FASN inhibition sensitizes metastatic OSCC cells to cisplatin and paclitaxel by downregulating cyclin B1.

OBJECTIVES: To investigate the potential effect of fatty acid synthase (FASN) inhibitor orlistat to enhance the effectiveness of chemotherapy drugs widely used to treat oral squamous cell carcinomas (OSCC), such as 5-fluorouracil, cisplatin, and paclitaxel. METHODS: The OSCC SCC-9 LN-1 metastatic cell line, which expresses high levels of FASN, was used for drug combination experiments. Cell viability was analyzed by crystal violet staining and automatic cell counting. Apoptosis and cell cycle were analyzed by flow cytometry with Annexin-V/7-AAD and propidium iodide staining, respectively. Cyclin B1, Cdc25C, Cdk1, FASN, and ERBB2 levels were assessed by Western blotting. Finally, cell scratch and transwell assays were performed to assess cell migration and invasion. RESULTS: Inhibition of FASN with orlistat sensitized SCC-9 LN-1 cells to the cytotoxic effects of paclitaxel and cisplatin, but not 5-fluorouracil, which was accompanied by a significant reduction in cyclin B1. The suppression of proliferation, migration, and invasion of SCC-9 LN-1 cells induced by orlistat plus cisplatin or paclitaxel was not superior to the effects of chemotherapy drugs alone. CONCLUSION: Our results suggest that orlistat enhances the chemosensitivity of SCC-9 LN-1 cells to cisplatin and paclitaxel by downregulating cyclin B1.

Oral squamous cell carcinomas and oral potentially malignant disorders: A Latin American study.

OBJECTIVE: To determine the frequency of oral squamous cell carcinoma (OSCC) associated or not with oral potentially malignant disorders (OPMD), and the epidemiological profile and traditional risk factors in Latin America. METHODS: A retrospective observational study was conducted in 17 Latin American centres. There were included cases of OSCC, analysing age, gender, OSCC and their association with previous OPMD. Clinicopathological variables were retrieved. The condition of sequential-OSCC versus OSCC-de novo (OSCC-dn) was analysed concerning the aforementioned variables. Quantitative variables were analysed using Student's t-test, and qualitative variables with chi-square. RESULTS: In total, 2705 OSCC were included with a mean age of 62.8 years old. 55.8% were men. 53.75% of the patients were smokers and 38% were common drinkers. The lateral tongue border was the most affected site (24.65%). There were regional variations in OPMD, being leukoplakia the most frequent. Of the overall 2705 OSCC cases, 81.4% corresponded to OSCC-dn, while s-OSCC were 18.6%. Regarding lip vermillion SCC, 35.7% corresponded to de novo lip SCC and 64.3% were associated with previous OPMD. CONCLUSIONS: In Latin America, OSCC-dn seems to be more frequent with regional variations of some clinical and histopathological features. Further prospective studies are needed to analyse this phenomenon.

Global prevalence of human papillomavirus-related oral and oropharyngeal squamous cell carcinomas: a systematic review and meta-analysis.

OBJECTIVE: To conduct a systematic review to determine the global prevalence of HPV in oral squamous cell carcinoma (OSCC) and oropharyngeal squamous cell carcinoma (OPSCC). MATERIALS AND METHODS: Literature was searched through October 2022 in main databases to address the question "What is the global prevalence of Human Papillomavirus in oral and oropharyngeal cancer?" Studies had to identify HPV by PCR, ISH, or p16 immunohistochemistry to be eligible. Quality was assessed using the JBI checklist for prevalence studies. Meta-analyses were performed, and reporting followed PRISMA guidelines. RESULTS: Sixty-five studies were included, and most of them had methodological limitations related to sampling and the HPV detection tool. The pooled prevalence of HPV-positivity was 10% (event rate = 0.1; 95% CI: 0.07, 0.13; P < 0.01; I2 = 88%) in the oral cavity and 42% (event rate = 0.42; 95% CI: 0.36, 0.49; P = 0.02; I2 = 97%) in oropharynx. The highest HPV prevalence in OSCC was reached by Japan, meanwhile, in OPSCC, Finland and Sweden were the most prevalent. HPV16 is the genotype most frequent with 69% in OSCC and 89% in OPSCC, being the tonsils the intraoral location more affected by HPV (63%, p < 0.01, I2 76%). CONCLUSION: The evidence points to an apparent burden in HPV-related OPSCC, mostly in North America, Northern Europe, and Oceania, especially due to the HPV16 infection suggesting different trends across continents. CLINICAL RELEVANCE: This updated systematic review and meta-analysis provide sufficient evidence about the global HPV prevalence in OSCC and OPSCC and the most frequent HPV subtype worldwide.

