The Dental effects of head and neck rhabdomyosarcoma treatment: a case series

Rhabdomyosarcoma (RMS) is a malignant soft tissue neoplasm of skeletal muscle origin. It is reportedly the third most common extracranial solid tumour of childhood after Wilms' tumour and neuroblastoma.^1,2,3,4 RMS is the most frequent soft tissue sarcoma encountered and accounts for approximately 6% of all malignancies in children under 15 years of age.³ Approximately 65% of cases are diagnosed in children younger than 6 years of age.^2,5 There is a slight predilection for disease in males, with a male-to-female ratio of 1.3–1.5.²

The most common site for RMS, accounting for approximately 40% of cases, is the head and neck region.¹ RMS of the head and neck are anatomically divided into two categories:

• Parameningeal: including the nose, nasopharynx, paranasal sinuses, middle ear, mastoid, infratemporal fossa and pterygopalatine fossa;
• Non-parameningeal: including the scalp, orbit, parotid gland, oral cavity, oropharynx, and larynx.³ RMS of the oral cavity accounts for 10–12% of all head and neck RMS cases.³ The most common site in the oral cavity is the tongue, followed by the soft palate, hard palate, and buccal mucosa.^6,7 Jaw involvement is extremely rare.⁶ Other commonly reported areas are the genitourinary tract, retroperitoneum and the extremities.

Three basic types of RMS are described: embryonal (60% cases), alveolar (20–30% cases), and pleomorphic (5% cases). Embryonic cases mainly occur in those aged up to 10 years, alveolar cases tend to present at around 10–25 years and pleomorphic RMS present most commonly in those aged 40+ years.¹ In the head and neck region, embryonal RMS is most prevalent. The cells of embryonal RMS resemble that of the developing muscle cells of a 6–8-week-old fetus.¹

RMS appears to be sporadic in nature and no definitive aetiological factors have been reported. However, there is some evidence suggesting gene abnormalities may have a role.⁸ Furthermore, familial syndromes such as neurofibromatosis, and the Li–Fraumeni syndrome have been associated with RMS.^2,9

Clinical manifestations of RMS in the head and neck region may vary from a fast-growing and extensive facial swelling to a small cutaneous nodule. Symptoms may include pain, ptosis, trismus, paraesthesia, facial palsy and nasal discharge; however, RMS may also be symptomless.^3,10,11

Of consideration are possible differential diagnoses of RMS, which may include Ewing sarcoma, Wilms' tumour, lymphoma, neuroblastoma, alveolar soft-part sarcoma, fibrosarcoma and leiomyosarcoma.¹

Once appropriately diagnosed, treatment for RMS involves a multimodality approach with surgery, chemotherapy and radiotherapy. When children are exposed to such treatments, there are often associated long-term adverse effects that may affect the patients dento-alveolar growth and development, and may adversely affect the patient's quality of life. It is often reported that the younger the age of treatment and the greater the dose of radiotherapy and/or chemotherapy, the increased severity of side effects.¹²

Some of the side effects of radiation and chemotherapy can occur immediately after treatment, such as mucositis, increased risk of candidiasis and oral infection, or can be delayed, such as delayed eruption of teeth, hypodontia/regional oligodontia and retarded tooth and bone development. This disruption to tooth development can affect odontogenesis leading to enamel, dentine and cementum malformation affecting the crowns and roots of the teeth.^{1,5,6,7,12,13,14,15} Not only may this have functional and aesthetic issues for the patient, for the restorative dentist, it poses an increased challenge for restoration and a possibly decreased predictability for any treatment provided.

In one study by Estilo et al,⁵ bony hypoplasia or facial asymmetry was the most common late presenting clinical finding after radiotherapy treatment for RMS. Radiographically, evidence of underdevelopment of the mandible and root formation disturbance, such as incomplete root development, root stunting/tapering and in severe cases root agenesis, were most often discovered.⁵

Further effects may include tooth discolouration, hyposalivation/xerostomia, increased risk of caries, trismus, altered/loss of taste and scar-tissue formation.^1,5,12,13,15 It is well established that osteoradionecrosis can occur following radiotherapy to a region, and this must be monitored for and taken into consideration when planning any treatment. These side effects can make oral rehabilitation by the restorative dentist challenging. This case series looks at three patients who were successfully treated for RMS in the head and neck region. It highlights the dento-alveolar issues that can arise and discusses the restorative treatment approaches that may be used for oral rehabilitation.

Case A

Patient A was 17 years old at the time of presentation to the adult dental health unit. She had no complaints with regards to symptoms, function or the aesthetics of her dentition. She had an awareness of retained primary teeth and that the roots of her teeth had been affected by her RMS treatment.

