History

Fact Explanation
Localized limb or bone pain Progressively increasing on and off dull pain in the bone. Osteosarcoma can affect any bone, most commonly metaphysis of long bones such as distal femur, proximal tibia, proximal humerus where rapid bone growth occur. Less commonly the axial skeleton can also be affected. (10%) Pain is attributed to micro-infarcts caused by rapidly a growing tumor obstructing small blood vessels. Pain may be so severe at night that sleep gets disturbed often. [1,2]
Localized limb swelling [1,2] Pain is followed by swelling if the tumor is large. Commonly a swelling/palpable mass is noted at the first visit.
Pathological fractures [1] Can present in patients with telangiectatic osteosarcoma compared to the conventional osteosarcomas [3]
Limping [2] If osteosarcoma is in a leg bone, the patient may limp.50% of the time it affects around the knee.
Reduced range of movements [1] Due to the associated pain.
Fever, malaise [1] Those constitutional symptoms are not typical of osteosarcoma
Common in the adolescent age group [1] Osteosarcoma is more common in 15-19 years age group. Males are affected more than females. though an exact etiology has not been found,it is thought to correlates with rapid bone growth of this age. Osteosarcoma is the most common primary malignant neoplasm of bone in children and adolescents.[1]
Exposure to the radiation or alkylating agents [1] Though an exact etiology has not been found radiation/radiotherapy or alkylating agents are thought to be a rare cause.
Associated with several genetic syndromes [1] Osteosarcoma is associated with several hereditary forms of retinoblastoma, Li-Fraumeni syndrome and Rothmund-Thomson syndrome. All of them are well-defined hereditary disorders associated with germline alterations of tumor suppressor genes.
Respiratory symptoms and bone pain Lungs and skeleton are the commonest cites where the cancer is metastasized [1]
References
  1. BIELACK S., CARRLE D., CASALI P. G.. Osteosarcoma: ESMO Clinical Recommendations for diagnosis, treatment and follow-up. Annals of Oncology [online] December, 20(Supplement 4):iv137-iv139 [viewed 08 April 2014] Available from: doi:10.1093/annonc/mdp154
  2. PICCI PIERO. . Orphanet J Rare Dis [online] 2007 December [viewed 08 April 2014] Available from: doi:10.1186/1750-1172-2-6
  3. COLOMINA,J. et al. Telangiectatic osteosarcoma,Journal of Orthopaedic Surgery 2013,21(1),96-9 [viewed 8 April 2014]. Available from: http://www.josonline.org/pdf/v21i1p96.pdf

Examination

Fact Explanation
Localized tenderness [1,2] Tenderness is due to ischemia caused by local micro infarcts.
Palpable mass [1,2] The pain/tenderness is followed by a mass only if the tumor is large.
Reduced range of movements of the affected limb [1,2] Due to the pain.
Limp [1] An abnormality in the gait may be detected if osteosarcoma is in a leg bone.
Lymphadenopathies [1] Very rarely osteosarcoma can spread to the local or regional lymph nodes.
Crepitations and rhonchi Lung is the commonest site of metastasis. However respiratory findings are only present in later stages. [1,3]
References
  1. BIELACK S., CARRLE D., CASALI P. G.. Osteosarcoma: ESMO Clinical Recommendations for diagnosis, treatment and follow-up. Annals of Oncology [online] December, 20(Supplement 4):iv137-iv139 [viewed 08 April 2014] Available from: doi:10.1093/annonc/mdp154
  2. PICCI PIERO. . Orphanet J Rare Dis [online] 2007 December [viewed 08 April 2014] Available from: doi:10.1186/1750-1172-2-6
  3. ALJUBRAN,A.H. et al.Osteosarcoma in adolescents and adults: survival analysis with and without lung metastases, Ann Oncol. 2009 Jun,20(6),1136-41. [viewed 8 April 2014]. Available from:doi: 10.1093/annonc/mdn731.

