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Paraneoplastic musculoskeletal disorders: review and update for radiologists

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Abstract

Rheumatic paraneoplastic syndromes are rare syndromes that occur at distant sites from the underlying tumor and may involve the bones, joints, fasciae, muscles, or vessels. In the absence of a known tumor, early recognition of a rheumatic syndrome as paraneoplastic permits dedicated work-up for, and potentially early treatment of an occult malignancy. Although there is a continuously growing list of paraneoplastic rheumatic disorders, not all of these disorders have a well-established association with a neoplastic process. The goals of this article are to review the clinical characteristics, diagnostic work-up, and imaging findings of well-documented rheumatic paraneoplastic disorders.

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References

  1. Hashefi M. The relationship between rheumatologic disorders and malignancies. Rheum Dis Clin North Am. 2018;44(3):405–18.

    Article  Google Scholar 

  2. Manger B, Schett G. Rheumatic paraneoplastic syndromes—a clinical link between malignancy and autoimmunity. Clin Immunol. 2018;186:67–70.

    Article  CAS  Google Scholar 

  3. Rennie JA, Auchterlonie IA. Rheumatological manifestations of the leukaemias and graft versus host disease. Baillieres Clin Rheumatol. 1991;5(2):231–51.

    Article  CAS  Google Scholar 

  4. Florenzano P, Hartley IR, Jimenez M, Roszko K, Gafni RI, Collins MT. Tumor-induced osteomalacia. Calcif Tissue Int. 2021;108(1):128–42.

    Article  CAS  Google Scholar 

  5. Folpe AL. Phosphaturic mesenchymal tumors: a review and update. Semin Diagn Pathol. 2019;36(4):260–8.

    Article  Google Scholar 

  6. Li X, Jiang Y, Huo L, et al. Nonremission and recurrent tumor-induced osteomalacia: a retrospective study. J Bone Miner Res. 2020;35(3):469–77.

    Article  CAS  Google Scholar 

  7. ADHR Consortium. Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23. Nat Genet. 2000;26(3):345–8.

    Article  Google Scholar 

  8. Riminucci M, Collins MT, Fedarko NS, et al. FGF-23 in fibrous dysplasia of bone and its relationship to renal phosphate wasting. J Clin Invest. 2003;112(5):683–92.

    Article  CAS  Google Scholar 

  9. Endo I, Fukumoto S, Ozono K, et al. Nationwide survey of fibroblast growth factor 23 (FGF23)-related hypophosphatemic diseases in Japan: prevalence, biochemical data and treatment. Endocr J. 2015;62(9):811–6.

    Article  CAS  Google Scholar 

  10. Feng J, Jiang Y, Wang O, et al. The diagnostic dilemma of tumor induced osteomalacia: a retrospective analysis of 144 cases. Endocr J. 2017;64(7):675–83.

    Article  Google Scholar 

  11. Chong WH, Molinolo AA, Chen CC, Collins MT. Tumor-induced osteomalacia. Endocr Relat Cancer. 2011;18(3):R53-77.

    Article  CAS  Google Scholar 

  12. Broski SM, Folpe AL, Wenger DE. Imaging features of phosphaturic mesenchymal tumors. Skeletal Radiol. 2019;48(1):119–27.

    Article  Google Scholar 

  13. Reubi JC, Waser B, Schaer JC, Laissue JA. Somatostatin receptor sst1-sst5 expression in normal and neoplastic human tissues using receptor autoradiography with subtype-selective ligands. Eur J Nucl Med. 2001;28(7):836–46.

    Article  CAS  Google Scholar 

  14. Rayamajhi SJ, Yeh R, Wong T, et al. Tumor-induced osteomalacia—current imaging modalities and a systematic approach for tumor localization. Clin Imaging. 2019;56:114–23.

    Article  Google Scholar 

  15. Jing H, Li F, Zhuang H, et al. Effective detection of the tumors causing osteomalacia using [Tc-99m]-HYNIC-octreotide (99mTc-HYNIC-TOC) whole body scan. Eur J Radiol. 2013;82(11):2028–34.

    Article  Google Scholar 

  16. Houang M, Clarkson A, Sioson L, et al. Phosphaturic mesenchymal tumors show positive staining for somatostatin receptor 2A (SSTR2A). Hum Pathol. 2013;44(12):2711–8.

