Treatment of Newly Diagnosed Childhood Soft Tissue Sarcoma
Extraskeletal chondrosarcoma (mesenchymal and other variants)
Inflammatory myofibroblastic tumor
Low-grade fibromyxoid sarcoma
Myxofibrosarcoma, low grade
Sclerosing epithelioid fibrosarcoma
Skeletal Muscle Tumors
Smooth Muscle Tumors
So-called Fibrohistiocytic Tumors
Plexiform fibrohistiocytic tumor
Undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma (high-grade)
Tumors of Peripheral Nerves
Malignant peripheral nerve sheath tumor
Tumors of Uncertain Differentiation
Alveolar soft part sarcoma
Clear cell sarcoma of soft tissue
Desmoplastic small round cell tumor
Extrarenal (extracranial) rhabdoid tumor
Extraskeletal myxoid chondrosarcoma
Primitive neuroectodermal tumor (PNET)/extraskeletal Ewing tumor
Undifferentiated sarcoma; sarcoma, NOS
Current Clinical Trials
Liposarcoma is rare in the pediatric population. In a review of 182 pediatric patients with adult-type sarcomas, only 14 had a diagnosis of liposarcoma. One retrospective study identified 34 patients younger than 22 years from 1960 to 2011. There were roughly equal numbers of male and female patients and the median age was 18 years. In an international clinicopathological review, the characteristics of 82 cases of pediatric liposarcoma were reported. The median age was 15.5 years and females were more commonly affected. In both reports, the great majority of patients had myxoid liposarcoma.
Liposarcomas can be roughly divided into the following four large groups:
- Atypical lipomatous neoplasm/well-differentiated liposarcoma. These tumors do not metastasize unless they undergo dedifferentiation.
- Myxoid liposarcoma. Pure myxoid liposarcomas are characterized by a t(12;16)(q13;p11) translocation and can metastasize but usually have an excellent outcome in the absence of a round cell component.
- Dedifferentiated liposarcoma.
- Pleomorphic liposarcoma.
The great majority of liposarcomas in the pediatric and adolescent age range are low grade. Myxoid liposarcoma is typically low grade. Pleomorphic liposarcoma is typically high grade and much more likely to develop metastasis. Metastasis to lymph nodes is very uncommon, and the great majority of metastases are pulmonary. Tumors arising in the periphery are more likely to be low grade and myxoid. Tumors arising centrally are more likely to be high grade, pleomorphic, and present with metastasis or recur with metastasis.Treatment
Surgery is the most important treatment for liposarcoma. After surgical resection of myxoid liposarcoma, event-free survival (EFS) and overall survival (OS) are roughly 90%. Local recurrences have been seen and are controlled with a second resection of the tumor. Higher grade or central tumors are associated with a significantly higher risk of death. In a retrospective review, 5-year survival for central tumors was 42%. In the international review, seven of ten patients with pleomorphic myxoid liposarcoma died because of their disease. If initial surgery is incomplete, re-excision should be performed to achieve a wide margin of resection. There are reports of the use of chemotherapy to decrease the size of liposarcoma before surgery to facilitate complete resection, particularly in central tumors.[4,5] The role of adjuvant chemotherapy for liposarcoma is poorly defined. There does not appear to be a need for any adjuvant therapy for completely resected myxoid liposarcoma. Even with the use of adjuvant chemotherapy, the survival of pleomorphic liposarcoma remains poor.Chondro-osseous Tumors
Chondro-osseous tumors include the following tumor subtypes:
- Extraskeletal chondrosarcoma (mesenchymal and other variants).
- Extraskeletal osteosarcoma.
Mesenchymal chondrosarcoma is a highly malignant tumor with a propensity to spread to the lungs.Treatment
A review of 15 patients younger than 26 years from the German Cooperative Soft Tissue Sarcoma Study Group (11 with soft-tissue lesions) and the German-Austrian-Swiss Cooperative Osteosarcoma Study Group (four with primary bone lesions) protocols suggests that complete surgical removal, or incomplete resection followed by radiation therapy, is necessary for local control.[Level of evidence: 3iiA]
Multiagent chemotherapy may decrease the likelihood of lung metastases: OS at 10 years was 67%, compared with approximately 20% in an earlier series of young patients.Extraskeletal osteosarcoma
Extraskeletal osteosarcoma is extremely rare in the pediatric and adolescent age range. A 2003 review identified only ten case reports in the medical literature.
Extraskeletal osteosarcoma is associated with a high risk of local recurrence and pulmonary metastasis.Treatment
The primary therapy for extraskeletal osteosarcoma is surgical resection of the primary tumor. Chemotherapy for extraskeletal osteosarcoma has not been well studied. It has been recommended that the treatment for extraskeletal osteosarcoma abide by the soft tissue sarcoma (STS) guidelines, rather than the guidelines for osteosarcoma of bone. A report of a series of adult patients with extraskeletal osteosarcoma suggested that adjuvant chemotherapy reduced the risk of recurrence. Extraskeletal osteosarcoma may be more chemosensitive in young patients than in adults. A retrospective analysis of the German Cooperative Osteosarcoma Study identified a favorable outcome for extraskeletal osteosarcoma treated with surgery and conventional osteosarcoma chemotherapy. (Refer to the PDQ summary on Osteosarcoma and Malignant Fibrous Histiocytoma of Bone Treatment for more information.)Fibroblastic/Myofibroblastic Tumors
Fibroblastic/myofibroblastic tumors include the following tumor subtypes:
- Desmoid tumor.a
- Infant fibrosarcoma.
- Adult-type fibrosarcoma.
- Inflammatory myofibroblastic tumor.a
- Low-grade fibromyxoid sarcoma.
- Sclerosing epithelioid fibrosarcoma.
[Note: aNot a high-grade tumor.]Desmoid tumors
Desmoid tumors are also known as aggressive fibromatoses.
Desmoid tumors are low-grade malignancies with extremely low potential to metastasize. The tumors are locally infiltrating, and surgical control can be difficult because of the need to preserve normal structures. These tumors also have a high potential for local recurrence. Desmoid tumors have a highly variable natural history, including well documented examples of spontaneous regression. Mutations in exon 3 of the beta-catenin gene are seen in over 80% of desmoid tumors and the mutation 45F has been associated with an increased risk of disease recurrence. Repeated surgical resection can sometimes bring recurrent lesions under control.
A small number of desmoid tumors may occur in association with a mutation in the adenomatous polyposis coli (APC) gene (associated with intestinal polyps and a high incidence of colon cancer). In a study of 519 patients older than 10 years with a diagnosis of desmoid-type fibromatosis, 39 (7.5%) were found to have familial adenomatous polyposis (FAP) (a possible underestimation). The patients with FAP and desmoid tumors were younger, more often male, and had more abdominal wall or mesenteric tumors than did patients with desmoid tumors without FAP. A family history of colon cancer or the presence of congenital hyperplasia of the retinal pigment epithelium [16,17] or location of the desmoid tumor in the abdomen or abdominal wall  should prompt referral to a genetic counselor. Currently, there are no general recommendations for genetic testing in children with desmoid tumors. Pathology and molecular characteristics of the tumor only provide guidance for screening. If the tumor has a somatic CTNNB1 mutation, screening is not necessary, because the APC gene mutation has not been described in this setting. If a CTNNB1 mutation is not identified, screening for the APC mutation may be warranted.[18,19]Treatment
The treatment of choice is resection to achieve clear margins. However, a retrospective review of children who underwent surgery for desmoid tumors at the St. Jude Children’s Research Hospital reported no correlation between surgical margins and risk of recurrence. Postoperative radiation therapy is a consideration when progression would entail additional surgery that might cause functional or cosmetic compromise and if radiation is considered acceptable in terms of morbidities. When the diagnosis is known and complete surgical excision is not feasible, and if the tumor poses significant potential for mortality or morbidity, preoperative strategies may include the following:[21,22]
- Antiestrogen therapy.
- Nonsteroidal anti-inflammatory agent therapy.
- External-beam radiation therapy.
Evaluation of the benefit of interventions for treatment of desmoid tumors has been extremely difficult, because desmoid tumors have a highly variable natural history.
Large adult series and smaller pediatric series have reported long periods of disease stabilization and even regression without systemic therapy.[14,23]; [Level of evidence: 3iiiDi] Combination chemotherapy using vinblastine and methotrexate produced objective responses in about one-third of patients with recurrent or unresectable desmoid tumors. A small series of mainly adult patients (N = 19) with desmoid tumors were treated with imatinib mesylate and showed infrequent objective responses. A series of mainly adult patients with familial adenomatous polyposis and unresectable desmoid tumors that were unresponsive to hormone therapy showed that doxorubicin plus dacarbazine followed by meloxicam (a nonsteroidal anti-inflammatory agent) can be safely administered and can induce responses. Pegylated liposomal doxorubicin has also been used with some responses. Hydroxyurea may be useful, but more data are needed.
Nonsteroidal anti-inflammatory drugs (NSAIDs) such as sulindac have been used in single cases for desmoid tumors; the responses seen were usually disease stabilization. Similar results have been seen with antiestrogen treatment, usually tamoxifen. A prospective trial of the combination of tamoxifen and sulindac reported few side effects, although asymptomatic ovarian cysts were common in girls. This combination showed relatively little activity, as measured by rates of response and progression-free survival.[Level of evidence: 2Diii]
Radiation has been used for unresectable desmoid tumors or adjuvantly for tumors with inadequate resections. The potential long-term complications of radiation therapy, especially subsequent neoplasms, make using this modality less appealing in a young population.
