European Journal of Cardiovascular Medicine

Osteo sarcoma or osteogenic sarcoma is cancerous tumor of the bone. It is a malignant neoplasm that arises from the primitive cells of mesenchymal origin and exhibits osteoblastic differentiation and produces malignant osteoid. It is characterized by local aggressive and highly metastatic behavior. Treatment consists of amputation of the affected limb or resection of the tumor along with adjuvent chemotherapy. The estimated 1 year survival rate after amputation as the only treatment is about 14% but this rate increases to approximately 55% after added chemotherapy protocols.

Is a spindle cell malignant tumor characteristic by formation of immature bone  or osteoid or both by the tumour cells. It is divided into several histological subtypes like osteoblastic, fibroblastic, chondroblastic and others. The tumor shows various types of well and undifferentiated cells in a bony matrix.

The histological grading of this tumor serves as a good indicator for prognosis. The histological tumor grade should be an important criteria before surgery and achievement chemotherapy. Good histological grade is associated with increased survival and disease free intervals. In the present study the importance of histological grading is a significant factor in evaluating the clinical outcomes of osteosarcoma.

All the patience who have been diagnosed as Osteosarcoma between 1st  January 2022 to 31st December 2023 have been qualified as participants for the study. it was noted that a total of 170 patients have been diagnosed as osteosarcoma. Paraffin embedded blocks or Formalin or ethyl fixed material was available for evaluation.

Clinical data included age, gender, weight, affected bone, location of the tumour, fine needle aspiration biopsy, plasma alkaline phosphatase levels, presence of metastasis at the time of diagnosis and type of surgical and medical therapy. If the margins of the tumour where free from the tumor it was categorised as totally resected .

Biopsy specimens : Tumour tissue samples where collected either by trephine biopsy or wedge biopsy. Specimens were fixed in neutral buffer 10% formalin and processed for routine histological examination. Hard specimens with fixed in 70% ethanol and cut using microtome. All histological slides with stand with hematoxylin and eosin.

All the histological samples with evaluated by two pathologists and diagnosed as osteosaroma when osteoid was produced by the tumor cells. They were again histologically  sub divided into osteoblastic, chondroblastic, fibroblastic and teleangectatic.

The histological findings that were considered include 1. Cell pleomorphism 2.amount of tumour matrix 3. Density of tumour cells 4. Tumor necrosis 5. Multi nucleated giant cells 6. Mitotic count 7.bizarre cells 8. Lymphovascular invasion.

Classification of tumor grade is determined by histological scores for osteosarcoma is given below

Statistical analysis :

Chi square analysis was used to compare categories data and frequency distribution. Category data was analysed using variance analysis. Multivariate analysis was performed using linear model procedure to evaluate interactions between different dependent variables and independent variables. Paired t-test was used to compare primary tumours and their metastasis. If variables were not normally distributed, a logarithmic transformation was perform. If logarithmic transformation did not result in normal distribution a non parametric test such as Wilcoxon single rank test was used for comparison. Factors evaluated include age, weight, gender, tumor location and side of the tumor, alkaline phosphase,  type of surgical excision , type of chemotherapy histological subtypes ,whorl formation and histological tumor grade. Patients who did not come for follow up or died from non tumor related disease or were free from metastasis at the time of analysis were not included in the survival analysis. Difference with a P value of less than 0.05 was considered significant.

In the study conducted at Government Medical College and Hospital Suryapet a total of 170 cases of Osteo sarcoma were diagnosed. It is the second most common bone malignancy after myeloma. It shows bimodel age distribution most commonly seen in patients in second decade of life and the second peak is seen between 50 to 60 years old. Males are affected more frequently than females. Craniofacial osteosarcomas represent about 6.5% to 7% of all osteosarcomas. Conventional Osteosarcomas are the most common variants.

