Giant Cell Epulis as a Presenting Manifestation of Primary Hyperparathyroidism: A Case Series from a Tertiary Care Center

INTRODUCTION

Primary hyperparathyroidism (PHPT) is an endocrine disorder characterized by inappropriate excessive secretion of parathyroid hormone (PTH) which leads to hypercalcemia by various mechanisms, one of which is via increased bone resorption. There is increase in osteoclastic activity which may result in changes in the skeletal system ranging from generalized osteopenia or osteoporosis to localized lesions like subperiosteal resorption, bone cysts, fractures, and osteoclastomas or brown tumors.¹ Oral manifestations of PHPT include brown tumors, giant cell epulis, oral tori, soft tissue calcifications, mobile teeth, and various other dental problems. These may manifest as facial asymmetry, facial swelling, pain, dental malocclusion, dental spacing, delay in dental development, caries and post-extraction complications.² The most common oral manifestation of PHPT is thinning of lamina dura, while giant cell epulis are seen in less than 10% of cases; epulis as presenting manifestation of PHPT is extremely rare.^3,4 Giant cell epulis or peripheral giant cell granuloma is a benign lesion, which maybe sessile or pedunculated and arises from the mandible in most of the cases.⁵

CASE SERIES

We retrospectively analyzed 579 patients from a tertiary care center in North India. Patients were analyzed for the prevalence of oral manifestations in PHPT. Thirteen of 579 patients (2.24%) presented with maxillofacial brown tumor. Eight of these 13 patients presented with an oral manifestation as a first presentation of PHPT; six patients presented with facial asymmetry and two had difficulty in mouth opening. Maxillary and mandibular involvement was present in four patients each.

Age of presentation varied from 25 to 48 years, all except one patient were females. Hypercalcemic was present in all and PTH levels ranged from 324.3 to 1291.5 pg/mL (Table 1).

DISCUSSION

Jaffe first coined the term giant cell reparative granuloma Epulis which is a benign, nonodontogenic tumor, originates from molar and premolar regions of gingiva and have female predominance.⁵ It is well demarcated, sessile or pedunculated, red or bluish red in color. Sometimes giant cell epulis is also associated with xerostomia, causing reduced cleansing action of saliva which facilitates accumulation of local irritants.⁶

The term Giant cell lesions of the oral cavity have three pathologic entities: (1) The giant cell tumor which is a true neoplastic tumor and represents one of the oral manifestations of hyperparathyroidism; (2) Giant cell reparative granuloma, also known as giant cell epulis, which may be either central (intraosseous) or peripheral (extraosseous); (3) The central giant cell granuloma which is slowly growing or aggressive lesion causing pain and local destruction of bone. Giant cell lesion is usually associated with Cherubism, Noonan syndrome, Jaffe-Campanacci syndrome, Neurofibromatosis type I, or Ramon syndrome.⁷

The term tumor is a misnomer because the lesion, although invasive in some instances, does not have a neoplastic potential and should be differentiated from true giant cell tumors of bone. Brown tumors are very similar to giant cell tumors, but in the context of hyperparathyroidism they are considered as reparative granulomas. The histological feature of brown tumor is delineated by soft tissue swelling consisted of hemorrhage foci, cystic areas lined with connective contexture, and fibrovascular tissue surrounding multinucleated cells.

The prevalence of hyperparathyroidism associated with giant cell lesions is 5.9% and is rarely observed as initial manifestation.⁸ Giansanti and Waldron reviewed 720 cases of giant cell lesions and did not find any association with hyperparathyroidism.⁹ Eighty percent of patients are identified on the basis of an incidental discovery of hypercalcemia. In severe and late stages of hyperparathyroidism, skeletal changes can be observed. These changes include an increased number of osteoclasts, which erode bone matrix and increase bone resorption. This in turn causes increased osteoblastic activity, which results in new bone formation. The bone loss predisposes individuals to microfractures and hemorrhages, which result in an influx of macrophages and increased fibrous tissue, creating a mass of reactive tissue known as osteitis fibrosa cystica. It is also known as brown tumor, the color of which can be attributed to the increased hemorrhage and hemosiderin deposition.

