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Oral Mucoceles: A Clinicopathologic Review of 1,824 Cases, Including Unusual Variants
PATHOLOGY J Oral Maxillofac Surg 69:1086-1093, 2011
Oral Mucoceles: A Clinicopathologic Review of 1,824 Cases, Including Unusual Variants Angela C. Chi, DMD,* Paul R. Lambert III, BS, MBA,† Mary S. Richardson, DDS, MD,‡ and Brad W. Neville, DDS§ Purpose: To review the clinicopathologic features of oral mucoceles, with special consideration given
to unusual variants and exclusion of salivary duct cysts. Materials and Methods: This was a retrospective consecutive case review of all oral mucoceles diagnosed by the Medical University of South Carolina, Oral Pathology Biopsy Laboratory, from 1997 to 2006. The following data were recorded: patient demographics, clinical features (anatomic location, color, size, and consistency), clinical impression, history of trauma, history of periodic rupture, and occurrence of unusual mucocele variants. Results: During the study period, 1,824 oral mucoceles were diagnosed. Of these cases, 1,715 represented histopathologically confirmed cases that were not recurrences. There was no significant gender predilection, and the average age was 24.9 years. The most common locations were the lower labial mucosa (81.9%), floor of mouth (5.8%), ventral tongue (5.0%), and buccal mucosa (4.8%); infrequent sites included the palate (1.3%) and retromolar area (0.5%). The lesions most often were described as blue/purple/gray or normal in color. The mean maximum diameter was 0.8 cm (range, 0.1 to 4.0 cm). In 456 cases, a history of trauma was reported, and in 366 cases a history of periodic rupture was reported. Unusual variants included superficial mucoceles (n ⫽ 3), mucoceles with myxoglobulosis (n ⫽ 6), and mucoceles with papillary synovial metaplasialike change (n ⫽ 2). Conclusions: Our results confirm the findings of previous investigators regarding the major clinicopathologic features of oral mucoceles. Special variants of oral mucoceles occur infrequently, although it is important to recognize these variants to avoid misdiagnosis. © 2011 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 69:1086-1093, 2011 Mucoceles are common lesions of the oral mucosa.1,2 These lesions result from rupture of a salivary gland duct and extravasation of mucus into the surrounding soft tissue. According to early descriptions, the oral mucocele represented a cyst lined by salivary ductal epithelium and resulting from ductal obstruction.3 However, this Received from the Medical University of South Carolina, Charleston, SC. *Associate Professor, Division of Oral Pathology, Department of Stomatology, College of Dental Medicine. †Doctoral Student, College of Dental Medicine. ‡Professor of Pathology, Director, Surgical Pathology, College of Medicine. §Distinguished University Professor, Director, Division of Oral Pathology, Department of Stomatology, College of Dental Medicine.
concept was questioned because several investigators reported an epithelial lining to be a rare or altogether absent finding in these lesions.4-6 Further evidence against this theory was provided by Bhaskar et al,4,7 Chaudhry et al,8 and Standish and Shafer,9 who reported that mucoceles could be produced experimentally in mice or rats by severing but not ligating salivary ducts. This paper was presented in part at the 61st annual meeting of the American Academy of Oral and Maxillofacial Pathology, Kansas City, MO, 2007. Address correspondence and reprint requests to Dr Chi: Division of Oral Pathology, College of Dental Medicine, Medical University of South Carolina, 173 Ashley Ave, MSC 507, Charleston, SC 29425; e-mail: [email protected] © 2011 American Association of Oral and Maxillofacial Surgeons
0278-2391/11/6904-0028$36.00/0 doi:10.1016/j.joms.2010.02.052
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Currently, we prefer to reserve the term “mucocele” (also known as mucus extravasation phenomenon or mucus escape reaction) for lesions resulting from mucin spillage from a ruptured salivary duct. The characteristic microscopic findings include mucus extravasation with an associated inflamed granulation tissue response. In some cases, there is a discrete pool of mucin surrounded by a wall of granulation tissue, whereas in other cases, the spilled mucin and associated granulation tissue response is distributed more diffusely. According to this definition, mucoceles do not exhibit a true cystic epithelial lining, although a ruptured salivary duct occasionally may be found adjacent to a mucocele. In contrast, we prefer to use the term “salivary duct cyst” (also known as the “mucus retention cyst,” “sialocyst,” or “mucus duct cyst”) for cysts lined by salivary ductal epithelium. In this report, we use the terms “mucocele” and “salivary duct cyst” as per these definitions. There have been several previously published large series of oral mucoceles. Unfortunately, it is difficult to compare findings across studies because of confusion in terminology. In some studies, the term “mucocele” has been used to refer to both extravasation and retention phenomena,10-13 and the data for each lesion type may have been reported either in aggregate10,13 or separately.11,12 In other reported large series, investigators have recognized that oral mucoceles represent extravasation phenomena; however, in some of these analyses, it is unclear whether any of the epithelial-lined lesions described represented salivary duct cysts rather than oral mucoceles.14,15 Other studies have been limited by failure to provide histopathologic inclusion criteria16 or the confusing use of the terms “mucus retention phenomenon” and “mucus retention cyst” to refer to extravasation phenomena.6,14 Also, of interest are several reports in the literature of unusual mucocele variants, including superficial mucoceles, mucoceles with myxoglobulosis (or “collagenous spherulosis”), and mucoceles with papillary synovial metaplasialike change.17-25 The superficial mucocele was first described by Eveson in 1988 as a small, translucent, tense subepithelial vesicle.17 These lesions may be solitary or multiple. Their clinical and microscopic features may be mistaken for other conditions, such as pemphigoid, bullous lichen planus, or recurrent herpes simplex virus infection.19 Myxoglobulosis is an uncommon phenomenon first described within the context of mucoceles of the vermiform appendix.26 More recently, a few cases of myxoglobulosis-like change (or “collagenous spherulosis”) within oral mucoceles have been reported as an incidental finding.21-24 This variant is characterized by eosinophilic globular structures either within the lumen or budding from the wall of oral mucoceles.
More recently, we reported 2 unusual cases of papillary synovial metaplasialike change within oral mucoceles.25 In these cases, the typical mucocele granulation tissue wall was partially replaced by a membrane exhibiting villous folds, a thin superficial band of eosinophilic matrix, and an underlying condensation of palisaded histiocytes, fibrohistiocytes, and/or multinucleated giant cells. Synovial metaplasia typically is seen in other settings, such as in association with breast implants, the bone-cement interface of hip prostheses, tendon implants, testicular implants, and traumatized skin. We believe these changes represent a response to trauma and only rarely arise within oral mucoceles. Although these mucocele variants are uncommon, we find it curious that there has been no mention of these variants in previously published large case series of oral mucoceles. Therefore, in this study, the objective was to review the clinicopathologic features of oral mucoceles. In particular, we aimed to limit our analysis to oral mucoceles (with the exclusion of salivary duct cysts) and to give special consideration to unusual mucocele variants.
