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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
b
Department of Orthopedic Surgery, Medical University of Graz, Auenbruggerplatz 5, A-8036 Graz, Austria
c
Clinical Department of Pathology and Cytology, Medical School University of Zagreb, Clinical Hospital Centre Zagreb, Salata 10, HR-10000 Zagreb, Croatia
d
Childrens University Hospital Zagreb, Klaiceva 16, HR-10000 Zagreb, Croatia

A R T I C L E I N F O A B S T R A C T

Article history: Aim of the study: Musculoskeletal tumors are relatively rare, and their geographic distribution varies
Received 12 October 2014 greatly around the world. In this study, we present the incidence, age distribution and localization of
Received in revised form 11 January 2015 musculoskeletal tumors diagnosed and/or treated at a tertiary referral orthopedic department, catering
Accepted 31 January 2015
to an entire Southeastern European country.
Available online xxx
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 (19812010)
Keywords:
were included.
Osteosarcoma
Chondrosarcoma
Results: Data of a total of 3482 patients with musculoskeletal tumors were collected. Average age of
Sarcoma patients was 33.5 years (range, 2 months88 years), with even distribution according to sex. Malignant
Ewing tumors were seen in 20.7% of patients, more often in men (56.9%). Most common malignant tumors were
Osteochondroma osteosarcoma (estimated incidence: 1.68/million/year), chondrosarcoma (0.79/million/year) and Ewing
Chondroma sarcoma (0.76/million/year). Benign tumors and tumor-like lesions were found in 79.3% of patients, with
Bone cysts slight female predominance. Most common benign bone lesions were osteochondroma (5.81/million/
Incidence year), simple bone cyst (2.13/million/year), and enchondroma (2.05/million/year).
Conclusion: This report represents a rst 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.
2015 Elsevier Ltd. All rights reserved.

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 non-
communicable 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: bergovec@gmail.com (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
0.20.5% of all malignancies in all ages [5,6]. They are most often
seen in children and adolescents, and for example, comprise 35%
of all tumors diagnosed in European children younger than 15
years, and 78% 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/ 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 Table 1

Distribution of musculoskeletal tumors diagnosed and/or treated in our Depart-
is reported in Western Europe and the USA, mainly osteosarcoma
ment in the period of 19812010. The tumors are classied according to the 2002
and Ewing sarcoma [8]. World Health Organization classication of tumors. The data is given in total
It is very important to raise global awareness of the growing number of diagnosed tumors of a certain histological type (second column), and as a
burden of cancer, and to help improve knowledge of cancer percentage of all tumors in this study (third column).
epidemiology, various forms of presentations and populations at Total % of all
risk. Exact information on epidemiology of musculoskeletal number tumors
tumors in Central, Southern and Eastern Europe are scarce. The
A. Bone tumors
aim of this study was to describe the incidence, age and sex I. Cartilage tumors
distribution, location and histology of benign and malignant 1. Osteochondroma 741 21.3
musculoskeletal tumors diagnosed and/or treated at a tertiary 2. Chondroma 262 7.5
3. Chondroblastoma 32 0.9
referral orthopedic department serving the whole country of
4. Chondromyxoid broma 12 0.3
Croatia. 5. Synovial chondromatosis 45 1.3
6. Chondrosarcoma 101 2.9
II. Osteogenic tumors
2. Patients and methods 1. Osteoma 30 0.9
2. Osteoid-osteoma 191 5.5
This was a retrospective analysis of prospectively collected data 3. Osteoblastoma 33 0.9
of medical records of all patients diagnosed and/or treated for any 4. Osteosarcoma 214 6.1
III. Fibrogenic tumors
type of musculoskeletal tumor at our Department, in the period 1. Desmoplastic broma 10 0.3
from 1981 to 2010. The Departmental central archive contains 2. Fibrosarcoma 4 0.1
medical records of all patients treated at our facilities. In patients IV. Fibrohistiocytic tumors
who had a biopsy, or had a tissue sample acquired, all histology 1. Non-ossifying broma 56 1.6
2. Malignant brous histiocytoma 14 0.4
ndings are included in the records. In patients with conrmed
V. Ewing sarcoma/PNET 97 2.8
diagnosis of a musculoskeletal tumor, whose data was used for this VI. Hematopoietic tumors
study, data on both patient and tumor (name, gender, age, tumor 1. Plasma cell myeloma 19 0.5
localization, tumor histology) were collected in a separate, tumor 2. Malignant lymphoma 4 0.1
database that was kept and updated parallel with the main archive. VII. Giant cell tumor of bone 121 3.5
VIII. Vascular tumors
All of the specimens acquired by biopsy or resection were analyzed 1. Hemangioma 12 0.3
at our Institutions Department of clinical pathology and cytology. 2. Angiosarcoma 3 0.1
The nal histology diagnosis had been correlated with clinical XI. Smooth muscle tumors
presentation and imaging ndings by two authors (M.B. and D.O.). 1. Leiomyoma 36 1.0
2. Leiomyosarcoma 14 0.4
The tumors were classied according to the 2002 World Health
X. Lipogenic tumors
Organization classication of tumors of soft tissue and bone, and 1. Lipoma 41 1.2
stratied into main groups; cartilage-forming tumors, bone 2. Liposarcoma 4 0.1
forming tumors, tumor-like lesions, connective tissue tumors XI. Neural tumors
and soft tissue tumors [5]. 1. Neurilemmoma 4 0.1
Miscellaneous tumors
Descriptive statistics were carried out to calculate the 1. Adamantinoma 2 0.1
frequency and percentages of the aforementioned variables. Age 2. Metastatic malignancy 149 4.3
distribution was stratied into different groups at 5-year intervals. Miscellaneous/tumor-like lesions
The statistical analysis was done using the Statistica 10 software 1. Aneurysmal bone cyst 75 2.2
2. Simple cyst 272 7.8
for Windows operating system (StatSoft, Tulsa, OK, USA).
3. Fibrous dysplasia 31 0.9
4. Langerhans cell histiocytosis 23 0.7
5. Non-classied miscellaneous lesions 69 2.0
3. Results
B. Soft tissue tumors
In the reviewed 30-year period, we identied 3482 patients I. Adipocytic tumors
1. Lipoma 253 7.3
who underwent surgery due to a diagnosis of tumor or tumor-like
2. Liposarcoma 25 0.7
lesions of the musculoskeletal system at our Department. The II. Fibroblastic/myobroblastic tumors
average age of patients with musculoskeletal tumors was 33.5 1. Fibroma 28 0.8
years (range, 2 months88 years). An even distribution according 2. Myositis ossicans 16 0.5
3. Hemangiopericytoma 3 0.1
to sex, with 1745 (50.1%) men and 1737 (49.9%) women, was
4. Fibrosarcoma 22 0.6
noted. III. Fibrohistiocytic tumors
Out of the total 3482 patients with musculoskeletal tumors 1. Giant cell tumor of tendon sheath 12 0.3
diagnosed and/or treated at our Department, 79.3% of tumors were 2. Diffuse-type giant cell tumor 60 1.7
benign and 20.7% (n = 721) malignant. Out of malignant tumors, 3. Undifferentiated pleomorphic sarcoma 27 0.8
IV. Smooth muscle tumors
the most common were osteosarcoma (29.7%), chondrosarcoma
1. Leiomyosarcoma 4 0.1
(14.0%) and Ewing sarcoma (13.5%). Malignant tumors were more V. Pericytic (perivascular) tumors
often seen in men (56.9%) than women (43.1%). A very slight 1. Glomus tumor 5 0.1
female predominance was seen in the total number of benign VI. Vascular tumors
1. Hemangiomas 68 2.0
tumors, affecting 51.9% of women and 48.1% of men in the study.
2. Lymphangioma 2 0.1
The most commonly seen tumor groups were cartilage-forming 3. Kaposi sarcoma 1 0.0
tumors (n = 1193, 34.3%), tumor-like lesions (n = 470, 13.5%), and 4. Angiosarcoma 2 0.1
bone forming tumors (n = 468, 13.4%) (Table 1). In regard to VII. Chondro-osseous tumors
diagnosis, osteochondroma was the most commonly seen tumor 1. Extraskeletal osteosarcoma 3 0.1
Tumors of uncertain differentiation
with 21.3% incidence, followed by chondroma (7.5%), simple bone
1. Synovial sarcoma 26 0.7
cyst (7.8%), soft-tissue lipoma (7.3%), osteosarcoma (6.1%), osteoid

