Squamous cell carcinoma (SCC) is the sixth most common malignant type of cancer worldwide. And it accounts for approximately 90% of malignancies occurring in the oral cavity. It is defined as a malignant neoplasm which originates in the stratified epithelium and is typically found in men over the age of 60 who are habitual alcohol and tobacco users. However, such demographic has been shifting toward patients under the age of 40, and even in children, adolescents, and in women who do not have these aforementioned risk factors^1,2). Some other risk factors of SCC include: exposure to ionizing radiation, the existence of nutritional deficiencies, immunosuppressant drug^3,4). While the epidemiologic profile of oral squamous cell carcinoma (OSCC) has been shifting, utilization of dental implants has been steadily increasing. Oral rehabilitation using dental implants has become one of the best options for the treatment of edentulous patients and is considered by some to be the only type of treatment for partial or total edentulism. Because of the increase in the use of dental implants, literature has also reported an increase in the number of complications associated with dental implants.

Most complications are associated with the inflammatory processes that affect the bone and soft tissues surrounding dental implants, which are known as peri-implantitis. In Peri-implantitis, the soft tissues become inflamed whereas the alveolar bone, which surrounds the implant for the purposes of retention, is lost over time. This state is described as ‘implant histoclasia’ or ‘perimplantoclasia’. The primary cause of peri-implantitis is dental plaque deposition that initiates gingivitis, later progresses to pocketing, and finally results in alveolar bone resorption.

Repeated irritation and chronic inflammation are well-known risk factors for malignancy. Early malignant lesions can be confused with peri-implantitis, which could delay the early diagnosis of oral malignancy.

This report presents a clinical case in which an advanced stage of OSCC around a dental implant was diagnosed in a patient who failed to follow-up for a routine exam for over two years. We need more evidence to prove any causal relationship between dental implants and OSCC; however, the case emphasizes the importance of differential diagnosis in peri-implantitis, due to its similarity in clinical presentation with OSCC.

A 57-year-old male patient was referred from the local clinic to address white, large ulcerative lesion (Fig. 1A, B) around the implant to the department of Oral & Maxillofacial Surgery in Kyunghee university, Seoul, Korea. The patient was present with a maxillary Lt. 1^st molar implant with extensive ulcerative lesions and significant bone resorption around the implant (Fig. 1C, D) that was placed 17 years ago. The patient had been periodically checked after implant placement in 2003 until February 2020, however, no follow-up exam has been completed since then until 2022 April. The patient reports smoking, but no alcohol consumption. The patient’s medical history includes diabetes and a history of cerebral infarction treatment. The presence of a suspicious ulcerous lesion around the implant prompted a biopsy. Microscopic examination revealed a moderately well-differentiated squamous cell carcinoma. From the image taken two weeks after the first visit on April 2022, OSCC proliferated toward the palate (Fig. 2A). The surgery was performed a month after the initial visit. Within one month, the size of the lesion increased, and keratinized tissue completely covered the implant (Fig. 2B). The TNM stage was diagnosed as cT4N1Mo. Modified RND (type III) with preservation of the spinal accessory nerve of the left neck and a partial maxillectomy (#24∼#26i) was performed as surgical interventions. Complete excision was performed for the primary lesion with a safety margin. The RFFF (Radial forearm free flap) was harvested with the radial. a. and cephalic vein which is considered one of the best options for reconstruction of soft tissue defects in the oral cavity and oropharynx⁵⁾ after tumor resection using a pneumatic tourniquet (Fig. 3, 4). And the histopathologic diagnosis of the main mass was SCC, a verrucous subtype (Fig. 5).

Figure 1. Clinical pictures, panoramic radiograph, and contrast-enhanced CT image (A), (B) In the first visit of the clinical picture, an extensive whitish ulcerative lesion was observed around the maxillary Lt. 1st molar implant. (C) Panoramic radiograph showing significant bone resorption around Lt. 1st molar implant. (D) Bone resorption is observed in contrast-enhanced CT image (marked with an arrow).

