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Contents lists available at ScienceDirect
Cancer Epidemiology The International Journal of Cancer Epidemiology, Detection, and Prevention journal homepage: www.cancerepidemiology.net
Epidemiology of musculoskeletal tumors in a national referral orthopedic department. A study of 3482 cases Marko Bergovec a,b,*, Ozren Kubat a, Miroslav Smerdelj a, Sven Seiwerth c, Aleksandra Bonevski d, Dubravko Orlic a a
Department of Orthopaedic Surgery, Medical School University of Zagreb, Clinical Hospital Centre Zagreb, Salata 6-7, HR-10000 Zagreb, Croatia Department of Orthopedic Surgery, Medical University of Graz, Auenbruggerplatz 5, A-8036 Graz, Austria Clinical Department of Pathology and Cytology, Medical School University of Zagreb, Clinical Hospital Centre Zagreb, Salata 10, HR-10000 Zagreb, Croatia d Children’s University Hospital Zagreb, Klaiceva 16, HR-10000 Zagreb, Croatia b c
A R T I C L E I N F O
A B S T R A C T
Article history: Received 12 October 2014 Received in revised form 11 January 2015 Accepted 31 January 2015 Available online xxx
Aim of the study: Musculoskeletal tumors are relatively rare, and their geographic distribution varies greatly around the world. In this study, we present the incidence, age distribution and localization of musculoskeletal tumors diagnosed and/or treated at a tertiary referral orthopedic department, catering to an entire Southeastern European country. Methods: This was a retrospective study of prospectively collected data, in which all patients diagnosed and/or treated for musculoskeletal tumors at our Department in the period of 30 years (1981–2010) were included. Results: Data of a total of 3482 patients with musculoskeletal tumors were collected. Average age of patients was 33.5 years (range, 2 months–88 years), with even distribution according to sex. Malignant tumors were seen in 20.7% of patients, more often in men (56.9%). Most common malignant tumors were osteosarcoma (estimated incidence: 1.68/million/year), chondrosarcoma (0.79/million/year) and Ewing sarcoma (0.76/million/year). Benign tumors and tumor-like lesions were found in 79.3% of patients, with slight female predominance. Most common benign bone lesions were osteochondroma (5.81/million/ year), simple bone cyst (2.13/million/year), and enchondroma (2.05/million/year). Conclusion: This report represents a first of its kind in our region, and gives representative results to be compared to other middle and south European countries. Further nationwide studies are needed to improve strategies in bone tumor diagnosis and treatment. ß 2015 Elsevier Ltd. All rights reserved.
Keywords: Osteosarcoma Chondrosarcoma Sarcoma Ewing Osteochondroma Chondroma Bone cysts Incidence
1. Introduction Malignant neoplasms pose a serious public health problem in the modern world. Estimates from the GLOBOCAN project show that in the year 2008 there were approximately 12.7 million new cancer cases, and 7.6 million deaths related to cancer in the World [1]. The newest study of incidence and mortality projects a worldwide incidence of over 15.2 million new cases of cancer, as well as a death count of over 8.8 million for the year 2015 [2]. After a transition over the last decade, the greatest burden of noncommunicable diseases, up to 80%, is now borne by low-income
* Corresponding author at: Department of Orthopaedic Surgery, Medical School University of Zagreb, Clinical Hospital Centre Zagreb, Salata 7, HR-10000 Zagreb, Croatia. Tel.: +385 01 2368 986; fax: +385 01 2379 913. E-mail address: [email protected] (M. Bergovec).
and middle-income countries [3]. This is a cause for alarm mainly because many, if not most, of these countries lack affordable, universally available quality healthcare. The burden of cancer carries with it substantial economical issues for societies worldwide. Although it is not possible to determine the exact cost of the burden of non-communicable diseases, a good example comes from a model for the productivity costs of cancer mortality that projected the annual expenses for the United States of America (USA) at approximately $115.8 billion in the year 2000, and $147.6 billion for 2020 [4]. Musculoskeletal tumors are relatively rare, as they account for 0.2–0.5% of all malignancies in all ages [5,6]. They are most often seen in children and adolescents, and for example, comprise 3–5% of all tumors diagnosed in European children younger than 15 years, and 7–8% in adolescents from 15 to 19 years of age [7]. Geographic distribution of these tumors varies greatly around the world. Countries like India, China and Japan have a very low
http://dx.doi.org/10.1016/j.canep.2015.01.015 1877-7821/ß 2015 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Bergovec M, et al. Epidemiology of musculoskeletal tumors in a national referral orthopedic department. A study of 3482 cases. Cancer Epidemiology (2015), http://dx.doi.org/10.1016/j.canep.2015.01.015
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incidence of musculoskeletal tumors, while the highest incidence is reported in Western Europe and the USA, mainly osteosarcoma and Ewing sarcoma [8]. It is very important to raise global awareness of the growing burden of cancer, and to help improve knowledge of cancer epidemiology, various forms of presentations and populations at risk. Exact information on epidemiology of musculoskeletal tumors in Central, Southern and Eastern Europe are scarce. The aim of this study was to describe the incidence, age and sex distribution, location and histology of benign and malignant musculoskeletal tumors diagnosed and/or treated at a tertiary referral orthopedic department serving the whole country of Croatia. 2. Patients and methods This was a retrospective analysis of prospectively collected data of medical records of all patients diagnosed and/or treated for any type of musculoskeletal tumor at our Department, in the period from 1981 to 2010. The Departmental central archive contains medical records of all patients treated at our facilities. In patients who had a biopsy, or had a tissue sample acquired, all histology findings are included in the records. In patients with confirmed diagnosis of a musculoskeletal tumor, whose data was used for this study, data on both patient and tumor (name, gender, age, tumor localization, tumor histology) were collected in a separate, tumor database that was kept and updated parallel with the main archive. All of the specimens acquired by biopsy or resection were analyzed at our Institution’s Department of clinical pathology and cytology. The final histology diagnosis had been correlated with clinical presentation and imaging findings by two authors (M.B. and D.O.). The tumors were classified according to the 2002 World Health Organization classification of tumors of soft tissue and bone, and stratified into main groups; cartilage-forming tumors, bone forming tumors, tumor-like lesions, connective tissue tumors and soft tissue tumors [5]. Descriptive statistics were carried out to calculate the frequency and percentages of the aforementioned variables. Age distribution was stratified into different groups at 5-year intervals. The statistical analysis was done using the Statistica 10 software for Windows operating system (StatSoft, Tulsa, OK, USA). 3. Results In the reviewed 30-year period, we identified 3482 patients who underwent surgery due to a diagnosis of tumor or tumor-like lesions of the musculoskeletal system at our Department. The average age of patients with musculoskeletal tumors was 33.5 years (range, 2 months–88 years). An even distribution according to sex, with 1745 (50.1%) men and 1737 (49.9%) women, was noted. Out of the total 3482 patients with musculoskeletal tumors diagnosed and/or treated at our Department, 79.3% of tumors were benign and 20.7% (n = 721) malignant. Out of malignant tumors, the most common were osteosarcoma (29.7%), chondrosarcoma (14.0%) and Ewing sarcoma (13.5%). Malignant tumors were more often seen in men (56.9%) than women (43.1%). A very slight female predominance was seen in the total number of benign tumors, affecting 51.9% of women and 48.1% of men in the study. The most commonly seen tumor groups were cartilage-forming tumors (n = 1193, 34.3%), tumor-like lesions (n = 470, 13.5%), and bone forming tumors (n = 468, 13.4%) (Table 1). In regard to diagnosis, osteochondroma was the most commonly seen tumor with 21.3% incidence, followed by chondroma (7.5%), simple bone cyst (7.8%), soft-tissue lipoma (7.3%), osteosarcoma (6.1%), osteoid
Table 1 Distribution of musculoskeletal tumors diagnosed and/or treated in our Department in the period of 1981–2010. The tumors are classified according to the 2002 World Health Organization classification of tumors. The data is given in total number of diagnosed tumors of a certain histological type (second column), and as a percentage of all tumors in this study (third column).
