Unusual OdontogenicKeratocyst of the Maxillary SinusConstantinos Houpis, DDS, PhD, MSc,Konstantinos I. Tosios, DDS, PhD, Stavroula Merkourea, DDS,Stylianos Krithinakis, DDS, Nicolaos Nikitakis, DDS, PhD,Alexandra Sklavounou, DDS, PhD, MScAbstract:An odontogenic keratocyst that eroded into the sinusthrough the maxillary bone and occupied it, showed replacement ofthe sinus respiratory epithelium by lesional epithelium, and wasassociated with fungal rhinosinusitis is presented. A review of theliterature disclosed that epithelial replacement has been described in2 previous case reports, although there is no report on the coexis-tence of odontogenic keratocyst with fungal rhinosinusitis.Key Words:Odontogenic keratocyst, maxilla, fungal rhinosinusitis

Odontogenic keratocyst (OKC) is established as a distinct en-tity because of its specific microscopic features and aggres-sive behavior that manifests with infiltration of adjacent anatomicFrom the Department of Oral Pathology and Surgery, Dental School,National and Kapodistrian University of Athens, Athens, Greece. Drs.Houpis, Merkourea, and Krithinakis are in private practice.Received June 15, 2010.Accepted for publication July 4, 2010.Address correspondence and reprint requests to Constantinos Houpis,DDS, PhD, MSc, Pl Esperidon 2A, 16674 Glyfada, Greece;E-mail: kchoupis@otenet.grPresented as a poster at the American Academy of Oral & MaxillofacialPathology annual meeting, May 16Y20, 2009, Montreal, Canada.The authors report no conflicts of interest.Copyright*2011 by Mutaz B. Habal, MDISSN: 1049-2275DOI: 10.1097/SCS.0b013e31820747b7The Journal of Craniofacial Surgery&Volume 22, Number 2, March 2011Brief Clinical Studies*2011 Mutaz B. Habal, MD

721Copyright © 2011 Mutaz B. Habal, MD. Unauthorized reproduction of this article is prohibited.structures and high recurrence rate. This behavior is emphasizedby the introduction of the termkeratocystic odontogenic tumorin the recent classification of the World Health Organization,1

although its neoplastic nature is debated. We describe an OKC thateroded into the sinus through the maxillary bone and replaced thesinus respiratory epithelium, while it was associated with fungal

rhinosinusitis.CLINICAL REPORTA 38-year-old man presented with intermittent pain, swelling, anda feeling of ‘‘fullness and pressure’’ on the left side of his face thathe had first noticed about 1 year ago and got worse during scubadiving. His medical history was significant for chronic rhinosinus-itis that had repeatedly been treated with administration of anti-biotics and local corticosteroids. He was otherwise healthy and notin any other kind of medication.Clinical examination revealed a hard, nonfluctuant, and slightlytender swelling covered by normal mucosa in the maxillary vesti-bule, distant to the first molar tooth. Regional lymph nodes were notpalpable. According to the referring dentist, the associated teethwere vital. Panoramic radiograph showed a well-circumscribed ra-diolucent lesion apical to the first molar tooth (Fig. 1).A provisional diagnosis of OKC was made, and an incisionalbiopsy was performed under local anesthesia. Intraoperatively, thecystic cavity was found to contain a whitish material. Microscopicexamination of 5-Km-thick, formalin-fixed, and paraffin-embeddedtissue sections showed connective tissue lined by a uniformly thinparakeratinized epithelium without rete ridges that had a corru-gated parakeratinized surface and a basal layer composed of co-lumnar cells with reverse nuclear polarity (Fig. 2). Focal separationof the epithelium from the connective tissue was seen. The con-nective tissue was mildly infiltrated by inflammatory cells, pre-dominantly lymphoplasmacytes. The diagnosis was OKC.A computed tomography scan revealed a diffuse radiopacitymainly toward the floor of the left maxillary sinus. Bone resorptionwas evident at the anterolateral wall of the maxilla close to thealveolar process (Fig. 3). Radiopacity of the sinus with microcal-cifications or ‘‘metallic dense’’spots were interpreted as ‘‘consistentwith aspergillomas.’’The cyst was enucleated, the sinus cleaned through a Caldwell-Luc approach, and a drain was placed through a rhinoantrostomy.The patient was administered amoxicillin 500 mg plus clavulanicacid 125 mg, 3 times daily, for 5 days. The drain was removed after72 hours; his postoperative recovery was uneventful, and 19 monthsafteroperation,heisfreeofdisease.Macroscopically, the cyst measured about 3.521 cm.Microscopic examination confirmed the diagnosis of OKC.Focally, the epithelium showed increased cellularity and drop-shaped rete ridges, whereas the cells in the basal third had largeand hyperchromatic nuclei (Fig. 4). Mitoses were not identified.In addition, there was a focus of abrupt transition of the cysticepithelium to respiratory pseudostratified columnar epitheliumthat gave the impression of active replacement or ‘‘pushing’’(Fig. 5). The connective tissue of the cystic wall was vascular,edematous, with foci of calcifications, cholesterol crystals, andmild lymphoplasmacytic infiltration, whereas no granulomatousFIGURE 1.

