1

1 Case report

2 Minimally Invasive Two-staged Surgery in the Treatment of

3 Large Cystic Lesions of the Jaw
4 Andreea Irimia 1, Liliana Moraru 1,2, Diana Alina Ciubotaru 1,3, Constantin Caruntu 3,4,*, Titus Farcasiu 5,* and Ana
5 Caruntu 1,2

6 1
Department of Oral and Maxillofacial Surgery, “Carol Davila” Central Military Emergency Hospital, 010825 Bucharest, Romania;
7 irimia.andreeaioana@yahoo.com; liliana.moraru@yahoo.com; ciubotarudianaalina@gmail.com;
8 2
Department of Oral and Maxillofacial Surgery, Faculty of Dental Medicine, “Titu Maiorescu” University, 031593 Bucharest, Romania;
9 ana.caruntu@gmail.com;
10 3
Department of Physiology, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania;
11 costin.caruntu@gmail.com
12 4
Department of Dermatology, “Prof. N.C. Paulescu” National Institute of Diabetes, Nutrition and Metabolic Diseases,
13 011233 Bucharest, Romania;
14 5
Department of Removable Prosthodontics, “Carol Davila” University of Medicine and Pharmacy, 020021
15 Bucharest, Romania; alexandru.farcasiu@umfcd.ro
16
17 * Correspondence: costin.caruntu@gmail.com (C.C.); alexandru.farcasiu@umfcd.ro

18 Abstract: Background: Cystic lesions of the jaw are commonly found in clinical practice. Large,
19 expansive cysts raise challenges for the clinician from both diagnostic and surgical perspectives.
20 The aim of our work is to present a combined, two-staged surgical approach in histologically
21 confirmed non-aggressive cystic lesions of the jaw. Methods and Results: We report the case of an
22 extensive mandibular cyst, associating a high risk of bone fracture, that is treated in the initial
23 stage by cystic decompression through marsupialization with concomitant histological diagnostic
24 confirmation, followed in the second stage by radical excision and mandibular reconstruction with
25 titanium mesh, with the purpose of prevention for oro-cystic chronic fistula formation.
26 Citation: Lastname, F.; Lastname, F.; Conclusions: Large odontogenic mandibular cysts imply a meticulously conducted clinico-
27 Lastname, F. Title. Healthcare 2021, 9, pathological assessment and treatment. Marsupialization should be taken into consideration for
28 x. https://doi.org/10.3390/xxxxx the treatment of large cystic lesions, followed by secondary tumor enucleation, with minimal risks
29 for the patient. Soft tissue healing process can be optimized with the use of titanium meshes, as an
30 Academic Editor: Firstname alternative for other reconstructive techniques, in the management of large cystic lesions.
Lastname
31 Keywords: minimally invasive; mandibular cyst; marsupialization; reconstruction
32 Received: date
Accepted: date
Published: date

33 1. Introduction
Publisher’s Note: MDPI stays
34 neutral with regard to jurisdictional Odontogenic cysts are the most common cause of jaw radiolucent lesions and
35 claims in published maps and include a wide range of pathological entities. Radicular or residual cysts, keratocysts,
36 institutional affiliations. dentigerous cysts and osteonecrosis of the jaw represent the vast majority of
37 odontogenic lesions found in clinical practice [1, 2]. Radiolucent lesions can also be the
38 result of wrong chosen therapies, infections, primary tumors, metastasis, radio-therapy
39 or medication-related osteonecrosis. radicular and residual lesions, known as
40 Copyright: © 2021 by the authors. inflammatory cysts, usually have a limited growth, with no major consequences on
Submitted for possible open access
41 mandibular resistance. However, in isolated cases, these cysts can have an aggressive
publication under the terms and
42 growth pattern, with extensive bone resorption, that can significantly impair mandibular
conditions of the Creative Commons
43 resistance [3, 4]. The intracystic increased fluid pressure has been shown to influence the
Attribution (CC BY) license
44 dimensions of the lesions, especially in the initial stages of cystic development [5, 6].
(https://creativecommons.org/license
45 s/by/4.0/).
This increased pressure is most probably caused by epithelial cells desquamation from