A. Bone tumors I. Cartilage tumors 1. Osteochondroma 2. Chondroma 3. Chondroblastoma 4. Chondromyxoid fibroma 5. Synovial chondromatosis 6. Chondrosarcoma II. Osteogenic tumors 1. Osteoma 2. Osteoid-osteoma 3. Osteoblastoma 4. Osteosarcoma III. Fibrogenic tumors 1. Desmoplastic fibroma 2. Fibrosarcoma IV. Fibrohistiocytic tumors 1. Non-ossifying fibroma 2. Malignant fibrous histiocytoma V. Ewing sarcoma/PNET VI. Hematopoietic tumors 1. Plasma cell myeloma 2. Malignant lymphoma VII. Giant cell tumor of bone VIII. Vascular tumors 1. Hemangioma 2. Angiosarcoma XI. Smooth muscle tumors 1. Leiomyoma 2. Leiomyosarcoma X. Lipogenic tumors 1. Lipoma 2. Liposarcoma XI. Neural tumors 1. Neurilemmoma Miscellaneous tumors 1. Adamantinoma 2. Metastatic malignancy Miscellaneous/tumor-like lesions 1. Aneurysmal bone cyst 2. Simple cyst 3. Fibrous dysplasia 4. Langerhans cell histiocytosis 5. Non-classified miscellaneous lesions B. Soft tissue tumors I. Adipocytic tumors 1. Lipoma 2. Liposarcoma II. Fibroblastic/myofibroblastic tumors 1. Fibroma 2. Myositis ossificans 3. Hemangiopericytoma 4. Fibrosarcoma III. Fibrohistiocytic tumors 1. Giant cell tumor of tendon sheath 2. Diffuse-type giant cell tumor 3. Undifferentiated pleomorphic sarcoma IV. Smooth muscle tumors 1. Leiomyosarcoma V. Pericytic (perivascular) tumors 1. Glomus tumor VI. Vascular tumors 1. Hemangiomas 2. Lymphangioma 3. Kaposi sarcoma 4. Angiosarcoma VII. Chondro-osseous tumors 1. Extraskeletal osteosarcoma Tumors of uncertain differentiation 1. Synovial sarcoma
Total number
% of all tumors
741 262 32 12 45 101
21.3 7.5 0.9 0.3 1.3 2.9
30 191 33 214
0.9 5.5 0.9 6.1
10 4
0.3 0.1
56 14 97
1.6 0.4 2.8
19 4 121
0.5 0.1 3.5
12 3
0.3 0.1
36 14
1.0 0.4
41 4
1.2 0.1
4
0.1
2 149
0.1 4.3
75 272 31 23 69
2.2 7.8 0.9 0.7 2.0
253 25
7.3 0.7
28 16 3 22
0.8 0.5 0.1 0.6
12 60 27
0.3 1.7 0.8
4
0.1
5
0.1
68 2 1 2
2.0 0.1 0.0 0.1
3
0.1
26
0.7
Please cite this article in press as: Bergovec M, et al. Epidemiology of musculoskeletal tumors in a national referral orthopedic department. A study of 3482 cases. Cancer Epidemiology (2015), http://dx.doi.org/10.1016/j.canep.2015.01.015
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97 107
% of all tumors 2.8 3.1
osteoma (5.5%), giant cell tumor of bone (3.5%), chondrosarcoma (2.9%), and Ewing sarcoma (2.8%) (Table 1). Regarding localization of the musculoskeletal tumors, the long bones of the lower extremity (femur 26.7%, tibia 20.3%) held primacy over all other localizations (Fig. 1). The knee joint was involved in more than one fifth of the total number of patient. The hand was involved in 14.4% of all musculoskeletal tumors; making it the third most often affected sight in the body (Fig. 1). The anatomical distribution of benign tumors corresponded to that of malignant tumors. According to the age distribution of musculoskeletal tumors, people aged 11–20 years were most often affected (Fig. 2). The number of benign tumors occurring in this age group is far greater than the number of malignant tumors, and then follows a mostly steady decline as age progresses. The malignant tumors show a
Fig. 1. The distribution of musculoskeletal tumors according to localization, given in percentage of all tumors. Tumors are sorted by affected bone/region, as a percentage of all tumors in this study. The humerus, femur and tibia are divided into thirds: p – proximal, m – mid part, d – distal. The number in front of brackets represents total percentage of tumors affecting that bone/region; the numbers inside the brackets represent the percentage of benign plus malignant tumors for that bone/region.
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bimodal distribution, with a primary peak at the age group of 16– 20 and the second peak at age group of 51–55 (Fig. 2). After reviewing and comparing the results for the three decades in question (1980s, 1990s, 2000s), we have not observed an increase in overall musculoskeletal tumor incidence or any change in trends. Table 2 shows the calculated estimated incidence, most common localization and age group affected for the five most common benign and three most common malignant musculoskeletal tumors seen at our Department for the given period of time.
