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Year : 2021  |  Volume : 64  |  Issue : 2  |  Page : 339-342
Nine cases of soft tissue keratocysts arising from buccal mucosa and lateral fascial deep region: Clinicopathological and immunohistochemical study

1 Department of Oral Pathology, Faculty of Dental Sciences, Sri Ramachandra Medical College and Research Institute, Chennai, Tamil Nadu, India
2 Department of Oral Pathology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, National Clinical Research Centre of Stomatology, China

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Date of Submission21-Apr-2020
Date of Decision12-Jun-2020
Date of Acceptance28-Oct-2020
Date of Web Publication9-Apr-2021


Background: Soft tissue keratocysts (SKC) are extremely rare and show similar microscopic morphology to keratocystic odontogenic tumor. The aim was to investigate immunohistochemical (IHC) features and origin of SKCs developing in buccal mucosa and lateral facial deep region. Material and Methods: Expression of CK19, CK10/13, Ki67, Cyclin D1 and Osteopontin (OPN) of 9 SKCS were investigated using IHC. Forty different types of cysts in jaw/soft tissue were used as control. Follow-up was performed. Results: CK10/13 positivity occurred more frequently and intensely in SKC and intraosseous parakeratinized odontogenic keratocysts (COKC). However, OPN positivity was observed only in COKC. Conclusion: This is the largest case series of SKCs; along with first attempt to investigate the expression of OPN on SKC. Given the microscopic and immunohistochemical features, we prefer the view that SKC is odontogenic origin but represents the soft tissue counterpart of COKC, since their expressions of OPN were extremely different.

Keywords: Osteopontin, peripheral odontogenic keratocyst, soft tissue keratocyst

How to cite this article:
Khare P, Sun J, Wang L, Tian Z, Zhang C, Hu Y, Xia R, Li J. Nine cases of soft tissue keratocysts arising from buccal mucosa and lateral fascial deep region: Clinicopathological and immunohistochemical study. Indian J Pathol Microbiol 2021;64:339-42

How to cite this URL:
Khare P, Sun J, Wang L, Tian Z, Zhang C, Hu Y, Xia R, Li J. Nine cases of soft tissue keratocysts arising from buccal mucosa and lateral fascial deep region: Clinicopathological and immunohistochemical study. Indian J Pathol Microbiol [serial online] 2021 [cited 2021 May 16];64:339-42. Available from: https://www.ijpmonline.org/text.asp?2021/64/2/339/313294

   Introduction Top

The odontogenic keratocyst (OKC) was first described by Philipsen in 1956[1] and is a frequently encountered developmental cyst of significant importance because of its potential for aggressive clinical behavior and recurrence.[2] The conventional OKC has central origin that is "intrasosseous variant" and mostly occurs within the jaw.[3] The rare variant of it is called "peripheral OKC," lesions that occur absolutely in the soft tissues overlying the alveolar bone. Till date few cases of peripheral lesion of OKC[4] in extragnathic site like buccal mucosa have been reported.[5]

This study reports series of nine cases of of soft tissue keratocysts (SKCs) originating within the buccal mucosa (7 cases), left pterygopalatine space (1 case) [Figure 1], and pterygomandibular space (1 case). Further clinicopathology, histopathogenesis, and biological behavior of keratocysts occurring in soft tissues other than the gingiva have been investigated. Additionally, the immunohistochemical markers osteopontin (OPN) and cyclinD1 were used to study the biological features of SKCs for the first time.
Figure 1: Computed Tomography (CT) images featuring SKC with arrows depicting cystic area in (a) right pterygomandibular space, (b) left pterygopalatine space, and (c) right buccal mucosa

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   Materials and Methods Top

Nine cases of SKC and control cases including 10 classic intraosseous (parakeratinized) odontogenic keratocyst (COKC), 10 orthokeratinized odontogenic keratocyst (OOKC), 10 epidermoid cyst (EC), 5 salivary gland cyst (SGC), and 5 mucous retention cyst (mucocele) were retrieved retrospectively from 2011 to 2015, Jiao Tong University 9th People Hospital. The rationale behind choosing this particular set of control samples was that they all could develop in the soft tissue regions. SKC can mimic clinical features as those of the control samples and can be overlooked in routine clinical practice. Also, the set of control samples was composed of cysts from three different origins; odontogenic epithelium, squamous epithelium, and ductal epithelium of salivary glands. Their immunohistochemistry profile can be compared with SKC to help exploring the origin of SKC. Further, these nine cases were followed up. The present study was undertaken with the approval of ethical committee of the University. The Helsinki Declaration guidelines have been followed in this investigation.