Differential Diagnoses

Fact Explanation
Giant Cell Tumor[1,2] Presented with the limb pain,swelling and reduced range of movements. [1,3]
malignant fibrous histiocytoma (Pleomorphic undifferentiated sarcoma) [2] Occurs most commonly in the extremities as a painless palpable soft tissue mass.[5]
Ewings sarcoma [2] Can occur in any bone,but more commonly in the back. Therefore patients can present with back pain and a palpable mass. [6]
Osteomyelitis [2] Presented with pain, swelling, redness of the affected bone/limb.Fever is a differentiating feature.[7]
References
  1. BIELACK S., CARRLE D., CASALI P. G.. Osteosarcoma: ESMO Clinical Recommendations for diagnosis, treatment and follow-up. Annals of Oncology [online] December, 20(Supplement 4):iv137-iv139 [viewed 08 April 2014] Available from: doi:10.1093/annonc/mdp154
  2. PICCI PIERO. . Orphanet J Rare Dis [online] 2007 December [viewed 08 April 2014] Available from: doi:10.1186/1750-1172-2-6
  3. SHEKHER,A. et al. Synchronous Multicentric Giant Cell Tumour (GCT)-A Rare Case Report,J Clin Diagn Res. 2014 Feb,8(2),185-6. [viewed 8 April 2014]. Available from: doi: 10.7860/JCDR/2014/8153.4055.
  4. KONISHI,Y. et al. Malignant fibrous histiocytoma. Am J Pathol, Jun 1984,115(3),469–472. [viewed 8 April 2014]. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1900519/pdf/amjpathol00183-0153.pdf
  5. CAVAZZANA,A.O et al. Experimental evidence for a neural origin of Ewing's sarcoma of bone,Am J Pathol. Jun 1987,127(3): 507–518.[viewed 8 April 2014]. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1899764/pdf/amjpathol00147-0107.pdf
  6. PRIETO-PEREZ,L. et al. Osteomyelitis: a descriptive study. Clin Orthop Surg,2014 Mar,6(1),20-5. .[viewed 8 April 2014]. Available from: doi: 10.4055/cios.2014.6.1.20.

Investigations - for Diagnosis

Fact Explanation
Plain X-ray Usually an ill defined intramedullary lesion can be seen.Surrounding soft tissue may have calcifications if the tumor has invaded the cortex. Tumor extension through the periosteum may result in a so-called sunburst or hair on end appearance. Osseous changes can be detected such as osteoblastic, osteolytic or mixed appearance according to the content of the tumor. Codman triangle is the hallmark radiological finding of osteosarcoma. It's a triangular area of periosteal calcification in the border region of tumor and healthy tissue. [1,2,3]
MRI Surrounding soft tissue mass is best assessed with MRI.Surrounding vessels,nerves and the intramedullary extension of the osteosarcoma is assessed.So MRI plays an essential part of pre-operative assessment. [1.2]
CT Not of much use in diagnosis. However CT chest is useful to detect lung metastasis. [1,2,3]
Angiogram Detect the vascularity of the tumor.Angiogram gives details such as relationship of vessels to the tumor that helps the surgeon to decide the type of surgical intervention. [3]
Bone scan This helps to rule out multifocal disease or to look for skeletal metastasis.Technetium–99-m bone scans helps in monitoring the effects of chemotherapy and in detecting local recurrence of tumor.[1,2]
Biopsy Is essentially done to confirm the diagnosis.Can be done as an open biopsy or a true-cut biopsy, Fine needle aspiration is not appropriate. [1,2,3]
Serum lactate dehydrogenase (LDH) Has been found to be elevated in some patients.However it doesn't have a diagnostic value.[1]
Serum alkaline phosphatase (ALP) It has been found to be elevated in some patients due to high osteoclastic activity in the tumor.However it doesn't have a diagnostic value. [1]
References
  1. RITTER,J ,S.S.BIELACK. Osteosarcoma,Ann Oncol,2009,20(4),iv137-iv139. [viewed 8 April 2014]. Available from: doi: 10.1093/annonc/mdp154.
  2. FEDERMAN,N. et al. The Multidisciplinary Management of Osteosarcoma,Curr Treat Options Oncol. 2009 Apr,10(1-2),82-93. [viewed 8 April 2014]. Available from: doi: 10.1007/s11864-009-0087-3
  3. CAMPANACCI,M. et al.Parosteal osteosarcoma,J Bone Joint Surg Br.1984, May,66(3),313-21. [viewed 8 April 2014]. Available from: http://www.bjj.boneandjoint.org.uk/content/66-B/3/313.full.pdf

Investigations - Fitness for Management

Fact Explanation
Echocardiography Is done as a baseline investigation as polychemotherapy can result in cardiac dysfunction. [1]
audiogram Is done as a baseline investigation as polychemotherapy can result in auditory dysfunction.[1]
Kidney function tests Is done as a baseline investigation as polychemotherapy can result in significant renal toxicity. [1]
Liver function tests Is done as a baseline investigation as polychemotherapy can result in significant hepatic toxicity. [1]
References
  1. RITTER,J ,S.S.BIELACK. Osteosarcoma,Ann Oncol,2009,20(4),iv137-iv139. [viewed 8 April 2014]. Available from: doi: 10.1093/annonc/mdp154.

