Brown tumor as an unusual but preventable cause of spinal cord compression: Case report and review of the literature.

Brown tumor (BT), also known as osteoclastoma, may appear in the context of primary and secondary hyperparathyroidism. Spinal cord compression due to the BT is extremely rare. We present here an unusual case of BT involving thoracal spine and mandible. A 26-year-old woman, who had been on hemodialysis for chronic renal failure for over 6 years, got admitted with dorsal pain and progressive weakness in her lower extremities and gait disturbances. Neurological examination revealed spastic paraparesis and symmetrically hyperactive tendon reflex in the lower extremities. She had hypoesthesia under T10 level. On physical examination, a swelling on the left side of her jaw was also detected. Magnetic resonance imaging (MRI) showed cord compression due to an extradural mass lesion at T8 level. A computerized tomography (CT) scan showed that this expansile lytic lesion was caused by the collapse of vertebra corpus (T8) at that level. CT of the mandible revealed an expansile lytic lesion on left arm of the mandible. Laboratory findings were nearly normal except parathormone level elevation to 1289 pg/mL (normal 30-70 pg/mL). Ultrasound examination showed enlargement of the parathyroid glands. The patient underwent an emergency decompression and stabilization surgery. The lesion was fragile and reddish in appearance and was easy to aspirate. The tumor was reported as "BT." Her weakness in the lower extremities improved in the early postoperative period. Following surgical intervention, the patient was transferred to nephrology clinic for additional medical treatment.

Introduction

Brown tumor (BT), also termed osteoclastoma, is a histologically benign focal lytic bone tumor caused by primary or secondary hyperparathyroidism.[1] It is called BT because high hemosiderin level of localized accumulation of osteoclasts, fibrous tissue, and blood gives characteristic brown color.[2] The first case of primary hyperparathyroidism involving the spine was reported by Shaw and Davies[3] in 1968. BT is found in 3 and 1.5-1.7% of patients with primary and secondary hyperparathyroidism, respectively.[4] The most common cause of BT is a solitary adenoma, followed by hyperplasia and carcinoma in primary hyperparathyroidism[56] and long-term hemodialysis therapy in secondary hyperparathyroidism.[78]

BT can emerge as solitary or multiple lesions and can be seen both within bone and adjacent tissue and mainly involves facial bones (mandible, maxilla), pelvic bones, sternum, ribs, phalanx, and femur.[1249] Multiple BT rarely is rarely found in a patient[101112] and it rarely locates in vertebra,[13] In this report, a case of a BT located in mandible and thoracal vertebra is presented with an extensive review of the literature.

Case Report

A 26-year-old woman, who had been on hemodialysis for chronic renal failure for over 6 years, got admitted with a 10-day history of dorsal pain, progressive weakness in her lower extremities, and gait disturbances. Neurological examination revealed spastic paraparesis and symmetrically hyperactive tendon reflexes in the lower extremities. She had bilateral Achilles clonus and hypoesthesia under T10 level. On physical examination, a swelling on her left side of jaw was also detected. Magnetic resonance imaging (MRI) showed cord compression due to an extradural mass lesion at T8 level [Figure 1a]. The lesion had a heterogeneous intensity on T2-weighted images. A computerized tomography (CT) scan [Figure 1b] showed that this expansile lytic lesion was caused by the collapse of vertebra corpus (T8) at that level. CT of the mandible revealed an expansile lytic lesion on left arm of the mandible [Figure 1c]. Laboratory findings were nearly normal except parathormone (PTH) level elevation to 1289 pg/mL (normal 30-70 pg/mL), and total serum calcium and serum phosphorus were 9.8 mg/dL (8.4-10.2 mg/dL) and 3.8 mmol/L (2.7-4.5 mmol/L), respectively. Ultrasound examination showed enlargement of the parathyroid glands. The patient consulted with nephrology clinic and an emergency surgery was planned as she had progressive neurological deficit. The lesion was fragile and reddish in appearance and was easy to aspirate. The tumor was removed and rigid T5–11 stabilization was performed [Figure 1d]. The lesion was reported as “BT” [Figure 2]. Her weakness in the lower extremities improved in the early postoperative period. Following surgical intervention, the patient was transferred to nephrology clinic for additional medical treatment.

Figure 1

(a) Sagittal T2-weighted MRI demonstrating a heterogeneous lesion at T8 level. (b) On CT scan, the destruction of the corpus of the vertebra is seen clearly. The hyperdensity of the lesion on non-contrast sagittal CT image is remarkable. (c) Tumor is located on the mandible (black arrow). (d) The postoperative sagittal CT image showing the posterior fixation of the spine

Figure 2

Hematoxylin and eosin with ×100 magnification; lots of multinucleated giant cells (black arrows) separated by spindle-shaped mononuclear cells

In the literature, including the presented case, we found 42 cases of vertebral BT (27 cases caused in secondary and 15 cases in primary hyperparathyroidism). Thirteen of the 27 BTs due to secondary hyperparathyroidism were females. The average age of them was 38.7 years (range 19-69 years) and dorsal vertebrae were the most commonly involved site in 16 cases [Table 1]. Ten of the 15 BT cases due to primary hyperparathyroidism were females. The average age of them was 48.4 years (range 23-69 years) and dorsal vertebrae were the most commonly involved site in 9 cases [Table 2].

Table 1

Review of the reported cases of spinal brown tumors due to secondary hyperparathyroidism

Table 2

Review of the reported cases of spinal brown tumors due to primary hyperparathyroidism

Paraparesis and paraplegia were the most seen symptoms due to the spinal cord compression. Pain, radiculopathy, and numbness were the other presenting symptoms of the patients.

