The applicability of immunohistochemistry in the diagnosis and differential diagnosis of malignant soft tissue tumors. A reevaluation based on the material of the Kiel Pediatric Tumor Registry

The diagnosis and differential diagnosis of malignant soft tissue tumors not infrequently poses great difficulties, especially in those cases which lack any feature of differentiation by conventional light microscopy. These difficulties have been partially resolved through the application of ultrastructural investigations. Recently considerable progress has been achieved using immunohistochemistry. At the Kiel Pediatric Tumor Registry we were able to reduce the percentage of unclassified soft tissue sarcomas from 17.6% in 1982 to 4.5% in 1989. Particularly useful were antibodies against the different types of intermediate filaments, muscle-specific actin, myoglobin, and the neural markers neuron-specific enolase and protein S-100. In contrast to the expected immunophenotype rhabdomyosarcomas, malignant peripheral neuroectodermal tumors and malignant schwannomas showed expression of cytokeratins. Moreover, in many cases rhabdomyosarcomas and synovial sarcomas expressed neural markers. Ewing's sarcoma and malignant peripheral neuroectodermal tumor are histogenetically related, but differ in grade of neural differentiation. In all soft tissue sarcomas immunohistochemistry is very useful to obtain information on the cellular heterogeneity. Despite the great achievements not every soft tissue sarcoma can be diagnosed with certainty. There will always be a baseline of unclassified cases due to problems which are not caused by the tumor itself but rather by diagnostic circumstances.     

Pathology of soft tissue sarcomas: 238 cases of the childhood tumor registry

Until April 1981 malignant soft tissue sarcomas were registered from 238 patients. Rhabdomyosarcoma was the most common tumor (115/238 = 48.3%). The embryonal subtype was predominantly seen among the rhabdomyosarcomas (83/115 = 72.2%). Rhabdomyosarcomas were localized most frequently in the head and neck area (40/115 = 34.8%), followed by genitourinary system (15/115), pelvis soft tissue (12), abdomen (10) and extremities (10). Non-rhabdomyosarcomatous soft tissue sarcomas (123/238 = 51.7%) were synovial sarcomas (20 = 8.4%), fibrosarcomas including spindle cell sarcoma (17 = 7.4%), leiomyosarcomas (12 = 5.0%), malignant tumors of the vascular system (11 = 4.6%) and neurofibrosarcomas (9 = 3.8%). Other types of sarcoma were extremely rare. 42 (17.6%) of all soft tissue sarcomas could not be classified histogenetically. Rhabdomyosarcomas could be diagnosed much more accurately (105/115 = 91.3%), compared to all other soft tissue sarcomas (99/121 = 81.8%). At present, the most difficult diagnostic problems remain with the tumors of connective tissue, in particular with fibrosarcomas and with the differential diagnosis of juvenile fibrosarcomas versus juvenile fibromatoses.     

Aberrant Immunohistochemical Expression in Nonrhabdomyosarcoma Soft Tissue Sarcomas of Infancy: Retrospective Review of Clinical Material

Malignant soft tissue tumors other than rhabdomyosarcoma (RMS) are uncommon in infancy, representing approximately 5% of pediatric sarcomas. The pathological categorization of non-RMS soft tissue malignancies from these young patients is complicated by variation in both morphologic and immunohistochemical features. A search covering an 11-year period identified 19 patients presenting at birth or in infancy with a clinical or referral diagnosis of soft tissue sarcoma. After histologic and immunohistochemical review, nine of these tumors were classified as primitive neuroectodermal tumor (PNET), three as infantile hemangiopericytoma (HPC), two as infantile fibrosarcoma (FS), and five as undifferentiated sarcoma. Those identified as undifferentiated sarcomas showed an atypical spindle and ovoid cell morphology, with cellular pleomorphism and high mitotic rate, but lacking the fascicular growth pattern of classic infantile fibrosarcoma. Immunohistochemical staining in this group showed variable weak positivity for a range of markers (desmin, smooth muscle actin, Myo-D1, PGP, NSE, S100, CO56, cytokeratin, and CD99), and did not fit readily into any distinct diagnostic category. In this series, tumors classified as soft tissue PNETs had a poor prognosis despite aggressive treatment. However, once RMS, PNET, and other rare specific lesions are excluded, the remaining undifferentiated sarcomas, despite their unusual morphology and immunohistochemistry, appear to behave in a similar favorable manner to infantile fibrosarcoma.     