    Article  CAS  Google Scholar 

  17. Zhang J, Zhu Z, Zhong D, et al. 68Ga DOTATATE PET/CT is an accurate imaging modality in the detection of culprit tumors causing osteomalacia. Clin Nucl Med. 2015;40(8):642–6.

    Article  Google Scholar 

  18. Bhavani N, Reena Asirvatham A, Kallur K, et al. Utility of Gallium-68 DOTANOC PET/CT in the localization of tumour-induced osteomalacia. Clin Endocrinol (Oxf). 2016;84(1):134–40.

    Article  CAS  Google Scholar 

  19. Yu WJ, He JW, Fu WZ, Wang C, Zhang ZL. Reports of 17 Chinese patients with tumor-induced osteomalacia. J Bone Miner Metab. 2017;35(3):298–307.

    Article  CAS  Google Scholar 

  20. Jiang Y, Xia WB, Xing XP, et al. Tumor-induced osteomalacia: an important cause of adult-onset hypophosphatemic osteomalacia in China: Report of 39 cases and review of the literature. J Bone Miner Res. 2012;27(9):1967–75.

    Article  Google Scholar 

  21. Avila NA, Skarulis M, Rubino DM, Doppman JL. Oncogenic osteomalacia: lesion detection by MR skeletal survey. AJR Am J Roentgenol. 1996;167(2):343–5.

    Article  CAS  Google Scholar 

  22. Ashton C, Paramalingam S, Stevenson B, Brusch A, Needham M. Idiopathic inflammatory myopathies: a review. Intern Med J. 2021;51(6):845–52.

    Article  Google Scholar 

  23. Tiniakou E, Mammen AL. Idiopathic inflammatory myopathies and malignancy: a comprehensive review. Clin Rev Allergy Immunol. 2017;52(1):20–33.

    Article  CAS  Google Scholar 

  24. Yang Z, Lin F, Qin B, Liang Y, Zhong R. Polymyositis/dermatomyositis and malignancy risk: a metaanalysis study. J Rheumatol. 2015;42(2):282–91.

    Article  Google Scholar 

  25. Moghadam-Kia S, Oddis CV, Ascherman DP, Aggarwal R. Risk factors and cancer screening in myositis. Rheum Dis Clin North Am. 2020;46(3):565–76.

    Article  Google Scholar 

  26. Kang EH, Lee SJ, Ascherman DP, et al. Temporal relationship between cancer and myositis identifies two distinctive subgroups of cancers: impact on cancer risk and survival in patients with myositis. Rheumatology (Oxford). 2016;55(9):1631–41.

    Article  CAS  Google Scholar 

  27. Manger B, Schett G. Paraneoplastic syndromes in rheumatology. Nat Rev Rheumatol. 2014;10(11):662–70.

    Article  CAS  Google Scholar 

  28. Qiang JK, Kim WB, Baibergenova A, Alhusayen R. Risk of malignancy in dermatomyositis and polymyositis. J Cutan Med Surg. 2017;21(2):131–6.

    Article  Google Scholar 

  29. Ichimura Y, Matsushita T, Hamaguchi Y, et al. Anti-NXP2 autoantibodies in adult patients with idiopathic inflammatory myopathies: possible association with malignancy. Ann Rheum Dis. 2012;71(5):710–3.

    Article  CAS  Google Scholar 

  30. Kaji K, Fujimoto M, Hasegawa M, et al. Identification of a novel autoantibody reactive with 155 and 140 kDa nuclear proteins in patients with dermatomyositis: an association with malignancy. Rheumatology (Oxford). 2007;46(1):25–8.

    Article  CAS  Google Scholar 

  31. Targoff IN, Mamyrova G, Trieu EP, et al. A novel autoantibody to a 155-kd protein is associated with dermatomyositis. Arthritis Rheum. 2006;54(11):3682–9.

    Article  CAS  Google Scholar 

  32. Fayyaz B, Rehman HJ, Uqdah H. Cancer-associated myositis: an elusive entity. J Community Hosp Intern Med Perspect. 92019. p. 45–9.

  33. Owada T, Maezawa R, Kurasawa K, Okada H, Arai S, Fukuda T. Detection of inflammatory lesions by f-18 fluorodeoxyglucose positron emission tomography in patients with polymyositis and dermatomyositis. J Rheumatol. 2012;39(8):1659–65.

    Article  CAS  Google Scholar 

  34. András C, Ponyi A, Constantin T, et al. Dermatomyositis and polymyositis associated with malignancy: a 21-year retrospective study. J Rheumatol. 2008;35(3):438–44.

