TMJ pain as a presentation of metastatic breast cancer to the right mandibular condyle

Abstract

Cancer metastasis to the oral and maxillofacial region is uncommon, and metastasis to the mandibular condyle is considered rare. We present a case of a 56-year-old woman with a history of invasive ductal cell carcinoma of the right breast, 10 years in remission, presenting with a 6-month history of symptoms typical of temporomandibular joint (TMJ) dysfunction. Imaging revealed an osteolytic lesion of her right TMJ and subsequent open biopsy confirmed the diagnosis of metastatic breast cancer. Despite the rarity of metastatic cancer to the head and neck region, it is still important for clinicians from both medical and dental backgrounds to consider this differential diagnosis, particularly in patients with a history of hormonal positive subtype of breast cancer. Given that bony metastasis can manifest even 10 years after initial diagnosis, surveillance which includes examination of the head and neck region is important, and may include routine plain-film imaging surveillance with an orthopantomogram (OPG).

Background

Breast cancers have the tendency for bony metastasis, occurring in approximately 70% of patients with metastatic spread, and 13.6% of stage I–III patients at 15 years follow-up.¹ However, metastasis to the oral cavity involving both soft and bony tissues accounts for only 1% of all oral malignancies.² The most common primary sites of metastatic spread to the mandible include breast, lungs, kidneys and prostate.^{3 4} The frequency of metastasis to the head and neck region varies between the genders, with breast cancer being more common in women, compared with lung cancer, which is more common in men.^{2 5} The mandible is the most common location for metastasis involving the head and neck region due to its greater haematopoietic tissue compared with the maxilla.⁶ However, metastasis to the condyle is considered rare, with the most frequently involved site being the body of mandible around the molars and premolars.^{6 7} The reason for this is unclear, but speculatively related to limited vascularity of the condylar head and limited haematopoietic marrow.⁸

Temporomandibular dysfunction (TMD) is an umbrella term for clinical problems relating to the masticatory musculature, the temporomandibular joint (TMJ), surrounding soft tissue structures or a combination of these problems.⁹ TMD is present in 5% of the population and more prevalent in women. Pain is a common symptom of TMD, and it can present as earaches, tinnitus or headaches. Other presentations of TMD include limitations to opening, locking and clicking of the joints.¹⁰ Pain is also a well-documented symptom of malignancy, reported in up to 70% of all patients with cancer.¹¹ Consequently, it can be difficult to differentiate between TMD and malignancy as pain is a common presentation of both.

The diagnosis of metastatic spread to the head and neck region can be challenging given the rarity. However, a clinician must be cognisant that lesions found in the head and neck can represent a metastasis, often the first indicator of an undiscovered primary.⁵ However, in some cases, the primary is already known and treated.²

Case presentation

A 56-year-old woman was referred to our maxillofacial surgery unit for opinion and management of a right condylar lesion which was found incidentally on imaging arranged by her general practitioner (GP). She had a history of grade I invasive ductal carcinoma of the right breast, treated with lumpectomy and right sided axillary clearance in 2010, followed by completion of adjuvant chemoradiotherapy in the same year. She was also on tamoxifen therapy up until 2015 and was discharge from oncology in 2017 with yearly surveillance mammograms. Her last scan was in June 2019 and was unremarkable for any local recurrence.

Several months prior to the referral, the patient reported progressive otalgia and pain in her right pre-auricular region which was exacerbated by excessive use of the jaw and worse with mastication. This was initially attributed to referred pain from a known right submandibular gland sialolithiasis which the patient suffering intermittent flare ups over the past 4–5 years. However, TMD was also a differential diagnosis that the GP had considered given that the character of the pain was different to what the patient had experienced previously. On examination, the patient had minor tenderness to palpation of her right TMJ but no grossly appreciable swelling. She did not have any trismus, nor deviation of the jaw on opening, with a full range of movement and no clinically appreciable clicking or crepitus of the joint. Her occlusion was stable while facial nerve and mandibular branch of trigeminal nerve were also fully intact. Ultimately, clinical examination was largely unremarkable.

