Brown tumor of hyperparathyroidism with multiple lesions

Sumit Majumdar; Divya Uppala; Sreekanth Kotina; Bandi Alekhya

doi:10.4103/jomfp.jomfp_409_20



CASE REPORT

Year : 2022 \| Volume : 26 \| Issue : 5 \| Page : 111-115

Brown tumor of hyperparathyroidism with multiple lesions

Sumit Majumdar, Divya Uppala, Sreekanth Kotina, Bandi Alekhya
Department of Oral Pathology and Microbiology, GITAM Dental College and Hospital, Visakhapatnam, Andhra Pradesh, India

Date of Submission	02-Oct-2020
Date of Decision	03-Aug-2021
Date of Acceptance	06-Aug-2021
Date of Web Publication	28-Feb-2022

Correspondence Address:
Bandi Alekhya
Department of Oral Pathology and Microbiology, GITAM Dental College and Hospital, Visakhapatnam - 530 045, Andhra Pradesh
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/jomfp.jomfp_409_20

Abstract

Brown tumors are rare focal giant-cell lesions that arise as a direct result of the effect of parathyroid hormone (PTH) on bone tissue in some patients with hyperparathyroidism. Browns tumor is a syndrome associated with an increase in PTH levels by parathyroid glands resulting in hypercalcemia. In the present case report, a 44-year-old female patient presented with a rare case of brown tumor with multiple lesions in the head-and-neck region. The recent advance in various diagnostic and biochemical tests helps in early diagnosis of hyperparathyroidism cases. The dentist should be aware of oral manifestations associated with this type of systemic disease.

Keywords: Central giant cell lesion, osteitis fibrosa cystica, osteoclastoma

How to cite this article:
Majumdar S, Uppala D, Kotina S, Alekhya B. Brown tumor of hyperparathyroidism with multiple lesions. J Oral Maxillofac Pathol 2022;26:111-5

How to cite this URL:
Majumdar S, Uppala D, Kotina S, Alekhya B. Brown tumor of hyperparathyroidism with multiple lesions. J Oral Maxillofac Pathol [serial online] 2022 [cited 2023 Mar 22];26:111-5. Available from: https://www.jomfp.in/text.asp?2022/26/5/111/338761

Introduction

Browns tumor is a syndrome associated with an increase in parathyroid hormone (PTH) levels by parathyroid glands resulting in hypercalcemia. Parathyroid glands monitor the serum calcium concentration. In the nonpathologic state, PTH secretion increases in response to low serum calcium concentrations, thereby enhancing calcium reabsorption and osteoclastic bone resorption. When parathyroid glands become abnormal, there is abnormal increase in PTH secretion result in increased reabsorption of calcium and increased bone resorption.

In the present case report, a 44-year-old female from Visakhapatnam reported to the outpatient department with a chief complaint of swelling in the lower left back tooth region. Advised radiological investigations. On cone-beam computed tomography (CBCT), shocking multiple hypodense areas with aggressive bone resorption were observed and on blood investigations observed elevated serum parathormone levels: 890 ng/mL.

Case Report

A 44-year-old female reported outpatient clinic of GITAM Dental College and Hospital with a chief complaint of swelling in the lower left back tooth region for 5 months. On past dental history, the patient gives the history of enucleation and extraction in relation to 35. It was diagnosed as dentigerous cyst on histopathological examination.

On extraoral examination

Swelling was observed on lower one-third of the face on the left side which extending from the left corner of the mouth to tragus anteroposteriorly were as superoinferiorly from alatragal line to 0.5 cm below the lower border of mandible. On intraoral examination, ill-defined swelling with obliteration of buccal vestibule was observed in relation to 34, 36 teeth.

Based on clinical features, a provisionally diagnosed as odontogenic cyst was given. On aspiration, blood-tinged fluid was aspirated.

Radiological investigations

On panoramic radiography, a well-defined radiolucent lesion was observed in relation to 46, 47 and right parasymphyseal region and left posterior mandible and on ascending ramus region [Figure 1]. On the occlusal radiograph, bicortical plate expansion on the left side. CBCT revealed an ill-defined bone with hypodense areas involving alveolus of 17 (right maxilla), right body of mandible, left ramus of mandible and right frontal sinus noted. Bilateral temporomandibular joints (TMJs) showed mild degenerative changes [Figure 2]. On hand and wrist radiograph, subperiosteal bone resorption and metastatic calcium deposition were observed. Posteroanterior skull view: multiple punched out radiolucent areas were observed. Based on the above radiological features, the lesion was diagnosed as multiple osteolytic lesions (multiple myeloma, osteodystrophic lesion, Noonan-like multiple giant cell lesion syndrome, hyperparathyroidism).