Radiation therapy for non-rhabdomyosarcoma soft tissue sarcomas in adolescents and young adults

Non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) are less responsive to radiotherapy than the more common pediatric soft tissue sarcomas, rhabdomyosarcoma and Ewing sarcoma of soft tissue. However, radiation therapy does play an important role in the treatment of NRSTS, including synovial sarcoma. Little data exists regarding the behavior or treatment of these tumors in adolescents and young adults compared to older populations. Limb-preservation with adjuvant radiation thereby is standard. There is a greater incentive to reduce long-term complications of radiation in younger patients and thus smaller margins, lower doses, and conformal techniques should be considered. Results of anticipated cooperative group studies promise to guide future therapy for the various types of NRSTS.     

"POLYPHENOTYPIC" TUMORS IN THE CENTRAL NERVOUS SYSTEM: Problems in Nosology and Classification

In recent years, there is increasing recognition of polyphenotypic high-grade malignancies in the non-central nervous system (CNS) tumor literature. Some of these tumors have been regarded as variants of primitive neuroectodermal tumor (PNET) or as extrarenal malignant rhabdoid tumors (MRTs). This report concerns two posterior fossa neoplasms, both of which displayed a "polyphenotypic" expression of neural, epithelial, myogenic, and glial markers, including synaptophysin, neurofilament, vimentin, glial fibrillary acidic protein, S-100, neuron-specific enolase, desmin, S antigen, MIC2, cytokeratin, epithelial membrane antigen, and carcinoembryonic antigen. One tumor showed complex intercellular junctions, cytoplasmic intermediate filaments, well-developed rough and smooth endoplasmic reticulum and Golgi apparatus, cilia, and neurosecretory granules. The other neoplasm showed pools of glycogen, desmosomes, and tonofilaments. The histological and ultrastructural appearances were inconsistent with glioma, PNET, meningioma, ependymoma, choroid plexus carcinoma, sarcoma, germ cell tumor, and other tumors in the World Health Organization classification. Although the polyphenotype raises the issue that these may represent variants of MRT or the atypical teratoid-rhabdoid tumor, the morphologic findings in the two cases were very dissimilar. Our two cases underscore the problems in nosology and classification of polyphenotypic tumors of the CNS. This is particularly significant, as therapeutic protocols for PNET, MRT, and non-CNS polyphenotypic tumors are different. We review the literature on polyphenotypic tumors and reiterate the difficulties in precise classification of these complex tumors.     

Cooperative Ewing's Sarcoma Studies 81/86: pathologico-anatomic and immunohistochemical findings and differential diagnosis of Ewing sarcoma

158 cases of the Cooperative Ewing's Sarcoma Trials (CESS 81/86), which have been documented at the Pediatric Tumor Registry, Kiel, were studied by conventional light microscopy and immunohistochemistry. There were 77 cases of typical Ewing's sarcoma with 70 cases being located in the skeleton and 7 in soft tissues. Of the 14 cases of atypical Ewing's sarcoma 7 cases each were localized in bone and in soft tissue, respectively. In contrast to typical Ewing's sarcoma, cells of atypical Ewing's sarcoma were larger and displayed more heterochromatin. Both, typical and atypical Ewing's sarcoma reacted positively for vimentin. Other stains were negative, notably the neuron specific enolase (NSE). In 55 cases a diagnosis of malignant peripheral neuroectodermal tumor (MPNT) was made. Histologically most of these tumors resembled atypical Ewing's sarcoma. By immunohistochemistry positive reactions were found for NSE, vimentin, protein S-100, neurofilaments and glial fibrillary acidic protein. In 3 cases a diagnosis of small cell osteosarcoma was made. There were 2 cases of undifferentiated sarcoma of bone, 2 cases of soft tissue sarcoma of undetermined histogenesis and 2 cases of rhabdomyosarcoma. Of the 4 tumors which could be investigated for response to polychemotherapy, 1 each corresponded to grade II and III, respectively, and 2 to grade IV according to the classification of histologic grade of regression established by Salzer-Kuntschik et al. (1983).     

Immunopathology of brain tumors

The various classifications of brain tumors are characterized by a rather disturbing diversity of tumor designations. This diversity results from the heterogeneity of human brain tumors, but also from the lack of knowledge about the histogenesis of many of these tumors. The histogenesis of some of the different types of tumor could be resolved by the application of electron microscopical studies. New aspects are gained from immunohistochemical investigations using mono- and polyclonal antibodies against intermediate filaments (GFAP, vimentin, cytokeratins), neuron-specific enolase (NSE), protein S-100, carcinoembryonic antigen (CEA), myelin-associated glycoprotein (Leu 7), synaptophysin and nuclear proliferating antigen (Ki-67). The present paper gives a survey on how immunohistochemistry can be advantageously used in the diagnosis of brain tumors.     

