C.E. Credit: A Mandibular Adenomatoid Odontongenic Tumor With a Novel Treatment Utilizing Platelet-Rich Fibrin

Tarun Mundluru, DDS, MSc, is a graduate of the orofacial pain and oral medicine advanced specialty program at the Herman Ostrow School of Dentistry of USC. He practices in Pecos, Texas. Conflict of Interest Disclosure: None reported.

David Pilgrim, DDS, is a graduate of the advanced graduate program, Master of Science program in orofacial pain and oral medicine at the Herman Ostrow School of Dentistry of USC. He is a dental surgeon in Barbados. Conflict of Interest Disclosure: None reported.

Reyes Enciso, PhD, is an associate professor in the department of geriatrics, special needs and behavioral sciences at the Herman Ostrow School of Dentistry of USC. Conflict of Interest Disclosure: None reported.

Parish P. Sedghizadeh, DDS, MS, is an associate professor in the clinical dentistry division of periodontology, diagnostic sciences and dental hygiene at the Herman Ostrow School of Dentistry of USC. Conflict of Interest Disclosure: None reported.

Mohammad A. Khalifeh, DDS, MS, is an adjunct instructor of clinical dentistry in the division of periodontology, diagnostic sciences and dental hygiene at the Herman Ostrow School of Dentistry of USC. Conflict of Interest Disclosure: None reported.

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ABSTRACT

Background: Adenomatoid odontogenic tumor (AOT) is an uncommon odontogenic tumor that originates from odontogenic epithelium. It is predominantly found in young women, particularly in the maxilla in association with an unerupted permanent tooth.

Case description: This is a case report of an AOT in a 60-year-old male with an asymptomatic mandibular lesion that radiographically presented as a mixed lesion.

Conclusions: Enucleation was performed and the defect was treated with bone grafting and platelet-rich fibrin with no recurrence at follow-up.

Keywords: Adenomatoid odontogenic tumor, platelet-rich fibrin, bone graft, mandibular lesion

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The adenomatoid odontogenic tumor (AOT) has been categorized by the World Health Organization (WHO) as a benign odontogenic tumor of epithelial origin even though there is admission that this lesion has always been difficult to classify. [1] The nomenclature of this lesion has changed several times over its history, and the term AOT was accepted by the WHO in 1971. This tumor has also been dubbed the “tumor of two-thirds,” because about two-thirds of the cases occur in females, two-thirds of the cases occur in the second to third decade of life, two-thirds of the cases occur in the anterior maxilla and twothirds of the cases occur in association with an unerupted permanent canine. [2]

AOT has been described as having three variant types, [3] a follicular type, an extrafollicular type and a peripheral variant. The follicular variant has been described as being associated with the crown of an unerupted tooth, usually a canine. The extrafollicular type has no direct tooth association, while the peripheral variant occurs in gingival tissues. [4] Recurrence of AOT has been found to be rare, [5] and conservative treatment options of curettage or enucleation are implemented even though cases treated with marginal and segmental resection have also been reported.

We present a case of AOT in a 60-year-old male. The tumor created a large and expansile defect in the mandible, which can be challenging to surgically manage and reconstruct given the amount of bone destruction, less than ideal blood supply and potential for tumor recurrence without adequate excision. The tumor was treated by a novel technique involving enucleation with repair using xenograft bone mixed with injectable platelet-rich fibrin (I-PRF) and advanced platelet-rich fibrin (A-PRF). This graft type was implemented with the aim of improving the rate of healing and the quality of bone fill in the critical size defect. Experimental models have shown that cell-based tissue engineering with the use of PRF can augment new bone formation and thus can have direct positive effects on bone healing. [6]

Case Report

A 60-year-old male patient of African ethnicity presented to the Herman Ostrow School of Dentistry of USC with a referral from his dentist with concerns of a right mandibular swelling in the premolar area. The patient indicated that he had been observing this swelling for several years, and it had remained relatively constant in size for the past two years. The patient indicated no pain, discomfort or changes in sensation with respect to this swelling. His medical history was significant only for Type II diabetes mellitus, which was controlled with metformin.

Clinical examination revealed a 3 x 3 cm, smooth, unifocal circumscribed swelling, with thin mucosa covering the buccal surface of dentoalveolar bone, extending from the right mandibular canine to the right mandibular first molar (FIGURE 1A). Palpation of the growth revealed a smooth surface with well-defined borders, and an eggshell consistency was appreciated on palpation and application of firm pressure; however, this pressure was not associated with pain or discomfort.