Acquired oral syphilis: A multicenter study of 339 patients from South America.

OBJECTIVE: To report the clinicopathologic features of acquired oral syphilis cases in South American countries. MATERIALS AND METHODS: Clinical data were retrospectively collected from the records of 18 oral diagnostic services in Argentina, Brazil, Chile, Colombia, Venezuela, Uruguay, and Peru. Serologies of nontreponemal and treponemal tests were used for diagnosis. RESULTS: The series comprised 339 cases of acquired oral syphilis. Secondary syphilis ranked as the most common stage (86.7%). Lesions were more frequent among males (58.0%) and young adults with a mean age of 33.3 years. Individuals aged 20-29 years were most affected (35.3%). The most commonly involved sites were the tongue (31.6%), lip/labial commissure (25.1%), and hard/soft palate (20.4%). Clinically, acquired oral syphilis usually presented as mucous patches (28.4%), papules (25.7%), and ulcers (18.1%). Skin manifestations occurred in 67.7% of individuals, while lymphadenopathy and fever were observed in 61.3% and 11.6% of all subjects, respectively. Most patients were treated with the benzathine penicillin G antibiotic. CONCLUSION: This report validates the spread of acquired oral syphilis infection among young adults in South America. Our directives include accessible diagnostic tools for proper disease screening, surveillance, and counselling of affected individuals, especially in low- and middle-income countries.

Sialolipomas of minor salivary glands: A multi-institutional study and literature review.

BACKGROUND: Sialolipoma is a rare histological variant of lipoma commonly misdiagnosed and composed of a proliferation of mature adipocytes with secondary entrapment of normal salivary gland tissue. The purpose of the present study is to report the clinicopathologic and immunohistochemical features of 10 new cases of sialolipomas in conjunction with a review of the literature. METHODS: A retrospective descriptive cross-sectional study was performed. A total of 54,190 biopsy records of oral and maxillofacial lesions from four oral and maxillofacial pathology services in Brazil were analysed. All cases of lipomas were reviewed, and clinical, demographic and histopathological data were collected of all cases compatible with sialolipomas. In addition, immunohistochemistry stains (AE1/AE3, CK7, 34ßE12, S-100, HHF35, α-SMA and Ki-67) and a literature review based on a search of three electronic databases (PubMed, Web of Science and Scopus) were performed. RESULTS: Among all lipomas reviewed, there were 10 cases of sialolipomas. The series comprised of 7 females (70.0%) and 3 males (30.0%), with a mean age of 46.1 ± 21.5 years (range: 11-71 years) and a 2.3:1 female-to-male ratio. The lower lip (n = 3, 30.0%) and tongue (n = 2, 20.0%) were the most common locations, presenting clinically as a nodule of slow growth and normal colour. Conservative surgical excision was the treatment in all cases. No recurrence was observed. CONCLUSION: Sialolipomas are a rare histological variant of lipoma, affecting the salivary glands, mainly in the parotid gland and palate of female adults. Pathologists must recognise sialolipomas to avoid misdiagnoses with other lipomatous tumours that can affect salivary glands.

Oral and oropharyngeal lymphomas: A multi-institutional collaborative study.

BACKGROUND: Lymphomas in the oral and oropharyngeal regions are relatively uncommon, and their diagnosis is challenging and complex due to the myriad histopathological subtypes. Herein, we report a large series of oral and oropharyngeal lymphomas and compare our data with the currently available literature. METHODS: All cases diagnosed as lymphomas affecting the oral and oropharyngeal regions were retrospectively retrieved from seven Brazilian institutions. Clinicodemographic data and histopathological features were evaluated and described, while a comprehensive literature review was undertaken in order to compare our findings. RESULTS: A total of 304 cases of oral and oropharyngeal lymphomas were obtained, mostly affecting individuals aged 60-69 years (n = 68) with a mean age at diagnosis of 54.2 ± 20.1 years. Males and females were equally affected. Mature B-cell neoplasms (87.2%) were the most common group, followed by mature T- and NK-cell neoplasms (11.2%) and precursor lymphoid neoplasms (1.6%). The most frequent subtypes in each group were diffuse large B-cell lymphomas, not otherwise specified (n = 99), extranodal NK/T-cell lymphomas, nasal type (n = 12), and B-lymphoblastic leukaemia/lymphomas, not otherwise specified (n = 4). The most commonly involved sites were the palate (26.3%), mandible (13%), and maxilla (10.5%). CONCLUSION: Diffuse large B-cell lymphoma, not otherwise specified, remains the most common subtype of lymphomas in the oral and oropharyngeal region. Older patients are the most affected, with no gender predilection and the palate and jaw are usually affected.

