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PubMed2006

Epithelioid sarcoma in the thoracic spine.

Epithelioid sarcoma is a rare and highly malignant soft tissue tumor that is commonly found in the extremities and rarely in the trunk area. This malignant tumor often mimics granuloma or nodular fasciitis, which causes a delay in establishing the diagnosis. This type of cancer has a high recurrence rate. Surgical treatment requires wide radical resection. The objective of this case report is to highlight the unique location of a rare neoplasm and to illustrate the relentless course of epithelioid sarcoma despite initial radical resection. A 14-year-old boy was admitted to our facility with a soft tissue mass on the right lower thoracic spine. The large tumor mass had deeply penetrated into the muscles, infiltrated the neuroforamen of T9-T10 level, and compressed the dural sac. Immunohistological study of the biopsy was highly consistent with an epithelioid sarcoma. Wide excision of the mass, laminectomy and spine fusion with instrumentation was performed. The patient received chemotherapy and irradiation. The first recurrence of the neoplasm was seen as a contralateral metastasis 21 months after the resection. On the last follow-up, 3 years postoperatively, the patient was in a good general condition. However, further progression of the sarcoma had to be recognized. Our case encompasses multiple features that represent negative prognostic factors. Initial wide excision of the neoplasm and adjuvant therapy including chemotherapy and irradiation seem to slow down the relentless course of epithelioid sarcoma in the trunk.

Adolescent↗

PubMed2000

Undifferentiated spindle-cell sarcoma of the chest wall with vascular endothelial growth factor expression: report of a case.

The expressions of some growth factors have been immunohistochemically confirmed in several kinds of tumors, and in particular the expression of vascular endothelial growth factor (VEGF) has been reported to be closely related to tumor cell proliferation. We report herein a case of undifferentiated spindle-cell sarcoma arising in the chest wall with VEGF expression. A 67-year-old man, who presented with coughing, was found to have an abnormal shadow on his right chest wall. He was admitted to Chiba Rosai Hospital and preoperative diagnosis of the tumor was sarcoma. The tumor was thus resected along with the right chest wall and right lower lobe of the lung. Histopathologically, the tumor cells were spindle-shaped and showed severe atypism. The tumor cells were positive for vimentin and VEGF antibody with immunohistochemical staining, but they did not show differentiation to any special type of sarcoma. The tumor was diagnosed to be undifferentiated spindle-cell sarcoma. The microvessel density of the tumor was measured using CD34 and it was found to be higher than the average density of usual sarcomas. The prognosis of this case was poor. The patient died of tumor metastasis to the lung and bone 1 year later in spite of the fact that the tumor was resected.

Aged↗

PubMed2002

Ultrastructure of oral sarcoma.

Sarcoma of the oral region is extremely rare and ultrastructural studies of the tumor are limited in number. We collected oral sarcomas, such as fibrosarcoma, malignant fibrous histiocytoma, liposarcoma, leiomyosarcoma, rhabdomyosarcoma, angiosarcoma, alveolar soft-part sarcoma, solitary plasmacytoma, and osteosarcoma, and performed ultrastructural studies of these tumors. The value of these studies for an understanding of the biological behavior of the tumors was then investigated. In these studies, electron microscopic examinations of oral sarcoma were of assistance in our attempt to establish correct diagnosis and histogenesis. Data from the studies of oral sarcoma by light microscopy, electron microscopy, and immunohistochemistry should be accumulated.

Fibrosarcoma↗

PubMed2002

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.

Humans↗

PubMed2002

Real-time polymerase chain reaction as an aid for the detection of SYT-SSX1 and SYT-SSX2 transcripts in fresh and archival pediatric synovial sarcoma specimens: report of 25 cases from St. Jude Children's Research Hospital.