Histopathology routine H and E staining was done.

Immunohistochemical staining pattern: The results were interpreted in four subgroups, of different epithelial layers in SKC, COKC, and EC. These were superficial layer, middle layer, parabasal layer, and basal layer. Whereas in glandular cysts, only two subgroups were divided and these are myoepithelial cells/basal cells layer and glandular cells layer.

Stain intensity grading: Based on the average number of positively stained cells in ten high power fields (40X) of each slide under light microscopy, the ki67 labelling index (number of positive cells/100 cells) was calculated for all six types of cysts. For OPN, CK19, CK10/13, cyclinD1, cells were evaluated in following criteria: strong staining(dark brown)scored 3, moderate(brown)scored 2, weak (light brown) scored 1, and negative scored 0.

Statistical analysis

Statistical analysis was performed using SPSS 17.0 software (SPSS Inc., Chicago, IL, USA). The statistical significance of differences in the expression of each protein in different cyst lesions was estimated by one-way analysis of variance. A P value of < 0.05 was defined as statistically significant.

   Results Top

Histopathology: on HE staining, all the tissue sections of SKCs showed more or less similar histopathological findings, a well-defined cystic lumen, epithelium-connective tissue junction smooth and flat with no rete ridges formation, connective tissue walls with no daughter cysts and epithelial islands, with an exception of single case [Figure 2]a,[Figure 2]b,[Figure 2]c,[Figure 2]d,[Figure 2]e,[Figure 2]f,[Figure 2]g,[Figure 2]h,[Figure 2]i.
Figure 2: Photomicrography demonstrates nine cases of keratocysts (H&E) at 200X magnification. Left pterygopalatine space (a), right pterygomandibular space (b), buccal mucosa (c-i). Epithelial islands seen in the cyst wall (insert F)

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Immunohistochemistry: showed negative expression for OPN, while COKC showed diffuse and strong expression for OPN as compared to any other cystic lesions

(p < 0.05). CK19 was faintly demonstrated in the entire epithelial lining of some cases of SKC and COKC. CK19 expression was not seen in OOKC and EC, and was diffuse and strong expressed in glandular cysts SGC and mucocele, the difference showed statistical significance (p < 0.05). Restricted to the parabasal, middle, and superficial zone, SKC exhibited strong positive staining for CK10/13, which was consistent with the expression pattern of COKC and EC. On the contrary, CK10/13 expression was seen/absent in the entire epithelium of OOKC, SGC, and mucocele. In general, the expressions of ki67 and cyclinD1 were low in all the cystic lesions. In spite of this, the expression of cyclinD1 was much lower in OOKC than COKC, EC, and mucocele (p < 0.05). Whereas the differences of ki67 index in all cysts showed no significance (p > 0.05) [Figure 3].
Figure 3: Comparative immunohistochemical profiles among cystic lesions at 400X magnification. H and E (A-F), IHC for osteopontin OPN: (A-F1), CK19 (A2-F2), CK10/13 (A3-F3), cyclinD1 (A4-F4), and ki67 (A5-F5). SKC: A-A5, COKC: B-B5, OOKC: C-C5, EC: D-D5, SGC: E-E5, mucocele: F-F5

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   Discussion Top

The precise epidemiology of this lesion is not clear owing to rarity and limited published literature. Review by Chi et al.[6] showed the average age of occurrence range: 37–81 years with the female: male ratio of 2.3:1. Our patients were within the age range of 44-78 years from middle age and above (average 58.2 years) compared to COKCs that peek at 2nd to 3rd decade[7] of life. Contrary from the previous literature wherein female predominance was seen, in our series male predominance was noted, which was similar to COKC.

