Somayeh Rahmani,
1and Soudeh Jafari
11Department of Oral Medicine, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2Department of Oral and Maxillofacial Radiology, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Correspondence should be addressed to Maryam Baharvand; m.baharvand@gmail.com Received 23 January 2017; Revised 14 March 2017; Accepted 17 May 2017; Published 5 July 2017 Academic Editor: Chia-Tze Kao
Copyright © 2017 Hamed Mortazavi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Diagnosis of peripheral oral exophytic lesions might be quite challenging. This review article aimed to introduce a decision tree for oral exophytic lesions according to their clinical features. General search engines and specialized databases including PubMed, PubMed Central, Medline Plus, EBSCO, Science Direct, Scopus, Embase, and authenticated textbooks were used to find relevant topics by means of keywords such as “oral soft tissue lesion,” “oral tumor like lesion,” “oral mucosal enlargement,” and
“oral exophytic lesion.” Related English-language articles published since 1988 to 2016 in both medical and dental journals were appraised. Upon compilation of data, peripheral oral exophytic lesions were categorized into two major groups according to their surface texture: smooth (mesenchymal or nonsquamous epithelium-originated) and rough (squamous epithelium-originated).
Lesions with smooth surface were also categorized into three subgroups according to their general frequency: reactive hyperplastic lesions/inflammatory hyperplasia, salivary gland lesions (nonneoplastic and neoplastic), and mesenchymal lesions (benign and malignant neoplasms). In addition, lesions with rough surface were summarized in six more common lesions. In total, 29 entities were organized in the form of a decision tree in order to help clinicians establish a logical diagnosis by a stepwise progression method.
1. Introduction
Lesions in the oral cavity generally present as ulcerations, red- white lesions, pigmentations, and exophytic lesions. Clinical classification of oral lesions is of great importance in the diagnostic process [1, 2]. The term oral exophytic lesions is described as pathologic growths projecting above the normal contours of the oral mucosa [2]. There are several underlying mechanisms responsible for oral exophytic lesions such as hypertrophy, hyperplasia, neoplasia, and pooling of the fluid [1], which makes it difficult to approach such lesions clinically [3, 4]. According to a national epidemiologic study by Zain et al., exophytic lesions account for 26% of all oral lesions [3]. Therefore, attempts should be done to arrive at a timely diagnosis via more logical routes like decision trees rather than test-and-error methods [3, 4]. Exophytic lesions can be classified according to their surface texture (smooth and rough), type of base (pedunculated, sessile, nodular, and dome shape), and consistency (soft, cheesy, rubbery, firm,
and bony hard) [1, 4]. This narrative review paper, however, focuses on the surface shapes of the lesions as the main clinical feature in order to build a diagnostic decision tree.
In this regard, oral peripheral exophytic lesions are classified as lesions with rough surface and those with smoothly contoured shape [1, 5, 6].
2. Methodology
General search engines and specialized databases including PubMed, PubMed Central, Medline Plus, EBSCO, Science Direct, Scopus, Embase, and authenticated textbooks were used by the first author and the corresponding author to find relevant topics by means of MeSH keywords such as “oral soft tissue lesion,” “oral tumor like lesion,” “oral mucosal enlargement,” and “oral exophytic lesion.” Related English-language articles published since 1988 to 2016 in both medical and dental journals including reviews, meta- analyses, original papers (randomized or nonrandomized
89 articled89 118 articles with full texts
78 articles was used
40 excluded
(not English or repetitive material)
Figure 1: Flowchart for choosing eligible articles.
Characteristics
Surface
Base
Pattern
Smooth Granular Verrucous Papillomatous
Papillomatosis Papillomatosis (pebbly)
Bosselated Lobulated
Pedunculated Sessile Nodular Dome-shaped
(cobblestone)
Figure 2: Schematic view of surface and base characteristics of oral exophytic lesions.
clinical trials; prospective or retrospective cohort studies), case reports, and case series on oral disease were appraised.
Out of about 150 related articles, 72 were excluded due to lack of full texts, being written in languages other than English or containing repetitive material. Finally, three textbooks and 78 papers were selected including 13 reviews,
55 case reports or case series, and 10 original articles (Figure 1). In this article, peripheral oral exophytic lesions were categorized into two major groups according to their surface texture: smooth (mesenchymal or nonsquamous epithelium-originated) and rough (squamous epithelium- originated) (Figure 2). Lesions with smooth surface were also
Peripheral oral exophytic lesions
Lesions with rough surface
Salivary gland lesions
Mesenchymal lesions
(i) Squamous papilloma (ii) Verruca vulgaris
(i) Mucocele (ii) Ranula
(i) Pleomorphic adenoma (ii) Mucoepidermoid carcinoma (iii) Adenoid cystic carcinoma
(i) Neurofibroma (ii) Schwannoma (iii) Lipoma (iv) Lymphoma Traumatic or
reactive lesions
Neoplastic lesions
Benign or malignant tumors
(iii) Condyloma acuminatum (iv) Verrucous carcinoma (v) Squamous cell carcinoma (vi) Multifocal epithelial hyperplasia
(Heck’s disease)
(vi) Lymphangiom；∗(sometimes rough) (v) Hemangiom；∗(sometimes rough)
Figure 3: Decision tree for peripheral oral exophytic lesions.
categorized into three subgroups according to their general frequency: reactive hyperplastic lesions/inflammatory hyper- plasia, salivary gland lesions (nonneoplastic and neoplastic), and mesenchymal lesions (benign and malignant neoplasms).