4. Discussion This paper presents a large record of musculoskeletal tumors from a single Institution that caters to an entire country. Although relatively small, with a population of 4.7 million in the 1980s to 4.3 million according to the most recent population census, Croatia is representative of neighboring Central, Southern and Eastern European countries. The Croatian population is of Slavic origin, very much uniform and settled. This makes the results of this study very applicable for comparison with other countries in the region, making it a potential model for others. Caution should be exercised when comparing these results to those acquired from societies with greater heterogeneity, such as Western Europe and North America, due to racial and social differences. This study has several limitations. This is a retrospective review of prospectively gathered data, and as the data was collected, we noted a 2% of lost data due to incomplete medical records. Although the diagnostic criteria have changed for some tumors over the past 30 years, we did not perform repeated pathology review. After the edition of 2002 World Health Organization bone tumor classification, all tumors in our database from the time before 2002 were regrouped accordingly. Although comprehensive, this report does not show the true incidence of all musculoskeletal tumors in our nation, but instead shows the incidence of those that were diagnosed and/or treated in our Department in a period of 30 years. Some patients with malignant tumors were referred to, or chose to have surgery done outside Croatia, but the vast majority of the diagnostic procedures including biopsy were performed in our Department, and those patients were included in this report. Thus, the presented incidence of malignant musculoskeletal tumors in this report is assumed to be very accurate, and gives a quality representation of the epidemiology of malignant musculoskeletal tumors in our nation. It is the belief of the authors, after reviewing all cases, that the catchment area of this analysis was, in the greatest part, limited to our country, since neighboring countries like Serbia, Bosnia and Herzegovina, and Slovenia, all have university hospitals, which offer orthopedic oncology services to their population. In a tightly knit part of the world, such as the Balkan region of Europe, patient migration is an everyday possibility, but we believe that the influence of those migrations on definite numbers given in Section 3 was minute. A number of smaller, benign tumors were probably omitted from our review, due to the fact that some could have been treated at regional hospitals throughout the country, so we can assume their incidence is probably higher than reported here. Also, as our Department is not the referral center for spinal surgery, we assume the incidence of musculoskeletal tumors affecting the spine is greater than reported in this study. Some tumor-like and benign lesions, like non-ossifying fibroma, unicameral bone cyst or enchondroma, often do not need biopsy or surgical treatment. They could be asymptomatic, discovered accidentally, and undoubtedly there are a number of these lesions, which remain undiscovered throughout the patients’ lifespan. Since this paper contains only data about surgically treated tumors, it is clear that the incidence
Please cite this article in press as: Bergovec M, et al. Epidemiology of musculoskeletal tumors in a national referral orthopedic department. A study of 3482 cases. Cancer Epidemiology (2015), http://dx.doi.org/10.1016/j.canep.2015.01.015
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Fig. 2. Depiction of the age distribution of total percentage of benign and malignant tumors shown in form of a bar graph. The results are sorted in five-year intervals.
of such lesions is much higher than reported, but there is no method to determine it exactly. The results of similar epidemiologic studies conducted at Institutions around the World show clear primacy of benign musculoskeletal tumors over the malignant ones [9–17]. In our study, 79.3% of the reviewed tumors were benign in nature. Osteochondroma, chondroma and simple bone cyst were the three most common benign lesions identified, in that order. Osteochondroma accounted for 21.3% of all the tumors, making it the most commonly seen musculoskeletal tumor and the most common benign musculoskeletal tumor, which is in concordance with the medical literature [6,9–11,15]. However, discrepancies can be found, as Unni et al. reported that osteochondroma made up 9.9%
of all the tumors in their study, while Baena-Ocampo et al. found the percentage of osteochondroma among all tumors to be at 28.5% [15,18]. Interestingly, juvenile bone cysts followed as the second most common tumor–tumor like lesion, constituting a relatively high percentage of all tumors, 7.8%. Chondroma constituted 7.5% of all tumors, as in the study from Mexico [15]. There is controversy related to the incidence of giant cell tumor of bone. In our study it was found to be the fourth most common benign tumor, making up 3.5% of all studied tumors. Turcotte reported an incidence of giant cell tumor of bone to represent 5% of all bone tumors, while Unni et al. found the incidence to be 21.9% [18,19]. Malignant musculoskeletal tumors accounted for 20.7% of the studied tumor cases. This number is high when compared to
Table 2 Incidence, localization and typical age affected by the most common bone tumors. The calculated estimated incidence, most common localization and age group affected for the most commonly seen benign and malignant tumors at our department, in the period from 1981 to 2010. Musculoskeletal tumor
Incidence (no. of cases/million people/year)
Most common localization (% of total)
Most common age group affected (% of total)
Osteochondroma
5.81
20–30 years (51%)
Simple bone cyst
2.13
Enchondroma
2.05
Osteoid osteoma
1.50
Giant cell tumor of bone
0.95
Osteosarcoma
1.68
Chondrosarcoma
0.79
Ewing’s sarcoma
0.76
Distal femur (30%) Proximal tibia (16%) Proximal/diaphysis of humerus (67%) Proximal femur (21%) Metacarpals (28%) Proximal phalanges of hand (40%) Middle and distal phalanges of hand (19%) Femur (44%) Tibia (29%) Distal femur (34%) Proximal tibia (29%) Femur (59% - with the distal femur affected in 84% of the total) Tibia (24% - with the proximal tibia affected in 85% of the total) Femur (39%) Humerus (17%) Pelvis (16%) Hand (16%) Femur (48%) Pelvis (17%) Tibia (16%) Humerus (10%)
0–19 years (96%) 20–60 years
10–19 years (53%) 20–30 years (45%) 10–19 years (48%)
50+ years (40%)
0–19 years (70%)
Please cite this article in press as: Bergovec M, et al. Epidemiology of musculoskeletal tumors in a national referral orthopedic department. A study of 3482 cases. Cancer Epidemiology (2015), http://dx.doi.org/10.1016/j.canep.2015.01.015