WHO Classification for osteosarcoma is as follows

• Low grade osteosarcoma
• Convention osteosarcoma (Osteoblastic, Chondroblastic, fibroblastic, Secondary)
• Small cell osteosarcoma
• Telangiectatic osteosarcoma
• Parosteal osteosarcoma
• Periosteal osteosarcoma

Most common sites of Osteo sarcoma were found to be mandible, maxillary lesions along the alveolar ridge, sinus floor and palate. Patients usually presented to the hospital with complaints of pain, swelling, paresthesia and ulceration over the region. The average weight of the patients was 75 Kgs. The tumor was located on the right side in 90 patients left side in 62 patients and in the centre in 8 patients . Biopsy from the tumor site was performed in 40 patients where as fine needle aspiration was done in 25 patients. 18 patients had an increased alkaline phosphase  level compared with reference values. There was no significant difference in mean Alkaline phosphatase levels for different tumor grades. Complete surgical reception with wide margins has been reported as the most significant prognostic factor. Metastasis was less frequent than local recurrence and occurred in about 1/3 of all patients with craniofacial Osteosarcomas. Radio therapy in addition to surgery improved overall survival, disease specific survival and local control in osteosarcomas with positive or uncertain resection margins.

Microscopically Osteo sarcoma where composed of tumor cells which produced malignant bone or osteoid. The individual tumor cells had densely eosinophilic cytoplasm resembling osteoblast but often were larger than normal osteoblast and varied in size with nuclear atypia . The osteoid was thin lace like and consisted of broad irregular trabeculae.The osteoid varied in amount.

Table 1. Histological Findings

Fig 1. Histological Finding

Table 2. Subtypes of Osteosarcoma

Fig 2. Subtypes of Osteosarcoma

Image 1 : Low power view of osteosarcoma in a 17 year old patient.

Image 2 : High power view showing increased tumour cell density, increased mitosis and multinucleated cells

The clinical data presented in our study is comparable to those of previous studies9,10,11.However the histologic data was more difficult to interpret as the previous studies in this tumour had any classification systems were rarely . In 2010, Cho WH, Song WS, Jeon DG and Kong CB presented data for 144 patients with OS that were evaluated by multivariate analysis10. In their study of 144 cases of OS, 47% were osteoblastic, 23% were osteoblastic-chondroblastic, 14% were osteoblastic-fibroblastic, and15% were osteoblastic-chondroblastic-fibroblastic. The findings of the present study are Low grade osteosarcoma 9 cases , osteoblastic osteosarcoma 92 cases , Chondroblastic osteosarcoma 17 cases, Fibroblastic osteosarcoma 17 cases, Secondary osteosarcoma 8 cases , Small cell osteosarcoma 9 cases , Telangiectatic osteosarcoma 7 cases , Parosteal osteosarcoma 10 cases and Periosteal osteosarcoma 1 case .Prognosticators that were used earlier studies, such as fibroblastic25,26 and teleangectatic18 osteosarcoma, were not associated with a significant better or worse prognosis in this study. Histologic grade provides a better assessment of the biologic aggressiveness of the tumor13.High grade (grade III) osteosarcoma in general has a high cell: matrix ratio, poor differentiation  and malignant cytologic characteristics, such as degree of pleomorphism, mitotic index, lymphovascular invasion, amount of necrosis, and invasiveness30. In two studies, tumor grade of osteosarcoma was evaluated using multivariate analysis, but higher risk was not associated with higher tumor grade36.

Both studies, however, included very small populations and one specific tumor site. Tumor grading is a simple procedure without any  additional costs and should be performed before further therapeutic measures are undertaken. Grade I and grade II Osteosarcoma,  have a significantly better prognosis than grade III Osteosarcoma. All researchers that use multivariate analysis to evaluate  should be aware that the grade of Osteosarcoma may significantly influence the outcome. In our study several specific histologic variables, such as cell pleomorphism,  amount of tumour matrix, density of tumour cells , tumour necrosis, multinucleated giant cells ,mitotic count and invasiveness, did not show any significant effect on survival data. The histological findings associated with an increased mortality were the mitotic count, bizarre cells and presence of lymphovascular invasion of tumor cells in blood vessels. Of all the features that were evaluated as prognostic indicators for survival using multivariate analysis, only a few appeared to be significant. Although complete surgical resection without adjunctive chemotherapy should be viewed as a purely palliative procedure, it did increase survival compared incomplete or no resection at all. Also an increased level of Alkaline phosphatase was associated with a shorter Disease free Interval and Survival time.