Materials and Methods We performed a retrospective consecutive case review of all oral mucoceles diagnosed by the Medical University of South Carolina, Oral Pathology Biopsy Laboratory, from 1997 to 2006. For each case, we reviewed the pathology report and biopsy requisition form to obtain the patient demographic data (age, gender, and ethnicity), anatomic location, clinical description (color, size, and consistency), and clinical impression. For classification purposes, we considered the lower labial mucosa to include the lower labial vestibule and the buccal mucosa to include the buccal vestibule and commissure. For cases in which the clinical impression consisted of 2 or more diagnoses, we recorded the first diagnosis listed. In addition, we noted whether there was a known history of trauma, a reported history of periodic rupture, or the presence of multiple concurrent lesions. For cases that represented a recurrence of a previously biopsied lesion, the clinical and histopathologic data were tabulated only once. An oral and maxillofacial pathologist (A.C.) reviewed the slides for each case. The microscopic diagnosis was confirmed according to the following histopathologic criteria: mucin spillage (evident with a hematoxylin and eosin stain and/or mucicarmine stain) with an associated inflamed granulation tissue response. Occurrence of the following variants was also noted: 1) superficial mucoceles, 2) mucoceles with myxoglobulosis, and 3) mucoceles exhibiting papillary synovial metaplasialike change. Superficial
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FIGURE 1. Superficial mucocele. Characteristic microscopic features include a subepithelial vesicle containing mucin and surfaced by attenuated epithelium (hematoxylin and eosin stain, original magnification 100⫻). Chi et al. Oral Mucoceles. J Oral Maxillofac Surg 2011.
mucoceles were defined according to the clinical and microscopic features described by Eveson.17 The clinical features included a small (ⱕ5 mm), clear/translucent vesicle; the microscopic features included the following: 1) subepithelial blister containing mucin, 2) often attenuated surface epithelium, 3) possible regeneration of the epithelium across the floor of the blister, and 4) no evidence of extension of subepithelial separation at the periphery of the lesion (Fig 1). Myxoglobulosis was defined as the presence of hyalinized globular structures either free within the lumen or attached to the granulation tissue wall (Fig 2). For the purposes of this study, we classified lesions as exhibiting myxoglobulosis when these changes involved 30% or more of the lesion. Papillary synovial
FIGURE 3. Mucocele with papillary synovial metaplasialike change. A, The granulation tissue wall exhibits papillary intraluminal folds (hematoxylin and eosin, original magnification 40⫻). B, The papillary projections are surfaced by a membrane exhibiting a thin band of acellular eosinophilic matrix with an underlying condensation of palisaded histiocytes and fibrohistiocytes (hematoxylin and eosin stain, original magnification 200⫻). Chi et al. Oral Mucoceles. J Oral Maxillofac Surg 2011.
metaplasialike change was defined by the following criteria: 1) synovial-like membranes thrown into papillary folds and 2) the membrane surface included a thin band of acellular eosinophilic matrix with an underlying condensation of palisaded histiocytes, fibrohistiocytes, and/or multinucleated giant cells (Fig 3).25
Results
FIGURE 2. Mucocele with myxoglobulosis. Numerous hyalinized globular structures are seen, either free within the lumen or attached to the granulation tissue wall of this mucocele (hematoxylin and eosin stain, original magnification 100⫻). Chi et al. Oral Mucoceles. J Oral Maxillofac Surg 2011.
Out of 34,415 cases accessioned over the 10-year study period, 1,824 cases (5.3%) were diagnosed as oral mucoceles. Upon microscopic review, we excluded 15 equivocal cases in which definite mucin spillage was not evident. Among the remaining 1,809 histopathologically confirmed cases, 94 cases represented recurrences of a previously biopsied lesion. These recurrences were excluded, and the clinical
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Table 1. CLINICAL FEATURES OF ORAL MUCOCELES (N ⴝ 1,715)
Feature Gender, n (%) Male Female Age at biopsy Mean (yr) Standard error of the mean (yr) SD (yr) Range (yr) Peak decade Age not provided (n) Ethnicity, n (%) Caucasian African American Hispanic Other Ethnicity not provided Anatomic location, n (%) Lower labial mucosa Floor of mouth Ventral tongue Buccal mucosa Palate Retromolar area Location not provided Upper lip Color, n (%) Blue, purple, or gray Normal or pink Tan or white Clear Erythematous Yellow Color not provided Size of lesion (maximum diameter) Mean (cm) Standard error of the mean (cm) SD (cm) Range (cm) Size not provided (n) Consistency [No. (%)] Firm Fluctuant or soft Consistency not stated Clinical impression, n (%) Mucocele Fibroma or “tissue tag” Papilloma or verruca vulgaris Sialolithiasis Pyogenic granuloma, hemangioma, varix, or “vascular lesion” Lymphoepithelial cyst Lipoma Nonspecific inflammation/irritation Lichen planus Lymphangioma Nevus Sialadenitis Salivary neoplasm Vesiculobullous condition
Table 1. (Cont’d)
Feature
Value
Congenital epulis Clinical impression not stated Reported history of periodic rupture, n (%) Reported history of trauma, n (%) Multiple lesions present, n (%)
1 (0.1) 45 (2.6) 366 (21.3) 456 (26.6) 36 (2.1)
Value 870 (50.7) 845 (49.3) 24.9 0.4 16.1 1-87 2nd 29 1,352 (78.8) 174 (10.1) 26 (1.5) 24 (1.4) 139 (8.1) 1,405 (81.9) 99 (5.8) 86 (5.0) 82 (4.8) 23 (1.3) 9 (0.5) 11 (0.6) 0 (0) 501 (29.2) 426 (24.8) 207 (12.1) 107 (6.2) 91 (5.3) 44 (2.6) 339 (19.8) 0.8 0.1 0.5 0.1-4.0 110 173 (10.1) 268 (15.6) 1,274 (74.3) 1,431 (83.4) 159 (9.3) 29 (1.7) 16 (0.9) 12 (0.7) 7 (0.4) 6 (0.3) 3 (0.2) 1 (0.1) 1 (0.1) 1 (0.1) 1 (0.1) 1 (0.1) 1 (0.1)
Chi et al. Oral Mucoceles. J Oral Maxillofac Surg 2011.
data for the 1,715 oral mucoceles included in our analysis are presented in Table 1. With regard to superficial mucoceles, 43 cases (2.5%) fulfilled the clinical definition only, 27 cases (1.6%) fulfilled the microscopic definition only, and 3 cases (0.2%) fulfilled both the clinical and microscopic definitions. There were only 530 cases for which the clinical description was adequate enough to assess whether the clinical case definition was met. The 3 cases that fulfilled both the clinical and microscopic definitions included a 65-year-old woman with a 3-mm lesion on the buccal mucosa, a 36-year-old woman with a 3-mm lesion on the floor of the mouth, and a woman of unknown age with a 2-mm lesion on the lower labial mucosa. Myxoglobulosis was evident in 6 cases (0.4%), and papillary synovial metaplasialike change was present in only 2 cases (0.1%).
Discussion This study represents the second largest case series of oral mucoceles reported to date. Our results confirm the findings of previous investigators regarding the clinical features of oral mucoceles (Table 2). We found no significant gender predilection, which is consistent with most other large case series.6,8,11,13-15 Most of our cases (66%) arose in children or young adults (ie, patients ⱕ30 years old). Similarly, more than half (57% to 78%) of cases occurred in the first 3 decades in the series reported by Harrison,11 Cohen,12 Oliveira et al,13 Robinson and Hjørting-Hansen,14 Elzay et al,16 Praetorius and Hammerström,27 and Koudelka.28 In our study, the lower lip was the most common site, followed by the floor of mouth, ventral tongue, and buccal mucosa. Likewise, most previous authors have reported the lower lip as the most common site with the buccal mucosa, floor of mouth, and/or tongue as additional frequent sites.6,11-16,27,28 We recognize that there is some potential for confusion when comparing anatomic distribution between studies. For instance, some authors may have included ventral tongue lesions among lesions involving the floor of mouth, and lesions in the commissure region may have been classified as involving either the buccal or labial mucosa.