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similar epidemiological studies, the explanation being that the data is most likely skewed due to a large number of tumor-like lesions and benign tumors that remain undiscovered and omitted from the analysis. This number may well represent the percentage of tumors that present to the hospital and require treatment, instead of all musculoskeletal tumors. Among the malignant tumors, osteosarcoma was the most commonly encountered, with 214 cases or 6.1% of all musculoskeletal tumors. This fact is well described in the literature, and osteosarcoma is considered to be the most common bone malignancy [9–18]. Regarding the age distribution, we found no cases of osteosarcoma in patients younger than 6 years. The second most common malignant tumor in our study was chondrosarcoma (101 cases, 2.9% of all tumors). This finding concurs with the literature, as Dorfman et al. reported on primary bone sarcomas and placed chondrosarcoma second on the list, with it accounting for 25.8% of all sarcomas [6]. Unni et al. in a study of bone malignancies, reported chondrosarcoma to be the third most common of all bone tumors, at 10.7% [18]. The third most common bone malignancy in our study were secondary bone tumors (149 cases, 4.3% of all tumors), which were not specifically reviewed due to the fact that many regional hospitals treat these patients, who are referred to our Department only in case of impending pathological fracture or the need for reconstruction. This study gives an overview of trends in musculoskeletal tumors in a uniform middle-European population over a 30-year period, with data applicable to a number of neighboring countries. The anatomical distribution of tumors given here further asserts that these tumors have consistent predilection for specific localizations, and being aware of the anatomical location affected can prompt the correct diagnosis, enabling faster treatment. In spite of vast differences in geographic and sociologic background among studies covering these issues, one can clearly note repetitive patterns in their results. Further studies of this topic are warranted, retrospective as well as prospective (i.e. tumor registries), as the one which exists in England, namely the National Cancer Data Repository, reported on by Whelan et al., which could shed more light on any changes in trends of musculoskeletal tumors, enabling creation of better strategies for diagnosing and treatment [20–22]. Conflict of interest statement None of the authors have any financial or other conflict of interest. Authorship contribution Marko Bergovec: conception and design, acquisition of data, analysis of data, interpretation of data, drafting the article, final approval of the version to be published Ozren Kubat: analysis of data, interpretation of data, drafting the article, final approval of the version to be published. Miroslav Smerdelj: conception and design, interpretation of data, revising the article, final approval of the version to be published. Sven Seiwerth: analysis of data, interpretation of data, revising the article, final approval of the
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version to be published. Aleksandra Bonevski: acquisition of data, analysis of data, interpretation of data, revising the article, final approval of the version to be published. Dubravko Orlic: conception and design, acquisition of data, analysis of data, interpretation of data, revising the article, final approval of the version to be published. References [1] Bray F, Ren JS, Masuyer E, Ferlay J. Estimates of global cancer prevalence for 27 sites in the adult population in 2008. Int J Cancer 2013;132:1133–45. http://dx.doi.org/10.1002/ijc.27711. [2] Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, et al. GLOBOCAN 2012 v1.0, cancer incidence and mortality worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer, 2013, http://globocan.iarc.fr [accessed 26.08.14]. [3] Bray F, Ahmedin J, Grey N, Ferlay J, Forman D. Global cancer transitions according to the Human Development Index (2008–2030): a population-based study. Lancet Oncol 2012;13:790–801. http://dx.doi.org/10.1016/S14702045(12)70211-5. [4] Bradley CJ, Yabroff KR, Dahman B, Feuer EJ, Mariotto A, Brown ML. Productivity costs of cancer mortality in the United States: 2000–2020. J Natl Cancer Inst 2008;100:1763–70. http://dx.doi.org/10.1093/jnci/djn384. [5] Fletcher CD, Unni KK, Fletcher F. Pathology and genetics of tumors of soft tissue and bone. Lyon: IARC Press, 2002. [6] Dorfman HD, Czerniak B. Bone cancers. Cancer 1995;75:203–10. [7] Stiller CA, Craft AW, Corazziari I. Survival of children with bone sarcoma in Europe since 1978: results from the EUROCARE study. Eur J Cancer 2001;37:760–6. [8] Eyre R, Feltbower RG, Mubwandarikwa E, Eden TOB, McNally RJQ. Epidemiology of bone tumors in children and young adults. Pediatr Blood Cancer 2009;53:941–52. http://dx.doi.org/10.1002/pbc.22194. [9] Valdespino-Gomez VM, Cintra-McGlone EA, Figueroa-Beltran MA. Bone tumors. Their prevalence. Gac Med Mex 1990;126:325–34. [10] Barbosa CS, Araujo AB, Miranda D. Incidence of primary benign and malignant neoplasms and bone pseudotumoral lesions. An epidemiologic analysis of 585 cases diagnosed at the Facultad de Medicina of the Universidad Federal de Minas Gerais. AMB Rev Assoc Med Bras 1991;37:187–92. [11] Rao VS, Pai MR, Rao RC, Adhikary MM. Incidence of primary bone tumours and tumour like lesions in and around Dakshina Kannada district of Karnataka. J Indian Med Assoc 1996;94:103–4. [12] Bahebeck J, Antangana R, Eyenga V, Pisoh A, Sando Z, Hoffmeyer P. Bone tumours in Cameroon: incidence, demography and histopathology. Int Orthop 2003;27:315–7. [13] Settakorn J, Lekawanvijit S, Arpornchayanon O, Rangdaeng S, Vanitanakom P, Kongkarnka S, et al. Spectrum of bone tumors in Chiang Mai University Hospital Thailand according to WHO classification 2002: a study of 1001 cases. J Med Assoc Thai 2006;89:780–7. [14] Blackwell JB, Thelfall TJ, McCaul KA. Primary malignant bone tumours in Western Australia, 1972–1996. Pathology 2005;37:278–83. [15] Baena-Ocampo LdC, Ramirez-Perez E, Linares-Gonzalez LM, Delgado-Chavez R. Epidemiology of bone tumors in Mexico City: retrospective clinicopathological study of 566 patients at a referral institution. Ann Diagn Pathol 2009;13:16–21. http://dx.doi.org/10.1016/j.anndiagpath.2008.07.005. [16] Solooki S, Vosoughi AR, Masoomi V. Epidemiology of musculoskeletal tumors in Shiraz, south of Iran. Indian J Med Paediatr Oncol 2011;32:187–91. http:// dx.doi.org/10.4103/0971-5851.95138. [17] Campanacci M. Bone and soft tissue tumors: clinical features, imaging, pathology and treatment. 2nd ed. New York: Springer-Verlag, 1999. [18] Unni KK, Inwards CY, Bridge JA, Kindblom LG, Wold LE. Tumors of the bones and joints. Series 4. Fascicle 2. Silver Spring: ARP Press, 2005. [19] Turcotte RE. Giant cell tumor of bone. Orthop Clin North Am 2006;37:35–51. [20] Coleman RE. Clinical features of metastatic bone disease and risk of skeletal morbidity. Clin Cancer Res 2006;12(20 Suppl.):6243–9. [21] Yu¨cetu¨rk G, Sabah D, Kececi B, Kara AD, Yalcinkaya S. Prevalence of bone and soft tissue tumors. Acta Orthop Traumatol Turc 2011;45:135–43. http:// dx.doi.org/10.3944/AOTT.2011.2504. [22] Whelan J, McTiernan A, Cooper N, Wong YK, Francis M, Vernon S, et al. Incidence and survival of malignant bone sarcomas in England 1979–2007. Int J Cancer 2012;131:E508–17. http://dx.doi.org/10.1002/ijc.26426.