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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Table 1 (Continued )
Total % of all
number tumors
Miscellaneous soft tissue tumors
1. Schwannoma 97 2.8
2. Non-dened soft tissue tumors 107 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 fth 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 1120 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.
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
3
bimodal distribution, with a primary peak at the age group of 16
20 and the second peak at age group of 5155 (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 ve most
common benign and three most common malignant musculoskel-
etal 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 classication, all tumors in our database from the time
before 2002 were regrouped accordingly. Although comprehen-
sive, 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
inuence of those migrations on denite 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 broma, 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
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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 ve-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 [917]. 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 identied, in that order. Osteochon-
droma 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 [6,911,15]. 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 tumortumor 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 Most common localization (% of total) Most common age group
(no. of cases/million affected (% of total)
people/year)

Osteochondroma 5.81 Distal femur (30%) 2030 years (51%)

Proximal tibia (16%)
Simple bone cyst 2.13 Proximal/diaphysis of humerus (67%) 019 years (96%)
Proximal femur (21%)
Enchondroma 2.05 Metacarpals (28%) 2060 years
Proximal phalanges of hand (40%)
Middle and distal phalanges of hand (19%)
Osteoid osteoma 1.50 Femur (44%) 1019 years (53%)
Tibia (29%)
Giant cell tumor of bone 0.95 Distal femur (34%) 2030 years (45%)
Proximal tibia (29%)
Osteosarcoma 1.68 Femur (59% - with the distal femur affected 1019 years (48%)
in 84% of the total)
Tibia (24% - with the proximal tibia affected
in 85% of the total)
Chondrosarcoma 0.79 Femur (39%) 50+ years (40%)
Humerus (17%)
Pelvis (16%)
Hand (16%)
Ewings sarcoma 0.76 Femur (48%) 019 years (70%)
Pelvis (17%)
Tibia (16%)
Humerus (10%)

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
G Model
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M. Bergovec et al. / Cancer Epidemiology xxx (2015) xxxxxx
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 [918]. 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 nding 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 specically
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 specic
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 [2022].
Conict of interest statement
None of the authors have any nancial or other conict of
interest.
Authorship contribution
Marko Bergovec: conception and design, acquisition of data,
analysis of data, interpretation of data, drafting the article, nal
approval of the version to be published Ozren Kubat: analysis of
data, interpretation of data, drafting the article, nal approval of
the version to be published. Miroslav Smerdelj: conception and
design, interpretation of data, revising the article, nal approval of
the version to be published. Sven Seiwerth: analysis of data,
interpretation of data, revising the article, nal approval of the
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
5
version to be published. Aleksandra Bonevski: acquisition of data,
analysis of data, interpretation of data, revising the article, nal
approval of the version to be published. Dubravko Orlic:
conception and design, acquisition of data, analysis of data,
interpretation of data, revising the article, nal approval of the
version to be published.
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