Brown tumour mimicking skeletal metastasis

Abstract

Brown tumours of bone are highly vascular osteolytic lesions that depict a reparative cellular process instead of a neoplastic process in hyperparathyroidism (HPT) patients. These tumours have the potential to be aggressive and destructive. We report a case of a 30-year-old woman who presented with left thigh and lower back pain. The radiological evaluation showed multiple bony lesions in the pelvis and the spine, which mimicked multiple metastatic tumours. However, on biochemistry evaluation, serum calcium, alkaline phosphatase, and parathyroid hormone were all high, while serum phosphate was low, indicating primary HPT (PHPT), which was confirmed by parathyroid scintigraphy showing left parathyroid adenoma. Hence, the bony lesions were diagnosed as brown tumours secondary to PHPT. The patient underwent parathyroidectomy and developed severe hungry bone syndrome requiring parenteral calcium infusion along with oral calcium and active vitamin D supplementation. The clinical symptoms of bone pain improved after surgery.

Background

The word ‘brown tumour’ is a misnomer. It is not a neoplasm, but rather simply a mass. They are usually associated with the longstanding high parathyroid hormone (PTH) secretion, like in primary or secondary hyperparathyroidism (HPT). It is suggestive of increased osteoclastic activity due to chronic high parathormone secretion. This results in the degradation of cortical bone and the development of a fibrous cyst with haemosiderin deposits. They are a form of osteitis fibrosa cystica. It is usually seen in the fifth or sixth decade of life. There can be a single bony lesion or multiple bony lesions in different sites. The most commonly affected sites are the skull, jaw, clavicle, ribs, pelvis, phalanges and femur. These are benign lesions that may resolve after a successful parathyroidectomy.

Case presentation

A 30-year-old woman with no comorbidities presented with left-sided hip pain and backache of 7 months’ duration. The left-sided hip pain was localised, moderate in intensity, increased with hip movements and relieved minimally with rest without any joint stiffness. Backache was insidious in onset, located in the lumbosacral region, not associated with radicular pain or girdle-like pain with normal bowel–bladder function. No history of trauma preceding these reports. No history of nephrolithiasis or fractures in the past. On examination, she had a left-sided neck swelling with its lower border palpable, firm in consistency and non-tender. No cervical lymphadenopathy. Hip movements were restricted due to pain. The rest of the systemic examination was unremarkable.

Investigations

X-ray of the pelvis with hip was performed to rule out any local pathology, which showed multiple small osteolytic lesions in the pelvic bone and femur with thinning of cortices (figure 1).

Figure 1.

X-ray of pelvis with both hips showing multiple small osteolytic lesions in the pelvic bone and femur with thinning of cortices (white arrows).

MRI spine with hip showed multiple well-defined lobulated lesions in the left half of L3 lumbar vertebral body and its spinous process, left lamina and pedicle of L1 vertebra, bilateral iliac bones and left ilium, and head of the proximal shaft of the left femur. The lesions were hyperintense on the T1-weighted image (T1WI) and isohypointense on T2WI (figure 2). Multiple bony metastases was one of the differential diagnosis at this point.

Figure 2.

Plain and contrast MRI spine with hip showing well-defined lobulated lesions noted involvement of the left half of L3 vertebral body and its spinous process, left lamina and pedicle of L1 vertebra. (A) The lesions are hyperintense on sagittal T1-weighted image (T1WI) and (B) isohypointense on sagittal T2WI. (C) Diffusion restriction is seen on sagittal diffusion WI. (D) Postcontrast axial T1WI shows homogeneous enhancement of the lesion involving the left half of L3 vertebral body. (E) Postcontrast axial T1WI showing well-defined lobulated lesions of bilateral iliac bones and the head of the proximal shaft of left femur.

