Incidence of soft tissue sarcoma and beyond

A population-based prospective study in 3 European regions




The objectives of this study were to measure the incidence of sarcomas, including viscerally sited tumors that are not reported in cancer statistics, and to draw explanatory clues from a large and reliable sarcoma incidence data set.


Cases of sarcomas regardless of primary site (except bone and joints) were collected during 2 years in 3 European regions totaling approximately 26,000,000 person-years. The sources used were pathology reports and hospital discharges forms. Diagnoses were reviewed by expert sarcoma pathologists and were classified according to 2002 World Health Organization criteria. Soft tissue sarcomas (STS) were considered those located in arms, legs, trunk, head, neck, and retroperitoneum; visceral sarcomas (VS) were considered those that arose in internal organs. Rates were age standardized using the European (ASR-E) and the USA standard population. The rate of coexistence of VS and STS was calculated by dividing the 2 corresponding ASRs.


There were 1558 sarcomas, 968 STS, and 590 VS. The ASRs-USA per 100,000 person-years was 5.12 × 105 among males and 4.58 × 105 among females for all sarcomas. For males and females, respectively, the ASR-E per 100,000 person-years was 3.58 × 105 and 2.55 × 105, respectively, for STS; 1.47 × 105 and 1.97 × 105, respectively, for VS; and 0.55 × 105 and 0.10 × 105, respectively, for Kaposi sarcoma. The coexistence rate of VS and STS was 0.41 for males and 0.77 for females. For dermatofibrosarcoma (both sexes), uterine sarcoma, liposarcoma (females), and leiomyosarcoma, including or excluding the uterus (females), the age-specific rates depicted a curve with a rapid increasing trend until ages 40 to 50 years and little variation thereafter.


Compared with the incidence of STS, VS incidence made up an additional 41% in males and 77% in females. Because the shape of age-specific curves for some histotypes was similar to that of breast cancer, the authors concluded that sex hormones (plus many chemicals that act as endocrine disruptors) may be involved in carcinogenesis. This evidence could pave the way to investigate alternative treatments and to explore etiology. Cancer 2012. © 2012 American Cancer Society.


Sarcomas are rare cancers (1% of all tumors) with mesenchymal differentiation. They are classified according to topography and morphology. In relation to topography, sarcoma terminology is confusing. A widely used term is soft tissue, which most likely was introduced by early radiologists to make a distinction between dense tissue like bone, which partially blocked x-rays, and the surrounding tissues, which allowed x-rays to pass easily. Two types of sarcoma were then described: osteosarcoma (which develops from bone) and soft tissue sarcoma (STS). The latter tumors, according to the American Cancer Society,1 can arise in any part of the body, including the arms, legs, trunk, head, neck, retroperitoneum, and internal organs. However, the World Health Organization (WHO) classification of STS reports that these tumors are located in the extremities, trunk wall, and retroperitoneum, but not in internal organs.2 According to WHO criteria, in the current study, a distinction was made between STS and visceral sarcoma (VS). In standard reports, VS usually are attributed to the organ of origin, not taking into account the histology; therefore, it is likely that sarcoma incidence is widely underestimated. In relation to morphology, sarcomas are categorized according to the normal tissue that they resemble. Liposarcoma, for instance, does not indicate a lesion arising from fat but designates a malignant mesenchymal tumor that has differentiated into tissue that microscopically resembles normal adult or embryonic fat. Although they are rare tumors, sarcomas include more than 70 different histologic types.

A pathologic diagnosis is the gold standard that indicates the presence, grade, and classification of cancer. There is evidence that this gold standard is not consistently reliable for sarcoma. For example, in a study from the United States, a major discrepancy was observed in 25% of 266 cases of soft tissue lesions reviewed by an expert sarcoma pathologist.3 In the United Kingdom, the diagnosis was confirmed in only 76% of 413 sarcomas that were reviewed. The authors concluded that a second opinion is necessary for patients who have a presumed sarcoma to ensure that appropriate treatment is chosen.4 However, some of those studies were conducted before the advent of ancillary methods, such as immunohistochemistry and molecular genetics/molecular cytogenetics, which have improved and validated the morphology-based classification scheme. In view of the studies described above, a population-based, prospective collection of new sarcoma cases was conducted in 3 European regions (Veneto in Italy and Rhone-Alps and Aquitaine in France, totaling approximately 13,000,000 inhabitants) over 2 years using diagnoses that were validated by expert sarcoma pathologists and classified according to 2002 WHO criteria to more accurately determine STS incidence by including viscerally sited tumors and to draw explanatory clues from a large and reliable sarcoma incidence data set.


