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BMJ Case Rep. 2010; 2010: bcr0220102750.
Published online 2010 October 8. doi:  10.1136/bcr.02.2010.2750
PMCID: PMC3028388
Rare disease

Imaging of tumour-induced osteomalacia using a gallium-68 labelled somatostatin analogue

Abstract

A 51-year-old man presented with generalised bone pain. Initial evaluation revealed a low serum phosphorus level and elevated urinary phosphorus excretion. Aminoaciduria was normal. Standard imaging showed only minimal changes. The patient was treated with daily oral supplementation with phosphate (1 g/day) and 1,25-dihydroxyvitamin D3 (1 μg/day) to maintain euphosphataemia. In spite of the fact that this treatment was maintained for 3 years, there was no modification of renal phosphate clearance. A diagnosis of hypophosphataemic osteomalacia with renal phosphate wasting was proposed. Therefore, tumour-induced osteomalacia was suspected, triggering a diagnostic workup to find the primary tumour. These tumours are known to express somatostatin receptors, so whole body positron emission tomography (CT) imaging was performed after intravenous administration of 68Ga-DOTA-TOC (68Ga-DOTA-D-Phe1-Tyr3-pentreotide). A solitary intense hot spot was detected in soft tissue near the right femoral internal condyle. Based on this result, curative resection of the tumour was performed.

Case presentation

A 51-year-old man presented with generalised bone pain involving the spine, rib cage and talalgia. Initial evaluation revealed a low serum phosphorus level (1.8 mmol/l; normal range: 2.5–4.5 mmol/l) and elevated urinary phosphorus excretion (2833 mg/day; normal range: 400–1300 mg/day). Aminoaciduria was within the normal range.

The patient was treated with daily oral supplementation with phosphate (1 g/day) and 1,25-dihydroxyvitamin D3 (1 μg/day) to maintain the euphosphataemia. In spite of the fact that this treatment was maintained for 3 years, there was no modification of the renal phosphate clearance. The diagnosis of hypophosphataemic osteomalacia with renal phosphate wasting was proposed. Therefore, a tumour-induced osteomalacia was suspected, triggering a diagnostic workup to find the primary tumour.

Investigations

Standard radiological imaging (planar radiographs of the hips, spine and pelvis) showed the presence of enthesopathy and minimal changes compatible with osteomalacia. Bone densitometry indicated lumbar osteopenia.

Positron emission tomography coupled with CT (PET-CT) imaging was performed 90 min after the administration of 67 MBq (1.8 mCi) 68Ga-DOTA-TOC (68Ga-DOTA-D-Phe1-Tyr3-pentreotide). Whole body PET-CT including the lower limbs within the field of view was performed. An intense hot spot was detected in the soft tissues near the right femoral internal condyle which coincided with a dense nodule on CT images measuring 20 × 14 × 15 mm (figure 1). PET-guided MRI confirmed this tumour which appeared intensely hypervascularised and contained haemosiderin deposits.

Figure 1
(A) 68Ga-DOTA-TOC PET (axial view) shows an intense hot spot near the right femoral internal condyle. (B) CT (axial view) shows a dense nodule in the same region measuring 20 × 14 × 15 mm (white arrow). (C) PET/CT fusion confirms agreement ...

Treatment

Surgical resection of the tumour was performed.

Outcome and follow-up

Histopathological examination showed a proliferation of small round tumour cells with a well-developed capillary network. Tumour cells with ovoid homogeneous nuclei were occasionally observed, but mitotic changes were not seen. The matrix contained smudgy blue-grey material (grungy calcifications), typical of tumour inducing osteomalacia.

Surgical resection of the mass resulted in the normalisation of serum phosphorous and calcitriol concentrations, and in the reversal of phosphaturia.

The generalised bone pain experienced by the patient only partially reduced after surgery, probably because of the long evolution of the osteomalacia until discovery of the causal tumour.