The response of Osteosarcoma to chemotherapy is variable. Some tumors appear to respond very well to adjuvant chemotherapy, but others show little or no effect. Patients with an increased AP value did not benefit from additional chemotherapy. Osteosarcoma is known as a highly metastatic tumor that supposedly metastasizes through mainly hematogenous routes. The routine evaluation of regional lymph nodes in the staging procedure of the Osteosarcoma is therefore necessary to fully comprehend the metastatic behavior of this tumor type. In this study, the histologic variables of the primary tumor and the corresponding metastases were compared. Most histologic variables were identical, and the histologic subtypes corresponded in most cases. Because the histologic grade was predicted correctly in most cases, the evaluation of biopsy specimens is recommended and may aid in the selection and prediction of outcome for certain therapy protocols. An incisional biopsy of softer outer parts of the Osteosarcoma combined with a core biopsy from the calcified inner part will result in the best chances for accurate diagnosis.

Ultrasound-guided FNAB of bone lesions is another reported way of obtaining a preliminary diagnosis. Osteosarcoma presents with heterogenous histologic and clinical features, of which tumor grade, best predicted by lymphovascular invasion , bizarre cells and  increased mitotic index and AP levels seem to be most important for evaluating the prognosis for survival. Patients with high-grade tumors and elevated AP should be carefully evaluated for the presence of possible metastatic disease before starting adjunctive therapy protocols.

