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ERROR: type should be string, got "https://profreg.medscape.com/px/getpracticeprofile.do?method=getProfessionalProfile&urlCache=aHR0cHM6Ly9lbWVkaWNpbmUubWVkc2NhcGUuY29tL2FydGljbGUvMTI1Njg1Ny13b3JrdXA=\nDrugs & Diseases > Orthopedic Surgery\nOsteosarcoma Workup\nAuthor: Charles T Mehlman, DO, MPH; Chief Editor: Omohodion (Odion) Binitie, MD more...\nSections Osteosarcoma\nWide Resection\nLong-Term Monitoring\nMost of the laboratory studies that are obtained relate to the use of chemotherapy. It is important to assess organ function before administering chemotherapy and to monitor function after chemotherapy. Important laboratory studies include the following:\nLactic dehydrogenase (LDH)\nAlkaline phosphatase (ALP)\nComplete blood count (CBC), including differential\nLiver function tests - Aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin, and albumin\nElectrolyte levels - Sodium, potassium, chloride, bicarbonate, calcium, magnesium, phosphorus\nRenal function tests - Blood urea nitrogen (BUN), creatinine\nThe only blood tests with prognostic significance are LDH and ALP. Patients with an elevated ALP at diagnosis are more likely to have pulmonary metastases. In patients without metastases, those with an elevated LDH are less likely to do well than are those with a normal LDH.\nPlain radiography\nPlain radiography in primary, posteroanterior (PA), and lateral chest views is helpful (see the image below). Plain films of the suspected lesions should be obtained in two views. No single feature on a radiograph is diagnostic. Osteosarcoma lesions can be purely osteolytic (~30% of cases), purely osteoblastic (~45% of cases), or a mixture of both.\nRadiographic appearance (plain radiograph) of a proximal humeral osteosarcoma (same patient as previous image). Note the radiodense matrix of the intramedullary portion of the lesion, as well as the soft-tissue extension and aggressive periosteal reaction.\nElevation of the periosteum may appear as the characteristic Codman triangle. Codman described this entity in 1909, stating, \"In many cases near the junction of the healthy bone with the tumor, there is a reactive new bone formation beneath the periosteum. At the edge of the tumor, this layer of new bone ends abruptly and gives a characteristic appearance in the skiagraph [radiograph].\" [3]\nExtension of the tumor through the periosteum may result in a so-called sunburst appearance (~60% of cases). An image of the entire bone and the adjacent joint should be obtained to assess for skip lesions or joint involvement. Telangiectatic osteosarcomas are often very cystic and can be mistaken for an aneurysmal bone cyst.\nBone scanning\nRadionuclide bone scanning with technetium-99 (99mTc)-methylene diphosphonate (MDP/MDI) is important in evaluating for the presence of metastatic or multifocal disease (see the images below). After the bone scan, an image of abnormal areas should be obtained with computed tomography (CT) or magnetic resonance imaging (MRI).\nIntense radionuclide uptake of the proximal humerus is noted on a bone scan (same patient as previous 2 images).\nA comparison bone scan of the involved shoulder (right image) with the uninvolved shoulder (left image) (same patient as previous 3 images).\nA CT scan of the primary lesion and a CT scan of the chest (high resolution) should be obtained. CT of the primary lesion helps delineate the location and extent of the tumor and is critical for surgical planning.\nCT of the chest is more sensitive than plain film radiography is for assessing pulmonary metastases. Ideally, the chest CT scan of the chest should be obtained before a biopsy is performed so as to avoid the ambiguity that can arise from postanesthesia atelectasis.