Our protocol for epidemiologic research was published previously.5 Briefly, patients were individuals of both sexes and any age who were residents in each European region and had a histologically proven, malignant sarcoma diagnosed as a first cancer in a 2-year period, although distant metastasis were present at initial diagnosis. Patients (any histology) who developed a recurrent sarcoma during the observation period were excluded along with those who had sarcomas of bone and joints, sarcomatoid carcinoma, mesothelioma, neuroblastoma, paraganglioma, and mixed (epithelial and mesenchymal) tumors of the female genital tract. Clearance was obtained from the ethical committee at each European center, and all study participants signed an informed consent form. The source of patients was the regional network of pathologists, which had agreed to use the morphologic WHO classification in daily practice. Experts in second opinions for sarcoma in each region supported the study and reviewed the diagnoses of local pathologists. Incident cases of sarcoma were searched through parallel scrutiny of the archives of hospital discharge forms. Repeated admissions of the same patient were identified, and prevalent cases (patients hospitalized with the relevant diagnoses in the previous years) were excluded. Because there is a reference center for the management of sarcoma in all 3 regions, health care migration to nearby regions by patients with sarcoma (resulting in an underestimation of sarcoma incidence rates) was limited.

The diagnosis was made on surgical specimen (instead of biopsy) in 75.8% of patients with sarcoma in Aquitaine, 79.4% of patients with sarcoma in Rhone-Alps, and 87.7% patients with sarcoma in Veneto. Immunohistochemistry contributed to the diagnosis in 84% of patients, and molecular genetics or cytogenetics contributed in 48.7% of patients. A review of the pathologic diagnosis by an expert sarcoma pathologist was made in 99.5%, 97.3%, and 79.2% of patients in Aquitaine, Rhone-Alps, and Veneto, respectively. Individual histologies were categorized according to the latest 2002 WHO classification of STS2 with the advice of sarcoma pathologists. STS or VS location also was assigned by the pathologists. VS included the same histotypes as STS and also included gastrointestinal stromal tumors (GISTs) and endometrial stromal tumors.

Methodological Differences Among Regions

In Veneto, sarcoma cases were collected in 2007 and 2008. Of 25 pathology laboratories in Veneto, 1 laboratory refused to participate; therefore, the corresponding patients and population were not included in the analysis. Five patients (or their next of kin) refused to be included to the study. For patients who signed the informed consent, hospital admission records were retrieved, and medical records were reviewed to exclude prevalent cases.

In Aquitaine, sarcoma cases were collected in 2007 and 2008. All 25 pathology laboratories in the region agreed to participate. Exhaustiveness of the data was verified by using multiple sources of information, including hospital discharge forms.

In Rhone-Alps, sarcoma cases were collected in 2005 and 2006. All 43 pathology laboratories in the region agreed to participate. Patients were notified prospectively by the local pathologists. Patients with sarcoma aged <15 years were identified in the Childhood Cancer Registry of Rhone-Alps. Exhaustiveness of the data was verified by using hospital discharge forms.

Unlike in other regions, the sarcoma pathologists in Rhone-Alps did not differentiate pleomorphic sarcoma from sarcoma not otherwise specified (NOS). Thus, incidence rates for both histotypes were calculated using the patients and population of Veneto and Aquitaine only.

Statistical Analysis

All data from the 3 regions and from 2 years of observation were used in the statistical analyses. Age-standardized rates (ASRs) were obtained with the direct method using age-specific rates (in 5-year classes) and 3 standard populations (European [ASR-E], World [ASR-W], and US 2000 [ASR-USA]) and are expressed per 100,000 person-years. Because they are adjusted for age, ASRs can be used for any comparison.

Likewise, for sarcoma, sex (males vs females) had a reverse modality: STS versus VS. The coexistence rate—the ratio of 1 modality (quantity or frequency) divided by the other modality (quantity or frequency)—was calculated by dividing the corresponding ASRs in males and females separately.

