Oral cavity lipoma : a study of 101 cases in a Brazilian population Lipoma de cavidade oral : um estudo de 101 casos em uma população brasileira

Introduction: Lipomas are benign soft tissue tumors commonly found in the human body. Although common in the head and neck region, in the oral cavity region they are uncommon, accounting for only 1% to 4% of benign oral cavity lesions. Objective: This study aims to identify the clinical and histopathological characteristics of oral cavity lipomas subjected to histopathological analysis at a pathology laboratory in the city of Fortaleza, Ceará, Brazil. Methods: Data from all cases of oral lesions diagnosed as lipoma and confirmed by histopathological examination over a period of 10 years were collected, including: gender, age, anatomical location, clinical diagnosis and histopathological subtypes. Results: During the period evaluated, 101 cases were diagnosed as lipomas, representing 1.01% of oral cavity biopsies. Females were more affected, with a male/female ratio of 1: 1.8, and with a peak of incidence between 50 and 70 years of age. The buccal mucosa was the most affected anatomical region, followed by the lower lip. Classic lipoma and fibrolipoma were the histological variants of lipoma most commonly found in the oral cavity, with 64 cases of classic lipoma and 29 cases of fibrolipoma. Other histological variants were: sialolipoma, angiolipoma, chondrolipoma, myxolipoma and intramuscular lipoma. Conclusion: Lipomas are uncommon lesions in the oral cavity, which present a higher prevalence in the buccal mucosa of adults, aged between 50 and 70 years, and with higher female preference.

In the oral cavity, lipomas typically present as a wellcircumscribed, slow-growing, solitary, painless submucosal nodule.Clinical diagnosis is usually apparent, but they can be confused with other neoplasms of oral cavity (7) .The buccal mucosa is the most affected site, although the lipoma can appear in several locations (5,7,8) .This neoplasm can occur in all ages, despite being uncommon at young ages (5,9) .Some case series have demonstrated a slight female predilection (1,3,7) .
Palabras clave: lipoma; patología; neoplasias bucales. of these histopathological variants of oral cavity lipomas.This study analyzed the clinicopathological features of benign oral cavity lipomas in a Brazilian population.

MEthoDS
The files from 2000 to 2015 of the Oral Pathology Department, University of Fortaleza (Unifor), were reviewed and all cases with histopathological diagnosis of lipoma of the oral cavity were retrieved.Information regarding patients' gender and age, site, size and duration of the lesions before diagnosis and clinical diagnosis were obtained from the patients' records.
The research was developed in accordance with Resolution 466/12 of the National Committee for Ethics in Research (CONEP)/National Health Council, which deals with researches involving humans, and the Code of Medical Ethics (1998).This cross-sectional study was approved by the Institutional Ethics Committee (ethics approval number 1104619).The data was collected and the results obtained in the SPSS Statistics 20.0 software were described by using simple descriptive statistics.
Oral cavity lipoma: a study of 101 cases in a Brazilian population rESuLtS One hundred and six cases of lipoma were identified during the study, but five cases were excluded because they affected the maxillofacial region (four in parotid region, one in submandibular region), resulting in 101 cases of oral cavity lipoma, representing 1.01% of all biopsy specimens stored in the files of the Oral and Maxillofacial Pathology Service of Unifor.Females were affected in 64.3% of cases, with a female/male ratio of 1.8:1.Patients' age ranged from 10 to 84 years, with a peak of incidence between the fifth and sixth decades of life, presenting 56.4% of all cases (age distribution is shown in the Table and the Figure).The buccal mucosa was the most common location (n = 45; 44.5%), followed by the lower lip (n = 12; 11.8%), the retromolar area (n = 10; 9.9%), and the tongue (n = 7; 6.9%).All sites are presented in the Table .Fibroma/fibroepithelial hyperplasia was the most cited clinical diagnosis in 43 cases; lipoma was cited in 35 cases; inflammatory fibrous hyperplasia was cited in five cases; mucocele, in four cases; neural tumors, in two cases (encapsulated neuroma and neurofibroma); diagnosis has not been informed in eight cases; and hemangioma, condyloma, gingival hyperplasia and others were cited once each.
Classic lipomas, followed by fibrolipoma, were the most frequent histological variants of lipoma found in the oral cavity, with 64 and 29 cases each.The mean age for classic lipoma was 56.2 years; and for fibrolipoma, 49 years.A female preference was found for both lipoma and fibrolipoma, with a male/female ratio of 1:1.3 for classic lipomas and 2.2:1 for fibrolipomas.The other histological variants found were sialolipoma, with three cases: a 31-year-old, a 38-year-old and a 70-year-old, all females; angiolipoma, with two cases: a 54-year-old and an 81-year-old, both females; chondrolipoma, with one case: a 68-year-old female; myxolipoma, with one case: a 66-year-old male; and intramuscular lipoma, with also one case: a 24-yearold male.

