Final Diagnosis -- Osteosarcoma and Pagetís disease of bone



Osteosarcoma is the most commonly diagnosed primary malignancy of bone, particularly among children and adolescents. Osteosarcoma arising in a background of paget's disease of bone and post-radiation osteosarcoma are examples of secondary osteosarcoma. The former affects elderly patients, and has a poor prognosis and response to treatment1. The later affects a wide age group, and has a prognosis and response to treatment comparable with primary osteosarcoma. Unlike primary osteosarcoma in young patients, which arises most often in the metaphyses of long bones, such as the distal femur, proximal tibia, and proximal humerus, secondary osteosarcoma tends to occur more commonly in axial locations and in areas that have been previously exposure to radiation therapy2, alkylating agents2 or that have underlying diseases such as paget's disease3, Rothmund-Thompson4, retinoblastoma5, Ewing's sarcoma6 and Li-Fraumeni syndrome7.

Paget disease, originally described by Sir James Paget in 1877, is a focal disorder of bone remodelling, involving increased bone resorption and formation. The etiology is uncertain but both environmental and genetic factors are thought to be involved in pathogenesis. Recent study suggested that sporadic Paget disease of bone may due to somatic mutations in SQSTM18. It is generally considered when there is radiographic evidence of cortical destruction, expansion of bone, coarsened trabeculae, and/or bone sclerosis. Paget disease usually affects bones of the skull, spine, pelvis, and lower extremities, but it also reported in hand9. Paget disease is associated with significant disability, impaired quality of life and a variety of complications such as pathological fracture, arthritis in adjacent joints, hearing loss, other neurological and cardiac complications, and lastly, secondary osteosarcoma10.

Secondary osteosarocma is a rare but serious complication of paget's disease and paget's osteosarcoma mainly affect elderly population. Most recent study by Mirabello et al11 shows that age-adjusted incidence rates in 0-24 years age group is 4.4 per million, which represents approximately 53% of all reported osteosarcoma cases with only 1 case of Paget's osteosarcoma in this age group. Individuals ages 25 to 59 years had the lowest incidence rates of osteosarcoma (1.7 per million) that included 4 cases of osteosarcoma in Paget's disease. Osteosarcoma in elderly (>60 years old) represented approximately 19% of all reported osteosarcoma cases (4.2 per million) with 62 cases of osteosarcoma occurring in Pagets disease11.

Although the overall survival rate for secondary osteosarcomas is arguable similar to primary osteosarcomas 12-14, paget's osteosarcoma remains an incurable disease with a poor prognosis. Shaylor et al15 reported in their study of 26 patient with osteosarcoma in Paget' s disease .The survival rate was 53% at 1 year, 25% at 2 years and no patient survived for 5 years despite modern methods of management of bone tumors. All patients died of metastatic disease. The median survival was 21 months for those treated with curative intent and 7 months for those treated palliatively. Four of the five patients treated with limb sparing surgery developed local recurrence between 5 and 12 months, the fifth died at 14 months. There was no difference in survival between amputation and limb salvage.


  1. Dray MS, Miller MV. Paget's osteosarcoma and post-radiation osteosarcoma: secondary osteosarcoma at Middlemore Hospital, New Zealand. Pathology 2008;40(6):604-10.
  2. Le Vu B, de Vathaire F, Shamsaldin A, et al. Radiation dose, chemotherapy and risk of osteosarcoma after solid tumours during childhood. International journal of cancer 1998;77(3):370-7.
  3. Nellissery MJ, Padalecki SS, Brkanac Z, et al. Evidence for a novel osteosarcoma tumor-suppressor gene in the chromosome 18 region genetically linked with Paget disease of bone. American journal of human genetics 1998;63(3):817-24.
  4. Spurney C, Gorlick R, Meyers PA, Healey JH, Huvos AG. Multicentric osteosarcoma, Rothmund-Thomson syndrome, and secondary nasopharyngeal non-Hodgkin's lymphoma: a case report and review of the literature. J Pediatr Hematol Oncol 1998;20(5):494-7.
  5. Smith LM, Donaldson SS. Incidence and management of secondary malignancies in patients with retinoblastoma and Ewing's sarcoma. Oncology (Williston Park, NY 1991;5(5):135-41; discussion 42, 47-8.
  6. Smith LM, Cox RS, Donaldson SS. Second cancers in long-term survivors of Ewing's sarcoma. Clinical orthopaedics and related research 1992(274):275-81.
  7. Porter DE, Holden ST, Steel CM, Cohen BB, Wallace MR, Reid R. A significant proportion of patients with osteosarcoma may belong to Li-Fraumeni cancer families. The Journal of bone and joint surgery 1992;74(6):883-6.
  8. Merchant A, Smielewska M, Patel N, et al. Somatic Mutations in SQSTM1 Detected in Affected Tissues from Patients with Sporadic Paget Disease of Bone. J Bone Miner Res 2008.
  9. Friedman AC, Orcutt J, Madewell JE. Paget disease of the hand: radiographic spectrum. Ajr 1982;138(4):691-3.
  10. Kotowicz MA. Paget disease of bone. Diagnosis and indications for treatment. Australian family physician 2004;33(3):127-31.
  11. Mirabello L, Troisi RJ, Savage SA. Osteosarcoma incidence and survival rates from 1973 to 2004: data from the Surveillance, Epidemiology, and End Results Program. Cancer 2009.
  12. Bielack SS, Tabone MD. Osteosarcomas occurring as second malignant neoplasms. Radiother Oncol 2003;68(1):89.
  13. Hamre MR, Severson RK, Chuba P, Lucas DR, Thomas RL, Mott MP. Osteosarcoma as a second malignant neoplasm. Radiother Oncol 2002;65(3):153-7.
  14. Bielack SS, Kempf-Bielack B, Heise U, Schwenzer D, Winkler K. Combined modality treatment for osteosarcoma occurring as a second malignant disease. Cooperative German-Austrian-Swiss Osteosarcoma Study Group. J Clin Oncol 1999;17(4):1164.
  15. Shaylor PJ, Peake D, Grimer RJ, Carter SR, Tillman RM, Spooner D. Paget's Osteosarcoma - no Cure in Sight. Sarcoma 1999;3(3-4):191-2.

Contributed by Faye F Gao, MD., PHD and Uma N.M. Rao, MD

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