Partially excised or recurrent lesions that do not pose a significant danger to vital organs may be monitored closely if other treatment alternatives are not available.[14,20,32-35] Whenever possible, however, the treatment of choice is complete resection.Fibrosarcoma
There are two distinct types of fibrosarcoma in children and adolescents: infantile fibrosarcoma (also called congenital fibrosarcoma) and fibrosarcoma that is indistinguishable from fibrosarcoma seen in adults. These are two distinct pathologic diagnoses.Infantile fibrosarcoma
Infantile fibrosarcoma usually occurs in children younger than 1 year. It occasionally occurs in children up to age 4 years. It usually presents with a rapidly growing mass, often noted at birth or even seen in prenatal ultrasound. The tumors are often quite large at the time of presentation. The tumor usually has a characteristic cytogenetic translocation t(12;15)(ETV-NTRK3). Infantile fibrosarcoma shares this translocation and a virtually identical histologic appearance with mesoblastic nephroma. These tumors have a low incidence of metastases at diagnosis.Treatment
Complete resection is curative in the majority of patients with infantile fibrosarcoma. However the large size of the lesion frequently makes resection without major functional consequences impossible (for instance, tumors of the extremities often require amputation for complete excision). Preoperative chemotherapy has made a more conservative surgical approach possible; agents active in this setting include vincristine, dactinomycin, cyclophosphamide, and ifosfamide.[37-39]; [Level of evidence: 3iiA]; [Level of evidence: 3iiB]Adult-type fibrosarcoma
These tumors lack the translocation seen in infantile fibrosarcomas. They present like the great majority of nonrhabdomyosarcomas and the management approach is similar.Dermatofibrosarcoma protuberans
Dermatofibrosarcoma is a rare tumor, but many of the reported cases arise in children. The tumor has a consistent chromosomal translocation t(17;22)(q22;q13) that juxtaposes the COL1A1 gene with the PDGF-beta gene.Treatment
Most dermatofibrosarcoma tumors can be cured by complete surgical resection. Wide excision with negative margins or Mohs or modified Mohs surgery will prevent most tumors from recurring.
Guidelines for workup and management of dermatofibrosarcoma protuberans have been published.Inflammatory myofibroblastic tumor
Inflammatory myofibroblastic tumor is an incompletely characterized neoplasm of intermediate biologic potential. It recurs frequently but metastasizes rarely.[50-52] Roughly half of inflammatory myofibroblastic tumors exhibit a clonal mutation that activates the anaplastic lymphoma kinase (ALK)-receptor tyrosine kinase gene at chromosome 2p23.
Complete surgical removal, when feasible, is the mainstay of therapy. In a series of nine patients, four patients who had a complete resection achieved continuous remission, three patients who had residual disease had a high recurrence rate and achieved continuous remission, and one patient who had metastatic disease responded to multiagent chemotherapy.[Level of evidence: 3iiA] There are case reports of response to either steroids or NSAIDs.[56,57]Low-grade fibromyxoid sarcoma
Low-grade fibromyxoid sarcoma is somewhat misnamed, because its appearance is deceptively benign, but its behavior is malignant, although rather indolent. In a review, 21 of 33 patients had local recurrences after intervals of up to 15 years (median, 3.5 years) and 15 had metastases, mostly in the lungs and pleura, after periods of up to 45 years (median, 5 years), indicating that follow-up must be lifelong. Even after metastases occur, the course may be indolent.
The limited treatment information for low-grade fibromyxoid sarcoma is summarized in the review above. This tumor is not very chemosensitive and there are little data regarding the use of chemotherapy and/or radiation therapy.Myxofibrosarcoma, low grade
Myxofibrosarcoma, low grade, is a rare lesion, especially in childhood. It is typically treated with complete surgical resection.Sclerosing epithelioid fibrosarcoma
Sclerosing epithelioid fibrosarcoma is another rare, usually low-grade, sarcoma. It is typically treated with complete surgical excision.Skeletal Muscle Tumors
There are three forms of rhabdomyosarcoma:
- Embryonal, plus subtypes of botryoid and spindle cells.
- Pleomorphic, also known as anaplastic sarcoma.
Refer to the PDQ summary on Childhood Rhabdomyosarcoma Treatment for more information.Smooth Muscle Tumors
A 24-year retrospective analysis of the Italian cooperative group identified one child with leiomyosarcoma. A retrospective analysis of the St. Jude Children’s Research Hospital (SJCRH) experience from 1962 to 1996 identified 40 children with nonrhabdomyosarcomatous STS; none had leiomyosarcoma. Among 43 children with HIV/AIDS who developed tumors, eight developed Epstein-Barr virus–associated leiomyosarcoma. Survivors of hereditary retinoblastoma have a statistically significant increased risk of developing leiomyosarcoma and 78% of these were diagnosed 30 or more years after the initial diagnosis of retinoblastoma.So-called Fibrohistiocytic Tumors
So-called fibrohistiocytic tumors include the following tumor subtypes:
- Plexiform fibrohistiocytic tumor.
- Undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma.
- Giant cell.
- Myxoid/high-grade myxofibrosarcoma.
Plexiform histiocytic tumor is a rare, low- to intermediate-grade tumor that most commonly affects children and young adults. Depending on the series, the median age at presentation ranges from 8 to 14.5 years; however, the tumor has been described in patients as young as 3 months.[63,64]
The tumor commonly arises as a painless mass in the skin or subcutaneous tissue and most often involves the upper extremities, including the fingers, hand, and wrist.[65-67] There are rare reports of spread to regional lymph nodes or the lungs.[63,67,68]
No consistent chromosomal anomalies have been detected but a t(4;15)(q21;q15) has been reported.Treatment
Surgery is the treatment of choice but local recurrence has been reported in 12% to 50% of cases.Undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma (high-grade)
At one time, malignant fibrous histiocytoma was the single most common histiotype among adults with STSs. Since it was first recognized in the early 1960s, malignant fibrous histiocytoma has been plagued by controversy in terms of both its histogenesis and its validity as a clinicopathologic entity. The latest World Health Organization classification no longer includes malignant fibrous histiocytoma as a distinct diagnostic category but rather as a subtype of an undifferentiated pleomorphic sarcoma.
This entity accounts for 2% to 6% of all childhood STSs. These tumors can arise in previously irradiated sites or as a second malignancy in patients with retinoblastoma.
These tumors occur mainly in the second decade of life. In a series of ten patients, the median age was 10 years and the tumor was most commonly located in the extremities. In this series, all tumors were localized and five of nine (for whom follow-up was available) were alive in first remission. In another series of 17 pediatric patients with malignant fibrous histiocytoma, the median age at diagnosis was 5 years and the extremities were involved in eight cases. All patients with metastatic disease died and two patients experienced a clinical response to a doxorubicin-based regimen.Tumors of Peripheral Nerves
Malignant peripheral nerve sheath tumor
Malignant peripheral nerve sheath tumor arises in children with type 1 neurofibromatosis (NF1), and it arises sporadically.
- Smaller tumor size—In a multivariate analysis, only tumor size and nuclear p53 expression were found to be independent predictors of disease-specific survival.
- Localized disease; no metastasis at presentation—A retrospective review of 140 patients with malignant peripheral nerve sheath tumor from the MD Anderson Cancer Center included children and adolescents. The disease-specific survival at 10 years was 32%. In this series, presence of metastatic disease was associated with a much worse prognosis. For patients with localized disease, there was no significant difference in outcome between patients with and without NF1.
- Lower stage.
- Lower histologic grade.
- Extremity as the primary site.
There is agreement that complete surgical removal of the tumor, whenever possible, is the mainstay of treatment. The role of radiation therapy is difficult to assess, but durable local control of known postsurgical microscopic residual tumor is not assured after radiation therapy. Chemotherapy has achieved objective responses in childhood malignant peripheral nerve sheath tumor. A large retrospective analysis of the German and Italian experience with malignant peripheral nerve sheath tumor reported that 65% of measurable tumors had objective responses to ifosfamide-containing chemotherapy regimens, but the analysis did not conclusively demonstrate improved survival for chemotherapy. This retrospective analysis also noted a trend toward improved outcome with adjuvant radiation therapy. A series of 37 young patients with malignant peripheral nerve sheath tumor and NF1 showed that most patients had large invasive tumors that were poorly responsive to chemotherapy; progression-free survival was 19% and 5-year OS was 28%. The role of adjuvant chemotherapy after resection of malignant peripheral nerve sheath tumor has not been prospectively evaluated.Tumors of Uncertain Differentiation
Tumors of uncertain differentiation include the following tumor subtypes:
- Alveolar soft part sarcoma.
- Clear cell sarcoma of soft tissue.
- Desmoplastic small round cell tumor.
- Epithelioid sarcoma.
- Extrarenal rhabdoid tumor.
- Extraskeletal myxoid chondrosarcoma.
- Primitive neuroectodermal tumor (PNET)/extraskeletal Ewing tumor.
- Synovial sarcoma.
- Undifferentiated sarcoma; sarcoma, not otherwise specified (NOS).
This is a tumor of uncertain histogenesis. A consistent chromosomal translocation t(X;17)(p11.2;q25) juxtaposes the ASPSCR1 gene with the TFE3 gene.[79,80] In children, alveolar soft part sarcoma often presents with metastases  and sometimes has a very indolent course. A subset of renal tumors found in young people was previously considered to be renal cell carcinoma, but the subset now appears to be genetically related to alveolar soft part sarcoma.
In a series of 19 treated patients, one group reported a 5-year OS rate of 80%, a 91% OS rate for patients with localized disease, a 100% OS rate for patients with tumors 5 cm or smaller, and a 31% OS rate for patients with tumors larger than 5 cm. In another series of 33 patients, OS was 68% at 5 years from diagnosis and 53% at 10 years from diagnosis. Survival was better for smaller tumors (≤5 cm) and completely resected tumors.[Level of evidence: 3iiA]Treatment
The standard approach is complete resection of the primary lesion. If complete excision is not feasible, radiation therapy should be administered.
A series of 51 pediatric patients aged 0 to 21 years with alveolar soft part sarcoma found an OS rate at 10 years of 78% and an EFS rate of about 63%. Patients with localized disease (n = 37) had a 10-year OS of 87%, and the 14 patients with metastases at diagnosis had a 10-year OS of 44%, partly resulting from surgical removal of primary tumor and lung metastases in some patients. Only 3 of 18 patients (17%) with measurable disease had a response to conventional antisarcoma chemotherapy, but two of four patients treated with sunitinib had a partial response.[Level of evidence: 3iiiA] There have been sporadic reports of objective responses to interferon-alpha and bevacizumab.[85-87] In a phase II trial of cediranib, an inhibitor of all three known vascular epidermal growth factor receptors, 15 of 43 patients (35%) with metastatic alveolar soft part sarcoma had a partial response.[Level of evidence: 3iiDiv]
Patients with alveolar soft part sarcoma may relapse several years after a prolonged period of apparent remission. Because these tumors are rare, all children with alveolar soft part sarcoma should be considered for prospective clinical trials.Treatment options under clinical evaluation for alveolar soft part sarcoma
The following is an example of a national and/or institutional clinical trial that is currently being conducted. Information about ongoing clinical trials is available from the NCI Web site.
- NCT00942877 (Phase II Study of Cediranib [AZD2171] in Patients With Alveolar Soft Part Sarcoma): A phase II study of cediranib in patients with alveolar soft part sarcoma is being conducted in patients younger than 16 years at the Clinical Center of the National Institutes of Health.
