Selective venous catheterization for the localization of phosphaturic mesenchymal tumors

Abstract

Tumor-induced osteomalacia (TIO) is characterized by renal phosphate wasting, hypophosphatemia, and aberrant vitamin D(3) metabolism and is caused by fibroblast growth factor 23 (FGF-23)-producing mesenchymal tumors, which are often difficult to locate. We investigated the utility of selective venous sampling in tumor localization. The primary endpoint was identification of the FGF-23 concentration ratio between the venous drainage of the tumor bed and the general circulation that was diagnostic of the location of an FGF-23-secreting tumor. Fourteen subjects underwent 15 sampling procedures after functional and anatomic imaging studies. Subjects fit into three imaging categories: no suspicious site, multiple sites, and single site (positive controls). FGF-23 levels were measured by ELISA. Suspicious tumors were resected for diagnosis, confirmation, and cure. In subjects with a positive venous sampling study and subsequent cure, a minimum ratio of 1.6 was diagnostic. In 7 of 14 subjects there was suggestive imaging, a diagnostic ratio, and an associated TIO tumor (true positive). Four of these required complicated resection procedures. In 4 of 14 subjects with no suspicious site on imaging studies, an FGF-23 diagnostic ratio was not detected (true negative). Biopsy or resection of a single lesion in 2 of 14 subjects with a diagnostic ratio failed to identify a TIO tumor (false positive). A diagnostic FGF-23 ratio was absent in 1 of 14 subjects whose tumor was a single highly suspicious lesion on imaging studies (false negative). These data yield a sensitivity of 0.87 [95% confidence interval (CI) 0.47-0.99] and a specificity of 0.71 (95% CI 0.29-0.96). Selective venous sampling for FGF-23 was particularly useful in subjects with multiple suspicious sites or an anatomically challenging planned resection but not in the absence of a suspicious lesion on imaging studies.

Fig. 1

Example of a positive result on selective venous sampling. A suspicious lesion was identified by indium-111 pentetreotide scintigraphy (A) and FDG-PET scan (B) that correlated with an ill-defined lesion in the fat pad of the heel on MRI (C). Surgical removal of the fat pad would entail an extensive procedure that involved the translocation of a vascularized muscle flap from the arm. The results of the selective venous sampling measurements of FGF-23, which confirmed that the lesion was the FGF-23-secreting lesion, are shown (D) The tumor is indicated by the arrows.

Fig. 2

Example of a venous sampling that distinguished between multiple positive images. FDG-PET imaging identified suspicious lesions in both the acetabulum (A) and the patella (B) that were suspicious for the FGF-23-secreting tumor. The results of the selective venous sampling measurements of FGF-23 (C) confirmed that the lesion in the acetabulum was the FGF-23-secreting tumor. The suspicious lesions are indicated by the arrows. This was confirmed by surgical removal and resolution of hypophosphatemia.

Fig. 3

Example of a false-negative selective venous sampling. The pentetreotide scan (A), FDG-PET/CT scan (B) and CT scan (C) identified a lesion in the T₈ vertebra. However, the results of the selective venous sampling measurements of FGF-23, sorted from lowest to highest (D) or anatomically (E), failed to identify a confirmatory FGF-23 concentration ratio. Fine-needle aspiration of the lesion and determination of FGF-23 in the aspirate confirmed that the lesion was the FGF-23-secreting tumor. The tumor is indicated by arrows. Surgical excision of the vertebra resulted in cure.(17)

Fig. 4

Example of a selective venous sampling that distinguished between conflicting imaging results. For a lesion that ultimately was found adjacent to the brain, FDG-PET/CT scan (A) was negative owing to the intense physiologic uptake of FDG by the brain. The pentetreotide/CT scan was positive (B), but the MRI findings (C) were felt to be most consistent with a meningioma, which also takes up pentetreotide. To resolve the matter, the superior sagittal sinus was catheterized from a transjugular approach (D), and FGF-23 concentrations were determined (E). The catheter and catheter tip are identified as indicated by white arrows. The results of the venous sampling were consistent with the fact that the lesion identified on pentetreotide scan and MRI was the FGF-23-secreting tumor.