Dentomaxillofacial Radiology (2009) 38, 53-58
© 2009 British Institute of Radiology
doi: 10.1259/dmfr/81694583
Brown tumour of the maxilla and mandible: a rare complication of tertiary hyperparathyroidism
F Selvi*,1,
S Cakarer1,
R Tanakol2,
SD Guler3 and
C Keskin1
1Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Istanbul University, Turkey; 2Department of Endocrinology and Metabolism, Istanbul Faculty of Medicine, Istanbul University, Turkey; 3Department of Tumour Pathology and Oncology Cytology, Istanbul University, Turkey
*Correspondence to: Firat Selvi, Istanbul University, Faculty of Dentistry, Department of Oral and Maxillofacial Surgery, Istanbul, Turkey. E-mail: firatselvi{at}gmail.com
Received 31 December 2007;
revised 11 February 2008;
accepted 15 February 2008
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Abstract
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Hyperparathyroidism is nowadays diagnosed early and asymptomatically with the improvements in routine biochemical tests and radiological procedures. The late bony complications of the disease have therefore started to decline rapidly. Brown tumours are one of the bony complications of hyperparathyroidism. The mandible is the predominantly affected site in the maxillofacial area. Maxillary involvement is rare. Here, an extremely rare case of a 19-year-old male patient with brown tumours in his maxilla and mandible associated with tertiary hyperparathyroidism is presented. A thorough diagnostic work-up was carried out and treatment options for both hyperparathyroidism and brown tumours were discussed. The importance of different radiological evaluation methods and the consultation between the oral and maxillofacial surgeons, general practitioner dentists, endocrinologists and radiologists are emphasised.
Keywords: brown tumour; maxilla; mandible; hyperparathyroidism; panoramic radiograph
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Introduction
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Parathyroid hormone (PTH) is produced and secreted by the parathyroid glands, whose activity is controlled by the free (ionized) serum calcium level.1 Increased PTH secretion results in a condition called hyperparathyroidism (HPT). HPT is divided into primary, secondary and tertiary types. Primary HPT is characterized by increased parathyroid hormone secretion occurring as a result of abnormality in one or more of the parathyroid glands.2 Adenomas are the main cause in about 85% of primary HPT cases. Most cases of primary HPT are identified by the presence of hypercalcaemia and hypophosphataemia on routine multipanel serum testing.3
Secondary HPT is caused by hypocalcaemia or vitamin D deficiency acting as a stimulus for excessive PTH production. Chronic renal failure is the main cause of secondary HPT.3 It results in hypocalcaemia and the parathyroid glands over-function to compensate for this low serum calcium level.
Sometimes, in long-standing secondary HPT cases, the parathyroid glands gain an autonomous character.4 This phenomenon is known as tertiary HPT. Some authors also report a fourth type of HPT which is thought to arise from increased PTH levels synthesized in patients with a malignant disease.4, 5
Because of the progress in routine biochemical screening, today HPT can be diagnosed much earlier, mainly in the asymptomatic stage, whereas it was generally diagnosed as an overt disease with predominantly skeletal manifestations in the 1970s.6 Late bony manifestations of the disease include generalized osteoporosis, multiple focal areas of demineralization of the skull, and osteitis fibrosa cystica (brown tumour).7
Brown tumours are non-neoplastic lesions resulting from abnormal bone metabolism in HPT that creates a local destructive phenomenon.8, 9 The ribs, femora and pelvis are the most commonly seen sites of brown tumours.2 This bony lesion of the HPT is caused by increased circulating levels of parathyroid hormone, which result in increased osteoclastic bone resorption, primarily in cortical bone.5 This may explain why the mandible, a cortical bone, is the most commonly affected site,10 whereas maxillary involvement is less common3, 7, 9, 11, 12 in the maxillofacial area. Here, a rare case of a young male patient with brown tumours in his maxilla and mandible associated with tertiary hyperparathyroidism, will be presented and the importance of a thorough diagnostic work-up, as well as the contemporary treatment options, will be emphasised.
