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Hypervascular but Metabolically Inactive Brown Tumours’: Novel Insights into Parathyroid Imaging with 68Ga RGD PET/CT
*Corresponding author: Ameya D Puranik, Department of Nuclear Medicine and Molecular Imaging, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, 400012, Maharashtra, India. ameya2812@gmail.com
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Received: ,
Accepted: ,
How to cite this article: Nair SJ, Mahambre S, Rangarajan V, Pantvaidya G, Puranik AD. Hypervascular but Metabolically Inactive Brown Tumours’: Novel Insights into Parathyroid Imaging with 68Ga RGD PET/CT. Indian J Nucl Med. doi: 10.25259/IJNM_52_2026
Abstract
We report a case of a middle-aged woman who initially presented elsewhere with left elbow pain, whose initial MRI revealed an expansile lytic lesion in the proximal ulna. The first biopsy report done was misinterpreted as a giant cell tumour. Upon referral to our centre, further evaluation established the diagnosis of brown tumour secondary to primary hyperparathyroidism. Notably, while the Tc-99m Sestamibi scan showed uptake at the site of parathyroid adenoma, it failed to show uptake in the bone lesions, while 68Ga RGD PET/CT revealed uptake in the multiple sites of brown tumours, suggesting a unique pattern of metabolic inactivity but persistent vascularity in the bone lesions. This case demonstrates the interplay of different biological pathways unlocked by advanced nuclear imaging in detecting brown tumours based on their evolving biological behaviour.
Keywords
Brown tumors
Gallium-68
Parathyroid adenoma
PET/CT
RGD
INTRODUCTION
Brown tumours are rare, non-neoplastic, osteolytic lesions that arise as a late manifestation of hyperparathyroidism, most commonly due to parathyroid adenoma.[1] They result from excessive osteoclastic bone resorption under the influence of elevated parathyroid hormone (PTH).[2] Although their incidence has declined with earlier detection of hyperparathyroidism, brown tumours remain a diagnostic challenge, often mimicking primary bone malignancies or metastatic disease, especially when presenting as solitary or multifocal lytic lesions.[3,4] The radiological and histopathological overlap with giant cell tumours and other bone lesions further complicates diagnosis.[5,6] Imaging modalities such as magnetic resonance imaging (MRI), computed tomography (CT) and nuclear medicine scans [including Tc-99m Sestamibi and positron emission tomography/computed tomography (PET/ CT)] play a crucial role in the workup, but their sensitivity and specificity for brown tumours vary.[7] Here, we present a case that underscores the importance of a multidisciplinary approach and considering alternate radiopharmaceutical tracers in the accurate diagnosis and follow-up of brown tumours.
CASE REPORT
A 45-year-old woman presented with persistent left elbow pain. MRI performed at an outside facility revealed an expansile lytic lesion in the proximal ulna, raising suspicion for a primary bone tumour. A biopsy was performed, and the lesion was misinterpreted as a giant cell tumour. Seeking a second opinion, the patient was referred to our tertiary care centre. On review of the biopsy slides, the histone (H3.3 G34W) mutation was negative on immunohistochemistry, and a diagnosis of brown tumour was considered more likely.[1] Further laboratory investigations revealed: elevated serum calcium of 13.2 mg/dL (8.6-10), low serum phosphate of 2.1 mg/dL (2.7-4.5) and markedly raised serum parathormone (PTH) of 1,209 pg/mL (15-65). Given the biochemical profile, primary hyperparathyroidism was strongly suspected. 99mTcsestamibi scan was performed to localize the parathyroid lesion and assess for skeletal involvement [Fig 1a-e]. Planar images demonstrated increased tracer uptake in the right side of the neck [Fig 1a], which on SPECT/CT revealed a tracer concentrating lesion posterior to the superior pole of the right lobe of the thyroid gland [Fig 1b and c], consistent with parathyroid adenoma. However, there was no abnormal tracer uptake in the ulna or other skeletal sites [Fig 1d], raising questions about the metabolic activity of the bone lesions. To further characterise the skeletal involvement, a 68Ga NODAGA-RGD PET/CT scan was performed [Fig 2]. This showed faint tracer localisation in the parathyroid [Fig. 2a-c, SUVmax 2.73] but revealed multiple sites of focally increased tracer uptake corresponding to expansile lytic and sclerotic lesions throughout the skeletal system, consistent with brown tumours [Fig 2d]. The SUVmax of the representative lytic lesion in the sternum is 6.44 [Fig. 2d and e]. The patient underwent parathyroidectomy, and histopathology confirmed parathyroid adenoma. Postoperatively, PTH and calcium levels normalised [Serum PTH- 6.60 pg/mL (15-65) and Calcium-9.90 mg/dL (2.7-4.5)]. She is currently under follow-up, with a plan for serial imaging to monitor regression of the brown tumours.