DiSCuSSion
Lipomas and lipoma variants are common soft tissue tumors in humans, but are infrequently lesions in the oral cavity, with an overall incidence between 1% and 4.4% of all benign oral lesions (1,2,5) ; just a single study report higher incidence (7.5%) (3) .An earlier study in Fortaleza, Ceará, Brazil, showed that this benign neoplasm is responsible for 2% of benign neoplasms in the oral cavity (6) .In the present study, oral lipomas represented 1.01% of all oral lesions stored in the files of the Oral and Maxillofacial Pathology Service of Unifor.
The etiology of lipomas remains unknown.Although some authors suggest that lipomas are more common in obese individuals (2) , the metabolism of lipomas is completely independent of the body fat (3) .Some authors reported no gender difference (4) , but oral and maxillofacial lipomas are more common in men (8,9) .When considering only oral cavity lipomas, this benign neoplasm affect more females than males (1,3,5,7) , with a female:male ratio of 1.8:1 in the present study.Lipomas can occur in all ages, but are lesions frequently diagnosed in adults (3,5,7) , with few cases being diagnosed in pediatric patients (1,8) .Avelar et al. (2008) (9) reported a case of lipoma in a 7-month-old patient.In the present series, lipomas occurred in a wide age range, from 10 to 84-year-olds, and four cases of classic lipoma were diagnosed under the age of 19: two cases in a 10-year-old and a 13-year-old, both males, and two cases in 17-year-old females.Of all cases diagnosed in this study, 86.27% occurred in patients older than 40 years old, with a median age of 56.8 years.In the literature, the median age for diagnosis ranges from 50.2 to 60 years (1,3,4,8) .
Intraoral lipomas can occur in any location of the oral cavity (1,7,9,12) , but the buccal mucosa is the most affected single intraoral site (7,8) .Coherently, in this research, the buccal mucosa was the most frequent site for lipomas (44.1%), followed by lower lip area, retromolar, tongue, floor of the mouth and palate.The palate is an unusual location for a lipoma.In a study on 126 cases of oral and maxillofacial lipomas, only six cases involved the palate, three cases being classic lipomas and three cases being spindle-cell lipomas (8) .In the present study, five lipomas affected the palate: two of the cases were diagnosed as fibrolipoma; lipoma, sialolipoma and angiolipoma presented one case each.
Oral cavity lipomas are usually not a diagnostic challenge for the clinician when the tumor is in a superficial location and presents a yellowish color; and it is mainly represented as a solitary and asymptomatic, smooth-surfaced nodular mass, that can be sessile or pedunculated (1) .Deep infiltrating lesions, or lesions without the typical yellowish color may represent a diagnostic challenge, and may have as differential diagnosis many other lesions, such as fibroma, granular cell tumor, salivary gland neoplasm and other benign soft tissue tumors; also dermoid cyst and oral lymphoepithelial cyst can be included in the differential diagnosis.In the present study, the most quoted clinical diagnosis was fibroma/fibroepithelial hyperplasia (42.2%), followed by lipoma (33.3%).In agreement with a study of de Freitas et al. (2009) (7) , also in a Brazilian population, lipoma was mentioned in the clinical diagnosis in 65.8% of cases, and fibroma in only 19.23% of cases.Intraoral lipomas can also be confused with herniated adipose tissue (1,5) .Classic lipomas, followed by fibrolipoma are the most common histological variants of lipoma found in the oral cavity.The prevalence of the classic lipoma can range from 41.5% to 92.86% of all oral cavity lipomas (1,3,5,7,9) .In this study, classic lipoma represented 63.3% of all histological variants.This large difference in prevalence of histological variants of lipomas may be due to geographic and racial differences, or may represent differences in diagnostic criteria (1) .Classic lipoma is a well-delimited lesion composed of lobules of mature adipocytes, which can show a slight variation in size and shape.Thin septa of connective tissue separate the lobules (2,3) .Fibrolipomas are characterized by the presence of mature adipocytes interspersed with broad bands or fascicles of dense connective tissue (1) .Features such as being well circumscribed and thinly encapsulated help differing lipoma and fibrolipoma from herniated adipose tissue and fibrous polyp with fat entrapment, respectively (10,11) .