\nMRI of the primary lesion is the best method of assessing the extent of intramedullary disease, as well as associated soft-tissue masses and skip lesions (see the image below). This imaging modality is perhaps the single most important study for accurate surgical staging of the lesion with use of the Enneking staging system. The MRI should be of the entire bone (compartment).\nMagnetic resonance image appearance (T1-weighted image) of osteosarcoma of the proximal humerus (same patient as previous 4 images). Note the dramatic tumor extension into the adjacent soft-tissue regions.\nIn a meta-analysis of six studies including a total of 66 patients, Kupo et al found that percent slope analysis of dynamic MRI was useful for preoperative evaluation of the response of osteosarcoma patients to neoadjuvant chemotherapy. [24]\nEchocardiography or multiple gated acquisition (MUGA) scanning may be useful. Cardiac function should be assessed before and at various intervals after treatment with doxorubicin hydrochloride.\nAudiography may be considered. Hearing loss is an adverse effect of cisplatin. It typically occurs during treatment; once treatment is completed, obtaining audiograms is not typically a part of long-term follow-up care.\nTwo elements are important to the histologic examination of the tumor. The first, tumor type, can be assessed on the biopsy. The second, response to treatment, can be assessed on the definitive resection following chemotherapy.\nIn general, the characteristic feature of osteosarcoma is the presence of osteoid in the lesion, even at sites distant from bone (eg, lung). Although osteoid formation is usually obvious, electron microscopy occasionally may be required to reveal this process. Stromal cells may be spindle-shaped and atypical, with irregularly shaped nuclei.\nA number of different histologic types of osteosarcoma exist, as follows:\nThe conventional type is the most common in childhood and adolescence and has been subdivided according to the predominant features of the cells (osteoblastic, chondroblastic, or fibroblastic), though the subtypes are clinically indistinguishable\nThe telangiectatic type contains large, blood-filled spaces and is commonly seen in adolescence and early adulthood\nThe parosteal type usually arises from the bone cortex, is commonly a low grade tumor, and can be seen in childhood or adulthood; it most commonly arises on the distal posterior aspect of the femur\nThe periosteal type is a low- to intermediate-grade tumor that typically arises immediately below the periosteum in children; it most frequently involves the tibia and is more common in adults.\nThe purpose of staging tumors is to stratify risk groups. The conventional staging used for other solid tumors is not appropriate for skeletal tumors, because these tumors rarely involve lymph nodes or regional spread.\nInstead, the staging system introduced by Enneking in 1980 is based on histologic grade (low vs high), anatomic location (intracompartmental vs extracompartmental), and presence or absence of metastases. [25, 26] This system (also referred to as the staging system of the Musculoskeletal Tumor Society [MSTS]) applies to all musculoskeletal tumors (both bone and soft tissue). It has been credited with bringing order to the surgical treatment of a group of tumors for which treatment was previously approached rather haphazardly.\nThe Enneking staging system is typically outlined as follows:\nLow-grade tumor, intracompartmental – IA\nLow-grade tumor, extracompartmental – IB\nHigh-grade tumor, intracompartmental – IIA\nHigh-grade tumor, extracompartmental – IIB\nAny tumor (low- or high-grade, intra- or extracompartmental) with evidence of metastasis – III\nThe definition of a compartment is a central and crucial concept in this staging system. In general, a compartment may be defined as any individual bone (ie, each bone is a compartment unto itself), intra-articular space (ie, a purely intra-articular lesion is intracompartmental), or clearly identified fascially enclosed space (eg, the anterior compartment of the lower leg). Many of these compartments are the same ones that a surgeon would release in the setting of compartment syndrome; these relate much more to soft-tissue tumors than to bone tumors.