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Table 2. CLINICAL FEATURES OF ORAL MUCOCELES FOUND IN THE CURRENT STUDY AND PREVIOUSLY REPORTED LARGE CASE SERIES IN THE ENGLISH-LANGUAGE LITERATURE Authors
N
Gender, n (%)
1,715
Males: 870 (51) Females: 845 (49)
Cataldo and Mosadomi15
594
Males: 292 (49) Females: 302 (51)
Chaudhry et al8
66
Males: 36 (55) Females: 27 (41) Not provided: 3 (5)
Cohen12
80
Males: 48 (60) Females: 32 (40)
161
Males: 92 (58) Females: 67 (42) Gender not provided: 2 (1)
45
Males: 22 (49) Females: 23 (51)
Chi et al
Elzay16
Harrison11
Koudelka28 (AFIP Registry)
2,339
3:1 Male-tofemale ratio; among civilian cases only: 53.1% male and 46.9% female
Age Distribution by Decade, n (%) 1st decade: 344 (20) 2nd decade: 507 (30) 3rd decade: 280 (16) 4th decade: 249 (15) 5th decade: 164 (10) 6th decade: 90 (5) 7th decade: 40 (2) 8th decade: 11 (⬍1) 9th decade: 1 (⬍1) Age not provided: 29 (2) 1st decade: 44 (7) 2nd decade: 96 (16) 3rd decade: 156 (26) 4th decade: 92 (15) 5th decade: 70 (12) 6th decade: 58 (10) 7th decade: 34 (6) 8th decade: 31 (5) 9th decade: 10 (2) 10th decade: 2 (⬍1) 11th decade: 1 (⬍1) 1st decade: 5 (8) 2nd decade: 13 (20) 3rd decade: 14 (21) 4th decade: 5 (8) 5th decade: 5 (8) 6th decade: 3 (5) 7th decade: 4 (6) 8th decade: 2 (3) Age not provided: 15 (23) 1st decade: 10 (13) 2nd decade: 17 (21) 3rd decade: 21 (26) 4th decade: 14 (18) 5th decade: 7 (9) 6th decade: 6 (8) 7th decade: 2 (3) Age not provided: 3 (4) 1st decade: 23 (11) 2nd decade: 42 (26) 3rd decade: 30 (20) 4th decade: 21 (14) 5th decade: 13 (9) 6th decade: 10 (7) 7th decade: 9 (6) 8th decade: 1 (⬍1) Age not provided: 12 (7) 1st decade: 7 (16) 2nd decade: 11 (24) 3rd decade: 8 (18) 4th decade: 9 (20) 5th decade: 6 (13) 6th decade: 3 (7) 7th decade: 1 (2) (Age distribution by decade not stated)
Anatomic Location, n (%)
Comment
Lower lip: 1,405 (82) Floor of mouth: 99 (6) Ventral tongue: 86 (5) Buccal mucosa: 82 (5) Palate: 23 (1) Retromolar area: 9 (⬍1) Location not provided: 11 (⬍1)
Lower lip: 348 (59) Buccal mucosa: 101 (17) Floor of mouth: 73 (12) Palate: 25 (4) Tongue: 15 (3) Upper lip: 11 (2) Other: 21 (4)
24 cases had an epithelial lining and may have been salivary duct cysts
Lower lip: 45 (68) Buccal: 7 (11) Alveolar ridge: 3 (5) Palate: 2 (3) Tonsillar region: 2 (3) Upper lip: 2 (3) Vestibule: 1 (2) Floor of mouth: 1 (2) Location not provided: 3 (5) Lower lip: 52 (65) Floor of mouth: 16 (20) Cheek: 8 (10) Retromolar fossa: 2 (3) Tongue: 1 (⬍1) Junction of hard and soft palates: 1 (⬍1)
10 cases appear to have been salivary duct cysts
Lower lip: 101 (63) Floor of mouth: 19 (12) Buccal mucosa: 16 (10) Palate: number not stated Retromolar: number not stated Alveolar ridge: number not stated Upper lip: number not stated
Histopathologic inclusion criteria not stated
Lower lip: 33 (7) Floor of mouth: 3 (7) Cheek: 5 (11) Tongue: 2 (4) Upper lip: 1 (2) Retromolar: 1 (2)
Data are for “extravasation type” mucoceles only
Lower lip: 766 (36) Lip (not otherwise specified): 727 (34) Buccal mucosa: 179 (8) Floor of mouth: 148 (7) Tongue: 143 (7) Palate: 82 (4) Oral cavity (not otherwise specified): 73 (3) Upper lip: 9 (⬍1) Mandible: 9 (⬍1) Gingiva: 8 (⬍1) Retromolar area: 4 (⬍1) Minor salivary glands: 4 (⬍1) Maxilla: 1 (⬍1) Site not stated: 115 (5)
Location data shown here for intraoral cases only (total number of cases and age data refer to entire data set, which included major gland and oropharyngeal case)
7 cases were salivary duct cysts
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Table 2. (Cont’d) Authors
N
Gender, n (%)
Oliveira et al13
112
“Evenly distributed between genders” (numbers not given)
Praetorius and Hammarström27
188
Males: 108 (57) Females: 80 (43)
Robinson and HjørtingHansen14
125
Males: 54 (43) Females: 59 (47) Gender not provided: 16 (13)
Standish and Shafer6
97
Males: 48 (51) Females: 47 (49)
Age Distribution by Decade, n (%) 1st decade: 16 (14) 2nd decade: 51 (46) 3rd decade: 20 (18) 4th decade: 6 (5) 5th decade: 8 (7) 6th decade: 7 (6) Age not provided: 4 (4) 1st decade: 21 (11) 2nd decade: 71 (38) 3rd decade: 42 (22) 4th decade: 22 (12) 5th decade: 19 (10) 6th decade: 7 (4) 7th decade: 4 (2) 8th decade: 2 (1) 1st decade: 20 (16) 2nd decade: 35 (28) 3rd decade: 24 (19) 4th decade: 13 (10) 5th decade: 10 (8) 6th decade: 7 (6) 7th decade and older: 4 (3) Age not provided: 12 (10)
1st decade: 11 (12) 2nd decade: 17 (18) 3rd decade: 15 (16) 4th decade: 16 (17) 5th decade: 14 (15) 6th decade: 11 (11) 7th decade and older: 5 (5) Age not provided: 6 (6)
Anatomic Location, n (%) Lower lip: 58 (52) Tongue: 16 (14) Buccal mucosa: 6 (5) Floor of mouth: 6 (5) Other: 7 (6) Upper lip: 3 (3) Location not provided: 16 (7) Lower lip: 129 (69) Floor of mouth: 29 (15) Buccal mucosa: 22 (12) Ventral tongue: 3 (2) Palate: 2 (1) Upper lip: 2 (1) Gingiva: 1 (1) Lower lip: 64 (52) Buccal mucosa: 13 (11) Floor of mouth: 13 (11) Tongue: 6 (4) Lip (not otherwise specified): 6 (4) Gingiva: 4 (3) Palate: 3 (2) Upper lip: 3 (2) Location not provided: 13 (11) Lower lip: 43 (44) Buccal mucosa: 15 (16) Floor of mouth and ventral tongue: 15 (16) Palate: 7 (7) Retromolar region: 5 (5) Location not provided: 12 (12)
Comment
Did not have an epithelial lining except for possibly an adjacent salivary duct
11 cases may have been salivary duct cysts
6 cases had a partial or complete epithelial lining, although most of these lesions appeared to have opened up to mucous pools
Chi et al. Oral Mucoceles. J Oral Maxillofac Surg 2011.