1. Mirabello L, Troisi RJ, Savage SA (2009) International osteosarcoma incidence patterns in children and adolescents, middle ages and elderly persons. Int J Cancer 125, 229–234.
2. Harvei S, Solheim Ø (1981) The prognosis in osteosarcoma: Norwegian national data. Cancer 48, 1719–1723.
3. Sutow WW, Sullivan MP, Fernbach DJ, Cangir A, George SL (1975) Adjuvant chemotherapy in primary treatment of osteogenic sarcoma. A Southwest Oncology Group study. Cancer 36, 1598–1602.
4. Eilber ByF, Giuliano A, Eckardt J, Patterson K, Moseley S, Goodnight J (1987) Adjuvant chemotherapy for osteosarcoma: a randomized prospective trial. J Clin Oncol 5, 21–26.
5. Simon MA, Aschilman MA, Thomas N, Mankin HJ (1986) Limb-salvage treatment versus amputation for osteosarcoma of the distal end of the femur. J Bone Joint Surg Am 68, 1331–1337.
6. Raymond AK, Jaffe N (2009) Osteosarcoma multidisciplinary approach to the management from the pathologist’s perspective, in Pediatric and Adolescent Osteosarcoma. p. 63–84.
7. Abate ME, Longhi A, Galletti S, Ferrari S, Bacci G (2010) Non-metastatic osteosarcoma of the extremities in children aged 5 years or younger. Pediatr Blood Cancer 55, 652–654.
8. Kager L, Zoubek A, Potschger U, Kastner U, Flege S, Kempf-Bielack B, Branscheid D, et al. (2003) Primary metastatic osteosarcoma: presentation and outcome of patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J Clin Oncol 21, 2011–2018.
9. Pakos EE, Nearchou AD, Grimer RJ, Koumoullis HD, Abudu A, Bramer JAM, Jeys LM, et al. (2009) Prognostic factors and outcomes for osteosarcoma: an international collaboration. Eur J Cancer 45, 2367–2375.
10. Cho WH, Song WS, Jeon DG, Kong CB, Kim MS, Lee JA, Yoo JY, Kim JD, Lee SY (2010) Differential presentations, clinical courses, and survivals of osteosarcomas of the proximal humerus over other extremity locations. Ann Surg Oncol 17, 702–708.
11. Kaste SueC, Liu T, Billups CA, Daw NC, Pratt CB, Meyer WH (2004) Tumor size as a predictor of outcome in pediatric non-metastatic osteosarcoma of the extremity. Pediatr Blood Cancer 43, 723–728.
12. Kager L, Zoubek A, Dominkus M, Lang S, Bodmer N, Jundt G, Klingebiel T, Jürgens H, Gadner H, Bielack S (2010) Osteosarcoma in very young children. Cancer 116, 5316–5324.
13. Hayden JB, Hoang BH (2006) Osteosarcoma: basic science and clinical implications. Orthop Clin North Am 37, 1–7.
14. Ozaki T, Flege S, Liljenqvist U, Hillmann A, Delling G, Salzer-Kuntschik M, Jürgens H, Kotz R, Winkelmann W, Bielack SS (2002) Osteosarcoma of the spine: experience of the cooperative osteosarcoma study group. Cancer 94, 1069–1077.
15. Bielack SS, Kempf-Bielack B, Delling G, Exner GU, Flege S, Helmke K, Kotz R, et al. (2002) Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J Clin Oncol 20, 776–790.
16. Klein MJ, Siegal GP (2006) Osteosarcoma anatomic and histologic variants. Am J Clin Pathol 125, 555–581.
17. Fletcher CD, Krishnan Unni K, Mertens F (2002) Pathology and genetics of tumours of soft tissue and bone. IARC 4.
18. Murphey MD, wan Jaovisidha S, Temple HT, Gannon FH, Jelinek JS, Malawer MM (2003) Telangiectatic osteosarcoma: radiologic-pathologic comparison. Radiology 229, 545–553.
19. Kaufman RA, Towbin RB (1981) Telangiectatic osteosarcoma simulating the appearance of an aneurysmal bone cyst. Pediatr Radiol 11, 102–104.
20. Kransdorf MJ, Sweet DE (1995) Aneurysmal bone cyst: concept, controversy, clinical presentation, and imaging. AJR Am J Roentgenol 164, 573–580.
21. Mervak TR, Krishnan Unni K, DJ Pritchard, RA Mcleod (1990) Telangiectatic osteosarcoma. Clin Orthop Relat Res 270, 135–139.
22. Weiss A, Khoury JD, Hoffer FA, Jianrong Wu, Billups CA, Heck RK, Quintana Juan, Poe Debbie, Rao BN, Daw NC (2007) Telangiectatic osteosarcoma: the St. Jude Children’s Research Hospital’s experience. Cancer 109, 1627–1637.
23. Bacci G, Ferrari S, Ruggieri P, Biagini R, Fabbri N, Campanacci L, Bacchini P, Longhi A, Forni C, Bertoni F (2001) Telangiectatic osteosarcoma of the extremity: neoadjuvant chemotherapy in 24 cases. Acta Orthop Scand 72, 167–172.
24. Sim FH, Unni KK, Beabout JW, Dahlin DC (1979) Osteosarcoma with small cells simulating Ewing’s tumor. J Bone Joint Surg Am 61, 207–215.
25. Nakajima H, Sim FH, Bond JR, Unni KK (1997) Small cell osteosarcoma of bone. Review of 72 cases. Cancer 79, 2095–2106.