Age-specific incidence rates (ages 0-9 years, 10-19 years, 20-29 years, 30-39 years, 40-49 years, 50-59 years, 60-69 years, 70-79 years, and ≥80 years) were calculated and depicted in a scatter plot on a logarithmic scale versus age at diagnosis in males and females separately. The points were fitted by a nonparametric regression method (locally weighted scatter plot smoothing [LOWESS]) for a visual assessment of the relation between incidence and age. The method is primarily graphic and does not yield an explicit model or formula for the regression function.


Incidence of sarcomas (all cases and each histotype separately) was compared in 3 regions with Poisson regression analysis. The incidence rate ratio with 95% confidence interval (CI) and the 2-tailed error probability (P value) were obtained after taking into account age and sex. Statistical analyses were carried out using the STATA11 software package (Stata Corporation, College Station, Tex).


In a population of approximately 26,000,000 person-years, only 1660 sarcomas were identified. The different histotypes are reported in alphabetic order in Tables 1 and 2, with liposarcoma, rhabdomyosarcoma, and synovial sarcoma divided according to subtype (rows in italics) and with rare sarcomas with <5 patients grouped into 1 category (other sarcomas).

Table 1. Absolute Frequencies and Crude Rates of Sarcomas Broken Down by Morphology (Rows: Histotypes in Alphabetic Order) and Topography (Columns: All Sarcomas, Soft Tissue Sarcomas, and Viscera Sarcomas) in 3 European Regions (Rhone-Alps, Veneto, and Aquitaine)
 Total SarcomasSoft Tissue SarcomasViscera Sarcomas
HistotypeNo. of CasesRateNo. of CasesRateCasesRate
  • Abbreviations: GIST, gastrointestinal stromal tumor; MFH, malignant fibrous histiocytoma; NOS, not otherwise specified; PNET, primitive neuroectodermal tumor.

  • a

    This category includes alveolar soft part sarcoma, chondrosarcoma NOS, clear cell sarcoma of kidney, epithelioid hemangioendothelioma, extrarenal rhabdoid tumor, intimal sarcoma, malignant cell granular tumor, malignant epithelioid angiomyolipoma, malignant glomus tumor, malignant myoepitelioma, malignant myopericitoma, and rhabdoid tumor.

  • b

    This nosological category was calculated in Veneto and Aquitaine but not in Rhone-Alps.

Dermatofibrosarcoma protuberans980.36980.36
Desmoplastic round cell tumor60.0230.0130.01
Endometrial stromal sarcoma330.12330.12
Epithelioid sarcoma80.0370.0310.00
Ewing/PNET sarcoma210.08200.0710.00
Extraskeletal osteosarcoma110.04100.0410.00
 Mixed type30.0120.0110.00
 Round cell100.0490.0310.00
 Well differentiated1390.511360.5030.01
Low-grade fibromyxoid sarcoma100.04100.04
Malignant peripheral nerve sheath tumor200.07200.07
Malignant solitary fibrous tumor110.0470.0340.01
Other sarcomasa240.09180.0760.02
Pleomorphic sarcoma/MFHb560.37510.3450.03
 Spindle cell40.0120.0120.01
Sarcoma, NOSb530.35430.28100.07
Synovial sarcoma340.13280.1060.02
 Poorly differentiated20.0120.01
All sarcomas (except Kaposi)15585.769683.585902.18
Table 2. Sarcomas by Histotype in 3 European Regions (Rhone-Alps, Aquitaine, and Veneto): Number of Cases, Crude Rate, and Age-Standardized Rates According to European, World, and US 2000 Standard Populations in Males and Females
   Age-Standardized Rates  Age-Standardized Rates
HistotypeNo. of CasesCrude RateEuropeWorldUSNo. of CasesCrude RateEuropeWorldUS
  • Abbreviations: GIST, gastrointestinal stromal tumor; MFH, malignant fibrous histiocytoma; NOS, not otherwise specified; PNET, primitive neuroectodermal tumor.

  • a

    This category includes alveolar soft part sarcoma, chondrosarcoma NOS, clear cell sarcoma of kidney, epithelioid hemangioendothelioma, extrarenal rhabdoid tumor, intimal sarcoma, malignant cell granular tumor, malignant epithelioid angiomyolipoma, malignant glomus tumor, malignant myoepitelioma, malignant myopericitoma, rhabdoid tumor.

  • b

    This nosological category was calculated in Veneto and Aquitaine but not in Rhone-Alps.

