Case Report and Literature Review of a Pathologic Mandibular Fracture from Metastatic Esophageal Adenocarcinoma

Distant metastasis to the jaws, including the maxilla or mandible, is very rare. Although the mandible is the preferred sight of these rare metastases, it is extremely rare for oral cavity malignancies to present as pathological mandibular fractures. Here, we present a case of esophageal adenocarcinoma metastasizing to the mandible, and the first reported case presenting with a pathological mandibular fracture secondary to esophageal adenocarcinoma. We also review the 9 other reported cases of metastatic esophageal adenocarcinoma to either the maxilla or mandible.


Introduction
Pathological mandibular fractures are rare and account for only 2% of all mandibular fractures. Causes of pathological mandibular fractures have been reported following tooth removal, dental implant placement, secondary to benign and malignant mandibular pathology, osteomyelitis, osteoradionecrosis, bisphosphonate-related osteonecrosis, and Gorham's disease [1]. Even though only 1% of all oral cavity malignancies are metastatic in origin, when these metastases arise, they are the first sign of the primary disease about 25% of the time [2]. Pathological mandibular fractures caused by metastatic disease often present at a late stage. Secondary to advanced stage at presentation, treatment generally consists of chemotherapy or radiation therapy as a means of palliation. If the tumor is resectable, the gold standard of therapy is primary radical surgery [1].
is case report was reviewed by the University of West Virginia Institutional Review Board and found to be exempt and did not require full IRB review.

Case Report
A 69-year-old Caucasian male with a past medical history of hypertension, oromandibular dystonia treated with Botox, and recent diagnosis of gastroesophageal reflux disease (GERD) presented to his primary care provider noting an area of his left chin that was numb. e area was small and could be covered with 1 finger. He followed up acutely three weeks later with significant dysphagia for solids, but not liquids. He was urgently referred for an upper endoscopy. Upper endoscopy revealed LA Class D esophagitis with ulceration in the distal esophagus, and biopsies showed inflamed glandular mucosa with at least high-grade dysplasia. ese findings were consistent with a diagnosis of Barrett's esophagus secondary to GERD. ree weeks after his upper endoscopy, he presented to the emergency department with right jaw pain and swelling after hitting his jaw on a work bench. A CT revealed right mandibular angle fracture and coronoid fracture ( Figure 1). e facial trauma team was consulted and, secondary to his oromandibular dystonia, he was discharged on a liquid diet with Augmentin, Peridex, and close follow-up. He was seen in the clinic a week later and denied trismus, malocclusion, or difficulty with his liquid diet. On examination, he was found to have an exophytic mass of the right retromolar trigone, which he noted his teeth had been hitting. is mass was present before his fracture and had gotten larger over time. is mass was biopsied in the clinic and came back as likely metastatic adenocarcinoma ( Figure 2). e patient underwent a second upper endoscopy. Biopsy taken during this second endoscopy was consistent with a moderately differentiated adenocarcinoma of the distal esophagus. A PET/CT revealed a large, hypermetabolic distal esophageal mass consistent with the given diagnosis of esophageal adenocarcinoma. Hypermetabolic lesions involving the regional lymph nodes, lungs, spine, and right mandible, as shown in Figure 3, were found on PET/CT. ese findings were consistent with a Stage IV, TX, NX, M1, and G2, esophageal adenocarcinoma. At that time, he denied smoking, alcohol, illicit drugs, and/or exposure to radiation and carcinogenic chemicals. e hypermetabolic area of the right mandible, in conjunction with the previous retromolar trigone biopsy, confirmed a likely pathological fracture of the mandible secondary to metastatic esophageal adenocarcinoma. e advanced stage of the cancer made him a poor candidate for surgical intervention for either primary tumor or mandibular metastasis. He was referred for palliative chemoradiotherapy. He passed away one month after diagnosis.

Discussion
We are reporting a case of a 69-year-old Caucasian male sustaining a pathological mandibular fracture from metastatic esophageal adenocarcinoma. His pathological mandibular fracture occurred 1 week prior to his diagnosis of esophageal adenocarcinoma.
ere have been 9 previous cases of metastatic esophageal adenocarcinoma to the jaws reported in the literature and are listed in Table 1. None of these cases were associated with a pathological fracture of the mandible or maxilla [3][4][5][6][7][8][9][10][11].
e only reported case of metastatic esophageal carcinoma causing a pathologic fracture was secondary to an esophageal squamous cell carcinoma. In this previous case, the primary tumor was diagnosed prior to the pathological mandibular fracture [12].
Only 1% of all oral cavity malignancies arise from metastatic disease, and metastasis to the jaw bones is more common than oral soft tissues [2]. Metastasis to the jaws are thought to be by hematogenous spread, with the posterior portion of the mandible, molar, premolar, and angle of the ramus being the most common sites. Metastasis settles in these areas most commonly secondary to the red bone marrow located in these subsites [2,13]. Tooth extraction is commonly associated with metastasis to the oral cavity. In some cases, metastatic disease causes loosening of the teeth necessitating extraction, and in other cases, extraction of the teeth provides the inflammatory environment favorable to attract cancer cells. e growth factors provided by the bone marrow stromal cells and gingival inflammation are thought to provide a nurturing environment for cancer cells to thrive [2,13].
In a review of 453 cases of metastatic disease to the jaw bones, the male-to-female ratio was reported as between 1.2 and 1 with a mean age of 53.4 years old at diagnosis [13]. e most common origin for metastasis to the jaw include lung, kidney, liver, and prostate in men and breast, female genital organs, kidney, and colon in women. Metastatic tumors to the oral cavity most commonly present as exophytic lesions. e survival rate of patients with oral metastasis is reported to be 7 months secondary to the severity and progression associated with metastasis [2]. Secondary to significant disease burden, treatment is generally limited to chemotherapy or radiation therapy as a means of palliation, however, radical resection, if possible, has been described [14]. Classic symptoms of metastatic disease to the jaws include rapid, progressive swelling, pain, and paresthesia.  Numb chin syndrome or mental nerve neuropathy is characteristic of metastasis to the mandible and includes anesthesia and paresthesia over the chin, lower lip, and submental area. It is worth noting that, in this case, the paresthesia was of the opposite chin from the side of mandibular metastasis. Metastatic disease to the oral cavity should be considered in any patient with symptoms of numb chin syndrome, pain, swelling, or an exophytic lesion [2]. Esophageal adenocarcinoma has become increasingly more common over the last several decades, and it is now more common than esophageal squamous cell carcinoma in the United States. Men have approximately 6-fold higher risk of developing esophageal adenocarcinoma as compared to women [14]. Our patient's only risk factor for developing esophageal adenocarcinoma was being an elderly Caucasian male with GERD. Other risk factors for developing esophageal adenocarcinoma include central adiposity and tobacco consumption, while NSAIDs and H pylori are thought to be protective. Alcohol is not considered a risk factor [14]. In recent years, males >65 years old have seen the greatest increase in incidence of esophageal adenocarcinoma [15].

Conclusion
We report a case of esophageal adenocarcinoma presenting as a pathological mandibular fracture. Review of the literature shows this is the 10 th reported case of esophageal adenocarcinoma metastasizing to either the mandible or maxilla and the first reported case of esophageal adenocarcinoma to present as a pathological mandibular fracture.

Conflicts of Interest
e authors declare that they have no conflicts of interest.