Summary

Brown tumors (BTs) are expansile osteolytic lesions complicating severe primary hyperparathyroidism (PHPT). Clinical, radiological and histological features of BTs share many similarities with other giant cell-containing lesions of the bone, which can make their diagnosis challenging. We report the case of a 32-year-old man in whom an aggressive osteolytic lesion of the iliac crest was initially diagnosed as a giant cell tumor by biopsy. The patient was scheduled for surgical curettage, with a course of neoadjuvant denosumab. Routine biochemical workup prior to denosumab administration incidentally revealed high serum calcium levels. The patient was diagnosed with PHPT and a parathyroid adenoma was identified. In light of these findings, histological slices of the iliac lesion were reviewed and diagnosis of a BT was confirmed. Follow-up CT-scans performed 2 and 7 months after parathyroidectomy showed regression and re-ossification of the bone lesion. The aim of this case report is to underline the importance of distinguishing BTs from other giant cell-containing lesions of the bone and to highlight the relevance of measuring serum calcium as part of the initial evaluation of osteolytic bone lesions. This can have a major impact on patients’ management and can prevent unnecessary invasive surgical interventions.

Learning points:

• Although rare, brown tumors should always be considered in the differential diagnosis of osteolytic giant cell-containing bone lesions.

• Among giant cell-containing lesions of the bone, the main differential diagnoses of brown tumors are giant cell tumors and aneurysmal bone cysts.

• Clinical, radiological and histological characteristics can be non-discriminating between brown tumors and giant cell tumors. One of the best ways to distinguish these two diagnoses appears to be through biochemical workup.

• Differentiating brown tumors from giant cell tumors and aneurysmal bone cysts is crucial in order to ensure better patient care and prevent unnecessary morbid surgical interventions.

Summary

Denosumab is a fully human MAB that acts as a potent anti-resorptive by inhibiting activation of osteoclasts by inhibiting the receptor activator of nuclear factor-kappa B (RANK) ligand. Hypocalcaemia has been reported as one of the serious adverse sequelae of use of denosumab. We present a case of refractory hypocalcaemia following administration of a single dose of denosumab in a patient with metastatic castrate-resistant prostate cancer. The patient’s serum calcium and vitamin D concentrations and renal function were normal prior to denosumab administration. Serum alkaline phosphatase (ALP) level was however elevated pre-morbidly consistent with known bone metastases. The patient was treated with high-dose oral and IV calcium without any appreciable response in serum calcium. During his 30-day hospital admission, he demonstrated disease progression with development of new liver metastases and bone marrow involvement. Normocalcaemia was not achieved despite 1 month of aggressive therapy. Given the patient was asymptomatic and prognosis guarded, he was eventually discharged for ongoing supportive care under the palliative care team.

Learning points:

• Denosumab is a potent anti-resorptive therapy and hypocalcaemia is one of the known adverse effects.

• Serum calcium and vitamin D concentrations must be replete prior to administration of denosumab to reduce the risk of hypocalcaemia.

• Denosumab has been proven to be more effective than zoledronic acid in preventing skeletal-related adverse effects in patients with metastatic castrate-resistant prostate cancer.