• epithelioid;
  • sarcoma;
  • surgery;
  • sentinel node biopsy;
  • perfusion


  1. Top of page
  2. Abstract


Epithelioid sarcoma is a rare soft tissue sarcoma with a known high propensity for locoregional recurrence and distant metastases. The clinical behavior and prognostic factors that influence the survival of patients with epithelioid sarcoma were studied.


Twenty-three patients, including 16 men (70%) and 7 women (30%), who were treated for epithelioid sarcoma between 1979–2003 at the University Medical Center Groningen and Radboud University Nijmegen Medical Center, were reviewed retrospectively. The median age at diagnosis was 22 years (range, 1–54 years). At the time of diagnosis, 11 patients (48%) had metastases. Six patients with distant metastasis and 1 patient with an unresectable tumor received palliative treatment (30%). The remaining 16 patients underwent surgical treatment of local disease (11 patients) or locoregional disease (5 patients). Five patients in that group received isolated limb perfusion with tumor necrosis factor and melphalan.


The 5-year and 10-year disease-free survival rates for all patients were 34% and 17%, respectively; for the 16 patients who received curative treatment, both rates were 56%. In the latter group, 8 patients developed local recurrence (50%) after a median follow-up of 4 months (range, 1–14 months). Nine patients were disease free after a median follow-up of 50 months (range, 6–290 months). Tumor size >5 cm (P < .0026) at diagnosis and local recurrence (P<.0008) were significant predictors of survival.


The prognosis for patients with epithelioid sarcoma is poor, because a substantial number of patients present with extensive disease, lymph node metastases, and/or distant metastases. Treatment consists of radical surgical excision of the tumor and, if indicated, therapeutic lymph node dissection. In patients who have large tumors, isolated limb perfusion may be useful. Cancer 2006. © 2006 American Cancer Society.

Epithelioid sarcomas are rare soft tissue tumors that originate from mesenchymal tissue and have unclear histogenesis.1–3 Clinically, the tumor usually is characterized as a slow-growing, painless swelling. It shows preference for the distal part of the extremities, particularly the hand.1–16 Other localizations, although very rare, are the perineum, penis, and vulva.1, 2, 4, 6–18 The tumor can originate superficially in the dermis or deeply under the fascia. The more deeply lying tumors often are larger and are fixed to tendons, tendon sheaths, or fascia, and they are poorly differentiated.1, 2, 5, 12 Treatment depends mainly on the presence or absence of regional and/or distant metastases. When surgery can be applied with curative intent, there is still a high risk of local recurrence, regional metastases, and/or distant metastases.1, 4–8, 11, 17, 19, 20

To gain greater insight into the current treatment modalities for epithelioid sarcomas and treatment outcomes, a retrospective study was performed at the University Medical Center Groningen and the Radboud University Nijmegen Medical Center, the Netherlands. In this report, new treatment options for epithelioid sarcomas are discussed, and the literature is reviewed.


  1. Top of page
  2. Abstract

From 1979 to 2003, epithelioid sarcomas were diagnosed in 23 patients with a median age of 22 years (range, 1–54 years), including 16 men (70%) and 7 women (30%). For the purpose of staging, all patients underwent computer tomography (CT) imaging of the lungs and CT or magnetic resonance imaging (MRI) of the tumor. At the time of diagnosis, 5 patients had lymph node metastases (22%), 5 patients had lymph node and distant metastases (22%), and 1 patient had distant metastases only (4%). According to the American Joint Committee on Cancer/International Union Against Cancer staging system, there were 8 patients with Stage IIA/B tumors (35%), 4 patients with Stage III tumors (17%), and 11 patients with Stage IV tumors (48%).21, 22 Table 1 shows the patient and tumor data.