In 10 of the 15 primary hyperparathyroidism cases, parathyroid adenoma resection with tumor excision was the choice of the treatment. In one case, parathyroid adenoma resection following BT excision was not accepted by the patient. The number of patients who underwent parathyroid adenoma resection with tumor excision were only 8 among 27 cases of secondary hyperparathyroidism. In six cases including the presented case, only tumor resection was performed. Only biopsy was performed in three cases of the secondary BT tumors.

Discussion

When the homeostasis is disturbed between PTH and calcium, hyperparathyroidism occurs with an excess of PTH that causes multiple actions on bone, both directly or indirectly.[12] Peritrabecular fibrosis (osteitis fibrosa) and increased osteoclastic activity secondary to phosphate retention and impaired vitamin D synthesis cause erosive bony lesions that are called BTs or osteitis fibrosa cystica.[14] BT is a classic manifestation of hyperparathyroidism (primary and/or secondary) and is characterized by bone pain and radiographic changes typically showing bone resorption.[15] As the primary hyperparathyroidism was responsible for BT mostly in the past, the secondary hyperparathyroidism is on the rise nowadays probably because of advances in treatment of the patients with end-stage renal disease receiving hemodialysis.[10] The first case of secondary hyperparathyroidism involving the spine was reported by Ericsson et al.[16] in 1978. BT occurs mostly as isolated masses, but disseminated ones mimicking metastases have also been reported.[5111213171819] Joyce et al.[20] were the first who reported multiple BTs in primary hyperparathyroidism due to adenoma mimicking metastasis in 1994. In the presented case, there were two BTs which were localized: One in spine and the other in mandible.

The clinical symptoms of spinal BTs consist of pain,[212223] radiculopathy,[2425] cauda equina syndrome,[1426] paraparesis,[3102728] and paraplegia.[132930] In the presented case, swelling and pain of the jaw were additional to the paraparesis and dorsal pain.

Diagnosis of BTs depends on clinical, biochemical, radiological, and pathological factors.[4] BT does not have specific imaging characteristics; it can mimic metastases or multiple myeloma. Sarcomas as well as giant cell reparative granulomas, lymphangiomatosis, leukemia, Langerhans cell histiocytosis, multiple bone cysts, aneurysmal bone cysts, and non-ossifying fibromas are the other lesions that should be kept in mind as the differential diagnosis.[41323] BT is represented with an area of expending osteolysis with jagged sharp outline and sclerotic rim on plain radiographs.[111] Radiographs can also show compression[617] or collapse[7] of the vertebra corpus as in the presented case. On CT, osteolytic and expansile tumor with soft tissue density replaces the cancellous bone of the corpus of the vertebra.[71023] Spinal magnetic resonance imaging (MRI) can show bone infiltration and paravertebral and intraspinal soft tissue masses with neural compression.[14] On MRI, BT is hypointense on T1-weighted images and hyper/hypointense on T2-weighted images.[1023] Similarly, in the present case, T2-weighted images demonstrated a lesion with heterogeneous intensity. There were both hypointense and hyperintense areas in the lesion; the center of the lesion was hyperintense and the surrounding area was isointense. On CT, the osteolytic and soft tissue parts of the tumor were easily seen.

True neoplastic lesions such as giant cell tumor of the bone may have very similar findings as BT. The histologic similarities between a giant cell tumor of hyperthyroidism and a BT were pointed out by Jaffe[31] in 1933. Giant cell tumor of bone most commonly involves the epiphyses of the long bones. In the microscope, giant cells of BT are usually arranged in clusters, but in giant cell tumor the giant cells tend to be disturbed regularly and uniformly.[13] Beside the proliferation of multinucleated giant cells and fibrous stroma with spindle-shaped mononuclear cells, focal hemorrhage and hemosiderin deposition can be observed.[111214] Neither cellular atypia nor mitotic figures are observed in BT.[28] But indeed, there are no available histological criteria distinguishing BT from giant cell tumor.[1] Presence of severe hyperparathyroidism and widespread bony changes with patient's medical history help in diagnosis of BT.

The best treatment for BT is to prevent it. Secondary hyperparathyroidism should be monitored and prevented with prolonged dialysis sessions.[7817] Normalizing blood levels of calcium and phosphate should be the goal of prevention in dialysis-dependent patients. Serum phosphate levels should be controlled, dietary phosphorus intake should be restricted, and a high phosphate clearance dialyzer should be selected. Use of phosphate binders, vitamin D, oral calcium supplements, and calcimimetics is recommended for treatment. Biphosphonate infusion therapy – before and after operation[32] or preoperative[33] – is recommended for resolution of the clinical symptoms.[3233] Total or subtotal parathyroidectomy is valuable for treatment of BT; it usually provides complete clearance of the lesions with remineralization of the vertebra.[11223] It eliminates excessive activation of the PTH and usually leads to significant regression of BT.[18] Fargen et al.[10] reported a case of spinal BT which occurred 7 years after subtotal parathyroidectomy and stressed that it will be wise to monitor the laboratory findings of the patients for avoiding recurrence in case of presence of residual parathyroid tissue. Parathyroidectomy and medical treatment may be used together.[3233] The neurological situation of the patient is very important in case of spinal involvement. Emergency decompression can be mandatory for achieving good outcome.[17832] Extensive osteolysis and involvement of the mobile vertebral segment requires fixation of the vertebra[18101732] as the presented case. If the spinal alignment is confirmed radiologically and/or intraoperatively, the patient can be subjected to orthosis without spinal fixation.[1046]

In conclusion, BT should be remembered in the differential diagnosis of spinal cord compression, especially in the patients with end-stage renal disease. Prevention should be the goal for treatment and patients with the end-stage renal disease should be monitored. Promptly performed decompression surgery may improve the neurological deficits of the patients.