In addition, lesions with rough surface were summarized in six more common lesions. In total, 29 entities were organized in the form of a decision tree (Figure 3) in order to help clinicians establish a logical diagnosis by a stepwise progression method.
3. Lesions with Smooth Surface
3.1. Reactive Hyperplastic Lesions/Inflammatory Hyperplasias.
Reactive hyperplasia is the most frequent phenomenon responsible for exophytic lesions in the oral cavity (Table 1).
These lesions represent a reaction to some kind of chronic trauma or low grade injuries such as fractured tooth, calcu- lus, chewing, and iatrogenic factors including overextended flange of dentures and overhanging dental restorations [7].
Reactive lesions are usually seen on the gingivae followed by the tongue, buccal mucosa, and floor of the mouth.
Clinically, they appear as pedunculated or sessile masses with smooth surface. Lesions are varied from pink to red and soft to firm in terms of color and consistency [7, 8].
However, the clinical features resemble neoplastic lesions in
some instances, which cause a diagnostic dilemma. The most common entities of reactive nature are pyogenic granuloma, pregnancy epulis, irritation fibroma, peripheral ossifying fibroma, peripheral giant cell granuloma, epulis fissuratum, leaf-like fibroma/fibroepithelial polyp, parulis, pulp polyp, epulis granulomatosum, giant cell fibroma, and inflammatory papillary hyperplasia/palatal papillomatosis [1, 4, 7].
3.1.1. Pyogenic Granuloma. Pyogenic granuloma is a com- mon tumor-like lesion in the oral cavity appearing as a smooth or lobulated, asymptomatic mass that is usually pedunculated or sessile. The surface is characteristically ulcerated and friable, which may be covered by a yellow fibrinous membrane (Figure 4) [4, 9]. Depending on the duration of the lesion, its color ranges from shiny red to pink to purple with soft to firm in palpation. It often bleeds easily because of its extreme vascularity. Approximately in one-third of the lesions a history of trauma can be detected [10]. Pyogenic granuloma may exhibit a rapid growth, but it usually reaches its maximum size within weeks or months.
The size of the lesion varies from a few millimeters to several centimeters in diameter. In 75% of all cases, the most frequently affected site is the gingivae followed by the lips, tongue, and buccal mucosa. Maxillary gingivae are more affected than mandibular gingivae, and anterior areas more
Table1:Generalcharacteristicsofsmooth-surfacedoralexophyticlesionsofreactiveorigin. EntityAgeGenderSiteofinvolvementSurfacetextureTypeofbaseConsistencyColorSizeSymptom&sign PyogenicgranulomaChildren/young adultFemaleGingivaeSmooth/lobulatedPedunculated/sessileSofttofirmShinyred/pink/purpleAfewmmto severalcmAsymptomatic PregnancytumorPregnancy periodFemaleGingivaeSmooth/lobulatedSessileSofttofirmShinyred/pink/purpleAfewmmto severalcmAsymptomatic Irritationfibroma4–6decadesFemaleBuccalmucosaSmoothPedunculated/sessileFirmorsoftSimilartoadjacent mucosa≤1.5cmAsymptomatic Peripheralossifying fibroma10–19yearsoldFemaleExclusivelygingivaeSmoothPedunculated/sessileFirmtohardRedtopink<2cmToothmobility Toothmigratio Boneloss Peripheralgiantcell granuloma5-6decadesFemaleExclusively edentulousridge& gingivaeSmoothPedunculated/ sessile/nodularFirmBluishpurple<2cmor>2cmBoneloss Rootresorption Epulis granulomatosum>40yearsFemaleDentalsocketSmooth—SofttofirmSimilartoadjacent mucosa<1cmto massivelesionsAsymptomatic Leaf-likefibroma——PalateSmoothPedunculated/sessileFirmPinkUptoseveral cmAsymptomatic Epulisfissuratum——Maxillaryalveolar ridgeSmooth/ulcerativePedunculated/sessileFirmReddishUptoseveral cmNontender/easil bleeding PulppolypChildren/young adults—
Cariouslesionsof deciduousteeth& firstpermanent molars
SmoothPedunculated/sessileSofttofirmRedtopink<1cmtolarge massesDiscomfort GiantcellFibroma3rddecadeFemaleGingivaeRoughsurfacePedunculated/sessileFirmPink<1cm(often)Asymptomatic Inflammatory papillaryhyperplasia3–5thdecadesMalePalatePebbly/cobblestone—SofttofirmRedtopinkUptoseveral cmAsymptomatic symptomatic
Figure 4: Pyogenic granuloma as a sessile lesion on mandibular labial gingivae with an ulcerated smooth surface.
frequently involved than posterior areas [9–11]. There is a female predilection and a tendency to affect children and young adults. Patients with pyogenic granuloma are treated by conservative surgical excision. However, recurrence is not uncommon [9].
3.1.2. Pregnancy Tumor. Pregnancy tumor or granuloma gravidarum is a reactive lesion with the same clinical features to pyogenic granuloma. The lesion may emerge during the first trimester with a gradual increasing incidence to the seventh months of pregnancy, which is presumably related to the rising levels of estrogen and progesterone. Some of these lesions resolve spontaneously after delivery or undergo fibrous maturation mimicking an irritation fibroma [4, 10].