Overview of sarcomas in the adolescent and young adult population

Based on the data of the Surveillance, Epidemiology and End Results Section of the National Cancer Institute (SEER) program, soft tissue and bone sarcomas account for about 1% of all new malignancies diagnosed in the United States each year. However, there are numerous different histologic types, and any given type of sarcoma is extremely rare. Determining the incidence of sarcomas by age and type is difficult due to the limited data reported. The SEER program collects data regarding age but only limited data on histology, while most series reported in the literature include either adults or pediatric patients, but rarely both. In an effort to estimate the frequency and absolute numbers of different sarcomas in the adolescent and young adult population, the University of Texas M. D. Anderson Cancer Center (MDACC) tumor registry was queried for all soft tissue sarcomas from 1990 through 2003, and all bone sarcomas from 1990 through 2002. Based on this query, an overview of sarcomas that occur predominantly in the adolescent and young adult (AYA) population is presented. These sarcomas include rhabdomyosarcoma, synovial sarcoma, neurogenic sarcoma, epithelioid sarcomas, alveolar soft parts sarcoma, Ewing sarcoma, and osteosarcoma. Using the percentages for occurrence of each histologic type determined from the MDACC database, and the SEER estimate of overall sarcoma incidence, an estimate of the number of new cases in 2004 for the predominant histologic types occurring in the AYA population are presented. Also reviewed are the chromosomal translocations that occur frequently in sarcomas presenting in the AYA population.     

18F-fluorodeoxyglucose uptake of bone and soft tissue sarcomas in pediatric patients

A high (18)F-fluorodeoxyglucose (FDG) uptake by positron emission tomography/computed tomography (PET/CT) imaging in sarcomas of adults has been reported. The current study aimed at defining the degree of (18)F-FDG uptake of pediatric sarcomas. This retrospective study included 29 patients (23 males, 6 females; mean age 14 ± 5 years) with soft tissue (n = 9) or bone (n = 20) sarcomas. Twenty-two patients (76%) underwent (18)F-FDG PET/CT and 7 (24%) had dedicated (18)F-FDG PET studies. Tumor (18)F-FDG uptake was quantified by standard uptake value (SUV)(max) and tumor-to-liver ratios (SUV ratios; tumor SUV(max)/liver SUV(mean)). Tumor SUV(max) and SUV ratios were correlated with tumor Ki-67 expression. SUV(max) ranged from 1.4 to 24 g/mL (median 2.5 g/mL) in soft tissue sarcomas and 1.6 to 20.4 g/mL (median 6.9 g/mL) in bone sarcomas (P = .03), and from 1.6 to 9.2 g/mL (median 3.9 g/mL) and 3.5 to 20.4 g/mL (median 12 g/mL) in Ewing sarcoma and osteosarcoma, respectively (P = .009). Tumor SUV ratios ranged from 0.8 to 8.7 (median 1.9) in soft tissue sarcomas and 1.4 to 8.9 (median 3.8) in bone sarcomas (P = .08). Ewing sarcoma had a significantly lower tumor SUV ratio than osteosarcoma (P = .01). Ki-67 expression correlated significantly with the (18)F-FDG uptake in bone but not in soft tissue sarcomas. All sarcomas were visualized by (18)F-FDG PET/CT imaging. A higher (18)F-FDG uptake was observed in osteosarcoma than in Ewing and soft tissue sarcomas. The results of this study suggest that the degree of tumor (18)F-FDG uptake is sufficient to allow for monitoring of therapeutic responses in pediatric sarcomas.     

Comparative genomic hybridization analysis of clear cell sarcoma of the kidney

BACKGROUND: Clear cell sarcoma of the kidney (CCSK) is a rare malignant pediatric tumor, distinguished from the Wilms tumor by its characteristic histologic features and a more aggressive clinical behavior with a tendency to metastasize to bone. Genetic studies on CCSK are limited and no consistent findings have been reported. PROCEDURE: We examined four cases of CCSK for presence of consistent genetic alterations using comparative genomic hybridization (CGH). This is the first report concerning CGH analysis of CCSK. RESULTS: Three of the tumors showed no chromosome gains or losses. One of the tumors had gains of 1 q and the terminal end of 11 q. CONCLUSIONS: These results are consistent with previous findings of limited chromosomal changes in CCSK karyotypes. Gain of 1 q in CCSK warrants further investigation. Copy number gains of 1 q have been repeatedly demonstrated in soft tissue and bone sarcomas, as well as other tumors, implying the presence of genes involved in tumor development and/or progression.     