\nThe Enneking staging system considers some areas of the body to be extracompartmental by definition, including the antecubital fossa, the inguinal region, the popliteal space, and intrapelvic and paraspinal lesions. Because of the unique challenges of spinal tumors, Weinstein, Boriani, and Biagin proposed an entirely separate staging system for these areas, commonly referred to as the WBB staging system.\nFirst introduced in 1996, the WBB system focuses on the general anatomic location about the spine (conceptualizing a spinal segment as if it were the face of a clock), as well as the specific anatomic location about the spine (eg, extraosseous soft-tissue extension into muscular areas vs intradural extraosseous extension). [27, 28] Just as spinal anatomy is complex, the WBB staging system is complex, but its use is slowly increasing.\nIn osteosarcoma, the foremost initial question for staging is whether the tumor has metastasized. Other tumor features, though not technically used in staging, may impact the prognosis. These include the following:\nLDH and ALP measurements\nSite of primary tumor (mostly related to ease of complete resection)\nHistologic response to chemotherapy\nCause of the disease (patients with osteosarcomas arising from Paget disease have a particularly poor prognosis)\nPatients with isolated jaw lesions tend to do better and have a lower incidence of metastases.\nDifferent primary tumor sites are associated with differing prognoses, as follows:\nDistal extremity – Best\nDistal femur – Intermediate\nAxial skeleton – Worst\nIn a retrospective study by Kim et al, the records of 331 patients with stage II osteosarcoma who underwent surgery and chemotherapy were reviewed. [29] The authors found that the initial tumor size appears to be associated with histologic response and is an important prognostic factor in osteosarcoma.\nPatients with tumors that have a good histologic response (the definition of which is still under debate) to preoperative chemotherapy appear to have a better prognosis, though this still is under investigation.\nThe National Comprehensive Cancer Network (NCCN) [30] follows both the tumor-node-metastasis (TNM) classification of the American Joint Cancer Committee/Union for International Cancer Control (AJCC/UICC) and the Surgical Staging System from the Musculoskeletal Tumor Society (MTS) for staging. The European Society for Medical Oncology (ESMO), the European Reference Network for Paediatric Cancers (PaedCan), and the European Network for Rare Adult Solid Cancer (EURACAN) [31] do not provide a specific recommendation for which system should be followed.\nMarulanda GA, Henderson ER, Johnson DA, Letson GD, Cheong D. Orthopedic surgery options for the treatment of primary osteosarcoma. Cancer Control. 2008 Jan. 15(1):13-20. [Medline]. [Full Text].\nVander Griend RA. Osteosarcoma and its variants. Orthop Clin North Am. 1996 Jul. 27(3):575-81. [Medline].\nPeltier LF. Tumors of bone and soft tissues. Orthopedics: A History and Iconography. San Francisco: Norman Publishing; 1993. 264-91.\nCampanacci M. Preface. Bone and Soft Tissue Tumors: Clinical Features, Imaging, Pathology and Treatment. 2nd ed. New York: Springer-Verlag; 1999.\nWeis LD. Common malignant bone tumors: osteosarcoma. Simon MA, Springfield D, eds. Surgery for Bone and Soft-Tissue Tumors. Philadelphia: Lippincott-Raven; 1998. 265-74.