3 Healthcare 2021, 9, x. https://doi.org/10.3390/xxxxx www.mdpi.com/journal/healthcare

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46 the cystic walls, releasing their intracellular content into the cystic cavity. This leads to
47 an increased osmotic pressure, which in consequence induces an elevation of the
48 intracystic hydrostatic pressure [7]. An intense inflammatory activity within the cystic
49 membrane, specific for residual and radicular cysts, has also been considered to play an
50 important role in cystic growth and peripheral bone resorption [8]. However, in most
51 cases these mechanisms coexist and contribute to lesion expansion and peripheral bone
52 resorption, leading to the development of giant cysts, associated with an impaired
53 mandibular resistance, prone to fracture.
54 It is very important to differentiate radicular or residual cysts from other bone
55 lesions [9], that can exhibit similar clinical and imagistic characteristics, such as unicystic
56 ameloblastoma or odontogenic keratocyst [10, 11]. These lesions have distinct clinic-
57 pathological behavior, associating high rates of recurrence, and imply completely
58 different therapeutic approaches 1. Thus, a diagnostic biopsy is strongly recommended
59 before any radical treatment, in order to rule out aggressive bone lesions. Primary
60 excision of large mandibular cysts, that have severely undermined the mandibular bone
61 structure, is not feasible due to the high risk of jaw fractures, challenging to treat
62 considering the lack of bony tissue for stable plating [4]. The risk-benefit balance in
63 patients with giant cystic lesions, that do not exhibit other aggressiveness features, does
64 not favor extensive, complex reconstructive surgery in most cases, due to the increased
65 incidence of perioperative complications [12, 13]. Cystic decompression through
66 marsupialization followed by second stage tumor excision can be a valid therapeutic
67 option in these patients, providing several advantages: cystic decompression with
68 simultaneous biopsy for diagnostic confirmation, minimally invasive surgery conducted
69 under local anesthesia, outpatient care or reduced hospitalization time and rapid post-
70 surgical recovery [14]. The main disadvantage is the temporary presence of an oro-cystic
71 fistula during the interval between the two surgeries, that requires daily care and
72 frequent follow-up visits, that might be challenging for some patients. Another potential
73 complication after the two staged approach – marsupialization and excision – is the
74 persistent oro-cystic fistula after secondary surgery, that can be sometimes difficult to
75 manage.
76 The present case report depicts the clinical characteristics and the therapeutic
77 approach of a massive residual mandibular cyst, treated through a two-stage approach:
78 initial cystic decompression with simultaneous diagnostic biopsy, followed by
79 secondary tumor excision. In order to reduce the risk of persistent oro-cystic fistula,
80 bone reconstruction with titanium mesh was performed for the mandibular fenestration,
81 thus providing solid support for the adjacent soft tissues. The particularities of this case
82 are related to an atypical clinical behavior, with an aggressive growth pattern for an
83 otherwise inoffensive clinical entity, and the therapeutic approach that allowed an
84 accurate diagnosis and simultaneous treatment, through minimally invasive techniques,
85 leading to optimal therapeutic results and no complications.

86 2. Case Report
87 In February 2019, a 53 year-old female patient was admitted to the Department of
88 Oral and Maxillofacial Surgery, “Dr. Carol Davila” Central Military Hospital, Bucharest,
89 with an important facial asymmetry on the left side, caused by the presence of a swelling
90 affecting the middle and lower thirds of the face, that was noticed by the patient about
91 three months before admission [Figure 1(a)]. The lesion was asymptomatic, painless at
92 palpation, overall of hard consistency except for small renitent areas at the intraoral
93 examination. The patient reported no history of infectious exacerbations. The skin lining
94 the affected area did no present any changes in color, temperature and turgor and did
95 not associate any motor or sensory deficit. There were no other significant pathological
96 changes at the general examination of the patient.
97 A detailed dental history from the patient revealed having multiple teeth
98 extractions in the third quadrant a few years before with no other history of swelling
99 and pain until now. Intraoral examination showed a bilateral terminal edentulous lower
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100 arch, severe attrition and a bicortical swelling on the left side of the mandible. The oral
101 mucosa lining was of normal appearance, except for a small central area of translucent
102 color, corresponding to the previously mentioned renitent area [Figure 1(b)].
103

104

105 Figure 1. Clinical and imagistic aspect at presentation. (a)Extraoral aspect; (b) Intraoral aspect; (c)
106 Preoperative panoramic x-ray; (d) Preoperative native CT scan: sagittal view; (e) axial view; (f)
107 Intraoral aspect after marsupialization of the cyst.

