Ethanol Ablation for Odontogenic myxoma: New alternative of conservative treatment.

the lesion in a period of 5 months. Finally, the patient decided a conservative treatment by intra-lesional ethanol ablation. Informed consent was signed. A 5 mm gauge silastic cannula was installed in the osteolytic expansive lesion as a drainage tube. Intralesional irrigation through the canulla was performed under local anaesthesia (Lidocaine 2% 1:100.000 epinephrine). The lesion was treated with 3 ml of sterile 98 % ethanol followed by profuse saline


INTRODUCTION
Odontogenic myxoma is an uncommon maxillofacial tumor that is benign in nature.It is characterized by a slow-growing, painless, and site-aggressive behavior.A main feature is that it is not encapsulated so it has high potential of invasiveness and penetration into peripheral tissues.Large lesions may cause extensive compromise of the region.Tooth dislodgement with cortical bone expansion may be present, and in some more severe cases it can cause facial asymmetry.This odontogenic neoplasm originates from mesenchyme or odontogenic ectomesenchyme.Histologically is characterized by stellate and spindleshaped cells dispersed in an abundant myxoid extracellular matrix (1,2) .It is the third most frequent odontogenic tumor, with a reported incidence of approximately 0.07 cases per million people per year.It affects patients between the second and fourth decade of life.Females are affected predominantly in the ratio 2:1.Mandible is where they are most commonly found (1,3) .Clinically, it exhibits a slow growing pattern, with local bone destruction, cortical bone expansion, soft tissue infiltration, root resorption, and tooth malposition.Computed tomography is necessary for diagnosis and surgical treatment planning (3) .Imaging demonstrates a unilocular or multilocular radiolucency, sometimes showing a fine "soapbubble" or "honeycomb appearance", occasionally with fine straight tennis racket trabeculations, with or without clearly defined borders.Differential diagnosis should include ameloblastoma, dentigerous cyst, odontogenic keratocyst, intraosseous hemangioma, aneurysmal bone cyst and central giant cell granuloma (1,3) .It has a recurrence rate from 10% to 43% with a mean of 25%.This high recurrence is attributed to its myxomatous nature, lack of a capsule, and the penetration of the lesion into the surrounding tissue.This feature makes effective curettage difficult (1,2) .Treatment for OM is mainly surgical.Most of cases in literature are treated with surgical resection with recurrence rates between 6 -13%.Another option described was enucleation and curettage, with higher recurrence rates from 19% to 25% (2,3) .To prevent recurrence, many authors recommend resection with 1 cm linear bony margins (4) .Aggressive resection has the disadvantage of functional and aesthetic deterioration and morbidity in donor site (2) .By the other side, conservative treatment for young patients can be considered as an alternative to avoid resection morbidity (5) .
In this case report we present an alternative therapy by ethanol ablation.This technique consists in injections of pure alcohol into the tumor´s body to induce dehydration, denaturation, and necrosis of tumor´s cells accompanied by small vessel thrombosis.This leads to tumor ischemia and destruction (6) .The purpose of this study is to report a new conservative treatment for mandibular odontogenic myxoma with adequate results.

CASE REPORT
A 16-year-old female patient with no medical history, was referred to the author's private office for evaluation because of an imaging finding of an asymptomatic mandibular tumor.Dental Cone Beam CT of the mandible showed extensive radiolucent and multilocular area with blurred borders that extended from the mandibular left body to the ipsilateral ramus with a "soap bubble" appearance (Fig 1).Biopsy was taken and histopathological results revealed a proliferation of stellate and spindle cells in loose myxoid stroma, with no atypias or mitosis observed, confirming odontogenic myxoma.The patient was given all treatment modalities: conservative enucleation and curettage with coayudants (or block resection and hemimandibulectomy.The initially proposed adjuvants were Carnoy's Solution and liquid nitrogen.The patient's parents asked about the possibility of using an adjuvant that would help reduce the size of the lesion and would have a lower neurotoxic risk.A search for alternative treatments was carried out, finding absolute alcohol ablation of bone lesions in the scientific literature.However, as its use was not reported in odontogenic myxoma, it was decided to stop its use if there was no change in the size of the lesion in a period of 5 months.Finally, the patient decided a conservative treatment by intra-lesional ethanol ablation.Informed consent was signed.A 5 mm gauge silastic cannula was installed in the osteolytic expansive lesion as a drainage tube.Intralesional irrigation through the canulla was performed under local anaesthesia (Lidocaine 2% 1:100.000epinephrine).The lesion was treated with 3 ml of sterile 98 % ethanol followed by profuse saline

CLINICAL REPORT
Ethanol Ablation for Odontogenic myxoma: New alternative of conservative treatment.
Rodrigo Fariña-Sirandoni .As there is no specific protocol for this type of lesion using absolute alcohol, these rinses were performed long enough to ensure a reduction in the size of the lesion and to obtain an objective measurement by observing changes in radiographic radiopacity.Management of the remaining lesion was performed by surgical curettage and chemical treatment of the lesion with both Carnoy's solution and liquid nitrogen.Ipsilateral Coronoidectomy was done under general anesthesia to decrease local masticatory loads.A three-year follow -up was done.No recurrence of the lesion was present (Fig 3).