Biochemical evaluation, which showed serum calcium 13.6 mg/dL, serum phosphorus 1.9 mg/dL, alkaline phosphatase (ALP) 365 U/L with high PTH 896.3 pg/mL was suggestive of Primary Hyperparathyroidism. Ultrasound neck showed a heterogeneously hypoechoic nodule in the posterior–inferior side of the left thyroid lobe, which was suggestive of parathyroid adenoma with a differential of left thyroid lobe nodule.

For confirmation of parathyroid adenoma, Tc-99 sestamibi scintigraphy was performed, which showed increased tracer uptake in a well-defined soft tissue density lesion measuring 2×2×3 cm in the posterior part of the left thyroid gland with a normal surrounding flat plane (figure 3).

Figure 3.

Whole body 99mTc-methyl diphosphonate bone scan showing increased tracer uptake in multiple bilateral ribs, L3, right iliac bone and left distal femur.

A whole-body 99mTc-methyl diphosphonate (Tc99MDP) bone scan was performed to assess the bony lesion, which showed increased tracer uptake in multiple bilateral ribs, L3 vertebrae, distal femur and right iliac bones. This was suggestive of increased osteoblastic activity at the abovementioned sites (figure 4).

Figure 4.

Single photon emission CT and TC-99 sestamibi parathyroid scan showing increased tracer uptake in early sweep and early static phase posterior to the left thyroid gland.

A dual-energy X-ray absorptiometry scan showed a total z score of −5.3 at the hip and a total z score of −4.8 at the spine, which was suggestive of severe osteoporosis.

Based on the findings of high serum calcium, high PTH with correlation to left parathyroid adenoma and multiple bony lesions and severe osteoporosis, diagnosis of primary HPT (PHPT) secondary to left parathyroid adenoma with brown tumour and secondary osteoporosis was made.

Treatment

Severe hypercalcaemia was treated with hydration, saline diuresis, intravenous zoledronic acid and calcitonin before surgery to normalise calcium. The patient underwent excision of left parathyroid adenoma with intraoperative serum PTH levels dropping by 90% to 89.2 mg/dL.

Postoperatively, the patient developed prolonged severe hypocalcaemia with hypophosphataemia secondary to hungry bone syndrome (HBS), which was treated by intravenous calcium gluconate for 2 weeks, along with oral calcium carbonate and active vitamin D, which was continued for 3 months.

Outcome and follow-up

At the 3-month follow-up, the patient had significant clinical improvement with reduction in back pain and left hip pain, and normalisation of serum calcium and phosphorus.

Discussion

The incidence of PHPT is estimated to be 50 cases/100 000 population. The incidence of the brown tumour is 3%/year in PHPT, and it is caused by parathyroid adenoma or parathyroid gland hyperplasia.¹

A single adenoma is observed to be the cause of PHPT in 80%–85% of cases, multiple adenomas in 5%, parathyroid dysplasia in 15%, and parathyroid carcinoma in less than 1%–5% of cases. Secondary HPT is usually seen in end-stage renal disease with renal osteodystrophy.²

Despite the fact that PHPT can manifest in a variety of ways (the classic ‘bones, stones, abdominal groans and psychic moans’), only skeletal manifestations with brown tumour is a very rare entity, as in this case. In recent years, elevated serum calcium during normal or unrelated blood screening has been the most common way to diagnose PHPT.^{1 3}

Brown tumours can present as monostotic and polyostotic forms. The metacarpals, phalanges, chin, skull, pelvis, clavicle, ribs, femur, spine and, occasionally, the sphenoid sinus are the most commonly affected locations for brown tumours.²

Macroscopically, brown tumours are brown-coloured smooth masses that may have cystic spaces. Microscopically, they represent localised areas of marrow replacement by vascularised fibrous tissue and osteoclast-like giant cells; haemorrhage and haemosiderin pigmentation impart the characteristic brown colour. It is difficult to say the difference between a brown cell tumour and a reparative granuloma on histological grounds, as they both demonstrate multinucleated macrophages with reactive fibrous tissue ingrowth caused by microfractures of the thinned bone.¹ The pathological examination could exclude malignancy. Due to the radiological and histological similarities between brown tumours, true giant cell tumours and reparative granulomas, diagnosis of brown tumour is based on finding evidence of HPT.¹