The lesions do not occur in people with optimum oral hygiene suggesting local irritation as an important etiologic factor [4]. Patients with small isolated lesions and otherwise healthy gingivae might be monitored for shrinkage after delivery, but large lesions or generalized pregnancy gingivitis or periodontitis warrants the need for treatment during pregnancy [4].
3.1.3. Irritation Fibroma. Irritation fibroma or focal fibrous hyperplasia is the most common tumor-like lesion of the oral cavity with the prevalence of 1-2% in general population.
It appears as an asymptomatic, pedunculated, or sessile exophytic lesion with a smooth surface and being similar to the surrounding mucosa in color (Figure 5). However, the surface may show hyperkeratosis from secondary trauma. It can be firm and resilient or soft with spongy consistency.
Although fibromas usually reach to 1.5 cm or less in diameter they might appear as very tiny to quite large lesions. The most commonly affected site is the buccal mucosa along the line of occlusion; however it can occur anywhere in the oral cavity.
The labial mucosa, tongue, and gingivae can be involved as well. It is likely that many fibromas represent fibrous maturation of a preexisting pyogenic granuloma. There is a female predilection with female to male ratio of 2 : 1 with the majority of cases being reported in the fourth to sixth
Figure 5: Irritation fibroma on the buccal mucosa with a smooth surface and dome-shaped base.
decades of life. Conservative surgical excision is the treatment of choice for irritation fibroma with a low recurrence rate.
3.1.4. Peripheral Ossifying Fibroma. Peripheral ossifying fibroma also called peripheral fibroma with calcification, ossifying fibroid epulis, and calcifying fibroblastic granuloma is a reactive gingival enlargement [10]. It represents 2% to 9%
of all gingival lesions and 3% of all oral lesion biopsy samples [12, 13]. The lesion appears as a smooth, pedunculated, or sessile, firm to hard mass that usually emanates from the interdental papilla. It is a red to pink lesion often less than 2 cm in diameter, but lesions up to 8 cm have been reported as well [10, 13]. Tooth mobility, tooth migration, and bone destruction have been noticed in some cases [13]. This lesion occurs exclusively on the gingivae with up to 60% of cases being reported in the anterior areas of the maxilla (incisor- cuspid region) [12, 13]. Two theories have been proposed to explain the pathogenesis of the lesion: it might originate from a calcified pyogenic granuloma, or it may arise from an overgrowth and proliferation of different components of connective tissue in the periodontium, but the main etiology is yet to be elucidated [12, 14]. Peripheral ossifying fibroma is predominantly a lesion of teenagers and young adults with a peak prevalence being between 10 to 19 years [10]. Females are more affected than males, mainly during their second decade of life, due to fluctuations of estrogen and progesterone [12].
Treatment usually involves surgical excision, and the lesion should be excised down to the periosteum. The recurrence rate has been estimated to be between 8% and 20% [10, 12].
3.1.5. Peripheral Giant Cell Granuloma. Peripheral giant cell granuloma is a common tumor-like lesion of the oral cav- ity that conveys a reactive response in the periodontium, periodontal ligament and gingivae. It occurs exclusively on the edentulous alveolar ridge and gingivae as a smooth, reddish-blue, pedunculated, sessile, or nodular mass, which is firm to palpation. In some cases the clinical appearance of the lesion is similar to pyogenic granuloma; however peripheral giant cell granuloma is more bluish-purple colored
Figure 6: PGCG with an ulcerated, smooth surface and purplish color located buccolingually on the left mandibular ridge.
as compared with bright red color of pyogenic granuloma (Figure 6) [10, 15]. It is usually less than 2 cm in diameter, but larger sizes are seen occasionally. Progressive growth in some cases may lead to bone and root resorption [16].
The mandible is more affected than the maxilla, and there is a female predilection with female to male ratio of 2 : 1 [15, 16]. As the giant cells are found to act as a potential target for estrogen, it is not surprising that the lesions are triggered by sex hormones [17]. The lesions can develop at any age; however peak prevalence was found in the fifth and sixth decades of life [10]. Hyperparathyroidism should be considered in differential diagnosis in case of multiple lesions especially with a history of recurrences. In spite of adequate treatment, children with hypophosphatemic rickets are also at a higher risk for developing such lesions [16, 17]. Complete surgical excision with elimination of the entire base of the lesion is the accepted treatment plan for this lesion [15–17].
3.1.6. Epulis Fissuratum. Epulis fissuratum or denture- induced hyperplasia is a reactive lesion of the oral cavity caused by low grade chronic trauma from dentures [18].
About 70% of patients wear ill-fit dentures continuously all day long for more than 10 years [19]. The lesion appears as an asymptomatic single fold or multiple folds of hyperplastic tissues in the alveolar vestibule along denture flanges with a smooth surface, soft to firm consistency, and a normal coloration (Figure 7) [18, 20]. In some cases, severe inflam- mation or ulceration may be seen in the bottom of the folds [18]. It has been reported in 5% to 10% of the jaws fitted with dentures and is more prevalent in the maxilla than the mandible, especially on the facial aspect of the alveolar ridges [18, 19]. The anterior portions of the jaws are more often affected; however epulis fissuratum of the soft palate has been reported in the literature [20]. Two-thirds to three- fourths of all cases have been found in females [19, 20].