DISCUSSION
Odontogenic Myxoma have a high recurrence rate and it is attributed to its nature, lack of a capsule, and the penetration of the lesion into the surrounding tissue.This features makes conservative treatment by curettage uneffective, so resection is the preferred treatment modality.M. Saalim et al reported in their systematic review the overall recurrence rate of odontogenic mixoma.He published that OM recurrence was 13% during a mean follow up period of 10 years.With conservative treatment the recurrence rate was 19% (mean follow up 11 years) and after resection it was 6% (mean follow up nine years) (2) .
A search in PUBMED was conducted to assess whether there was literature about de use of alcohol for the treatment of these lesions using the following searching strategy (((odontogenic myxoma[Title])

OR odontogenic myxoma[Abstract])) AND ((alcohol[Abstract]) OR alcohol[Title]) & (((odontogenic myxoma[Title]) OR odontogenic myxoma[Abstract])) AND ((Alcohols[MeSH Terms]) OR Ethanol[MeSH Terms]
) " finding no publications about this modality.However there are reports of its use in other types of bone and extra-bone lesions, with a reduction of their initial volumes and in some cases total remission (Table 1) (6,8,11,13) Bening tumors and metastatic bone lesions can be managed by ablation techniques.These treatment modalities include ethanol or acetic acid injection, thermal ablation by laser, radiofrequency, microwave, cryoablation and radiofrequency ionization (2) .Ethanol injection produces coagulative necrosis of targeted tissue due to cell dehydration and protein denaturation.Also induces ischemic necrosis due to small blood vessel thrombus formation and inhibition of enzymatic activity in surrounding tissues which result in local fibrosis and tissue atrophy (7) .Reported experience with ethanol ablation has focused mainly on therapy for hepatocelular carcinoma (8,9) .Likewise, there are studies that show excellent results with ethanol injection for the treatment of giant cell tumors, osteoid osteomas, skeletal metastasis, and other bone lesions (9)(10)(11) .In this case report we present an unconventional conservative management for a mandibular odontogenic myxoma by recurrent continuous intralesional "absolute alcohol" rinses that were performed through a cannula.Regarding the alcohol volume used, it is reported that it depends on the size of the lesion to be treated (2,9) .
Regarding the decompression of mandibular keratocysts, it is indicated that 6-12 months after decompression is considered a period in which there is sufficient bone formation to perform enucleation.Even at 3 months there is a decrease in the volume of these lesions by 55%, increasing bone density by 46% (12) .Taking as reference the times in the treatment in keratocysts, a CT control was performed at 5 months, observing a significant decrease in the size of the lesion, surgical treatment of the remaining odontogenic myxoma was performed.
The disadvantage of this technique is the unpredictable alcohol diffusion, but several published studies report excellent results concerning safety and efficacy in bone and soft tissue lesions (9,13) .This approach was chosen to avoid functional and aesthetic disadvantages associated to resective treatment.Considerable reduction of the lesion's volume was achieved which allowed a "minimal overall resection" and in a final stage the remaining lesion was managed with surgical curettage and chemical treatment by the combination of Carnoy's solution and cryoablation with liquid nitrogen as local adjuvant applied locally to induce tissue ischemia and trigger protein denaturation with cell membrane breakdown, with remarkable results.This outcome is similar as described in literature where positive response is demonstrated when using high concentration alcohol injections associated with aggressive curettage of the lesions (6,8,11,14) .It is outlined that Carnoy's solution is effective as coadyuvant treatment for odontogenic myxoma (5) but in our case it was discarded in the initial stages due to the neurotoxic properties of this solution and its possible damage to the inferior alveolar nerve (15) .
In this case the conservative approach was an effective therapy and no recurrence was found after a 3 year follow-up, however the patient should be monitored once a year.

CONCLUSION
There are no reports in the literature about the use of alcohol as a chemoablative agent for the treatment of odontogenic myxoma.This study reveals a conservative treatment with no signs of recurrence after a three-year follow-up.Additionally, high concentration ethanol is a lowcost and relatively safe treatment alternative.Thus, it is proposed that this treatment modality may be helpful in similar cases, however more studies are needed to prove it´s long term efficacy.

INFORMED CONSENT
Written informed consent was obtained.

INTEREST CONFLICT
The authors declare no conflict of interest

Figure 1 .
Figure 1.Odontogenic myxoma.Dental Cone Beam CT of the mandible showed extensive radiolucent and multilocular area with imprecise borders that extended from the mandibular left body, to the ipsilateral ramus with a "soap bubble" appearance

Figure 2 .
Figure 2. Control five months after washing with absolute alcohol

Figure 3 .
Figure 3.Control three years post ethanol Ablation and Enucleation of mandibular Myxoma 3,2*, Lorena Núñez-Castañeda 2 , Matías Andreo-Donoso3, Juan Pablo Deramond-Díaz 4ABSTRACTOdontogenic myxoma is a maxillofacial tumor that is benign in nature. It is characterized by a slow-growing, painless, and site-aggressive behavior.A main feature is that it is not encapsulated so it has high potential of invasiveness and penetration into peripheral tissues.Large lesions may cause extensive compromise of the region.Treatment strategy for Odontogenic Myxoma is still controversial.Radical resection with an appropriate surgical margin is recommended, but emerging evidence has suggested that a more conservative approach will result in less morbidity and adequate results.This report shows a remarkable result on a 16-year-old patient who had a Mandibular Odontogenic Myxoma treated with a conservative approach.Intra-lesional absolute alcohol irrigation was performed during a 5-month period.Considerable volume reduction of the lesion happened which allowed a minimal overall resection.No recurrence was found after a 3 year follow-up.

Table 1 .
Bone lesions can be treated by different ablation techniques