Dermatofibrosarcoma protuberans480.360.350.320.36500.360.350.310.35
Desmoplastic round cell tumor40.
Endometrial stromal sarcoma     330.
Epithelioid sarcoma60.
Ewing/PNET sarcoma90.
Extraskeletal osteosarcoma50.
 Mixed type30.
 Round cell60.
Well differentiated880.670.600.430.5630.
Low-grade fibromyxoid sarcoma70.
Malignant peripheral nerve sheath tumor80.
Malignant solitary fibrous tumor60.
Other sarcomasa150.
Pleomorphic sarcoma MFHb320.430.330.220.37240.310.170.120.20
 Spindle cell30.
Sarcoma, NOSb330.450.380.300.39200.
Synovial sarcoma170.
 Poorly differentiated20.
All sarcomas (except Kaposi)7625.785.033.935.127965.734.563.564.58
Soft tissue sarcomas (except Kaposi)5253.983.522.843.594433.192.542.042.51
Visceral sarcomas (except Kaposi)2371.801.501.081.523532.542.021.522.00

Table 1 provides the absolute frequencies and crude rates (per 100,000) of sarcomas broken down by morphology (histotypes) and topography (all sites, STS, and VS). Excluding patients with Kaposi sarcoma and 2 patients with unknown tumor sites, there were 1558 patients, including 968 STS and 590 VS (see Table 1, far right row). The latter numbers should be used in computing the percentage of histotypes, except for pleomorphic sarcoma and sarcoma NOS—for which the appropriate numbers should be 922 (all sarcomas), 561 (STS) and 361 (VS)—because they were diagnosed as distinct nosological entities in Aquitaine and Veneto but not in Rhone-Alps. GIST (62.3%), leiomyosarcoma (16.2%), and endometrial stromal sarcoma (5.5%) were the leading histotypes among VS; whereas the main STS were liposarcoma (26.2%), leiomyosarcoma (16.1%), and dermatofibrosarcoma protuberans (10.1%).

Table 2 lists the sarcomas identified among males and females (Kaposi sarcoma excluded) by histotypes, including frequencies, crude rates, and ASRs. The age-specific rates for the main histotypes are displayed in Figure 1. The more common histotypes among males were GIST (24%), liposarcoma (22%), and leiomyosarcoma (11%). The more frequent histotypes among females were GIST (24%), leiomyosarcoma (21%), and liposarcoma (13%). The incidence of VS was greater among females because of the contribution of uterine leiomyosarcoma and endometrial stromal sarcoma. Angiosarcoma incidence also was greater among females that among males.

Figure 1.

Age-specific incidence rates (y-axis, logarithmic scale) of sarcoma are illustrated according to age class at diagnosis (x-axis: age class 1, ages birth to 9 years; age class 2, ages 10-19 years; age class 3, ages 20-29 years; age class 4, ages 30-39 years; age class 5, ages 40-49 years; age class 6, ages 50-59 years; age class 7, ages 60-69 years; age class 8, ages 70-79 years; age class 9, aged ≥80 years) among males and females according to the more common histotype (as indicates angiosarcoma; ks, Kaposi sarcoma; rms, rhabdomyosarcoma; gist, gastrointestinal stromal tumor; lps, liposarcoma; dfsp, dermatofibrosarcoma protuberans; lms, leiomyosarcoma). In the bottom row, middle and right graphs, lms (sts) or (vs) indicates leiomyosarcoma in soft tissue or viscera, respectively; lms (F), leiomyosarcoma in females at any site, including or excluding the uterus; uterus lms&ess, uterine leiomyosarcoma and endometrial stromal sarcoma. Scatter of points and fitted lines were determined using the locally weighted scatter plot smoothing (LOWESS) method. Data were from 3 European regions (Rhone-Alps, Aquitaine, and Veneto).

Considering the ASR-USA, the coexistence rate for VS and STS was 0.423 (=1.52/3.59) in males and 0.797 (=2.00/2.51) in females. The incidence of STS is easily available from the nearest cancer registry, whereas the incidence of VS is generally unknown. The coexistence rate predicts that the incidence of VS is approximately 42% that of STS in males and approximately 80% that of STS in females; eg, an additional 42% must be added to the reported STS rate (the rate usually presented in standard reports from cancer registries) to estimate the total sarcoma incidence in males.