In women, postmenopausal hormonal imbalance makes the oral mucosa susceptible to a hyperplastic growth [18]. It is more frequent in patients over 40 years; however this entity has been reported in patients from childhood to elderly [1].
Figure 7: Massive epulis fissuratum presenting as an exophytic lesion with smooth surface associated with an ill-fit mandibular denture.
The size of the lesion varies from less than 1 cm in diameter to massive lesions involving extensive areas on the vestibule [19, 20]. Epulis fissuratum can be treated conservatively or surgically depending on the size of the lesion.
3.1.7. Leaf-Like Fibroma. Ill-fit dentures worn for many years can cause benign hyperplastic fibrous growths or epulides.
When a fibrous epulis forms underneath the palatal base of a denture, it is known as a leaf-like denture fibroma or fibroepithelial polyp [21]. It is characterized as a pain less, flattened, pink, firm mass attached to the palate by a narrow stalk or a broad base (pedunculated or sessile) which can reach to several centimeters in diameter. The edge of the lesion is serrated resembling a leaf. In most cases, the flattened mass is closely located to the palate and sits in a slightly cupped-out depression [10, 22]. Treatment is accomplished by means of conservative surgical removal and fabrication of new dentures. While altering the denture may decrease the size of the lesion, adjustment alone will not lead to complete regression due to dense nature of the scar tissue. Recurrence is not uncommon [21].
3.1.8. Epulis Granulomatosum. Epulis granulomatosum or epulis hemangiomatosis—a variant of pyogenic granuloma—
presents as an overgrowth arising from a recently extracted tooth socket [23–25]. The precipitating factor in most patients is sharp specula of the alveolar bone left in the walls of the socket [1]. Clinically, it is characterized by reddish, smooth, pedunculated or sessile, nontender, rapidly growing mass with soft to firm in palpation. Surface of the lesion may be ulcerative due to secondary trauma [23, 24]. It often bleeds easily because of its high vascular content [23]. The growth may become apparent in one or two weeks after tooth extraction [1]. Lesions of larger sizes were also incidentally seen as an oral finding in patients with Klippel-Trenaunay syndrome [23]. Evaluation of socket and removal of any bony spicules or tooth fragments at the time of extraction prevent formation of an epulis granulomatosum. Excision of the raised mass and curettage of the alveolus to ensure the
Figure 8: Pulp polyp associated with carious first mandibular molar with smooth surface and sessile base.
elimination of irritating particles is needed to treat the lesion [23–25].
3.1.9. Pulp Polyp. Pulp polyp or chronic hyperplastic pulpitis or pulpitis aperta is an uncommon reactive lesion, which occurs when caries have destroyed the tooth crown [1]. It appears as a smooth, soft to firm, red to pink, pedunculated, or sessile mass occupying the entire carious cavity in the affected tooth resembling an enlarged gingival tissue (Fig- ure 8) [26, 27]. The size of the lesion varies from less than 1 cm in diameter to large masses (about 4 cm) [26, 27]. It is most frequently found in the deciduous and permanent first molars of children and young adults and is a rare phenomenon in the middle-aged adults [1, 28]. It is usually asymptomatic, but discomfort can occur during mastication.
Response to electrical and thermal stimuli may be normal [28]. Periapical radiographs may show an incipient chronic apical periodontitis when pulp involvement is extensive or lingering [28]. The polyp may cover most of the remaining crown of the tooth, giving the lesion an appearance of a flashy mass [29]. A similar hyperplastic mass around a draining sinus tract of a tooth with pulpoperiapical pathology is called parulis [4]. The treatment plan of this lesion includes endodontic treatment or tooth extraction [28].
3.1.10. Giant Cell Fibroma. Giant cell fibroma is a fibrous hyperplastic soft tissue lesion classified as an inflamma- tory hyperplasia [1]. However, a controversy exists about the origin and etiology of this entity [30]. It represents approximately 2% to 5% of all oral fibrous lesions and 0.4%
to 1% of all oral biopsy samples [31]. Clinically, it appears as an asymptomatic, sessile, or pedunculated mass with rough surface (papillary or granular) and firm in palpation (Figure 9) [30, 31]. Despite previously mentioned reactive lesions, giant cell fibroma did not have a completely smooth surface; hence it may clinically be mistaken with lesions of squamous epithelium origin such as papilloma [10]. The color of the lesion is pink or similar to the surrounding normal
Figure 9: Pedunculated lesion of giant cell fibroma with granular surface on the palatal gingivae of maxillary central incisors.
mucosa and is usually less than 1 cm in diameter [10, 31]. In about 60% of cases, the lesion is diagnosed in the second to third decade of life with only 4% to 17% of giant cell fibromas being found in children younger than 10 years [31, 32]. There is a slight female predilection and gingivae are the most affected site (about 50% of cases) followed by the tongue, palate, buccal mucosa, lips, and floor of the mouth [10, 31].
Moreover, mandibular gingivae are affected twice as often as the maxillary gingivae [32]. Giant cell fibroma usually is treated by conservative surgical excision. Electrosurgery and laser therapy have been suggested as alternative modalities especially in children. Recurrence is rare [10, 28].