Please cite this article in press as: Bergovec M, et al. Epidemiology of musculoskeletal tumors in a national referral orthopedic department. A study of 3482 cases. Cancer Epidemiology (2015), http://dx.doi.org/10.1016/j.canep.2015.01.015
CANEP-815; No. of Pages 5 Cancer Epidemiology xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Cancer Epidemiology The International Journal of Cancer Epidemiology, Detection, and Prevention journal homepage: www.cancerepidemiology.net
Epidemiology of musculoskeletal tumors in a national referral orthopedic department. A study of 3482 cases Marko Bergovec a,b,*, Ozren Kubat a, Miroslav Smerdelj a, Sven Seiwerth c, Aleksandra Bonevski d, Dubravko Orlic a a
Department of Orthopaedic Surgery, Medical School University of Zagreb, Clinical Hospital Centre Zagreb, Salata 6-7, HR-10000 Zagreb, Croatia Department of Orthopedic Surgery, Medical University of Graz, Auenbruggerplatz 5, A-8036 Graz, Austria Clinical Department of Pathology and Cytology, Medical School University of Zagreb, Clinical Hospital Centre Zagreb, Salata 10, HR-10000 Zagreb, Croatia d Children’s University Hospital Zagreb, Klaiceva 16, HR-10000 Zagreb, Croatia b c
A R T I C L E I N F O
A B S T R A C T
Article history: Received 12 October 2014 Received in revised form 11 January 2015 Accepted 31 January 2015 Available online xxx
Aim of the study: Musculoskeletal tumors are relatively rare, and their geographic distribution varies greatly around the world. In this study, we present the incidence, age distribution and localization of musculoskeletal tumors diagnosed and/or treated at a tertiary referral orthopedic department, catering to an entire Southeastern European country. Methods: This was a retrospective study of prospectively collected data, in which all patients diagnosed and/or treated for musculoskeletal tumors at our Department in the period of 30 years (1981–2010) were included. Results: Data of a total of 3482 patients with musculoskeletal tumors were collected. Average age of patients was 33.5 years (range, 2 months–88 years), with even distribution according to sex. Malignant tumors were seen in 20.7% of patients, more often in men (56.9%). Most common malignant tumors were osteosarcoma (estimated incidence: 1.68/million/year), chondrosarcoma (0.79/million/year) and Ewing sarcoma (0.76/million/year). Benign tumors and tumor-like lesions were found in 79.3% of patients, with slight female predominance. Most common benign bone lesions were osteochondroma (5.81/million/ year), simple bone cyst (2.13/million/year), and enchondroma (2.05/million/year). Conclusion: This report represents a first of its kind in our region, and gives representative results to be compared to other middle and south European countries. Further nationwide studies are needed to improve strategies in bone tumor diagnosis and treatment. ß 2015 Elsevier Ltd. All rights reserved.
Keywords: Osteosarcoma Chondrosarcoma Sarcoma Ewing Osteochondroma Chondroma Bone cysts Incidence
1. Introduction Malignant neoplasms pose a serious public health problem in the modern world. Estimates from the GLOBOCAN project show that in the year 2008 there were approximately 12.7 million new cancer cases, and 7.6 million deaths related to cancer in the World [1]. The newest study of incidence and mortality projects a worldwide incidence of over 15.2 million new cases of cancer, as well as a death count of over 8.8 million for the year 2015 [2]. After a transition over the last decade, the greatest burden of noncommunicable diseases, up to 80%, is now borne by low-income
* Corresponding author at: Department of Orthopaedic Surgery, Medical School University of Zagreb, Clinical Hospital Centre Zagreb, Salata 7, HR-10000 Zagreb, Croatia. Tel.: +385 01 2368 986; fax: +385 01 2379 913. E-mail address: [email protected] (M. Bergovec).
and middle-income countries [3]. This is a cause for alarm mainly because many, if not most, of these countries lack affordable, universally available quality healthcare. The burden of cancer carries with it substantial economical issues for societies worldwide. Although it is not possible to determine the exact cost of the burden of non-communicable diseases, a good example comes from a model for the productivity costs of cancer mortality that projected the annual expenses for the United States of America (USA) at approximately $115.8 billion in the year 2000, and $147.6 billion for 2020 [4]. Musculoskeletal tumors are relatively rare, as they account for 0.2–0.5% of all malignancies in all ages [5,6]. They are most often seen in children and adolescents, and for example, comprise 3–5% of all tumors diagnosed in European children younger than 15 years, and 7–8% in adolescents from 15 to 19 years of age [7]. Geographic distribution of these tumors varies greatly around the world. Countries like India, China and Japan have a very low
http://dx.doi.org/10.1016/j.canep.2015.01.015 1877-7821/ß 2015 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Bergovec M, et al. Epidemiology of musculoskeletal tumors in a national referral orthopedic department. A study of 3482 cases. Cancer Epidemiology (2015), http://dx.doi.org/10.1016/j.canep.2015.01.015
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incidence of musculoskeletal tumors, while the highest incidence is reported in Western Europe and the USA, mainly osteosarcoma and Ewing sarcoma [8]. It is very important to raise global awareness of the growing burden of cancer, and to help improve knowledge of cancer epidemiology, various forms of presentations and populations at risk. Exact information on epidemiology of musculoskeletal tumors in Central, Southern and Eastern Europe are scarce. The aim of this study was to describe the incidence, age and sex distribution, location and histology of benign and malignant musculoskeletal tumors diagnosed and/or treated at a tertiary referral orthopedic department serving the whole country of Croatia. 2. Patients and methods This was a retrospective analysis of prospectively collected data of medical records of all patients diagnosed and/or treated for any type of musculoskeletal tumor at our Department, in the period from 1981 to 2010. The Departmental central archive contains medical records of all patients treated at our facilities. In patients who had a biopsy, or had a tissue sample acquired, all histology findings are included in the records. In patients with confirmed diagnosis of a musculoskeletal tumor, whose data was used for this study, data on both patient and tumor (name, gender, age, tumor localization, tumor histology) were collected in a separate, tumor database that was kept and updated parallel with the main archive. All of the specimens acquired by biopsy or resection were analyzed at our Institution’s Department of clinical pathology and cytology. The final histology diagnosis had been correlated with clinical presentation and imaging findings by two authors (M.B. and D.O.). The tumors were classified according to the 2002 World Health Organization classification of tumors of soft tissue and bone, and stratified into main groups; cartilage-forming tumors, bone forming tumors, tumor-like lesions, connective tissue tumors and soft tissue tumors [5]. Descriptive statistics were carried out to calculate the frequency and percentages of the aforementioned variables. Age distribution was stratified into different groups at 5-year intervals. The statistical analysis was done using the Statistica 10 software for Windows operating system (StatSoft, Tulsa, OK, USA). 3. Results In the reviewed 30-year period, we identified 3482 patients who underwent surgery due to a diagnosis of tumor or tumor-like lesions of the musculoskeletal system at our Department. The average age of patients with musculoskeletal tumors was 33.5 years (range, 2 months–88 years). An even distribution according to sex, with 1745 (50.1%) men and 1737 (49.9%) women, was noted. Out of the total 3482 patients with musculoskeletal tumors diagnosed and/or treated at our Department, 79.3% of tumors were benign and 20.7% (n = 721) malignant. Out of malignant tumors, the most common were osteosarcoma (29.7%), chondrosarcoma (14.0%) and Ewing sarcoma (13.5%). Malignant tumors were more often seen in men (56.9%) than women (43.1%). A very slight female predominance was seen in the total number of benign tumors, affecting 51.9% of women and 48.1% of men in the study. The most commonly seen tumor groups were cartilage-forming tumors (n = 1193, 34.3%), tumor-like lesions (n = 470, 13.5%), and bone forming tumors (n = 468, 13.4%) (Table 1). In regard to diagnosis, osteochondroma was the most commonly seen tumor with 21.3% incidence, followed by chondroma (7.5%), simple bone cyst (7.8%), soft-tissue lipoma (7.3%), osteosarcoma (6.1%), osteoid
Table 1 Distribution of musculoskeletal tumors diagnosed and/or treated in our Department in the period of 1981–2010. The tumors are classified according to the 2002 World Health Organization classification of tumors. The data is given in total number of diagnosed tumors of a certain histological type (second column), and as a percentage of all tumors in this study (third column).
