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Lymphatic vessels are present in phosphaturic mesenchymal tumours

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Abstract

Oncogenic osteomalacia (OO) is an acquired form of hypophosphataemic osteomalacia, which is associated most commonly with the development of a benign phosphaturic mesenchymal tumour mixed connective tissue type (PMTMCT). PMTMCTs are generally well‑vascularised tumours, and many have in the past been classified as haemangiomas and haemangiopericytomas. Although these tumours show some morphological variation, it has been proposed that they represent a distinct histopathological entity. Our aim in this study was to determine by immunohistochemistry the vascular profile of PMTMCT. Using monoclonal antibodies directed against several vascular markers, including the lymphatic endothelial cell antigens LYVE‑1 and podoplanin, we found that PMTMCTs, in contrast to haemangiomas and haemangiopericytomas, contain lymphatic vessels. Taken with previous observations that PMTMCTs over‑express FGF23 and other gene products, this finding provides further evidence that most osteomalacia‑associated mesenchymal tumours represent a discrete pathological entity.

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References

  1. Aschinberg LC, Solomon LM, Zeis PM, Justice P, Rosenthal IM (1977) Vitamin D‑resistant rickets associated with epidermal nevus syndrome: demonstration of a phosphaturic substance in the dermal lesions. J Pediatr 91:56–60

    Article  PubMed  CAS  Google Scholar 

  2. Auguste P, Javerzat S, Bikfalvi A (2003) Regulation of vascular development by fibroblast growth factors. Cell Tissue Res 314:157–166

    Article  PubMed  CAS  Google Scholar 

  3. Banerji S, Ni J, Wang SX, Clasper S, Su J, Tammi R, Jones M, Jackson DG (1999) LYVE‑1, a new homologue of the CD44 glycoprotein, is a lymph‑specific receptor for hyaluronan. J Cell Biol 144:789–801

    Article  PubMed  CAS  Google Scholar 

  4. Breiteneder-Geleff S, Soleiman A, Kowalski H, Horvat R, Amann G, Kriehuber E, Diem K, Weninger W, Tschachler E, Alitalo K, Kerjaschki D (1999) Angiosarcomas express mixed endothelial phenotypes of blood and lymphatic capillaries: podoplanin as a specific marker for lymphatic endothelium. Am J Pathol 154:385–394

    PubMed  CAS  Google Scholar 

  5. Cotton GE (1994) Oncogenic osteomalacia. N Engl J Med 331:1023

    Article  PubMed  CAS  Google Scholar 

  6. De Beur SM, Finnegan RB, Vassiliadis J, Cook B, Barberio D, Estes S, Manavalan P, Petroziello J, Madden SL, Cho JY, Kumar R, Levine MA, Schiavi SC (2002) Tumors associated with oncogenic osteomalacia express genes important in bone and mineral metabolism. J Bone Miner Res 17:1102–1110

    Article  PubMed  Google Scholar 

  7. Drezner MK (1999) Tumour‑induced osteomalacia. In: Favus MJ (ed) Primer on the metabolic bone diseases and disorders of mineral metabolism. Lippincott Williams and Wilkins, Washington, pp 331–337

  8. 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 (2004) 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 28:1–30

    Article  PubMed  Google Scholar 

  9. Fukumoto S, Yamashita T (2002) Fibroblast growth factor‑23 is the phosphaturic factor in tumor‑induced osteomalacia and may be phosphatonin. Curr Opin Nephrol Hypertens 11:385–389

    Article  PubMed  Google Scholar 

  10. Haviv YS, Silver J (2000) Late onset oncogenic osteomalacia‑associated with neurofibromatosis type II. Clin Nephrol 54:429–430

    PubMed  CAS  Google Scholar 

  11. Hultberg BM, Svanholm H (1989) Immunohistochemical differentiation between lymphangiographically verified lymphatic vessels and blood vessels. Virchows Arch A Pathol Anat Histopathol 414:209–215

    Article  PubMed  CAS  Google Scholar 

  12. Kubo H, Cao R, Brakenhielm E, Makinen T, Cao Y, Alitalo K (2002) Blockade of vascular endothelial growth factor receptor‑3 signaling inhibits fibroblast growth factor‑2‑induced lymphangiogenesis in mouse cornea. Proc Natl Acad Sci U S A 99:8868–8873

