Peripheral odontogenic myxoma: Clinical case with a literature review

Peripheral odontogenic myxoma (POM) is a rare and extra-osseous variant of odontogenic myxoma (OM), classified as a relatively rare benign odontogenic tumor, yet presenting locally aggressive behavior. The objective this manuscript is to report a case of POM in a 75-year-old patient, located in the right maxilla, and in addition, to perform a literature review of the data in relation to clinical, radiographic aspects, hypothesis of diagnosis, and treatment. A male patient, 75 years old, clinical examination constact the presence of a nodule, with a smooth surface, on the right upper alveolar ridge, measuring 20 x 25 mm, with a color similar to the mucosa, a softened consistency, involving teeth 14 and 15, and with an undetermined time of evolution was observed. The diagnostic hypothesis was a peripheral ossifying fibroma and differential diagnosis of peripheral giant cell lesion. An excisional biopsy was performed together with extraction of the involved teeth. Histopathological examination and histochemical reaction was confirm the histopathological diagnosis of POM. The reported case is extremely rare due to the clinical presentation of the lesion, causing bone resorption with tooth mobility. In addition, the age range of involvement is very different from that presented in the literature, between the second and fourth decade of life. The final diagnosis was very important, as it is a lesion with a great potential for recurrence, long-term follow-up should be more careful, and in case of recurrence, a new intervention must be performed.


Introduction
Odontogenic myxoma (OM) is an unusual, slow growth, benign mesenchymal tumor, locally invasive, and classified as an odontogenic tumor due to the great histological similarity that it presents with the odontogenic ectomesenchyme (Dotta et al, 2020;Francisco et al, 2016;Kawase-Koga et al, 2014;Leiser et al, 2009). This is in addition to its location in areas of tooth support in the maxillary bones, and its occasional association with missing or unbroken teeth (Oliveira et al, 2018;Raubenheimer et al, 2012;Aytac-Yazicioglu et al, 2008;Kapoor et al, 2015). OMs are classified into two variants: central odontogenic myxoma, (the most commonly found), and peripheral odontogenic myxoma (POM) (Aytac-Yazicioglu et al, 2008;Tasnime et al, 2016;Singh et al, 2013).
POM is considered a rare variation of OM, with few cases present in the literature, it is characterized as less aggressive in terms of local infiltration, and also presents a lower recurrence rate (Raubenheimer et al, 2012;Aytac-Yazicioglu et al, 2008;Kapoor et al, 2015). Some theories argue that it forms through the action of altered fibroblasts and myofibroblasts, considered capable of producing excess muco-polysaccharides yet generally unable to form mature collagen (Aytac-Yazicioglu et al, 2008;Perrotti et al, 2006). However, there is no consensus in the literature as to the formation of this OM subtype (Aytac-Yazicioglu et al, 2008;Perrotti et al, 2006;Chrcanovic & Gomez, 2019).
Currently, there is little data in the literature that compare POMs to central odontogenic myxomas, however, some studies argue that these lesions have a predilection for males and are usually located on the hard palate, parotid region, jugal mucosa, or mouth floor (Perrotti et al, 2006;Shimoyama et al, 2000;Elzay et al, 1978;Singh et al, 2013;Chrcanovic & Gomez, 2019).
Due to the wide spectrum of soft tissue injuries described in the literature with similarity to POM clinical characteristics, diagnosis of this tumor is a major challenge (Kanitkar et al, 2017). A definitive diagnosis and appropriate treatment can only be formulated when clinical, histological, and radiographic components are combined (Dotta et al, 2020;Kanitkar et al, 2017). The objective of this work is to report a rare clinical case of a POM, while conducting a comprehensive review of the cases reported in the literature.

Methodology
This article focuses on the search for a practical answer for healthcare professionals on how to deal with cases of rare oral lesions that are difficult to diagnose and with varied therapeutic possibilities. This article is a clinical case report and Research, Society andDevelopment, v. 10, n. 6, e26910615797, 2021 (CC BY 4.0) | ISSN 2525-3409 | DOI: http://dx.doi.org/10.33448/rsd-v10i6.15797 literature review with both a qualitative and descriptive approach. According to Estrela et al. (2018), such a study is characterized as a research in which direct data collection occurs, with the researcher being the primary instrument. This study was legally supported by an Informed Consent Form (TCLE) from the Federal University of Ceará -Campus Sobral.
The literature review was carried out, with no date restrictions until December 2019, in the PubMed / Medline database. The terms used were: "peripheral myxoma" and "oral". The inclusion criteria were: 1. Case report or series of cases of POM containing complete information on the clinical and histopathological aspects, and 2. a series of cases of odontogenic tumor, reporting at least one case of POM properly characterized. The exclusion criteria were: 1. Animal studies and literature reviews; 2. POM articles with a different focus than the one mentioned in the inclusion criteria; 3. hybrid tumors partially composed of a POM, (which may behave differently); and 4. any language other than English.
The focus made only on the peripheral myxoma variant, which is considered rare, greatly reduced our findings compared to other similar reviews that addressed the myxoma entirely (Dotta et al, 2020).
The review resulted in a total of 42 titles / abstracts, with 11 meeting the inclusion criteria. Of the 11 articles selected for review, nine were clinical case reports and two involved more than one clinical case (two cases and four cases), totaling 15 cases diagnosed with PMD. The information was compiled into a spreadsheet by one reviewer and verified by a second reviewer.

