in vivo 24: 567-570 (2010)

Ameloblastoma of the Maxillary Sinus 11 Years after Extirpation of Extensive Dentigerous Cysts and Dystopic Wisdom Tooth

REINHARD E. FRIEDRICH1 and JOZEF ZUSTIN2

1Oral and Maxillofacial Surgery, and 2Pathology, Eppendorf University Hospital, University of Hamburg, Germany

Abstract. We present the case of a 36-year-old patient with bone is depicted on adequate radiographs. The tumor replaces ameloblastoma of the maxillary sinus. The history of the the bone by small, radiographically well-defined areas often patient was extraordinary with respect to the diagnosis of an resulting in a honey comb-like translucency (2). This feature is extensive odontogenic cyst of this sinus with a maxillary supported by the insufficient regeneration of bone that might wisdom tooth located far from the region of origin. Both cyst result in osseous expansion of the affected site (8). Association and tooth had been completely extirpated more than 10 years of ameloblastoma with dentigerous cysts is well-documented, prior to the current tumor diagnosis. Diagnosis of in particular the development of ameloblastoma in a ameloblastoma was based on routinely processed specimen and histologically proven cyst with the retained tooth inside the supported by immunohistochemical markers. Localization and bone, and in keratocystic odontogenic tumor (12-14). The extension of both cyst and neoplasm support the assumption amount of tumor inside a dentigerous cyst might vary that both entities arose from the same area. Long-term follow- considerably. On the other hand the association of dentigerous up is recommended in the treatment of odontogenic cysts. cysts with ameloblastomas was called into question (15). Conventional histological diagnosis based on representative Ameloblastoma is a benign neoplasm of epithelial origin with slices allows the clear distinction between dentigerous cyst and invasive and destructive growth characteristics (1). The ameloblastoma (16). The follow-up examination of patients recurrence rate of ameloblastoma is high in cases of incomplete treated for odontogenic cysts might contribute to the differential surgical resection (2). Whereas distant metastasis of diagnosis of odontogenic lesions. The aim of this report is to ameloblastoma is a very rare phenomenon (3), the local tumor alert clinicians to the importance of follow-up for patients with behaviour of this entity is that of a low-grade malignant tumor dentigerous cysts of the jaws. (1, 2). The tumor grows very slowly and physical findings resulting in seeking medical advice are discrete, such as a Case Report gradually increasing deformity of the jaws and/or face, loosening of teeth, or an unspecified intraoral swelling (4-6). Medical history and findings. A 36-year-old patient was The ratio of mandibular to maxillary ameloblastoma is about referred for treatment of a radiopaque tumor of the left 5.8:1 (7). The radiological appearance varies substantially (2, 7- maxillary sinus depicted on both an orthopantomograpic 10). A subtyping of ameloblastoma was suggested based on radiograph and Water’s view. General medical history of the morphological and radiological findings, emphasizing patient was unsuspicious. differences in tumor biologies delineated from this classification Physical investigation of the patient revealed a scar of the (2, 7). The solid/multicystic subtype is by far the most common left upper vestibule. The patient mentioned that about eleven type of ameloblastoma. Typically, a multilocular destruction of years earlier, at the age of 25 years, the left maxillary sinus had been surgically involved for extirpation of a cyst and wisdom tooth lying in the sinus. The patient provided radiographs of the former treatment and a medical report. The Correspondence to: Professor Reinhard E. Friedrich, MD, DMD, report detailed the transantral access to a completely extirpated Ph.D., FEBOMFS, Oral and Maxillofacial Surgery, Eppendorf large dentigerous cyst of the maxillary sinus and a dystopic University Hospital, University of Hamburg, Martinist. 52, D-20246 tooth, the upper left wisdom tooth. The radiographs at that Hamburg, Germany. Tel: +49 40741053259, Fax: +49 40741058120, e-mail: [email protected] time depict tooth 28 (FDI nomenclature) to be located at the upper medial side of the maxillary sinus, in close proximity Key Words: Ameloblastoma, dentigerous cyst, maxillary sinus to the orbital floor. On lateral and anterior radiographs of the tumor, calretinin, 3D-reconstruction of facial bone. maxillary sinus, this tooth appears to have had a malformed