DISCUSSION
Brown tumours, or osteitis fibrosa cystica, are rare skeletal manifestations of hyperparathyroidism, occurring in 1.5–4.5% of cases.[1,2] They are more frequently seen in developing countries or in patients with delayed diagnosis of hyperparathyroidism.[4,8] The pathogenesis involves excessive PTH-driven osteoclastic bone resorption, leading to fibrous tissue proliferation, hemorrhage, and formation of giant cell-rich lesions.[5] Brown tumor evolves from an early hypervascular fibroblastic phase (involving fibroblasts, capillaries, osteoclast precursors) to a giant cell–rich resorptive phase (involving osteoclast-type multinucleated giant cells within fibrovascular stroma), followed by a hemorrhagic/hemosiderin phase (hemosiderin-laden macrophages and RBC extravasation). The resulting lesions are highly vascular, with hemosiderin deposition giving them their characteristic brown colour.[3,5] Brown tumours can mimic primary bone tumours (e.g., giant cell tumour) or metastatic disease, both radiologically and histologically.[3,4,7] MRI typically shows expansile, lytic lesions with variable signal intensity and enhancement patterns, sometimes with ‘fluid-fluid’ levels due to haemorrhage.[5] Histopathology may be inconclusive, as both brown tumours and giant cell tumours share similar features (fibroblastic stroma, multinucleated giant cells).[5,6] Tc-99m Sestamibi scan is sensitive for detecting hyperfunctioning parathyroid tissue, but may not always show uptake in brown tumours.[6] As Sestamibi uptake is related to increased cellular mitochondria content within the cells[6], it is logical to assume that the bone lesions may not show uptake if they are metabolically inactive or in the reparative phase. 68Ga RGD PET/CT targets αvβ3 integrin, which is highly expressed on activated endothelial cells of newly formed blood vessels and hence is a marker for angiogenesis. It has been used previously in parathyroid imaging and has shown increased uptake in both the parathyroid adenoma and the associated bone lesions.[9] Its positivity in brown tumours suggest high vascularity. With this case report, we hypothesise that brown tumours may persist as vascular, RGD-avid lesions even after their metabolic activity has declined, possibly representing a reparative or quiescent phase when the Sestamibi uptake may be lacking.
CONCLUSION
Hence, RGD PET/CT can be used as an adjunct to the conventional Sestamibi imaging to evaluate the brown tumours. This may also be useful to evaluate the response to parathyroidectomy in brown tumours in follow-up imaging in the absence of Sestamibi uptake in the baseline scan.
Author contributions:
SJN: Concept and writing first draft; SM: Imaging assessment; VR: Scan interpretation; GP: Clinical assessment and follow up; ADP: Final draft
Ethical approval:
Institutional Review Board approval is not required.
Declaration of patient consent:
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given consent for their images and other clinical information to be reported in the journal. The patient understand that the patient’s names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Conflicts of interest:
There are no conflicts of interest.
Use of artificial intelligence (AI)-assisted technology for manuscript preparation:
The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript, and no images were manipulated using AI.
Financial support and sponsorship: Nil.
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