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Case report
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In July 2007, a 19-year-old male was referred to the Department of Oral and Maxillofacial Surgery of the Faculty of Dentistry, Istanbul University, by his endocrinologist for consultation regarding large swellings of his mandible and maxilla. The patient's medical history disclosed that he had had chronic renal failure for about 10 years and was on a regular haemodialysis programme three times a week for the past 9 years. 3 years prior to his referral, he was diagnosed with hyperparathyroidism. Since then, he was treated with vitamin D therapy. Family history revealed that his younger sister died due to renal insufficiency at 12 years of age. The patient's older and younger brothers, along with his parents, were healthy.
On clinical oral examination, a severe exophytic mass was found in the mandible starting at the left canine tooth and extending to the right second molar tooth, causing displacement of the related teeth and forcing the tongue into the pharynx, nearly obstructing the airway (Figure 1
). The related teeth were also mobile (Miller's grade II/III). The patient had difficulty in eating and speaking. There was a minor ulcerated area on the occlusal side of the lesion, probably due to chewing with the antagonist maxillary teeth. The maxillary enlargement was smaller in size, presenting as a swelling on the right side of the palate at the level of the apices of the molar teeth (Figure 2). Both of the lesions were non-tender and firm on palpation. They appeared to be attached to the bone; the overlying mucosa was freely mobile. The mucosa over the mandibular lesion was highly vascular. The mandibular lesion caused asymmetry of the face on the right side. The patient indicated that these lesions had been present for about 3 years, but had enlarged rapidly in the last year.
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Figure 1 Severe enlargement of the mandible. Note displacement of the teeth in the related area and the tongue being forced to the pharynx, nearly obstructing the airway. Minor ulceration visible on the dorsum of the lesion
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Figure 2 Maxillary enlargement. Expansive mass at the level of the apices of the right maxillary molar teeth
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On physical examination the patient was thin and short in stature, despite his age (height 1.35 meters/4' 4.4'' and weight 25.5 kg/56.1 lbs; body mass index: 14.4 kg m–2). The patient complained of generalized weakness and difficulty in performing daily domestic work. A deficiency of secondary male sex characteristics, such as lack of pubic and axillary hair and a deep voice, was also observed. The thyroid gland was minimally enlarged.
On the panoramic radiograph, a well-demarcated radiolucent area starting at the left mandibular canine tooth and extending to the right second molar tooth was observed (Figure 3). The maxillary lesion was not clearly visible on the panoramic radiograph, but upon close observation of the radiograph, another radiolucent area was noticed on the left side of the mandible, causing local destruction of the basal bone under the area of the apices of the left mandibular molar teeth. A generalized loss of lamina dura was noticeable on the panoramic radiograph. CT scans of the mandible confirmed the presence of these intraosseous radiolucent lesions (Figure 4). According to the CT scans, the right mandibular lesion measured 3.45x5.45x3.46 cm. The CT scan also revealed that the maxillary lesion (measuring 1.28x1.46x1.36 cm) had infiltrated into the maxillary sinus (Figure 5).
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Figure 3 Panoramic radiograph of the maxillary and mandibular lesions. A well-demarcated radiolucent area, starting at the left mandibular canine tooth and extending to the right second molar tooth is shown. Another osteolytic area is visible at the apex of the left mandibular molar teeth. The maxillary lesion is not clearly distinguishable on this panaromic radiograph
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Figure 4 CT scans of the related areas confirmed the presence of intraosseous radiolucent lesions. The brown tumours on both sides of the mandible are clearly visible
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Figure 5 CT scans of the maxillary lesion reveal the lesion to be penetrating the right maxillary sinus
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The laboratory findings were as follows: intact PTH 2415 pg ml–1 (15–65 pg ml–1), calcium 11.0 mg dl–1 (8.5–10.5 mg dl–1), phosphate 6.7 mg dl–1 (2.7–4.5 mg dl–1), alkaline phosphatase 1270 U L–1 (90-260 L–1).