Discussion

Weidner and Santa Cruz1 described the pathological features of 17 mesenchymal tumours that caused osteomalacia or rickets. The large number of histological diagnostic terms used to classify these tumours reflects their pathological diversity. At the time of the diagnostic workup, it was not possible to use immunohistochemistry to look for fibroblast growth factor 23 since a suitable technique was not available in our institution at that time; this was a limitation in the workup of this patient.

Nevertheless, locating the underlying tumour is essential because complete surgical removal resolves the disordered phosphocalcic metabolism. The majority of these tumours are small and often occur in the extremities (skin, muscles, bones) or around the head (paranasal sinuses). Due to the different possible locations of this tumour, whole body imaging including the lower limbs is required.

At the molecular level, this type of tumour is characterised by an overexpression of somatostatin receptors (SSTR).2 3

The introduction of radiolabelled somatostatin analogues for molecular imaging of neuroendocrine tumours was a major breakthrough in the detection and management of these neoplasms. Gamma camera imaging based on scintigraphy classically includes whole body planar and tomography acquisition (SPECT) performed 6, 24 and often 48 h after the intravenous administration of a tracer dose of radiolabelled somatostatin analogues, most often 111In-DTPA-D-Phe1-octreotide (OctreoScan, Covidien). Some reports confirm the successful visualisation of this type of tumour using this technique.4 5

Recently, the use of 68Ga-labelled DOTA-conjugated peptides for PET has become more common. This imaging technique has been reported in patients with suspected tumour-induced osteomalacia.6 PET is theoretically the preferred molecular imaging technique because it has a sensitivity (to detect molecular processes) 50 times higher than SPECT and 5 × 106 times higher than MRI spectroscopy.7 As regards radioprotection, 68Ga has a favourable half life (68 min) compared to 111In (67 h). Also, the small in-house 68Germanium/68Gallium generator can be used for a long time period, up to 1 year or more at a relatively low cost.8

Learning points

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Mesenchymal tumours, often overexpressing somatostatin receptors, can cause osteomalacia or rickets.
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Locating the underlying tumour is essential because complete surgical removal can resolve disordered phosphocalcic metabolism.
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Due to the different possible locations of this tumour, whole body imaging including the lower limbs, is required.
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PET-CT with a gallium-68 labelled octreotide analogue produced in-house is a highly sensitive whole-body combined molecular and anatomical imaging technique for this type of tumour.

Footnotes

Competing interests None.

Patient consent Obtained.

References

1. Weidner N, Santa Cruz D. Phosphaturic mesenchymal tumors. A polymorphous group causing osteomalacia or rickets. Cancer 1987;59:1442–54. [PubMed]
2. Jan de Beur SM, Streeten EA, Civelek AC, et al. Localisation of mesenchymal tumours by somatostatin receptor imaging. Lancet 2002; 359:761–3. [PubMed]
3. Folpe AL, Fanburg-Smith JC, Billings SD, et al. Most osteomalacia-associated mesenchymal tumours are a single histopathologic entity: an analysis of 32 cases and a comprehensive review of the literature. Am J Surg Pathol 2004;28:1–30. [PubMed]
4. Rhee Y, Lee JD, Shin KH, et al. Oncogenic osteomalacia associated with mesenchymal tumour detected by indium-111 octreotide scintigraphy. Clin Endocrinol (Oxf) 2001;54:551–4. [PubMed]
5. Seufert J, Ebert K, Müller J, et al. Octreotide therapy for tumor-induced osteomalacia. N Engl J Med 2001;345:1883–8. [PubMed]
6. Hesse E, Moessinger E, Rosenthal H, et al. Oncogenic osteomalacia: exact tumor localization by co-registration of positron emission and computed tomography. J Bone Miner Res 2007;22:158–62. [PubMed]
7. Frangioni JV. New technologies for human cancer imaging. J Clin Oncol 2008;26:4012–21. [PMC free article] [PubMed]
8. Al-Nahhas A, Win Z, Szyszko T, et al. What can gallium-68 PET add to receptor and molecular imaging? Eur J Nucl Med Mol Imaging 2007;34:1897–901. [PubMed]

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