Unusual presentation of pulmonary adenocarcinoma metastases in the mandibular condyle: A case report

Introduction Mandibular bone metastases should be suspected in all patients with temporomandibular joint disorder symptoms and lung cancer history. The purpose of this report is to present a case of metastasis to the mandibular condyle following pulmonary adenocarcinoma. Case presentation In December 2020, a 71-year-old patient was evaluated by the Department of Maxillofacial Surgery for the presence of a large osteolytic lesion in the left mandibular condyle. There were no changes to the face or occlusion, and mandibular movements were preserved. After surgical removal, histology revealed pulmonary adenocarcinoma metastasis. Discussion To date, only 7 cases of condylar metastases are described by lung cancer. This pathology's clinical and radiological features are almost always shaded and not specific. Conclusion This study also focuses on rare conditions, such as metastases to the mandibular condyle. It also stresses the importance of a multidisciplinary approach both in the diagnostic and therapeutic process.


Introduction
Lung cancer represents approximately 12 % of worldwide new cancer diagnoses [1].In the initial stages, it is almost always asymptomatic, and therefore the diagnosis is late, in the advanced stage when the patient has already developed metastases.Indeed, bone metastases are reported in the literature in 65-75 % of patients with advanced-stage lung, breast, prostate, and bladder cancer [2].Metastases at the level of the facial massif are rare: they account for about 1-8 % of oral cancer [3][4][5][6] and in 60-80 % of cases involve the body of the mandible [7][8][9].Mandibular condyle involvement is extremely rare.To date, only a few cases have been reported [4] with non-specific symptoms such as pain, swelling, temporomandibular joint dysfunction, lockjaw, and sometimes even pathological fractures [4][5][6][7]9].Both the rarity of the condylar disease and the absence of specific signs and symptoms (both clinical and radiological) generally lead to a delay in diagnosis and treatment, thus worsening the prognosis of the disease.Below we present a case of a patient with metastases in the left mandibular condyle originating from lung cancer that showed slight and temporary common temporomandibular joint disorder (TMJ)-like symptoms.The work has been reported in line with the SCARE criteria [10].

Case presentation
A 71-year-old white man presented to the Maxillofacial Unit in December 2020 for a specialist surgical consultation.The patient's medical history was positive for lung adenocarcinoma; He had undergone right upper lung lobectomy surgery and mediastinal lymph node sampling in 2019.He also underwent four cycles of adjuvant chemotherapy in 2019.During the Positron Emission Tomography (PET) follow-up, the presence of an osteolytic area in the left condyle was highlighted in December 2020 (Fig. 1).This lesion featured focal impregnation of the radiopharmaceutical of dubious significance, with a maximum SUV (Standardized Uptake Value) of 3.6.There were no facial or occlusion alterations on inspection, and the mandibular movements were preserved.Furthermore, the patient did not report pain or sensorineural alterations.Computed tomography (CT) showed the presence of a lesion of the left mandibular condyle with partial erosion of the cortical bone (Fig. 2 A-B).Magnetic resonance imaging (MRI) also showed a subtle alteration in the surrounding muscles.A multidisciplinary team was created with maxillofacial surgeons, oncologists, and radiotherapists.It was decided to proceed with tumorectomy and subsequent adjuvant radiotherapy.In January 2021 he underwent a left condilectomy under general anesthesia (Fig. 3 A-B).Surgery was extensive: 1.5-2 cm removal from seemingly healthy margins.Then a condylar implant was inserted to restore function.Histopathological analysis revealed bone localization of lung adenocarcinoma; and positive immunophenotype for TTF1 and CK7.The surgical scar healed well and a follow-up CT scan in 3 months displayed no evidence of tumor recurrence.In May 2021, he underwent Stereotactic Body Radiation Therapy every other day for a total of 3000 cGy.In December 2021 RM showed the presence of an expansive solid mass (26 × 23 × 35 mm -AP × LL × SC) in correspondence to the residual condylar region.It presented a homogeneously intermediate signal intensity in both T1w and T2w; a modest alteration of the signal in the neighboring soft tissues was associated (absence of clear signs of the infiltration of the masseter and lateral pterygoid muscles).The patient underwent chemotherapy.The patient, 32 months after surgery, is free from disease.

Discussion
Metastases are the most important cause of cancer-related morbidity and mortality.Literature suggests that jaws are not a common site of metastasis and condylar metastases are even rarer.These account for 5.7 % of all maxillary metastases [8] and only a few cases have been reported in the literature [9].To date, only 7 cases of condylar metastases are described.In most cases (22.5 %) they originate from occult pulmonary adenocarcinoma at the metastatic stage [11][12][13].Other primary cancers are breast, kidney, liver, prostate, and bladder [3,[14][15][16][17][18].This low rate of condylar localization is linked to two pathophysiological hypotheses [4,[12][13][14]19]: (1) TMJ has a lower amount of red marrow than other bones of the body; (2) the condyle has a separate blood supply to the mandibular body, so the likelihood of metastases hitting the condyle is lower.Recent literature suggests that metastases mainly affect bones rich in red marrow; at the endothelium level, there is a microenvironment ideal for their proliferation.This theory explains why bone metastases are more frequent in the vertebrae, ribs, pelvis, and extremities of long bones; on the contrary, they are infrequent in the hands, feet, and mandibular condyles.The reason for this selectivity is little known, but it is thought to be due to the concomitant presence of some factors at the level of trabeculae.They are: higher rates of bone turnover; abundant vascularization; microenvironment made of adipocytes, fibroblasts, chemokines, reticulocytes, chondrocytes, endothelial cells, pericytes, hematopoietic and mesenchymal stem cells; bone matrix (made of inorganic salts and organic matrix) acts as structural support for both bone cells and metastases.All this therefore contributes to the seeding of cancer cells and their growth [20].
The clinical presentation of this pathology, as in the case report presented, is shaded and non-specific.Swelling, pain, click joint, and lockjaw are symptoms common to all joint pathologies, especially in patients with comorbidities or known dysfunctional pathologies.Instrumental examinations are also not very specific [4,9,14].Nonspecific symptoms and little knowledge of the pathology (given its rarity) lead to a misdiagnosis and therefore diagnostic delay.In the case presented, the CT and MRI scans reported the presence of an osteolytic   lesion; it also highlighted osteoarthrosis processes and inflammation, all confounding factors in the diagnostic process.Surely, the presence of masticatory muscle involvement drove the diagnostic suspect.A possible confounding factor in the present case was the ambiguity of the outcome of the PET examination.The PET has evidenced the presence of osteolytic lesion to condylar level in the absence of an elevated SUV, characterizing a frankly neoplastic lesion.Therefore, a multidisciplinary approach is fundamental in diagnosis: a positive history of pulmonary adenocarcinoma suggests it may have been pulmonary metastasis with rare localization to the mandibular condyle.

Conclusion
Although metastases are the most important cause of cancer-related morbidity and mortality in the world, lung cancer rarely metastasizes to the maxillary bones.In addition, signs and symptoms associated with the presence of maxillary metastases are nonspecific.These two characteristics make the eventual diagnosis of mandibular metastases, especially condylar, difficult, leading to misdiagnosis.Faced with such conditions, therefore, a multidisciplinary approach is fundamental.It allows you to get to the correct diagnosis faster and then set up a suitable and timely therapy.

Consent
Written informed consent was obtained from the patient for publication and any accompanying images.A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

Fig. 1 .
Fig. 1.PET examination showing the presence of a focal impregnation area of the radiopharmaceutical of dubious nature (highlighted in the circle) in the left mandibular condyle.