Synovial sarcoma is the most common nonrhabdomyosarcomatous soft tissue sarcoma in children and adolescents and is characterized by a reciprocal t(X;18)(p11;q11) which results in the fusion of the SYT gene on chromosome 18q11 to either of two closely related genes, SSX1 (Xp11.23) or SSX2 (Xp11.21). Detection of this translocation or its resultant gene fusion by molecular methods is helpful in the pathologic diagnosis of synovial sarcoma, especially in poorly differentiated tumors. This study was designed to evaluate the utility of a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay to detect and distinguish SYT-SSX1 and SYT-SSX2 fusions in fresh and archival specimens of synovial sarcoma in pediatric patients seen at St. Jude Children's Research Hospital. In addition, the clinicopathologic features of the tumors with SYT-SSX1 vs. SYT-SSX2 fusions were compared. The 25 patients studied had a median age of 13 years 9 months (range 5 to 19 years). Estimates of survival and event-free survival at 5 years were 78.7 +/- 10.5% and 56.2 +/- 13.2%, respectively. Seventeen (68%) tumors were monophasic, eight (32%) were biphasic. Seven tumors contained poorly differentiated areas. Positive results for either SYT-SSX1 or SYT-SSX2 were obtained in 21/25 (84%) cases. Three cases did not have a detectable gene fusion and one had no amplifiable RNA. SYT-SSX1 transcripts were found in 18/24 (75%) of the tumors while SYT-SSX2 transcripts were identified in 3/24 (12.5%). All of the poorly differentiated tumors and seven out of eight tumors from patients who developed lung metastases had an SYT-SSX1 fusion transcript. Real-time PCR is useful in detecting and distinguishing SYT-SSX1 from SYT-SSX2 gene fusions in synovial sarcoma. Valuable aspects of this methodology are the applicability to both frozen and formalin-fixed samples, decreased labor costs, and the rapidity of results. In addition, distinguishing SYT-SSX1 from SYT-SSX2 fusions with these methods allow for prospective collection of information that may clarify issues of prognostic relevance.

Adolescent↗

PubMed2005

Detection of SYT-SSX rearrangements in synovial sarcomas by real-time one-step RT-PCR.

Synovial sarcomas are aggressive tumors of adolescent and young adults that account for up to 10% of soft tissue sarcomas. Cytogenetically, they are characterized by translocation t(X;18), which is found in more than 95% of tumors. In most cases, it results in fusion of the SYT gene with the SSX1 or SSX2 gene, thus creating SYT-SSX1 or SYT-SSX2 rearrangement. The 2 types of gene fusion have been correlated with histologic variants and prognosis of synovial sarcomas. In this study, we developed a simple and rapid method for the simultaneous detection of SYT-SSX1 and SYT-SSX2 rearrangements by using a LightCycler real-time one-step reverse transcriptase polymerase chain reaction (RT-PCR) technology (Roche). Oligonucleotide probes were designed so that the donor probe would span a fusion point and the acceptor probe would be complementary to the SSX1 sequence but have 2 nucleotide mismatches with SSX2 sequence. Such a design allows simultaneous amplification of 2 types of rearrangement in the same reaction but distinguishes them based on differences in melting temperature detected by melting curve analysis after PCR. With this method, 27 tumors (9 synovial sarcomas and 18 nonsynovial sarcomas) were studied and showed SYT-SSX1 rearrangement in 6 cases and SYT-SSX2 in 3 cases. These results had complete correlation with the finding of conventional RT-PCR and direct sequencing. In conclusion, we have developed a fast, accurate, and simple method for the detection of 2 major types of SYT-SSX rearrangement by using LightCycler RT-PCR and melting curve analysis.

Biomarkers, Tumor↗

PubMed2003

Definitive intraoperative radiotherapy for musculoskeletal sarcomas and malignant lymphoma in combination with surgical excision.