Investigations

An ultrasound scan ordered by the GP confirmed stable appearance of a known 7 mm intraglandular calcification of the submandibular gland. Of interest, there was an incident finding of a radiolucent lesion associated with the right mandibular condyle. A CT scan was ordered showing a 22×23×23 mm expansile lesion of the right condyle with cortical thinning and areas of cortical breach (figure 1). After referral, a fine needle aspiratory cytology of the lesion was arranged, revealing basaloid features in keeping with ameloblastoma. An initial MRI was conducted showing the lesion was confined to the condyle with no involvement of the pterygoid or masseter muscles.

Figure 1.

Coronal view CT showing a 22×23×26 mm expansile osteolytic mass with significant cortical thinning and areas of breach involving the right condylar head of the mandible.

The patient was investigated further with positron emission tomography (PET), with results showing an intensely glucose avid destructive lesion of the right condyle (figure 2).

Figure 2.

The right condylar lesion is intensely FDG avid on positron emission tomography scan. There was no evidence of any other bony or distant metastases. There was also no evidence of recurrence of breast cancer. FDG, Fluorodeoxyglucose F 18.

Given the unlikelihood of ameloblastoma to occur in the condylar head, the decision was made by our maxillofacial surgery unit to perform an open biopsy of this lesion. Biopsy result showed moderately differentiated malignant glandular tissue structures forming irregular angulated tubules. The sample was positive for oestrogen receptor (ER) and progesterone receptor (PR) but negative for human epidermal growth factor receptor 2 (HER-2). In keeping with the clinical background of the patient, this was consistent with metastatic breast cancer to the right mandibular condyle.

Differential diagnosis

Differential diagnoses of the mandibular condylar lesion can be classified as either of odontogenic or non-odontogenic in origin. Odontogenic lesions that would present as well-defined radiolucencies include ameloblastoma, odontogenic keratocyst (OKC) and ameloblastic fibroma. While it is very rare for odontogenic lesions to occur in the condyle, there has been a case reports of OKC occurring as an isolated lesion of the condyle.¹²

More likely diagnoses consistent with the radiological appearance are non-odontogenic lesions including aneurysmal bone cyst, traumatic bone cyst, central giant cell granuloma and vascular malformations—all of which have been documented to occur in the condyle in previous case reports. Additionally, the consideration of a metastatic lesion to the condyle was also considered based on the patient’s background of breast cancer.

Given that many of these lesions share similar appearance on imaging, a formal biopsy is essential for histological diagnosis which ultimately led to the final diagnosis of metastatic breast cancer.

Treatment

This patient was discussed at our hospital head and neck cancer multidisciplinary team (MDT) meeting. A repeat MRI was performed prior to this discussion, as our patient had presented with worsening TMJ symptomatology. Unfortunately for the patient, repeat MRI showed local and extracondylar disease progression with tumour involvement of the masticator space with close proximity to the auditory canal (figure 3). Given the new findings, group consensus was that surgical resection to achieve clear margins would be too risky and highly morbid. As such, the decision was made for palliative treatment with chemoradiation therapy.

Figure 3.

Axial view T2 fat saturation phase MRI showed progression of right condylar lesion involving the medial and lateral pterygoid muscles.

Outcome and follow-up

Since discharge from our maxillofacial surgery unit, the patient has been under the care of both medical and radiation oncology teams. Decision was made by the oncology teams to continue the patient on a period of anastrozole prior to commencing radiation as this would decrease tumour bulk and optimise the effectiveness of treatment. The patient completed radiation with a total dose of 60 Gy over 20 fractions to the right TMJ in August 2020.

At the last phone review with the patient in November 2020, she reported improvement of pain in the right TMJ with improved functioning and mouth opening. There remains some discomfort with contralateral excursive movements. She remains on anastrozole and is due to commence a period of palbociclib as part of her ongoing palliative management of metastatic breast cancer to her right mandibular condyle.

Discussion

Metastatic jaw lesions can present in a number of different ways depending on their location. Some symptoms include paraesthesia involving the inferior alveolar nerve distribution, swelling, exophytic growths and mobile teeth.^{3 13} Pain is the most common symptom of malignancy, reported in up to 70% of all patients and is also the most common jaw symptom with metastasis to the mandible.^{3 11} In this case, we presented a patient with pain in the pre-auricular region which is also highly typical of TMD, so initial suspicion of a metastatic process was not immediately obvious.