Table 1. Tumor and Treatment Characteristics of 23 Patients with Epithelioid Sarcoma
CharacteristicNo. of patients%
  • *

    Stage was determined according to the International Union Against Cancer/American Joint Committee on Cancer 2002 staging classification.21, 22

Median age, y (range)22 (1–54) 
Treatment delay, mo (range)3.5 (1–36) 
Site of primary tumor
 Distal upper limb417
 Proximal upper limb29
 Distal lower limb522
 Proximal lower limb29
 Perineal region14
 Head and neck29
Tumor size, cm
 2 to <5730.5
 5 to <1073.5
 10 to <15313
Palliative treatment730
Curative treatment1670

Sixteen patients (70%) underwent curative treatment, which consisted of a local resection (n = 5 patients), a local resection and lymph node dissection (n = 1 patient), a lymph node dissection plus isolated limb perfusion (ILP) with tumor necrosis factor (TNF) and melphalan and a local excision (n = 3 patients), an amputation (n = 5 patients), an amputation and lymph node dissection combined with ILP (n = 1 patient), and an amputation and ILP (n = 1 patient). Lymph nodes were examined for metastases by palpation and ultrasound scanning or fine-needle aspiration. Indications for regional lymph node dissection included regional lymph node metastases without distant metastases. Elective regional lymph node dissections were not performed. Indications for ILP consisted of patients with in-transit metastases and large or multifocal tumors without distant metastases. When a curative resection (R0 resection) was achieved, no postoperative radiation therapy (RT) was given. Indications for the use of postoperative RT were a marginal primary resection (R1), local regional recurrence (without distant metastases), or palliative treatment. One patient who underwent an R1 resection and 6 patients who were treated with palliative intent received RT.

The remaining 7 patients (6 patients with distant metastases and 1 patient with an inoperable tumor) received palliative treatment (30%) with chemotherapy (doxorubicin, cyclophosphamide, iphosphamide, and/or vincristine) and RT. None of these patients were eligible for resection of the primary tumor and/or metastases.

Overall survival and disease-free survival were calculated with the Kaplan–Meier method. Prognostic factors for survival were analyzed with a univariate log-rank test.23


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  2. Abstract

The median interval between observing the first symptoms, making the diagnosis, and starting treatment (delay) was 3.5 months (range, 1–36 months). The median patient age at the time of diagnosis was 22 years (range, 1–54 years). The male: female ratio was 2:1. After a median follow-up of 17 months (range, 2–290 months), 14 of 23 patients died of disease (61%), and 9 patients were alive with no evidence of disease (39%).

In the group of 16 patients who received curative treatment, the median follow-up was 47 months (range, 3–290 months); 7 patients were tumor free (44%) after a median follow-up of 50 months (range, 12–218 months); and, 9 patients developed tumor recurrence (56%), including 8 patients with local recurrence (median follow-up, 4 months; range, 1–14 months) who underwent local resection and 1 patient with locoregional recurrence (after 8 months) who underwent inguinal lymph node dissection and received adjuvant RT (40 grays).

In the group of 8 patients who underwent surgical treatment with curative intent for their recurrence, 1 patient developed locoregional recurrence and underwent axillary lymph node dissection; 7 patients developed distant metastases, and in 3 of them, this was combined with locoregional recurrence. Four of those 7 patients received palliative RT.

Figure 1 shows the follow-up of the 16 patients after their first treatment with curative intent. The survival of 16 patients who were treated with curative intent and 7 patients who were treated with palliative intent is shown in Figure 2. The 5-year and 10-year survival rate of the curative group was 56% (P < .001).

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Figure 1. Follow-up results are illustrated for 16 patients who had epithelioid sarcoma after they were treated with curative intent. LNM indicates lymph node metastases; LR, local recurrence; DM, distant metastases; NED, no evidence of disease; DOD, dead of disease; RT, radiotherapy.

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thumbnail image

Figure 2. This Kaplan–Meier curve compares 16 patients who received treatment with curative intent versus 7 patients who received treatment with palliative intent.

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In the curative group, tumor size (>5 cm; P = .0256) and the development of local recurrence (P = .0008) influenced survival significantly (Table 2). Furthermore, in the total group of 23 patients, female gender (P = .0096) and the presence of distant or lymph node metastases (P = .0101) were unfavorable prognostic factors. Patients who had distant metastases (Stage IV) had a significantly poorer prognosis compared with patients who had regional lymph node metastases (P = .0001). Nine of 13 patients (69%) who presented with or developed distant metastases had lung metastases. Five patients underwent lymph node dissection plus ILP, including 3 patients who died from regional and distant metastases and 2 patients who were disease free after 12 months and 218 months follow-up, respectively.

