ORTHOPAEDIC ONCOLOGY
Epidemiology of bone and
soft-tissue sarcomas
Thomas B Beckingsale
Colin Shaw
Abstract
This paper reviews the current literature on the epidemiology of bone
and soft-tissue sarcomas and includes the latest World Health Organi-
zation classication of these tumours, up-to-date statistics on inci-
dence from the National Cancer Intelligence Network and Public
Health England, new advances in genetic predisposition and diag-
nostic criteria, as well as covering environmental and occupation risk
factors.
Keywords classication; epidemiology; risk factors; sarcoma
Introduction
Sarcomas are a rare and diverse group of malignant tumours
which arise in connective tissues embryologically derived from
the mesenchyme. The mesenchyme develops into the circulatory
and lymphatic systems, as well as structural and connective tis-
sues such as muscle, bone, cartilage and fat. Although peripheral
nerves originate embryologically from the neural crest, tumours
that arise from them are, by convention, grouped with tumours
of mesenchymal origin. Sarcomas present a clinical challenge
because they are so rare, often resulting in a delay in diagnosis.
Best practice guidelines in the UK recommend that they are
treated in specialist centres to which suspected cases should be
referred under the 2 week rule according to National Institute
for Health and Care Excellence (NICE) criteria.1
WHO classication2
As part of the International Classification of Diseases (ICD), the
World Health Organization (WHO) publishes classification systems
for all types of cancer. The WHO Classification of Tumours of Soft
Tissue and Bone, a sub-classification of ICD, covers sarcomas. This
was revised in 2013 and published in a 4th Edition and provides a
universal nomenclature, which helps to ensure comparability
of international clinical trials and translational research.
Many of the changes from the 3rd Edition have been driven by
advances in molecular biology and the rapidly increasing
knowledge of the genetics of tumours. As such, the new system
of classification includes much more detailed cytogenetic and
Thomas B Beckingsale MBBS (Newcastle) MSc (Durham) FRCS
Tr & Orth (Royal College of Surgeons. England) Consultant
Orthopaedic Oncology Surgeon, North of England Bone and Soft
Tissue Tumour Service, Newcastle upon Tyne, UK. Conicts of
interest: none declared.
Colin Shaw MBChB (Glasgow) BSc (hons) (Edinburgh) MSc
(Glasgow) CT1 Orthopaedics, Royal Victoria Inrmary, Newcastle
upon Tyne, UK. Conicts of interest: none declared.
ORTHOPAEDICS AND TRAUMA --:-
Please cite this article in press as: Beckingsale TB, Shaw C, Epidemiology of bone and soft-tissue sarcomas, Orthopaedics and Trauma (2017),
http://dx.doi.org/10.1016/j.mporth.2017.03.005
molecular data. One significant change is the removal of the
term, malignant fibrous histiocytoma (MFH). This was previ-
ously one of the most common diagnoses within soft-tissue sar-
comas, but advances in molecular diagnosis have shown that the
majority of these tumours should be classified with other more
specific sarcoma types. However, there remains a small number
of tumours that do not readily fall under the diagnostic criteria of
other specific types. This diagnosis of exclusion is now termed
undifferentiated pleiomorphic sarcoma.
There are over 100 morphological subtypes of sarcoma, which
for brevity will not be listed in detail here. Instead, this list can be
broadly classified as, follows, corresponding to chapters in the
WHO classification. More detailed information, can be found on
the International Agency for Research on Cancer (IARC) website.
Soft-tissue tumours are broadly categorized into:
 adipocytic tumours
 fibroblastic/myofibroblastic tumours
 fibrohistiocytic tumours
 smooth muscle tumours
 pericytic (perivascular) tumours
 skeletal muscle tumours
 vascular tumour
 chondro-osseous tumours
 gastrointestinal stromal tumours
 nerve sheath tumours
 tumours of uncertain differentiation
 undifferentiated/unclassified sarcomas.
Bone tumours are broadly categorized into:
 chondrogenic tumours
 osteogenic tumours
 fibrogenic tumours
 fibrohistiocytic tumours
 ewing sarcoma
 haematopoietic neoplasms
 osteoclastic giant cell-rich tumours
 notochordal tumours
 vascular tumours
 myogenic, lipogenic and epithelial tumours
 tumours of undefined neoplastic nature.
