Top

Clinical Orthopaedics and Related Research®

Published in:

01-11-2013 | Clinical Research

The Phosphaturic Mesenchymal Tumor: Why is Definitive Diagnosis and Curative Surgery Often Delayed?

Authors: Cameron K. Ledford, MD, Nicole A. Zelenski, BS, Diana M. Cardona, MD, Brian E. Brigman, MD, PhD, William C. Eward, DVM, MD

Published in: Clinical Orthopaedics and Related Research® | Issue 11/2013

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.

Level of Evidence

Level IV, therapeutic study. See the Instructions for Authors for a complete description of levels of evidence.

Bahrami A, Weiss SW, Montgomery E, Horvai AE, Jin L, Inwards CY, Folpe AL. RT-PCR analysis for FGF23 using paraffin sections in the diagnosis of phosphaturic mesenchymal tumors with and without known tumor induced osteomalacia. Am J Surg Pathol. 2009;33:1348–1354.PubMedCrossRef

Carpenter TO. Oncogenic osteomalacia: a complex dance of factors. N Engl J Med. 2003;348:1705–1708.PubMedCrossRef

Chong WH, Molinolo AA, Chen CC, Collins MT. Tumor-induced osteomalacia. Endocr Relat Cancer. 2011;18:R53–77.PubMedCrossRef

Duet M, Kerkeni S, Sfar R, Bazille C, Liote F, Orcel P. Clinical impact of somatostatin receptor scintigraphy in the management of tumor-induced osteomalacia. Clin Nucl Med. 2008;33:752–756.PubMedCrossRef

Fletcher CDM, Bridge JA, Hogendoorn P, Mertens F, eds. WHO Classification of Tumours of Soft Tissue and Bone. Geneva, Switzerland: WHO Press; 2013.

Folpe AL, Fanburg-Smith JC, Billings SD, Bisceglia M, Bertoni F, Cho JY, Econs MJ, Inwards CY, Jan de Beur SM, Mentzel T, Montgomery E, Michal M, Miettinen M, Mills SE, Reith JD, O’Connell JX, Rosenberg AE, Rubin BP, Sweet DE, Vinh TN, Wold LE, Wehrli BM, White KE, Zaino RJ, Weiss SW. Most osteomalacia-associated mesenchymal tumors 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.PubMedCrossRef

Ito N, Shimizu Y, Suzuki H, Saito T, Okamoto T, Hori M, Akahane M, Fukumoto S, Fujita T. Clinical utility of systemic venous sampling of FGF23 for identifying tumours responsible for tumour-induced osteomalacia. J Intern Med. 2010;268:390–394.PubMedCrossRef

Jan de Beur SM, Levine MA. Molecular pathogenesis of hypophosphatemic rickets. J Clin Endocrinol Metab. 2002;87:2467–2473.

Jan de Beur SM, Streeten EA, Civelek AC, McCarthy EF, Uribe L, Marx SJ, Onobrakpeya O, Raisz LG, Watts NB, Sharon M, Levine MA. Localisation of mesenchymal tumours by somatostatin receptor imaging. Lancet. 2002;359:761–763.

10.

Jonsson KB, Zahradnik R, Larsson T, White KE, Sugimoto T, Imanishi Y, Yamamoto T, Hampson G, Koshiyama H, Ljunggren O, Oba K, Yang IM, Miyauchi A, Econs MJ, Lavigne J, Juppner H. Fibroblast growth factor 23 in oncogenic osteomalacia and X-linked hypophosphatemia. N Engl J Med. 2003;348:1656–1663.PubMedCrossRef

11.

Kumar R. Tumor-induced osteomalacia and the regulation of phosphate homeostasis. Bone. 2000;27:333–338.PubMedCrossRef

12.

McCance RA. Osteomalacia with Looser’s nodes (Milkman’s syndrome) due to a raised resistance to vitamin D acquired about the age of 15 years. Q J Med. 1947;16:33–46.PubMed

13.

Mekinian A, Ladsous M, Balavoine AS, Carnaille B, Aubert S, Soudan B, Wemeau JL. Curative surgical treatment after inefficient long-acting somatostatin analogues therapy of a tumor-induced osteomalacia. Presse Med. 2011;40:309–313.PubMedCrossRef

14.