Figure 1 displays the age-specific incidence rates of the more common sarcoma histotypes, in which the scatter of points can be observed as well as the fitted line obtained with the LOWESS method in males and females. Angiosarcoma, Kaposi sarcoma, GIST, and leiomyosarcoma among males had a pattern (a straight line on logarithmic scale) that frequently is observed when an exogenous agent, acting continuously throughout life, is believed to be the major etiological stimulus.6 A bimodal trend (a peak in childhood and a rapid increase in later life) was observed for rhabdomyosarcoma in both sexes; this may indicate exposure to 2 different risk factors—the first acting in the fetal or neonatal period and the second acting in adult life.6 The shape of the age-specific incidence rates for dermatofibrosarcoma in both sexes suggested that the etiological stimuli were strongest in early life, and the decrease in incidence in old age might be explained by a diminished exposure to exogenous stimuli, elimination of a susceptible population subgroup, or changes in the host occurring in middle age, like the changes observed at menopause.6 This pattern was observed for uterine sarcomas, and particularly for uterine leiomyosarcoma and endometrial stromal sarcoma, in which the decrease in incidence could be explained by menopause. A similar but less marked trend was observed for liposarcoma, GIST, and leiomyosarcoma, including leiomyosarcoma in females ay any site, including or excluding the uterus.

Table 3 lists the number of patients, crude rates, and ASRs for sarcomas (Kaposi sarcoma excluded, for both sexes combined) according to the more common body sites of occurrence. After adjusting for age and sex, there were no significant differences in the incidence of sarcoma histotypes among the 3 European regions except for Kaposi sarcoma, for which the incidence rate ratio was 1.77 (95% CI, 1.04-2.84; P = .035) in Veneto and 0.70 (95% CI, 0.39-1.26; P = .237) in Rhone-Alps (with Aquitaine as the reference group).

Table 3. Topographic Classification of Sarcoma (Kaposi Sarcoma Excluded) by Anatomic Site: Number of Cases, Crude and Age-Standardized Rates
   Age-Standardized Rates
Body SiteNo. of CasesCrude RateEuropeWorldUS
Head and neck920.340.280.250.29
Trunk wall2080.770.660.540.67
Upper extremity1450.540.460.370.47
Lower extremity3291.221.010.801.02
Small intestine970.360.280.200.28
Other and unknown1270.470.390.300.39


Articles recommending histopathologic peer reviews for sarcoma have continued to appear in recent years.7-10 Therefore, 1 strength of the current study is the systematic use of an expert second opinion for sarcoma diagnosis. Moreover, we used 2002 WHO classification criteria to define STS histologic groups. Another strength is that we assessed the incidence of these rare tumors among the residents of 3 European regions (approximately 13,000,000 individuals) for 2 years, totaling more than 26,000,000 person-years of observation. This population-based study avoids the biases associated with hospital and clinical series and provides enough statistical power to calculate incidence at least for the principal histotypes.

All Sarcomas, Soft Tissue Sarcomas, and Visceral Sarcomas

Similar to our study, all mesenchymal neoplasms regardless of primary site, except bones or joints and excluding Kaposi sarcoma, were collected from 12 population-based registries of the US Surveillance, Epidemiology, and End Results (SEER) Program from 1978 to 2001 by Toro et al11 using criteria from the 2002 WHO classification and using the 2000 US population to standardize all rates. In that study, the incidence rates of all sarcomas per 100,000 person-years were 5.5 × 105 and 4.6 × 105 among white males and white females, respectively. These estimates are close to the ASRs-USA of 5.12 × 105 and 4.58 × 105 per 100,000 person-years among males and females, respectively, reported in our Table 2. This inference may be meaningless, however, because there are several methodological differences between the 2 studies: 1) The overall incidence represents an average across a span of 24 years of follow-up (from 1978 to 2001) in the report by Toro et al,11 whereas it is an average of 2 recent years in the current study; 2) no case of GIST is reported by Toro et al,11 whereas this histotype constituted 23.6% of tumors in the current study; and 3) fibrosarcoma, malignant fibrous histiocytoma (or pleomorphic sarcoma), and sarcoma NOS in both sexes were 2 times greater in the report by Toro et al11 than in our current report. Daugaard12 reviewed pathologic material from 281 patients who had STS of the extremities to analyze the impact of WHO sarcoma classification criteria. The most frequent original diagnoses were malignant fibrous histiocytoma (26%), liposarcoma (21%), fibrosarcoma (11%), and leiomyosarcoma (10%). After reclassification, the largest groups were leiomyosarcoma (20%), liposarcoma (17%), synovial sarcoma (14%), and sarcoma NOS (11%). The original diagnosis was changed in 57% of tumors, and it was determined that 20 tumors (7%) were not sarcomas. Therefore, the WHO histologic classification probably was adopted too late or was adopted only to a partial extent in the study by Toro et al.11