The incidence of sarcomas
The National Cancer Intelligence Network (NCIN) is a UK-wide
partnership operated by Public Health England, which provides
a wealth of information about all types of cancer in the UK. The
NCIN analyses common national cancer datasets to monitor pat-
terns of care, drive improvement, and support research and audit.
Much of the following information has been drawn from NCIN
reports, and further information is available at www.ncin.org.uk.
Another excellent source of information is the research charity
Cancer Research UK and further data are available at www.
cancerresearchuk.org.
Sarcomas are extremely rare; soft-tissue sarcomas account for
only 1% of malignancies diagnosed in the UK and of those bone
sarcomas as a whole are only 0.2% of all diagnosed cancer
cases.3 They have an age-standardized incidence of 45 per
million per year as reported from 2010 data. This has increased
1 2017 Elsevier Ltd. All rights reserved.
 ORTHOPAEDIC ONCOLOGY
over time from an incidence of 39 per million per year in 1996,
although it should be stressed that this increase may simply
reflect improved diagnostic techniques rather than a true in-
crease in incidence. In 2010, there were 3298 new cases of soft-
tissue sarcoma diagnosed in the UK, of which 51% affected
males, and 49% affected females. The yearly incidence of soft-
tissue sarcoma is consistently higher in males than females
although this difference is rarely statistically significant.3
The age-standardized incidence of bone sarcoma has
remained fairly constant in the UK since 1996 at around 7.9 per
million per year, and the incidence from 2010 was reported by
the NCIN as 8.2 per million per year. In 2011, there were 559 new
cases of bone sarcoma diagnosed in the UK of which 58%
occurred in males and 42% in females, an incidence ratio of more
than 13:10. The increased incidence of bone sarcomas in males
compared to females is also consistent, but in this case the dif-
ference is statistically significant.3
The diagnosis, age and site of presenting tumours
Until recently lists of the most common types of soft-tissue sar-
coma included malignant fibrous histiocytoma, which has been
removed from the WHO classification system. Now the two most
common soft-tissue sarcomas in the UK are leiomyosarcoma
(22%) and liposarcoma (12%).
The most common site for soft-tissue sarcomas in general is in
the extremities (23%) with approximately two thirds of these
arising in the lower limbs. In children below the age of 10, the
most common site is in the head and neck (23%) with a pre-
dominance of rhabdomyosarcoma4 (Figure 1).
Overall, the incidence of soft-tissue sarcomas increases
significantly with age, with more than 65% of cases occurring in
patients aged 50 and over. The highest incidence is seen in the
over 85 year old age group, particularly males, where the inci-
dence reaches 230 per million per year and exceeds the rate for
females of that age by a ratio of 1.9:1. In females, the incidence of
soft-tissue sarcomas exceeds that of males between the ages of 45
and 59, due to the preponderance of gynaecological sarcomas in
that age group. The incidence of leiomyosarcomas mirrors the
increased incidence of sarcomas seen with advancing age,
whereas synovial sarcomas are seen more commonly in young
Figure 1 Proportion of soft-tissue sarcomas diagnosed in each age group and anatomical site (England: 1985e2009). Reproduced with permission
of Public Health England.4
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Please cite this article in press as: Beckingsale TB, Shaw C, Epidemiology of bone and soft-tissue sarcomas, Orthopaedics and Trauma (2017),
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adults in their third and fourth decade, and rhabdomyosarcomas
predominate in early childhood.4
The most common types of bone sarcoma are osteosarcoma,
Ewings sarcoma, chondrosarcoma and chordoma. Overall, bone
sarcomas arise most commonly in the lower limbs (38%), with
other common areas being the pelvis (16%) and upper limbs
(14%). With increasing age the pattern changes, with fewer tu-
mours presenting in the limbs and more being diagnosed in the
pelvis. In patients under the age of 20 years, 70% of tumours
occur in the extremities, whereas only 40% of bone sarcomas
present in the limbs in patients over the age of 40.5 For further
information on the incidence by age of the four most common
bone sarcomas see Figure 2, and for more detailed information
on the most common sites of presentation, see Figure 3.