On parathyroid ultrasonography, bilateral thyroid lobes showed no enlargement, whereas a hypoechogenic solid lesion 6.3x10 mm in size was observed in the left thyroid lobe's posteroinferior localization (Figure 6). Other than that lesion, two more hypoechogenic solid lesions with some punctate micro-calcifications were observed: (i) in the region of the right thyroid lobe's posteroinferior region measuring 8.8x6.7 mm and (ii) in the inferomedial of the latter, measuring 9.7x17.3 mm.
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Figure 6 Ultrasonography of the parathyroid glands revealed solid hypoechogenic parathyroid lesions on both sides of the lower poles of the thyroid lobes. Arrow indicates the hypoechogenic solid parathyroid lesion at the lower pole of the right thyroid lobe.
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Parathyroid technetium scintiscan (99Tcm sestamibi scintigraphy; MIBI, methoxy-isobutyl-isonitrile) showed abnormally high uptake at the lower and superior poles of the left lobe of the thyroid, and also at the lower pole of the right lobe of the thyroid. These were interpreted as parathyroid hyperplasia. Other than the thyroid gland, abnormally high uptake was also shown on both sides of the mandible, at both of the shoulders, the right anterior part of the ribs and the sternum. These high uptakes were consistent with brown tumours (Figure 7).
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Figure 7 Parathyroid technetium scintiscan showing abnormally high uptake in both sides of the mandible and shoulders as well as on the sternum and right anterior part of the ribs. Abnormally high uptake is also observed at the lower pole of the right and left thyroid lobes
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Fine needle aspiration biopsies were then performed on the mandibular and maxillary lesions. On microscopic examination, many multinucleated giant cells arranged in groups adjacent to haemosiderin granules within a fibrovascular haemorrhagic stroma were observed (Figure 8). These findings were compatible with a diagnosis of brown tumours of the jaws, associated with hyperparathyroidism.
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Figure 8 Giemsa stain. Histopathological examination showing a multinucleated giant cell arranged within erythrocytes and some connective tissue elements (magnification x 200)
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Finally, based on the thorough diagnostic work-up including medical history, clinical manifestations, radiographic findings and consecutive routine laboratory findings, the patient was diagnosed as having tertiary hyperparathyroidism with brown tumours of both jaws as a result of long-term renal disease.
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Discussion
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With new and more objective diagnostic PTH radioimmunoassay techniques, along with the successful treatment of the disease, bony complications of HPT have started to decline rapidly. The earliest and most reliable changes seen with hyperparathyroidism are subtle erosion of bone on the subperiosteal surfaces of the phalanges.13 Osteitis fibrosa cystica is a late manifestation of severe HPT. Overt findings of osteitis fibrosa cystica include generalized demineralization of bone, "salt and pepper" appearance of the skull, bone cysts and brown tumours.6, 14
Brown tumours, or osteoclastomas, are caused by localized, rapid, osteoclastic removal of bone secondary to the direct effects of PTH on the bone. The name "brown tumour" derives from the colour, which is caused by the vascularity, haemorrhage, and deposits of haemosiderin.6, 15, 16 Brown tumour is actually a giant cell lesion and often appears as an expansile osteolytic lesion of the bone. The lesion usually presents as a slight swelling in the jaw bones.8 However, similar to the case presented by Dinkar et al,2 this case differs from previously presented cases in its gross mandibular destruction. Histological and radiographically, it is very similar to the other giant cell lesions (true giant cell tumour, reparative giant cell granuloma, cherubism and aneurysmal bone cyst).15 On clinical examination and using only routine panoramic radiography, the lesions may resemble osteosarcoma, bone metastases of a carcinoma, multiple myeloma, Langerhan's cell histiocytosis, Paget's disease, osteomyelitis or osteonecrosis secondary to bisphosphonate therapy. The differential diagnosis is based on the clinical findings and the presence of hyperparathyroidism, which is confirmed with biochemical tests including PTH level.
Even though the younger sister of the patient died of renal failure at 12 years of age, this was not thought to be a case of hyperparathyroidism–jaw tumour syndrome (HPT-JT syndrome), because this autosomal dominantly inherited condition is only seen in primary hyperparathyroidism.17
Secondary and tertiary HPT are mostly seen in patients with chronic renal disease. Secondary HPT usually affects older adults (50–80 years) with a 2:1 female predominance,16 so the patient in this report was unusual for his young age and gender.
