The phosphaturic mesenchymal tumor: why is definitive diagnosis and curative surgery often delayed?

Abstract

Background: Tumor-induced osteomalacia is a paraneoplastic syndrome resulting in renal phosphate wasting and decreased bone mineralization. Phosphaturic mesenchymal tumors represent a rare etiology of tumor-induced osteomalacia. Nonspecific symptoms of fatigue, bone pain, and musculoskeletal weakness make the diagnosis elusive and lead to a delay in surgical treatment.

Questions/purposes: In this case series, the following three questions were asked: (1) How do the clinical presentation and features of phosphaturic mesenchymal tumors delay the diagnosis? (2) What is the clinical course after surgical treatment of phosphaturic mesenchymal tumors? (3) How frequently do phosphaturic mesenchymal tumors recur and are there factors associated with recurrence?

Methods: This study retrospectively reviewed the cases of five adults diagnosed and treated for phosphaturic mesenchymal tumors. Patients were identified through an internal orthopaedic oncology database with clinical, surgical, and histologic data obtained through a systematic chart review.

Results: Five patients presented with a long-standing history of osteomalacia, generalized fatigue, pain, and weakness before the diagnosis was reached at an average of 7.2 years (range, 2-12 years) after initial symptom onset. The diagnosis appeared to be delayed owing to the cryptic medical presentation, difficulty in locating tumor by imaging, and confirming histologic appearance. Two patients treated with wide surgical resection did not experience recurrence compared with three patients who did show recurrent signs and symptoms after marginal excision. A postoperative increase in fibroblast-derived growth factor-23 was associated with recurrent disease.

Conclusions: Although uncommon, the diagnosis of phosphaturic mesenchymal tumor should be considered in any patient who presents with hypophosphaturic osteomalacia and no other physiologic cause. Definitive treatment is early, wide surgical resection.

Fig. 1A–E

(A) The lateral radiograph from Patient 3 shows a phosphaturic mesenchymal tumor in the calcaneus with generalized increased sclerosis and mixed lucency. Octreotide scans from Patient 5 show (B) positive somatostatin receptor enhancement in anteromedial proximal right thigh while (C) no such enhancement is seen posterior. A heterogeneous mass is seen in the proximal anteromedial right thigh that invades the femoral vein with increased signal on (D) coronal T2-weighted and (E) intermediate signal on axial T1-weighted MR images. The findings are consistent with the diagnosis of tumor-induced osteomalacia with this patient’s clinical history.

Fig. 2A–D

(A) The primary tumor from Patient 1 has a smudgy matrix with bland spindle cells, occasional osteoclast-like giant cells, and prominent blood vessels (Stain, hematoxylin & eosin; original magnification, ×10). (B) The tumor from Patient 3 shows more prominent osteoclast-like giant cell population, prominent vascularity, and focal matrix production with stellate cells (Stain, hematoxylin & eosin; original magnification, ×10). (C) Histologic examination of the recurrent tumor in Patient 1 showed a hypercellular spindle cell tumor with moderate atypia, increased mitotic activity (arrows), occasional multinucleated giant cells, and lack of matrix production (Stain, hematoxylin & eosin; original magnification, ×20). (D) The patient had lung metastasis. Histologic examination appeared similar to that seen with the patient’s primary tumor, with bland spindle cells, prominent vessels, and a calcified matrix (Stain, hematoxylin & eosin; original magnification, ×10).

Fig. 3

The laboratory values for Patient 1, who experienced multiple recurrences of her primary tumor in addition to lung metastasis, are shown. The patient’s phosphorus levels remained unstable, often decreasing to below normal levels however usually normalizing after resection. The FGF-23 showed periodic decreases after complete reresection but currently has increased possibly indicating recurrence.