There is resorption of secondary trabeculae (non-weight-bearing trabeculae) and accentuation of primary trabeculae (weight-bearing trabeculae) as a result of excessive osteoclastic activity and vascularised fibrous tissue seen in PHPT. The most common skeletal finding in the PHPT is generalised and asymmetric osteopenia with overall reduced bone mineral density (BMD) in the modern era. The prevalence of osteoporosis in PHPT varies from 39% to 62.9% in newer studies, which depends on the severity of PHPT.⁴ The human eye can detect reduced BMD on radiological modalities only after 30%–50% bone loss.⁵

In patients with low BMD caused by PHPT, a parathyroidectomy will help to restore bone density.⁶ Four years post parathyroidectomy, up to 20% increase in BMD was noted in the lumbar spine of patients with PHPT.^{5 7} Many studies have shown an increase in BMD at the lumbar vertebrae and hips 6 months postop.⁸

Hungry Bone Syndrome (HBS) is defined as ‘rapid, profound and prolonged hypocalcaemia associated with hypophosphataemia and hypomagnesaemia, and is exacerbated by suppressed PTH levels, which follows parathyroidectomy in patients with severe PHPT and preoperative high bone turnover’.⁹

Hypocalcaemia is seen in approximately 13%–40% of patients undergoing parathyroidectomy for PHPT. Ninety per cent of patients with PHPT with osteitis fibrosa cystica and severe osteoporosis develop postoperative hypocalcaemia due to HBS.¹⁰

Sudden reduction of PTH postoperatively aggravates uptake of calcium, phosphorus and magnesium in the bone due to increased osteoblastic activity and reduced osteoclastic activity. The osteoblast has a longer half-life, so its physiological anabolic function persists even after a low level of serum PTH. However, osteoclast has a shorter life span, hence its catabolic function decreases before any change in osteoblast action. This causes a mismatch between bone formation and bone resorption, leading to severe hypocalcaemia of HBS.¹¹

Patients with severe osteoporosis, preoperative high ALP, low preoperative vitamin D level and older age, and patients with multiple and large brown tumours have a high risk of developing HBS postoperatively. Treatment with active vitamin D (calcitriol) with concomitant calcium supplementation is important and needs to be started as early as possible.¹²

It is clear that in this case, hypercalcaemia was caused by PHPT. Initially, the MRI spine and a bone scan showing multiple bony lytic lesions in the iliac bone, ribs, and lumbar spine made high suspicion of a metastatic bone lesion. However high serum calcium and high serum PTH and increased parathyroid uptake in sestamibi scan confirmed the diagnosis of PHPT. Multiple site bone uptake in bone MDP scan can be associated with brown tumours. The histopathological result of parathyroid adenoma further confirmed the diagnosis.

This report highlights the importance of biochemical evaluation for metabolic bone disease in patients presenting with the bony lesion. In the absence of a biochemical picture of PTH-dependant hypercalcaemia, the diagnosis would be delayed as the imaging with MRI spine showing multiple well-defined lobulated lesions in the vertebrae, bilateral iliac bones and proximal shaft of the left femur, hyperintense on the T1WI, isohypointense on T2WI with Tc99MDP bone scan showing increased tracer uptake in these lesions was favouring a skeletal metastasis. Detail history, clinical examination and biochemical evaluation for metabolic bone diseases and localisation studies are the main key for early diagnosis and management.

Learning points.

• Brown tumours secondary to primary hyperparathyroidism (PHPT) must be considered in the differential diagnosis of osteolytic bony lesions.

• Metabolic bone disease evaluation is vital for correct diagnosis and appropriate management in every patient presenting with skeletal pathology.

• Brown tumours are reversible skeletal manifestations of PHPT.

Ethics statements

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