- NCT01391962 (Sunitinib or Cediranib for Alveolar Soft Part Sarcoma): A phase II trial in which patients with metastatic alveolar soft part sarcoma are randomly assigned to either sunitinib or cediranib monotherapy, with crossover at disease progression. Patients aged 16 years and older are eligible. This study is being conducted at the Clinical Center of the National Institutes of Health.
Clear cell sarcoma (formerly and inappropriately called malignant melanoma of soft parts), also called clear cell sarcoma of tendons and aponeuroses, is somewhat similar to cutaneous malignant melanoma but is cytogenetically distinct; most cases have a t(12;22)(q13;q12) translocation that has not been reported in melanoma. In one series, clear cell sarcoma demonstrated a propensity to metastasize to regional lymph nodes (12%–43%).
Patients who have small, localized tumors with low mitotic rate and intermediate histologic grade fare best.
The primary treatment for clear cell sarcoma is complete surgical resection, with the addition of radiation therapy for uncertain or involved margins. Chemotherapy is rarely effective.; [Level of evidence: 3iiDii]Desmoplastic small round cell tumor
Desmoplastic small round cell tumor is a primitive sarcoma that most frequently involves the abdomen, pelvis, or tissues around the testes.[95-97] The tumor occurs more commonly in males and may spread to the lungs and elsewhere. Peritoneal and pelvic lesions frequently have widespread peritoneal implants. In a large, single-institution series of 65 patients, a correlation was made between computed tomography (CT) scans in most patients and positron-emission tomography (PET)/CT scans in 11 patients. PET/CT scans had very few false-negative results and detected metastatic sites missed on conventional CT scans.
Cytogenetic studies of these tumors have demonstrated the recurrent translocation t(11;22)(p13;q12), which has been characterized as a fusion of the WT1 and EWS genes.Treatment
There is no standard approach to the treatment of desmoplastic small round cell tumor. Complete surgical resections are rare, and the overall prognosis for desmoplastic small round cell tumor remains extremely poor, with reported rates of death at 90%. A small series of patients who were treated with hyperthermic intraperitoneal chemotherapy with acceptable toxicity has been reported.
Greater than 90% tumor resection either at presentation or after neoadjuvant chemotherapy may be a favorable prognostic factor for OS.[101,102] Treatment may include chemotherapy, surgery, and radiation therapy. Multiagent chemotherapy analogous to that used for sarcomas has been used, as well as total abdominal radiation therapy.[95,96,101,103,104]Epithelioid sarcoma
Epithelioid sarcoma is a rare mesenchymal tumor of uncertain histogenesis which displays multilineage differentiation. It is characterized by inactivation of the SMARC gene, which is present in both conventional and proximal types of epithelioid sarcoma.
Epithelioid sarcoma commonly presents as a slowly growing firm nodule based in the deep soft tissue; the proximal type predominantly affects adults and involves the axial skeleton and proximal sites. The tumor is highly aggressive and has a propensity for lymph node metastases.
In a review of 30 pediatric patients with epithelioid sarcoma (median age at presentation, 12 years), responses to chemotherapy were reported in 40% of patients using sarcoma-based regimens, and 60% of patients were alive at 5 years after initial diagnosis. A single-institution retrospective review of 20 patients, including children and adults, found no difference in the probability of recurrence between patients who received chemotherapy and those who did not receive chemotherapy and suggested that radiation therapy may be useful. Surgical removal of primary and recurrent tumor(s) was most effective.[Level of evidence: 3iiiA]Perivascular epithelioid cell tumors (PEComas)
PEComas (tumors showing perivascular epithelioid cell differentiation) include the following:
- Clear cell "sugar" tumor.
Benign PEComas are common in tuberous sclerosis, an autosomal dominant syndrome that also predisposes to renal cell cancer and brain tumors. Tuberous sclerosis is caused by germline inactivation of either TSC1 (9q34) or TSC2 (16p13.3), and the same tumor suppressor genes are inactivated somatically in sporadic PEComas. Inactivation of either gene results in stimulation of the mTOR pathway, providing the basis for the treatment of nonsurgically curable PEComas with mTOR inhibitors.[110,111]
PEComas occur in various rare gastrointestinal, pulmonary, gynecologic, and genitourinary sites. Soft tissue, visceral, and gynecologic PEComas are more commonly seen in middle-aged female patients and are usually not associated with the tuberous sclerosis complex. Most PEComas have a benign clinical course, but malignant behavior has been reported and can be predicted based on the size of the tumor, mitotic rate, and presence of necrosis.Extrarenal (extracranial) rhabdoid tumor
Malignant rhabdoid tumors were first described in children with renal tumors in 1981 (refer to the Wilms Tumor and Other Childhood Kidney Tumors Treatment summary for more information) and were later found in a variety of extrarenal sites. They are uncommon and highly malignant, especially in children younger than 2 years. The first sizeable series of 26 childhood patients with extrarenal extracranial malignant rhabdoid tumor of soft tissues came from patients enrolled on the Intergroup Rhabdomyosarcoma Studies I through III during a review of pathology material. Only five patients (19%) were alive without disease. Later, investigation of children with atypical teratoid/rhabdoid tumors of the brain, as well as those with renal and extrarenal malignant rhabdoid tumors, found germline and acquired mutations of the SMARCB1 gene in all 29 tumors tested. Rhabdoid tumors may be associated with germline mutations of the SMARCB1 gene and may be inherited from an apparently unaffected parent. This observation was extended to 32 malignant rhabdoid tumors at all sites in patients whose mean age at diagnosis was 12 months. The disease can occur congenitally  and is uncommon in older children and adults.
In a Surveillance, Epidemiology, and End Results (SEER) study of 229 patients with renal, central nervous system, and extrarenal malignant rhabdoid tumor, patients aged 2 to 18 years, limited extent of tumor, and delivery of radiation therapy were shown to affect the outcome favorably compared with other patients (P < .002 for each comparison). Site of the primary tumor was not prognostically significant. OS at 5 years was 33%.
Treatment includes surgical removal when possible, chemotherapy as used for STSs (but no single regimen is currently accepted as best), and radiation therapy.[Level of evidence: 3iA]; [121,122][Level of evidence: 3iiiB]Extraskeletal myxoid chondrosarcoma
Extraskeletal myxoid chondrosarcoma is a multinodular neoplasm. The rounded cells are arranged in cords and strands in a chondroitin sulfate myxoid background. Several cytogenetic abnormalities have been identified (see Table 2), with the most frequent being the translocation t(9;22)(q22;q12), involving the EWSR1/NR4A3 genes. The tumor has traditionally been considered of low-grade malignant potential. However, recent reports from large institutions showed that extraskeletal myxoid chondrosarcoma has significant malignant potential, especially if patients are followed for a long time.[127,128] Patients tend to have slow protracted courses. Nodal involvement has been well described. Local recurrence (57%) and metastatic spread to lungs (26%) have been reported.Treatment
The therapeutic benefit of chemotherapy has not been established. Aggressive local control and aggressive resection of metastases led to OS of 87% at 5 years and 63% at 10 years. There may be potential genetic targets for small molecules, but these should be studied as part of a clinical trial.Primitive neuroectodermal tumor (PNET)/extraskeletal Ewing tumor
(Refer to the PDQ summary on Ewing Sarcoma Treatment for more information.)Synovial sarcoma
Synovial sarcoma is one of the most common nonrhabdomyosarcomatous STSs in children and adolescents. In a SEER review from 1973 to 2005, 1,268 patients with synovial sarcoma were identified. Approximately 17% of these patients were children and adolescents and the median age at diagnosis was 34 years. The most common location is the extremities, followed by trunk and head and neck. Patients younger than 10 years have more favorable outcomes and clinical features, including extremity primaries, smaller tumors, and localized disease, than do older patients.
Synovial sarcoma can be subclassified as the following types:
- Monophasic fibrous type.
- Biphasic type with distinct epithelial and spindle cell components.
- Poorly differentiated. Poorly differentiated synovial sarcoma has features of monophasic or biphasic synovial sarcoma but also has a variable proportion of poorly differentiated areas characterized by high cellularity, pleomorphism, and polygonal or small round-cell morphology, numerous mitoses, and often necrosis.
The diagnosis of synovial sarcoma is made by immunohistochemical analysis, ultrastructural findings, and demonstration of the specific chromosomal translocation t(x;18)(p11.2;q11.2). This abnormality is specific for synovial sarcoma and is found in all morphologic subtypes. Synovial sarcoma results in rearrangement of the SYT gene on chromosome 18 with one of the subtypes (1, 2, or 4) of the SSX gene on chromosome X.[131,132] It is thought that the SYT/SSX18 transcript promotes epigenetic silencing of key tumor suppressor genes. Reduced INI1 nuclear reactivity on immunohistochemical staining is typical of most synovial sarcomas examined and does not occur with other similar histologies, thus providing a fast diagnosis while awaiting genetic studies.
The most common site of metastasis is the lung.[135,136] The risk of metastases is highly influenced by tumor size; it is estimated that patients with tumors that measure greater than 5 cm have a 32-fold risk of developing metastases when compared with other patients.
In a retrospective analysis of synovial sarcoma in children and adolescents who were treated in Germany and Italy, tumor size (>5 cm or ≤5 cm in greatest dimension) was an important predictor of EFS. In this analysis, local invasiveness conferred an inferior probability of EFS, but surgical margins were not associated with clinical outcome. In a single-institution retrospective analysis of 111 patients with synovial sarcoma who were younger than 22 years at diagnosis, larger tumor size, greater depth in tissue, greater local invasiveness, and more proximal tumor location were associated with poorer OS.[Level of evidence: 3iiA] A multicenter analysis of 219 children from various treating centers including Germany, SJCRH, Instituto Tumori, and MD Anderson Cancer Center reported an estimated 5-year OS of 80% and EFS rate of 72%. In this analysis, an interaction between tumor size and invasiveness was observed; in multivariate analysis, patients with large or invasive tumors or with Intergroup Rhabdomyosarcoma Study Clinical Group III and IV disease had decreased OS. Treatment with radiation therapy was related to improved OS (hazard ratio, 0.4; 95% confidence interval, 0.2–0.7). In Intergroup Rhabdomyosarcoma Study Group III patients, objective response to chemotherapy (18 of 30 [60%]) correlated with improved survival. In adults, factors such as International Union Against Cancer/American Joint Committee on Cancer stage III and stage IVA, tumor necrosis, truncal location, elevated mitotic rate, age, and histologic grade have been associated with a worse prognosis.[139-141] Expression and genomic index prognostic signatures have been studied in synovial sarcoma. More complex genomic profiles, with greater rearrangement of the genome, are more common in adults than in younger patients with synovial sarcoma and are associated with a higher risk for metastasis.Treatment
Synovial sarcoma appears to be more sensitive to chemotherapy than many other STSs, and children with synovial sarcoma seem to have a better prognosis when compared with adults.[5,136,141,143-148] The most commonly used regimens for the treatment of synovial sarcoma incorporate ifosfamide and doxorubicin.[146,149,150] Response rates to the ifosfamide and doxorubicin regimen are higher than in other nonrhabdomyosarcomatous STSs. A meta-analysis also suggested that response to chemotherapy was correlated with improved survival.