Lipoma and fibrolipoma occurred more in buccal mucosa.Although some authors reported male/female ratio of 1:1 for fibrolipomas (1) , in the current survey a female predilection for both lipoma and fibrolipoma was found (male/female ratio of 1:1.3 for classic lipomas and 2.2:1 for fibrolipomas).A higher female predominance of fibrolipomas (3.6:1) was found by Juliasse et al. (2010) (5) .In this article, the average age for classic lipoma was 56.2 years and for fibrolipomas, 49 years.
Sialolipoma was first described by Nagao et al. (2001) (13) , and was recognized by the World Health Organization (WHO) in 2005, and only few cases were described (5,(14)(15)(16) .This variant of lipoma is characterized by a lipomatous proliferation containing glandular structures with varying degrees of acinar atrophy and ductal ectasia, surrounded by a thin fibrous tissue (13,16) .This lesion has been described to affect all ages, from 7 weeks to 84 years (16) .In this research, three cases were found: one case occurred in a 70-year-old female, diagnosed in the retromolar area.The other ones were in a 31-year-old female, diagnosed in the palate area, and a 38-year-old female, diagnosed in the lower alveolar ridge.A male predominance of sialolipoma was described by some (14,17) , but Jang et al. (2009) (15) , in a review of 28 cases found no gender predilection.Controversially, all cases of sialolipoma reported by Juliasse et al. (2010) (5) were observed in female patients.Sialolipomas are more common in major salivary glands: the parotid gland is the single most affected site (14,16) .No anatomical site predilection was described for oral sialolipomas (14) .
A vascular variant of lipoma, angiolipoma, usually appears as subcutaneous nodules consisting in mature adipocytes, intermingled with small thin-walled vessels, which can contain fibrin thrombi (2) .First described as a distinct entity by Bowen (1912) (18) , angiolipoma is frequently diagnosed in trunk and extremities (2,19) , and is a rare oral cavity lesion (19)(20)(21) .Oral angiolipoma seems to affect more males than females, with a male/female ratio of 1.5:1.This variant of lipoma has been described to affect patients from 4 to 81 years old, with a mean age of 37 years, and the buccal mucosa is the most involved site (19) .In the present study, one case occurred in the buccal mucosa of an 81-year-old female; and the other case, in the palate of a 54-yearold female.
Chondrolipoma is a rare variant of lipoma in the oral cavity (22) , and is characterized by the proliferation of mature adipocytes associated with deposition of mature cartilaginous tissue (23,24) .It has been reported to affect mainly the tongue and lips, with no gender predilection, occurring in patients from 2 to 72 years (22)(23)(24)(25)(26) .The case in the present study occurred in the tongue of a 68-year-old female.There is no consensus whether the cartilaginous tissue is a metaplastic process in a lipoma or if the cartilaginous components are derived from undifferentiated pluripotent mesenchymal cells (8,11,24) .This unique variant of lipoma must not be confused with chondroid lipoma, a rare lesion in oral cavity (8) , characterized by the presence of lipoblasts, mature fat and chondroid matrix, which can resemble a myxoid liposarcoma or an extraskeletal myxoid chondrosarcoma (2) .
Other variants of lipoma, such as osteolipoma, spindlecell lipoma, chondroid lipoma, benign lipoblastoma, that can appear in oral cavity (1,3,5) , are extremely rare lesions and were not found in the present series.Although the growth of oral lipomas is usually limited, they can reach great dimension, interfering with speech and mastication (27) .The treatment for oral cavity lipomas, including all the histologic variants, is simple conservative surgical excision, and recurrence is rare (4,9) .One limitation of this research was the fact that some of the histopathological request forms were not completely fulfilled, leaving some important information like age, gender, clinical and anatomic diagnosis with no answer, resulting in missing data.The information about race was not added in the results because the WHO recommends that patients have to categorize their race by themselves, what could create a false result in the study of the Brazilian population, which is mixed.

ConCLuSion
The results of this research found that there are a lot of similarities with other studies previously described in the literature.They confirmed that the oral cavity lipoma is uncommon and it affects more the buccal mucosa of adults between the 50 th and the 70 th decades of life.A gender predilection for females was found, with a male/female ratio of 1:1,8.The most common histological subtypes found were classic fibroma and fibrolipoma.

FigurE
FigurE − Age and sex distribution of the oral cavity lipomas