In striking contrast with the lower labial mucosa, which was by far the most commonly involved anatomic location (82% of cases), not a single case occurred in the upper labial mucosa. Similarly, Standish and Shafer6 and Cohen12 found no upper lip involvement in their reported series, and other authors have found only a small number of cases arising in the upper lip (1% to 3%) in their series.8,11,13-16,27 It is uncertain whether any of these upper lip cases actually may have represented salivary duct cysts instead of mucoceles. The reason for this marked predilection for the lower lip is uncertain. Some authors have proposed that parafunctional habits, such as lip biting, may favor mucocele development in the lower lip.29 In addition, in contrast to the upper lip, the lower lip possesses greater mass, kinematic demands during speech, force generating capability, and force control.30 Perhaps such differences in physical properties may account in part for the striking disparity between lower and upper lip involvement. Furthermore, we surmise that the greater number and density of salivary glands in the lower lip compared with the upper lip,31,32 combined with downward forces of gravity, may play a role in the predilection for mucocele development in the lower lip. A few previously published large case series appear to have included salivary duct cysts in their analysis of oral mucoceles.14,15 However, we felt it was important to
exclude salivary duct cysts from our analysis on the basis of previous reports suggesting that salivary duct cysts and mucoceles exhibit distinct clinicopathologic features. In particular, salivary duct cysts of the oral minor salivary glands appear to be less common and tend to arise in an older patient population compared with mucoceles. In addition, salivary duct cysts do not exhibit such a marked predilection for the lower lip as do mucoceles.11,12,27,33 In a review of 121 cases of salivary duct cysts, Eversole33 noted 3 histopathologic subtypes: 1) “true mucous retention cysts” lined by nononcocytic ductal epithelium and exhibiting minimal inflammation, 2) “reactive oncocytoid cysts” exhibiting oncocytic metaplasia, and 3) “mucopapillary cysts” with a papillary, multicystic growth pattern and regions of pronounced mucous metaplasia. Given that salivary duct cysts are much less common than mucoceles, including them in an aggregate analysis of oral mucoceles probably would not have altered the results significantly. Nevertheless, we believe it is important to distinguish between the 2 lesion types because they do appear to represent distinct clinicopathologic entities. There are limited data in the existing literature regarding the frequency of unusual mucocele variants. To the best of our knowledge, we are the only authors to have reported papillary synovial metaplasialike change within oral mucoceles,25 and this re-
1092 view of cases shows this variant to be extremely rare (0.1% of cases). Our attempt to determine the frequency of superficial mucoceles was limited by the large number of cases with incomplete clinical descriptions. We identified only 3 cases (0.2%) that met both the clinical and microscopic case definitions for a superficial mucocele; however, we believe the true frequency was likely greater. In addition, we acknowledge that superficial mucoceles often are not biopsied because of their transient nature. Our cases are consistent with previous reports suggesting that superficial muco celes most commonly arise in women aged 30 years or older.17,19,20,34,35 Among previously reported superficial mucoceles, the most commonly involved sites have included the soft palate, retromolar pad, and buccal mucosa.17,19,20,34-36 Our 3 cases arose on the buccal mucosa, lower labial mucosa, and floor of mouth. A few authors have observed an association between superficial mucoceles and lichen planus or lichenoid graft-versus-host disease17,19,36; however, we did not find any such disease associations among our cases. Reports regarding the frequency of myxoglobulosis in oral mucoceles are variable. A few authors have found this variant to be rare. In their report of a 10-year-old girl with a mucocele exhibiting myxoglobulosis, Li et al21 noted no other myxoglobulosis cases after reviewing 657 oral mucoceles in their files. In addition, Ide and Kusama24 found only 1 such case after reviewing all mucoceles diagnosed over a 30year period. Likewise, we found a very low frequency of myxoglobulosis (0.4%) among the 1,715 oral mucoceles we reviewed over a 10-year study period. In contrast, Shah23 observed globular structures consistent with myxoglobulosis in 22 of 71 (31%) extravasation mucoceles diagnosed over a period of 32 months. We believe the higher frequency of myxoglobulosis reported by Shah compared with our study and those of other authors may be related to differences in case definition. We surmise that Shah likely included cases with only focal features of myxoglobulosis. Indeed, we found isolated globular structures to be a fairly common finding among oral mucoceles; however, only a small number of cases fulfilled our myxoglobulosis case definition, which required characteristic microscopic features to occupy 30% or more of the lesion. Myxoglobulosis and papillary synovial metaplasialike changes appear to represent incidental findings among oral mucoceles. The clinical presentation for these variants did not differ significantly from the overall mucocele dataset. However, a notable finding was that in 1 case of papillary synovial metaplasialike change, the patient had a history of rubbing the lower labial lesion against the adjacent mandibular teeth.
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We surmise that this habit was a source of gliding trauma, which stimulated the development of synovial metaplasialike change. It is peculiar that in other large case series of oral mucoceles, there has been no mention of unusual mucocele variants. In these variants, the classic histopathologic findings of a mucocele typically are present in at least part of the lesion. Therefore, perhaps other authors have not remarked on such cases because they deemed the diagnosis to be readily evident. Nevertheless, we feel that it is important for pathologists to be aware of these rare variants to avoid misdiagnosis. In particular, the superficial mucocele potentially may be confused with immunemediated subepithelial vesiculobullous conditions (such as pemphigoid or bullous lichen planus) or the vesicles of recurrent herpes simplex virus infection.19 Also, mucoceles with papillary synovial metaplasialike change should be distinguished from salivary neoplasms with a papillary cystic growth pattern (such as oncocytic papillary cystadenoma or Warthin tumor).25 In conclusion, we have presented one of the largest case series of oral mucoceles reported to date. Our results confirm the findings of previous investigators regarding the major clinicopathologic features of oral mucoceles, including a marked predilection for the lower lip and young individuals. Special variants of oral mucoceles occur infrequently, although it is important to recognize these variants to avoid misdiagnosis.
References 1. Bouquot JE: Common oral lesions found during a mass screening examination. J Am Dent Assoc 112:50, 1986 2. Shulman JD, Beach MM, Rivera-Hidalgo F: The prevalence of oral mucosal lesions in U.S. adults: Data from the third national health and nutrition examination survey, 1988-94. J Am Dent Assoc 135:1279, 2004 3. Thoma KH: Cysts of the Salivary and Mucous Glands: Oral Pathology (ed 3). St. Louis, MO, CV Mosby, 1950, pp 1260-1265 4. Bhaskar SN, Bolden TE, Weinmann JP: Pathogenesis of mucoceles. J Dent Res 35:863, 1956 5. Moller JF, Mukosacyster: I mundhulen. Tandlaegebladet 62: 263, 1958 6. Standish SM, Shafer WG: The mucus retention phenomenon. J Oral Surg Anesth Hosp Dent Serv 17:15, 1959 7. Bhaskar SN, Bolden TE, Weinmann JP: Experimental obstructive adenitis in the mouse. J Dent Res 35:852, 1956 8. Chaudhry AP, Reynolds DH, Lachapelle CF, et al: A clinical and experimental study of mucocele (retention cyst). J Dent Res 39:1253, 1960 9. Standish SM, Shafer WG: Serial histologic effects of rat submaxillary and sublingual salivary gland duct and blood vessel ligation. J Dent Res 36:866, 1957 10. Yamasoba T, Tayama N, Syoji M, et al: Clinicostatistical study of lower lip mucoceles. Head Neck 12:316, 1990 11. Harrison JD: Salivary mucoceles. Oral Surg Oral Med Oral Pathol 39:268, 1975 12. Cohen L: Mucoceles of the oral cavity. Oral Surg Oral Med Oral Pathol 19:365, 1965 13. Oliveira DT, Consolaro A, Freitas FJ: Histopathological spectrum of 112 cases of mucocele. Braz Dent J 4:29, 1993