BACKGROUND: . The purpose was to estimate retrospectively the outcome of patients with musculoskeletal sarcoma or malignant lymphoma treated with intraoperative radiotherapy (IORT). METHODS: Between 1988 and 1999, definitive IORT in combination with surgical excision was performed in 24 patients with musculoskeletal sarcoma (malignant fibrous histiocytoma, 10; osteosarcoma, 6; liposarcoma, 2; chondrosarcoma, 1; synovial sarcoma, 1; Ewing's sarcoma, 1; angiosarcoma, 1; epithelioid sarcoma, 1; malignant schwannoma, 1) and 3 patients with malignant lymphoma. The tumor was excised by marginal margin excision, intralesional margin excision, or wide margin excision; 15-45 Gy electrons was then delivered to the affected sites. RESULTS: In the 8 patients without distant metastases at the first visit, 4 patients are alive 6.5-11.5 years after IORT, and 4 patients died <4.5 years after IORT. The incidence of local recurrence was 13%. In the 19 patients with distant metastases at the first visit, 3 patients are alive 2.5-6.7 years after IORT, and 16 patients died 0.2-5.7 years after IORT. The incidence of local recurrence was 45%. Complications after IORT were found in 5 patients: neuropathy, 1 patient; skin necrosis, 1 patient; myelopathy, 1 patient; enteritis ileus, 1 patient; and edema, 1 patient. CONCLUSION: IORT with a radiation dose of 15-45 Gy in combination with surgical excision appeared to be useful for local control and to be more effective in patients without distant metastases at the first visit than in patients with distant metastases.

Adolescent↗

PubMed2000

Hyperthermic isolated limb perfusion with tumor necrosis factor-alpha and melphalan in advanced soft-tissue sarcomas: histopathological considerations.

BACKGROUND: Hyperthermic isolated limb perfusion with tumor necrosis factor-alpha and melphalan was used as induction treatment in locally advanced extremity soft-tissue sarcomas for limb sparing surgery. The typical histopathological changes that occur in these tumoral masses are described in a series of 30 patients. METHODS: Fresh tumor specimens of 27 high grade extensive soft-tissue sarcomas and 3 recurrent desmoid tumors of the extremities were collected 6 to 8 weeks after hyperthermic isolated limb perfusion with tumor necrosis factor-alpha plus melphalan. The specimens were studied for surgical margins, extent and type of tumor necrosis, lymph node involvement, perineural and vascular invasion, and the effects on adjacent normal tissues such as nerves, muscles, and blood vessels. RESULTS: The typical histological changes were central cystic hemorrhagic necrosis with pericystic extensive fibrosis. Some nonspecific changes were noted in the soft tissues around the mass. In eight cases, more than 90% necrosis was found. In 17 cases, the extent of necrosis ranged between 60% and 90% (80%-90% in 4 of 17 cases). In five cases, less than 60% necrosis was noted. The best responses (>90% necrosis) were observed in distally located tumors. The responsive types were malignant fibrous histiocytoma, followed by myxoid liposarcoma and synovial sarcoma. Desmoid tumors showed less necrosis than high grade sarcomas. Vascular invasion was observed in two cases and intralesional venous thrombosis in one case. No perineural invasion or lymph nodes involvement were observed. The soft tissues adjacent to the tumor bed did not show major morphological changes. No correlation was found between the histological changes and each of the following: the anatomical (upper vs. lower limb) or compartmental location of the tumor; whether the tumor was primary or recurrent; and the types of previous treatment (systemic chemotherapy or radiotherapy) and tumor size. CONCLUSIONS: This is the first serial histological description of the effects of tumor necrosis factor-alpha and melphalan administered via hyperthermic isolated limb perfusion on the tumoral masses of limb soft-tissue sarcomas. The small number of specimens and, especially, the variability of tumors preclude definite conclusions. Larger numbers and more homogeneity are needed in future studies.

Adolescent↗

PubMed2000

Retroperitoneal sarcomas.

The approach to the management of retroperitoneal tumors begins with a complete history and physical examination. Imaging of the abdomen and pelvis by computed tomography (CT) provides both an imaging modality and a method by which to obtain tissue for diagnosis. Because a histologic diagnosis is essential in treatment planning, adequate tissue can usually be obtained by a CT-guided core biopsy. If the diagnosis is sarcoma, additional tests necessary for staging include plain chest radiography and evaluation of the liver by either CT scan or magnetic resonance imaging (MRI). The treatment options for primary retroperitoneal sarcomas include chemotherapy, radiation therapy, surgery, or a combination of these modalities; therefore, a multidisciplinary group best manages treatment planning. Primary radiation therapy for cure is seldom effective for retroperitoneal sarcomas but can provide palliation in select cases. Systemic chemotherapy for chemosensitive lesions, such as poorly differentiated liposarcoma, malignant fibrous histiocytoma (MFH), synovial cell sarcoma, and primitive neuroectodermal tumors (PNET), can be useful when used in a neoadjuvant manner. Consequently, surgical resection continues to be the mainstay of treatment for retroperitoneal sarcomas and requires en bloc resection of the primary tumor. Frequently this includes adjacent organs such as colon, small bowel, kidney, adrenal, and pancreas. Postoperative adjuvant therapy with chemotherapy or radiation has not been proven to be of any additional benefit. Overall treatment results are predominantly influenced by tumor stage, grade, size, and margins of surgical resection. Follow-up CT scans at 6-month intervals and surgical resection of recurrences can be valuable.