A. Bone tumors I. Cartilage tumors 1. Osteochondroma 2. Chondroma 3. Chondroblastoma 4. Chondromyxoid fibroma 5. Synovial chondromatosis 6. Chondrosarcoma II. Osteogenic tumors 1. Osteoma 2. Osteoid-osteoma 3. Osteoblastoma 4. Osteosarcoma III. Fibrogenic tumors 1. Desmoplastic fibroma 2. Fibrosarcoma IV. Fibrohistiocytic tumors 1. Non-ossifying fibroma 2. Malignant fibrous histiocytoma V. Ewing sarcoma/PNET VI. Hematopoietic tumors 1. Plasma cell myeloma 2. Malignant lymphoma VII. Giant cell tumor of bone VIII. Vascular tumors 1. Hemangioma 2. Angiosarcoma XI. Smooth muscle tumors 1. Leiomyoma 2. Leiomyosarcoma X. Lipogenic tumors 1. Lipoma 2. Liposarcoma XI. Neural tumors 1. Neurilemmoma Miscellaneous tumors 1. Adamantinoma 2. Metastatic malignancy Miscellaneous/tumor-like lesions 1. Aneurysmal bone cyst 2. Simple cyst 3. Fibrous dysplasia 4. Langerhans cell histiocytosis 5. Non-classified miscellaneous lesions B. Soft tissue tumors I. Adipocytic tumors 1. Lipoma 2. Liposarcoma II. Fibroblastic/myofibroblastic tumors 1. Fibroma 2. Myositis ossificans 3. Hemangiopericytoma 4. Fibrosarcoma III. Fibrohistiocytic tumors 1. Giant cell tumor of tendon sheath 2. Diffuse-type giant cell tumor 3. Undifferentiated pleomorphic sarcoma IV. Smooth muscle tumors 1. Leiomyosarcoma V. Pericytic (perivascular) tumors 1. Glomus tumor VI. Vascular tumors 1. Hemangiomas 2. Lymphangioma 3. Kaposi sarcoma 4. Angiosarcoma VII. Chondro-osseous tumors 1. Extraskeletal osteosarcoma Tumors of uncertain differentiation 1. Synovial sarcoma
Total number
% of all tumors
741 262 32 12 45 101
21.3 7.5 0.9 0.3 1.3 2.9
30 191 33 214
0.9 5.5 0.9 6.1
10 4
0.3 0.1
56 14 97
1.6 0.4 2.8
19 4 121
0.5 0.1 3.5
12 3
0.3 0.1
36 14
1.0 0.4
41 4
1.2 0.1
4
0.1
2 149
0.1 4.3
75 272 31 23 69
2.2 7.8 0.9 0.7 2.0
253 25
7.3 0.7
28 16 3 22
0.8 0.5 0.1 0.6
12 60 27
0.3 1.7 0.8
4
0.1
5
0.1
68 2 1 2
2.0 0.1 0.0 0.1
3
0.1
26
0.7
Please cite this article in press as: Bergovec M, et al. Epidemiology of musculoskeletal tumors in a national referral orthopedic department. A study of 3482 cases. Cancer Epidemiology (2015), http://dx.doi.org/10.1016/j.canep.2015.01.015
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97 107
% of all tumors 2.8 3.1
osteoma (5.5%), giant cell tumor of bone (3.5%), chondrosarcoma (2.9%), and Ewing sarcoma (2.8%) (Table 1). Regarding localization of the musculoskeletal tumors, the long bones of the lower extremity (femur 26.7%, tibia 20.3%) held primacy over all other localizations (Fig. 1). The knee joint was involved in more than one fifth of the total number of patient. The hand was involved in 14.4% of all musculoskeletal tumors; making it the third most often affected sight in the body (Fig. 1). The anatomical distribution of benign tumors corresponded to that of malignant tumors. According to the age distribution of musculoskeletal tumors, people aged 11–20 years were most often affected (Fig. 2). The number of benign tumors occurring in this age group is far greater than the number of malignant tumors, and then follows a mostly steady decline as age progresses. The malignant tumors show a
Fig. 1. The distribution of musculoskeletal tumors according to localization, given in percentage of all tumors. Tumors are sorted by affected bone/region, as a percentage of all tumors in this study. The humerus, femur and tibia are divided into thirds: p – proximal, m – mid part, d – distal. The number in front of brackets represents total percentage of tumors affecting that bone/region; the numbers inside the brackets represent the percentage of benign plus malignant tumors for that bone/region.
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bimodal distribution, with a primary peak at the age group of 16– 20 and the second peak at age group of 51–55 (Fig. 2). After reviewing and comparing the results for the three decades in question (1980s, 1990s, 2000s), we have not observed an increase in overall musculoskeletal tumor incidence or any change in trends. Table 2 shows the calculated estimated incidence, most common localization and age group affected for the five most common benign and three most common malignant musculoskeletal tumors seen at our Department for the given period of time.