3.1.11. Inflammatory Papillary Hyperplasia. Inflammatory papillary hyperplasia (palatal papillomatosis and denture papillomatosis) is a reactive lesion seen most often in patients with an ill-fit denture wearing all-day-long and poor oral hygiene [10, 33]. This condition is encountered in 10% to 20% of denture wearers [1, 10]. It is featured by exophytic masses with pebbly or cobblestone appearance on the hard palate beneath a denture base with or without symptoms [10]. Although these lesions appear as red, soft masses in the inflammatory stage they convert to pink and firm when they mature to fibrous stage [1]. In some cases, denture papil- lomatosis develops on the edentulous mandibular alveolar ridge or on the surface of an epulis fissuratum [10]. It can occur at any age. However, it is most frequently encountered in the third to fifth decade of life with a male predilection [33]. In addition to frictional irritation provoked by loose- fit dentures, Candida albicans has an etiologic role in this entity [1]. On rare occasions, this condition occurs on the palate of patients without denture especially in people who habitually breathe through their mouth or have a high palatal vault [10]. Less extensive lesions are resolved by removing the denture at night and improving oral hygiene. Patients can also benefit from antifungal agents. Various surgical methods have been suggested for the treatment of this lesion such as partial thickness or full thickness surgical blade excision, curettage, electro surgery, and cryosurgery [10, 34, 35].
Figure 10: Nodular mucocele of the lower lip with smooth surface.
3.2. Salivary Gland Lesions. A wide range of lesions arise from intraoral salivary glands, which are categorized as nonneoplastic and neoplastic entities. According to a 15-year- retrospective study by Mohan et al., 55% of lesions were nonneoplastic and 45% were neoplastic [36]. When salivary gland lesions appear as an exophytic lesion they are usually characterized by a dome-shaped or nodular mass with a smooth surface and fluctuant to firm in palpation [1]. The most common lesions of salivary gland origin are as follows (Table 2).
3.2.1. Mucocele and Ranula. Mucocele is a common nonneo- plastic lesion of salivary gland origin resulting from breaking or dilation of salivary ducts secondary to obstruction or local trauma [37]. Clinically, it appears as an asymptomatic, fluctuant to firm, bluish to pink, nodular, or dome-shaped mass with a smooth surface (Figure 10) [1, 37]. The size of the lesion varies from 1-2 mm to several centimeters but remains smaller than 1.5 cm in diameter [37]. The incidence is pretty high, 2.5 cases per 1000 persons with no sex predilection [38].
Lesions last from a few days to several months. Many patients mention a history of recurrent swelling with periodic rupture and release of fluid content [10, 38]. The majority of cases have been reported in the first three decades of life, and it is rare among children younger than 1 year of age [37, 38]. The lower lip is the most frequently (60%) affected site followed by buccal mucosa, anterior ventral tongue, floor of the mouth, and upper lip [10]. In some cases, mucoceles rupture and heal spontaneously; however conventional surgical treatment may be suggested in large lesions. Some alternative modalities such as cryosurgery, intralesional injection of steroids, and laser therapy have been implemented as well [37].
When a mucocele occurs in the floor of the mouth it is called ranula featuring as a bluish, dome-shaped or nodular; fluctuant exophytic lesion with a smooth surface usually located lateral to the midline [10]. Fluctuation in size considered as a pertinent feature noticed in the history of ranula. The lesion measures its smallest size early in the morning and reaches to the largest scale at the time of meals [1]. A prevalence of 0.2 cases per 1000 persons has been found, and it accounts for 6% of all oral sialocysts [39]. Most of the patients are young adults with peak frequency being in the second decade of life [39]. This lesion is treated by
Figure 11: Pleomorphic adenoma involving upper lip presented as a dome-shaped exophytic lesion with smooth surface.
marsupialization or removal of the feeding sublingual gland;
however marsupialization leads to recurrence in 25% of cases [1, 10].
3.2.2. Pleomorphic Adenoma. Pleomorphic adenoma or mixed tumor is a benign salivary gland tumor which consti- tutes 3% to 10% of head and neck neoplasms and about 1%
of all body tumors [40, 41]. It is the most common (73%) tumor of both minor and major salivary glands [41, 42].
Corresponding to minor salivary glands, the palate is the most affected site followed by lips, buccal mucosa, tongue, floor of the mouth, pharynx, retromolar area, and the nasal cavity [41]. It is suspected when a clinician encounters a unilateral, asymptomatic, slow growing, firm, nodular, or dome-shaped mass covered by a normal-colored mucosa (Figure 11) [40, 41]. The surface of the lesion is usually intact, but ulceration of the overlying mucosa has been reported in some instances [40]. The size of the lesion varies from 1 to 5 cm with the average of 2.6 cm in diameter [41]. In large cases bone resorption has been reported [40]. It can occur at any age, but majority of patients have been reported in their fifth to sixth decades of life [41, 42]. Lip lesions tend to occur at an earlier age than that of other locations [41]. There is a female predilection with female to male ratio of 7 : 3 [41]. Malignant transformation to pleomorphic adenocarcinoma has been noticed in about 6% of cases [42].
Surgical excision usually yields promising results treated with good prognosis. A recurrence rate of 2% to 44% has been reported, and patients younger than 30 years are more likely to have relapsing lesions [41]. Risk for recurrence seems to be lower in the minor salivary gland tumors than that of major salivary glands [41].
