An Unusual Case of Maxillary Sinus Odontogenic Keratocyst: An Insightful Report With Review of the Literature

Maxillary sinus odontogenic keratocyst (OKC) is very rare and occupies less than 1% of the total OKC cases reported in the literature. OKCs have characteristic features that are unique compared to other cysts of the maxillofacial region. Considering their peculiar behaviour, varied origin, debated development, discourse treatment modalities, and high recurrence rate, OKCs have been a subject of interest for various oral surgeons and pathologists globally. This case report presents an unusual case of invasive maxillary sinus OKC into the orbital floor, pterygoid plates, and hard palate in a 30-year-old female. The case report confers that cystic maxillary sinus lesions should always be treated very extensively irrespective of the nature of the lesion as the site makes it highly susceptible to secondary infection and recurrence. The case also establishes a set of imaging modalities and specific treatment approaches to be followed for maxillary sinus OKC based on the literature of all the previous cases reported.


Introduction
Odontogenic keratocyst (OKC) is a distinctive form of developmental odontogenic cyst comprising 12% of the entire jaw cysts [1]. Considering their peculiar behaviour, varied origin, debated development, discourse treatment modalities, and high recurrence rate, OKCs have been a subject of interest for various oral surgeons and pathologists globally [2].
The most common site as per the occurrence rate of OKC is the mandible (73%) compared with 27% in the maxilla [3]. OKCs of the maxillary sinus are even rarer with less than 1% of cases reported in the literature [4]. This case report is of an unusual presentation of an aggressive left maxillary sinus OKC in a 30-year-old female. Lesions involving the sinus always pose a diagnostic challenge as the margins are difficult to identify and sinus pathology of odontogenic origin holds high chances of secondary infection [5]. A brief review of all the reported maxillary sinus OKCs of the past 20 years has also been compiled with this case for understanding their behaviour patterns in terms of clinical, radiological, and treatment outcomes considering its rare occurrence in this site.

Case Presentation
A 30-year-old female patient reported to the department of dentistry with the chief complaint of swelling on the left upper back region of the jaw for three years with mild heaviness for a month on the same side of the face. The patient gave a history of gradual increase in the size of the swelling to the present size with no association of pain or any other symptom. No significant personal, medical, or family history was reported. Slight facial asymmetry was present extraorally on the affected side ( Figure 1). 1 2 3 4 5

FIGURE 1: Extraoral clinical image
Extraoral clinical image showing no visible gross facial asymmetry.
Intraoral examination revealed diffuse swelling on the buccal aspect of the maxilla completely obliterating the vestibule region of 23-27 extending palatally involving the hard palate ( Figure 2). On palpation, the swelling was non-tender and firm in consistency. Hard tissue examination revealed no clinical decay or mobility in the tooth in relation to the swelling, nor was there any history of discharge. The vitality of the teeth was assessed, and all the teeth were vital. Chronic generalized periodontitis with the presence of dental fluorosis was seen ( Figure 2). Considering the site and extent of the swelling on intraoral examination without any oral symptoms, a clinical differential diagnosis of maxillary odontogenic sinusitis, periodontal cyst, and deep fungal infection of the maxillary sinus was considered. Hence, an orthopantomogram (OPG) ( Figure 3) and a paranasal sinus view followed by contrast-enhanced computed tomography (CECT) were advised. The paranasal sinus view showed complete obliteration of the left maxillary sinus (Figure 4).   CT report concluded it to be a benign cystic lesion. Fine needle aspiration cytology (FNAC) was done, and aspirate yielded cream-coloured fluid and cytology revealed the presence of necrosis with cholesterol crystals.
The surgical enucleation of the lesion was planned under local anaesthesia and antibiotic coverage with an intra-oral approach ( Figure 6).

FIGURE 6: Surgical exploration through intra-oral approach: thinning and expansion of cortical plates
During surgical exploration, an abundance of white-cheesy content was collected. The lesion was highly aggressive with invasion into the pterygoid plates and orbital floor. The fragile cyst lining was enucleated, and curettage was done. Considering the invasive nature of the lesion, extended chemical cauterization was done using freshly prepared Carnoy's solution. The cyst cavity was inspected to ensure complete excision, and an iodoform-medicated gauze pack was kept inside the cavity with one end out. This gauze pack was removed after three days.
The enucleated specimen was sent for histopathological examination. Gross examination showed a thin cyst wall, which on microscopy revealed a cystic lining with parakeratinized stratified squamous epithelium with palisaded cuboidal basal cells. The cystic wall was fibrous with focal areas of dense chronic inflammatory infiltrate predominantly plasma cells and lymphocytes ( Figure 7). Therefore, the histopathological diagnosis of OKC of the maxillary sinus was made.

FIGURE 7: Fibro-dense cyst wall lined with para keratinization stratified squamous lining with palisaded cuboidal basal cells. The cystic wall is fibrous with focal areas of moderately dense chronic inflammatory cells
The patient was followed up after four months and had no fresh complaints in accordance with the site of the lesion operated, and intraorally the site seemed to have restored its normal anatomy ( Figure 8).

FIGURE 8: Post-operative follow-up image after four months postsurgery
The patient was kept in periodic follow-up, and OPG was repeated six months post-surgery, which showed no recurrence ( Figure 9). CECT is to be repeated at the one-year post-surgery visit.