Table 2. Statistical Analysis of Treatment Outcomes for 16 Patients with Epithelioid Sarcoma Treated with Curative Intent
CharacteristicNo. of patientsMean distant metastases-free survival (95% CI), monthsP
  1. AJCC indicates American Joint Committee on Cancer.

Tumor size, cm
 <59231.11 (159.09–303.13).0256
 >5732.00 (14.19–49.81)
 Proximal334.33 (9.26–59.41).9894
 Distal13146.22 (63.55–228.90)
 Male13163.87 (76.93–250.81).1980
 Female324.33 (5.82–42.84)
Local recurrence
 Yes828.00 (13.66–42.34).0008
 No8Mean follow-up, 98.3
Lymph node metastases
 Yes584.33 (3.38–165.29).5014
 No11191.00 (113.53–268.47)
AJCC stage
 Stage II8222.75 (141.93–303.75).1569
 Stage III/IV871.93 (4.95–138.9)


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  2. Abstract

Epithelioid sarcomas are very rare, high-grade, soft tissue sarcomas that constitute <1% of all soft tissue sarcomas.11, 17 The current results study confirmed earlier reports that the tumor is diagnosed mainly between ages 10 years and 35 years in males.1, 2, 4–6, 8–11, 13, 18–20, 24, 25 The tumor can consist of 1 or more lymph nodes that vary in size from a few millimeters to several centimeters.1–6, 18 The surface of the tumor often is yellowy-brown because of focal necrosis and bleeding.1, 2, 4, 5, 9 In view of the innocent appearance of the tumor, sometimes, there is great delay, even up to a number of years. It should be realized that clinical manifestation can vary widely. The current study showed that the prognosis depended on the initial tumor stage at presentation. The high percentage of patients with initial metastases and local recurrence, lymph node metastases, and distant metastases after surgical treatment with curative intent is characteristic of epithelioid sarcomas.1, 2, 4–8, 10–12, 16, 17, 20, 26 The size of the tumor (>5 cm) is important for the prognosis, although it remains difficult to determine tumor size in patients who have multifocal disease.1, 2, 4, 6, 8, 10, 11, 16, 18, 27, 28 Epithelioid sarcomas are localized mainly on the upper extremity. In the current study, no significant difference was observed between proximal or distal tumor localization and survival (Table 2). This is in contrast to the literature, in which it was reported that patients with distal localization had a significantly better prognosis.1, 4, 8, 16, 29 It is possible that the biologic behavior of proximally localized epithelioid sarcoma is more aggressive, which can be explained by possible rhabdoid characteristics and/or classic prognostic characteristics, such as size, depth, vascular invasion, and resectability.8, 15

Table 3 shows an overview of the anatomic localizations of the epithelioid sarcomas described in this series and in the literature. In the majority of studies, the prognosis for patients with epithelioid sarcoma was better among women.2, 3, 6, 16, 17, 20, 29 Ross et al. reported a significant correlation between male gender and shorter survival in a meta-analysis of 269 patients with epithelioid sarcomas.17 We could not confirm this correlation in our analyses on the total population or in the group of patients who were treated with curative intent. In the total population, the prognosis was significantly poorer among women (P = .0096) because of their presentation with widespread and metastatic disease.

Table 3. Sites of Primary Epithelioid Sarcoma as Published in Various Studies in the Literature
StudyYearNo. of patientsUpper extremity (%)Lower extremity (%)Perineum and trunk (%)Head and neck (%)
Prat et al.5197822682705
Chase and Enzinger41985241682731
Bos et al.6198851752014
Whitworth et al.20199142604000
Ross et al.171996162531440
Halling et al.18199655751591
Spillane et al.112000375724163
Callister et al.8200124292937.54.5
Matsushita et al.192002837.562.500
Livi et al.162003394933153
de Visscher et al. (current study)2006234335139
Total 620622873

