1

Introduction

Metastatic lesions to the oral cavity are rare, accounting for only 1–8% of all oral malignancies [ ], and involvement of mandibular condyle is highly unusual [ ]. The presenting signs and symptoms include pain and swelling in the pre-auricular region, limited mouth opening, clicking, and crepitus, mimicking temporomandibular joint (TMJ) disorders [ ], causing a delay in diagnosis. Prompt diagnosis and management are crucial for improved outcomes. A complete and precise history of the present illness, past and current medical and surgical history, family history, a thorough review of systems, comprehensive physical examination, appropriate imaging, laboratory studies, and tissue biopsy are essential to achieving a diagnosis [ ].

Metastatic spread to the condyle is uncommon due to the sparse hematopoietic bone marrow, limited local vascular supply, and the presence of an osseous plate that prevents the spread of malignant cells into the condylar marrow space [ , , ]. Primary tumors of the breast, lung, kidney, prostate, and less often from the pancreas, rectum, stomach, liver, and colon [ ] can rarely metastasize to the condyle. Even less common is the metastatic spread from the bladder. There has been only one documented case of condylar metastatic carcinoma from the bladder [ ]. We report the second case of metastasis to the mandibular condyle from a known primary urothelial carcinoma of the bladder. Furthermore, we have performed a thorough review of the literature to include all the documented cases of metastasis to the condyle, from its first case in 1947 [ ] to the present. To the authors’ knowledge, this is the first comprehensive literature review reporting 98 published cases of condylar metastases.

2

Report of case

83-year-old man presented to Strong Memorial Hospital for evaluation of a lytic lesion of his right mandibular condyle. Several weeks before the presentation, he experienced a sudden onset of pain in the right preauricular region while eating. He also reported limited maximal incisal opening (MIO). This prompted the patient to visit his primary care physician, who obtained a maxillofacial computed tomography (CT) scan that revealed “a lytic lesion of the right mandibular condyle with possible fracture concerning for malignancy”.

The patient’s past medical history was significant for urothelial carcinoma of the bladder, diabetes mellitus, chronic kidney disease, nephrolithiasis, hyperlipidemia, and hypothyroidism. His past surgical history included transurethral resection of the tumor, bilateral knee replacement, and colonoscopy. His medications comprised of levothyroxine, atorvastatin, colchicine, tramadol, as well as his chemotherapeutic regimen (5-FU, Mitomycin, Cisplatin, Gemzar, Pembrolizumab) for the urothelial carcinoma of the bladder. He also received radiation therapy in conjunction with chemotherapy. He had no known drug allergies. His social history was positive for a brief smoking period of three years in the 1960s and occasional cigar smoking.

A head and neck examination revealed mild swelling and tenderness to the right preauricular region. He had limited mouth opening with MIO of approximately 20 mm. Intraoral examination was unremarkable and there was no palpable cervical lymphadenopathy. Cranial nerve examination was normal as well.

Imaging included a panoramic radiograph and a maxillofacial CT scan without contrast revealing a small lytic osseous lesion involving the right condylar head and neck with an associated pathologic fracture ( Fig. 1 A, B, C). The CT scan also showed significant destruction of the mandibular cortex in this location, suggesting a “malignant process”. Biopsy was obtained utilizing the fine needle aspiration (FNA) technique. The cytopathology team reviewed the specimen and confirmed the presence of malignant cells, a diagnosis consistent with metastatic bladder cancer was established ( Fig. 2 A, B).

A: Coronal view of CT scan showing small lytic osseous lesion involving the right condylar head. B: Axial view of CT scan showing small lytic osseous lesion involving the right condylar head. C: Sagittal view of CT scan demonstrating small lytic osseous lesion involving the right condylar head and neck with an associated pathologic fracture.