CHI ET AL 14. Robinson L, Hjørting-Hansen E: Pathologic changes associated with mucous retention cysts of minor salivary glands. Oral Surg Oral Med Oral Pathol 18:191, 1964 15. Cataldo E, Mosadomi A: Mucoceles of the oral mucous membrane. Arch Otolaryngol 91:360, 1970 16. Elzay RP, Sweeney WT, Peters PB, et al: Oral mucoceles: A review of 161 cases. Va Dent J 45:15, 1968 17. Eveson JW: Superficial mucoceles: Pitfall in clinical and microscopic diagnosis. Oral Surg Oral Med Oral Pathol 66:318, 1988 18. Flaitz CM: Superficial mucoceles of the lower lip. Am J Dent 14:187, 2001 19. Bermejo A, Aguirre JM, Lopez P, et al: Superficial mucocele: Report of 4 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 88:469, 1999 20. Jensen JL: Superficial mucoceles of the oral mucosa. Am J Dermatopathol 12:88, 1990 21. Li TJ, Kitano M, Yoshida A, et al: Myxoglobulosis in an extravasation mucocele of the lower lip. J Oral Pathol Med 26:342, 1997 22. Henry CR, Nace M, Helm KF: Collagenous spherulosis in an oral mucous cyst. J Cutan Pathol 35:428, 2008 23. Shah KA: Myxoglobulosis in oral extravasation mucocele: An entity? Histopathology 43:291, 2003 24. Ide F, Kusama K: Myxoglobulosis-like change in a lower lip mucocele. Histopathology 40:575, 2002 25. Chi AC, Haigney RJ, Spagnoli DB, et al: Papillary synovial metaplasia-like change in oral mucoceles: A rare and previously undescribed histopathologic variant of a common oral lesion. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 109:268, 2010
1093 26. Lubin J, Berle E: Myxoglobulosis of the appendix. Report of two cases. Arch Pathol 94:533, 1972 27. Praetorius F, Hammarström L: A new concept of the pathogenesis of oral mucous cysts based on a study of 200 cases. J Dent Assoc S Afr 47:226, 1992 28. Koudelka BM: Obstructive disorders, in Ellis GL, Auclair PL, Gnepp DR (eds): Surgical Pathology of the Salivary Glands. Philadelphia, PA, Saunders, 1991, pp 26-38 29. Mustapha IZ, Boucree SA Jr: Mucocele of the upper lip: Case report of an uncommon presentation and its differential diagnosis. J Can Dent Assoc 70:318, 2004 30. Barlow SM, Rath EM: Maximum voluntary closing forces in the upper and lower lips of humans. J Speech Hear Res 28:373, 1985 31. Sumi M, Yamada T, Takagi Y, et al: MR imaging of labial glands. AJNR Am J Neuroradiol 28:1552, 2007 32. Gaubenshtok LM, Leont’ev VK: [The quantitative topographic characteristics of the minor salivary glands of the lips]. Stomatologiia (Mosk) 69:28, 1990 33. Eversole LR: Oral sialocysts. Arch Otolaryngol Head Neck Surg 113:51, 1987 34. Mandel L: Multiple superficial oral mucoceles: Case report. J Oral Maxillofac Surg 59:928, 2001 35. Jinbu Y, Tsukinoki K, Kusama M, et al: Recurrent multiple superficial mucocele on the palate: Histopathology and laser vaporization. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 95:193, 2003 36. Garcia FVMJ, Pascual-Lopez M, Elices M, et al: Superficial mucoceles and lichenoid graft versus host disease: Report of three cases. Acta Derm Venereol 82:453, 2002
Oral Mucoceles: A Clinicopathologic Review of 1,824 Cases, Including Unusual Variants Angela C. Chi, DMD,* Paul R. Lambert III, BS, MBA,† Mary S. Richardson, DDS, MD,‡ and Brad W. Neville, DDS§ Purpose: To review the clinicopathologic features of oral mucoceles, with special consideration given
to unusual variants and exclusion of salivary duct cysts. Materials and Methods: This was a retrospective consecutive case review of all oral mucoceles diagnosed by the Medical University of South Carolina, Oral Pathology Biopsy Laboratory, from 1997 to 2006. The following data were recorded: patient demographics, clinical features (anatomic location, color, size, and consistency), clinical impression, history of trauma, history of periodic rupture, and occurrence of unusual mucocele variants. Results: During the study period, 1,824 oral mucoceles were diagnosed. Of these cases, 1,715 represented histopathologically confirmed cases that were not recurrences. There was no significant gender predilection, and the average age was 24.9 years. The most common locations were the lower labial mucosa (81.9%), floor of mouth (5.8%), ventral tongue (5.0%), and buccal mucosa (4.8%); infrequent sites included the palate (1.3%) and retromolar area (0.5%). The lesions most often were described as blue/purple/gray or normal in color. The mean maximum diameter was 0.8 cm (range, 0.1 to 4.0 cm). In 456 cases, a history of trauma was reported, and in 366 cases a history of periodic rupture was reported. Unusual variants included superficial mucoceles (n ⫽ 3), mucoceles with myxoglobulosis (n ⫽ 6), and mucoceles with papillary synovial metaplasialike change (n ⫽ 2). Conclusions: Our results confirm the findings of previous investigators regarding the major clinicopathologic features of oral mucoceles. Special variants of oral mucoceles occur infrequently, although it is important to recognize these variants to avoid misdiagnosis. © 2011 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 69:1086-1093, 2011 Mucoceles are common lesions of the oral mucosa.1,2 These lesions result from rupture of a salivary gland duct and extravasation of mucus into the surrounding soft tissue. According to early descriptions, the oral mucocele represented a cyst lined by salivary ductal epithelium and resulting from ductal obstruction.3 However, this Received from the Medical University of South Carolina, Charleston, SC. *Associate Professor, Division of Oral Pathology, Department of Stomatology, College of Dental Medicine. †Doctoral Student, College of Dental Medicine. ‡Professor of Pathology, Director, Surgical Pathology, College of Medicine. §Distinguished University Professor, Director, Division of Oral Pathology, Department of Stomatology, College of Dental Medicine.
concept was questioned because several investigators reported an epithelial lining to be a rare or altogether absent finding in these lesions.4-6 Further evidence against this theory was provided by Bhaskar et al,4,7 Chaudhry et al,8 and Standish and Shafer,9 who reported that mucoceles could be produced experimentally in mice or rats by severing but not ligating salivary ducts. This paper was presented in part at the 61st annual meeting of the American Academy of Oral and Maxillofacial Pathology, Kansas City, MO, 2007. Address correspondence and reprint requests to Dr Chi: Division of Oral Pathology, College of Dental Medicine, Medical University of South Carolina, 173 Ashley Ave, MSC 507, Charleston, SC 29425; e-mail: [email protected] © 2011 American Association of Oral and Maxillofacial Surgeons
0278-2391/11/6904-0028$36.00/0 doi:10.1016/j.joms.2010.02.052
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Currently, we prefer to reserve the term “mucocele” (also known as mucus extravasation phenomenon or mucus escape reaction) for lesions resulting from mucin spillage from a ruptured salivary duct. The characteristic microscopic findings include mucus extravasation with an associated inflamed granulation tissue response. In some cases, there is a discrete pool of mucin surrounded by a wall of granulation tissue, whereas in other cases, the spilled mucin and associated granulation tissue response is distributed more diffusely. According to this definition, mucoceles do not exhibit a true cystic epithelial lining, although a ruptured salivary duct occasionally may be found adjacent to a mucocele. In contrast, we prefer to use the term “salivary duct cyst” (also known as the “mucus retention cyst,” “sialocyst,” or “mucus duct cyst”) for cysts lined by salivary ductal epithelium. In this report, we use the terms “mucocele” and “salivary duct cyst” as per these definitions. There have been several previously published large series of oral mucoceles. Unfortunately, it is difficult to compare findings across studies because of confusion in terminology. In some studies, the term “mucocele” has been used to refer to both extravasation and retention phenomena,10-13 and the data for each lesion type may have been reported either in aggregate10,13 or separately.11,12 In other reported large series, investigators have recognized that oral mucoceles represent extravasation phenomena; however, in some of these analyses, it is unclear whether any of the epithelial-lined lesions described represented salivary duct cysts rather than oral mucoceles.14,15 Other studies have been limited by failure to provide histopathologic inclusion criteria16 or the confusing use of the terms “mucus retention phenomenon” and “mucus retention cyst” to refer to extravasation phenomena.6,14 Also, of interest are several reports in the literature of unusual mucocele variants, including superficial mucoceles, mucoceles with myxoglobulosis (or “collagenous spherulosis”), and mucoceles with papillary synovial metaplasialike change.17-25 The superficial mucocele was first described by Eveson in 1988 as a small, translucent, tense subepithelial vesicle.17 These lesions may be solitary or multiple. Their clinical and microscopic features may be mistaken for other conditions, such as pemphigoid, bullous lichen planus, or recurrent herpes simplex virus infection.19 Myxoglobulosis is an uncommon phenomenon first described within the context of mucoceles of the vermiform appendix.26 More recently, a few cases of myxoglobulosis-like change (or “collagenous spherulosis”) within oral mucoceles have been reported as an incidental finding.21-24 This variant is characterized by eosinophilic globular structures either within the lumen or budding from the wall of oral mucoceles.