Nguyen BD, Wang EA. Indium-111 pentetreotide scintigraphy of mesenchymal tumor with oncogenic osteomalacia. Clin Nucl Med. 1999;24:130–131.PubMedCrossRef

15.

Ogose A, Hotta T, Emura I, Hatano H, Inoue Y, Umezu H, Endo N. Recurrent malignant variant of phosphaturic mesenchymal tumor with oncogenic osteomalacia. Skeletal Radiol. 2001;30:99–103.PubMedCrossRef

16.

Paglia F, Dionisi S, Minisola S. Octreotide for tumor-induced osteomalacia. N Engl J Med. 2002;346:1748–1749; author reply 1748–1749.

17.

Prader A, Illig R, Uehlinger E, Stalder G. [Rickets following bone tumor][in German]. Helv Paediatr Acta. 1959;14:554–565.PubMed

18.

Rhee Y, Lee JD, Shin KH, Lee HC, Huh KB, Lim SK. Oncogenic osteomalacia associated with mesenchymal tumour detected by indium-111 octreotide scintigraphy. Clin Endocrinol (Oxf). 2001;54:551–554.PubMedCrossRef

19.

Rosen CH, ed. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. Ames, IA, Wiley-Blackwell; 2013.

20.

Seufert J, Ebert K, Muller J, Eulert J, Hendrich C, Werner E, Schuuze N, Schulz G, Kenn W, Richtmann H, Palitzsch KD, Jakob F. Octreotide therapy for tumor-induced osteomalacia. N Engl J Med. 2001;345:1883–1888.PubMedCrossRef

21.

Shimada T, Mizutani S, Muto T, Yoneya T, Hino R, Takeda S, Takeuchi Y, Fujita T, Fukumoto S, Yamashita T. Cloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia. Proc Natl Acad Sci U S A. 2001;98:6500–6505.PubMedCrossRef

22.

Sidell D, Lai C, Bhuta S, Barnes L, Chhetri DK. Malignant phosphaturic mesenchymal tumor of the larynx. Laryngoscope. 2011;121:1860–1863.PubMedCrossRef

23.

Terek RM, Nielsen GP. Case records of the Massachusetts General Hospital: weekly clinicopathological exercises. Case 29-2001. A 14-year-old with abnormal bones and a sacral mass. N Engl J Med. 2001;345:903–908.CrossRef

24.

Uramoto N, Furukawa M, Yoshizaki T. Malignant phosphaturic mesenchymal tumor, mixed connective tissue variant of the tongue. Auris Nasus Larynx. 2009;36:104–105.PubMedCrossRef

Title: The Phosphaturic Mesenchymal Tumor: Why is Definitive Diagnosis and Curative Surgery Often Delayed?
Authors: Cameron K. Ledford, MD
Nicole A. Zelenski, BS
Diana M. Cardona, MD
Brian E. Brigman, MD, PhD
William C. Eward, DVM, MD
Publication date: 01-11-2013
Publisher: Springer US
Published in: Clinical Orthopaedics and Related Research® / Issue 11/2013
Print ISSN: 0009-921X
Electronic ISSN: 1528-1132
DOI: https://doi.org/10.1007/s11999-013-3178-1

ACC 2024 Congress

Springer Medicine

The Phosphaturic Mesenchymal Tumor: Why is Definitive Diagnosis and Curative Surgery Often Delayed?

Abstract

Background

Questions/purposes

Methods

Results

Conclusions

Level of Evidence

ACC 2024 Congress

Springer Medicine

Abstract

Background

Questions/purposes

Methods

Results

Conclusions

Level of Evidence

Please log in to get access to this content

Other articles of this Issue 11/2013

Low Wear of a Second-generation Highly Crosslinked Polyethylene Liner: A 5-year Radiostereometric Analysis Study

Trabecular Metal in Total Knee Arthroplasty Associated with Higher Knee Scores: A Randomized Controlled Trial

What Is Normal Femoral Head/Neck Anatomy? An Analysis of Radial CT Reconstructions in Adolescents

Image Guided Core Needle Biopsy of Musculoskeletal Lesions: Are Nondiagnostic Results Clinically Useful?

Integrating Patient-reported Outcomes Into Orthopaedic Clinical Practice: Proof of Concept From FORCE-TJR

What Is the Current Status of Global Health Activities and Opportunities in US Orthopaedic Residency Programs?