Osteosarcomas are most common in childhood, with a peak
incidence during the adolescent growth spurt. However, they
follow a bimodal distribution, with a second peak in late adult
life where they currently occur as late sequelae of radiation
exposure or Pagets disease (both covered later).5
Ewings sarcoma is most common in childhood and adoles-
cence, the incidence thereafter tailing off such that it is very
uncommon after the age of 30. Proportionally Ewings sarcoma is
the most common bone sarcoma in the under-10 age group,
whereas osteosarcoma is proportionally the most common bone
sarcoma in the 10e19 year old age group. Ewings sarcoma has a
median age of onset of 15 years.5
Chondrosarcoma is the second most common primary bone
tumour. It is exceptionally rare in childhood and adolescence and
its incidence increases steadily with age. Between the ages of 50
and 59, chondrosarcoma comprises 50% of all primary bone
tumours. Although the incidence continues to increase beyond
this age, as a proportion of all bone sarcomas its prevalence
decreases due to the second peak of osteosarcoma cases in the
elderly.5 Figure 4 shows a chondrosarcoma of the pelvis.
Chordoma, the least common of the four predominant bone
sarcomas, arises from remnants of the embryological notochord
and thus presents in the axial skeleton. Like chondrosarcoma, it
is exceptionally rare in childhood and adolescence, and its inci-
dence increases with age. The overall incidence of chordoma is
approximately 1 per million per year.5
2 2017 Elsevier Ltd. All rights reserved.
 ORTHOPAEDIC ONCOLOGY

Figure 2 Age-specic incidence of the most common bone sarcoma variants (England: 1985e2009). Reproduced with permission of Public Health
England.5

Figure 3 Proportion of bone sarcomas diagnosed by age group and anatomical site (England: 1985e2009). Reproduced with permission of Public
Health England.5

Environmental risk factors
Radiation
A causal link between radiation exposure and cancer in general is
well established and was noted in the pathogenesis of both soft-
tissue and bone sarcoma formation from as far back as the early
1900s. Georg Perthes, a German surgeon, was a pioneer of early
Figure 4 Chondrosarcoma of the pelvis.
radiation treatments and radiography and described a case of a
spindle cell sarcoma in a patient treated with radiation for lupus
as far back as 1904.6
It is a sad irony that radiation, used in the treatment of around
60% of patients with cancer, can itself be a causative agent. The
attributable risk of second malignancy after radiotherapy is not
without controversy. Carcinomas often occur in sites remote
from the treatment field and this, combined with genetic and
lifestyle predispositions, can confound the exact role of radiation
in the formation of these second malignancies. However, as
regards post-radiation sarcomas the excess incidence is noted in
the heavily irradiated in-field tissues, implying a much more
direct causative link.7
Previously, the risk of developing a soft-tissue sarcoma after
low to moderate radiation exposure was unknown, and the for-
mation of secondary bone sarcomas was thought to occur only
after very high levels of radiation exposure (>10 Gy). However,
recent studies of atomic bomb survivors in Japan concluded that
much lower levels of radiation exposure than previously thought
could cause both soft-tissue and bone sarcomas.7 Chemotherapy
has also been associated with an increased risk of secondary soft-
tissue sarcoma formation and, when combined with radio-
therapy, the risk rises still further. In a review of survivors of
childhood cancer, the standardized incidence ratio (SIR) of
developing a soft-tissue sarcoma was 113 after chemotherapy

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 ORTHOPAEDIC ONCOLOGY
and radiotherapy. In contrast, the SIR after chemotherapy alone
was 28, and the SIR after radiotherapy alone was 19. This also
suggests that chemotherapy is a risk factor for soft-tissue sar-
coma in its own right.8
A dose threshold for the formation of secondary bone sarcomas
has been reported at 0.85 Gy, with a linear dose response beyond
that level. The linear slope equals an excess relative-risk of 7.5 per
Gy. For soft-tissue sarcoma exposure to 1 Gy doubles the risk of
secondary tumour formation and further exposure also follows a
linear dose response. Several long-term studies of cancer survi-
vors from childhood have also noted a linear relationship between
radiation dose and subsequent sarcoma formation.9 A British
cohort of childhood cancer survivors demonstrated a 16 times
higher risk of secondary soft-tissue sarcoma formation in those
who received radiotherapy compared to those who did not. The
risk was again reported to increase with cumulative radiation dose
in this group and was around 50 times higher in those who
received the highest radiation dose.10
Certain familial genetic syndromes predisposing to sarcoma
formation (covered later in this article) may also increase sus-
ceptibility to radiation exposure and the subsequent secondary
formation of sarcomas. For example, Li Fraumeni syndrome has
previously been linked to an increased risk of sarcoma formation
after radiotherapy for breast cancer, and it is also suggested that
patients with Nijmegan breakage syndrome may be at particu-
larly high risk after radiation exposure.