Several treatment centers advocate adjuvant chemotherapy after resection and radiation therapy of synovial sarcoma in children and young adults.[137,147,150,152-154] The International Society of Pediatric Oncology-Malignant Mesenchymal Tumors studies showed that select patients (young age, < 5 cm resected tumors) with nonmetastatic synovial sarcoma can have excellent outcome in the absence of radiation, but it is still unclear whether that approach obviates an advantage of radiation for local or regional control. A German trial suggested a benefit for adjuvant chemotherapy in children with synovial sarcoma. A meta-analysis also suggested that chemotherapy may provide benefit. However, unequivocal proof of the value of adjuvant chemotherapy from prospective, randomized clinical trials is lacking and the results of COG-ARST0332 are pending. Survival after relapse is poor (30% at 5 years). Factors associated with outcome after relapse include duration of first remission (> or ≤ 18 months) and lack of a second remission.Undifferentiated sarcoma; sarcoma, NOS
Patients with undifferentiated STS had been eligible for participation in rhabdomyosarcoma trials coordinated by the Intergroup Rhabdomyosarcoma Study Group and the Children’s Oncology Group (COG) from 1972 to 2006. The rationale was the observation that patients with undifferentiated STS had similar sites of disease and outcome as those with alveolar rhabdomyosarcoma. Therapeutic trials for adults with STS include patients with undifferentiated STS and other histologies, which are treated similarly, using ifosfamide and doxorubicin, and sometimes with other chemotherapy agents, surgery, and radiation therapy. Currently in the COG, they are treated on clinical trials for patients with nonrhabdomyosarcomatous STSs.Vascular Tumors
Vascular tumors vary from hemangiomas, which are always considered benign, to angiosarcomas, which are highly malignant. Vascular tumors include the following tumor subtypes:
- Epithelioid hemangioendothelioma.
- Angiosarcoma (deep).
- Hemangiopericytoma (infantile).
Hemangioendotheliomas are tumors found in infants that arise within the liver or elsewhere and usually remain benign.[157,158] Liver hemangioendotheliomas may regress then enlarge. These tumors may also become malignant. The tumors are sometimes associated with consumptive coagulopathy, also known as the Kasabach-Merritt syndrome (or phenomenon).[159-162] Chemotherapy and interferon have had some benefit in isolated cases of hemangioendothelioma associated with Kasabach-Merritt syndrome.[160,161] A report from Spain indicated good control of severe thrombocytopenia of less than 30,000/mm3 in 11 patients with hemangioendothelioma or tufted angioma treated with weekly vincristine, and daily low-dose aspirin and ticlodipine.[Level of evidence: 3iiiA]
In older children and adults, hemangioendotheliomas may occur elsewhere in the body and can metastasize to lungs, lymph nodes, bones, and within the pleural or peritoneal cavities. The preferred pathologic designation for these lesions in older persons is epithelioid hemangioendothelioma, which connotes the possibility of distant spread. These latter lesions are considered to be of intermediate malignant potential, between benign hemangioma and angiosarcoma.[164,165] Epithelioid hemangioendothelioma of the liver is usually managed surgically. Some patients may need orthotopic liver transplantation because this disease does not respond to radiation therapy or chemotherapy. In more extensive hemangioendothelioma, inhibition of the mTOR pathway may be helpful. However, this should be investigated as part of a clinical trial before use in the clinical setting.
Treatment of asymptomatic liver hemangioendothelioma in a child younger than 1 year may include close observation, because some tumors will regress. Symptomatic lesions require urgent medical or surgical management, especially if coagulopathy is present.[157,159-161,163]Angiosarcoma (deep)
Angiosarcomas may arise in a setting of benign vascular anomalies or vascular malformations.[167-169] Angiosarcomas have also been described in previously benign hemangiomas and hemangioendotheliomas. Of five girls, three infants younger than 4 months with cutaneous hemangiomas and two girls with multinodular liver hemangiomas developed angiosarcomas. All three girls initially diagnosed with cutaneous hemangiomas died. Liver size initially decreased; however, at age 2.5 to 5 years, their livers enlarged, and all three girls died of angiosarcoma. The other two girls presented with vascular liver tumors at age 2 and 3.5 years, without previous histories. The younger girl had a benign unifocal hemangioendothelioma on biopsy; 3 months later, another biopsy showed both benign and malignant histology, and she died. The older girl had multinodular angiosarcomas without metastases, underwent liver transplantation, and was recurrence free 2 years later. The authors recommend liver ultrasound surveillance every 6 months for infants with multinodular liver hemangiomas.
Complete surgical excision appears to be crucial for angiosarcomas and lymphangiosarcomas despite evidence of tumor shrinkage in some patients in response to local or systemic therapy.[170-173] A review of 222 patients (median age, 62 years; range, age 15–90 years) showed an overall disease-specific survival (DSS) rate of 38% at 5 years. Five-year DSS was 44% in 138 patients with localized, resected tumors but only 16% in 43 patients with metastases at diagnosis. Data on liver transplantation for localized angiosarcoma are limited.[Level of evidence: 3iiA]
Chemotherapy may be effective for the treatment of angiosarcoma. A review of 20 years of experience in the Italian and German Soft Tissue Sarcoma Cooperative Group identified 12 children with angiosarcoma. One objective response to chemotherapy was observed, and the overall behavior of this tumor was identical to angiosarcoma in adults. A subsequent retrospective study of 14 children with angiosarcoma performed by the Polish and German Cooperative Paediatric Soft Tissue Sarcoma Study Groups identified four chemotherapy responses in ten children. Another review of 15 patients demonstrated a 33% survival rate.
Anti-angiogenesis therapy may prove useful in the treatment of this group of neoplasms.Hemangiopericytoma (infantile)
Hemangiopericytoma is a highly vascularized tumor of uncertain origin. Hemangiopericytoma in children younger than 1 year seems to have a better prognosis than in children older than 1 year.[177-179] Histologically, hemangiopericytomas are composed of packed round or fusiform cells that are arranged around a complex vasculature, forming many branch-like structures. Hyalinization is often present. Infantile hemangiopericytomas have similar histology but many are multilobular with vasculature outside the tumor mass.
In a series of 17 children, the differences in metastatic potential and response to treatment were clearly demonstrated for adult and infantile hemangiopericytomas. Eleven children were older than 1 year. Several of these patients had disease in the lymph nodes or lungs. Six patients with stage II and III disease progressed and died. Three patients with stage I disease survived, although one had recurrence in the lungs. Six patients had infantile hemangiopericytoma, most were greater than stage I (5 of 6). All six survived and three had good responses to vincristine, actinomycin, and cyclophosphamide.Current Clinical Trials
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with nonmetastatic childhood soft tissue sarcoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.References
- Ferrari A, Casanova M, Collini P, et al.: Adult-type soft tissue sarcomas in pediatric-age patients: experience at the Istituto Nazionale Tumori in Milan. J Clin Oncol 23 (18): 4021-30, 2005. [PUBMED Abstract]
- Stanelle EJ, Christison-Lagay ER, Sidebotham EL, et al.: Prognostic factors and survival in pediatric and adolescent liposarcoma. Sarcoma 2012: 870910, 2012. [PUBMED Abstract]
- Alaggio R, Coffin CM, Weiss SW, et al.: Liposarcomas in young patients: a study of 82 cases occurring in patients younger than 22 years of age. Am J Surg Pathol 33 (5): 645-58, 2009. [PUBMED Abstract]
- Ferrari A, Casanova M, Spreafico F, et al.: Childhood liposarcoma: a single-institutional twenty-year experience. Pediatr Hematol Oncol 16 (5): 415-21, 1999 Sep-Oct. [PUBMED Abstract]
- Cecchetto G, Alaggio R, Dall'Igna P, et al.: Localized unresectable non-rhabdo soft tissue sarcomas of the extremities in pediatric age: results from the Italian studies. Cancer 104 (9): 2006-12, 2005. [PUBMED Abstract]
- Huh WW, Yuen C, Munsell M, et al.: Liposarcoma in children and young adults: a multi-institutional experience. Pediatr Blood Cancer 57 (7): 1142-6, 2011. [PUBMED Abstract]