Antineoplastic Agents↗

PubMed2005

The potential for molecular therapeutic targets in Ewing's sarcoma.

Ewing's sarcoma is an uncompromising tumor of children and young adults. Before the introduction of chemotherapy for Ewing's sarcoma, nearly all patients succumbed to their disease, even with highly aggressive approaches to local control. The realization that most patients have micrometastatic disease at presentation, and the identification of active chemotherapeutic agents for this tumor, have resulted in significant improvements in patient survival. Modern therapy for Ewing's sarcoma combines high-dose chemotherapy for systemic control of disease, with advanced surgical and/or radiation therapeutic approaches for local control. Current therapy remains imperfect. Despite optimal management, the cure rate for localized disease is only approximately 70%, whereas the cure rate for metastatic disease at presentation is less than 30%. Patients who experience long-term disease-free survival are at risk for significant side effects of therapy, including infertility, limb dysfunction, and an increased risk for second malignancies. More effective and less toxic therapies are needed. This report presents an overview of dysregulated molecular pathways in Ewing's sarcoma and highlights the possibility that they may serve as therapeutic targets for the disease. Although a great deal of additional investigation is required before most of these approaches can be assessed in the clinic, we think that these potential new targets offer a great deal of hope for patients with Ewing's sarcoma.

Adolescent↗

PubMed2002

Sarcomas of the head and neck.

Sarcomas of the head and neck are extremely rare, accounting for less than 1% of all neoplasms of the head and neck. These sarcomas arise in both soft tissues and bone and thus cannot be treated by a single approach. The clinical behavior of these tumors varies considerably. Patients with low-grade lesions are prone to local recurrence, whereas those with high-grade lesions develop both local recurrence and disseminated disease. An additional complicating factor is the multiple sites in which sarcomas may arise in the head and neck. All of these factors make it difficult to ascertain the optimal treatment approach for sarcomas. This article reviews the current literature (as well as the author's own experience) and provides a general treatment guideline for sarcomas of the head and neck.

Clinical Trials as Topic↗

PubMed2003

Immunity against soft-tissue sarcomas.

Recent advances in basic medical sciences have led to a deeper understanding of the molecular characteristics of soft-tissue sarcomas. Likewise, novel technologies have led to a better appreciation of the relationship between an antigenic stimulus and the subsequent immune response against the antigen. In the past few years, the intersection of the understanding of the immune system and the knowledge of sarcoma biology has become apparent. As seen with other forms of cancer, there is a detectable autologous immune response against sarcomas. It is the hope of many investigators that the hints of a tumor-specific immune response will be enough to generate a signal that can be amplified and directed against the host sarcoma. The data regarding the initial evidence of immune responses against sarcomas are reviewed in the context of current or potential clinical studies.

Antigens, Neoplasm↗

PubMed1981

Kaposi's sarcoma complicating corticosteroid therapy for temporal arteritis.

Combination immunosuppressive therapy, particularly in renal transplant recipients, is associated with a higher than expected risk of development of Kaposi's sarcoma, In this report, cutaneous dissemination of Kaposi's sarcoma occurred in a patient with temporal arteritis who was treated with corticosteroids. Reduction of the steroid dosage was followed by regression of the tumor. This sequence of events suggests a causal relationship between the evolution of the sarcoma and corticosteroid therapy. Although Kaposi's sarcoma may complicate corticosteroid therapy alone, the incidence is considerably lower than in renal transplant recipients receiving combination immunosuppressive therapy. Considering the large number of patients with temporal arteritis who are treated with steroids and that this is the first report of its association with Kaposi's sarcoma, it seems that other factors, perhaps genetic, might be important in the development of this neoplasm.