Occupational and chemical risk factors
Sir Andrew Dilnot, Chairman of the UK Statisics Authority, in his
book The Tiger That Isnt: Seeing Through a World of Numbers,
describes cancer clusters and putative causative agents as
follows:
Unusual patterns of numbers in life, including the incidence
of illness, are not at all unusual, not necessarily due to some
guiding force or single obvious culprit, but callously routine,
normal and sadly to be expected
Indeed, attributing clusters of cancer cases to particular
causative agents, especially when the numbers are small, is
fraught with a myriad of heterogeneous influences and statistical
difficulties, resulting in conflicting literature. Thus, while Swe-
den demonstrated an elevated risk of soft tissue-sarcoma in
forestry workers using phenoxy herbicides, a similar risk was not
noted in America.11,12 Polychlorophenols and 2,3,7,8-
tetrachlorodibenzodioxin (TCDD) are classified by the Interna-
tional Agency for Research on Cancer as possible causes of soft-
tissue sarcoma, but again, not all studies have agreed that there
is a link between exposure and elevated risks. Some studies have
suggested a link between dioxins and soft-tissue sarcoma, but
again these noted clusters around municipal incinerators might
be purely by chance.13,14
Adults exposed to pesticides through their work may have
around double the risk of bone sarcoma (osteosarcoma or
chondrosarcoma), and this has also been reported in wood-
workers, blacksmiths, toolmakers, and machine-tool workers,
according to a European caseecontrol study. However, no dose
eresponse effect was observed in this study, again suggesting
that these associations should be interpreted with caution.15
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Please cite this article in press as: Beckingsale TB, Shaw C, Epidemiology of bone and soft-tissue sarcomas, Orthopaedics and Trauma (2017),
http://dx.doi.org/10.1016/j.mporth.2017.03.005
Host factors and genetic risk factors
The 3rd Edition of the WHO Classification of Tumours of Soft
Tissue and Bone listed 24 congenital tumour syndromes. The 4th
Edition includes 70 different tumour syndromes with known
specific genetic involvement. This reflects the advances in mo-
lecular biology that have revolutionized the identification of
cancer-related germline mutations.2
The genetic syndromes most relevant to general orthopaedic
practice include Olliers disease and Maffuccis syndrome, mul-
tiple hereditary exostoses, McCuneeAlbright syndrome, Neuro-
fibromatosis (Types 1 and 2), and Pagets disease.
Progeroid syndromes arise from mutations of RecQ, a family
of five genes encoding helicases essential for DNA repair, which
prevent deleterious recombination and genomic instability. De-
fects in RECQL2/WRN, RECQL3/BLM and RECQL4 lead to
Werner syndrome, Bloom syndrome, and RothmundeThomson
syndrome, respectively. These predispose to sarcoma formation,
and in particular osteosarcoma.16
Activated p53 plays an important anti-cancer role in main-
taining genomic stability, inhibiting angiogenesis, and triggering
apoptosis. Germline mutations of TP53, the tumour suppressor
gene located on the short arm of chromosome 17 (17q13), lead to
perhaps the most well known pro-cancerous disposition, Li
Fraumeni syndrome. This syndrome greatly increases suscepti-
bility to many different cancers, including sarcomas.16
Enchondromatosis: Olliers disease and Maffuccis
syndrome17,18
Olliers disease is a non-familial, sporadic disorder characterized
by multiple cartilaginous tumours most commonly seen in the
small bones of the hand. The causative genetic mutations are
most likely heterogeneous, with more than one mutation
required, resulting in the classic mosaic presentation. As such,
bony lesions tend to be seen unilaterally, and are most
commonly confined to a single limb. The incidence is approxi-
mately 1:100,000. When the presentation of multiple enchon-
dromas is combined with widespread haemangiomas in a similar
distribution, the condition is known as Maffuccis syndrome,
which is rarer than Olliers disease.