More recently, we reported 2 unusual cases of papillary synovial metaplasialike change within oral mucoceles.25 In these cases, the typical mucocele granulation tissue wall was partially replaced by a membrane exhibiting villous folds, a thin superficial band of eosinophilic matrix, and an underlying condensation of palisaded histiocytes, fibrohistiocytes, and/or multinucleated giant cells. Synovial metaplasia typically is seen in other settings, such as in association with breast implants, the bone-cement interface of hip prostheses, tendon implants, testicular implants, and traumatized skin. We believe these changes represent a response to trauma and only rarely arise within oral mucoceles. Although these mucocele variants are uncommon, we find it curious that there has been no mention of these variants in previously published large case series of oral mucoceles. Therefore, in this study, the objective was to review the clinicopathologic features of oral mucoceles. In particular, we aimed to limit our analysis to oral mucoceles (with the exclusion of salivary duct cysts) and to give special consideration to unusual mucocele variants.
Materials and Methods We performed a retrospective consecutive case review of all oral mucoceles diagnosed by the Medical University of South Carolina, Oral Pathology Biopsy Laboratory, from 1997 to 2006. For each case, we reviewed the pathology report and biopsy requisition form to obtain the patient demographic data (age, gender, and ethnicity), anatomic location, clinical description (color, size, and consistency), and clinical impression. For classification purposes, we considered the lower labial mucosa to include the lower labial vestibule and the buccal mucosa to include the buccal vestibule and commissure. For cases in which the clinical impression consisted of 2 or more diagnoses, we recorded the first diagnosis listed. In addition, we noted whether there was a known history of trauma, a reported history of periodic rupture, or the presence of multiple concurrent lesions. For cases that represented a recurrence of a previously biopsied lesion, the clinical and histopathologic data were tabulated only once. An oral and maxillofacial pathologist (A.C.) reviewed the slides for each case. The microscopic diagnosis was confirmed according to the following histopathologic criteria: mucin spillage (evident with a hematoxylin and eosin stain and/or mucicarmine stain) with an associated inflamed granulation tissue response. Occurrence of the following variants was also noted: 1) superficial mucoceles, 2) mucoceles with myxoglobulosis, and 3) mucoceles exhibiting papillary synovial metaplasialike change. Superficial
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FIGURE 1. Superficial mucocele. Characteristic microscopic features include a subepithelial vesicle containing mucin and surfaced by attenuated epithelium (hematoxylin and eosin stain, original magnification 100⫻). Chi et al. Oral Mucoceles. J Oral Maxillofac Surg 2011.
mucoceles were defined according to the clinical and microscopic features described by Eveson.17 The clinical features included a small (ⱕ5 mm), clear/translucent vesicle; the microscopic features included the following: 1) subepithelial blister containing mucin, 2) often attenuated surface epithelium, 3) possible regeneration of the epithelium across the floor of the blister, and 4) no evidence of extension of subepithelial separation at the periphery of the lesion (Fig 1). Myxoglobulosis was defined as the presence of hyalinized globular structures either free within the lumen or attached to the granulation tissue wall (Fig 2). For the purposes of this study, we classified lesions as exhibiting myxoglobulosis when these changes involved 30% or more of the lesion. Papillary synovial
FIGURE 3. Mucocele with papillary synovial metaplasialike change. A, The granulation tissue wall exhibits papillary intraluminal folds (hematoxylin and eosin, original magnification 40⫻). B, The papillary projections are surfaced by a membrane exhibiting a thin band of acellular eosinophilic matrix with an underlying condensation of palisaded histiocytes and fibrohistiocytes (hematoxylin and eosin stain, original magnification 200⫻). Chi et al. Oral Mucoceles. J Oral Maxillofac Surg 2011.
metaplasialike change was defined by the following criteria: 1) synovial-like membranes thrown into papillary folds and 2) the membrane surface included a thin band of acellular eosinophilic matrix with an underlying condensation of palisaded histiocytes, fibrohistiocytes, and/or multinucleated giant cells (Fig 3).25
Results
FIGURE 2. Mucocele with myxoglobulosis. Numerous hyalinized globular structures are seen, either free within the lumen or attached to the granulation tissue wall of this mucocele (hematoxylin and eosin stain, original magnification 100⫻). Chi et al. Oral Mucoceles. J Oral Maxillofac Surg 2011.
Out of 34,415 cases accessioned over the 10-year study period, 1,824 cases (5.3%) were diagnosed as oral mucoceles. Upon microscopic review, we excluded 15 equivocal cases in which definite mucin spillage was not evident. Among the remaining 1,809 histopathologically confirmed cases, 94 cases represented recurrences of a previously biopsied lesion. These recurrences were excluded, and the clinical
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Table 1. CLINICAL FEATURES OF ORAL MUCOCELES (N ⴝ 1,715)
Feature Gender, n (%) Male Female Age at biopsy Mean (yr) Standard error of the mean (yr) SD (yr) Range (yr) Peak decade Age not provided (n) Ethnicity, n (%) Caucasian African American Hispanic Other Ethnicity not provided Anatomic location, n (%) Lower labial mucosa Floor of mouth Ventral tongue Buccal mucosa Palate Retromolar area Location not provided Upper lip Color, n (%) Blue, purple, or gray Normal or pink Tan or white Clear Erythematous Yellow Color not provided Size of lesion (maximum diameter) Mean (cm) Standard error of the mean (cm) SD (cm) Range (cm) Size not provided (n) Consistency [No. (%)] Firm Fluctuant or soft Consistency not stated Clinical impression, n (%) Mucocele Fibroma or “tissue tag” Papilloma or verruca vulgaris Sialolithiasis Pyogenic granuloma, hemangioma, varix, or “vascular lesion” Lymphoepithelial cyst Lipoma Nonspecific inflammation/irritation Lichen planus Lymphangioma Nevus Sialadenitis Salivary neoplasm Vesiculobullous condition
Table 1. (Cont’d)
Feature
Value
Congenital epulis Clinical impression not stated Reported history of periodic rupture, n (%) Reported history of trauma, n (%) Multiple lesions present, n (%)
1 (0.1) 45 (2.6) 366 (21.3) 456 (26.6) 36 (2.1)
Value 870 (50.7) 845 (49.3) 24.9 0.4 16.1 1-87 2nd 29 1,352 (78.8) 174 (10.1) 26 (1.5) 24 (1.4) 139 (8.1) 1,405 (81.9) 99 (5.8) 86 (5.0) 82 (4.8) 23 (1.3) 9 (0.5) 11 (0.6) 0 (0) 501 (29.2) 426 (24.8) 207 (12.1) 107 (6.2) 91 (5.3) 44 (2.6) 339 (19.8) 0.8 0.1 0.5 0.1-4.0 110 173 (10.1) 268 (15.6) 1,274 (74.3) 1,431 (83.4) 159 (9.3) 29 (1.7) 16 (0.9) 12 (0.7) 7 (0.4) 6 (0.3) 3 (0.2) 1 (0.1) 1 (0.1) 1 (0.1) 1 (0.1) 1 (0.1) 1 (0.1)
Chi et al. Oral Mucoceles. J Oral Maxillofac Surg 2011.
data for the 1,715 oral mucoceles included in our analysis are presented in Table 1. With regard to superficial mucoceles, 43 cases (2.5%) fulfilled the clinical definition only, 27 cases (1.6%) fulfilled the microscopic definition only, and 3 cases (0.2%) fulfilled both the clinical and microscopic definitions. There were only 530 cases for which the clinical description was adequate enough to assess whether the clinical case definition was met. The 3 cases that fulfilled both the clinical and microscopic definitions included a 65-year-old woman with a 3-mm lesion on the buccal mucosa, a 36-year-old woman with a 3-mm lesion on the floor of the mouth, and a woman of unknown age with a 2-mm lesion on the lower labial mucosa. Myxoglobulosis was evident in 6 cases (0.4%), and papillary synovial metaplasialike change was present in only 2 cases (0.1%).