\nGorlick R, Janeway K, Marina N. Osteosarcoma. Pizzo PA, Poplack DG, eds. Principles and Practice of Pediatric Oncology. 7th ed. Philadelphia: Wolters Kluwer; 2016. 876-97.\nArceci RJ, Weinstein HJ. Neoplasia. MacDonald MG, Seshia MMK, eds. Avery's Neonatology: Pathophysiology and Management of the Newborn. 7th ed. Philadelphia: Wolters Kluwer; 2016. 1048-60.\nKim SY, Helman LJ. Strategies to Explore New Approaches in the Investigation and Treatment of Osteosarcoma. Cancer Treat Res. 2010. 152:517-528. [Medline].\nClark JC, Dass CR, Choong PF. A review of clinical and molecular prognostic factors in osteosarcoma. J Cancer Res Clin Oncol. 2008 Mar. 134(3):281-97. [Medline].\nPochanugool L, Subhadharaphandou T, Dhanachai M, et al. Prognostic factors among 130 patients with osteosarcoma. Clin Orthop Relat Res. 1997 Dec. 345:206-14. [Medline].\nTsuchiya H, Tomita K. Prognosis of osteosarcoma treated by limb-salvage surgery: the ten-year intergroup study in Japan. Jpn J Clin Oncol. 1992 Oct. 22(5):347-53. [Medline].\nTaylor WF, Ivins JC, Unni KK, et al. Prognostic variables in osteosarcoma: a multi-institutional study. J Natl Cancer Inst. 1989 Jan 4. 81(1):21-30. [Medline].\nHudson M, Jaffe MR, Jaffe N, et al. Pediatric osteosarcoma: therapeutic strategies, results, and prognostic factors derived from a 10-year experience. J Clin Oncol. 1990 Dec. 8(12):1988-97. [Medline].\nMeyer WH, Schell MJ, Kumar AP, et al. Thoracotomy for pulmonary metastatic osteosarcoma. An analysis of prognostic indicators of survival. Cancer. 1987 Jan 15. 59(2):374-9. [Medline].\nYang J, Yang D, Cogdell D, Du X, Li H, Pang Y, et al. APEX1 gene amplification and its protein overexpression in osteosarcoma: correlation with recurrence, metastasis, and survival. Technol Cancer Res Treat. 2010 Apr. 9(2):161-9. [Medline].\nKubista B, Klinglmueller F, Bilban M, Pfeiffer M, Lass R, Giurea A, et al. Microarray analysis identifies distinct gene expression profiles associated with histological subtype in human osteosarcoma. Int Orthop. 2011 Mar. 35 (3):401-11. [Medline].\nMirabello 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 Apr 1. 115 (7):1531-43. [Medline].\nPunzalan M, Hyden G. The role of physical therapy and occupational therapy in the rehabilitation of pediatric and adolescent patients with osteosarcoma. Cancer Treat Res. 2010. 152:367-84. [Medline].\nSong WS, Kong CB, Jeon DG, Cho WH, Kim MS, Lee JA, et al. Prognosis of extremity osteosarcoma in patients aged 40-60 years: a cohort/case controlled study at a single institute. Eur J Surg Oncol. 2010 May. 36 (5):483-8. [Medline].\nBu J, Li H, Liu LH, Ouyang YR, Guo HB, Li XY, et al. P16INK4a overexpression and survival in osteosarcoma patients: a meta analysis. Int J Clin Exp Pathol. 2014. 7 (9):6091-6. [Medline]. [Full Text].\nMa W, Zhang X, Chai J, Chen P, Ren P, Gong M. Circulating miR-148a is a significant diagnostic and prognostic biomarker for patients with osteosarcoma. Tumour Biol. 2014 Dec. 35 (12):12467-72. [Medline].\nZhao W, Xu H. High expression of TRPM8 predicts poor prognosis in patients with osteosarcoma. Oncol Lett. 2016 Aug. 12 (2):1373-1379. [Medline].\nKim MS, Lee SY, Cho WH, et al. Initial tumor size predicts histologic response and survival in localized osteosarcoma patients. 1: J Surg Oncol. 2008 Feb 12. 97(5):456-61. [Medline].\nKubo T, Furuta T, Johan MP, Adachi N, Ochi M. Percent slope analysis of dynamic magnetic resonance imaging for assessment of chemotherapy response of osteosarcoma or Ewing sarcoma: systematic review and meta-analysis. Skeletal Radiol. 2016 Sep. 45 (9):1235-42. [Medline].\nEnneking WF, Spanier SS, Goodman MA. A system for the surgical staging of musculoskeletal sarcoma. Clin Orthop Relat Res. 1980 Nov-Dec. 153:106-20. [Medline].