Kongenitaler melanotischer neuroektodermaler Tumor

Congenital melanotic tumors (MNT) are very rare tumors of childhood. Microscopic findings overlap with those of other small round cell tumors. The neoplasia is almost always benign and generally arises in the maxilla in the 1st month of life. The histogenesis is still controversial today. The idea of a neuroectodermal origin is the most frequently advocated hypothesis. The diagnosis is possible by the coexpression of epithelioid antigen containing cells and melanotic-like cells. The differential diagnosis includes other small round blue cell tumors such as Ewing’s sarcoma, neuroblastoma, PNET, or malignant lymphoma. Treatment of MNT has typically been surgical. We report a case of a 3-month-old infant with an unusual recurrent tumor. Molecular cytogenetic studies in our case did not show numeric or structural genetic changes. The expression of the growth factor VEGF in the neuroblastic tumor cells was high and the growth factor angiopoietin-1 was strongly expressed in the melanotic tumor cells.     

Current management of pediatric soft tissue sarcomas

Pediatric soft tissue sarcomas are a group of malignant neoplasms arising within embryonic mesenchymal tissues during the process of differentiation into muscle, fascia and fat. The tumors have a biphasic peak for age of incidence. Rhabdomyosarcoma(RMS) is diagnosed more frequently in younger children, whereas adult-type non-RMS soft tissue sarcoma is predominately observed in adolescents. The latter group comprises a variety of rare tumors for which diagnosis can be difficult and typically requires special studies, including immunohistochemistry and molecular genetic analysis. Current management for the majority of pediatric sarcomas is based on the data from large multi-institutional trials, which has led to great improvements in outcomes over recent decades. Although surgery remains the mainstay of treatment, the curative aim cannot be achieved without adjuvant treatment. Pre-treatment staging and risk classification are of prime importance in selecting an effective treatment protocol. Tumor resectability, the response to induction chemotherapy, and radiation generally determine the risk-group, and these factors are functions of tumor site, size and biology. Surgery provides the best choice of local control of small resectable tumors in a favorable site. Radiation therapy is added when surgery leaves residual disease or there is evidence of regional spread. Chemotherapy aims to reduce the risk of relapse and improve overall survival. In addition, upfront chemotherapy reduces the aggressiveness of the required surgery and helps preserve organ function in a number of cases. Long-term survival in low-risk sarcomas is feasible, and the intensity of treatment can be reduced. In high-risk sarcoma, current research is allowing more effective disease control.     

Alveolar soft part sarcoma in children and adolescents: Clinical features and outcome of 11 patients

The clinical features and response to therapy of pediatric alveolar soft part sarcoma, a rare soft tissue sarcoma of uncertain histogenesis, have not been previously described in detail in the literature. We retrospectively reviewed the clinical characteristics of all patients with alveolar soft part sarcoma who were seen at our institution over a 32-year period. We found 11 patients with the diagnosis of alveolar soft part sarcoma. Their ages ranged from 2.8–16 years (median 9.8). Staging was determined using the Intergroup Rhabdomyosarcoma Study clinical grouping system and the UICC TNM system. Accordingly, there were six patients with grossly resected tumors (clinical groups I and II) and five with unresected or metastatic disease (clinical groups III and IV). Children with resected disease were more likely to have smaller noninvasive tumors. The main feature predictive of survival was tumor resectability, since chemotherapy in various combinations failed to produce significant tumor responses. Nine patients are disease-free with a median follow-up of 11.9 years. Surgical resection remains the mainstay of therapy for pediatric alveolar soft part sarcoma. Since active chemotherapy agents have not been identified, patients with unresected or metastatic disease may benefit from experimental agents. The survival rate of this cohort is superior to that seen in adults. © 1996 Wiley-Liss, Inc.     

