Different molecular imaging methods for localization and diagnosis of a mesenchymal tumor causing osteomalacia.

Introduction

Tumor-induced osteomalacia (TIO), also known as oncogenic osteomalacia (OOM), is a rare paraneoplastic syndrome caused by phosphaturic mesenchymal tumors (PMT) [1]. Although several hundred cases have been reported, the overall incidence remains unknown [1]. TIO is characterized by bone and muscle pain, pathologic fractures, weakness, and fatigue [1]. It typically affects adults, but has also been reported in children [1] [2]. The primary phosphatonin associated with TIO is fibroblast growth factor 23 (FGF-23), which leads to decreased tubular phosphate reabsorption, phosphaturia, and inhibited vitamin D activation, resulting in hypophosphatemia, bone demineralization, osteomalacia, and fractures [1]. Other causes of osteomalacia include severe vitamin D deficiency, hypophosphatemic rickets, renal or parathyroid disease, and certain drugs or toxins [1] [2] [3].

Laboratory findings often include hypophosphatemia, elevated or abnormally normal FGF-23, normal calcium, and normal or decreased vitamin D levels [2] [3]. Diagnosis is often delayed due to non-specific symptoms, small tumor size, and indolent tumor locations. Complete surgical resection of the FGF-23-secreting tumor is curative, with symptoms and biochemical abnormalities often improving within weeks of surgery [1] [2]. However, the tumors are typically small and difficult to detect with conventional imaging modalities such as ultrasound, CT or MRI. Whole-body functional imaging, in particular somatostatin receptor PET/CT, has a high success rate in localizing these tumors due to their overexpression of somatostatin 2A receptors (SSTR 2A) [1] [2] [3]. In some cases, venous sampling of FGF-23 may help to localize the tumor as well [4]. Preoperative biopsy is generally avoided because of the risk of cell spillage [5].

Most FGF-23-secreting tumors are benign mesenchymal tumors that occur in any bone or soft tissue [3]. These tumors histologically exhibit spindle cell proliferation with calcification, ossification, and osteoid-like matrix [1]. They are typically nonencapsulated and infiltrate adjacent tissues. There are rare reports of TIO associated with malignant adenocarcinoma [1] [2] [3].

Given the diagnostic challenges of this rare tumor, we present a case of an incidental diagnosis of TIO and PMT, respectively, identified during staging with bone scintigraphy in a breast cancer patient.

Publication History

Received: 09 September 2024

Accepted: 09 October 2024

Article published online:
20 November 2024

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