- Dantonello TM, Int-Veen C, Leuschner I, et al.: Mesenchymal chondrosarcoma of soft tissues and bone in children, adolescents, and young adults: experiences of the CWS and COSS study groups. Cancer 112 (11): 2424-31, 2008. [PUBMED Abstract]
- Dabska M, Huvos AG: Mesenchymal chondrosarcoma in the young. Virchows Arch A Pathol Anat Histopathol 399 (1): 89-104, 1983. [PUBMED Abstract]
- Wodowski K, Hill DA, Pappo AS, et al.: A chemosensitive pediatric extraosseous osteosarcoma: case report and review of the literature. J Pediatr Hematol Oncol 25 (1): 73-7, 2003. [PUBMED Abstract]
- Sordillo PP, Hajdu SI, Magill GB, et al.: Extraosseous osteogenic sarcoma. A review of 48 patients. Cancer 51 (4): 727-34, 1983. [PUBMED Abstract]
- Goldstein-Jackson SY, Gosheger G, Delling G, et al.: Extraskeletal osteosarcoma has a favourable prognosis when treated like conventional osteosarcoma. J Cancer Res Clin Oncol 131 (8): 520-6, 2005. [PUBMED Abstract]
- Lewis JJ, Boland PJ, Leung DH, et al.: The enigma of desmoid tumors. Ann Surg 229 (6): 866-72; discussion 872-3, 1999. [PUBMED Abstract]
- Lazar AJ, Tuvin D, Hajibashi S, et al.: Specific mutations in the beta-catenin gene (CTNNB1) correlate with local recurrence in sporadic desmoid tumors. Am J Pathol 173 (5): 1518-27, 2008. [PUBMED Abstract]
- Faulkner LB, Hajdu SI, Kher U, et al.: Pediatric desmoid tumor: retrospective analysis of 63 cases. J Clin Oncol 13 (11): 2813-8, 1995. [PUBMED Abstract]
- Nieuwenhuis MH, Casparie M, Mathus-Vliegen LM, et al.: A nation-wide study comparing sporadic and familial adenomatous polyposis-related desmoid-type fibromatoses. Int J Cancer 129 (1): 256-61, 2011. [PUBMED Abstract]
- Rossato M, Rigotti M, Grazia M, et al.: Congenital hypertrophy of the retinal pigment epithelium (CHRPE) and familial adenomatous polyposis (FAP). Acta Ophthalmol Scand 74 (4): 338-42, 1996. [PUBMED Abstract]
- Baker RH, Heinemann MH, Miller HH, et al.: Hyperpigmented lesions of the retinal pigment epithelium in familial adenomatous polyposis. Am J Med Genet 31 (2): 427-35, 1988. [PUBMED Abstract]
- Kattentidt Mouravieva AA, Geurts-Giele IR, de Krijger RR, et al.: Identification of Familial Adenomatous Polyposis carriers among children with desmoid tumours. Eur J Cancer 48 (12): 1867-74, 2012. [PUBMED Abstract]
- Wang WL, Nero C, Pappo A, et al.: CTNNB1 genotyping and APC screening in pediatric desmoid tumors: a proposed algorithm. Pediatr Dev Pathol 15 (5): 361-7, 2012 Sep-Oct. [PUBMED Abstract]
- Soto-Miranda MA, Sandoval JA, Rao B, et al.: Surgical treatment of pediatric desmoid tumors. A 12-year, single-center experience. Ann Surg Oncol 20 (11): 3384-90, 2013. [PUBMED Abstract]
- Skapek SX, Ferguson WS, Granowetter L, et al.: Vinblastine and methotrexate for desmoid fibromatosis in children: results of a Pediatric Oncology Group Phase II Trial. J Clin Oncol 25 (5): 501-6, 2007. [PUBMED Abstract]
- Gandhi MM, Nathan PC, Weitzman S, et al.: Successful treatment of life-threatening generalized infantile myofibromatosis using low-dose chemotherapy. J Pediatr Hematol Oncol 25 (9): 750-4, 2003. [PUBMED Abstract]
- Merchant NB, Lewis JJ, Woodruff JM, et al.: Extremity and trunk desmoid tumors: a multifactorial analysis of outcome. Cancer 86 (10): 2045-52, 1999. [PUBMED Abstract]
- Honeyman JN, Theilen TM, Knowles MA, et al.: Desmoid fibromatosis in children and adolescents: a conservative approach to management. J Pediatr Surg 48 (1): 62-6, 2013. [PUBMED Abstract]
- Heinrich MC, McArthur GA, Demetri GD, et al.: Clinical and molecular studies of the effect of imatinib on advanced aggressive fibromatosis (desmoid tumor). J Clin Oncol 24 (7): 1195-203, 2006. [PUBMED Abstract]
- Gega M, Yanagi H, Yoshikawa R, et al.: Successful chemotherapeutic modality of doxorubicin plus dacarbazine for the treatment of desmoid tumors in association with familial adenomatous polyposis. J Clin Oncol 24 (1): 102-5, 2006. [PUBMED Abstract]
- Constantinidou A, Jones RL, Scurr M, et al.: Pegylated liposomal doxorubicin, an effective, well-tolerated treatment for refractory aggressive fibromatosis. Eur J Cancer 45 (17): 2930-4, 2009. [PUBMED Abstract]
- Bisogno G, Tagarelli A, Stramare R, et al.: Hydroxyurea treatment can avoid the need for aggressive surgery in pediatric fibromatosis. J Pediatr Hematol Oncol 35 (4): e171-3, 2013. [PUBMED Abstract]
- Hansmann A, Adolph C, Vogel T, et al.: High-dose tamoxifen and sulindac as first-line treatment for desmoid tumors. Cancer 100 (3): 612-20, 2004. [PUBMED Abstract]
- Skapek SX, Anderson JR, Hill DA, et al.: Safety and efficacy of high-dose tamoxifen and sulindac for desmoid tumor in children: results of a Children's Oncology Group (COG) phase II study. Pediatr Blood Cancer 60 (7): 1108-12, 2013. [PUBMED Abstract]
- Rutenberg MS, Indelicato DJ, Knapik JA, et al.: External-beam radiotherapy for pediatric and young adult desmoid tumors. Pediatr Blood Cancer 57 (3): 435-42, 2011. [PUBMED Abstract]
- Merchant TE, Nguyen D, Walter AW, et al.: Long-term results with radiation therapy for pediatric desmoid tumors. Int J Radiat Oncol Biol Phys 47 (5): 1267-71, 2000. [PUBMED Abstract]
- Zelefsky MJ, Harrison LB, Shiu MH, et al.: Combined surgical resection and iridium 192 implantation for locally advanced and recurrent desmoid tumors. Cancer 67 (2): 380-4, 1991. [PUBMED Abstract]
- Weiss AJ, Lackman RD: Low-dose chemotherapy of desmoid tumors. Cancer 64 (6): 1192-4, 1989. [PUBMED Abstract]
- Klein WA, Miller HH, Anderson M, et al.: The use of indomethacin, sulindac, and tamoxifen for the treatment of desmoid tumors associated with familial polyposis. Cancer 60 (12): 2863-8, 1987. [PUBMED Abstract]
- Sulkowski JP, Raval MV, Browne M: Margin status and multimodal therapy in infantile fibrosarcoma. Pediatr Surg Int 29 (8): 771-6, 2013. [PUBMED Abstract]
- Okcu MF, Pappo AS, Hicks J, et al.: The nonrhabdomyosarcoma soft tissue sarcomas. In: Pizzo PA, Poplack DG, eds.: Principles and Practice of Pediatric Oncology. 6th ed. Philadelphia, Pa: Lippincott Williams and Wilkins, 2011, pp 954-86.
- Loh ML, Ahn P, Perez-Atayde AR, et al.: Treatment of infantile fibrosarcoma with chemotherapy and surgery: results from the Dana-Farber Cancer Institute and Children's Hospital, Boston. J Pediatr Hematol Oncol 24 (9): 722-6, 2002. [PUBMED Abstract]
- Fernandez-Pineda I, Parida L, Jenkins JJ, et al.: Childhood hemangiopericytoma: review of St Jude Children's Research Hospital. J Pediatr Hematol Oncol 33 (5): 356-9, 2011. [PUBMED Abstract]
- Akyüz C, Küpeli S, Varan A, et al.: Infantile fibrosarcoma: retrospective analysis of eleven patients. Tumori 97 (2): 166-9, 2011 Mar-Apr. [PUBMED Abstract]
- Gallego S, Pericas N, Barber I, et al.: Infantile fibrosarcoma of the retroperitoneum: a site of unfavorable prognosis? Pediatr Hematol Oncol 28 (5): 451-3, 2011. [PUBMED Abstract]
- Buckley PG, Mantripragada KK, Benetkiewicz M, et al.: A full-coverage, high-resolution human chromosome 22 genomic microarray for clinical and research applications. Hum Mol Genet 11 (25): 3221-9, 2002. [PUBMED Abstract]
- Meguerditchian AN, Wang J, Lema B, et al.: Wide excision or Mohs micrographic surgery for the treatment of primary dermatofibrosarcoma protuberans. Am J Clin Oncol 33 (3): 300-3, 2010. [PUBMED Abstract]
- Dagan R, Morris CG, Zlotecki RA, et al.: Radiotherapy in the treatment of dermatofibrosarcoma protuberans. Am J Clin Oncol 28 (6): 537-9, 2005. [PUBMED Abstract]
- Sun LM, Wang CJ, Huang CC, et al.: Dermatofibrosarcoma protuberans: treatment results of 35 cases. Radiother Oncol 57 (2): 175-81, 2000. [PUBMED Abstract]
- Price VE, Fletcher JA, Zielenska M, et al.: Imatinib mesylate: an attractive alternative in young children with large, surgically challenging dermatofibrosarcoma protuberans. Pediatr Blood Cancer 44 (5): 511-5, 2005. [PUBMED Abstract]
- McArthur GA, Demetri GD, van Oosterom A, et al.: Molecular and clinical analysis of locally advanced dermatofibrosarcoma protuberans treated with imatinib: Imatinib Target Exploration Consortium Study B2225. J Clin Oncol 23 (4): 866-73, 2005. [PUBMED Abstract]
- Rutkowski P, Van Glabbeke M, Rankin CJ, et al.: Imatinib mesylate in advanced dermatofibrosarcoma protuberans: pooled analysis of two phase II clinical trials. J Clin Oncol 28 (10): 1772-9, 2010. [PUBMED Abstract]
- Miller SJ, Alam M, Andersen JS, et al.: Dermatofibrosarcoma protuberans. J Natl Compr Canc Netw 10 (3): 312-8, 2012. [PUBMED Abstract]
- Kovach SJ, Fischer AC, Katzman PJ, et al.: Inflammatory myofibroblastic tumors. J Surg Oncol 94 (5): 385-91, 2006. [PUBMED Abstract]
- Brodlie M, Barwick SC, Wood KM, et al.: Inflammatory myofibroblastic tumours of the respiratory tract: paediatric case series with varying clinical presentations. J Laryngol Otol 125 (8): 865-8, 2011. [PUBMED Abstract]