Expression of WT-1, Bcl-2, and CD34 by Primary Renal Spindle Cell Tumors in Children

The confident diagnosis of renal spindle cell tumors in children is often difficult. An immunohistochemical study of WT-1, Bcl-2, and CD34 was performed to determine their expression profiles and to assess the potential utility of these immunohistochemical markers in the differential diagnosis of 36 cases of renal spindle cell tumors of childhood. The cases included 11 stromal predominant Wilms tumors, 12 cellular mesoblastic nephromas, 9 clear cell sarcomas of the kidney (CCSK), and 4 monophasic synovial sarcomas. WT-1 was uniformly positive in primitive undifferentiated stromal Wilms tumors (6 of 6) and negative in the differentiating and differentiated stromal elements of Wilms tumors (0 of 5). WT-1 was also negative in cellular mesoblastic nephromas (0 of 12), CCSKs (0 of 12), and synovial sarcomas (0 of 4). Bcl-2 was expressed in all stromal Wilms tumors (11 of 11), all synovial sarcomas (4 of 4), some CCSKs (4 of 9), and none of the cellular mesoblastic nephromas (0 of 12). Although CD34 was absent in the tumor cells of all the tumors studies (0 of 36), CD34 immunohistochemistry nicely demonstrated the evenly distributed septal capillaries characteristic of CCSK in all 9 cases of this tumor. We conclude that a combination of WT-1 and Bcl-2 immunohistochemistry may aid in the distinction of stromal Wilms tumor, monophasic synovial sarcoma, cellular mesoblastic nephroma, and CCSK.     

18F-FluoroDeoxyGlucose Uptake of Bone and Soft Tissue Sarcomas in Pediatric Patients

A high ¹⁸F-fluorodeoxyglucose (FDG) uptake by positron emission tomography/computed tomography (PET/CT) imaging in sarcomas of adults has been reported. The current study aimed at defining the degree of ¹⁸F-FDG uptake of pediatric sarcomas. This retrospective study included 29 patients (23 males, 6 females; mean age 14 ± 5 years) with soft tissue (n = 9) or bone (n = 20) sarcomas. Twenty-two patients (76%) underwent ¹⁸F-FDG PET/CT and 7 (24%) had dedicated ¹⁸F-FDG PET studies. Tumor ¹⁸F-FDG uptake was quantified by standard uptake value (SUV)_max and tumor-to-liver ratios (SUV ratios; tumor SUV_max/liver SUV_mean). Tumor SUV_max and SUV ratios were correlated with tumor Ki-67 expression. SUV_max ranged from 1.4 to 24 g/mL (median 2.5 g/mL) in soft tissue sarcomas and 1.6 to 20.4 g/mL (median 6.9 g/mL) in bone sarcomas (P = .03), and from 1.6 to 9.2 g/mL (median 3.9 g/mL) and 3.5 to 20.4 g/mL (median 12 g/mL) in Ewing sarcoma and osteosarcoma, respectively (P = .009). Tumor SUV ratios ranged from 0.8 to 8.7 (median 1.9) in soft tissue sarcomas and 1.4 to 8.9 (median 3.8) in bone sarcomas (P = .08). Ewing sarcoma had a significantly lower tumor SUV ratio than osteosarcoma (P = .01). Ki-67 expression correlated significantly with the ¹⁸F-FDG uptake in bone but not in soft tissue sarcomas. All sarcomas were visualized by ¹⁸F-FDG PET/CT imaging. A higher ¹⁸F-FDG uptake was observed in osteosarcoma than in Ewing and soft tissue sarcomas. The results of this study suggest that the degree of tumor ¹⁸F-FDG uptake is sufficient to allow for monitoring of therapeutic responses in pediatric sarcomas.     

Telomerase activity and telomere length in primary and metastatic tumors from pediatric bone cancer patients

The presence of telomerase activity has been analyzed in almost all tumor types and tumor-derived cell lines. However, there are very few studies that focus on the presence of telomerase activity in bone tumors, and most of them report analysis on very few samples or bone-derived cell lines. The objective of this study was to analyze the telomere length and telomerase activity in primary tumors and metastatic lesions from pediatric osteosarcoma and Ewing's sarcoma patients. The presence of telomerase activity was analyzed by the telomeric repeat amplification protocol assay, and the telomere length was measured by Southern blot. Results were related to survival and clinical outcome. Telomerase activity was detected in 85% of the bone tumor metastases (100% Ewing's sarcomas and 75% osteosarcomas) but only in 12% of the primary tumors (11.1% osteosarcomas and 12.5% Ewing's sarcomas). Bone tumor tissues with telomerase activity had mean telomere lengths 3 kb shorter than those with no detectable telomerase activity (p = 0.041). The presence of telomerase activity was associated with survival (p = 0.009), and longer event-free survival periods were found in patients who lacked telomerase activity compared with those who had detectable telomerase activity levels in their tumor tissues (p = 0.037). The presence of longer telomeres in primary pediatric bone tumors than in metastases could be indicative of alternative mechanisms of lengthening of telomeres for their telomere maintenance rather than telomerase activity. Nevertheless, the activation of telomerase seems to be a crucial step in the malignant progression and acquisition of invasive capability of bone tumors.     

