Bilateral Pulmonary Nodules after Surgery for Ameloblastoma: A Case of Misdiagnosis for 32 Years

Background: We describe a rare case of metastatic ameloblastoma in a 68-year-old Chinese woman diagnosed with ameloblastoma of the right mandible in 1974. Case presentation: Despite radical resection, she experienced repeated local recurrences, including asymptomatic bilateral pulmonary nodules, cough, and hemoptysis diagnosed as non-malignant inammatory cell inltration. The patient developed an aggravated cough, palpitations, and dyspnea and was admitted to our respiratory department in September 2018. Chest computed tomography revealed multiple bilateral lung nodules, masses, and soft tissue opacities. She was diagnosed with advanced metastatic ameloblastoma in bilateral lungs via bronchoscopic biopsy, with a misdiagnosis time of 32 years. Because her systemic condition was poor, systemic chemotherapy and radiotherapy were not recommended. Dyspnea signicantly improved after interventional bronchoscopic therapy and tumor electroexcision; she died of respiratory failure 1 year after diagnosis. Conclusions: Clinicians should carefully explore the medical histories of patients with surgical histories of ameloblastoma and subsequent unexplained pulmonary metastatic tumors to avoid misdiagnosis.


Background
Ameloblastomas are rare odontogenic tumors of epithelial origin that most frequently arise in the mandible. Radical resection is the mainstay of ameloblastoma treatment 1 . These tumors have a benign histopathological manifestation, they exhibit unique biological behaviors such as local invasiveness and repeated recurrence. Although reports suggesting the malignant potential of ameloblastoma 2 , metastasis is rare. Here, we report a rare case of a patient with ameloblastoma of the right mandible who presented with bilateral pulmonary metastases 12 years after radical resection and whose case remained misdiagnosed for 32 years.  Table 1. We reviewed her chest X-rays (Fig. 1A-1D). Since 1986, X-rays showed that her bilateral lung nodules increases slowly and continuously. The CT at the time of her admission in 2018 revealed soft tissue nodules in the left main trachea and right lower lobe bronchus, with enlarged mediastinal and bilateral hilar lymph nodes ( Fig. 2A-2B), and electronic bronchoscopy revealed 90% blockage of the left main trachea and full blockage of the ori ce of the right lower lobe basal bronchus by new lesions with abundant surface vasculature (Fig. 3A-3B). Biopsy on this tissue revealed a nest-like structure of tumor cells with surrounding cells exhibiting a high columnar shape and palisade-like arrangement and squamous metaplasia (Fig. 4A). Comparison of the recurrent right mandibular ameloblastoma with a sample resected in 2006 (Fig. 4B) led to a nal diagnosis of metastatic ameloblastoma (malignant ameloblastoma [MA]) in the bilateral lungs after misdiagnosis for 32 years. Because she could not tolerate systemic chemotherapy or radiotherapy, interventional bronchoscopic therapy and electroexcision of the left main tracheal tumor were performed 2 months post-diagnosis. An electric snare was connected to a high-frequency electrocautery and ligated to the bottom of the tumor in the left main trachea through the biopsy channel of the electronic bronchoscope. High-frequency electrotomy (power, 40 W for 5-10 s) was used to remove the tumor, and biopsy forceps were used to remove tumor tissue ( Fig. 3C-3D). The patient's respiratory function was satisfactory with an St. George's respiratory disease questionnaire score that uctuated by > 4 from before to after interventional therapy, indicating a clinically signi cant result. She died of respiratory failure 1 year later.

Discussion And Conclusions
Since 1923, approximately 100 cases have been reported since 3,4 . In 2005, the WHO de ned MA as a histologically benign-appearing ameloblastoma that has metastasized. Ameloblastomas are locally aggressive and rarely metastasize 5 . No standard treatment for MA exists, and most treatment decisions are based on case reports 6,7 . Curettage and radical resection are common treatments, radiotherapy and chemotherapy is recommended for inoperable metastatic lesions; however, its e cacy is unproven and it is considered a palliative treatment 8,9 . In our case, The patient is contraindication for operation due to poor physical condition and she could not tolerate systemic chemotherapy or radiotherapy due to extensive masses in both lungs. Interventional treatment under tracheoscopy can effectively unblock the her airway and relieve respiratory symptoms. The ndings from this case suggest that bilateral metastatic tumors should be considered in a patient with nodules or masses in both lungs, and that a careful medical history should be taken.
The mechanism of distant metastasis of ameloblastoma remains unclear; however, this tumor likely spreads via the blood, lymphatic vasculature and airway to local lymph nodes or distant organs, including the lungs, brain, and skin 5,10 . Metastasis usually follows multiple recurrences, frequently affects the lungs (≥ 80%), and may arise more than a decade after primary tumor resection [11][12][13][14][15] . In our case, bilateral pulmonary metastases were detected 12 years after primary tumor resection. However, the case was misdiagnosed for 32 years, likely due to the long asymptomatic period, inert growth of bilateral pulmonary tumors, and a lack of clinical understanding of the disease.
This case demonstrates several points: (1) Patient with a history of ameloblastoma who presents with pulmonary symptoms should be considered for metastases. (2) Electronic bronchoscopic biopsy can be used to con rm a diagnosis of bilateral pulmonary masses with less trauma and good tolerance. (3) Patient with intratracheal metastases of advanced ameloblastoma can achieve symptom relief from an interventional bronchoscopic treatment.

Declarations
Ethics approval and consent to participate The case report was approved by Wuxi People's Hospital Clinical New Technology and Research Ethics Committee (KS2019008).
Consent for publication: This case report obtained the consent for publication from the patient.
Availability of data and materials Not applicable.
Competing interests The authors declare that they have no competing interests.
Funding This research did not receive any speci c grant from funding agencies in the public, commercial, or not-for-pro t sectors.
Authors' contributions: J.L. drafted the manuscript. S.Y analyzed pathological results. Z.Y. and T.B. analyzed the case and revised the manuscript.