4. Discussion This paper presents a large record of musculoskeletal tumors from a single Institution that caters to an entire country. Although relatively small, with a population of 4.7 million in the 1980s to 4.3 million according to the most recent population census, Croatia is representative of neighboring Central, Southern and Eastern European countries. The Croatian population is of Slavic origin, very much uniform and settled. This makes the results of this study very applicable for comparison with other countries in the region, making it a potential model for others. Caution should be exercised when comparing these results to those acquired from societies with greater heterogeneity, such as Western Europe and North America, due to racial and social differences. This study has several limitations. This is a retrospective review of prospectively gathered data, and as the data was collected, we noted a 2% of lost data due to incomplete medical records. Although the diagnostic criteria have changed for some tumors over the past 30 years, we did not perform repeated pathology review. After the edition of 2002 World Health Organization bone tumor classification, all tumors in our database from the time before 2002 were regrouped accordingly. Although comprehensive, this report does not show the true incidence of all musculoskeletal tumors in our nation, but instead shows the incidence of those that were diagnosed and/or treated in our Department in a period of 30 years. Some patients with malignant tumors were referred to, or chose to have surgery done outside Croatia, but the vast majority of the diagnostic procedures including biopsy were performed in our Department, and those patients were included in this report. Thus, the presented incidence of malignant musculoskeletal tumors in this report is assumed to be very accurate, and gives a quality representation of the epidemiology of malignant musculoskeletal tumors in our nation. It is the belief of the authors, after reviewing all cases, that the catchment area of this analysis was, in the greatest part, limited to our country, since neighboring countries like Serbia, Bosnia and Herzegovina, and Slovenia, all have university hospitals, which offer orthopedic oncology services to their population. In a tightly knit part of the world, such as the Balkan region of Europe, patient migration is an everyday possibility, but we believe that the influence of those migrations on definite numbers given in Section 3 was minute. A number of smaller, benign tumors were probably omitted from our review, due to the fact that some could have been treated at regional hospitals throughout the country, so we can assume their incidence is probably higher than reported here. Also, as our Department is not the referral center for spinal surgery, we assume the incidence of musculoskeletal tumors affecting the spine is greater than reported in this study. Some tumor-like and benign lesions, like non-ossifying fibroma, unicameral bone cyst or enchondroma, often do not need biopsy or surgical treatment. They could be asymptomatic, discovered accidentally, and undoubtedly there are a number of these lesions, which remain undiscovered throughout the patients’ lifespan. Since this paper contains only data about surgically treated tumors, it is clear that the incidence
Please cite this article in press as: Bergovec M, et al. Epidemiology of musculoskeletal tumors in a national referral orthopedic department. A study of 3482 cases. Cancer Epidemiology (2015), http://dx.doi.org/10.1016/j.canep.2015.01.015
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Fig. 2. Depiction of the age distribution of total percentage of benign and malignant tumors shown in form of a bar graph. The results are sorted in five-year intervals.
of such lesions is much higher than reported, but there is no method to determine it exactly. The results of similar epidemiologic studies conducted at Institutions around the World show clear primacy of benign musculoskeletal tumors over the malignant ones [9–17]. In our study, 79.3% of the reviewed tumors were benign in nature. Osteochondroma, chondroma and simple bone cyst were the three most common benign lesions identified, in that order. Osteochondroma accounted for 21.3% of all the tumors, making it the most commonly seen musculoskeletal tumor and the most common benign musculoskeletal tumor, which is in concordance with the medical literature [6,9–11,15]. However, discrepancies can be found, as Unni et al. reported that osteochondroma made up 9.9%
of all the tumors in their study, while Baena-Ocampo et al. found the percentage of osteochondroma among all tumors to be at 28.5% [15,18]. Interestingly, juvenile bone cysts followed as the second most common tumor–tumor like lesion, constituting a relatively high percentage of all tumors, 7.8%. Chondroma constituted 7.5% of all tumors, as in the study from Mexico [15]. There is controversy related to the incidence of giant cell tumor of bone. In our study it was found to be the fourth most common benign tumor, making up 3.5% of all studied tumors. Turcotte reported an incidence of giant cell tumor of bone to represent 5% of all bone tumors, while Unni et al. found the incidence to be 21.9% [18,19]. Malignant musculoskeletal tumors accounted for 20.7% of the studied tumor cases. This number is high when compared to
Table 2 Incidence, localization and typical age affected by the most common bone tumors. The calculated estimated incidence, most common localization and age group affected for the most commonly seen benign and malignant tumors at our department, in the period from 1981 to 2010. Musculoskeletal tumor
Incidence (no. of cases/million people/year)
Most common localization (% of total)
Most common age group affected (% of total)
Osteochondroma
5.81
20–30 years (51%)
Simple bone cyst
2.13
Enchondroma
2.05
Osteoid osteoma
1.50
Giant cell tumor of bone
0.95
Osteosarcoma
1.68
Chondrosarcoma
0.79
Ewing’s sarcoma
0.76
Distal femur (30%) Proximal tibia (16%) Proximal/diaphysis of humerus (67%) Proximal femur (21%) Metacarpals (28%) Proximal phalanges of hand (40%) Middle and distal phalanges of hand (19%) Femur (44%) Tibia (29%) Distal femur (34%) Proximal tibia (29%) Femur (59% - with the distal femur affected in 84% of the total) Tibia (24% - with the proximal tibia affected in 85% of the total) Femur (39%) Humerus (17%) Pelvis (16%) Hand (16%) Femur (48%) Pelvis (17%) Tibia (16%) Humerus (10%)
0–19 years (96%) 20–60 years
10–19 years (53%) 20–30 years (45%) 10–19 years (48%)
50+ years (40%)
0–19 years (70%)
Please cite this article in press as: Bergovec M, et al. Epidemiology of musculoskeletal tumors in a national referral orthopedic department. A study of 3482 cases. Cancer Epidemiology (2015), http://dx.doi.org/10.1016/j.canep.2015.01.015