Burkitt lymphoma of the head and neck: An international collaborative study.

BACKGROUND: Burkitt lymphoma (BL) is an aggressive B-cell lymphoma with three variants (endemic, sporadic, and immunodeficiency-associated), presenting with specific epidemiological and clinical features. Burkitt lymphoma affects the head and neck region (BLHN) in approximately 10% of cases. The aim of this study was to undertake a comparative analysis of the clinicopathologic and immunohistochemical (IHC) features of BLHN diagnosed in patients from Africa, Guatemala, and Brazil. METHODS: Cases diagnosed as BLHN were collected from the files of six oral pathology laboratory services (Brazil, South Africa, and Guatemala) and one Brazilian pediatric oncology hospital from 1986 to 2020. Clinicopathological and IHC data, and Epstein-Barr virus (EBV) status by in situ hybridization data for each case were reviewed and described. RESULTS: Of the 52 cases, BLHN was predominant in pediatric patients [43 (82.69%)] and males [43 (82.69%)], with a mean age of 11.26 ± 9.68 years (range, 1-39 years). Neck and cervical lymph nodes [14 (26.92%)], and involvement of both maxilla and mandible [8 (15.38%)], were the most common anatomical sites. Clinically, tumor/swelling [40 (31.25%)], cervical lymphadenopathy [14 (10.94%)], pain [12 (9.38%)], and bone destruction [12 (9.38%)] were frequent findings. All cases showed typical morphological characteristics of BL. IHC profiles included positivity for CD20 [52 (100%)], CD10 [38 (79.17%)], Bcl6 [29 (87.88%)], and c-Myc protein [18 (81.82%)]. EBV was positive in 18 cases (62.07%). The Ki-67 index ranged from 90 to 100%. CONCLUSION: The clinicopathological and EBV profile of BLHN in South African, Guatemalan, and Brazilian patients is similar.

Mature T/NK-Cell lymphomas of the oral and maxillofacial region: A multi-institutional collaborative study.

BACKGROUND: The diagnosis of oral and maxillofacial mature T/NK-cell neoplasms is challenging because of their rarity, morphological heterogeneity and complex immunophenotype with scarce available data describing their clinical and microscopic aspects. Therefore, in this study, we investigated a series of mature T/NK-cell neoplasms affecting this anatomical region and provided an updated literature review. METHODS: Cases diagnosed as mature T/NK-cell lymphomas affecting the oral and maxillofacial region were retrospectively retrieved from six pathology files and their diagnoses were confirmed using haematoxylin and eosin-stained slides, immunohistochemical reactions and in situ hybridization for Epstein-Barr virus (EBV) detection. Patients' clinical data were collected from their pathology forms. RESULTS: A total of 22 cases were included in this study. Eleven (50%) consisted of extranodal NK/T-cell lymphomas, nasal type; eight (36.4%) were peripheral T-cell lymphomas, NOS; two (9.1%) were adult T-cell leukaemia/lymphomas, and one (4.5%) was an ALK-positive anaplastic large cell lymphoma. Overall, males predominated, with a mean age of 55.7 years. The palate was the most affected site (50%), and tumours usually presented as destructive and painful ulcers. EBV was present in all cases of extranodal NK/T-cell lymphoma nasal type but was absent in the other subtypes. CONCLUSION: Among mature T/NK-cell lymphomas of the oral and maxillofacial region, extranodal NK/T-cell lymphoma, nasal type and peripheral T-cell lymphoma, NOS predominated. Older men were the most affected patients, and this heterogeneous group of neoplasms has a very aggressive clinical behaviour.

Solitary fibrous tumour of the oral cavity: An update.