Discussion This study represents the second largest case series of oral mucoceles reported to date. Our results confirm the findings of previous investigators regarding the clinical features of oral mucoceles (Table 2). We found no significant gender predilection, which is consistent with most other large case series.6,8,11,13-15 Most of our cases (66%) arose in children or young adults (ie, patients ⱕ30 years old). Similarly, more than half (57% to 78%) of cases occurred in the first 3 decades in the series reported by Harrison,11 Cohen,12 Oliveira et al,13 Robinson and Hjørting-Hansen,14 Elzay et al,16 Praetorius and Hammerström,27 and Koudelka.28 In our study, the lower lip was the most common site, followed by the floor of mouth, ventral tongue, and buccal mucosa. Likewise, most previous authors have reported the lower lip as the most common site with the buccal mucosa, floor of mouth, and/or tongue as additional frequent sites.6,11-16,27,28 We recognize that there is some potential for confusion when comparing anatomic distribution between studies. For instance, some authors may have included ventral tongue lesions among lesions involving the floor of mouth, and lesions in the commissure region may have been classified as involving either the buccal or labial mucosa.
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Table 2. CLINICAL FEATURES OF ORAL MUCOCELES FOUND IN THE CURRENT STUDY AND PREVIOUSLY REPORTED LARGE CASE SERIES IN THE ENGLISH-LANGUAGE LITERATURE Authors
N
Gender, n (%)
1,715
Males: 870 (51) Females: 845 (49)
Cataldo and Mosadomi15
594
Males: 292 (49) Females: 302 (51)
Chaudhry et al8
66
Males: 36 (55) Females: 27 (41) Not provided: 3 (5)
Cohen12
80
Males: 48 (60) Females: 32 (40)
161
Males: 92 (58) Females: 67 (42) Gender not provided: 2 (1)
45
Males: 22 (49) Females: 23 (51)
Chi et al
Elzay16
Harrison11
Koudelka28 (AFIP Registry)
2,339
3:1 Male-tofemale ratio; among civilian cases only: 53.1% male and 46.9% female
Age Distribution by Decade, n (%) 1st decade: 344 (20) 2nd decade: 507 (30) 3rd decade: 280 (16) 4th decade: 249 (15) 5th decade: 164 (10) 6th decade: 90 (5) 7th decade: 40 (2) 8th decade: 11 (⬍1) 9th decade: 1 (⬍1) Age not provided: 29 (2) 1st decade: 44 (7) 2nd decade: 96 (16) 3rd decade: 156 (26) 4th decade: 92 (15) 5th decade: 70 (12) 6th decade: 58 (10) 7th decade: 34 (6) 8th decade: 31 (5) 9th decade: 10 (2) 10th decade: 2 (⬍1) 11th decade: 1 (⬍1) 1st decade: 5 (8) 2nd decade: 13 (20) 3rd decade: 14 (21) 4th decade: 5 (8) 5th decade: 5 (8) 6th decade: 3 (5) 7th decade: 4 (6) 8th decade: 2 (3) Age not provided: 15 (23) 1st decade: 10 (13) 2nd decade: 17 (21) 3rd decade: 21 (26) 4th decade: 14 (18) 5th decade: 7 (9) 6th decade: 6 (8) 7th decade: 2 (3) Age not provided: 3 (4) 1st decade: 23 (11) 2nd decade: 42 (26) 3rd decade: 30 (20) 4th decade: 21 (14) 5th decade: 13 (9) 6th decade: 10 (7) 7th decade: 9 (6) 8th decade: 1 (⬍1) Age not provided: 12 (7) 1st decade: 7 (16) 2nd decade: 11 (24) 3rd decade: 8 (18) 4th decade: 9 (20) 5th decade: 6 (13) 6th decade: 3 (7) 7th decade: 1 (2) (Age distribution by decade not stated)
Anatomic Location, n (%)
Comment
Lower lip: 1,405 (82) Floor of mouth: 99 (6) Ventral tongue: 86 (5) Buccal mucosa: 82 (5) Palate: 23 (1) Retromolar area: 9 (⬍1) Location not provided: 11 (⬍1)
Lower lip: 348 (59) Buccal mucosa: 101 (17) Floor of mouth: 73 (12) Palate: 25 (4) Tongue: 15 (3) Upper lip: 11 (2) Other: 21 (4)
24 cases had an epithelial lining and may have been salivary duct cysts
Lower lip: 45 (68) Buccal: 7 (11) Alveolar ridge: 3 (5) Palate: 2 (3) Tonsillar region: 2 (3) Upper lip: 2 (3) Vestibule: 1 (2) Floor of mouth: 1 (2) Location not provided: 3 (5) Lower lip: 52 (65) Floor of mouth: 16 (20) Cheek: 8 (10) Retromolar fossa: 2 (3) Tongue: 1 (⬍1) Junction of hard and soft palates: 1 (⬍1)
10 cases appear to have been salivary duct cysts
Lower lip: 101 (63) Floor of mouth: 19 (12) Buccal mucosa: 16 (10) Palate: number not stated Retromolar: number not stated Alveolar ridge: number not stated Upper lip: number not stated
Histopathologic inclusion criteria not stated
Lower lip: 33 (7) Floor of mouth: 3 (7) Cheek: 5 (11) Tongue: 2 (4) Upper lip: 1 (2) Retromolar: 1 (2)
Data are for “extravasation type” mucoceles only
Lower lip: 766 (36) Lip (not otherwise specified): 727 (34) Buccal mucosa: 179 (8) Floor of mouth: 148 (7) Tongue: 143 (7) Palate: 82 (4) Oral cavity (not otherwise specified): 73 (3) Upper lip: 9 (⬍1) Mandible: 9 (⬍1) Gingiva: 8 (⬍1) Retromolar area: 4 (⬍1) Minor salivary glands: 4 (⬍1) Maxilla: 1 (⬍1) Site not stated: 115 (5)
Location data shown here for intraoral cases only (total number of cases and age data refer to entire data set, which included major gland and oropharyngeal case)
7 cases were salivary duct cysts
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Table 2. (Cont’d) Authors
N
Gender, n (%)
Oliveira et al13
112
“Evenly distributed between genders” (numbers not given)
Praetorius and Hammarström27
188
Males: 108 (57) Females: 80 (43)
Robinson and HjørtingHansen14
125
Males: 54 (43) Females: 59 (47) Gender not provided: 16 (13)
Standish and Shafer6
97
Males: 48 (51) Females: 47 (49)
Age Distribution by Decade, n (%) 1st decade: 16 (14) 2nd decade: 51 (46) 3rd decade: 20 (18) 4th decade: 6 (5) 5th decade: 8 (7) 6th decade: 7 (6) Age not provided: 4 (4) 1st decade: 21 (11) 2nd decade: 71 (38) 3rd decade: 42 (22) 4th decade: 22 (12) 5th decade: 19 (10) 6th decade: 7 (4) 7th decade: 4 (2) 8th decade: 2 (1) 1st decade: 20 (16) 2nd decade: 35 (28) 3rd decade: 24 (19) 4th decade: 13 (10) 5th decade: 10 (8) 6th decade: 7 (6) 7th decade and older: 4 (3) Age not provided: 12 (10)
1st decade: 11 (12) 2nd decade: 17 (18) 3rd decade: 15 (16) 4th decade: 16 (17) 5th decade: 14 (15) 6th decade: 11 (11) 7th decade and older: 5 (5) Age not provided: 6 (6)
Anatomic Location, n (%) Lower lip: 58 (52) Tongue: 16 (14) Buccal mucosa: 6 (5) Floor of mouth: 6 (5) Other: 7 (6) Upper lip: 3 (3) Location not provided: 16 (7) Lower lip: 129 (69) Floor of mouth: 29 (15) Buccal mucosa: 22 (12) Ventral tongue: 3 (2) Palate: 2 (1) Upper lip: 2 (1) Gingiva: 1 (1) Lower lip: 64 (52) Buccal mucosa: 13 (11) Floor of mouth: 13 (11) Tongue: 6 (4) Lip (not otherwise specified): 6 (4) Gingiva: 4 (3) Palate: 3 (2) Upper lip: 3 (2) Location not provided: 13 (11) Lower lip: 43 (44) Buccal mucosa: 15 (16) Floor of mouth and ventral tongue: 15 (16) Palate: 7 (7) Retromolar region: 5 (5) Location not provided: 12 (12)
Comment
Did not have an epithelial lining except for possibly an adjacent salivary duct
11 cases may have been salivary duct cysts
6 cases had a partial or complete epithelial lining, although most of these lesions appeared to have opened up to mucous pools
Chi et al. Oral Mucoceles. J Oral Maxillofac Surg 2011.