A: Photomicrograph showing large malignant cells arranged singly and in loosely cohesive clusters. The tumor cells demonstrate a high nuclear to cytoplasmic ratio and single “naked” nuclei with notable pleomorphism. Although a DiffQuik stain is not ideal for assessing nuclear features, we can see nucleoli (black arrows) and coarse chromatin (blue arrows). The cytoplasm is homogenous with fine vacuoles (black circle). Diff-Quik stain, 200× magnification. B: Loosely cohesive cluster of malignant cells with high nuclear to cytoplasmic ratio, pleomorphism, irregular nuclear contours, coarse chromatin (blue arrows), prominent nucleoli (black arrows), and homogeneous cytoplasm with fine vacuoles. Diff-Quik stain, 400× magnification. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

At the time of presentation, our patient was also noted to have a recurrent high-grade urothelial carcinoma with muscle invasion with metastasis to the lung found on a positron emission tomography (PET) scan. He was managed by radiation oncology with palliative radiation therapy.

3

Discussion

Metastatic spread to the mandibular condyle is a rare occurrence and potentially diagnostically challenging [ ]. Solitary metastasis to the mandibular condyle is rather infrequent, and in the majority of the cases, it is an indication of widespread metastases reflecting the terminal stage of malignancy [ ]. These are often suggestive of an undiagnosed distant primary tumor carrying a poor prognosis [ , ]. Due to the commonly acknowledged fact that the mandible lacks the lymphatic system, it is believed that the mechanism of spread to this area must occur via a hematogenous route [ , ]. Furthermore, the sparse hematopoietic bone marrow, limited local blood supply, and the presence of an osseous plate prevents the spread of malignant cells into the condylar marrow space, making this a rare phenomenon [ , , ].

Diagnosis can be challenging because clinical symptoms are usually nonspecific, often mimicking TMJ dysfunction or odontogenic infections [ , , ]. Commonly reported symptoms are pain and swelling in the TMJ region. Other symptoms include trismus, malocclusion, dysfunction, and paresthesia [ , , , ]. Our literature review consisted of 81 publications with a total of 98 published cases of metastasis to the condyle from years 1947–2020 ( Table 1 ). According to the review, the most common presenting signs and symptoms were pain (68 patients) and swelling (39 patients) in the TMJ region. 11 patients also reported trismus/difficulty opening. A few patients complained of paresthesia (6 patients), malocclusion (5 patients), and dysfunction (3 patients) ( Table 2 ).

Table 1

List of all published cases of metastatic spread to the condyle between 1947 and 2021.