Epithelioid sarcomas seem to grow by way of the tendon sheaths and fascia in a proximal direction.6 Subsequently, dissemination occurs through the lymph vessels and/or the blood stream.2, 3, 6–8, 11, 16, 20 Local recurrence is considered to be predictive of distant metastases and a significantly poorer survival.5, 6, 11, 19 In our series, 8 patients developed local recurrence (50%) after a median follow-up of 4 months (range, 1–14 months); in the literature, this rate varied from 29% to 85% (Table 4). Local recurrence mainly developed within 1 year after primary treatment.1, 2, 5, 11, 17 However, local recurrence also can occur after many years.1, 6, 16, 18 Only 1 patient from the current study remained disease-free after resection of the local recurrence; the other 7 patients (87.5%) developed distant metastases after the local recurrence. Our percentage of distant metastases corresponds with the 67% rate reported by Prat et al.5

Table 4. Literature Overview
StudyNo.Male (%)Female (%)Mean symptom duration before diagnosis, monthsMean age at first symptoms, yearsMean follow-up, yearsLocal recurrence (%)Lymph node metastases (%)Distant metastases (%)5-year survival (%)10-year survival (%)
  • AFIP indicates Armed Forces Institute of Pathology; NA, not available; MSKCC, Memorial Sloan-Kettering Cancer Center; MAYO, Mayo Clinic; MDACC, The University of Texas M. D. Anderson Cancer Center; MGH, Massachusetts General Hospital; RMH, Royal Marsden Hospital; CIH, Cancer Institute Hospital (Tokyo); UMCG, University Medical Center Groningen ; RUNMC, Radboud University Nijmegen Medical Center

  • *

    No patients were included who had lymph node metastasis or distant metastasis at first diagnosis.

  • Patients were included who had distant metastasis at first diagnosis.

  • Patients were included who had lymph node metastasis, but not distant metastasis, at first diagnosis.

Enzinger, 1970 (AFIP)1*547921Median, 9Median, 237 (median, 5)851130NANA
Prat et al., 1978 (MSKCC)52273273629863424760NA
Chase and Enzinger, 1985 (AFIP)4*202653529286.877102768NA
Bos et al., 1988 (MAYO)16*515941Median, 10.5Median, 2712.34122477050
Whithworth et al., 1991 (MDACC)20426633NA336294045NA58
Steinberg et al., 1992 (MGH)7*18613911397.3503333NANA
Ross et al., 1996 (MSKCC)1716693118334.769444466NA
Halling et al., 1996 (MAYO)18*555862353293827477874
Spillane et al., 2000 (RMH)11377327NA29Median, 7.33523407042
Callister et al., 2001 (MDACC)8*244258NA35Median, 10.92917426250
Matsushita et al., 2002 (CIH)19*85050NA416.5505062.52525
Current study, 2006  (UMCG, RUNMC)2370307.125.25.25065573232
Variation 42–7921–627.1–3623–414.7–12.329–8511–6521–62.525–7825–74

All 16 patients in our study who were treated with curative intent underwent curative resection (R0 resection). The degree of radicality of the excision determined the risk of local recurrence. In 2 studies in the literature, local recurrence rates after an R0 (radical resection) were 10% and 12%, respectively. After an R1 resection (microscopic, nonradical resection), these rates were 36% and 60%, respectively.8, 11 A central issue in local treatment, thus, is to achieve an R0 resection. Amputation does not lead to better survival than a successful local R0 resection. The benefit of an R0 resection also was emphasized in a series of patients with epithelioid sarcomas who were diagnosed incorrectly. Local recurrence rates and deaths from the disease were increased as a result of an inadequately performed surgical resection.1, 6 When multiple local recurrences were present, local resection generally no longer was possible, and amputation of the affected extremity was the only remaining option.6, 11, 16, 20

Our experience with ILP with TNF and melphalan during surgical treatment for epithelioid sarcoma is limited. Patients who present with multifocal and/or unresectable primary tumors probably will benefit from perfusion. ILP enables the administration of 10 times higher dosages of cytostatics without causing systemic toxicity. In the current study, the size of the tumor decreased after ILP, which presented the opportunity to perform an R0 resection.