    Google Scholar 

  35. Callemeyn J, Van Haecke P, Peetermans WE, Blockmans D. Clubbing and hypertrophic osteoarthropathy: insights in diagnosis, pathophysiology, and clinical significance. Acta Clin Belg. 2016;71(3):123–30.

    Article  Google Scholar 

  36. Krugh M, Vaidya PN. Osteoarthropathy hypertrophic. StatPearls. Treasure Island (FL): StatPearls PublishingCopyright © 2021.

  37. Yap FY, Skalski MR, Patel DB, et al. Hypertrophic osteoarthropathy: clinical and imaging Features. Radiographics. 2017;37(1):157–95.

    Article  Google Scholar 

  38. Yao Q, Altman RD, Brahn E. Periostitis and hypertrophic pulmonary osteoarthropathy: report of 2 cases and review of the literature. Semin Arthritis Rheum. 2009;38(6):458–66.

    Article  Google Scholar 

  39. Smets P, Devauchelle-Pensec V, Rouzaire PO, Pereira B, Andre M, Soubrier M. Vascular endothelial growth factor levels and rheumatic diseases of the elderly. Arthritis Res Ther. 2016;18(1):283.

    Article  Google Scholar 

  40. Vandemergel X, Blocklet D, Decaux G. Periostitis and hypertrophic osteoarthropathy: etiologies and bone scan patterns in 115 cases. Eur J Intern Med. 2004;15(6):375–80.

    Article  Google Scholar 

  41. Izumi M, Takayama K, Yabuuchi H, Abe K, Nakanishi Y. Incidence of hypertrophic pulmonary osteoarthropathy associated with primary lung cancer. Respirology. 2010;15(5):809–12.

    Article  Google Scholar 

  42. Abdel-Hamid MZ, Chang CH, Chan YS, et al. Arthroscopic evaluation of soft tissue injuries in tibial plateau fractures: retrospective analysis of 98 cases. Arthroscopy. 2006;22(6):669–75.

    Article  Google Scholar 

  43. Pineda C, Martínez-Lavín M. Hypertrophic osteoarthropathy: what a rheumatologist should know about this uncommon condition. Rheum Dis Clin North Am. 2013;39(2):383–400.

    Article  Google Scholar 

  44. Russo RR, Lee A, Mansberg R, Emmett L. Hypertrophic pulmonary osteoarthropathy demonstrated on SPECT/CT. Clin Nucl Med. 2009;34(9):628–31.

    Article  Google Scholar 

  45. Shih WJ. Pulmonary hypertrophic osteoarthropathy and its resolution. Semin Nucl Med. 2004;34(2):159–63.

    Article  Google Scholar 

  46. Capelastegui A, Astigarraga E, García-Iturraspe C. MR findings in pulmonary hypertrophic osteoarthropathy. Clin Radiol. 2000;55(1):72–5.

    Article  CAS  Google Scholar 

  47. Chakraborty RK, Sharma S. Secondary hypertrophic osteoarthropathy. StatPearls. Treasure Island (FL): StatPearls Publishing Copyright © 2021.

  48. Pines A, Kaplinsky N, Olchovsky D, Frankl O. Rheumatoid arthritis-like syndrome: a presenting symptom of malignancy. Report of 3 cases and review of the literature. Eur J Rheumatol Inflamm. 1984;7(2):51–5.

    CAS  Google Scholar 

  49. Khan F, Kleppel H, Meara A. Paraneoplastic musculoskeletal syndromes. Rheum Dis Clin North Am. 2020;46(3):577–86.

    Article  Google Scholar 

  50. Schultz H, Krenn V, Tony HP. Oligoarthritis mediated by tumor-specific T lymphocytes in renal-cell carcinoma. N Engl J Med. 1999;341(4):290–1.

    Article  CAS  Google Scholar 

  51. Parperis K, Constantinidou A, Panos G. Paraneoplastic arthritides: insights to pathogenesis, diagnostic approach, and treatment. J Clin Rheumatol. 2021;27(8):e505–9.

    Article  Google Scholar 

  52. Kisacik B, Onat AM, Kasifoglu T, et al. Diagnostic dilemma of paraneoplastic arthritis: case series. Int J Rheum Dis. 2014;17(6):640–5.