3.2.3. Mucoepidermoid Carcinoma. Mucoepidermoid carci- noma or mucoepidermoid tumor is the most common malignant salivary gland neoplasm. It accounts for about 3%
of all head and neck tumors [10, 43]. Two-thirds of the lesions arise within the parotid gland and one-third within the minor salivary glands. Intraorally, palate is the most affected site followed by retromolar area, floor of the mouth, buccal mucosa, lips, and tongue. Intraosseous lesions have been also reported in some cases [10, 43, 44]. The tumor can occur at
Table2:Generalcharacteristicsofsmooth-surfacedoralexophyticlesionsofsalivaryorigin. EntityAgeGenderSiteof involvementSurfacetextureTypeofbaseConsistencyColorSizeSymptom Mucocele&ranulaFirst3decadesof lifeNosex predilectionLowerlip/floorof themouthSmoothNodular/dome shapedFluctuanttofirmBluishtopink<1.5cmAsymp Pleomorphic adenoma5-6thdecadesFemalePalateSmoothNodular/dome shapedFirmNormalcolored1–5cmAsymp Mucoepidermoid carcinoma3–6thdecadesFemalePalateSmoothNodular/dome shapedFirmPink/bluishtored ornormalcoloredUptoseveralcmAsymptomat highG Adenoidcystic carcinoma5-6thdecadesFemalePalateSmooth/ulcerativeNodularFirmPink/normal coloredUptoseveralcmPainiscom destructio metast
Figure 12: Mucoepidermoid carcinoma of the palate, presented as an exophytic lesion with smooth, ulcerated surface, and nodular base.
any age, but the majority of patients have been diagnosed between the third and sixth decade of life with a female predilection. Although it is rare in children, mucoepidermoid carcinoma is the most common malignant salivary gland neoplasm in childhood [10, 43–45]. Clinically, it appears as a smooth-surfaced nodular or dome-shaped, firm mass with a diameter up to several centimeters. The color of the lesion may be pink, bluish to red, or even similar to the surrounding normal mucosa (Figure 12) [1, 10, 43]. Patients are usually asymptomatic, but high grade tumors might be painful [44].
Palatal neoplasms cause bone resorption, and an ulcerative surface might be found in some tumors. [10, 44]. Low grade neoplasms are treated by surgical excision with free surgical margins. High grade ones require wide surgical excision, neck dissection, and postoperative radiotherapy. Recurrence rate is up to 60%, which mostly occurs within 1 year after treatment [45].
3.2.4. Adenoid Cystic Carcinoma. Adenoid cystic carcinoma is the most common malignant tumor originated from the submandibular and minor salivary glands. It comprises 5% to 10% of all salivary gland neoplasms and 2% to 4% of all head and neck malignancies [4, 46]. It can occur in any salivary gland, but approximately 50% to 60% of cases develop within minor salivary glands. The palate is the most frequently affected site in the oral cavity. Clinically, it is characterized by a slow growing, pink to normal-colored nodular mass with a smooth surface and firm consistency [1, 46, 47]. An intraoral adenoid cystic carcinoma may exhibit mucosal ulceration, a feature that helps distinguish it from a benign pleomorphic adenoma [4]. Pain is a common finding and usually occurs early in the course of the disease before an apparent swelling develops [10]. In cases arising in the palate or maxilla, there is an evidence of bone destruction adjacent to the tumor [4, 47]. Local recurrences, perineural spreading, and distant metastases have been also reported as important features of this entity [4]. The peak prevalence of this tumor is in the fifth and sixth decades, and it is rare in people younger than 20 years [10, 46]. An almost equal sex distribution has been mentioned; however some studies showed a female predilection [10, 46, 47]. Because of the ability of this lesion to spread along the nerve sheets, radical surgical excision
Figure 13: Sessile-based and smooth-surfaced exophytic lesions of neurofibroma involving dorsal and lateral border of the tongue.
is suggested as the accepted treatment plan. The tumors of the minor salivary glands should be treated by local radical excision and postoperative radiotherapy. Chemotherapy is also recommended in the management of advanced and metastatic salivary gland tumors [47].
3.3. Mesenchymal Lesions. Peripheral oral mesenchymal tumors are considered among uncommon lesions of the oral cavity (Table 3). According to a 10-year-retrospective study by Mendez, only 4% of oral lesions were of mesenchymal origin [48]. Clinically, these lesions present as asymptomatic, slow growing, nodular, or dome-shaped masses with a smooth surface and firm consistency. These lesions are usually cov- ered with normal mucosa unless chronically traumatized.
They can be involved any site of the oral cavity [1]. The most common oral lesions with mesenchymal origin are lipoma, neurofibroma, schwannoma, lymphoma, hemangioma, and lymphangioma [49].
3.3.1. Neurofibroma. Neurofibroma is the most common peripheral nerve tumor; however it is rarely seen in the oral cavity. Most cases of oral neurofibroma are multiple and as a part of neurofibromatosis syndrome, but it rarely appears as a solitary mass without visceral manifestations [10, 50]. It has been demonstrated that solitary neurofibroma is a hyperplastic hamartomatous malformation rather than a neoplastic lesion [51]. It appears as an asymptomatic, slow growing, soft to firm, nodular, or sessile mass with a smooth surface (sometimes lobulated) and pink in coloration (Figure 13) [50, 51]. It most commonly develops on the tongue followed by palate, mandibular ridge/vestibule, maxillary ridge/vestibule, buccal mucosa, lips, floor of the mouth, and gingivae with up to several centimeters in diameter [50, 51].