Radiographic findings in this case were similar to those mentioned elsewhere.2, 8 CT scans were especially valuable for the determination of the exact borders and size of the brown tumours. Ultrasound and parathyroid scintiscans were also very useful in localizing the abnormalities in the skeletal bones and parathyroid glands.
The most significant point about the case described here is the simultaneous appearance of brown tumours in the maxilla and mandible. In the maxillofacial region, brown tumours are most commonly seen in the mandible; maxillary involvement is rarely reported. However, as far as the authors have been able to determine to date, there have only been five such cases of brown tumours appearing simultaneously in the maxilla and the mandible previously published in the English literature.6, 18–21
The various types of HPT manifest different laboratory findings. In primary HPT, the serum calcium level is usually elevated, with low or normal serum phosphate level. Patients with secondary HPT, on the other hand, usually present with hypocalcaemia and hyperphosphataemia. These findings are variable in tertiary HPT.16 This patient was slightly hypercalcaemic and definitely hyperphosphataemic. The level of alkaline phosphatase was about five times the normal level, which indicates high bone turnover.
In patients with a brown tumour, HPT should first be treated before considering resection of the tumour. In secondary and tertiary HPT, chronic renal failure should be managed by means of haemodialysis or, eventually, a renal transplant. In primary HPT, removal of the autonomous parathyroid glands should be performed.
Triantafillidou et al3 stated that the significant bone disease associated with secondary HPT may be prevented or reduced by medical treatment, such as calcium carbonate, vitamin D and aluminum hydroxide antacids for hyperphosphataemia. In contemporary medical treatment alternatives, lanthanum carbonate, sevelamer and calcimimetics such as cinacalcet are more commonly preferred. Parathyroidectomy should be the first choice of treatment in tertiary HPT when the disease is resistant to medical therapy.
Normalization of PTH levels will often cause the brown tumours to regress or sometimes even resolve spontaneously.14 Systemic corticosteroids can be used to reduce the size of the lesion; sometimes intralesional corticosteroid injections also give satisfactory results.11, 22
Large lesions may resolve very slowly or may regress with resultant asymmetry on the face. Surgery in the form of excision of the brown tumour and recontouring of the bone should therefore be done in such cases.5, 13
In the case presented, parathyroidectomy was indicated. With the removal of the autonomous parathyroid glands, the PTH level would eventually return to normal, thus leading to a spontaneous decrease in the sizes of the intraoral lesions within a few months. Resection of the right mandibular lesion would enhance the nutrition of the patient, resulting in an improvement in his systemic condition. In the long run his renal insufficiency must be treated, probably by means of a renal transplant, to prevent recurrent hyperparathyroidism. Unfortunately, the systemic status of the patient was not sufficient enough to tolerate these operations under general anaesthesia and none of these operations could be done at this time. The patient was hospitalized for close screening of the levels of serum calcium, PTH and phosphate; also cinacalcet was started to lower the PTH and calcium levels.
In conclusion, this dramatic entity therefore highlights the importance of early diagnosis of hyperparathyroidism with a thorough diagnostic work-up. Panoramic radiographs, CT scans, ultrasonography, and parathyroid scintiscan with 99Tcm sestamibi were all useful radiographic methods for the correct diagnosis of this tumour. This case should attract the attention of general practitioner dentists, oral and maxillofacial surgeons, endocrinologists and radiologists whose consultation may be vital for patients with hyperparathyroidism since the disease may result in nearly fatal results if neglected. Dentists should also be alert for the possible presence of brown tumours in the jaws of patients who have previously been diagnosed as having hyperparathyroidism.
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Acknowledgments
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The authors would like to thank Dr Daniel Laskin who critically revised the manuscript, Dr Yakup Akyol, Dr Sema Cantez, Dr Eylem Bastug, Dr Vakur Olgac and Dr Gulcin Erseven who provided the ultrasonographic images, parathyroid scintigraphy images and the histopathologic pictures.
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References
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Abstract
Introduction