Panoramic radiograph shows well-circumscribedradiolucent lesion apical to the first molar tooth.FIGURE 2.Connective tissue lined by a uniformly thinparakeratinized epithelium without rete ridges. Notice thecorrugated parakeratinized surface and a basal layercomposed of columnar cells with reverse nuclear polarity(hematoxylin-eosin stain, original magnification400).FIGURE 3.A, Computed tomography scan, coronal view,reveals diffuse radiopacity mainly toward the floor of the leftmaxillary sinus, bone resorption at the anterolateral wall of themaxilla close to the alveolar process, and microcalcifications(arrows). B, Computed tomography scan, sagittal view,reveals diffuse radiopacity mainly toward the floor of the leftmaxillary sinus and microcalcifications (arrows).FIGURE 4.Odontogenic keratocyst epithelium showsincreased cellularity, drop-shaped rete ridges, and cells withhyperchromatic nuclei in the basal compartment(hematoxylin-eosin stain, original magnification400).Brief Clinical StudiesThe Journal of Craniofacial Surgery&Volume 22, Number 2, March 2011

722*2011 Mutaz B. Habal, MDCopyright © 2011 Mutaz B. Habal, MD. Unauthorized reproduction of this article is prohibited.reaction, fibrosis, or necrotic foci were evident. Periodic acid-Schiff stain revealed fungal hyphae and spores in the mucosalconnective tissue, close to but not infiltrating vessels (Fig. 6).Final diagnosis was OKC with yeast.A complete blood count was not suggestive of hematologicdisease or diabetes mellitus, and an HIV test was negative.DISCUSSIONSinus involvement by OKCs is estimated to occur in less than 1% ofthe cases,2

but replacement of respiratory epithelium with OKCepithelium is unusual. Yamazaki et al3

described a case of an OKCin a 39-year-old woman that involved an impacted maxillary pre-molar, expanded to the maxillary sinus, and finally reached theinferior nasal meatus. Replacement of the OKC lining by respiratoryepithelium was attributed to the proximity of the cyst to the nasalcavity. Abrupt change of OKC lining to respiratory epithelium, asseen in our patient, was reported by Vencio et al4

in a 27-year-oldwoman. The cyst was associated with an impacted right secondmaxillary molar and also invaded the sinus floor.This microscopic finding is reminiscent of the extension of

intraepithelial neoplasia of the oral cavity5,6

and other carcinomas7

along adjacent ductal epithelium basement membrane. ‘‘Ductal orglandular involvement’’ is considered an important pathway ofspread of carcinomas. In our case, we assume that the OKC epi-thelium ‘‘crept’’ on the sinus wall replacing the normal respiratoryepithelium and extended to involve most of the antral cavity. Thus,we agree with Vencio et al4

in that replacement is consistent withthe infiltrative behavior of the OKC reflected in its classificationas a neoplasm. Dysplastic features, as seen in the present case,are occasionally described in OKCs, but have not been associatedwith an aggressive growth.Our patient had a history of chronic rhinosinusitis that is themost common form of rhinosinusitis, estimated to affect about20% of the population.8

Radiological evidence of sinus opaci-fication with calcifications was consistent with fungus balls oraspergillomas, defined as noninvasive accumulations of dense con-glomeration of fungal hyphae in 1 sinus cavity. Histological evi-dence, however, of spores and hyphae in the mucosal connectivetissue is diagnostic of an invasive fungal rhinosinusitis, in particularchronic invasive fungal rhinosinusitis. This form is usually associ-ated withAspergillus fumigatusand may appear in patients undercorticosteroid treatment who are subtly immunocompromised.No other case of OKC associated with fungal rhinosinusitisand fungus balls was found in the literature. In our patient, the rootcanal therapies in the central incisors and right lateral incisor werenot close to the sinus; thus, a role for the heavy metals from rootfilling materials, in particular, zinc from zinc oxideYcontainingmaterials, do not seem probable. The blockage of the ostium by theOKC, however, may have resulted in the obstruction of sinus ven-tilation and the creation of anaerobic conditions that allowed ger-mination of fungi, which probably became invasive because of thelocal immunosuppression caused by the prolonged corticosteroidtreatment.9,10

As our patient was proved to be immunocompetent, the com-plete surgical removal of the cyst and the sinus drainage and aera-tion achieved with the rhinoantrostomy were considered curative,both for the OKC and the fungal rhinosinusitis.11

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