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Do dental implants facilitate bone invasion in patients with oral squamous cell carcinoma? A case series

Open AccessPublished:August 22, 2022DOI:https://doi.org/10.1016/j.ijom.2022.08.004

      Abstract

      Osseointegrated dental implants in the vicinity of oral squamous cell carcinoma (OSCC) will become more common given the increasing popularity of dental implants. Reports and studies of OSCC around dental implants are rare, as is the topic of how to handle OSCC surgically when implants are in contact with the tumour. In view of this uncertainty, a histological study was performed to assess tumour behaviour around implants. The aim was to determine whether an implant facilitates inward growth of the tumour and how this should be taken into account during staging and treatment planning. A total of 20 specimens were collected. The implants were macroscopically in contact with OSCC in 13 of the 20 specimens. Histologically, tumour tissue near the implant was indeed confirmed in nine of these cases. In seven cases, tumour invasion had led to resorption of the underlying jaw bone; tumour between the bone–implant interface was identified in only two of these cases, but without downward growth along the implant. In conclusion, no proof was found to confirm that the bone–implant interface is a preferred route for invasion. Therefore, dental implants in the vicinity of OSCC should not influence staging and treatment planning in this regard.

      Keywords

      Dental rehabilitation using osseointegrated implants has become a popular treatment option. As the numbers of installed implants increase, it is likely that the incidence of oral cancers, in particular oral squamous cell carcinoma (OSCC), in relation to implants will also rise.
      • Schache A.
      • Thavaraj S.
      • Kalavrezos N.
      Osseointegrated implants: a potential route of entry for squamous cell carcinoma of the mandible.
      The first clinical appearance of OSCC near dental implants may present as peri-implantitis. In general, inflammatory responses can play a decisive role at different stages of tumour development; however, a direct link between the role of peri-implantitis and oral cancer has not yet been found.
      • Ito K.
      • Takahashi K.
      • Eda T.
      • Kondoh T.
      • Goss A.
      Peri-implant squamous cell carcinoma.
      • Raiser V.
      • Abu-El Naaj I.
      • Shlomi B.
      • Fliss D.M.
      • Kaplan I.
      Primary oral malignancy imitating peri-implantitis.
      • Ramos J.C.
      • Dos Santos E.S.
      • Normando A.G.C.
      • Alves F.A.
      • Kowalski L.P.
      • Santos-Silva A.R.
      • Vargas P.A.
      • Lopes M.A.
      Oral squamous cell carcinoma around dental implants: a systematic review.
      It cannot be emphasized enough that a high degree of vigilance is required in the evaluation of the peri-implant region when it lies in the vicinity of a tumour. In these cases, the presence of tumour must be excluded, which usually requires a biopsy.
      The most frequently used therapy for OSCC is surgical excision. Tumour invasion of the adjacent soft tissue and peri-implant bone must be accurately identified to ensure that the resection margins are tumour-negative. In the case of a tumour in or close to the margins, postoperative radiotherapy and/or chemotherapy is necessary.
      • Montero P.H.
      • Patel S.G.
      Cancer of the oral cavity.
      Reports and studies on OSCC around dental implants are rare, and the topic of the type of resection when dental implants are in contact with or close to the tumour is even more scarcely addressed.
      • Schache A.
      • Thavaraj S.
      • Kalavrezos N.
      Osseointegrated implants: a potential route of entry for squamous cell carcinoma of the mandible.
      • Meijer G.J.
      • Dieleman F.J.
      • Bergé S.J.
      • Merkx M.A.
      Removal of an oral squamous cell carcinoma including parts of osseointegrated implants in the marginal mandibulectomy. A case report.
      • Nariai Y.
      • Kanno T.
      • Sekine J.
      Histopathological features of secondary squamous cell carcinoma around a dental implant in the mandible after chemoradiotherapy: a case report with a clinicopathological review.
      In this study, 20 resection specimens containing implants were examined histologically to assess whether an implant facilitates the inward growth of tumour and therefore should be taken into account during staging and treatment planning.

      Materials and methods

      Patients treated in the Department of Oral and Maxillofacial Surgery of Radboud University Medical Center, Nijmegen, the Netherlands were included in the study. After establishing the definitive diagnosis, including tumour characteristics and the size of the tumour-free margins, 20 specimens containing implants, obtained during the period between 2015 and 2020, were collected. After macroscopic inspection, the gross appearance of 13 of the specimens indicated that it was likely that the tumour was in contact with the implant. To allow assessment of the bone–implant interface and thereby the possible presence of tumour, the specimens were first fixed in 10% neutral buffered formalin solution. Thereafter, those parts of the specimens that contained the implants with surrounding bone were dissected, dehydrated in a graded series of ethanol (70–100%), washed with acetone, and embedded in polymethylmethacrylate (PMMA) for 4 weeks. Subsequently, the blocks were sectioned in buccolingual slices with a thickness of 10–12 µm each.
      • van der Lubbe H.B.
      • Klein C.P.
      • de Groot K.
      A simple method for preparing thin (10 microM) histological sections of undecalcified plastic embedded bone with implants.
      After staining with methylene blue and basic fuchsin, the specimens were evaluated under an automated Axio Imager Z1 light microscope (Carl Zeiss, Oberkochen, Germany) at × 10, × 50, and × 200 magnification. A complete qualitative morphological description of the soft and hard tissue response was conducted by a pathologist (P.J.S.). The study was approved by the local ethics committee (2022–13501).