BACKGROUND: Solitary fibrous tumour is an unusual neoplasm of the oral cavity that is sometimes not clinically distinguishable from other lesions. The purpose of the present study was to review the clinical, microscopic and molecular aspects of malignant and benign solitary fibrous tumour of the oral cavity currently available in literature. METHODS: For our review, an electronic search was performed using PubMed, Scopus, Ovid/MedLine, Web of science and ProQuest Dissertations and Theses Global database. RESULTS: A total of 74 publications reporting 150 cases were included. Oral solitary fibrous tumours are most frequently described as submucosal, well-circumscribed, asymptomatic nodule, more prevalent in females in their fourth to fifth decades of life. Buccal mucosa is the most commonly affected site by the benign tumour variant, whereas the tongue is the most common location affected by the malignant form of the neoplasm. Most of the lesions were treated by conservative surgery. One recurrent malignant tumour and one metastasis are reported. CONCLUSION: Asymptomatic normal-coloured submucosal nodules located in the buccal mucosa and tongue in adult patients are suggestive of oral solitary fibrous tumour, but only a careful microscopic examination can differentiate benign from malignant variants and the use of immunohistochemistry (CD34, Bcl-2, CD99 and STAT6), and cytogenetic studies (NAB2-STAT6) contribute significantly to confirm the diagnosis of solitary fibrous tumour in difficult cases.

White sponge nevus: A condition not always clinically suspected.

White sponge nevus (WSN) is an uncommon benign inherited disorder characterized by white and diffuse painless lesions in oral, esophageal, or genital mucosa. The lesions may develop at birth or later in childhood or adolescence, with careful clinical examination being sufficient for diagnosis in most cases. However, microscopic analysis may be necessary particularly in adults in which other whitish oral lesions may be clinically suspected. Dermatologists, dentists, and pathologists should consider WSN when evaluating multiple white oral lesions, thus preventing unnecessary treatments. Herein, we report four additional cases of WSN with emphasis on its clinical and histopathological features.

A Brazilian multicentre study of 2,497 isolated cases of odontogenic keratocysts.

We present the frequency of cases of isolated odontogenic keratocysts submitted to microscopic examination at 10 Brazilian referral centres in Oral and Maxillofacial Pathology. In a retrospective (1953-2017) analysis, data on clinicoradiographic features and treatment of these lesions were collected and analysed descriptively. Among the 258,867 cases retrieved, 2,497 (0.96%) were isolated odontogenic keratocysts. In summary, an overview of individuals affected with isolated odontogenic keratocysts is reported herein. This lesion showed predilection for the posterior mandible of young adult men.

Development of a calcified odontogenic hamartoma following avulsion of a permanent central incisor.

The avulsion of a permanent immature tooth is a serious condition and a real emergency in dentistry. The management of a traumatized avulsed tooth is always a challenge to the clinician. This case report concerns the development of a calcified odontogenic hamartoma after the avulsion of an immature central incisor in an eight-year-old female. The patient presented for the treatment four months after the avulsion. Her intraoral examination showed complete healing of the area but an atypical appearance of the alveolar area of the missing tooth was observed in the periapical radiograph. A new radiographic scan performed six months later revealed the formation of a radiopaque irregular structure at the cervical level of the alveolar ridge at the site of the missing tooth. Surgical removal was performed, and the histopathological examination revealed a hamartomatous proliferation of odontogenic tissue with calcification. After healing, the lateral incisor was orthodontically moved mesially and restored to resemble the central incisor. An orthodontic device was installed to improve function and aesthetics of the patient.

Intraosseous xanthoma of the mandible: A multi-institutional case series with a literature review.

BACKGROUND: The aim of the present study was to report the clinicopathologic, radiographic and immunohistochemical features of five South American cases of intraosseous xanthomas of the mandible and to compare them to those detected in a literature review. METHODS: Clinical data were collected from the records of three Oral and Maxillofacial Pathology services in South America and compared with those compiled from a literature review based on a search of three electronic databases (PubMed, Web of Science and Scopus). All cases were evaluated by haematoxylin and eosin staining and immunohistochemistry for CD68 and S-100. RESULTS: The series comprised four females (80%) and one male (20%) with a mean age of 23.3 ± 10.9 years (range: 13-45 years). In four cases, there was involvement of the posterior region of the mandible (80%). The lesions presented radiographically as unilocular (60%) radiolucencies with punched-out margin (80%). All cases predominantly consisted of CD68-positive and S-100-negative xanthomatous cells. No recurrences were observed after curettage, with a median follow-up of 27 months. CONCLUSION: Intraosseous xanthoma of the jaws is a rare benign disorder. We report here five additional cases affecting the mandible, for a total of 36 cases of the jaws reported in the literature. Overall, this lesion has predilection for posterior sites of the mandible of asymptomatic young adults.