Wibmer et al13 collected data from the Austrian National Cancer Registry on 5333 patients who were registered from 1984 to 2004. In that report, the ASR-W per 100,000 person-years was 2.4 × 105 for both sexes versus 3.73 × 105 in the current study, the rate for sarcoma NOS was 36% (1915 of 5333 patients) versus 5.7% (53 of 922 patients) in the current study, and GIST was not considered. Once more, the WHO histologic classification probably was adopted too late or was adopted only to a partial extent in the study by Wibmer et al.13

Toro et al11 reported an incidence rate (for both sexes and all races) per 100,000 person-years of 2.40 × 105 and 2.62 × 105 for soft tissue (including heart) and all other sites, respectively. For both sexes, we observed an incidence rate per 100,000 person-years of 3.04 × 105 for STS and 1.76 × 105 for VS. The extent to which the definition of groups may explain this discrepancy remains unclear. An ASR-E incidence per 100,000 person-years of 3.52 × 105 among males and 2.54 × 105 among females for STS in the current study was higher than the incidence in the Italian cancer data of 2.7 × 105 among males and 2.1 × 105 among females reported by the Italian Network of Cancer Registries (AIRT) Working Group from 1998 to 2002.14 Note that the latter estimates did not take into account sarcomas of the retroperitoneum, which were included in the current study. Moreover, VS tumors are hidden in the standard reports from tumor registries, so no source is available for comparison.

A pilot project from Rhone-Alps, which serves as a trial undertaken before the current, full-scale study, recently was published in which the catch-all category unclassified sarcoma was 18% (vs 5.7% in the current study) after excluding bone sarcoma and Kaposi sarcoma from the denominator.15

Sarcoma Histotypes

GIST is a relatively newly discovered clinical and pathologic entity that has drawn much attention. In the current study, 1) the ASR-E per 100,000 person-years was 1.05 × 105 versus 0.90 × 105 reported by Rubio et al16 in Spain between 1994 and 2001 and versus 1.47 × 105 reported by Mazzola et al17 in Switzerland from 1999 to 2005; 2) the ASR-W per 100,000 person-years was 0.74 × 105 compared with 1.11 × 105 reported in Iceland using all GIST tumors diagnosed from 1990 to 2003 in the country18; and 3) the ASR-USA per 100,000 person-years was 1.06 × 105 versus 0.69 × 105 estimated in 2002 by Perez et al19 using the SEER database from 1992 to 2002. Thus, the incidence of GIST in the current study was intermediate between the incidence reported from different areas of the world.

The ASR-E per 100,000 person-years of 0.55 × 105 among males and 0.10 × 105 among females for Kaposi sarcoma in the current study was lower than the incidence reported in the Italian cancer data of 1.4 × 105 among males and 0.4 × 105 among females reported by AIRT Working Group from 1998 to 2002.14 By using the so-called rule of 9, which divides the entire body surface in areas corresponding to 9% or multiples of 9%; accordingly, 9% of sarcomas should have been located in the head and neck, 18% should have been located in the upper arms, 36% should have been located in the lower arms, and 36% should have been located at the trunk wall. The actual percentages were 12% head and neck, 19% upper arms, 32% trunk, and 38% lower arms for sarcomas other than Kaposi sarcoma and 9% head and neck, 19% upper arm, 8% trunk wall, and 61% lower arms for Kaposi sarcoma. Therefore, the higher sarcoma incidence in Italy compared with the French regions may be attributed to an excess of classic Kaposi sarcoma (rather than acquired immunodeficiency syndrome-associated Kaposi sarcoma), which is frequent mainly in Mediterranean regions and affects elderly males and lower extremities.20

Qubaiah et al21 used the SEER database to collect incidence data on 10,945 patients who had small intestinal cancers diagnosed from 1992 to 2006 and reported age-specific incidence according to histology. In that report, for sarcomas, the ASR-USA per 100,000 person-years was 0.20 × 105 in both males and females, and the rates generally were similar among whites, Hispanics, and blacks. In the current study, the corresponding estimate was very close (ASR-USA = 0.28 × 105 per 100,000 person-years).