The role of adjuvant RT in the treatment of marginally resected, high-grade sarcomas already has been established. Although epithelioid sarcomas belong under the classification of sarcomas, they behave more like malignant skin tumors. Several studies reported a lower risk of local recurrence of epithelioid sarcomas after preoperative or postoperative RT in combination with radical surgery.8, 12, 17, 18, 20 The studies by Bos et al. and Livi et al., however, did not confirm this lower risk.6, 16 In our study, of 16 patients who received treatment with curative intent, 1 patient received postoperative RT after an R1 resection, and 5 patients received RT after recurrence. Only 1 of those 5 patients presented with lymph node metastases only. The other 4 patients presented with distant metastases and/or lymph node metastases, and they received RT with palliative intent.

In contrast to many other studies, we did not observe that the presence of lymph node metastases was a significantly unfavorable factor.2, 4–6, 8, 10, 11, 16, 26, 2932 Callister et al. suggested that lymph node metastases may be a (first) symptom of widely disseminated disease rather than a purely locoregional process.8 If this is true, then lymph node metastases should be ascribed the same value as distant metastases. Fifteen patients (65%) in our series developed lymph node metastases after a median of 7 months (range, 4–108 months), and 10 of those patients subsequently manifested distant metastases (Table 4). Therefore, it is worthwhile to examine the regional lymph nodes after the primary diagnosis has been made.5 Currently, this can be accomplished noninvasively by means of ultrasound scanning of the regional lymph node basin in combination with fine-needle aspiration or sentinel lymph node biopsy. If lymph node metastases are present, then therapeutic lymph node dissection is indicated.5, 11, 26 It would be difficult to prove the extra value of ultrasound scanning or sentinel lymph node biopsy in relation to clinical palpation in the treatment of epithelioid sarcomas; however, on a theoretical basis, we strongly advise this approach in the current treatment for epithelioid sarcomas.

In the group of patients who were treated with curative intent, 7 patients developed distant metastases (43%); whereas, in the total series, 13 patients (57%) had distant metastases initially or during follow-up (Table 4). The most common site for dissemination was the lung.1, 4, 5, 11, 19 Other less frequent sites were the digestive tract, liver, kidneys, and skeletal system.1 In our series, 69% of the distant metastases were localized in the lungs. Distant metastases can differ from the primary tumor or local recurrence in terms of poorer differentiation and increased necrosis.1, 6 In the current study, distant metastases occurred after a median follow-up of 10 months (range, 2–29 months) in patients who had received treatment with curative intent. The median survival after a diagnosis of distant metastases in this study was only 5 months (range, 1–44 months). Others have reported a survival duration between 8 months and 28 months.11, 16, 19 Unfortunately, our study and other studies showed that chemotherapy is of little benefit in the palliative treatment of patients with disseminated epithelioid sarcomas.4, 6, 16

In the literature, there is wide variation in the 5-year and 10-year survival rates of between 25% to 78% and 25% to 74%, respectively. In the current study, the 5-year and 10-year survival rate was only 32% for 23 patients (Table 4). This finding raises thee question of whether these differences are based on the stage distribution. In agreement with Spillane et al. and Ramanath et al., we did not observed any differences in survival between the stages.11, 24 However, we did observe a significant difference in survival between patients with Stage IV disease who had lymph node metastases and patients with Stage IV disease who had distant metastases.

It may be concluded that surgery remains the only treatment option for patients with primary and disseminated epithelioid sarcoma. The role of postoperative RT after an R0 resection and the value of ILP with TNF and melphalan in patients with epithelioid sarcoma need further research. However, we believe that modern, minimally invasive diagnostics of the regional lymph node basins with ultrasound scanning and sentinel lymph node biopsy should become part of the preoperative staging procedure for patients with epithelioid sarcoma.


  1. Top of page
  2. Abstract
  • 1
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  • 2
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  • 3
    Molenaar WM, De Jong B, Dam-Meiring A, Postma A, De Vries J, Hoekstra HJ. Epithelioid sarcoma or malignant rhabdoid tumor of soft tissue? Epithelioid immunophenotype and rhabdoid karyotype. Hum Pathol. 1989; 20: 347351.
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