Oral intramuscular hemangioma: Report of three cases.

Intramuscular hemangioma (IMH) represents less than 1% of all hemangiomas. In the head and neck region, it occurs mostly in the masseter, temporalis and sternocleidomastoid muscles. Despite its infiltrative growth pattern and several worrisome histological features, such as increased mitotic activity, plumpness of the nuclei, intraluminal papillary projections or perineural infiltration, the lesion is benign, and complete surgical excision is the preferred treatment for such oral lesions. Herein, we report three rare cases of IMH in the tongue and lip, discuss the clinical and histological aspects, and review the literature regarding this lesion.

Clinical predictors of malignancy in palatal salivary gland tumors.

OBJECTIVES: To establish a predictive clinical index of malignancy risk in palatal salivary gland tumors (PSGT). MATERIALS AND METHODS: One hundred cases of PSGT were evaluated. Clinical data were retrieved from the patient's files. Representative clinical photographs of each tumor were evaluated to identify clinical features suggestive of a malignant tumor. Features significantly associated with malignancy were included in a binary logistic regression model. RESULTS: Malignant tumors were more common in the hard palate, in women and in older patients. Features associated with a malignant diagnosis included pain (p = .017), irregular surface (p = .004), bluish/purple coloration (p < .001), ulceration (p = .005), and telangiectasia (p = .015). After multivariate logistic regression, pain (OR: 4.017; 95% CI: 1.198-13.471; p = .024) and color alteration (OR: 7.243; 95% CI: 2.068-25.363; p = .002) were independently associated with malignancy. Including these factors in a predictive index, the proportion of malignant tumors in patients presenting none, one and two factors were 25% (95% CI: 0.13-0.40), 67% (95% CI: 0.48-0.83), and 85% (95% CI: 0.42-0.99), respectively. CONCLUSION: Pain and color alteration might be independent predictors of malignancy in PSGT, which could support the decision to perform an incisional or excisional biopsy.

Effects of fatty acid synthase inhibitors on lymphatic vessels: an in vitro and in vivo study in a melanoma model.

Fatty acid synthase (FASN) is responsible for the endogenous production of fatty acids from acetyl-CoA and malonyl-CoA. Its overexpression is associated with poor prognosis in human cancers including melanomas. Our group has previously shown that the inhibition of FASN with orlistat reduces spontaneous lymphatic metastasis in experimental B16-F10 melanomas, which is a consequence, at least in part, of the reduction of proliferation and induction of apoptosis. Here, we sought to investigate the effects of pharmacological FASN inhibition on lymphatic vessels by using cell culture and mouse models. The effects of FASN inhibitors cerulenin and orlistat on the proliferation, apoptosis, and migration of human lymphatic endothelial cells (HDLEC) were evaluated with in vitro models. The lymphatic outgrowth was evaluated by using a murine ex vivo assay. B16-F10 melanomas and surgical wounds were produced in the ears of C57Bl/6 and Balb-C mice, respectively, and their peripheral lymphatic vessels evaluated by fluorescent microlymphangiography. The secretion of vascular endothelial growth factor C and D (VEGF-C and -D) by melanoma cells was evaluated by ELISA and conditioned media used to study in vitro lymphangiogenesis. Here, we show that cerulenin and orlistat decrease the viability, proliferation, and migration of HDLEC cells. The volume of lymph node metastases from B16-F10 experimental melanomas was reduced by 39% in orlistat-treated animals as well as the expression of VEGF-C in these tissues. In addition, lymphatic vessels from orlistat-treated mice drained more efficiently the injected FITC-dextran. Orlistat and cerulenin reduced VEGF-C secretion and, increase production of VEGF-D by B16-F10 and SK-Mel-25 melanoma cells. Finally, reduced lymphatic cell extensions, were observed following the treatment with conditioned medium from cerulenin- and orlistat-treated B16-F10 cells. Altogether, our results show that FASN inhibitors have anti-metastatic effects by acting on lymphatic endothelium and melanoma cells regardless the increase of lymphatic permeability promoted by orlistat.