Year of publication	Author(s)	Presentation	Primary lesion	Diagnosis	Treatment	Age	Gender
2020	Shulz, Rocha [ ]	Pain/Paresthesia	Breast	No biopsy	Radiation	52	F
2018	Mauricio Hale [ ]	Pain	Lung*	Adenocarcinoma	Palliative	72	M
2017	Seo-Young An [ ]	Pain	Neck vs Lung	No biopsy	Palliative	75	F
2017	Guarda-Nardini [ ]	Pain/Deflection	Lung*	Carcinoma	Resection	59	F
2017	Dodo [ ]	Trismus/Difficulty chewing	Breast*	No biopsy	Chemotherapy	55	F
2014	Sugiyama [ ]	Pain	Uterus	Adenocarcinoma	Radiation	65	F
2014	Kolokythas [ ]	Pain	Pancreas*	Adenocarcinoma	Palliative	66	F
2014	Klasser [ ]	Pain/Difficulty opening	Liver	FNA HCC	Palliative	75	M
2014	Chiesa [ ]	Pain/Swelling	Breast	No biopsy	Radiation	48	F
2013	Qiu [ ]	Pain/Swelling	Bladder*	Carcinoma	Resection/Chemotherapy	49	M
		Swelling/Discomfort	Prostate*	Adenocarcinoma	Resection/Chemotherapy	85	M
		Pain/Paresthesia	Lung*	No biopsy	Chemotherapy	62	F
		Swelling/Paresthesia	Penis	FNA SCC	Chemotherapy	53	M
		Pain/Swelling	Colon	FNA Carcinoma	Chemotherapy	64	M
		Pain	Breast	Carcinoma	Resection/Radiation	47	F
2013	Puranik [ ]	Pain/Swelling	Cervix	FNA SCC	Palliative	63	F
2013	Peacock [ ]	Pain/Malocclusion	Kidney	RCC (Angiosarcoma)	Resection	64	M
2012	Scolozzi [ ]	Pain/Malocclusion	Lung*	Large cell lung CA	Palliative	72	F
2012	Gonzalez-Perez [ ]	Pain/Swelling	Breast*	Adenocarcinoma	Chemotherapy	73	M
2012	Kelles [ ]	Trismus	Kidney	Clear cell RCC	Unknown	59	F
2011	Patricia [ ]	Pain/Trismus	Breast	Adenocarcinoma	Palliative	51	F
2011	Tabib [ ]	Pain/Swelling	Lung*	No biopsy	Palliative	49	M
2011	Cristofaro [ ]	Pain/Swelling	Prostate*	Adenocarcinoma	Resection	60	M
2010	Katnelson [ ]	Pain/Trismus	Lung*	FNA Carcinoma	Chemotherapy	51	M
2010	Freudlsperger [ ]	Pain	Prostate*	Carcinoma	Radiation	75	M
2010	Kruse [ ]	Pain/Swelling	Lung*	Lung CA	Palliative	73	M
		Pain/Difficulty opening	Lung*	FNA Adenocarcinoma	Palliative	75	F
		Malocclusion	Thyroid	No biopsy	Palliative	85	M
2009	Shintaku [ ]	Pain	Lung*	Adenocarcinoma	Chemotherapy	71	F
2009	Panossian [ ]	Pain/Swelling	Breast*	Carcinoma	Chemoradiation	79	F
2009	Gomes [ ]	Swelling	Unknown	Adenocarcinoma	Palliative	51	F
2008	Baber [ ]	Pain/Swelling	Neural crest*	FNA Neuroblastoma	Chemotherapy	15	F
2008	Schulze [ ]	Pain/Swelling	Bronchus*	No biopsy	Unknown	52	F
2008	Menezes [ ]	Pain/Swelling	Breast*	Adenocarcinoma	Chemotherapy	42	F
2008	Boniello [ ]	Pain	Lung*	Adenocarcinoma	Radiation	60	M
2008	Kamatani [ ]	Pain/Swelling	Liver	HCC	Chemotherapy	59	M
2006	Miles [ ]	Trismus	Breast	Adenocarcinoma	Resection	78	F
2006	Sari [ ]	Pain/Dislocation	Bronchus*	SCC	Resection/Chemotherapy	65	M
2006	Duker [ ]	Pain	Breast	No biopsy	Unknown	60	F
2006	Jia [ ]	Paresthesia	Breast	No biopsy	Radiation	46	F
2005	Kaufmann [ ]	Discomfort	Lung	No biopsy	Radiation	48	M
2005	Mason [ ]	Pain/Swelling	Colon*	Adenocarcinoma	Palliative	73	M
2004	Smolka [ ]	Facial asymmetry	Stomach	Adenocarcinoma	Radiation	67	M
2003	Kolk [ ]	Malocclusion	Stomach	Adenocarcinoma	Resection	51	M
2002	Meneghini [ ]	Pain/Swelling	Sacro-coccygeal	Chordoma	Resection	63	F
2002	Bokelund [ ]	Paresthesia	Pancreas	Adenocarcinoma	Palliative	77	F
1999	Robiony [ ]	Swelling	Lung*	Adenocarcinoma	Radiation	64	F