    Article  Google Scholar 

  53. Hakkou J, Rostom S, Bahiri R, Hajjaj-Hassouni N. Paraneoplastic rheumatic syndromes: report of eight cases and review of literature. Rheumatol Int. 2012;32(6):1485–9.

    Article  Google Scholar 

  54. McCarty DJ, O’Duffy JD, Pearson L, Hunter JB. Remitting seronegative symmetrical synovitis with pitting edema. RS3PE syndrome. Jama. 1985;254(19):2763–7.

    Article  CAS  Google Scholar 

  55. Lakhmalla M, Dahiya DS, Kichloo A, Fatima T, Edigin E, Wani F. Remitting seronegative symmetrical synovitis with pitting edema: a review. J Investig Med. 2021;69(1):86–90.

    Article  Google Scholar 

  56. Origuchi T, Arima K, Kawashiri SY, et al. High serum matrix metalloproteinase 3 is characteristic of patients with paraneoplastic remitting seronegative symmetrical synovitis with pitting edema syndrome. Mod Rheumatol. 2012;22(4):584–8.

    Article  CAS  Google Scholar 

  57. Kawashiri SY, Suzuki T, Okada A, et al. Differences in musculoskeletal ultrasound findings between RS3PE syndrome and elderly-onset rheumatoid arthritis. Clin Rheumatol. 2020;39(6):1981–8.

    Article  Google Scholar 

  58. Unlu Z, Orguc S, Ovali GY, Tarhan S, Dayan I, Angin A. Magnetic resonance imaging findings in a case of remitting seronegative symmetrical synovitis with pitting edema. Clin Rheumatol. 2005;24(6):648–51.

    Article  Google Scholar 

  59. Hotta M, Minamimoto R, Kaneko H, Yamashita H. Fluorodeoxyglucose PET/CT of arthritis in rheumatic diseases: a pictorial review. Radiographics. 2020;40(1):223–40.

    Article  Google Scholar 

  60. Wang J, Pu C, Wang Z, Yang J. Remitting seronegative symmetrical synovitis with pitting edema: appearance on FDG PET/CT. Clin Nucl Med. 2017;42(6):492–5.

    Article  Google Scholar 

  61. Medsger TA, Dixon JA, Garwood VF. Palmar fasciitis and polyarthritis associated with ovarian carcinoma. Ann Intern Med. 1982;96(4):424–31.

    Article  CAS  Google Scholar 

  62. Manger B, Schett G. Palmar fasciitis and polyarthritis syndrome-systematic literature review of 100 cases. Semin Arthritis Rheum. 2014;44(1):105–11.

    Article  Google Scholar 

  63. Yoshioka K, Fukumoto T, Sowa-Osako J, Tateishi C. Idiopathic palmar fasciitis and polyarthritis syndrome. BMJ Case Rep. 2019;12(11):e232954.

  64. Celen H, Neerinckx B. Palmar fasciitis and polyarthritis: an uncommon but remarkable paraneoplastic syndrome. Clin Rheumatol. 40. Germany2021. p. 2507–8.

  65. Salmon C, Gill G, Loeuille D, Chary-Valckenaere I. Three new cases of palmar fasciitis with polyarthritis including a patient with atypical mutilating osteolysis. Joint Bone Spine. 2013;80(2):217–20.

    Article  Google Scholar 

  66. Qureshi AA, Saavedra A. Palmar fasciitis and polyarthritis syndrome in patients with ovarian cancer-a case report and review of the literature. Hand (N Y). 2011;6(2):220–3.

    Article  Google Scholar 

  67. Betrains A, Rosseels W, Van Mieghem E, Vanderschueren S, Nijs J. Clinical characteristics, treatment, and outcome of pancreatitis, panniculitis, and polyarthritis syndrome: a case-based review. Clin Rheumatol. 2021;40(4):1625–33.

    Article  Google Scholar 

  68. Yasuda MR, Roller LA, Fagenholz PJ, Hoang MP. Case 33–2020: A 55-year-old man with abdominal pain, joint swelling, and skin lesions. N Engl J Med. 2020;383(17):1664–71.

    Article  Google Scholar 

  69. Narváez J, Bianchi MM, Santo P, et al. Pancreatitis, panniculitis, and polyarthritis. Semin Arthritis Rheum. 2010;39(5):417–23.

    Article  Google Scholar 

  70. Ahn BC, Lee J, Suh KJ, et al. Intramedullary fat necrosis of multiple bones associated with pancreatitis. J Nucl Med. 1998;39(8):1401–4.