Figure 1: One well-defined radiolucent area in relation to 46, 47 and other parasymphysis region on the right side; one well-defined radiolucent area in relation to 36, 36 which is extending from root apex to beyond the lower boarder; other similar lesion was found on ascending ramus region

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Figure 2: Well defined hypodense bony lesion noted in right body of mandible. Large expansile well defined hypodense bony lesion noted in left Ascending ramus of mandible

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The blood reports as shown were serum alkaline phosphatase: 358 U/L, serum calcium: 14.0 mg/dl and serum parathormone levels: 890 ng/ml.

On histopathological examination

The hematoxylin and eosin-stained soft tissue section exhibited loosely arranged stroma with small capillaries and proliferating fibroblasts. The collagen fiber bundles were arranged in whorl pattern. There were abundant multinucleated giant cells present throughout the tissue. These giant cells consisted of 10–15 nuclei and many of them being prominent, thus showing features of active division. These giant cells were distributed near areas of hemorrhage, extravagated blood [Figure 3], [Figure 4], [Figure 5]. Based on the radiographical, histopathological features and blood investigations, it was diagnosed as brown tumor.

Figure 3: Haematoxylin and eosin stained soft tissue section exhibits loosely arranged connective tissue stroma with haematoxyphilic areas

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Figure 4: H&E stained soft tissue section exhibits multinucleated giant cells in the loosely arranged connective tissue stroma ,numerous blood capillaries and areas of hemorrhage

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Figure 5: H&E stained soft tissue section exhibits multinucleated giant cells having up to 10-15 nuclei close to the vascular spaces . The connective tissue also exhibits spindle shaped stroma cells in the loosely arranged stroma ,blood capillaries and areas of hemorrhage

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Discussion

The parathyroid glands are situated in the thyroid gland, which is not regulated by the pituitary gland, but directly under the control of serum ionized calcium concentrations.^[1],[2] Hyperparathyroidism occurs in three significant forms as primary, secondary and tertiary [Table 1].^[3]

Table 1: Classification of hyperparathyroidism^[1]

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The classic symptoms of the disease are bones, stones, abdominal groans and psychic moans.^[4] In developed nations, it is seen in elderly females with mild to moderate hypercalcemia and very few with classic symptoms.^[5]

Normal parathyroid

Physiology parathyroid glands constantly monitor serum calcium concentration.^[6] This involves a complex calcium-ion sensing receptor mechanism in the parathyroid cells that respond to changes in serum calcium concentration. This mechanism occurs in all normal parathyroid glands to maintain the normal serum calcium levels, i.e., 2.1 and 2.65 mmol/L, which is essential for normal bone metabolism, muscle and nerve physiology.^[7],[8]

The name “brown tumor” is a misnomer derived from the color, which is caused by the vascularity, hemorrhage and deposits of pigment hemosiderin.^[9] It is a nonneoplastic giant cell lesion which is slowing growing and locally destructive. Its vascularity, hemorrhage and hemosiderin impart the characteristic brown color. The PTH has a direct effect on bone.^{[10],[11],[12],[13],[14]}

Genetic causes of primary hyperparathyroidism

The MEN1 gene is located in 11q14 and consists of 10 exons that encode 610 amino acid proteins referred to as menin. This protein is present in on dividing cells.

Differentiating between a brown tumor and other giant cell tumors may be very difficult, even with histology [Table 2].

Table 2: Difference between brown tumor and other giant cell tumors

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Cases of giant cells associated with neurofibromatosis (type 1),^[18] Noonan-like syndrome or both have been reported. Histologically giant cell lesions are exhibiting rich osteoclast fields which could not be easily distinguished from cherubim and Noonan syndrome.^[19]

A reparative granuloma is different from the brown tumor by the absence of hyperparathyroidism. In histological section shows giant cells in the less dense stroma but more vascularized.^[20] Patients with giant-cell tumors associated with hyperparathyroidism and hypercalcemia to differentiate this granuloma from brown tumors.