In striking contrast with the lower labial mucosa, which was by far the most commonly involved anatomic location (82% of cases), not a single case occurred in the upper labial mucosa. Similarly, Standish and Shafer6 and Cohen12 found no upper lip involvement in their reported series, and other authors have found only a small number of cases arising in the upper lip (1% to 3%) in their series.8,11,13-16,27 It is uncertain whether any of these upper lip cases actually may have represented salivary duct cysts instead of mucoceles. The reason for this marked predilection for the lower lip is uncertain. Some authors have proposed that parafunctional habits, such as lip biting, may favor mucocele development in the lower lip.29 In addition, in contrast to the upper lip, the lower lip possesses greater mass, kinematic demands during speech, force generating capability, and force control.30 Perhaps such differences in physical properties may account in part for the striking disparity between lower and upper lip involvement. Furthermore, we surmise that the greater number and density of salivary glands in the lower lip compared with the upper lip,31,32 combined with downward forces of gravity, may play a role in the predilection for mucocele development in the lower lip. A few previously published large case series appear to have included salivary duct cysts in their analysis of oral mucoceles.14,15 However, we felt it was important to
exclude salivary duct cysts from our analysis on the basis of previous reports suggesting that salivary duct cysts and mucoceles exhibit distinct clinicopathologic features. In particular, salivary duct cysts of the oral minor salivary glands appear to be less common and tend to arise in an older patient population compared with mucoceles. In addition, salivary duct cysts do not exhibit such a marked predilection for the lower lip as do mucoceles.11,12,27,33 In a review of 121 cases of salivary duct cysts, Eversole33 noted 3 histopathologic subtypes: 1) “true mucous retention cysts” lined by nononcocytic ductal epithelium and exhibiting minimal inflammation, 2) “reactive oncocytoid cysts” exhibiting oncocytic metaplasia, and 3) “mucopapillary cysts” with a papillary, multicystic growth pattern and regions of pronounced mucous metaplasia. Given that salivary duct cysts are much less common than mucoceles, including them in an aggregate analysis of oral mucoceles probably would not have altered the results significantly. Nevertheless, we believe it is important to distinguish between the 2 lesion types because they do appear to represent distinct clinicopathologic entities. There are limited data in the existing literature regarding the frequency of unusual mucocele variants. To the best of our knowledge, we are the only authors to have reported papillary synovial metaplasialike change within oral mucoceles,25 and this re-
1092 view of cases shows this variant to be extremely rare (0.1% of cases). Our attempt to determine the frequency of superficial mucoceles was limited by the large number of cases with incomplete clinical descriptions. We identified only 3 cases (0.2%) that met both the clinical and microscopic case definitions for a superficial mucocele; however, we believe the true frequency was likely greater. In addition, we acknowledge that superficial mucoceles often are not biopsied because of their transient nature. Our cases are consistent with previous reports suggesting that superficial muco celes most commonly arise in women aged 30 years or older.17,19,20,34,35 Among previously reported superficial mucoceles, the most commonly involved sites have included the soft palate, retromolar pad, and buccal mucosa.17,19,20,34-36 Our 3 cases arose on the buccal mucosa, lower labial mucosa, and floor of mouth. A few authors have observed an association between superficial mucoceles and lichen planus or lichenoid graft-versus-host disease17,19,36; however, we did not find any such disease associations among our cases. Reports regarding the frequency of myxoglobulosis in oral mucoceles are variable. A few authors have found this variant to be rare. In their report of a 10-year-old girl with a mucocele exhibiting myxoglobulosis, Li et al21 noted no other myxoglobulosis cases after reviewing 657 oral mucoceles in their files. In addition, Ide and Kusama24 found only 1 such case after reviewing all mucoceles diagnosed over a 30year period. Likewise, we found a very low frequency of myxoglobulosis (0.4%) among the 1,715 oral mucoceles we reviewed over a 10-year study period. In contrast, Shah23 observed globular structures consistent with myxoglobulosis in 22 of 71 (31%) extravasation mucoceles diagnosed over a period of 32 months. We believe the higher frequency of myxoglobulosis reported by Shah compared with our study and those of other authors may be related to differences in case definition. We surmise that Shah likely included cases with only focal features of myxoglobulosis. Indeed, we found isolated globular structures to be a fairly common finding among oral mucoceles; however, only a small number of cases fulfilled our myxoglobulosis case definition, which required characteristic microscopic features to occupy 30% or more of the lesion. Myxoglobulosis and papillary synovial metaplasialike changes appear to represent incidental findings among oral mucoceles. The clinical presentation for these variants did not differ significantly from the overall mucocele dataset. However, a notable finding was that in 1 case of papillary synovial metaplasialike change, the patient had a history of rubbing the lower labial lesion against the adjacent mandibular teeth.
ORAL MUCOCELES
We surmise that this habit was a source of gliding trauma, which stimulated the development of synovial metaplasialike change. It is peculiar that in other large case series of oral mucoceles, there has been no mention of unusual mucocele variants. In these variants, the classic histopathologic findings of a mucocele typically are present in at least part of the lesion. Therefore, perhaps other authors have not remarked on such cases because they deemed the diagnosis to be readily evident. Nevertheless, we feel that it is important for pathologists to be aware of these rare variants to avoid misdiagnosis. In particular, the superficial mucocele potentially may be confused with immunemediated subepithelial vesiculobullous conditions (such as pemphigoid or bullous lichen planus) or the vesicles of recurrent herpes simplex virus infection.19 Also, mucoceles with papillary synovial metaplasialike change should be distinguished from salivary neoplasms with a papillary cystic growth pattern (such as oncocytic papillary cystadenoma or Warthin tumor).25 In conclusion, we have presented one of the largest case series of oral mucoceles reported to date. Our results confirm the findings of previous investigators regarding the major clinicopathologic features of oral mucoceles, including a marked predilection for the lower lip and young individuals. Special variants of oral mucoceles occur infrequently, although it is important to recognize these variants to avoid misdiagnosis.
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