- Xiao Y, Zhou S, Ma C, et al.: Radiological and histopathological features of hepatic inflammatory myofibroblastic tumour: analysis of 10 cases. Clin Radiol 68 (11): 1114-20, 2013. [PUBMED Abstract]
- Coffin CM, Hornick JL, Fletcher CD: Inflammatory myofibroblastic tumor: comparison of clinicopathologic, histologic, and immunohistochemical features including ALK expression in atypical and aggressive cases. Am J Surg Pathol 31 (4): 509-20, 2007. [PUBMED Abstract]
- Devaney KO, Lafeir DJ, Triantafyllou A, et al.: Inflammatory myofibroblastic tumors of the head and neck: evaluation of clinicopathologic and prognostic features. Eur Arch Otorhinolaryngol 269 (12): 2461-5, 2012. [PUBMED Abstract]
- Mehta B, Mascarenhas L, Zhou S, et al.: Inflammatory myofibroblastic tumors in childhood. Pediatr Hematol Oncol 30 (7): 640-5, 2013. [PUBMED Abstract]
- Doski JJ, Priebe CJ Jr, Driessnack M, et al.: Corticosteroids in the management of unresected plasma cell granuloma (inflammatory pseudotumor) of the lung. J Pediatr Surg 26 (9): 1064-6, 1991. [PUBMED Abstract]
- Diop B, Konate I, Ka S, et al.: Mesenteric myofibroblastic tumor: NSAID therapy after incomplete resection. J Visc Surg 148 (4): e311-4, 2011. [PUBMED Abstract]
- Evans HL: Low-grade fibromyxoid sarcoma: a clinicopathologic study of 33 cases with long-term follow-up. Am J Surg Pathol 35 (10): 1450-62, 2011. [PUBMED Abstract]
- O'Sullivan MJ, Sirgi KE, Dehner LP: Low-grade fibrosarcoma (hyalinizing spindle cell tumor with giant rosettes) with pulmonary metastases at presentation: case report and review of the literature. Int J Surg Pathol 10 (3): 211-6, 2002. [PUBMED Abstract]
- Spunt SL, Hill DA, Motosue AM, et al.: Clinical features and outcome of initially unresected nonmetastatic pediatric nonrhabdomyosarcoma soft tissue sarcoma. J Clin Oncol 20 (15): 3225-35, 2002. [PUBMED Abstract]
- Pollock BH, Jenson HB, Leach CT, et al.: Risk factors for pediatric human immunodeficiency virus-related malignancy. JAMA 289 (18): 2393-9, 2003. [PUBMED Abstract]
- Kleinerman RA, Tucker MA, Abramson DH, et al.: Risk of soft tissue sarcomas by individual subtype in survivors of hereditary retinoblastoma. J Natl Cancer Inst 99 (1): 24-31, 2007. [PUBMED Abstract]
- Enzinger FM, Zhang RY: Plexiform fibrohistiocytic tumor presenting in children and young adults. An analysis of 65 cases. Am J Surg Pathol 12 (11): 818-26, 1988. [PUBMED Abstract]
- Black J, Coffin CM, Dehner LP: Fibrohistiocytic tumors and related neoplasms in children and adolescents. Pediatr Dev Pathol 15 (1 Suppl): 181-210, 2012. [PUBMED Abstract]
- Moosavi C, Jha P, Fanburg-Smith JC: An update on plexiform fibrohistiocytic tumor and addition of 66 new cases from the Armed Forces Institute of Pathology, in honor of Franz M. Enzinger, MD. Ann Diagn Pathol 11 (5): 313-9, 2007. [PUBMED Abstract]
- Billings SD, Folpe AL: Cutaneous and subcutaneous fibrohistiocytic tumors of intermediate malignancy: an update. Am J Dermatopathol 26 (2): 141-55, 2004. [PUBMED Abstract]
- Remstein ED, Arndt CA, Nascimento AG: Plexiform fibrohistiocytic tumor: clinicopathologic analysis of 22 cases. Am J Surg Pathol 23 (6): 662-70, 1999. [PUBMED Abstract]
- Salomao DR, Nascimento AG: Plexiform fibrohistiocytic tumor with systemic metastases: a case report. Am J Surg Pathol 21 (4): 469-76, 1997. [PUBMED Abstract]
- Redlich GC, Montgomery KD, Allgood GA, et al.: Plexiform fibrohistiocytic tumor with a clonal cytogenetic anomaly. Cancer Genet Cytogenet 108 (2): 141-3, 1999. [PUBMED Abstract]
- Luzar B, Calonje E: Cutaneous fibrohistiocytic tumours - an update. Histopathology 56 (1): 148-65, 2010. [PUBMED Abstract]
- Randall RL, Albritton KH, Ferney BJ, et al.: Malignant fibrous histiocytoma of soft tissue: an abandoned diagnosis. Am J Orthop 33 (12): 602-8, 2004. [PUBMED Abstract]
- Alaggio R, Collini P, Randall RL, et al.: Undifferentiated high-grade pleomorphic sarcomas in children: a clinicopathologic study of 10 cases and review of literature. Pediatr Dev Pathol 13 (3): 209-17, 2010 May-Jun. [PUBMED Abstract]
- Daw NC, Billups CA, Pappo AS, et al.: Malignant fibrous histiocytoma and other fibrohistiocytic tumors in pediatric patients: the St. Jude Children's Research Hospital experience. Cancer 97 (11): 2839-47, 2003. [PUBMED Abstract]
- Carli M, Ferrari A, Mattke A, et al.: Pediatric malignant peripheral nerve sheath tumor: the Italian and German soft tissue sarcoma cooperative group. J Clin Oncol 23 (33): 8422-30, 2005. [PUBMED Abstract]
- Hagel C, Zils U, Peiper M, et al.: Histopathology and clinical outcome of NF1-associated vs. sporadic malignant peripheral nerve sheath tumors. J Neurooncol 82 (2): 187-92, 2007. [PUBMED Abstract]
- Zou C, Smith KD, Liu J, et al.: Clinical, pathological, and molecular variables predictive of malignant peripheral nerve sheath tumor outcome. Ann Surg 249 (6): 1014-22, 2009. [PUBMED Abstract]
- Okada K, Hasegawa T, Tajino T, et al.: Clinical relevance of pathological grades of malignant peripheral nerve sheath tumor: a multi-institution TMTS study of 56 cases in Northern Japan. Ann Surg Oncol 14 (2): 597-604, 2007. [PUBMED Abstract]
- Ferrari A, Bisogno G, Macaluso A, et al.: Soft-tissue sarcomas in children and adolescents with neurofibromatosis type 1. Cancer 109 (7): 1406-12, 2007. [PUBMED Abstract]
- Ladanyi M, Lui MY, Antonescu CR, et al.: The der(17)t(X;17)(p11;q25) of human alveolar soft part sarcoma fuses the TFE3 transcription factor gene to ASPL, a novel gene at 17q25. Oncogene 20 (1): 48-57, 2001. [PUBMED Abstract]
- Williams A, Bartle G, Sumathi VP, et al.: Detection of ASPL/TFE3 fusion transcripts and the TFE3 antigen in formalin-fixed, paraffin-embedded tissue in a series of 18 cases of alveolar soft part sarcoma: useful diagnostic tools in cases with unusual histological features. Virchows Arch 458 (3): 291-300, 2011. [PUBMED Abstract]
- Kayton ML, Meyers P, Wexler LH, et al.: Clinical presentation, treatment, and outcome of alveolar soft part sarcoma in children, adolescents, and young adults. J Pediatr Surg 41 (1): 187-93, 2006. [PUBMED Abstract]
- Argani P, Antonescu CR, Illei PB, et al.: Primary renal neoplasms with the ASPL-TFE3 gene fusion of alveolar soft part sarcoma: a distinctive tumor entity previously included among renal cell carcinomas of children and adolescents. Am J Pathol 159 (1): 179-92, 2001. [PUBMED Abstract]
- Casanova M, Ferrari A, Bisogno G, et al.: Alveolar soft part sarcoma in children and adolescents: A report from the Soft-Tissue Sarcoma Italian Cooperative Group. Ann Oncol 11 (11): 1445-9, 2000. [PUBMED Abstract]
- Pennacchioli E, Fiore M, Collini P, et al.: Alveolar soft part sarcoma: clinical presentation, treatment, and outcome in a series of 33 patients at a single institution. Ann Surg Oncol 17 (12): 3229-33, 2010. [PUBMED Abstract]
- Orbach D, Brennan B, Casanova M, et al.: Paediatric and adolescent alveolar soft part sarcoma: A joint series from European cooperative groups. Pediatr Blood Cancer 60 (11): 1826-32, 2013. [PUBMED Abstract]
- Roozendaal KJ, de Valk B, ten Velden JJ, et al.: Alveolar soft-part sarcoma responding to interferon alpha-2b. Br J Cancer 89 (2): 243-5, 2003. [PUBMED Abstract]
- Conde N, Cruz O, Albert A, et al.: Antiangiogenic treatment as a pre-operative management of alveolar soft-part sarcoma. Pediatr Blood Cancer 57 (6): 1071-3, 2011. [PUBMED Abstract]
- Kummar S, Allen D, Monks A, et al.: Cediranib for metastatic alveolar soft part sarcoma. J Clin Oncol 31 (18): 2296-302, 2013. [PUBMED Abstract]
- Lieberman PH, Brennan MF, Kimmel M, et al.: Alveolar soft-part sarcoma. A clinico-pathologic study of half a century. Cancer 63 (1): 1-13, 1989. [PUBMED Abstract]
- Speleman F, Delattre O, Peter M, et al.: Malignant melanoma of the soft parts (clear-cell sarcoma): confirmation of EWS and ATF-1 gene fusion caused by a t(12;22) translocation. Mod Pathol 10 (5): 496-9, 1997. [PUBMED Abstract]
- Blazer DG 3rd, Lazar AJ, Xing Y, et al.: Clinical outcomes of molecularly confirmed clear cell sarcoma from a single institution and in comparison with data from the Surveillance, Epidemiology, and End Results registry. Cancer 115 (13): 2971-9, 2009. [PUBMED Abstract]
- Coindre JM, Hostein I, Terrier P, et al.: Diagnosis of clear cell sarcoma by real-time reverse transcriptase-polymerase chain reaction analysis of paraffin embedded tissues: clinicopathologic and molecular analysis of 44 patients from the French sarcoma group. Cancer 107 (5): 1055-64, 2006. [PUBMED Abstract]
- Ferrari A, Casanova M, Bisogno G, et al.: Clear cell sarcoma of tendons and aponeuroses in pediatric patients: a report from the Italian and German Soft Tissue Sarcoma Cooperative Group. Cancer 94 (12): 3269-76, 2002. [PUBMED Abstract]