Figure 2. Clinical pictures (A) After two weeks, OSCC proliferated toward the palate. (B) Preoperative intraoral view, keratinized tissues covered the implants.

Figure 3. Harvested RFFF (Radial Forearm Free Flap).

Figure 4. Reconstruction with RFFF.

Figure 5. Histopathologic diagnosis of the main mass (A) Photomicrograph of oral squamous cell carcinoma. (B) Photomicrograph of biopsy showing islands of malignant squamous cells with keratin pearl formation (hematoxylin and eosin; original magnification ×20).

Since the oral cavity is constantly influenced by inflammation, DNA damage, chemical abuse, and poor oral hygiene, the oral mucosa becomes susceptible to malignant transformation. The gingival attachment in dental implants is an area where constant inflammation occurs, this may affect the stability of the mucosa, and this inflammation may be a major cause of the development of malignancy due to the action of cytokine mediators: prostaglandins, interleukin-1, interleukin-6, and tumor necrosis factor⁶⁾. Prostaglandin is responsible for the initiation, promotion, and progression of carcinogenesis. Its mechanism is that it reduces the activity of both humoral and cellular immune response, thus malignant cells are no longer removed^7,8). IL-6 causes keratinocytes to increase its activator protein-2 mRNA and protein, and it leads to increased skin inflammation, keratinocyte growth, and carcinogenesis⁹⁾. This, in turn, causes compensatory cell proliferation, which will promote the accumulation of DNA damages and gene mutations, and incorporate internal and external carcinogenic factors into the growth of stimulated normal cells¹⁰⁾. Also, titanium particles may leach into nearby tissues by surface corrosion, and friction, among others¹¹⁾. It has been shown that leaching affects macrophage’s immunomodulation. As a result, DNA damage, oxidative stress, and protein carbonylation are increased, causing increased inflammation^12,13). While the implant is suspected by some, to increase carcinogenicity, however, tobacco, betel quid chewing, alcohol consumption, and poor oral hygiene can have similar effects, by causing an increase in the action of cytokine mediator. Such risk factors have been supported with more evidence.

In the case of a 57-year-old patient, it cannot be concluded whether the implant contributed to the development of squamous cell carcinoma at all. More research is required to establish whether there is any causal relationship between peri-implantitis and malignancy as of today, since in many cases patients already had a history of some form of malignancy, or had risk factors such as chronic alcohol consumption, smoking, and nutritional deficiency^14-20). Synchronous exposure to chronic tobacco and alcohol use showed an increase in malignancy by five to thirteen folds^21,22).

While peri-implantitis or mucositis needs to be kept up with follow-up examination, the possibility of dismissing malignancy as peri-implantitis should not be neglected. OSCC, especially in its early stages, has clinical presentations similar to peri-implantitis. Peri-implantitis is generally treated by improving oral hygiene, periodontal debridement, and sometimes prescribing antibiotics but sometimes, peri-implantitis is surgically removed without performing a biopsy, thus a small number of studies are available regarding microscopic findings of peri-implantitis²³⁾. Whether dental implant causes malignancy or peri-implantitis has the potential to progress to OSCC is inconclusive, and more research needs to be conducted. However, as a clinician, a suspicious lesion around the dental implant should not be assumed as peri-implantitis that will resolve with conventional treatment. When the lesions do not respond to the treatment, a biopsy should be performed for histological analysis in order to rule out malignancy, as malignancy has certainly been found in the vicinity of dental implants, and the consequences of omitting them can be detrimental. As witnessed in this case of a 57-year-old patient, due to the rapid progression of malignancy, clinicians should not delay in providing diagnosis and treatment in suspected lesions.

Increased dental implant placement caused an increase in complications such as peri-implantitis. If peri-implantitis is unresolved despite constant treatment, it must be suspected of being malignant. In this case, the affected tissues should be taken for a biopsy for a histopathologic evaluation as soon as possible. Clinical and radiographic evaluation should be performed periodically after dental implants.