Histologically, the enchondromas of Olliers and Maffuccis,
tend to be more cellular and myxoid than solitary enchondromas,
and the rate of malignant transformation is consequently higher.
The risk of malignant transformation of enchondroma to chon-
drosarcoma is around 10e15% in Olliers disease and up to 30%
in Maffuccis syndrome. Both conditions also carry an increased
risk of other malignancies including CNS, pancreatic and
ovarian. Overall the risk of developing some form of malignancy
is around 25% in Olliers disease and is reported to be up to
100% in Maffuccis. Treatment is surgical to prevent deformity
and maintain function, but specialist interventions should be
sought for suspicious lesions that may have undergone malig-
nant transformation.
Hereditary multiple exostoses (HME)17
HME is the most common skeletal dysplasia. It is an autosomal
dominant condition and causes multiple osteo-cartilaginous ex-
ostoses. Given its dominant genetic pattern, it is usually familial
but around 10e20% of cases are sporadic. The severity of
4 2017 Elsevier Ltd. All rights reserved.
 ORTHOPAEDIC ONCOLOGY
Figure 5 Hereditary multiple exostoses.
presentation varies, but it can present as short stature with bony
deformities, commonly including a short ulna. The exostoses are
grossly and radiologically similar to solitary osteochondromas,
but histologically are more disorganized in structure with bos-
selated caps, (Figure 5). The cartilage cap of an osteochondroma
responds to the same hormonal influences as the physeal growth
plate and therefore growth of the lesions ceases with skeletal
maturity and continued growth after physeal closure raises the
suspicion of malignant transformation to a chondrosarcoma.
This occurs in 1e5% of patients with HME, whereas the occur-
rence is extremely rare in solitary osteochondromas.
The genetics responsible for HME have been identified as
mutations in one of three genes, EXT1, EXT2 and EXT3.
Respectively these are located on the long arm of chromosome 8,
the short arm of chromosome 11, and the short arm of chro-
mosome 19. Treatment is surgical excision for symptomatic le-
sions but, again, specialist advice should be sought regarding any
lesions suspicious for malignant transformation.
McCuneeAlbright syndrome17
McCuneeAlbright syndrome is characterized by polyostotic
fibrous dysplasia, hormonal disturbances including precocious
puberty, and cafe-au-lait spots, which have a jagged edge (coast
of Maine), are unilateral, and do not cross the midline. The
fibrous dysplasia most commonly affects the lower limbs and
pelvis (Figure 6) but can also frequently affect the skull and facial
bones.
The condition is non-familial and results from a post-zygotic
mutation to GNAS1 on the long arm of chromosome 20.
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Figure 6 McCuneeAlbright syndrome.
Presentation is therefore mosaic, explaining the variable pattern
of fibrous dysplasia. GNAS1 is one of a number of G-proteins,
which play a key role in many signal transduction pathways.
Neurobromatosis17
NF1 (von Recklinghausens disease) and NF2, are genetic dis-
orders of nerve development and growth.
NF1 has an incidence of around 1 in 4000, and results from
mutations in the neurofibromin 1 gene on the long arm of
chromosome 17. It has an autosomal dominant pattern of in-
heritance, but up to 50% of cases occur in a sporadic pattern.
Traditionally, NF1 is diagnosed when two or more of seven
cardinal clinical features are present. The seven diagnostic fea-
tures are:
 five or more cafe-au-lait spots
 two or more neurofibromas or 1 plexiform neurofibroma
 tumour of the optic nerve (optic glioma)
 benign growth on the iris (Lisch nodule)
 scoliosis
 deformity of other bone (especially tibial bowing)
 freckling of groin or armpit
 parent, sibling or child with NF1.