    Article  PubMed  CAS  Google Scholar 

  13. Lever EG, Pettingale KW (1983) Albright’s syndrome associated with a soft‑tissue myxoma and hypophosphataemic osteomalacia. Report of a case and review of the literature. J Bone Joint Surg Br 65:621–626

    PubMed  CAS  Google Scholar 

  14. McMurtry CT, Godschalk M, Malluche HH, Geng Z, Adler RA (1993) Oncogenic osteomalacia associated with metastatic prostate carcinoma: case report and review of the literature. J Am Geriatr Soc 41:983–985

    PubMed  CAS  Google Scholar 

  15. Riminucci M, Collins MT, Fedarko NS, Cherman N, Corsi A, White KE, Waguespack S, Gupta A, Hannon T, Econs MJ, Bianco P, Gehron Robey P (2003) FGF‑23 in fibrous dysplasia of bone and its relationship to renal phosphate wasting. J Clin Invest 112:683–692

    Article  PubMed  CAS  Google Scholar 

  16. Sauter B, Foedinger D, Sterniczky B, Wolff K, Rappersberger K (1998) Immunoelectron microscopic characterization of human dermal lymphatic microvascular endothelial cells. Differential expression of CD31, CD34, and type IV collagen with lymphatic endothelial cells vs blood capillary endothelial cells in normal human skin, lymphangioma, and hemangioma in situ. J Histochem Cytochem 46:165–176

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  18. Shin JW, Min M, Larrieu-Lahargue F, Canron X, Kunstfeld R, Nguyen L, Henderson JE, Bikfalvi A, Detmar M, Hong YK (2006) Prox1 promotes lineage‑specific expression of fibroblast growth factor (FGF) receptor‑3 in lymphatic endothelium: a role for FGF signaling in lymphangiogenesis. Mol Biol Cell 17:576–584

    Article  PubMed  CAS  Google Scholar 

  19. Takeuchi Y, Suzuki H, Ogura S, Imai R, Yamazaki Y, Yamashita T, Miyamoto Y, Okazaki H, Nakamura K, Nakahara K, Fukumoto S, Fujita T (2004) Venous sampling for fibroblast growth factor‑23 confirms preoperative diagnosis of tumor‑induced osteomalacia. J Clin Endocrinol Metab 89:3979–3982

    Article  PubMed  CAS  Google Scholar 

  20. Turner RR, Beckstead JH, Warnke RA, Wood GS (1987) Endothelial cell phenotypic diversity. In situ demonstration of immunologic and enzymatic heterogeneity that correlates with specific morphologic subtypes. Am J Clin Pathol 87:569–575

    PubMed  CAS  Google Scholar 

  21. Weidner N, Bar RS, Weiss D, Strottmann MP (1985) Neoplastic pathology of oncogenic osteomalacia/rickets. Cancer 55:1691–1705

    Article  PubMed  CAS  Google Scholar 

  22. Weidner N, Santa Cruz D (1987) Phosphaturic mesenchymal tumors. A polymorphous group causing osteomalacia or rickets. Cancer 59:1442–1454

    Article  PubMed  CAS  Google Scholar 

  23. Xu H, Edwards JR, Espinosa O, Banerji S, Jackson DG, Athanasou NA (2004) Expression of a lymphatic endothelial cell marker in benign and malignant vascular tumors. Hum Pathol 35:857–861

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Pathology, Nuffield Department of Orthopaedic Surgery, Nuffield Orthopaedic Centre University of Oxford, Oxford, OX3 7LD, UK

    K. Williams & N. A. Athanasou

  2. Histopathology Department, Royal National Orthopaedic Hospital, London, UK

    A. Flanagan

  3. Department of Pathology and Laboratory Medicine, H‑175 Emory University Hospital, 1364 Clifton Road, Atlanta, GA, 30322, USA

    A. Folpe

  4. MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, Oxford, UK

    R. Thakker

Authors
  1. K. Williams
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  2. A. Flanagan
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  3. A. Folpe
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  4. R. Thakker
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  5. N. A. Athanasou
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Correspondence to N. A. Athanasou.

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Williams, K., Flanagan, A., Folpe, A. et al. Lymphatic vessels are present in phosphaturic mesenchymal tumours. Virchows Arch 451, 871–875 (2007). https://doi.org/10.1007/s00428-007-0471-y

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  • DOI: https://doi.org/10.1007/s00428-007-0471-y

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