Diagnosing hyperparathyroidism can be challenging during the initial presentation of epulis, especially when there are no other features of PHPT. In a case report by Pattnaik et al., the suspicion of PHPT arose during the investigation of an epulis, which had a history of multiple excisions and recurrences.⁵ Similarly, Smith et al. reported a case of PHPT where the primary presentation was an intraoral lesion, and the diagnosis of PHPT was made based on the presence of hypercalcemia.³ In another instance, Choi et al. documented a case of giant cell epulis associated with end-stage renal failure due to secondary hyperparathyroidism.¹⁰

The presence of underlying PHPT should be sought in all unexplained mandibular or maxillary lesions. The majority of the lesions disappear with the removal of parathyroid pathology. Surgical resection of a brown tumor is generally not recommended and should only be considered if the patient wants quick resolution.

CONCLUSION

The presence of underlying PHPT should be sought in all unexplained mandibular and maxillary lesions as the surgery for parathyroid gland alleviates oral symptoms avoiding unnecessary oral surgery. It also saves the patient from developing other systemic manifestations of hyperparathyroidism.

ORCID

Kishore Abuji https://orcid.org/0000-0003-2904-195X

Divya Dahiya https://orcid.org/0000-0002-0237-8459

REFERENCES

1. Bringhurst FR, Demay MB, Kronenberg HM. Bone and Mineral Metabolism in Health and Disease. In: Jameson JL, Fauci AS, Kasper DL, Hauser SL, Longo DL, Loscalzo J, (Eds). Harrison’s Principles of Internal Medicine, 20e. New York, NY: McGraw-Hill Education; 2018. pp. 2909–2921.

2. Khalekar Y, Zope A, Brahmankar U, et al. Hyperparathyroidism in dentistry: Issues and challenges!! Indian J Endocrinol Metab 2016;20(4):581–582. DOI: 10.4103/2230-8210.183452.

3. Smith BR, Fowler CB, Svane TJ. Primary hyperparathyroidism presenting as a “peripheral” giant cell granuloma. J Oral Maxillofac Surg 1988;46(1):65–69. DOI: 10.1016/0278-2391(88)90303-5.

4. Parbatani R, Tinsley GF, Danford MH. Primary hyperparathyroidism presenting as a giant-cell epulis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1998;85(3):282–284. DOI: 10.1016/s1079-2104(98)90009-9.

5. Pattnaik N, Rajguru JP, Pattanaik SJ, et al. Coexistence of hyperparathyroidism and peripheral giant cell granuloma of the jaw: A rare case report. J Family Med Prim Care 2020;9(6):3142–3146. DOI: 10.4103/jfmpc.jfmpc_479_20.

6. Bodner L, Peist M, Gatot A, et al. Growth potential of peripheral giant cell granuloma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1997;83(5):548–551. DOI: 10.1016/s1079-2104(97)90118-9.

7. Chuong R, Kaban LB, Kozakewich H, et al. Central giant cell lesions of the jaws: A clinicopathologic study. J Oral Maxillofac Surg 1986;44(9):708–713. DOI: 10.1016/0278-2391(86)90040-6.

8. Triantafillidou K, Zouloumis L, Karakinaris G, et al. Brown tumors of the jaws associated with primary or secondary hyperparathyroidism. A clinical study and review of the literature. Am J Otolaryngol 2006;27(4):281–286. DOI: 10.1016/j.amjoto.2005.11.004.

9. Giansanti JS, Waldron CA. Peripheral giant cell granuloma: Review of 720 cases. J Oral Surg 1969;27(10):787–791. PMID: 5258991.

10. Choi C, Terzian E, Schneider R, et al. Peripheral giant cell granuloma associated with hyperparathyroidism secondary to end-stage renal disease: A case report. J Oral Maxillofac Surg 2008;66(5):1063–1066. DOI: 10.1016/j.joms.2007.11.030.