Case Description
Male patient, 75 years old, paraplegic, sought the stomatology service complaining of painless maxillary edema. We emphasize that during anamnesis and filling out the dental record, the patient was informed that the service environment was a dental teaching school and that his case would be the object of study, signing a free and informed consent form (ICF). On  The patient reported the absence of any previous surgical procedure in the area involved, and no symptoms or systemic comorbidity. Image examination revealed that the lesion generated irregular bone resorption involving teeth 14 and 15, which presented mobility, however the lesion did not present intraosseous involvement (Figure 2). Research, Society and Development, v. 10, n. 6, e26910615797, 2021 (CC BY 4.0) | ISSN 2525-3409 | DOI: http://dx.doi.org/10.33448/rsd-v10i6.15797 Source: Authors.
The diagnostic hypothesis was a peripheral ossifying fibroma and differential diagnosis of peripheral giant cell lesion.
An excisional biopsy was performed together with extraction of the involved teeth ( Figure 3).

Results and Discussion
The present study investigated the clinical-pathological aspects of POM as reported in the literature. The small number of reviewed cases is present in Table 1 and may suggest that it is a rare lesion.
In general, a slight predominance of females was observed. However, previous studies report a predilection for males (Aytac-Yazicioglu et al, 2008;Elzay et al, 1978;Tse & Vander, 1985). Due to the low number of cases of POM being reported in the literature, the oral region most affected by this lesion was not established by the authors. However, in this review, it was evidenced that the most common location in the 16 reported cases was the anterior region of the mandible, followed by the anterior region of the maxilla. As in the current report, Yazicioglu, Eren and Görgün in 2008 reported a case located in the posterior maxilla gingiva; and have also affirmed that myxomas located in the gingiva have an odontogenic origin and thus, cannot be classified as soft tissue myxomas (Aytac-Yazicioglu et al, 2008).
In the literature, other regions are also mentioned, such as the hard palate, the jugal mucosa, and the infra-temporal space (Kapoor et al, 2015;Elzay et al, 1978). POM, when presenting bone destruction tends to occur in elderly patients, yet less often in males (Miettinen et al, 1985;Hill et al, 1990). In addition, cases presenting bone destruction grow more rapidly when compared to those without bone destruction (Miettinen et al, 1985;Hill et al, 1990). The current case proved to be associated with an area of bone resorption involving teeth 14 and 15, which presented mobility.
Due to its rarity, clinical diagnosis of this type of lesion is unlikely to arrive at an initial diagnostic hypothesis of POM. Normally the lesion is initially diagnosed as a peripheral lesion of giant cells, peripheral ossifying fibroma, traumatic fibroma and lesions originating from minor salivary glands (Aytac-Yazicioglu et al, 2008;Tasnime et al, 2016;Perrotti et al, 2006;Shimoyama et al, 2000;Elzay et al, 1978;Kanitkar et al, 2017;Shenoy et al, 2014). This happened in the present case, where these were also the diagnostic hypotheses given, based on the clinical and radiographic appearance. Histopathological examination was necessary to confirm that it was a POM, where it was possible to observe a neoplasm of odontogenic origin (CC BY 4.0) | ISSN 2525-3409 | DOI: http://dx.doi.org/10.33448/rsd-v10i6.15797 made up of randomly arranged stellate, spindle-shaped, and round cells in a myxoid stroma (Leiser et al, 2009 Sometimes, in the face of a rare lesion, immunohistochemical analysis is performed to confirm the origin of the tumor cells. In the case of POM, the origin is myofibroblastic and histiocytic (Jain et al, 2013). Thus, in many studies, the immunohistochemical marker vimentin is the most used to confirm a myofibroblastic and histiocytic origin (Raubenheimer et al, 2012;Perrotti et al, 2006;Kanitkar et al, 2017). In addition to immunohistochemical analysis with vimentin, Tasmine et al., 2016 also performed histochemical analysis, (as in the present case) via Alcian-blue staining, which indicates the presence of acidic glycosaminoglycans in the myxoid stroma, confirming a histopathological diagnosis of POM.
Due to their low recurrence rates, intraoral approaches such as enucleation and curettage, have been described as an effective treatment procedure for POM (Perrotti et al, 2006;Shenoy et al, 2014). According to the literature, in current research, and in the present case as well, the most commonly performed treatment is simple surgical excision. However, the effectiveness of this type of treatment in the reported cases cannot be taken for granted, since sometimes follow-up is problematic (as was observed in these articles). Thus, whichever treatment is chosen, monitoring/patient follow-up is of fundamental importance in cases where the histopathological report reveals a POM (Perrotti et al, 2006;Kanitkar et al, 2017).
Upon reaching the diagnosis of OMP, the patient's treatment must be individualized taking into account the specific characteristics of the patient's injury (Francisco et al, 2016;Leiser et al, 2009). However, conservative treatment techniques are preferable compared to more aggressive techniques, as the potential for recurrence in surgical modalities is similar (Dotta et al, 2020 Research, Society andDevelopment, v. 10, n. 6, e26910615797, 2021 (CC BY 4.0) | ISSN 2525-3409 | DOI: http://dx.doi.org/10.33448/rsd-v10i6.15797 stay (Kawase-Koga et al, 2014). Thus, monitoring the patient to avoid possible relapses is more important than using aggressive techniques that cause marked morbidity and decrease in the patient's quality of life.

Conclusion
The final diagnosis was very important, as it is a lesion with great potential for recurrence, long-term follow-up should be more careful and, in case of recurrence, a new intervention should be performed.
New case reports should be published whenever professionals are faced with rare cases like this, demonstrating their conduct so that other professionals acquire this experience and know how to deal when they also come across cases like this.
In the near future, with a satisfactory number of reports and long-term follow-up, it is possible to carry out a systematic quality review in order to clarify exactly what is the best approach for rare injuries like this.