0258-851X/2010 $2.00+.40 567 in vivo 24: 567-570 (2010) root. On the panoramic radiograph, the tuber area of the Discussion maxilla is not as clearly demarcated as the opposite region. However, osteolysis of this area cannot be determined from This report describes the diagnosis and treatment of a maxillary this early radiograph (Figure 1 A). ameloblastoma. The history of the patient was extraordinary Current diagnostics included a panoramic radiograph with respect to the diagnosis of an extensive odontogenic cyst (Figure 1 B) and computed tomogram (CT) of the region of of this sinus with a maxillary wisdom tooth located far from interest (Figure 1 C – E). On the panoramic radiograph the the region of origin. Both cyst and tooth had been completely left tuber region of the maxilla was enlarged in size and extirpated more than 10 years prior to the current tumor showed irregular borders projecting into the maxillary sinus diagnosis. The histological diagnosis of the first space- and to the retromaxillary region. The adjacent molars were consuming entity of the maxillary sinus was a dentigerous cyst. in place but were incorporated into the lesion that was The diffential diagnosis of dentigerous cyst to ameloblastoma depicted by a somewhat oval shape. The CT scans and three- can be made positively on routinely processed slices by dimensional reconstruction of the bony surface revealed the experienced pathologists (16). The translocation of the wisdom osseous expansion of the distal parts of the left maxilla, with tooth to the orbital floor is probably the result of the cyst multiple defects of the cortex leading to a characteristic growth into the sinus, taking the path of least resistance. soap-bubble appearance. Inside the lesion, some areas The odontogenic tumor was quite large at the time of mimicking a trabecular pattern were isointense to bone diagnosis. The localization of the region giving rise to the (Figure 1 D). The cyst-like lesion filled the sinus to about tumor with respect to the extension of the entity at the time of two-thirds of its volume. Tentative diagnosis was an diagnosis has to take into consideration primarily the tuber odontogenic tumor. region of the left maxilla. In due consideration of the radiological center of the lesion, it is reasonable to assume that Surgery. The left maxillary sinus was opened transantrally and the tumor originated in the area of the left upper third molar. It a cyst-like tumor was located in the sinus filling the cavity to is likely that odontogenic epithelium in the tuber region gave more than half of its volume (Figure 1 F). The tumor was rise to the ameloblastoma. The imaging of the tumor and the extirpated with bone and teeth, and the antrum was closed with histogenesis of teeth make it likely that both space-occupying adjacent flaps by primary intention. Healing was uneventful. lesions come from the same area. Most ameloblastoma arise Despite the cyst-like appearance on images, the tumor proved inside the bone (2). With respect to the visible expansion of the to be macroscopically solid. Initially, the resection specimen upper jaw and the remnants of bone inside the intracavitary was diagnosed as a keratocystic odontogenic tumor. However, parts of the lesion, the current case confirms this growth careful inspection of the specimen disclosed an ameloblastoma pattern. of the solid and multicystic type (2). In order to verify clear The metachronous occurrence of both lesions in the same surgical margins, the patient underwent surgery for a second region might be coincidental. However, it is well recognized time and the margins of the first defect were resected to a that ameloblastoma might arise as a result of neoplastic distance of 10 to 15 mm. Histology of the specimen revealed alterations in the epithelia of dentigerous cysts and no tumor. Healing again was uneventful. transformation of the keratocystic odontogenic tumor (2). The neoplastic change inside a dentigerous cyst might be focal. Histology. Tissues were fixed in buffered formalin These findings and the collected data are deduced from surgical immediately after the surgery and sent to the histopathologic interventions and do not necessarily represent the biological laboratory. Five-μm thick sections were cut from the paraffin- profile of ameloblastoma in general. It cannot entirely be ruled embedded blocks and stained with hematoxylin-eosin. After out that the initial translatory movement of the retained tooth to deparaffinization, immunohistochemical stainings with the maxillary sinus was caused by neoplastic tissue (eventually calretinin (rabbit calretinin, No.18-0211; Zymed Laboratories, in a preliminary stage of tumor development). Indeed, the San Francisco, CA, USA) and p63 (mouse monoclonal, clone developmental stage of ameloblastoma at the time of diagnosis 4A4; Dako, Hamburg, Germany) were performed. The varies considerably. Ameloblastoma might be an incidental presence, distribution, and intensity of stained cells was finding following cyst extirpation (even as a focal neoplastic determined using conventional light microscopy, giving a part inside the cystic lumen), or an expansive tumor with bone descriptive grading of weak, moderate, or intense staining. The resorption and bone extension. Moreover, the variation of nucleus and the cytoplasm of the stellate reticulum-like cells ameloblastoma diagnosis related to chronological age, with a were moderately stained with calretinin antibody (17-19). The preference for the second decade of life, all show that the nuclei of virtually all cells (20, 21) were strongly positive for biological profiles of ameloblastomas do not fit into a single p63, but scattered superficial luminal cells were only diagnostic system (2, 22). The range of chronological ages of minimally stained or the immunohistochemical reaction was patients with ameloblastoma diagnosis covers the period from completely absent from this layer (Figure 2). early childhood to senility, i.e. the whole lifespan (1).