Our results revealed that SKC, similar to COKC, patchily faintly express CK19. Whereas in SGC and mucocele expression of CK19 is seen diffuse and strong positive. This supported the theory of odontogenic origin rather than glandular origin for SKC considering the intensity and number of positive cells. Similarly, the limited expression of CK10/13 in the parabasal, middle and superficial zone in EC, SKC, and COKC showed the same pattern of appearance, this suggested that SKC might have the possibility of epidermal origin[8] besides odontogenic origin. Pertaining to positive expression of ki67 in SKC our results were in concordance to Tatsuya Abé et al.[8] The expression of cyclinD1 in SKC was almost similar to other cysts, except that it was extremely low in OOKC (P < 0.05), indicating the low proliferation rate of OOKCs. Mounting evidences has indicated that aberrant expression of OPN is functionally associated with tumorigenesis, tumor cell migration, and invasion.[9] In our study, only COKC showed diffuse and strong staining for OPN, this was consistent with the aggressive nature and osteolytic ability of COKC evident in previous studies.[9] Because of this, we were more inclined to believe that COKC represented a benign cystic neoplasm rather than a simple cyst. Meanwhile, our results demonstrated negative expression for OPN in SKC, suggesting the favorable biological behaviour of SKC, unlike COKC.

Results of this study show that SKC was less aggressive than COKC and seemed to be a relatively an indolent lesion due to the low ki67 index and negative OPN expression, the follow-up of patients verified our observation. The clinical outcome of nine patients with SKC was collected with an average follow-up time of 38 months, and no recurrence of these lesion was observed. In addition to the biology, we assume that surgical ease of excision of buccal mucosa compared to intra-osseous sites has a role to play for recurrence free status in these patients.

   Conclusion Top

We examined thought-provoking group of lesions revealing a clinical presentation similar to that of the COKC, OOKC, EC, SGC, and mucocele with histomorphologic features of the odontogenic keratocyst. Based on microscopic and immunohistochemical features, we prefer the view that SKC is odontogenic origin but represents the soft tissue counterpart of the intraosseous OKC, since their expressions of OPN were extremely different and SKC is much indolent with minimal recurrence rate.

Financial support and sponsorship

Jiang Li is receiving two grands from Natural Science Fund of China (No 81872187). For the remaining authors none were declared.

Conflicts of interest

There are no conflicts of interest.

   References Top

Philipsen HP. Om keratocystedr (Kolesteratomer) and kaeberne. Tandlaegebladet 1956;60:963-71.  Back to cited text no. 1
Meara JG, Shah S, Li KK, Cunningham MJ. The odontogenic keratocyst: A 20-year clinicopathologic review. Laryngoscope 1998;108:280-3.  Back to cited text no. 2
Ide F, Kikuchi K, Miyazaki Y, Mishima K, Saito I, Kusama K. Keratocyst of the buccal mucosa: Is it odontogenic? Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010;110:e42-7.  Back to cited text no. 3
Satoh H, Fukuta Y, Izumisawa M, Ohya T, Kudo K, Takeda Y. A case of epidermoid cyst in the pterygomandibular space. Jpn J Oral Maxillofac Surg 1998;44:76-8.  Back to cited text no. 4
Ide F. Peripheral ameloblastoma of the buccal mucosa. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010;109:653-4.  Back to cited text no. 5
Chi AC, Owings JR, Muller S. Peripheral odontogenic keratocyst: Report of two cases and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2005;99:71-8.  Back to cited text no. 6
Eryilmaz T, Ozmen S, Findikcioglu K, Kandal S, Aral M. Odontogenic keratocyst: An unusual location and review of the literature. Ann Plast Surg 2009;62:210-2.  Back to cited text no. 7
Abé T, Maruyama S, Yamazaki M, Essa A, Babkair H, Mikami T, et al. Intramuscular keratocyst as a soft tissue counterpart of keratocystic odontogenic tumor: Differential diagnosis by immunohistochemistry. Hum Pathol 2014;45:110-8.  Back to cited text no. 8
Wang YP, Liu BY. High Expression of Osteopontin and CD44v6 in Odontogenic Keratocysts. J Formos Med Assoc 2009;108:286-92.  Back to cited text no. 9

Correspondence Address:
Jiang Li
Department of Oral Pathology, Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Key Laboratory of Stomatology, 639 Zhi-zao-ju Road, Shanghai 200011
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/IJPM.IJPM_423_20

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