Medically, she was diagnosed with retropharyngeal embryonal RMS at the age of 3 years. The treatment undertaken at that time was intravenous chemotherapy. She also reported hypopituitarism as a consequence of RMS treatment, with the patient taking pituitary hormone replacement injections. Extra-oral examination highlighted the patient had mild facial asymmetry that caused her no concern. Intra-orally, oral hygiene was good and the gingival tissues healthy. Generalized microdontia was evident. Retained primary teeth included a hypomineralized URE, LRE and an infra-occluded URE. The LRE and LR5 appeared to be fused coronally with the LR5 having severe microdontia. The patient had congenitally missing UR8, UR7, UL7, UL8, LL8 LL7, LR7, LR8.

Radiographic examination was undertaken (Figure 1). This highlighted an unerupted LR6, possible fusion of the LRE and LR5 and a horizontally impacted UR5. A lack of complete root formation was evident affecting the entire dentition. Special investigations revealed no mobile teeth or teeth tender to percussion. A diagnosis of generalized severe hypodontia, generalized microdontia, failure of complete root development, hypomineralized URE and LRE, impaction of UR5 and failure of eruption LR6.

Case B

Patient B was 16-years old at the time of presentation to the adult dental health unit. He was concerned with the aesthetics of a palatally placed lateral incisor, the mobility of his maxillary central incisors and the future of his dentition due to the stunted root development.

Medically, Patient B had been diagnosed with metastatic embryonal nasopharyngeal RMS at the age of 4 years. The treatment undertaken at that time was radiotherapy (41.4 Gy) followed by chemotherapy. He also reported hypopituitarism and hypothyroidism as a consequence of RMS treatment, with the patient taking growth hormones and thyroxine.

Extra-oral examination highlighted the patient had facial asymmetry, which caused some concern to the patient, and he was assessing the option of further facial surgery in an attempt to correct this issue. Intra-orally, the oral hygiene was fair. Generalized microdontia was evident. Missing teeth included the UR3 and UL3. UR2, UL2 and UL7 were grade I mobile, and UR1 and UL1 grade II mobile.

Radiographic examination was undertaken (Figure 2). This highlighted an unerupted LR6, possible fusion of the LRE and LR5, and a horizontally impacted UR5. A lack of complete root formation was evident affecting the entire dentition. A diagnosis of generalized microdontia, generalized root agenesis and unerupted UR3 and UL3 was made.

Treatment for Cases A and B

The treatment options available to A and B where quite similar even though different RMS sites were treated in childhood. Treatment options were discussed using a multidisciplinary approach (MDT), with orthodontics to re-align the dentition and bring the impacted UR5 into the arch. However, owing to shortened roots, this was deemed to be of high risk and could lead to tooth loss.

The risk of tooth loss for these patients is high. Options to replace missing teeth often include removable options, such as partial or complete dentures, which may be implant retained, or fixed options including conventional bridge work, resin-retained bridge work, and implant-supported prostheses. However, for these patients, there is difficulty providing conventional fixed restorative treatment, ie bridge work, because the lack of root development leaves no suitable abutment teeth. This would lead to the need for either a removable option, which many young patients do not wish to have, or an implant-retained prosthesis, which, at the patients' stage of growth and development, is contraindicated due to the risk of further growth leading to submerging implants.¹⁶

Both patients consented to a conservative treatment plan. Oral hygiene instruction (OHI) and caries preventive advice was given to help maintain the dentition in good oral health, along with the requirement for regular review. No active treatment was undertaken at that time. Should the teeth fail, simple removable mucosal-borne appliances without clasping would be provided in the first instance.

Case C

Patient C was first referred to the adult dental health clinic at 18 years of age in 2012. She complained of a recent loss of a front tooth, which her general dental practitioner had splinted to her adjacent teeth as a temporary measure because she did not wish to have a removable prosthesis. She was also aware of a mobile symptomatic tooth (UL2). She had awareness that the roots of her teeth had been affected by her RMS treatment.

Medically, Patient C had been diagnosed with right parameningeal (right ear, skull and pterigoids) embryonal RMS at the age of 3 years. The treatment undertaken at that time was intravenous chemotherapy and radiotherapy to the middle cranial fossa (45 Gy) and pituitary gland (25 Gy). She also reported, as a consequence of RMS treatment, hypopituitarism, facial hypoplasia of the right side, sensorineural hearing loss in the right ear and psychological issues. Current medication included growth hormone injections.

Extra-oral examination highlighted the patient had facial asymmetry and a decreased development of the mid-third of the face. Intra-orally, the oral hygiene was good, and the gingival tissues healthy. The UR2 was splinted to the UR3, UR1 and UL1. The UL2 was grade 2 mobile. Teeth missing included the UR7, UL7, LL7, LR7.

Radiographic examination was undertaken (Figure 3). This highlighted an unerupted UR7, UL7 and LR7. The LL8 had a disto-horizontal impaction. A lack of complete root formation was evident, with root agenesis affecting the entire maxillary dentition and root shortening of the lower incisors. A diagnosis of root agenesis of the maxillary dentition and partial root formation lower incisors, disto-horizontal impaction of LR8 and acquired tooth loss was given.