568 Friedrich and Zustin: Maxillary Sinus Ameloblastoma

Figure 1. A: Detail of orthopantomogram of the 25-year-old man prior to extirpation of the maxillary sinus cyst. The dystopic left upper wisdom tooth lies close to the roof of the sinus and appears to have a malformed root. B: Detail of orthopantomogram of the 36-year old man prior to extirpation of the maxillary sinus tumor. The inhomogeneous and partially radiopaque tumor fills the dorsal portion of the maxillary sinus. The tumor appears to have disintegrated the tuber region and the dorsal part of the maxillary sinus wall. C: CT-based three-dimensional reconstruction of the bony surface in an axial view reveals the combination of osseous expansion and osteolytic foci related to the soap-like maxillary tumor, also seen on the axial slice (D). E: The three-dimensional reconstruction of the bony surface in the en face view shows that osseous material also extends into the sinus. F: Intraoperative aspect of the cyst-like tumor after fenestration of the sinus wall.

Figure 2. Histological findings of maxillary ameloblastoma. A: Cystic area of the ameloblastoma demonstrated fibrous stroma and epithelial lining with basal palisading of nuclei and somewhat loosened luminal epithelial layers. B: Small parts of the tumor wall presented a follicular pattern of ameloblastoma infiltrates (A & B: hematoxylin-eosin). C: Uniform nuclear p63 positivity of the tumor epithelium and D: scattered moderate nuclear and cytoplasmatic calretinin-positive stellate reticulum-like cells.

Therefore, it cannot be excluded that the tumor was already on the evaluation of case reports alone, the mean age was 37.4 present at the time of cyst extirpation, e.g. in the tuber region of years and showed differences between gender (female: 35.2 the maxilla. According to Gardner, the mean age of patients years, male: 39.2 years) (2). The mean age of diagnosis for with solid/multicystic ameloblastoma is 39 years (23). Based maxillary ameloblastoma was higher, at 47 years (2). The