In total, Jawad et al analyzed 1631 patients with Ewing sarcoma who were reported in the SEER database from 1973 to 2005.22 Those authors reported a race-specific incidence per 100,000 indicating that Caucasians had the highest incidence (0.155), followed by Asians/Pacific Islanders (0.082), and African Americans (0.017), and the incidence of Ewing sarcoma increased over the past 3 decades among Caucasians (P < .05). In the current study, the ASR-USA for both sexes was 0.08 × 105 per 100,000 person-years.

Perspectives Beyond Incidence

Currently, complete surgical excision is the only curative approach for sarcoma; and, although local control can be achieved through surgery and radiation, up to 30% of patients with sarcoma present with a recurrence at distant sites, and many patients ultimately will die from the disease. Great efforts have been made to gain a better understanding of the molecular pathogenesis of these tumors, and these efforts already have led to the development of alternative treatments that interfere with specific molecules involved in carcinogenesis and tumor growth.

It is believed that estrogen initiates and promotes the process of breast carcinogenesis by enhancing the rate of cell division and reducing the time available for DNA repair. Two different strategies have been developed for the treatment of hormone-dependent breast cancer: antagonizing the estrogen receptors (ERs) by tamoxifen, and inhibiting estradiol biosynthesis by aromatase inhibitors.23 Aromatase P450 converts androstenedione into estrone (which is converted to the active compound estradiol by 17β-hydroxysteroid dehydrogenase) and is expressed in adipose tissue, bone, smooth muscle cells, chondrocytes, and other organs.24 In the study by Toro et al11 and in our current study, the rates for uterine leiomyosarcoma and endometrial stromal sarcoma increased rapidly during the childbearing years, peaked at approximately ages 40 to 50 years, and then plateaued or declined. The shape was similar to that of age-incidence curves for female breast cancer and suggested that sex hormones may be involved. We hypothesized that ER expression was common in uterine sarcomas and carried prognostic significance. Furthermore, we hypothesized that ER-positive uterine sarcomas responded to hormone therapy. Next, we searched the National Center for Biotechnology Information's PubMed database and identified several case reports on patients who were affected by endometrial stromal sarcoma25-27 or uterine leiomyosarcoma28 who had received treatment with aromatase inhibitors and had obtained prolonged disease-free survival.

We observed a similar shape of the age incidence for uterine sarcomas in the current study for liposarcoma in females and for leiomyosarcoma in females at any site (including or excluding uterus). These findings paralleled the evidence, both historic and recent, that ERs and androgen receptors (ARs) can be present in diverse human sarcomas located outside the reproductive tract. Chaudhuri et al29 reported ERs in 2 of 5 patients with angioblastic sarcoma (Kaposi sarcoma or angiosarcoma), in 3 of 5 patients with liposarcoma, and in 1 of 2 patients with leiomyosarcoma; the same authors described ARs in liposarcoma (1 of 5 patients), fibrosarcoma (4 of 8 patients), malignant fibrous histiocytoma (2 of 3 patients), and angioblastic sarcoma (2 of 4 patients). According to Li et al,30 ERs were expressed in dermatofibrosarcoma protuberans, well differentiated liposarcoma, myxoid liposarcoma, and myxoid malignant fibrous histiocytoma. Finally, hormone receptors reportedly were present in chondrosarcoma,23 rhabdomyosarcoma,31 and osteosarcoma.32

Endocrine-disrupting chemicals are chemicals that act as agonist or antagonist of natural sex hormones through binding to ERs or ARs.33 Approximately 105 pesticides have been identified as endocrine-disrupting chemicals.34 Herbicides, chlorophenol, other occupational exposures, and pollution from incinerators are suspected risk factors for STS, but the epidemiologic evidence is inconsistent. An exploratory analysis revealed that occupational risk factors for sarcoma are not uniform across histotypes.35 Studying all sarcomas combined may mask receptor-specific associations. Therefore, in view of all of the results described above, we suggest that, because the influence of hormones may be implicated in the development of sarcomas, sex hormone receptors should be quantified routinely in all patients with sarcoma with a view to paving the way for clinical trials and to further explore the etiologic differences underlying the morphologic and genetic diversity of these tumors.


This work was funded by a grant of the Commission of the European Communities—Research Directorate General (contract LSHC-CT-2005-018806), called CONective TIssue CAncer NETwork (CONTICANET), a network of excellence to integrate European experience.


The authors made no disclosures.