Teeth associated with the swelling had pathological migration, and Grade 2 to Grade 3 mobility of right mandibular incisors and canine was recorded. Vitality testing on the teeth associated with or adjacent to the lesion was performed, and these teeth were found to be normally responsive to cold stimulus similar to healthy control teeth tested in other quadrants. The lesion was subjected to panoramic radiography and CT imaging without intravenous contrast (FIGURE 1B). CT report findings indicated a large cystic lesion of the right mandible with multiple internal calcifications, thinning of the buccal and lingual cortical plates of bone with perforation of the buccal plate. Based on these findings, an incisional biopsy was recommended to the patient.

The working differential diagnosis based on clinical and radiographic findings at this point included central odontogenic fibroma, calcifying odontogenic cyst, ossifying fibroma, calcifying epithelial odontogenic tumor and AOT. An incisional biopsy on which histopathology was performed followed (FIGURE 2). The subsequent pathology report indicated the lesion was consistent with an AOT (ICD-10 No. D16.5). Microscopic findings indicated a wellcircumscribed proliferation of duct-like epithelium surrounding small foci of mineralization with various architecture including rosettes, trabeculae and cribriform patterns. Polyhedral, spindled and columnar type cells with basal nuclei and clear cytoplasm were noted. Given the diagnosis of AOT, enucleation of the lesion was carried out under local anesthesia, and the right mandibular lateral incisor and canine were also extracted (FIGURES 1C and 1D). Care was taken not to perforate the lingual plate, and the inferior alveolar/mental nerve was identified and preserved throughout the procedure.

The bony defect created by the enucleation was repaired with the use of a combination of bone graft (which utilized xenograft bone, A-PRF and I-PRF membranes) and tension- free closure obtained using interrupted polyglycolic acid 4.0 sutures. For this patient, the PRF fractions were produced by using blood taken from the patient’s left antecubital vein and centrifuged using the Choukroun DUO Quattro system. A-PRF was made under protocol of 1300 RPM spin for eight minutes in silica-coated tubes and I-PRF with 700 RPM spin for four minutes in noncoated tubes. The enucleated bony site was then filled and repaired with a mixture of 0.5 grams of xenograft bone (Bio-Oss, Geistlich Pharma North America, Princeton, N.J.) and I-PRF and membranes of A-PRF (FIGURES 3A–3D). This site was then closed using interrupted sutures of 4.0 polyglycolic acid suture.

The patient was dismissed with postoperative instructions (soft diet, oral hygiene, Medrol dosepak, chlorhexidine gluconate 0.16% rinses, 500 mg of nabumetone and amoxicillin three times daily for one week). The patient was recalled every three months after an initial visit and two-week follow-up for postoperative evaluations. Postoperative results six months after enucleation of the cyst are shown (FIGURES 1E and 1F). No signs of inferior alveolar nerve dysesthesia, anesthesia, numbness or paresthesia were noted, and no recurrence was detected on one-year follow-up. Periodontal management and prosthodontic restoration are currently being planned now that the pathology has been successfully treated without recurrence. Discussions for teeth replacement are ongoing with the patient and his general dentist.

Discussion

AOT constitutes between 3% to 7% of all benign odontogenic tumors. 7 This lesion usually presents in the anterior maxilla in association with an impacted tooth (generally a canine), has a female preponderance and occurs most commonly in the second to third decade of life. AOT occurs in three variants, the follicular, extrafollicular and the peripheral, where each variant is slow growing and has similar histology. The follicular and the extrafollicular variants account for 96% of all AOTs, of which 71% of these are of the follicular variant. [8] The follicular variant is intraosseous and associated with an impacted tooth, most commonly a maxillary canine. The extrafollicular type has no such relation to an impacted tooth, but more associated with the apex or sides of the tooth or with gingival tissues. [9]

PRF is a hematological fraction produced by the centrifugation of whole blood in a blood collection tube without heparin. The variation of centrifuge speed and centrifuge time will govern the production of the type of PRF product. A-PRF and I-PRF vary from standard PRF (S-PRF) both in preparation and composition. A-PRF and I-PRF are produced using slower centrifuge speeds, and these fractions have been shown to produce more neutrophils in the useful portion of the PRF clot. [10] A-PRF and I-PRF have been reported to provide platelet-derived growth factors, bone morphogenic proteins 2 and 7, transforming growth factor beta and thrombospondin and to stimulate formation of new blood vessels. [11] These growth factors can aid in the healing process. The platelets of the fraction also influence host response by their action on granulocytes, monocytes, endothelial cells and lymphocyte recruitment to the site of activity. These cells play a role in the regulation of the host response to foreign bodies, osteogenic and angiogenic initiation and tissue restoration potential brought about by the effects of macrophages. [12] I-PRF is a more liquid fraction and is better for mixing with bone substitute materials for grafting than the firmer A-PRF.