Discussion
OKCs are the third most common developmental jaw cysts. The term was broadly used for all keratinforming cysts during the 1950s. It was in 1956 that Phillipsen described OKC for epithelial developmental cysts [6]. OKCs show an occurrence of 65% to 83% in the mandible but their location in the maxillary site is conflicted [2,3]. OKCs that occur in regions other than the mandibular angle and especially those in the maxilla seem to be more related to systemic syndromes [3]. A literature search for case reports was conducted in PubMed, ClinicalKey, and Google Scholar databases using the keywords "maxillary sinus" and "invasive odontogenic keratocyst" and the available data for the last 20 years have been tabulated ( Table 1).  The case reports of maxillary sinus OKC compiled in the table including ours were all non-syndromic. OKCs cover a wide age range, from the first decade of life to as late as the ninth decade [2,3]. The peak occurrence is seen in the second and third decades, which was similar to the reported case [3,6].

Year
In the current case, the cyst extended into the floor of the orbit, hard plate, and pterygoid plates similar to the case reported by Goto et al. [13]. The majority of the maxillary sinus OKCs reported were symptomatic although this case was asymptomatic [2,4,[7][8][9]. As per the literature, 25% to 40% of the cases have involvement of an unerupted impacted, displaced, or incompletely formed tooth [2,4,[7][8][9][10][11][12][13][14]. In the reported case, there was no association with either any impacted or undeveloped tooth or any discharge associated with the lesion.
OKCs have a multifactorial theory of origin. Initially, the primordium of the tooth was thought by many authors to be the origin of these cysts and hence the name primordial cyst but now the dental lamina is considered to be the most likely origin. The basal cell layer of the oral epithelium is also thought to possibly play a role in the aetiology of these cysts [3]. The origin of OKC in the maxillary sinus is controversial, presumably arising from the entrapment of odontogenic epithelium within the sinus because of the close anatomy. A breach in the Schneiderian membrane due to odontogenic infection or odontogenic pathology of the maxillary bone can lead to maxillary sinus infection [14].
The theory of intrinsic growth potential of a cyst due to expression of Ki67, proliferating cell nuclear antigen (PCNA), and p-63 has also been proposed according to which patients who have the predisposition to form keratocyst will always have a higher risk of developing a cyst as long as a dental lamina or its remnant are present [15]. As per studies, Ki67 labelling is higher in cases with PTCH1 mutations. The theory specifically can be applied to syndromic patients (mutation rate > 85%) but sporadic OKC cases cannot be excluded (mutation rate < 30%). In the case of sporadic cases where there is epithelium separation from the connective tissue of the cyst, the PTCH1 mutation rate increases to 84% nearly equal to the syndromic OKC [16].
This theory could also be applied to the current case considering its behaviour and invasive potential but confirmation required evidence through genomic testing and immunohistochemistry (IHC) expression, which could not be done due to limited resources. Also, in the reported case, the cyst could have developed as a result of entrapment and proliferation of odontogenic epithelial cells or extensions of the basal cell layer of the epithelium of oral mucosa in the sinus. The patient had very poor oral hygiene and severe periodontitis, which could have additionally attributed to the infection of the sinus.
Several theories have been proposed for explaining the invasive and destructive nature of OKC. Growth in OKC is linked to unknown growth factors inherent in the epithelium itself or enzymatic activity in the fibrous wall [15]. Its invasion and infiltration are attributed to the multicentric growth potential that is cystic growth brought about by the proliferation of local groups of epithelial cells [17]. In the current case, the cyst was unilocular and there was no multicellularity seen in histopathology yet it was large, expansile, destroying the sinus floor, and perforating the cortical bone.
Aggressive maxillary sinus OKCs tend to penetrate into the surrounding soft tissues with expansion and perforation of cortical bone. The expansion has been reported to occur in up to 60% of cases, similar to the current case reported [3]. Advanced imaging techniques like CT and MRI are more useful as sometimes the pan tomographs can be misleading in viewing large lesions involving the maxillary sinus and those invading the skull base or surrounding spaces [13,18]. All case reports of sinus involvement used CT as their chief source of investigation as it not only demarcates the clear boundaries and extent of the lesion but also helps to demonstrate other features of OKCs, such as bony changes (expansion in buccolingual/palatal direction and erosion), internal density, and extension into soft tissue [19]. It also provides a better aid for the surgeons to prepare their procedures pre-operatively. Even in our case, OPG and the paranasal view did not give a clear interpretation of the lesion while CT demarcated the lesion boundaries discretely.
There is no universally accepted treatment for OKC. Considering its aggressive nature and history of recurrence, the primary aim of treatment is to achieve total eradication. The techniques involve decompression followed by enucleation and peripheral osteotomy, which show less recurrence, as compared to only enucleation, which has a recurrence rate of 17-56% [13]. The application of Carnoy's solution has been very effective in adjunct to peripheral osteotomy and enucleation in extensive lesions in reducing the recurrence rate [9]. For our case too, freshly prepared Carnoy's solution was used post-enucleation and curettage. Even with Carnoy's solution application, a recurrence rate of 1-8.7% is reported and hence patient has been kept under periodic follow-up [13].

Conclusions
Maxillary sinus OKCs are less in occurrence and every case has a varied presentation. FNAC is of limited help and CT imaging should be considered as the baseline radiological investigation to diagnose and plan treatment. Histopathology, genomic testing, and IHC should be considered as diagnostic criteria as they add better explanatory data on the aetiology and behaviour patterns of OKCs. Post-operative periodic follow-up should be mandatory irrespective of the operative procedure followed.

Additional Information Disclosures
Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.