569 in vivo 24: 567-570 (2010) patient was of relatively young age in our particular case of 8 Navarro CM, Principi SM, Massucato EM and Sposto MR: diagnosis of maxillary ameloblastoma. Maxillary unicystic ameloblastoma. Dentomaxillofac Radiol 33: Calretinin is a calcium-binding protein abundantly expressed 60-62, 2004. 9 Pekiner FN, Ozbayrak S, Sener BC, Olgaç V and Sinanoğlu A: in neuronal tissues. The biological function of calretinin is as Peripheral ameloblastoma: a case report. Dentomaxillofac Radiol yet unknown, but it has possible roles as a regulator of 36: 183-186, 2007. apoptosis, and a calcium buffer. Calretinin has been determined 10 Wassermann V and Huisman TA: Cystic ameloblastoma in a 5- as a sensitive marker to discriminate ameloblastoma from other year-old boy. Pediatr Radiol 38: 482, 2008. odontogenic tumors (18), including keratocystic odontogenic 11 Vanoven BJ, Parker NP and Petruzzelli GJ: Peripheral tumor (KOT) (19). However, scant positivity of basal epithelia ameloblastoma of the maxilla: a case report and literature review. was found in KOT in another study (24). In the present case, Am J Otolaryngol 29: 357-360, 2008. 12 Bailey JW: Dentigerous cyst with ameloblastoma: report of a case. the immunoreactivity of ameloblastoma was restricted to Oral Surg Oral Med Oral Pathol 4: 1122-1126, 1951. stellate reticulum-like neoplastic epithelial cells and widely 13 Houston GD: Oral pathology. Ameloblastoma arising in a expressed throughout the tumor (Figure 2). dentigerous cyst. J Okla Dent Assoc 98: 28-29, 2007. P63 expression was found in a variety of ameloblastomas 14 Cunha EM, Fernandes AV, Versiani MA and Loyola AM: Unicystic (21). P63 was also detected in other odontogenic lesions that ameloblastoma: a possible pitfall in periapical diagnosis. Int Endod share a locally aggressive phenotype (20). However, KOT also J 38: 334-340, 2005. expresses p63 (25). Topographical differences of p63 15 Shear M and Speight PM: Cysts of the Oral and Maxillofacial Regions, 4th edition, Oxford, Blackwell Munksgard, p. 74, 2004. expression were noted compared to solid odontogenic 16 Dunsche A, Babendererde O, Lüttges J and Springer IN: neoplasms, e.g. ameloblastoma, and cystic lesions (20), which Dentigerous cyst versus unicystic ameloblastoma – differential should be investigated in more detail. diagnosis in routine histology. J Oral Pathol Med 32: 486-491, 2003. Conclusion 17 Coleman H, Altini M, Ali H, Doglioni C, Favia G and Maiorano E: Use of calretinin in the differential diagnosis of unicystic Extirpation of odontogenic cysts and lesions is an everyday ameloblastomas. Histopathology 38: 312-317, 2001. 18 Alaeddini M, Etemad-Moghadam S and Baghaii F: Comparative task for dentists and oral/maxillofacial surgeons. The vast expression of calretinin in selected odontogenic tumours; a possible majority of these lesions are benign and are definitively treated relationship to histogenesis. Histopathology 52: 299-304, 2008. using adequate surgical technique. This report demonstrates 19 DeVilliers P, Liu H, Suggs C, Simmons D, Daly B, Zhang S, that follow-up control of patients treated for cystic lesions of Raubenheimer E, Larsson A and Wright T: Calretinin expression in the jaws is recommended and the need for thorough the differential diagnosis of human ameloblastoma and keratocystic investigation of the specimen is essential in adequate diagnosis odontogenic tumor. Am J Surg Pathol 32: 256-260, 2008. and therapy. 20 Gratzinger D, Salama ME, Poh CF and Rouse RV: Ameloblastoma, calcifying epithelial odontogenic tumor, and glandular odontogenic cyst show a distinctive immunophenotype with some myoepithelial References antigen expression. 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J Oral Maxillofac Surg 67: 1163- 1999. 1166, 2009. 24 Piattelli A, Fioroni M, Iezzi G and Rubini C: Calretinin expression 4 Nikitakis NG and Brooks JK: Hard swelling in the right mandible. in odontogenic cysts. J Endod 29: 394-396, 2003. Ameloblastoma. Gen Dent 56: 214-217, 2008. 25 Gurgel CA, Ramos EA, Azevedo RA, Sarmento VA, da Silva 5 Carr BM and Mohnac AM: Simple ameloblastoma within a Carvalho AM and dos Santos JN: Expression of Ki-67, p53 and follicular cyst of the maxilla. Report of a case. Oral Surg Oral Med p63 proteins in keratocyst odontogenic tumours: an Oral Pathol 15: 1136-1141, 1962. immunohistochemical study. J Mol Histol 39: 311-316, 2008. 6 Kim SG and Jang HS: Ameloblastoma: a clinical, radiographic, and histopathologic analysis of 71 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 91: 649-653, 2001. 7 Reichart PA, Philipsen HP and Sonner S: Ameloblastoma: Received November 11, 2009 biological profile of 3677 cases. Eur J Cancer B Oral Oncol 31B: Revised March 26, 2010 86-99, 1995. Accepted March 29, 2010

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