The case reported here is unique in several aspects in that it is a mandibular lesion, extrafollicular and not associated with an impacted tooth, developed in an older adult male and radiographically presented as a mixed and not lucent lesion. This is also the first case reporting management of AOT using bone graft substitute in combination with PRF congeners.

Conclusion

We present a rare case of mandibular adenomatoid odontogenic tumor with a novel treatment approach utilizing bone graft in combination with I-PRF and A-PRF membranes. Wound closure after surgical enucleation has not been standardized. In this case report, we sought to propose the use of bone graft in association with A-PRF and I-PRF as a useful technique for grafting and site closure, as there are indications that bone restitution time and healing time are improved.

This work was presented as a poster at 2019 Research Day organized by the Herman Ostrow School of Dentistry of USC.

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C.E. QUESTIONS

March 2022 Continuing Education Worksheet

This worksheet provides readers an opportunity to review C.E. questions for the article “A Mandibular Adenomatoid Odontogenic Tumor With a Novel Treatment Utilizing PRF: A Case Report” before taking the C.E. test online. You must first be registered at cdapresents360.com to take the test online. This activity counts as 0.5 of Core C.E.

1. The adenomatoid odontogenic tumor (AOT) has been dubbed the “tumor of two-thirds” for all but which one of the following reasons?

a. Approximately two-thirds of the cases occur in females.

b. Approximately two-thirds of the cases occur in the second to third decade of life.

c. Approximately two-thirds of the cases occur in the mandible.

d. Approximately two-thirds of the cases occur in association with an unerupted canine.

2. Which of the following describe the variant types associated with AOT (mark all that apply)?

a. Follicular

b. Marginal

c. Extrafollicular

d. Peripheral

e. All of the above

3. In the case presented, the working differential diagnosis based on clinical and radiographic findings included:

a. Central odontogenic fibroma

b. Calcifying odontogenic cyst

c. Ossifying fibroma

d. Calcifying epithelial odontogenic tumor

e. All of the above

4. The surgical aspects in this case included all but which one of the following?

a. Sedation utilizing oral medication

b. Enucleation of the lesion

c. Extraction of the right mandibular lateral incisor and canine

d. Grafting for bony defect repair

5. The I-PRF and A-PRF used to repair the surgical site were produced by centrifuging blood obtained from the patient.

a. True

b. False

6. Which of the following were not part of the postsurgical protocol for this patient?

a. Chlorhexidine gluconate rinse

b. Soft diet

c. Amoxicillin three times daily for one week

d. Oxycodone PRN to manage pain

7. What is the most common AOT variant?

a. Follicular

b. Marginal

c. Extrafollicular

d. Peripheral

8. Which of the following statement(s) applies to PRF (mark all that apply)?

a. PRF is a hematological fraction produced by centrifuging whole blood in a blood collection tube without heparin.

b. The variation of centrifuge speed and centrifuge time will govern the production of the type of PRF product.

c. A-PRF and I-PRF are produced using slower centrifuge speeds.

d. All of the above

9. A-PRF and I-PRF have been reported to stimulate formation of new blood vessels by providing all but which one of the following?

a. Platelet-derived growth factors

b. T-cell proliferation

c. Bone morphogenic proteins

d. Transforming growth factor beta

10. The authors conclude that the successful treatment of this mandibular adenomatoid odontogenic tumor utilizing bone graft in combination with I-PRF and A-PRF membranes to repair the surgical site reaffirms this standardized and reliable method for AOT treatment.

a. True

b. False

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ACKNOWLEDGMENT The authors thank Daniel Kohanchi, DDS, and Jasmine El Khoury, DDS, who assisted during the surgery, and advanced periodontology resident Sara Elhusseini DDS, MS.

REFERENCES

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7. Vasudevan K, Kumar S, Vigneswari S. Adenomatoid odontogenic tumor, an uncommon tumor. Contemp Clin Dent 2012 Apr–Jun;3(2):245–247. doi: 10.4103/0976- 237X.96837.

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9. Kundoor R, Maloth KN, Guguloth NN, Kesidi S. Extrafollicular adenomatoid odontogenic tumor: An unusual case presentation. J Dent (Shiraz) 2016 Dec;17(4):370– 374. PMCID: PMC5136418.

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12. Thanasrisuebwong P, Surarit R, Bencharit S, Ruangsawasdi N. Influence of fractionation methods on physical and biological properties of injectable platelet-rich fibrin: An exploratory study. Int J Mol Sci 2019 Apr;20(7):1657. doi: 10.3390/ijms20071657.

THE CORRESPONDING AUTHOR, Tarun Mundluru, DDS, MSc, can be reached at tarunvsdc@gmail.com.