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similar epidemiological studies, the explanation being that the data is most likely skewed due to a large number of tumor-like lesions and benign tumors that remain undiscovered and omitted from the analysis. This number may well represent the percentage of tumors that present to the hospital and require treatment, instead of all musculoskeletal tumors. Among the malignant tumors, osteosarcoma was the most commonly encountered, with 214 cases or 6.1% of all musculoskeletal tumors. This fact is well described in the literature, and osteosarcoma is considered to be the most common bone malignancy [9–18]. Regarding the age distribution, we found no cases of osteosarcoma in patients younger than 6 years. The second most common malignant tumor in our study was chondrosarcoma (101 cases, 2.9% of all tumors). This finding concurs with the literature, as Dorfman et al. reported on primary bone sarcomas and placed chondrosarcoma second on the list, with it accounting for 25.8% of all sarcomas [6]. Unni et al. in a study of bone malignancies, reported chondrosarcoma to be the third most common of all bone tumors, at 10.7% [18]. The third most common bone malignancy in our study were secondary bone tumors (149 cases, 4.3% of all tumors), which were not specifically reviewed due to the fact that many regional hospitals treat these patients, who are referred to our Department only in case of impending pathological fracture or the need for reconstruction. This study gives an overview of trends in musculoskeletal tumors in a uniform middle-European population over a 30-year period, with data applicable to a number of neighboring countries. The anatomical distribution of tumors given here further asserts that these tumors have consistent predilection for specific localizations, and being aware of the anatomical location affected can prompt the correct diagnosis, enabling faster treatment. In spite of vast differences in geographic and sociologic background among studies covering these issues, one can clearly note repetitive patterns in their results. Further studies of this topic are warranted, retrospective as well as prospective (i.e. tumor registries), as the one which exists in England, namely the National Cancer Data Repository, reported on by Whelan et al., which could shed more light on any changes in trends of musculoskeletal tumors, enabling creation of better strategies for diagnosing and treatment [20–22]. Conflict of interest statement None of the authors have any financial or other conflict of interest. Authorship contribution Marko Bergovec: conception and design, acquisition of data, analysis of data, interpretation of data, drafting the article, final approval of the version to be published Ozren Kubat: analysis of data, interpretation of data, drafting the article, final approval of the version to be published. Miroslav Smerdelj: conception and design, interpretation of data, revising the article, final approval of the version to be published. Sven Seiwerth: analysis of data, interpretation of data, revising the article, final approval of the
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version to be published. Aleksandra Bonevski: acquisition of data, analysis of data, interpretation of data, revising the article, final approval of the version to be published. Dubravko Orlic: conception and design, acquisition of data, analysis of data, interpretation of data, revising the article, final approval of the version to be published. References [1] Bray F, Ren JS, Masuyer E, Ferlay J. Estimates of global cancer prevalence for 27 sites in the adult population in 2008. Int J Cancer 2013;132:1133–45. http://dx.doi.org/10.1002/ijc.27711. [2] Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, et al. GLOBOCAN 2012 v1.0, cancer incidence and mortality worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer, 2013, http://globocan.iarc.fr [accessed 26.08.14]. [3] Bray F, Ahmedin J, Grey N, Ferlay J, Forman D. Global cancer transitions according to the Human Development Index (2008–2030): a population-based study. Lancet Oncol 2012;13:790–801. http://dx.doi.org/10.1016/S14702045(12)70211-5. [4] Bradley CJ, Yabroff KR, Dahman B, Feuer EJ, Mariotto A, Brown ML. Productivity costs of cancer mortality in the United States: 2000–2020. J Natl Cancer Inst 2008;100:1763–70. http://dx.doi.org/10.1093/jnci/djn384. [5] Fletcher CD, Unni KK, Fletcher F. Pathology and genetics of tumors of soft tissue and bone. Lyon: IARC Press, 2002. [6] Dorfman HD, Czerniak B. Bone cancers. Cancer 1995;75:203–10. [7] Stiller CA, Craft AW, Corazziari I. Survival of children with bone sarcoma in Europe since 1978: results from the EUROCARE study. Eur J Cancer 2001;37:760–6. [8] Eyre R, Feltbower RG, Mubwandarikwa E, Eden TOB, McNally RJQ. Epidemiology of bone tumors in children and young adults. Pediatr Blood Cancer 2009;53:941–52. http://dx.doi.org/10.1002/pbc.22194. [9] Valdespino-Gomez VM, Cintra-McGlone EA, Figueroa-Beltran MA. Bone tumors. Their prevalence. Gac Med Mex 1990;126:325–34. [10] Barbosa CS, Araujo AB, Miranda D. Incidence of primary benign and malignant neoplasms and bone pseudotumoral lesions. An epidemiologic analysis of 585 cases diagnosed at the Facultad de Medicina of the Universidad Federal de Minas Gerais. AMB Rev Assoc Med Bras 1991;37:187–92. [11] Rao VS, Pai MR, Rao RC, Adhikary MM. Incidence of primary bone tumours and tumour like lesions in and around Dakshina Kannada district of Karnataka. J Indian Med Assoc 1996;94:103–4. [12] Bahebeck J, Antangana R, Eyenga V, Pisoh A, Sando Z, Hoffmeyer P. Bone tumours in Cameroon: incidence, demography and histopathology. Int Orthop 2003;27:315–7. [13] Settakorn J, Lekawanvijit S, Arpornchayanon O, Rangdaeng S, Vanitanakom P, Kongkarnka S, et al. Spectrum of bone tumors in Chiang Mai University Hospital Thailand according to WHO classification 2002: a study of 1001 cases. J Med Assoc Thai 2006;89:780–7. [14] Blackwell JB, Thelfall TJ, McCaul KA. Primary malignant bone tumours in Western Australia, 1972–1996. Pathology 2005;37:278–83. [15] Baena-Ocampo LdC, Ramirez-Perez E, Linares-Gonzalez LM, Delgado-Chavez R. Epidemiology of bone tumors in Mexico City: retrospective clinicopathological study of 566 patients at a referral institution. Ann Diagn Pathol 2009;13:16–21. http://dx.doi.org/10.1016/j.anndiagpath.2008.07.005. [16] Solooki S, Vosoughi AR, Masoomi V. Epidemiology of musculoskeletal tumors in Shiraz, south of Iran. Indian J Med Paediatr Oncol 2011;32:187–91. http:// dx.doi.org/10.4103/0971-5851.95138. [17] Campanacci M. Bone and soft tissue tumors: clinical features, imaging, pathology and treatment. 2nd ed. New York: Springer-Verlag, 1999. [18] Unni KK, Inwards CY, Bridge JA, Kindblom LG, Wold LE. Tumors of the bones and joints. Series 4. Fascicle 2. Silver Spring: ARP Press, 2005. [19] Turcotte RE. Giant cell tumor of bone. Orthop Clin North Am 2006;37:35–51. [20] Coleman RE. Clinical features of metastatic bone disease and risk of skeletal morbidity. Clin Cancer Res 2006;12(20 Suppl.):6243–9. [21] Yu¨cetu¨rk G, Sabah D, Kececi B, Kara AD, Yalcinkaya S. Prevalence of bone and soft tissue tumors. Acta Orthop Traumatol Turc 2011;45:135–43. http:// dx.doi.org/10.3944/AOTT.2011.2504. [22] Whelan J, McTiernan A, Cooper N, Wong YK, Francis M, Vernon S, et al. Incidence and survival of malignant bone sarcomas in England 1979–2007. Int J Cancer 2012;131:E508–17. http://dx.doi.org/10.1002/ijc.26426.
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