    CAS  Google Scholar 

  71. Immelman EJ, Bank S, Krige H, Marks IN. Roentgenologic and clinical features of intramedullary fat necrosis in bones in acute and chronic pancreatitis. Am J Med. 1964;36:96–105.

    Article  CAS  Google Scholar 

  72. Tupalli A, Angamuthu M, Prashanth A, Singh R, Kumar R. Intraosseous medullary fat necrosis on 99mTc-MDP bone scan of patient with acute pancreatitis. Clin Nucl Med. 2020;45(6):e294–5.

    Article  Google Scholar 

  73. Kang DJ, Lee SJ, Choo HJ, Her M, Yoon HK. Pancreatitis, panniculitis, and polyarthritis (PPP) syndrome: MRI features of intraosseous fat necrosis involving the feet and knees. Skeletal Radiol. 2017;46(2):279–85.

    Article  Google Scholar 

  74. Karasick D, Schweitzer ME. Case 4: intraosseous fat necrosis associated with pancreatitis. Radiology. 1998;209(2):521–4.

    Article  CAS  Google Scholar 

  75. Dickerson LK, Sullivan KM, Chew FS, et al. A surgeon, a dermatologist, and a rheumatologist walk into a bar: pancreatitis, panniculitis, and polyarthritis (PPP) syndrome and the role of surgery in a systemic disease. ACS Case Reviews in Surgery. Publication in Press (per personal communication with Felix Chew, MD).

  76. Park HJ, Ranganathan P. Neoplastic and paraneoplastic vasculitis, vasculopathy, and hypercoagulability. Rheum Dis Clin North Am. 2011;37(4):593–606.

    Article  Google Scholar 

  77. Loricera J, Calvo-Río V, Ortiz-Sanjuán F, et al. The spectrum of paraneoplastic cutaneous vasculitis in a defined population: incidence and clinical features. Medicine (Baltimore). 2013;92(6):331–43.

    Article  Google Scholar 

  78. Villa-Forte A. Cutaneous Vasculitis - Musculoskeletal and Connective Tissue Disorders - Merck Manuals Professional Edition. 2020. https://www.merckmanuals.com/professional/musculoskeletal-and-connectivetissue-disorders/vasculitis/cutaneousvasculitis#:~:text=Cutaneous%20vasculitis%20refers%20to%20vasculitis,petechiae%2C%20or%20ulcers%20may%20develop. Last full review/revision Jul 2020| Content last modified Jul 2020.

  79. Dylewski J, Luterman L. Septic arthritis and Clostridium septicum: a clue to colon cancer. CMAJ. 2010;182(13):1446–7.

    Article  Google Scholar 

  80. García-Porrúa C, González-Gay MA, Monterroso JR, Sánchez-Andrade A, González-Ramirez A. Septic arthritis due to Streptococcus bovis as presenting sign of “silent” colon carcinoma. Rheumatology (Oxford). 2000;39(3):338–9.

    Article  Google Scholar 

  81. Hill AB. The environment and disease: association or causation? Proc R Soc Med. 1965;58(5):295–300.

    CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, USA

    Kimia Khalatbari Kani

  2. Yale School of Medicine, Radiology and Biomedical Imaging, New Haven, CT, 06520-8042, USA

    Jack A. Porrino

  3. Department of Diagnostic Radiology and Nuclear Medicine, School of Medicine, University of Maryland, Baltimore, MD, USA

    Michael E. Mulligan

  4. Department of Radiology, University of Washington, 4245 Roosevelt Way NE, Box 354755, Seattle, WA, 98105, USA

    Felix S. Chew

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  1. Kimia Khalatbari Kani
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  2. Jack A. Porrino
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  3. Michael E. Mulligan
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  4. Felix S. Chew
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Conception and design, or acquisition of data, or analysis and interpretation of data: KK, JP, MM, FS. Drafting the article or revising it critically for important intellectual content: KK, JP, MM, FS. Final approval of the version to be published: KK, JP, MM, FS. Agree to be accountable for all aspects of the work if questions arise related to its accuracy or integrity: KK, JP, MM, FS.

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Correspondence to Kimia Khalatbari Kani.

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Khalatbari Kani, K., Porrino, J.A., Mulligan, M.E. et al. Paraneoplastic musculoskeletal disorders: review and update for radiologists. Skeletal Radiol 52, 421–433 (2023). https://doi.org/10.1007/s00256-022-04074-w

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