26. Klein MJ, Siegal GP (2006) Osteosarcoma: anatomic and histologic variants. Am J Clin Pathol 125, 555–581.
27. Andresen KJ, Sundaram M, Unni KK, Sim FH (2004) Imaging features of low-grade central osteosarcoma of the long bones and pelvis. Skeletal Radiol 33, 373–379.
28. Bertoni F, Bacchini P, Fabbri N, Mercuri M, Picci P, Ruggieri P, Campanacci M (1993) Osteosarcoma. Low-grade intraosseous-type osteosarcoma, histologically resembling parosteal osteosarcoma, fibrous dysplasia, and desmoplastic fibroma. Cancer 71, 338–345.
29. Unni KK, Dahlin DC, McLeod RA, Pritchard DJ (1977) Intraosseous well-differentiated osteosarcoma. Cancer 40, 1337–1347.
30. Johnson K, Davies AM, Mangham DC, Grimer RJ (1999) Parosteal osteosarcoma of a metatarsal with intramedullary invasion. Skeletal Radiol 28, 111–115.
31. Hewitt KM, Ellis G, Wiggins R, Bentz BG (2008) Parosteal osteosarcoma: case report and review of the literature. Head Neck 30, 122–126.
32. Okada K, Frassica FJ, Sim FH, Beabout JW, Bond JR, Unni KK (1994) Parosteal osteosarcoma. A clinicopathological study. J Bone Joint Surg Am 76, 366–378.
33. Unni KK, Dahlin DC, Beabout JW (1976) Periosteal osteogenic sarcoma. Cancer 37, 2476–2485.
34. Wold LE, Unni KK, Beabout JW, Pritchard DJ (1984) High-grade surface osteosarcomas. Am J Surg Pathol 8, 181–186.
35. Okada K, Krishnan Unni K, Swee RG, Sim FH (1999) High grade surface osteosarcoma. Cancer 85, 1044–1054.
36. Mialou V, Philip T, Kalifa C, Perol D, Gentet JC, Marec-berard P, Pacquement Helene, Chastagner P, Defaschelles AS, Hartmann O (2005) Metastatic osteosarcoma at diagnosis prognostic factors and long-term outcome – the French pediatric experience. Cancer 104, 1100–1109.
37. Majó J, Cubedo R, Pardo N (2010) Treatment of osteosarcoma. A review. Rev Esp Cir Ortop Traumatol 54, 329–336.
38. Messerschmitt PJ, Garcia RM, Abdul-Karim FW, Greenfield EM, Getty PJ (2009) Osteosarcoma. J Am Acad Orthop Surg 17, 515–527.
39. Aboulafia AJ, Malawer MM (1993) Surgical management of pelvic and extremity osteosarcoma. Cancer 71, 3358–3366.
40. Geller DS, Gorlick R (2010) Osteosarcoma: a review of diagnosis, management, and treatment strategies. Clin Adv Hematol Oncol 8, 705–718.
41. Schima W, Amann G, Stiglbauer R, Windhager R, Kramer J, Nicolakis M, Farres MT, Imhof H (1994) Preoperative osteosarcoma: imaging staging of efficacy of MR in detecting joint involvement. Am J Roentgenol 163, 1171–1175.
42. Shuman WP, Patton AM, Baron AL, Uddell AM, Conrad EU, Richarson ML (1991) Comparison of STIR and spin-echo MA imaging at 1.5 T in 45 suspected extremity tumors: lesion conspicuity and extent. Radiology 179, 247–252.
43. Vormoor B, Knizia HK, Batey MA, Almeida GS, Wilson I, Dildey P, Sharma A, et al. (2014) Development of a preclinical orthotopic xenograft model of ewing sarcoma and other human malignant bone disease using advanced in vivo imaging. PLoS One 9 (1), e85128.
44. Welker JA, Henshaw RM, Jelinek J, Shmookler BM, Malawer MM (2000) The percutaneous needle biopsy is safe and recommended in the diagnosis of musculoskeletal masses. Cancer 89, 2677–2686.
45. Hau A, Kim I, Kattapuram S, Hornicek FJ, Rosenberg AE, Gebhardt MC, Mankin HJ (2002) Accuracy of CT-guided biopsies in 359 patients with musculoskeletal lesions. Skeletal Radiol 31, 349–353.
46. Skrzynski MC, Biermann JS, Montag A, Simon MA (1996) Diagnostic accuracy and charge-savings of outpatient core needle biopsy compared with open biopsy of musculoskeletal tumors. J Bone Joint Surg Am 78-A, 644–649.
47. Unni Krishnan K, Dahlin DC (1989) Osteosarcoma: pathology and classification. Semin Roentgenol 24, 143–152.
48. Mitsuyoshi G, Naito N, Kawai A, Kunisada T, Yoshida A, Yanai H, Dendo S, Yoshino T, Kanazawa S, Ozaki T (2006) Accurate diagnosis of musculoskeletal lesions by core needle biopsy. J Surg Oncol 94, 21–27.
49. Yi JH, Wang D, Li ZY, Hu J, Niu XF, Liu XL (2014) C-Reactive protein as a prognostic factor for human osteosarcoma: A meta-analysis and literature review. PLoS One 9, 1–7.
50. Funovics PT, Edelhauser G, Funovics MA, Laux C, Berzaczy D, Kubista B, Kotz RI, Dominkus M (2011) Pre-operative serum C-reactive protein as independent prognostic factor for survival but not infection in patients with high-grade osteosarcoma. Int Orthop 35, 1529–1536.