      Results

      Histologically, tumour tissue in the immediate vicinity of the implant was identified in nine of the 13 specimens, four from the lower jaw and five from the upper jaw. All nine cases involved OSCC.
      Surface erosion of the bone was noted in seven cases. Tumour-associated stroma was observed between the tumour itself and the bone, while the invasion proceeded horizontally (Fig. 1), thus exposing the implant surface hitherto covered with bone to tumour tissue. In all seven cases, a close bone–implant interface was observed; no evidence of downward growth of the tumour along the implant was discovered.
      Fig. 1
      Fig. 1Erosive bone invasion (black arrows) of OSCC (a) near the dental implant (b) was seen in seven patients. Tumour-associated stroma (c: white arrow) between the OSCC (a) and underlying bone (d), showed a horizontal invasion. In all seven cases, a close bone–implant interface was observed, but there was no evidence of downward growth of tumour along the implant.
      In the other two cases, tumour was identified between the bone surface and the implant. After reviewing the medical files, one patient had previously been diagnosed with peri-implantitis in 2012. Also loss of bone attachment was noticed in 2015, as deepened pockets with bleeding after probing were detected. In 2017, an OSCC was diagnosed in the upper left maxilla (Supplementary Material Fig. S1A). It appears as though the angular bone defect was filled with tumour; only a horizontal/oblique invasion of tumour could be observed (Supplementary Material Fig. S1B). It is likely that in this case, the tumour grew into the space between the bone and implant already created by the previous inflammation-associated bone loss with subsequent pocket formation.
      The second patient had an OSCC in the right mandible (Supplementary Material Fig. S2A). This patient had already been treated for an OSCC of the floor of the mouth 3 years earlier, for which postoperative radiotherapy was started due to tumour-positive resection margins. While the radiographs in 2013 showed no bone loss (Supplementary Material Fig. S2B), extensive osseous destruction was observed in 2016 for both implants (Supplementary Material Fig. S2C). The implant in the right mandibular cuspid region (43) was unfortunately lost during processing. Presumably due to osteoradionecrosis, the tumour in the right mandible progressed horizontally through the marrow spaces of the necrotic cancellous bone to the contralateral implant region (33), resulting in massive tumour ingrowth (Fig. 2). Thus, in this case, the presence of tumour near the implant surface was not due to vertical penetration between the bone and implant either.
      Fig. 2
      Fig. 2OSCC in the vicinity of a dental implant in the mandible, showing extensive osseous destruction. The tumour had spread through the irradiated cancellous bone and had enclosed the contralateral implant massively (black arrows).

      Discussion

      Since the replacement of lost teeth with implants is becoming more widespread, it is expected that in the future we will increasingly be confronted with patients with oral cancer who have had such implants placed in the past. Furthermore, with respect to rehabilitation, implant treatment is also conducted in patients who have already suffered from OSCC in the past. Therefore, the number of patients with primary tumours, recurrences, or even second primary tumours close to implants will increase.
      Whether the jawbone–implant interface could be a preferred route for a tumour to invade deep into the jawbone has only been studied to a limited extent. Nariai et al.
      • Nariai Y.
      • Kanno T.
      • Sekine J.
      Histopathological features of secondary squamous cell carcinoma around a dental implant in the mandible after chemoradiotherapy: a case report with a clinicopathological review.
      presented a case with a history of chemoradiotherapy. Similar to the case depicted in Fig. 2 here, the tumour had spread from the nearby cancellous bone and had enclosed the entire implant. This tumour behaviour is mainly seen in irradiated jaws, as the empty marrow spaces of necrotic cancellous bone offer no resistance to tumour invasion.
      • McGregor A.D.
      • MacDonald D.G.
      Routes of entry of squamous cell carcinoma to the mandible.
      No evidence of invasion was observed along the bone–implant interface in this reported case.
      OSCC ingrowth into bone occurs by invasion of the alveolar ridge and cortical plate.
      • McGregor A.D.
      • MacDonald D.G.
      Routes of entry of squamous cell carcinoma to the mandible.
      Many studies have proven that bone destruction is initiated via osteoclasts being activated by tumour-associated stroma and not by direct contact of the malignant epithelium.
      • Elmusrati A.A.
      • Pilborough A.E.
      • Khurram S.A.
      • Lambert D.W.
      Cancer-associated fibroblasts promote bone invasion in oral squamous cell carcinoma.
      This was also confirmed histologically in the present study. Only one case report has suggested that osseointegrated implants can facilitate the invasion and spread of OSCC along the bone–implant interface and thereby impact the staging and treatment planning.
      • Schache A.
      • Thavaraj S.
      • Kalavrezos N.
      Osseointegrated implants: a potential route of entry for squamous cell carcinoma of the mandible.
      After reviewing this publication, we are not convinced of invasion along the bone–implant interface; the illustration in this article shows horizontal bone loss as was seen in the cases presented here.
      • Schache A.
      • Thavaraj S.
      • Kalavrezos N.
      Osseointegrated implants: a potential route of entry for squamous cell carcinoma of the mandible.
      This study has its limitations due to the small number of cases (n = 9), including only one with peri-implantitis and one with osteoradionecrosis. Further studies with larger numbers are needed to confirm the findings.
      In conclusion, based on the seven implant-related tumours (exclusion of failing implants due to peri-implantitis and osteoradionecrosis) in the present study and after reviewing the literature, it appears that there is no evidence to corroborate that the bone–implant interface is a preferred route for tumour invasion. Therefore, dental implants in the vicinity of OSCC should not influence staging and treatment planning in this regard.

      Funding

      None.

      Competing interests

      None.

      Ethical approval

      Ethical approval was obtained (Ref. number: 2022–13501).

      Patient consent

      Written consent was obtained for this research and for the publication of the clinical data and clinical photographs.

      Appendix A. Supplementary material

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