- Karita M, Tsuchiya H, Yamamoto N, et al.: Caffeine-potentiated chemotherapy for clear cell sarcoma: a report of five cases. Int J Clin Oncol 18 (1): 33-7, 2013. [PUBMED Abstract]
- Leuschner I, Radig K, Harms D: Desmoplastic small round cell tumor. Semin Diagn Pathol 13 (3): 204-12, 1996. [PUBMED Abstract]
- Kushner BH, LaQuaglia MP, Wollner N, et al.: Desmoplastic small round-cell tumor: prolonged progression-free survival with aggressive multimodality therapy. J Clin Oncol 14 (5): 1526-31, 1996. [PUBMED Abstract]
- Saab R, Khoury JD, Krasin M, et al.: Desmoplastic small round cell tumor in childhood: the St. Jude Children's Research Hospital experience. Pediatr Blood Cancer 49 (3): 274-9, 2007. [PUBMED Abstract]
- Arora VC, Price AP, Fleming S, et al.: Characteristic imaging features of desmoplastic small round cell tumour. Pediatr Radiol 43 (1): 93-102, 2013. [PUBMED Abstract]
- Gerald WL, Ladanyi M, de Alava E, et al.: Clinical, pathologic, and molecular spectrum of tumors associated with t(11;22)(p13;q12): desmoplastic small round-cell tumor and its variants. J Clin Oncol 16 (9): 3028-36, 1998. [PUBMED Abstract]
- Hayes-Jordan A, Green H, Ludwig J, et al.: Toxicity of hyperthermic intraperitoneal chemotherapy (HIPEC) in pediatric patients with sarcomatosis/carcinomatosis: early experience and phase 1 results. Pediatr Blood Cancer 59 (2): 395-7, 2012. [PUBMED Abstract]
- Lal DR, Su WT, Wolden SL, et al.: Results of multimodal treatment for desmoplastic small round cell tumors. J Pediatr Surg 40 (1): 251-5, 2005. [PUBMED Abstract]
- Philippe-Chomette P, Kabbara N, Andre N, et al.: Desmoplastic small round cell tumors with EWS-WT1 fusion transcript in children and young adults. Pediatr Blood Cancer 58 (6): 891-7, 2012. [PUBMED Abstract]
- Schwarz RE, Gerald WL, Kushner BH, et al.: Desmoplastic small round cell tumors: prognostic indicators and results of surgical management. Ann Surg Oncol 5 (5): 416-22, 1998 Jul-Aug. [PUBMED Abstract]
- Goodman KA, Wolden SL, La Quaglia MP, et al.: Whole abdominopelvic radiotherapy for desmoplastic small round-cell tumor. Int J Radiat Oncol Biol Phys 54 (1): 170-6, 2002. [PUBMED Abstract]
- Chbani L, Guillou L, Terrier P, et al.: Epithelioid sarcoma: a clinicopathologic and immunohistochemical analysis of 106 cases from the French sarcoma group. Am J Clin Pathol 131 (2): 222-7, 2009. [PUBMED Abstract]
- Hornick JL, Dal Cin P, Fletcher CD: Loss of INI1 expression is characteristic of both conventional and proximal-type epithelioid sarcoma. Am J Surg Pathol 33 (4): 542-50, 2009. [PUBMED Abstract]
- Casanova M, Ferrari A, Collini P, et al.: Epithelioid sarcoma in children and adolescents: a report from the Italian Soft Tissue Sarcoma Committee. Cancer 106 (3): 708-17, 2006. [PUBMED Abstract]
- Guzzetta AA, Montgomery EA, Lyu H, et al.: Epithelioid sarcoma: one institution's experience with a rare sarcoma. J Surg Res 177 (1): 116-22, 2012. [PUBMED Abstract]
- Martignoni G, Pea M, Reghellin D, et al.: Molecular pathology of lymphangioleiomyomatosis and other perivascular epithelioid cell tumors. Arch Pathol Lab Med 134 (1): 33-40, 2010. [PUBMED Abstract]
- Bissler JJ, McCormack FX, Young LR, et al.: Sirolimus for angiomyolipoma in tuberous sclerosis complex or lymphangioleiomyomatosis. N Engl J Med 358 (2): 140-51, 2008. [PUBMED Abstract]
- Davies DM, Johnson SR, Tattersfield AE, et al.: Sirolimus therapy in tuberous sclerosis or sporadic lymphangioleiomyomatosis. N Engl J Med 358 (2): 200-3, 2008. [PUBMED Abstract]
- Folpe A, Inwards C, eds.: Bone and Soft Tissue Pathology: A Volume in the Foundations in Diagnostic Pathology. Philadelphia, Pa: WB Saunders Co, 2010.
- Armah HB, Parwani AV: Perivascular epithelioid cell tumor. Arch Pathol Lab Med 133 (4): 648-54, 2009. [PUBMED Abstract]
- Kodet R, Newton WA Jr, Sachs N, et al.: Rhabdoid tumors of soft tissues: a clinicopathologic study of 26 cases enrolled on the Intergroup Rhabdomyosarcoma Study. Hum Pathol 22 (7): 674-84, 1991. [PUBMED Abstract]
- Biegel JA, Zhou JY, Rorke LB, et al.: Germ-line and acquired mutations of INI1 in atypical teratoid and rhabdoid tumors. Cancer Res 59 (1): 74-9, 1999. [PUBMED Abstract]
- Eaton KW, Tooke LS, Wainwright LM, et al.: Spectrum of SMARCB1/INI1 mutations in familial and sporadic rhabdoid tumors. Pediatr Blood Cancer 56 (1): 7-15, 2011. [PUBMED Abstract]
- Lee RS, Stewart C, Carter SL, et al.: A remarkably simple genome underlies highly malignant pediatric rhabdoid cancers. J Clin Invest 122 (8): 2983-8, 2012. [PUBMED Abstract]
- Sajedi M, Wolff JE, Egeler RM, et al.: Congenital extrarenal non-central nervous system malignant rhabdoid tumor. J Pediatr Hematol Oncol 24 (4): 316-20, 2002. [PUBMED Abstract]
- Sultan I, Qaddoumi I, Rodríguez-Galindo C, et al.: Age, stage, and radiotherapy, but not primary tumor site, affects the outcome of patients with malignant rhabdoid tumors. Pediatr Blood Cancer 54 (1): 35-40, 2010. [PUBMED Abstract]
- Puri DR, Meyers PA, Kraus DH, et al.: Radiotherapy in the multimodal treatment of extrarenal extracranial malignant rhabdoid tumors. Pediatr Blood Cancer 50 (1): 167-9, 2008. [PUBMED Abstract]
- Madigan CE, Armenian SH, Malogolowkin MH, et al.: Extracranial malignant rhabdoid tumors in childhood: the Childrens Hospital Los Angeles experience. Cancer 110 (9): 2061-6, 2007. [PUBMED Abstract]
- Bourdeaut F, Fréneaux P, Thuille B, et al.: Extra-renal non-cerebral rhabdoid tumours. Pediatr Blood Cancer 51 (3): 363-8, 2008. [PUBMED Abstract]
- Tsuneyoshi M, Enjoji M, Iwasaki H, et al.: Extraskeletal myxoid chondrosarcoma--a clinicopathologic and electron microscopic study. Acta Pathol Jpn 31 (3): 439-47, 1981. [PUBMED Abstract]
- Hachitanda Y, Tsuneyoshi M, Daimaru Y, et al.: Extraskeletal myxoid chondrosarcoma in young children. Cancer 61 (12): 2521-6, 1988. [PUBMED Abstract]
- Hisaoka M, Ishida T, Imamura T, et al.: TFG is a novel fusion partner of NOR1 in extraskeletal myxoid chondrosarcoma. Genes Chromosomes Cancer 40 (4): 325-8, 2004. [PUBMED Abstract]
- Enzinger FM, Shiraki M: Extraskeletal myxoid chondrosarcoma. An analysis of 34 cases. Hum Pathol 3 (3): 421-35, 1972. [PUBMED Abstract]
- McGrory JE, Rock MG, Nascimento AG, et al.: Extraskeletal myxoid chondrosarcoma. Clin Orthop Relat Res (382): 185-90, 2001. [PUBMED Abstract]
- Drilon AD, Popat S, Bhuchar G, et al.: Extraskeletal myxoid chondrosarcoma: a retrospective review from 2 referral centers emphasizing long-term outcomes with surgery and chemotherapy. Cancer 113 (12): 3364-71, 2008. [PUBMED Abstract]
- Sultan I, Rodriguez-Galindo C, Saab R, et al.: Comparing children and adults with synovial sarcoma in the Surveillance, Epidemiology, and End Results program, 1983 to 2005: an analysis of 1268 patients. Cancer 115 (15): 3537-47, 2009. [PUBMED Abstract]
- van de Rijn M, Barr FG, Xiong QB, et al.: Poorly differentiated synovial sarcoma: an analysis of clinical, pathologic, and molecular genetic features. Am J Surg Pathol 23 (1): 106-12, 1999. [PUBMED Abstract]
- van de Rijn M, Barr FG, Collins MH, et al.: Absence of SYT-SSX fusion products in soft tissue tumors other than synovial sarcoma. Am J Clin Pathol 112 (1): 43-9, 1999. [PUBMED Abstract]
- Krsková L, Sumerauer D, Stejskalová E, et al.: A novel variant of SYT-SSX1 fusion gene in a case of spindle cell synovial sarcoma. Diagn Mol Pathol 16 (3): 179-83, 2007. [PUBMED Abstract]
- Su L, Sampaio AV, Jones KB, et al.: Deconstruction of the SS18-SSX fusion oncoprotein complex: insights into disease etiology and therapeutics. Cancer Cell 21 (3): 333-47, 2012. [PUBMED Abstract]
- Arnold MA, Arnold CA, Li G, et al.: A unique pattern of INI1 immunohistochemistry distinguishes synovial sarcoma from its histologic mimics. Hum Pathol 44 (5): 881-7, 2013. [PUBMED Abstract]
- Pappo AS, Fontanesi J, Luo X, et al.: Synovial sarcoma in children and adolescents: the St Jude Children's Research Hospital experience. J Clin Oncol 12 (11): 2360-6, 1994. [PUBMED Abstract]
- Ferrari A, De Salvo GL, Oberlin O, et al.: Synovial sarcoma in children and adolescents: a critical reappraisal of staging investigations in relation to the rate of metastatic involvement at diagnosis. Eur J Cancer 48 (9): 1370-5, 2012. [PUBMED Abstract]
- Brecht IB, Ferrari A, Int-Veen C, et al.: Grossly-resected synovial sarcoma treated by the German and Italian Pediatric Soft Tissue Sarcoma Cooperative Groups: discussion on the role of adjuvant therapies. Pediatr Blood Cancer 46 (1): 11-7, 2006. [PUBMED Abstract]
- Stanelle EJ, Christison-Lagay ER, Healey JH, et al.: Pediatric and adolescent synovial sarcoma: multivariate analysis of prognostic factors and survival outcomes. Ann Surg Oncol 20 (1): 73-9, 2013. [PUBMED Abstract]
- Trassard M, Le Doussal V, Hacène K, et al.: Prognostic factors in localized primary synovial sarcoma: a multicenter study of 128 adult patients. J Clin Oncol 19 (2): 525-34, 2001. [PUBMED Abstract]