The initial diagnosis based on fine needle aspiratory cytology showed features consistent with ameloblastoma. Ameloblastoma is a benign neoplasm of odontogenic origin and often affects the mandible (80% of cases) in tooth bearing areas around the molars and ramus.¹⁴ In 10%–15% of the time, these lesions are associated with impacted unerupted teeth.¹⁵ Given the origin of the neoplasm, it is therefore extremely unlikely for isolated ameloblastoma of the mandibular condyle as ectopic epithelial cellular elements and dental tissues of this region are rare. Previously published case reports of ameloblastoma with condylar involvement were large lesions also affecting the body and ramus of the mandible.^{14 16–19} In all of these cases, the neoplasms most likely originated in the body and ramus of the mandible before progression lead to involvement of the condyle. While condylectomy and reconstruction with joint replacement prosthesis has been successful,^{14 17} the subsequent diagnosis of metastatic breast cancer with masticator space involvement changed the management plan and prognosis for the patient.

Metastatic cancer to the mandible does not have a pathognomonic appearance on imaging which adds to diagnostic dilemma. Depending on the primary, the appearance on imaging can present as osteolytic or osteoblastic appearance. Classically, metastatic diseases appear as irregular radiolucent lesions with a ‘moth-eaten’ appearance.^{13 20} However, it is also possible for metastatic breast cancer to present as a mixed radio-opaque and radiolucent lesion due to reactive bone formation.²¹

Different molecular subtypes of breast cancer have different clinical and metastatic patterns. Molecular subtype of breast cancer is based on cellular receptors on tumour cells—ERs, PRs and HER-2. Histopathology from our open biopsy showed that our patient was ER/PR positive and HER-2 negative consistent with luminal A or B breast cancer subtype.²² While these subtypes tend to be of lower grade and occurring in older women with lowest incidence of metastases, it has the highest propensity for osseous metastases across all subtypes.^{22 23} It is also not unusual for first osseous metastasis to occur many years after the initial diagnosis, a large proportion occurring 5–10 years later.²⁴ Indeed, consistent with this case, around 25% of oral metastases is the first sign of metastatic spread from a known primary.²⁵

In the majority of published case reports, the prognosis of patients with metastatic lesions to the oral cavity is poor, with an average survival of approximately 7 months.^{25 26} This is likely related to delayed diagnosis as well as generalised micrometastases by the time of diagnosis.²⁷ The management of metastatic breast cancer involving the head and neck is primarily of palliative intent aiming to improve ‘quality of life’. Interventions may include a combination of radiotherapy, chemotherapy and hormonal therapy. In select cases where the oral tumour is the only evidence of metastatic lesion, resection may be offered and has been shown to improve prognosis.²⁸ This modality was not feasible for our patient as the tumour had invaded into the masticatory space and would involve a highly risky and morbid resection. At time of writing, the patient had already completed 60 Gy (20 fractions) to the right TMJ in August 2020 while being treated with anastrozole, an aromatase inhibitor used to treat hormonal positive breast cancers. She is due to commence chemotherapy with palbociclib.

This case highlighted the importance of understanding the pathophysiology and origin of neoplasm to ensure appropriate diagnosis is made for patients as it guides the appropriate treatment. It is also important for clinicians to keep in mind the possibility of metastatic cancer involving the jaw in those with a history of breast cancer, particular hormonal positive subtypes, with acute symptoms of TMD. While the majority of cases would be for palliation, early recognition is still important to prolong life expectancy, quality of life and early management for symptomatic control.

Learning points.

• Metastatic breast cancer to the mandibular condyle is rare but can masquerade as temporomandibular joint pathology.

• Metastatic cancer to the condyle can also masquerade as other pathology and it is important to be aware of the pathophysiology to ensure correct diagnosis.

• It is important that general practitioners as well as general dentists are aware of metastatic process as a differential, particularly with acute onset temporomandibular dysfunction symptoms.

• Management of condylar metastasis is often palliative but prompt investigation and referral for further management are important to prolong survival and improve quality of life.