Investigations - Followup

Fact Explanation
Chest X-ray and a X-ray of the primary site To detect any lung secondaries and recurrences of osteosarcoma. [1]
Echocardiography Is done as a baseline investigation as polychemotherapy can result in cardiac dysfunction.This should be done every 1-2 years during first 5 years and every 2-4 years thereafter. [1]
Audiogram Is done as a baseline investigation as polychemotherapy can result in auditory dysfunction.This should be done every 1-2 years during first 5 years. [1]
Kidney function tests Is done as a baseline investigation as polychemotherapy can result in significant renal toxicity.This should be done every 1-2 years during first 5 years. [1]
Liver function tests Is done as a baseline investigation as polychemotherapy can result in significant hepatic toxicity.This should be done every 1-2 years during first 5 years.[1]
References
  1. RITTER,J ,S.S.BIELACK. Osteosarcoma,Ann Oncol,2009,20(4),iv137-iv139. [viewed 8 April 2014]. Available from: doi: 10.1093/annonc/mdp154.

Investigations - Screening/Staging

Fact Explanation
Biopsy World Health Organization (WHO) classification has 3 major subtypes : osteoblastic, condroblastic and fibroblastic. In addition there are some additional histological variants, including telangiectatic osteosarcoma, small cell osteosarcoma, parosteal and periosteal osteosarcomas, as well as low grade central and high grade surface osteosarcomas. [1,2]
References
  1. SOBIN,L.H, et al. The World Health Organization's histologic classification of bone tumors. A commentary on the second edition, Cancer. 1995 Mar,1,75(5),1208-14. [viewed 16 March 2014]. Available from: http://www.iarc.fr/en/publications/pdfs-online/pat-gen/bb5/BB5.pdf
  2. ENNEKING, W.F, A system of staging musculoskeletal neoplasms,Clin Orthop Relat Res, 1986 Mar,(204),9-24. [viewed 16 March 2014]. Available from: http://sites.surgery.northwestern.edu/reading/Documents/curriculum/office_scans_5/Di470_0309181741.PDF

Management - General Measures

Fact Explanation
Opioids Used as analgesics for tumor pain. Opioids also improve chemotherapy-induced severe granulocytopenia. [1]
Hematopoetic growth factors Serotonin antagonists has been used successfully as the treatment of chemotherapy-induced emesis. [1]
References
  1. RITTER,J ,S.S.BIELACK. Osteosarcoma,Ann Oncol,2009,20(4),iv137-iv139. [viewed 8 April 2014]. Available from: doi: 10.1093/annonc/mdp154.

Management - Specific Treatments

Fact Explanation
Chemotherapy Chemotherapy is used pre-operatively (neoadjuvant) and post-operatively (adjuvant) to reduce tumor size and to prevent any recurrence respectively. Neoadjuvant chemotherapy makes a limb salvage operation easier. It may decrease the spread of tumor cells at the time of surgery and tumor progression. Neoadjuvant chemotherapy should be given for about 3-4 weeks before the surgery. Methotrexate, Doxorubicin, Cisplatin are carboplatin commonly used. [1,2,3]
Immunomodulation Is a new modality of treatment which has not fully studied. Studies involving alfa interferon and muramyl tripeptide phosphatidyl ethanolamine (MTP) have shown satisfactory results.[1,2]
Limb salvage surgery Removal of the malignant bone tumor without amputation is called limb salvage surgery. Currently,80-90% patients are treated with this technique.The defective bony part is replaced with allografts (cadaveric) or prosthetic devices. Rotationplasty can also be used instead. However,complete surgical resection should be assured for the cure of osteosarcoma. [1,2,3]
Rotationplasty This surgical technique is most commonly used for osteosarcomas of the distal femur when the neurovascular structures and distal aspect of the limb are retained.The distal segment is turned 180 degrees, so that the ankle joint functions as a knee joint in order for prosthetic use to be maximized. [1,2,3]
Amputation Amputation was the main surgical treatment modality in the past.It may be the treatment of choice in some circumstances even now. (eg- Grossly displaced pathologic fractures, Encasement of neurovascular bundle ) [1,2,3]
Radiotherapy Though it was considered to has no role in treating osteosarcoma, recent studies suggest that radiotherapy may be useful in patients who are unable to undergo complete resection.[1,2]
Exploratory thoracotomy Is performed in metastatic lung disease.Both lungs should be palpated during the surgery and all known metastatic foci should be excised. [1]
References
  1. RITTER,J ,S.S.BIELACK. Osteosarcoma,Ann Oncol,2009,20(4),iv137-iv139. [viewed 8 April 2014]. Available from: doi: 10.1093/annonc/mdp154.
  2. FEDERMAN,N. et al. The Multidisciplinary Management of Osteosarcoma,Curr Treat Options Oncol. 2009 Apr,10(1-2),82-93. [viewed 8 April 2014]. Available from: doi: 10.1007/s11864-009-0087-3
  3. PICCI,P. Osteosarcoma (Osteogenic sarcoma),Orphanet J Rare Dis, 2007 Jan, 23,2,6. [viewed 8 April 2014]. Available from: doi:10.1186/1750-1172-2-6.