Patients should be kept under observation and treatment aims
at symptomatic control. Surgical excision can be performed for
large or unsightly lesions. Malignant transformation occurs in up
to 5% and the resulting tumours should be treated as sarcoma-
tous lesions.
NF2 is rarer than von Recklinghausens disease with an inci-
dence of approximately 1 in 40,000. It results from mutations in
the neurofibromin 2 gene, a human tumour suppressor gene
whose resultant protein is sometimes referred to as the Merlin
protein (an acronym for moezin-ezrin-radixin-like protein). Pre-
sentation includes bilateral acoustic neurofibromas (CN VIII),
which leads to tinnitus and progressive deafness, but patients
may often also present with gliomas, meningiomas, other neu-
rofibromas, schwannomas and early cataract formation. Treat-
ment is generally aimed at surgical debulking of the acoustic
neuromas, with the aim of relieving compression but avoiding
complete deafness.
5 2017 Elsevier Ltd. All rights reserved.
 ORTHOPAEDIC ONCOLOGY

Pagets disease17,19
Pagets disease is a chronic disorder of bone, characterized by Commonly recognized chromosomal translocations in
excessive osteoblastic and osteoclastic activity, resulting in sarcoma
abnormal bone turnover and enlarged, misshapen bones. It is Diagnosis Chromosomal Genes
commoner among people of European descent and uncommon in abnormality involved
North and South America, Africa, Asia and the Middle East.
Incidence increases with age and affects about 3% of the popu- Alveolar rhabdomyosarcoma t(2;13) (q35;q14) PAX3-FKHR
lation over the age of 40, but it is uncommon before the age of 55. t(1;13) (p36;q14) PAX7-FKHR
It can lead to bone pain, deformity, arthritis, and deafness or Alveolar soft part sarcoma t(X;17) (p11.2;q25) TFE3-ASPL
blindness (when bony deformity compresses the acoustic or Angiomatoid fibrous t(12;16) (q13;p11) FUS-ATF1
optic nerves respectively). Treatment is initially with histiocytoma
bisphosphonates but surgery may also be helpful for arthritis, Clear cell sarcoma t(12;22) (q13;q12) EWS-ATF1
deformity and fractures through the abnormal bone. The most Congenital fibrosarcoma/ t(12;15) (p13;q25) ETV6-NTRK3
devastating potential complication of Pagets disease is malig- Congenital
nant degeneration, often into an osteogenic sarcoma. The prog- mesoblasticnephroma
nosis of an osteosarcoma in this setting is dismal, with 5-year Dermatofibrosarcoma t(17;22) (q22;q13) PDFGB-
survival close to zero. protuberans COL1A1
Desmoplastic small round t(11;22) (p13;q12) EWS-WT1
Chromosomal translocations in sarcomas2 cell tumour
Approximately one third of sarcomas are characterized by spe- Endometrial stromal sarcoma t(7;17) (p15;q21) JAZF1-JJAZ1
cific recurrent genetic changes known as chromosomal trans- Ewings sarcoma/ t(11;22) (q24;q12) EWS-FLI1
locations. Chromosomal translocations are structural Peripheral primitive t(21;22) (q22;q12) EWS-ERG
rearrangements where pieces of two non-homologous chromo- neuroectodermal tumour t(7;22) (p22;q12) EWS-ETV1
somes are swapped, creating chimeric chromosomes. This re- t(17;22) (q12;q12) EWS-FEV
sults in portions of two, normally separate, genes being joined t(2;22) (q33;q12) EWS-E1AF
together creating a novel fusion gene. These chimeric genes t(16;21) (p11;q22) FUS-ERG
result in the transcription of functional, pathogenic fusion pro- Inflammatory myofibroblastic t(1;2) (q22;p23) TPM3-ALK
teins, which deleteriously alter key cellular pathways resulting in tumour t(2;19) (p23;p13) TPM4-ALK
the genesis of a tumour. t(2;17) (p23;q23) CLTC-ALK
Knowledge of translocations serves several purposes clini- Low-grade fibromyxoid t(7;16) (q33;p11) FUS-CREB3l2
cally. Firstly it improves the reliability and accuracy of diagnosis, sarcoma
playing a much greater role in the recent update of the WHO Myxoid chondrosarcoma t(9;22) (q22;q12) EWS-CHN
classification system. Secondly it can give prognostic informa- t(9;15) (q22;q21) TFC12-CHN
tion. For instance, in patients with localized synovial sarcoma, t(9;17)(q22;q11) TAF2N-CHN
better outcomes are seen in those with the SSX2-SYT fusion than Myxoid liposarcoma t(12;16) (q13;p11) TLS-CHOP
the SSX1-SYT fusion. Finally, fusion genes and their resultant t(12;22) (q13;q12) EWS-CHOP