108 The initial panoramic x-ray showed a very large radiolucent lesion, extended from
109 the region of the first molar – angle of the mandible – vertical ramus – coronoid process,
110 leaving intact only the left condyle. The contour of the mandible was altered and areas
111 of peripheral sclerosis were present. The projection of the left mandibular canal was
112 displaced downwards. There were no teeth, impacted or erupted, in relation with the
113 lesion [Figure 1(c)].
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114 Native Computed Tomography (CT) revealed the presence of a large bony cavity
115 extended in the left body and ramus of the mandible, measuring 80 mm x 35 mm in size.
116 The cavity presented several areas of complete bone loss, with fenestration of the lingual
117 and basilar cortical bone, deviation of the mandibular canal and complete disruption of
118 the superior wall of the canal [Figure 1(d) and (e)].
119 Considering the major bone loss with a very high risk of mandibular fracture and
120 the unknown diagnosis, we initiated a minimally invasive two-staged approach to treat
121 this patient. In the first stage, the decompression of the cyst through marsupialization
122 was performed. Under local anesthesia, we created an ellipsoidal incision with the
123 excision of an area of oral mucosa and adjacent cystic membrane. The cystic content was
124 evacuated and the edges of the oral mucosa were sutured to the cystic lining, thus
125 preventing wound closure. The removed cystic tissue was sent for pathological
126 assessment, that described presence of inflamed non-keratinized squamous epithelium
127 with cholesterol clefs and fibro-vascular tissues, suggestive for a residual cyst [Figure
128 1(f)].
129

130

131 Figure 2. Clinical and imagistic aspect at 3 months after marsupialization. (a) Extraoral aspect; (b)
132 Intraoral aspect; (c) Panoramic x-ray; (d) CBCT with 3D reconstruction; (e) CBCT axial view.

133 The patient was instructed on daily oral hygiene routine and was called every two
134 weeks for follow up visits. After 3 months, the patients’ appearance improved
135 significantly, with almost complete restauration of facial symmetry [Figure 2(a) and (b)]
136 The imagistic examination - panoramic x-ray and Cone Beam Computed Tomography
137 (CBCT) - evidenced an important reduction of the cystic dimensions, with restauration
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138 of the normal mandibular contour and significant circumferential bone apposition, as a
139 witness for active bone regeneration [Figure 2 (c), (d) and (e)].
140 At 6 months, the decompression effects were stable, and the patient underwent the
141 second stage of the treatment. Under general anesthesia, radical cystic excision was
142 performed. The bone defect corresponding to the marsupialization window was
143 reconstructed with a titanium mesh fixed with screws, in order to prevent the formation
144 of a chronic oro-cystic fistula [Figure 3 (a)]. Postoperative care included local cold packs,
145 antibiotic prophylaxis and anti-inflammatory drugs. The sutures were removed two
146 weeks after surgery, revealing a complete wound closure with no mesh exposure. At 12
147 months follow-up visit, clinical and imagistic assessments revealed appropriate bone
148 formation, comparable to the contralateral healthy side of the mandible [Figure 3 (b)].
149

150

151 Figure 3. Intraoperative aspect from second stage surgery and imagistic aspect at 12 months
152 follow-up (a) intraoperative aspect depicting the titanium mesh fixed with titanium screws; (b)
153 panoramic x-ray at 12 months follow-up.