Intraosseous lesions have been also reported in the posterior mandible as a well-defined or poorly defined unilocular or multilocular radiolucency [51, 52]. It is most commonly observed in young adults with a peak prevalence in the third decade of life with the sex predilection being still debatable [50, 51]. The tumor is usually treated by complete excision
Table3:Generalcharacteristicsofsmooth-surfacedoralexophyticlesionsofmesenchymalorigin. EntityAgeGenderSiteofinvolvementSurfacetextureTypeofbaseConsistencyColorSizeSymptom Neurofibroma3rddecadeNosex predilectionTongueSmoothNodular/sessileSofttofirmPinkUptoseveral centimetersAsymptom SchwannomaAverage:34 yearsFemaleTongueSmoothNodular/sessileRubberySametonormal mucosa0.5–4cmAsympto Lipoma>40yearsMaleBuccal mucosa/vestibuleSmoothNodular/sessile/ pedunculatedSoft/fluctuantPinktoyellowish<3cm(often)Asympto LymphomaAverage:59 yearsMaleBuccalvestibule& postpalateSmooth/ulcerativeNodularSofttofirmPink/purplish/normalUptoseveralcmNontenderp intraosseous HemangiomaEarlyinfancyFemaleLipsSmooth/lobulatedSessileSoftPinktoredpurpleUptoseveralcmAsympto Lymphangioma1stdecadeNosex predilectionTongueSmooth/pebblySessileSoftPinktoyellowishor normalcolorUptoseveralcm Macrogloss obstru tion/sialorr deformi
Figure 14: A dome-shaped schwannoma on the ventral surface of the tongue with smooth surface.
with a low recurrence rate. However, neurofibroma may convert to neurofibrosarcoma in 5% to 15% of cases especially in multiple lesions [51].
3.3.2. Schwannoma. Schwannoma, also called neurilem- moma, neurinoma, or perineural fibroblastoma, is a benign tumor of neuroectodermal origin [53, 54]. Approximately 25% to 45% of lesions are seen in the head and neck with 1% being reported in the oral cavity as well [53]. Clinically, it is characterized by solitary, asymptomatic, rubbery, nodular, or sessile mass with a smooth surface and is similar to the normal mucosa in coloration (Figure 14). The size of the lesion varies from 0.5 to 4 cm in diameter [53, 54]. Intraoral lesions are frequently located in the tongue followed by palate, floor of the mouth, buccal mucosa, gingivae, lips, and vestibu- lar mucosa [55]. Schwannoma can occur as an intraosseous lesion, which accounts for 1% of all benign primary bony tumors [54, 55]. Intrabony lesions appear as either unilocular or multilocular radiolucencies [53]. Peripheral lesions are usually painless, but tenderness may occur in some instances [10]. Pain and paresthesia are not uncommon for intrabony tumors [10]. Schwannoma has been reported in the age range of 8 to 72 years with an average age of 34 years with a slight female predilection (female to male ratio of 1.6 : 1) [53, 55].
Surgical excision is the treatment of choice and recurrence and malignant transformation are extremely rare [55].
3.3.3. Lipoma. Lipoma is a benign tumor, which seldom occurs in the mouth. It constitutes 4% to 5% of all benign tumors in the body representing about 1% to 5% of all neoplasms of the oral cavity [56]. Generally, the prevalence of the lesion is balanced in both genders; however a slight male predilection has been reported. Lipoma is a rare entity in children, and most of the patients are over 40 years [57]. It presents as a slow growing, nodular, sessile, or even pedunculated mass with a smooth surface and fluctuant to soft in palpation. The superficial lesions usually show yellowish hue, while more deeply seated ones appear as a pink mass [10, 56, 57]. Lipoma varies in size from small to large masses mostly measuring less than 3 cm in diameter [10, 56]. The buccal mucosa and buccal vestibule are the most
Figure 15: Lymphoma presented as a nodular exophytic lesion with smooth surface on the palate.
commonly affected sites, which accounts for about 50% of all cases [10]. Less affected sites include the tongue, floor of the mouth, and lips [10]. Lipoma is treated by conservative surgical excision and usually does not recur. Intramuscular lipoma has a somewhat higher recurrence rate because of problems to remove completely [4].
3.3.4. Lymphoma. Lymphomas are heterogeneous malignant neoplasms of the lymphocyte cell lines. They can be divided as Hodgkin and non-Hodgkin lymphoma (HL and NHL).
Hodgkin lymphoma rarely shows extra-nodal disease (1%
of cases) unlike NHL, which arises from extra-nodal sites in 20% to 30% of patients [58, 59]. Extra-nodal lymphoma is the second most commonly encountered neoplasm after squamous cell carcinoma in the head and neck region, which accounts for 5% of all malignancies of head and neck [59–
61]. Oral lymphomas usually occur secondary to a more widespread involvement through the body; however it can present as a primary lesion in the oral cavity with the prevalence of 0.1% to 2% [60]. Clinically, it appears as a nontender, smooth surface, soft to firm mass in the mouth (Figure 15) [10, 58–60]. The size of lesion varies from small to large with a pink, purplish, or normal coloration. The surface of lesion may be intact or ulcerative [10, 59, 60].