products represent potential molecular targets for novel systemic Synovial sarcoma t(X;18) (p11;q11) SSX1-SYT
therapies, the ultimate goal being to produce more efficacious SSX2-SYT
targeted treatments with fewer side effects. SSX4-SYT
For commonly recognized chromosomal translocations in
sarcoma see Table 1. Table 1

Hormones and sarcoma formation20 Growth, development and sarcoma formation

Leiomyosarcoma is significantly more common in women than
men. A major factor accounting for this difference is the number
of tumours arising in the uterine myometrium. Oestrogen re-
ceptor (ER) positivity has been noted in approximately two thirds
(63%) of these tumours suggesting a hormonal role in the aeti-
ology. Oestrogen normally causes cells of the uterine myome-
trium to proliferate. It has been suggested that these tumours
may arise when mutations occur during this rapid proliferation.
ER positivity has also been noted in some extremity leiomyo-
sarcomas, but many argue that in women these should be
considered metastatic from a uterine primary until proven
otherwise. While hormones may play a role in the development
of these tumours, ER-positivity provides a therapeutic target
which results in improved overall survival compared to non-ER-
positive tumours.
Recent analyses suggest that osteosarcoma is more common in
people who were above average for birth weight. Similarly os-
teosarcoma diagnoses are more common in patients above
average height for their age at the time of diagnosis. This latter
finding would appear to be mirrored in the veterinary literature.
Osteosarcoma is 185 times more common in large dog breeds
than small dog breeds, suggesting that rapid growth is the most
likely contributory factor.21 This too, fits with the observation
that in humans the highest incidence of osteosarcoma occurs
during the adolescent growth spurt, when cell turnover and
growth is at its most rapid.
Infection and sarcoma formation
For the sake of completeness it is worth mentioning Kaposis
sarcoma. This condition normally falls outside the remit of most

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Please cite this article in press as: Beckingsale TB, Shaw C, Epidemiology of bone and soft-tissue sarcomas, Orthopaedics and Trauma (2017),
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 ORTHOPAEDIC ONCOLOGY
sarcoma services. It is the most common soft-tissue sarcoma
associated with a causal viral agent, in this case human herpes-
virus 8 (HHV8). This sarcoma is often associated with both HIV
positivity and AIDS; however, it is important to appreciate that
AIDS and HIV do not cause Kaposis sarcoma and that the role of
HHV8 is fundamental to the process. It is the acquired immu-
nodeficiency in these patients that makes them particularly sus-
ceptible to developing Kaposis sarcoma as a consequence of
HHV8 infection.
Although viral infection has been implicated in the develop-
ment of Pagets disease, there is no evidence that this infection
plays any role in the later malignant degeneration, and HHV8
remains the only infective agent clearly capable of causing sar-
coma formation.
Conclusion
Over the past few years much has changed in our understanding
of sarcomas. Better data collection and specialist cancer intelli-
gence networks have allowed us to gain a much clearer insight
into the incidence, sex distribution, anatomical presentation and
survival of sarcomas. Our understanding of the genetic changes
that occur within sarcomas has also dramatically evolved. This
has led to changes in how certain sarcomas are diagnosed, how
they are classified, but most importantly in some cases, how they
are treated. The biggest change in classification of soft-tissue
tumours has been the removal of the term malignant fibrous
histiocytoma as our developing understanding of tumour ge-
netics has allowed us to see that many of these tumours can
actually be more correctly classified as distinct entities. In the
future this will hopefully mean more targeted and personalized
therapies to treat these rare cancers. A 16 Beckingsale TB, Gerrand CH. Osteosarcoma. Orthopaedics and
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