\nEnneking WF, Spanier SS, Goodman MA. Current concepts review. The surgical staging of musculoskeletal sarcoma. J Bone Joint Surg Am. 1980 Sep. 62(6):1027-30. [Medline]. [Full Text].\nBoriani S, Weinstein JN, Biagini R. Primary bone tumors of the spine. Terminology and surgical staging. Spine. 1997 May 1. 22(9):1036-44. [Medline].\nHart RA, Boriani S, Biagini R, Currier B, Weinstein JN. A system for surgical staging and management of spine tumors. A clinical outcome study of giant cell tumors of the spine. Spine. 1997 Aug 1. 22(15):1773-82; discussion 1783. [Medline].\nWinkelmann WW. Rotationplasty. Orthop Clin North Am. 1996 Jul. 27(3):503-23. [Medline].\n[Guideline] NCCN Clinical Practice Guidelines in Oncology. Bone Cancer. Version 1.2019. National Comprehensive Cancer Network. Available at http://www.nccn.org/professionals/physician_gls/pdf/bone.pdf. August 3, 2018; Accessed: December 3, 2018.\n[Guideline] Casali PG, Bielack S, Abecassis N, Aro HT, Bauer S, Biagini R, et al. Bone sarcomas: ESMO-PaedCan-EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018 Oct 1. 29 (Supplement_4):iv79-iv95. [Medline]. [Full Text].\nOttaviani G, Robert RS, Huh WW, Jaffe N. Functional, psychosocial and professional outcomes in long-term survivors of lower-extremity osteosarcomas: amputation versus limb salvage. Cancer Treat Res. 2010. 152:421-36. [Medline].\nJaneway KA, Grier HE. Sequelae of osteosarcoma medical therapy: a review of rare acute toxicities and late effects. Lancet Oncol. 2010 Jul. 11 (7):670-8. [Medline].\nBlattmann C, Oertel S, Schulz-Ertner D, Rieken S, Haufe S, Ewerbeck V, et al. Non-randomized therapy trial to determine the safety and efficacy of heavy ion radiotherapy in patients with non-resectable osteosarcoma. BMC Cancer. 2010 Mar 12. 10:96. [Medline]. [Full Text].\nVos HI, Coenen MJ, Guchelaar HJ, Te Loo DM. The role of pharmacogenetics in the treatment of osteosarcoma. Drug Discov Today. 2016 Nov. 21 (11):1775-1786. [Medline].\nYang JZ, Ma SR, Rong XL, Zhu MJ, Ji QY, Meng LJ, et al. Characterization of multidrug‑resistant osteosarcoma sublines and the molecular mechanisms of resistance. Mol Med Rep. 2016 Oct. 14 (4):3269-76. [Medline].\nXiao X, Wang W, Wang Z. The role of chemotherapy for metastatic, relapsed and refractory osteosarcoma. Paediatr Drugs. 2014 Dec. 16 (6):503-12. [Medline].\nMarina NM, Smeland S, Bielack SS, Bernstein M, Jovic G, Krailo MD, et al. Comparison of MAPIE versus MAP in patients with a poor response to preoperative chemotherapy for newly diagnosed high-grade osteosarcoma (EURAMOS-1): an open-label, international, randomised controlled trial. Lancet Oncol. 2016 Oct. 17 (10):1396-1408. [Medline]. [Full Text].\nMankin HJ, Lange TA, Spanier SS. The hazards of biopsy in patients with malignant primary bone and soft-tissue tumors. J Bone Joint Surg Am. 1982 Oct. 64(8):1121-7. [Medline]. [Full Text].\nMankin HJ, Mankin CJ, Simon MA. The hazards of the biopsy, revisited. Members of the Musculoskeletal Tumor Society. J Bone Joint Surg Am. 1996 May. 78(5):656-63. [Medline].\nCraig FS. Vertebral-body biopsy. J Bone Joint Surg Am. 1956 Jan. 38-A(1):93-102. [Medline]. [Full Text].\nChest radiograph of patient with osteosarcoma who died from pulmonary metastatic disease. Note the presence of a pneumothorax as well as radiodense (bone-forming) metastatic lesions.\nClinical appearance of a teenager who presented with osteosarcoma of the proximal humerus (same patient as in the following images). Note the impressive swelling throughout the deltoid region, as well as the disuse atrophy of the pectoral musculature.\nCore needle biopsy instruments commonly used for bony specimens. Craig needle set.\nClose-up view of Craig needle biopsy instruments. Cutting cannula with T-handle attached (top) and sheath through which the cutting cannula passes (bottom).