Oral verruciform xanthoma: a clinicopathologic and immunohistochemical study of 20 cases.

Verruciform xanthoma of the oral cavity is an uncommon benign lesion that usually affects the palate and gingiva mainly as a well-circumscribed solitary yellowish to whitish plaque or nodule, which is promptly recognized microscopically by identification of sub-epithelial foamy macrophages. The aim of this study was to evaluate the clinicopathologic and immunohistochemical features of 20 cases of oral verruciform xanthoma. All cases were evaluated by conventional hematoxylin/eosin staining and six of those were submitted to immunohistochemical reactions for CD68, CD63, CD163, syndecan-1 (CD138), S-100 protein and cytokeratins (CK) 8, 14 and 19. Oral verruciform xanthoma presented as yellowish papillary nodules affecting mainly the palate (30%), buccal mucosa (30%) and gingiva (25%) of middle-aged male patients. Most cases presented papillary epithelial hyperplasia and sub-epithelial foamy cells, which were immunopositive for CD68, CD63 and CD163 in all cases. The orange parakeratin superficial layer was negative for CK14 and presented a distinct granular membrane pattern of positivity for CD138. S-100 protein, CK8, and CK19 were negative.

ADAM17 mediates OSCC development in an orthotopic murine model.

BACKGROUND: ADAM17 is one of the main sheddases of the cells and it is responsible for the cleavage and the release of ectodomains of important signaling molecules, such as EGFR ligands. Despite the known crosstalk between ADAM17 and EGFR, which has been considered a promising targeted therapy in oral squamous cell carcinoma (OSCC), the role of ADAM17 in OSCC development is not clear. METHOD: In this study the effect of overexpressing ADAM17 in cell migration, viability, adhesion and proliferation was comprehensively appraised in vitro. In addition, the tumor size, tumor proliferative activity, tumor collagenase activity and MS-based proteomics of tumor tissues have been evaluated by injecting tumorigenic squamous carcinoma cells (SCC-9) overexpressing ADAM17 in immunodeficient mice. RESULTS: The proteomic analysis has effectively identified a total of 2,194 proteins in control and tumor tissues. Among these, 110 proteins have been down-regulated and 90 have been up-regulated in tumor tissues. Biological network analysis has uncovered that overexpression of ADAM17 regulates Erk pathway in OSCC and further indicates proteins regulated by the overexpression of ADAM17 in the respective pathway. These results are also supported by the evidences of higher viability, migration, adhesion and proliferation in SCC-9 or A431 cells in vitro along with the increase of tumor size and proliferative activity and higher tissue collagenase activity as an outcome of ADAM17 overexpression. CONCLUSION: These findings contribute to understand the role of ADAM17 in oral cancer development and as a potential therapeutic target in oral cancer. In addition, our study also provides the basis for the development of novel and refined OSCC-targeting approaches.

Management and recurrence of the odontogenic keratocyst: an overview of systematic reviews.

MATERIALS AND METHODS: An extensive literature search among six eletronic databases and Grey Literature was used to identify systematic reviews (S) that could respond if: in individuals diagnosed with OKC (P), is there any influence of the treatment method (I/C) on the recurrence rate of the lesion (O)? After evaluating all titles and abstracts and then applying the eligibility criteria, the included studies were read in full, and data were extracted based on a standardized sheet ordered in the PICO sequence. The assessment of the quality of the systematic reviews included, was determined by AMSTAR2, and final synthesis were descriptively made based on the results and quality of the systematic reviews. RESULTS: From a total of 19 included systematic reviews, it was observed that the most used treatment for OKC was enucleation, followed by enucleation with adjuvant techniques and marsupialization. The mean percentage of recurrence was 16,2%, and the highest OKC recurrence rate was 43.2% after simple enucleation. The use of adjuvant techniques promoted reductions in OKC recurrence rates. The overall methodological quality of systematic reviews was critically low, and this parameter demonstrate the need for more studies to facilitate the choose of the treatment. CONCLUSION: Despite being the most used treatment, simple enucleation is related to the highest rate of recurrence, except when performed after marsupialization/decompression. In addition, the use of adjuvant techniques has a strong impact on reducing the likelihood of recurrence. However, these findings are not conclusive because of the critically low quality of the systematic reviews.