Treatment for Case C

The very poor long-term prognosis of the entire maxillary dentition was discussed with the patient in a sympathetic manner. The hopeless prognosis of the UL2 was also addressed. Treatment options were discussed with the patient as described for patients A and B. For Patient C, the maxilla had been included in the radiotherapy field, and the risk of osteoradionecrosis following implant placement was discussed at length. As discussed in Cases A and B, conventional tooth replacement options were limited because of the poor abutment teeth. Patient C desired a fixed prosthetic option rather than a removable replacement. In the first instance the splinted UR2 was removed, and the UL2 extracted. These were replaced with a resin-retained bridge of double abutment with cantilever design off the central incisors. Although the UR1 and UL1 were of poor long-term prognosis, the patient accepted that their use as abutments risked their loss, but this was preferable to wearing a removable prosthesis.

Regular review with the GDP was required and yearly reviews at Bristol Dental hospital were undertaken for an element of shared care to ensure the good dental health of the patient.

From 2012 to 2016, no further active treatment was required for the patient. However, in 2016, Patient C presented with grade III mobile maxillary canine teeth, and had exfoliated her posterior mandibular molars. The resin-retained bridge work replacing the upper lateral incisors was sound. As previously, treatment options to replace teeth were re-discussed and resin-retained bridge work was provided as a single cantilever design from the first premolars to replace the canines.

During 2017 the patient presented with further pain and mobility associated with her maxillary premolar teeth on both sides. An immediate partial denture was created. At this point, Patient C was 23 years old and her dentition entailed the maxillary central incisors being used as resin-bridge abutments to replace the lateral incisors and first permanent molars only.

Further discussions were undertaken regarding the options of a removable prosthesis or implant-retained prosthesis. A lack of sufficient bone volume in the maxilla was confirmed with cone beam CT scans (Figure 4). Using the multidisciplinary team and liaising closely with the oncologist to discuss radiotherapy fields and the risks of undertaking surgical procedures in the maxilla, the patient consented to a treatment plan of extraction of the UR6, UR1, UL1, UL6 and an immediate complete denture was fitted. Following this, onlay rib bone grafting and bilateral sinus lift procedures were undertaken under general anaesthetic (Figure 5).

In mid-2018, at the age of 24 years, Patient C received six dental implants in the central incisors, canines and premolar region prior to the construction of fixed implant-retained bridges (Figure 6).

Discussion

Treatment for RMS includes surgery, radiotherapy and chemotherapy. Radiation can directly and indirectly affect the developing dentition, directly inhibiting mitotic activity of odontoblasts. Children are more susceptible to the effects owing to the large quantity of rapidly dividing pre-secretory odontoblasts. Indirectly, radiation affects amelogenesis by inducing formation of ‘osteodentine’ instead of normal dentine. This osteodentine has reduced phosphorylated phosphoprotein, inhibiting nucleation of enamel crystals leading to deficient enamel mineralization.¹²

Chemotherapy treatment consists of antineoplastic medications that suppress the autoimmune system and/or directly kill cells. Most antineoplastic agents affect normal cells, as well as tumour cells. Antineoplastic agents, such as vincristine, actinomycin, and cyclophosphamide, can interfere with odontogenesis.¹ The delayed effects of such treatment can be delayed eruption of teeth, hypodontia and retarded tooth and bone development. Not only may this have functional and aesthetic issues for the patient, for the restorative dentist it poses an increased challenge to restore, and potentially a less predictable outcome for any treatment provided.

It is of utmost importance that sympathetic discussions are undertaken with the patient, and that the patient is informed of the risks of any treatment provided, including the potential loss of the entire dentition in severely affected cases.

Issues with prosthetic replacement must be discussed. Often the teeth available provide poor abutments, and their use may lead to an increased rate of loss of the abutment teeth. A multidisciplinary approach is often required, with the team including restorative dentists, orthodontists and maxillofacial surgeons. Continued communication with the patients' medical team, such as the oncologists, endocrinologists, cardiologists, plastic surgeon and psychologists, is also required to ensure a holistic approach is taken in the best interest of the patient.

Conclusion

This article highlights the effects of RMS treatment on dento-alveolar growth and development, and the issues this creates for the patient aesthetically and functionally. The issues surrounding restorative treatment are discussed, particularly the compromised approach to be undertaken in the first instance and prior to possible loss of most of the dentition. Age is a limiting factor for rehabilitation, and a removable prosthesis is likely to be required in the short to long term. Implant-retained prostheses are not always an option for these patients owing to the high risks of surgery on irradiated bone and also the general lack of bone volume because of the reduced development of the dento-alveolar complex. There is often a requirement for bone grafting procedures. For these cases, tailored and careful MDT planning is required to consider the best management to gain the safest and most effective solution.