154 3. Discussion
155 The surgical management of cystic lesions involving the jaws has become
156 progressively less invasive and the choice for a certain technique is influenced by cystic
157 characteristics, such as localization, dimension or rate of recurrence [15, 16]. In small
158 lesions, the diagnosis and definitive treatment can be done in one stage surgery,
159 consisting of radical tumor excision and pathology examination of the specimen, to rule
160 out an aggressive recurrent lesion, without high risks for complications[17]. However, in
161 large cystic mandibular lesions, one-stage radical surgery is rarely an option, due to the
162 increased risks of intraoperative and postoperative complications [18]. The main risk in
163 treating giant cystic tumors of the mandible with a one-stage approach is for an
164 immediate or secondary bone fracture, caused by the reduced bone resistance [19].
165 Furthermore, these fractures are challenging to treat, due to the lack of normal bone
166 structure and usually require complex reconstruction techniques in order to restore
167 mandibular continuity, with additional risks for the patient and financial burden for the
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168 healthcare system. Reconstructive surgery using avascular bone grafts or even free flap
169 grafts can be used as an alternative treatment option for these lesions. However, these
170 complex surgeries imply additional risks, like donor site morbidity, potential loss of the
171 flap or graft, or visible scars [20–22]. In our presentation, we emphasis the role and
172 benefits of a minimally invasive technique in the treatment of large mandibular cystic
173 lesions associated with a proactive management of potential complications. Our
174 conservative, two-staged surgery, consisting of initial marsupialization with
175 simultaneous diagnosis, followed by radical resection and reconstruction of the defect
176 with titanium mesh implant, provided an optimal therapeutic approach for an otherwise
177 aggressively growing lesion, with almost complete mandibular resorption.
178 Decompression of the cysts has been long documented with beneficial effects on bone
179 regeneration [23–25]. In our case, within three months, the dimensions of the lesion have
180 reduced by more than 50% and significant bone regeneration could be evidenced though
181 imagistic assessment, with new bone apposition within the cystic walls, ranging
182 between 1-5 mm of new bony tissue. The mechanisms underlying bone regeneration
183 following tumor decompression have been intensively studied and it is thought that
184 interleukin 1α (IL- 1α) might play an important role in this process. In odontogenic
185 cysts, an intense inhibition of IL-1α expression was found after tumor decompression
186 associated with important reduction in the size of the lesions [26]. Cystic decompression
187 through marsupialization is defined as a conservative treatment method that has several
188 advantages: it is an easy procedure, that can be conducted under local anesthesia,
189 requiring basic surgical equipment. Despite the simplicity, it is a highly tissue sparing
190 technique, allowing the preservation of bone height and anatomical structures, such as
191 inferior alveolar nerve or mental nerve [27, 28]. Another important advantage of the
192 procedure is its diagnostic character, allowing tissue sampling for histopathological
193 assessment and diagnostic confirmation. In dental practice, cystic-appearing lesions
194 represent a frequently encountered pathology, raising major diagnostic challenges for
195 the clinician [29]. In order to provide the best therapeutic option, it is important to have
196 a histological confirmation of the diagnosis [30]. An extensive study that collected data
197 over an interval of 30 years reported that out of 44000 specimens referred for pathology
198 assessment from the maxillo-facial department, 13.8% were odontogenic cysts, thus
199 confirming their high incidence in daily clinical practice. Other jaw affecting pathology:
200 non-odontogenic cysts, benign and malignant bone tumors, represented altogether 3.8%
201 of the cases [31]. Therefore, even though the majority of the cystic-like lesions found in
202 the oral and maxillofacial area are odontogenic cysts, clinicians always have to bare in
203 mind the locally aggressive and destructive entities during the examination process.
204 Bone lesions are frequently defined by similar clinical and imagistic characteristics, that
205 can lead to major diagnostic errors. Saghravanian et al. reported an accuracy rate of only
206 69.3% in patients that underwent surgery for clinically diagnosed odontogenic cysts,
207 after the specimen underwent pathology assessment [32]. A meticulous patient
208 examination and history, with careful consideration for the site of the lesion, its borders,
209 internal architecture, its effects on adjacent anatomical structures, generally can narrow
210 the wide rage of differential diagnostic options. In most cases, these lesions must be
211 surgically removed and examined microscopically to establish an accurate diagnosis.
212 Marsupialization technique implies the surgical creation of a fenestration in one of
213 the cystic walls and impediment of wound closure through specific sutures [33]. It
214 reduces the hydrostatic pressure within the cyst and the surrounding bone with the
215 direct consequence of blocking tumor growth and the underlying bone resorption.
216 Subsequently, through regenerative mechanism, fibroblasts migrate into the affected
217 area and produce important quantities of collagenous matrix. These cells respond
218 through complex signaling pathways by either proliferation or differentiation into a
219 variety of cells, like bone cells, fat cells or cartilaginous cells. The bone cells, osteoblasts,
220 alongside osteoclasts, are involved in the process of bone healing through resorption,
221 new bone apposition and remodeling, leading to bone regeneration [34]. Moreover, the
222 marsupialization technique should be taken into consideration as a primary approach in
223 patients with erupted or impacted teeth involved in the cystic area, in order to preserve
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224 the teeth and therefore improve the functional and aesthetic outcomes [35, 36]. For
225 maxillary lesions, an alternative decompression method using plastic tubes within the
226 cystic cavity have revealed great results in tumor size reduction [37].
227 The main drawbacks of marsupialization are related to the incomplete removal of
228 pathological tissue, that can associate higher rates of tumor recurrence, as well as the
229 prolonged time of healing [38]. Considering these limitations, decompression can be
230 used as an intermediate step in the treatment of large cystic lesions, with the intention of
231 reducing the cystic dimensions, rather than a definitive treatment alone. It is then
232 followed by radical tumor excision, with or without additional reconstructive
233 procedures, thus minimizing the risk of recurrence [39]. Therefore, any cystic lesion that
234 does not jeopardize the integrity of the mandible after surgical removal should to be
235 treated radically by first intent whenever possible. Radical surgical excision with
236 complete removal of the cystic capsule is the most important element for a predictable
237 result [40]. Another potential risk, when using marsupialization as a stand-alone
238 treatment, is the malignant transformation of the residual cystic membrane in time [41,
239 42]. In our case, radical cystic excision was conducted half a year after marsupialization,
240 with the addition of a titanium mesh reconstruction covering the mandibular
241 fenestration, in order to prevent dehiscence with subsequent chronic oro-cystic fistula.
242 At the one-year follow-up visit, the patient showed no history or signs of impaired
243 healing in the cystic area and the procedures for dental arch restoration were initiated.
244 The use of titanium mesh in the final surgery allowed optimal bone formation and soft
245 tissue healing, without the necessity of bone grafting with autologous bone grafts, that
246 would imply more complex surgeries with potential donor site morbidity, and no
247 additional costs associated to different market available grafting materials.