The mean age of patients with lymphoma is 56 years, and there is a male predilection [60, 61]. The most affected site for oral lesions is buccal vestibule, posterior palate, and gingivae [10, 60]. Intraosseous lesions were also reported in some cases. Bony lesions often present with low grade pain, which can mimic toothache [60]. Radiotherapy plus chemotherapy is recommended for intermediate and high grade tumors. A failure rate of 30% to 50% was demonstrated in intermediate grade lesions; however high grade lesions show a 60% mortality rate [10].
3.3.5. Hemangioma. Hemangioma is a benign common tumor in the head and neck region, but relatively rare in the mouth. In the oral cavity, it can cause esthetic and functional impairment depending on its location and size [62]. The peak prevalence of this entity is described soon after birth or in early infancy; however some cases have been reported
Figure 16: Lobulated hemangioma involving the right upper lip.
in adulthood [10, 62]. It is noted that hemangioma is the most common tumor of infancy, occurring in 5% to 10% of one-year-old children [10]. Oral lesions are most common in the lips, gingivae, tongue, and buccal mucosa [62, 63].
Eighty percent of cases occur as a single lesion, but 20% of affected patients present multiple tumors [10]. Clinically, it is characterized by an asymptomatic, soft, smooth, or lobulated, sessile mass with various sizes from a few millimeters to several centimeters (Figure 16). The color of the lesions ranges from pink to red purple, and tumor blanches on the application of pressure [63, 64]. Gingival lesions which arise from the interdental papillae can spread laterally to involve adjacent teeth [63]. There is a female predilection with female to male ratio of 3 : 1, and they usually occur in whites more often than other racial groups [10]. Treatment of hemangioma depends on its size and location. Small lesions are treated by sclerotherapy, conventional surgical excision, laser therapy, and cryotherapy. In large cases, treatment should include embolization or obliteration of the lesion and the adjacent vessels [62].
3.3.6. Lymphangioma. Lymphangioma is a benign, hamar- tomatous tumor of lymphatic vessel origin. It has a marked tendency for the head and neck region in a way that 75% of all cases occur in this area. Almost half of the lesions are noted at birth and about 90% developed by two years of age [65].
In the oral cavity, lymphangioma mostly occurs on the dorsal surface and lateral borders of the tongue followed by gingivae, buccal mucosa, and lips [65, 66]. Pathognomonic features of tongue lymphangioma are irregular nodularity of the surface with gray to pink projections and macroglossia [66]. There is no sex predilection, and oral lesions are most common in the first decade of life [66]. The clinical manifestation of the lesion varies based on whether it is superficial or deep. Superficial lesions appear as soft exophytic masses with rough (papillary or pebbly) surface and pink to yellowish coloration. Deeper lesions are described as soft diffuse masses with normal color and smooth surface [65, 67]. Massive lesions might cause macroglossia, obstruction in upper air way, sialorrhea, and jaw deformity as well as difficulties in mastication, speech, and oral hygiene [65]. Lymphangioma is treated by surgical
tongue with a sessile base and papillomatous surface.
excision, cryotherapy, electrocautery, sclerotherapy, steroid administration, embolization, laser surgery, and radiation therapy [65].
3.4. Lesions with Rough Surface. This group of lesions most frequently occurs as a result of epithelial proliferation due to reaction to human papilloma virus or a neoplastic process (Table 4).
3.4.1. Squamous Papilloma. Oral squamous papilloma is a benign proliferation of the stratified squamous epithelium.
It occurs in one of every 250 adults and constitutes approx- imately 3% of all oral biopsy lesions [10, 68]. The etiologic factor is the human papillomavirus (HPV), and viral subtypes 2 and 11 have been isolated from up to 50% of oral papillomas [10]. Clinically, it appears as a single, asymptomatic, pedun- culated or sessile, soft to firm mass with verrucous, granular, or papillomatous surface (Figure 17). The lesion may be white, slightly red, or normal in color [4, 68–70]. Papilloma usually enlarges rapidly to a maximum size of 5 mm with little or no change in diameter thereafter [10]. The most affected sites in the oral cavity are palatal mucosa and the tongue, but any oral surface may be involved [69]. Although papilloma can involve patients at any age it is diagnosed most often in people between 30 and 50 years [10]. Surgical excision by either scalpel or laser ablation is the treatment of choice. However, other modalities such as electro cautery, cryosurgery, and intralesional injection of interferon have been suggested [70].
Recurrence is uncommon, except for patients infected with human immunodeficiency virus [70].
3.4.2. Verruca Vulgaris. Verruca vulgaris is a benign virus- induced hyperplasia of stratified squamous epithelium. It is usually encountered in children with a peak incidence between 12 and 16 years. However, about 10% of general population affect the disease in their middle age [71, 72]. Most of oral lesions are located on the vermilion border, labial mucosa, or anterior tongue [4, 10]. Clinically, it appears as an exophytic, sessile, or pedunculated lesions with papillary projections (verrucous or papillomatous) or a rough pebbly surface [10, 71]. The lesions are asymptomatic and may be pink, yellowish, or white in coloration [10]. It usually