\nResected specimen of a proximal tibia osteosarcoma. The primary lesion was such that the knee joint was resected with the primary lesion. Note that the previous longitudinal biopsy tract was completely excised with the specimen.\nIntraoperative consultation with the pathologist, in which the surgeon and pathologist view the microscopic appearance of the biopsy specimen.\nIntraoperative consultation with the pathologist. A frozen section of the biopsy specimen is being performed.\nIntraoperative photograph of a Van Ness rotationplasty procedure. Osteosynthesis of the tibia to the residual femur is being performed. Courtesy of Alvin H. Crawford MD, FACS.\nClinical photograph taken at the conclusion of a Van Ness rotationplasty procedure (same patient as previous image). Note that the new \"knee\" of the operative side (left side) is purposely reconstructed distal to the normal right knee. This is in anticipation of the future growth potential of the unoperated limb. Courtesy of Alvin H. Crawford MD, FACS.\nCharles T Mehlman, DO, MPH Professor of Pediatrics and Pediatric Orthopedic Surgery, Division of Pediatric Orthopedic Surgery, Director, Musculoskeletal Outcomes Research, Cincinnati Children's Hospital Medical Center\nCharles T Mehlman, DO, MPH is a member of the following medical societies: American Academy of Pediatrics, American Fracture Association, Scoliosis Research Society, Pediatric Orthopaedic Society of North America, American Medical Association, American Orthopaedic Foot and Ankle Society, American Osteopathic Association, Arthroscopy Association of North America, North American Spine Society, Ohio State Medical Association\nTimothy P Cripe, MD, PhD, FAAP Chief, Division of Hematology/Oncology/BMT, Gordon Teter Endowed Chair in Pediatric Cancer, Nationwide Children's Hospital; Professor of Pediatrics, Ohio State University College of Medicine\nTimothy P Cripe, MD, PhD, FAAP is a member of the following medical societies: American Academy of Pediatrics, American Association for the Advancement of Science, American Association for Cancer Research, American Pediatric Society, American Society of Gene and Cell Therapy, American Society of Pediatric Hematology/Oncology, Connective Tissue Oncology Society, Society for Pediatric Research, Children's Oncology Group\nOmohodion (Odion) Binitie, MD Medical Director, Assistant Member, Department of Sarcoma, Section Head, Orthopedics, Adolescent/Young Adult and Pediatric Orthopedic Oncology, Medical Director, Physical Therapy, Speech Therapy, and Rehabilitation Services, Assistant Fellowship Program Director, Musculoskeletal Oncology, Moffitt Cancer Center; Assistant Professor, Department of Oncologic Sciences, Department of Ortho and Sports Medicine, University of South Florida Morsani College of Medicine\nOmohodion (Odion) Binitie, MD is a member of the following medical societies: American Academy of Orthopaedic Surgeons, Children's Oncology Group, Florida Orthopaedic Society, Musculoskeletal Tumor Society\nencoded search term (Osteosarcoma) and Osteosarcoma\nExtrapulmonary Small Cell Carcinoma\nBuccal Carcinoma\nMalignant Tumors of the Palate\nParathyroid Carcinoma\nLung Metastases Imaging\nPrimary Hepatic Carcinoma\nMalignant Tumors of the Sinuses\nShould Docs Rethink Saying 'I'm Sorry' After a Medical Error?\nThe Wild West of Anti-Aging Medicine\n'Pick the Winner' Trial in Rectal Cancer: Chemoradiation First\nChest X-Rays: 16 Subtle But Key Findings You Need to Know\nFast Five Quiz: How Much Do You Know About Metastatic Bone Disease?\nFast Five Quiz: How Much Do You Know About Diagnosing and Treating Metastatic Colorectal Cancer?\nNews Chinese Cancer Article Retraction Could Point to Regulators' Drive for Higher Clinical Research Standards\n2010 /viewarticle/896328 Self Assessment\nSelf Assessment Fast Five Quiz: Key Aspects of Metastatic Breast Cancer"