248 4. Conclusions
249 Large odontogenic mandibular cysts imply a meticulously conducted clinico-
250 pathological assessment and treatment. Marsupialization should be taken into
251 consideration in treatment planning of large cystic lesions, as an initial less invasive
252 surgical step that leads to the secondary tumor enucleation, with minimal risks for the
253 patient. Guided by the same principles of safety and simplicity, the healing process can
254 be optimized through the use of titanium meshes, as an alternative for other
255 reconstructive techniques, in the management of large cystic lesions.

256 Author Contributions: Conceptualization and methodology, A.C.; investigation, data curation
257 and writing—original draft preparation, A.I., L.M., D.A.C., C.C., T.F. and A.C.; writing—review
258 and editing, C.C., T.F. and A.C.; supervision, A.C.; project administration, A.C.; funding
259 acquisition, C.C., T.F. and A.C. All authors have read and agreed to the published version of the
260 manuscript.
261 Funding: This research was partially funded by the Romanian Ministry of Research and
262 Innovation (CCCDI-UEFISCDI), grant number: 271/2020, project code: PN-III-P2-2.1-PED-2019-
263 4569.
264 Institutional Review Board Statement: The study was conducted according to the guidelines of
265 the Declaration of Helsinki, and approved by the Ethics Committee of the “Carol Davila” Central
266 Military Emergency Hospital, Bucharest (No. 399/4 December 2020).
267 Informed Consent Statement: Written informed consent has been obtained from the patient to
268 publish this paper.
269 Data Availability Statement: The data used and/or analyzed during the present study are
270 available from the corresponding author.
271 Conflicts of Interest: The authors declare no conflict of interest.

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