- Guillou L, Benhattar J, Bonichon F, et al.: Histologic grade, but not SYT-SSX fusion type, is an important prognostic factor in patients with synovial sarcoma: a multicenter, retrospective analysis. J Clin Oncol 22 (20): 4040-50, 2004. [PUBMED Abstract]
- Ferrari A, Gronchi A, Casanova M, et al.: Synovial sarcoma: a retrospective analysis of 271 patients of all ages treated at a single institution. Cancer 101 (3): 627-34, 2004. [PUBMED Abstract]
- Lagarde P, Przybyl J, Brulard C, et al.: Chromosome instability accounts for reverse metastatic outcomes of pediatric and adult synovial sarcomas. J Clin Oncol 31 (5): 608-15, 2013. [PUBMED Abstract]
- McGrory JE, Pritchard DJ, Arndt CA, et al.: Nonrhabdomyosarcoma soft tissue sarcomas in children. The Mayo Clinic experience. Clin Orthop (374): 247-58, 2000. [PUBMED Abstract]
- Van Glabbeke M, van Oosterom AT, Oosterhuis JW, et al.: Prognostic factors for the outcome of chemotherapy in advanced soft tissue sarcoma: an analysis of 2,185 patients treated with anthracycline-containing first-line regimens--a European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study. J Clin Oncol 17 (1): 150-7, 1999. [PUBMED Abstract]
- Koscielniak E, Harms D, Henze G, et al.: Results of treatment for soft tissue sarcoma in childhood and adolescence: a final report of the German Cooperative Soft Tissue Sarcoma Study CWS-86. J Clin Oncol 17 (12): 3706-19, 1999. [PUBMED Abstract]
- Pappo AS, Devidas M, Jenkins J, et al.: Phase II trial of neoadjuvant vincristine, ifosfamide, and doxorubicin with granulocyte colony-stimulating factor support in children and adolescents with advanced-stage nonrhabdomyosarcomatous soft tissue sarcomas: a Pediatric Oncology Group Study. J Clin Oncol 23 (18): 4031-8, 2005. [PUBMED Abstract]
- Okcu MF, Despa S, Choroszy M, et al.: Synovial sarcoma in children and adolescents: thirty three years of experience with multimodal therapy. Med Pediatr Oncol 37 (2): 90-6, 2001. [PUBMED Abstract]
- Pappo AS, Rao BN, Jenkins JJ, et al.: Metastatic nonrhabdomyosarcomatous soft-tissue sarcomas in children and adolescents: the St. Jude Children's Research Hospital experience. Med Pediatr Oncol 33 (2): 76-82, 1999. [PUBMED Abstract]
- Brennan B, Stevens M, Kelsey A, et al.: Synovial sarcoma in childhood and adolescence: a retrospective series of 77 patients registered by the Children's Cancer and Leukaemia Group between 1991 and 2006. Pediatr Blood Cancer 55 (1): 85-90, 2010. [PUBMED Abstract]
- Okcu MF, Munsell M, Treuner J, et al.: Synovial sarcoma of childhood and adolescence: a multicenter, multivariate analysis of outcome. J Clin Oncol 21 (8): 1602-11, 2003. [PUBMED Abstract]
- Ferrari A, Miceli R, Rey A, et al.: Non-metastatic unresected paediatric non-rhabdomyosarcoma soft tissue sarcomas: results of a pooled analysis from United States and European groups. Eur J Cancer 47 (5): 724-31, 2011. [PUBMED Abstract]
- Raney RB: Synovial sarcoma in young people: background, prognostic factors, and therapeutic questions. J Pediatr Hematol Oncol 27 (4): 207-11, 2005. [PUBMED Abstract]
- Orbach D, Mc Dowell H, Rey A, et al.: Sparing strategy does not compromise prognosis in pediatric localized synovial sarcoma: experience of the International Society of Pediatric Oncology, Malignant Mesenchymal Tumors (SIOP-MMT) Working Group. Pediatr Blood Cancer 57 (7): 1130-6, 2011. [PUBMED Abstract]
- Ladenstein R, Treuner J, Koscielniak E, et al.: Synovial sarcoma of childhood and adolescence. Report of the German CWS-81 study. Cancer 71 (11): 3647-55, 1993. [PUBMED Abstract]
- Ferrari A, De Salvo GL, Dall'Igna P, et al.: Salvage rates and prognostic factors after relapse in children and adolescents with initially localised synovial sarcoma. Eur J Cancer 48 (18): 3448-55, 2012. [PUBMED Abstract]
- Coffin CM, Dehner LP: Vascular tumors in children and adolescents: a clinicopathologic study of 228 tumors in 222 patients. Pathol Annu 28 Pt 1: 97-120, 1993. [PUBMED Abstract]
- Daller JA, Bueno J, Gutierrez J, et al.: Hepatic hemangioendothelioma: clinical experience and management strategy. J Pediatr Surg 34 (1): 98-105; discussion 105-6, 1999. [PUBMED Abstract]
- Ackermann O, Fabre M, Franchi S, et al.: Widening spectrum of liver angiosarcoma in children. J Pediatr Gastroenterol Nutr 53 (6): 615-9, 2011. [PUBMED Abstract]
- Lyons LL, North PE, Mac-Moune Lai F, et al.: Kaposiform hemangioendothelioma: a study of 33 cases emphasizing its pathologic, immunophenotypic, and biologic uniqueness from juvenile hemangioma. Am J Surg Pathol 28 (5): 559-68, 2004. [PUBMED Abstract]
- Hu B, Lachman R, Phillips J, et al.: Kasabach-Merritt syndrome-associated kaposiform hemangioendothelioma successfully treated with cyclophosphamide, vincristine, and actinomycin D. J Pediatr Hematol Oncol 20 (6): 567-9, 1998 Nov-Dec. [PUBMED Abstract]
- Deb G, Jenkner A, De Sio L, et al.: Spindle cell (Kaposiform) hemangioendothelioma with Kasabach-Merritt syndrome in an infant: successful treatment with alpha-2A interferon. Med Pediatr Oncol 28 (5): 358-61, 1997. [PUBMED Abstract]
- Raabe EH, Keefer JR, Mitchell SE, et al.: Subtotal splenic embolization is a safe and effective treatment for isolated splenic vascular tumors associated with consumptive coagulopathy. J Pediatr Hematol Oncol 33 (5): 383-6, 2011. [PUBMED Abstract]
- Fernandez-Pineda I, Lopez-Gutierrez JC, Chocarro G, et al.: Long-term outcome of vincristine-aspirin-ticlopidine (VAT) therapy for vascular tumors associated with Kasabach-Merritt phenomenon. Pediatr Blood Cancer 60 (9): 1478-81, 2013. [PUBMED Abstract]
- Makhlouf HR, Ishak KG, Goodman ZD: Epithelioid hemangioendothelioma of the liver: a clinicopathologic study of 137 cases. Cancer 85 (3): 562-82, 1999. [PUBMED Abstract]
- Pinet C, Magnan A, Garbe L, et al.: Aggressive form of pleural epithelioid haemangioendothelioma: complete response after chemotherapy. Eur Respir J 14 (1): 237-8, 1999. [PUBMED Abstract]
- Hammill AM, Wentzel M, Gupta A, et al.: Sirolimus for the treatment of complicated vascular anomalies in children. Pediatr Blood Cancer 57 (6): 1018-24, 2011. [PUBMED Abstract]
- Deyrup AT, Miettinen M, North PE, et al.: Angiosarcomas arising in the viscera and soft tissue of children and young adults: a clinicopathologic study of 15 cases. Am J Surg Pathol 33 (2): 264-9, 2009. [PUBMED Abstract]
- Al Dhaybi R, Agoumi M, Powell J, et al.: Lymphangiosarcoma complicating extensive congenital mixed vascular malformations. Lymphat Res Biol 8 (3): 175-9, 2010. [PUBMED Abstract]
- Rossi S, Fletcher CD: Angiosarcoma arising in hemangioma/vascular malformation: report of four cases and review of the literature. Am J Surg Pathol 26 (10): 1319-29, 2002. [PUBMED Abstract]
- Lezama-del Valle P, Gerald WL, Tsai J, et al.: Malignant vascular tumors in young patients. Cancer 83 (8): 1634-9, 1998. [PUBMED Abstract]
- Fata F, O'Reilly E, Ilson D, et al.: Paclitaxel in the treatment of patients with angiosarcoma of the scalp or face. Cancer 86 (10): 2034-7, 1999. [PUBMED Abstract]
- Ferrari A, Casanova M, Bisogno G, et al.: Malignant vascular tumors in children and adolescents: a report from the Italian and German Soft Tissue Sarcoma Cooperative Group. Med Pediatr Oncol 39 (2): 109-14, 2002. [PUBMED Abstract]
- Lahat G, Dhuka AR, Hallevi H, et al.: Angiosarcoma: clinical and molecular insights. Ann Surg 251 (6): 1098-106, 2010. [PUBMED Abstract]
- Orlando G, Adam R, Mirza D, et al.: Hepatic hemangiosarcoma: an absolute contraindication to liver transplantation--the European Liver Transplant Registry experience. Transplantation 95 (6): 872-7, 2013. [PUBMED Abstract]
- Bien E, Kazanowska B, Dantonello T, et al.: Factors predicting survival in childhood malignant and intermediate vascular tumors : retrospective analysis of the Polish and German cooperative paediatric soft tissue sarcoma study groups and review of the literature. Ann Surg Oncol 17 (7): 1878-89, 2010. [PUBMED Abstract]
- Park MS, Ravi V, Araujo DM: Inhibiting the VEGF-VEGFR pathway in angiosarcoma, epithelioid hemangioendothelioma, and hemangiopericytoma/solitary fibrous tumor. Curr Opin Oncol 22 (4): 351-5, 2010. [PUBMED Abstract]
- Rodriguez-Galindo C, Ramsey K, Jenkins JJ, et al.: Hemangiopericytoma in children and infants. Cancer 88 (1): 198-204, 2000. [PUBMED Abstract]
- Ferrari A, Casanova M, Bisogno G, et al.: Hemangiopericytoma in pediatric ages: a report from the Italian and German Soft Tissue Sarcoma Cooperative Group. Cancer 92 (10): 2692-8, 2001. [PUBMED Abstract]
- Bien E, Stachowicz-Stencel T, Godzinski J, et al.: Retrospective multi-institutional study on hemangiopericytoma in Polish children. Pediatr Int 51 (1): 19-24, 2009. [PUBMED Abstract]
- Weiss SW, Goldblum JR: Enzinger and Weiss's Soft Tissue Tumors. 4th ed. St. Louis, Mo: Mosby, 2001.