1998	Cohen [ ]	Pain	Unknown	SCC	Unknown	66	M
1997	Balestreri [ ]	Swelling	Rectum	Adenocarcinoma	Palliative	57	M
1997	Yoshimura [ ]	Pain/Swelling	Liver	HCC	Chemotherapy	61	M
1997	Beck-Mannagetta [ ]	Pain	Lung	Adenocarcinoma	Radiation	67	F
1996	Porter [ ]	Pain/Swelling	Testicle	No biopsy	Radiation	43	M
1996	Nortje [ ]	Dysfunction	Nose	No biopsy	Chemotherapy	43	M
1994	Johal [ ]	Pain	Kidney*	Clear cell carcinoma	Palliative	65	F
1993	MacAfee [ ]	Swelling	Colorectal	Adenocarcinoma	Resection	59	M
1993	Stavropoulos [ ]	Malocclusion	Breast	Adenocarcinoma	Resection	55	F
1990	Rutsatz [ ]	Pain/Swelling	Lung	Adenocarcinoma	Radiation	76	F
1990	Catrambone [ ]	Pain/Swelling	Prostate*	Adenocarcinoma	None	78	M
1990	Bavitz [ ]	Pain/Swelling	Unknown*	Malignant Schwannoma	Radiation	48	F
1990	Sanchez [ ]	Swelling	Unknown*	Adenocarcinoma	Resection	30	M
1989	Rubin [ ]	Pain	Unknown*	Adenocarcinoma	Radiation	67	F
1988	Webster [ ]	Pain	Breast	No biopsy	Palliative	52	F
		Pain	Breast	No biopsy	Palliative	54	F
1987	Lowicke [ ]	Pain	Kidney	Hypernephroid Carcinoma	Unknown	Unknown	Unknown
1986	Thatcher [ ]	Swelling	Prostate*	Adenocarcinoma	Resection	68	M
1986	Sokolov [ ]	Pain	Breast	Adenocarcinoma	Radiation	52	F
		Pain	Breast	No biopsy	Chemotherapy/Radiation	54	F
1985	DeBoom [ ]	Pain	Prostate*	Adenocarcinoma	Chemotherapy	68	M
1985	Owen [ ]	Unknown	Lung	No biopsy	Palliative	Unknown	Unknown
1985	Hecker [ ]	Swelling/Trismus	Unknown*	Adenocarcinoma	Radiation	63	F
1985	Sailer [ ]	Pain	Breast	Adenocarcinoma	Radiation	56	F
1982	Gerlach [ ]	Pain/Swelling	Bronchus	SCC	Radiation	42	Unknown
1982	Peacock [ ]	Pain/Swelling/Trismus	Bronchus*	SCC	Radiation	53	M
1982	Giles [ ]	Dysfunction	Rectum	Adenocarcinoma	Radiation	55	F
1981	Peron [ ]	Pain	Intestine	Adenocarcinoma	Radiation	55	M
		Pain	Bronchus	Adenocarcinoma	Unknown	74	M
		Pain	Unknown	Unknown	Unknown	39	F
1981	Compere [ ]	Swelling	Bronchus*	SCC	Resection	48	M
		Swelling	Pancreas*	Adenocarcinoma	Resection	73	M
		Pain	Breast	Adenocarcinoma	Resection	65	F
1980	Wolujewicz [ ]	Swelling	Prostate*	Adenocarcinoma	Palliative	74	M
1980	Mizukawa [ ]	Pain	Breast	Adenocarcinoma	Radiation	32	F
1978	Mace [ ]	Trismus/Paresthesia	Breast	Adenocarcinoma	Palliative	54	F
1975	Butler [ ]	Pain/Dysfunction	Breast	Autopsy/Carcinoma	Palliative	49	F
1974	Agerberg [ ]	Pain	Breast	Ductal carcinoma	Radiation	46	F
1974	Winiker-Blanck	Unknown	Bronchus	Unknown	Unknown	Unknown	Unknown
1973	Hartman [ ]	Pain/Trismus	Breast	Autopsy	Radiation	52	F
1969	Epker [ ]	Pain/Swelling	Breast	No biopsy	Radiation	45	F
1966	Worth [ ]	Unknown	Rectum	Adenocarcinoma	Unknown	Unknown	M
1965	Ameli [ ]	Pain/Swelling	Bronchus	Bronchogenic carcinoma	Palliative	55	M
1956	Blackwood [ ]	Pain	Breast	Polygonal cell carcinoma	Palliative	24	F
1954	Salman [ ]	Pain	Breast	Adenocarcinoma	Palliative	53	F
		Pain	Renal	Adenocarcinoma	Palliative	62	F
		Pain	Uterus	Epidermoid carcinoma	Palliative	64	F
		Swelling	Prostate		Palliative	65	M
1954	Thoma [ ]	Pain/Swelling	Unknown*	Transitional cell Carcinoma	Resection	51	F
		Unknown	Toe	Melanosarcoma	Unknown	Unknown	Unknown
1947	Thoma [ ]	Pain/Swelling	Unknown	Adenocarcinoma	Resection	49	M

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