often changes the entire occlusal relationship of the opposing jaws. An implant-assisted removable prostheses can re-establish an occluding masticatory system capable of improved function and enhanced quality of life.

Patients who present for dental care often have underlying medical conditions that must be thoroughly explored through medical records and consultations. Adenoid cystic carcinoma of the submandibular gland is an insidious malignant disease often necessitating surgical excision followed by radiation therapy. If this is the case, it is critical to determine the type and extent of this radiation treatment, and when applicable, a careful review of the intensity map with radiation fields and consultation with the radiation oncologist is indicated. Only then can surgical intervention be safely planned and executed, or totally avoided if prohibited by previous radiation exposure.

In cases of mandibular resection from malignancy, careful treatment planning is essential. Dental implants can be a critical adjunct to improving masticatory function when restoring the dentition.