Conclusion

Brown tumor most commonly affects mandible rarely maxilla, but in our case, multiple lesions in skull, mandible, maxilla, TMJ. The recent advance in various diagnostic and biochemical tests helps in early diagnosis of hyperparathyroidism cases. The dentist should be aware of oral manifestations associated with this type of systemic disease.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initial s will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.	Arunkumar KV, Kumar S, Deepa D. Brown tumor in mandible as a first sign of Vitamin D deficiency: A rare case report and review. Indian J Endocrinol Metab 2012;16:310-5.
2.	Mackenzie-Feder J, Sirrs S, Anderson D, Sharif J, Khan A. Primary hyperparathyroidism: An overview. Int J Endocrinol 2011;2011:251410.
3.	Indumati Rao K, Priya N, Rao K, Ashwin D. Brown tumor of mandible in association with primary hyperparathyroidism. Indian J Oral Sci 2016;7:54-5.
4.	Pradeep PV, Jayashree B, Mishra A, Mishra SK. Systematic review of primary hyperparathyroidism in India: The past, present, and the future trends. Int J Endocrinol 2011;2011:921814.
5.	Lundgren E, Rastad J. A Diagnosis, Natural History and Intervention in Sporadic Primary Hyperparathyroidism, in Surgical Endocrinology. Philadelphi: Lippincott Williams and Wilkins; 2001. p. 137-62.
6.	Bilezikian JP, Silverberg SJ. Clinical practice. Asymptomatic primary hyperparathyroidism. N Engl J Med 2004;350:1746-51.
7.	Selvi F, Cakarer S, Tanakol R, Guler SD, Keskin C. Brown tumour of the maxilla and mandible: A rare complication of tertiary hyperparathyroidism. Dentomaxillofac Radiol 2009;38:53-8.
8.	Rai S, Rattan V, Bhadada SK. Giant cell lesions associated with primary hyperparathyroidism. J Maxillofac Oral Surg 2015;14:930-4.
9.	Maskey R, Panchani R, Varma T, Goyal A. Primary hyperparathyroidism in India: A cocktail of contemporary and classical presentations: Lesson from 47 cases. Indian J Endocrinol Metab 2013;17:S209-11.
10.	Rosenberg EH, Guralnick WC. Hyperparathyroidism, a review of 220 proved cases with special emphasis on findings in the jaws. Oral Surg Oral Med Oral Pathol 1962;15 Suppl 2:84-94.
11.	Haslett C, Chilvers ER, Hunter JA, Boon NA. Davidson's Principles and Practice of Medicine. 18^th ed. USA: Churchil Livingstone; 2000. p. 575-9.
12.	De Lange J, Van den Akker HP. Clinical and radiological features of central giant-cell lesions of the jaw. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2005;99:464-70.
13.	Teh BT, Kytölä S, Farnebo F, Bergman L, Wong FK, Weber G, et al. Mutation analysis of the MEN1 gene in multiple endocrine neoplasia type 1, familial acromegaly and familial isolated hyperparathyroidism. J Clin Endocrinol Metab 1998;83:2621-6.
14.	Carpten JD, Robbins CM, Villablanca A, Forsberg L, Presciuttini S, Bailey-Wilson J, et al. HRPT2, encoding parafibromin, is mutated in hyperparathyroidism-jaw tumor syndrome. Nat Genet 2002;32:676-80.
15.	Thakker RV. Multiple endocrine neoplasia--Syndromes of the twentieth century. J Clin Endocrinol Metab 1998;83:2617-20.
16.	Shattuck TM, Välimäki S, Obara T, Gaz RD, Clark OH, Shoback D, et al. Somatic and germ-line mutations of the HRPT2 gene in sporadic parathyroid carcinoma. N Engl J Med 2003;349:1722-9.
17.	Howell VM, Haven CJ, Kahnoski K, Khoo SK, Petillo D, Chen J, et al. HRPT2 mutations are associated with malignancy in sporadic parathyroid tumours. J Med Genet 2003;40:657-63.
18.	Ruggieri M, Pavone V, Polizzi A, Albanese S, Magro G, Merino M, et al. Unusual form of recurrent giant cell granuloma of the mandible and lower extremities in a patient with neurofibromatosis type 1. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;87:67-72.
19.	Idowu BD, Thomas G, Frow R, Diss TC, Flanagan AM. Mutations in SH3BP2, the cherubism gene, were not detected in central or peripheral giant cell tumours of the jaw. Br J Oral Maxillofac Surg 2008;46:229-30.
20.	Fernandez-Bustillo AJ, Martino-Gorvea R, Murillo-Cortes J, Garatea-Crelgo J, Palomero-Rodríguez R. Primary hyperparathyroidism. Presenting as brown tumors in the maxilla. Med Oral 2000;5:208-1.