Solid tumors of childhood

Objective : Cancer is one of the leading causes of death in children. There is the need to have the histologic review of malignancies in children from the Indian sub–continent.Methods : In the present study, malignant tumors received over 12 years were reviewed and re–classified according to classifications based on prognosis.Results : A total of 472 tumors were received over 12 years. Of these 318 were benign and 154 malignant. The commonest malignant solid tumor was lymphoma followed by pediatric renal tumors. The sarcomas included bone tumors, Rhabdomyosarcoma and synovial sarcoma. There were 13 germ cell tumors, 10 retinoblastomas and six neuroblastomas.Conclusion: The review revealed that a definite diagnosis or classification was not assigned in 21 cases in the original reporting. Of these 14 could be assigned a definite category on review and immuno-staining. These included five non-Wilms sarcomas, four Rhabdomyosarcomas, three Ewing’s sarcoma/ PNETs and two Synovial sarcomas. The study also revealed an unexpected high percentage (11%) of epithelial malignancies in children     

Pediatric undifferentiated sarcoma of the soft tissues: a clinicopathologic study.

Pediatric undifferentiated soft tissue sarcomas represent a major challenge for pathologists and clinicians. The goal of this study was to identify cases that warranted this diagnosis by current standards of analysis and then determine if there are clinicopathological commonalities that may be useful for diagnosis, management, and prognosis. Eighteen potential patients were identified using the institutional pathology database. Three cases were reclassified as specific sarcomas, and 2 cases had insufficient material for molecular analysis, leaving 13 cases for pathological review and 12 patients for radiological and clinical review. There were 7 males and 6 females. The median age at diagnosis was 11 years (1 month to 16 years). Tumors commonly involved the trunk (7 of 13; 54%) and ranged in size from 1.7 to 14.5 cm (mean, 6.7 cm). Eleven patients received ifosfamide/etoposide chemotherapy and 4 received irradiation. Five-year event-free and overall survival (EFS and OS) rates were 54% and 74%, respectively. The predominant histological pattern was round to plump spindled cells forming sheets (9 of 13; 69%) and severe atypia was associated with decreased survival (P = 0.048). Immunohistochemistry showed positivity for vimentin (92%), CD117 (92%), and vascular endothelial growth factor (69%), and 8% to 23% showed focal positivity for epithelial, neural, or myogenic markers. Tumors were uniformly negative for translocations associated with pediatric sarcomas. The presence of certain common morphological and immunohistochemical features in the absence of specific molecular genetic abnormalities allows for a diagnosis of pediatric undifferentiated soft tissue sarcoma; however, whether this group of neoplasms forms a unique category of tumors or a common precursor pathway for a number of different sarcomas awaits further study.     

Clear cell sarcoma of soft tissues in children and young adults: the St. Jude Children's Research Hospital experience

Clear cell sarcoma is a rare soft tissue neoplasm whose clinical behavior and outcome has not been previously characterized. This study reviewed the clinical characteristics and outcome of all children with clear cell sarcoma of the soft tissues who were treated at St. Jude Children's Research Hospital from March 1962 through August 1998. Of 225 children with nonrhabdomyosarcomatous soft tissue sarcomas, 5 (2.2%) were diagnosed with clear cell sarcoma. Median age at diagnosis was 15 years 3 months. Primary sites included the extremities (n = 3), chest wall (n = 1), and abdomen (n = 1). At diagnosis 3 patients had localized disease. Following surgical resection (n = 3), radiotherapy (n = 2), and chemotherapy (n = 1) all three survive disease-free 10, 11, and 90 months after diagnosis, respectively. The remaining two patients with metastatic disease at diagnosis died 21 days and 9 months after diagnosis. Clear cell sarcoma of the soft tissues is rare in pediatrics. Complete surgical resection with negative margins is the most effective treatment for this disease. Patients with metastatic disease are candidates for multiinstitutional chemotherapy trials.