Aged↗

PubMed1982

Outbreak of Kaposi's sarcoma with cytomegalovirus infection in young homosexual men.

Kaposi's sarcoma, a multicentric malignant neoplasm, occurs in certain geographic areas in the world. It is most common in Equatorial Africa and Eastern Europe. The annual incidence of Kaposi's sarcoma in the United States is between 0.021 and 0.061 per 100,000 persons. The appearance of an outbreak of Kaposi's sarcoma in young homosexual men in New York and California is a new and unique phenomenon. Certain differences are already recognized between the disease in these young men and the ordinary Kaposi's sarcoma. Herein we report our observations of the first 10 cases of Kaposi's sarcoma in young homosexual men. In these patients, the disease follows an aggressive clinical course characterized by widespread skin lesions with early involvement of the lymph nodes. In some of these patients, the result was death in a short period of time after initial diagnosis. In addition, cytomegalovirus infections were seen in these patients, which suggests at least a possible association between this viral and the disease.

Adult↗

PubMed1983

Chemotherapy in advanced Kaposi's sarcoma. Implications for current cases in homosexual men.

Kaposi's sarcoma has recently appeared in an aggressive form in young, previously healthy, homosexual men. The disease in these patients corresponds most closely to disseminated Kaposi's sarcoma common in areas of Africa. This and the underlying acquired immune deficiency in the current patients in the United States affect the choice of appropriate therapy. Because Kaposi's sarcoma in these patients is rapidly progressive, it often requires aggressive systemic therapy, but this can be difficult given the patients' susceptibility to opportunistic infections. Reports from Africa suggest that Kaposi's sarcoma is very responsive to several chemotherapeutic agents, but these data must be interpreted cautiously because of problems in study design and differences between cases in Africa and the United States. This report reviews the clinical classification of Kaposi's sarcoma and the reported results of chemotherapy in patients with advanced disease. Implications of this experience in the treatment of recent cases in the United States are discussed.

Acquired Immunodeficiency Syndrome↗

PubMed1986

Characterization of a distinct subgroup of high-risk persons with Kaposi's sarcoma and good prognosis who present with normal T4 cell number and T4:T8 ratio and negative HTLV-III/LAV serologic test results.

Three homosexual male patients with biopsy-proved Kaposi's sarcoma were classified as having the acquired immune deficiency syndrome (AIDS) by Centers for Disease Control criteria when first seen in 1983 and 1984. These patients, however, differed from most patients with AIDS and Kaposi's sarcoma in having normal CD4 cell numbers and normal CD4:CD8 ratio. Furthermore, these immunologic parameters remained normal for eight to 24 months of follow-up, and the disease did not progress. Results of recent testing of serum from these patients were negative for HTLV-III/LAV antibodies. The Kaposi's sarcoma was limited to skin (stage I tumors) and the patients did not have persistent lymphadenopathy, fever, night sweats, or weight loss. In contrast to AIDS, the serum immunoglobulin levels (IgG, IgA, IgM) and number of B cells that were spontaneously forming immunoglobulin were within normal range with no evidence of polyclonal activation. The lymphocyte proliferative responses to phytohemagglutinin and Candida were reduced in two of the three patients, and skin test anergy was observed in the two patients tested. These findings are not frequently encountered in other healthy, homosexually active men or in classic Kaposi's sarcoma. They may be indicative of functional T cell changes (without numerical changes) induced by factors other than HTLV-III/LAV virus, which made these homosexually active men susceptible to development of low-grade Kaposi's sarcoma lesions.

Acquired Immunodeficiency Syndrome↗

PubMed1976

Adenosine phosphyorylase activity as distinct from inosine-guanosine phosphorylase activity in Sarcoma 180 cells and rat liver.

Adenosine phosphorylase (EC 2.4.2.-) activity present in Sarcoma 180 cells grown in culture and in rat liver, is shown to be distinct from inosine-guanosine phosphorylase by several criteria: (a) treatment of Sarcoma 180 cell extract with p-chloromercuribenzoate inhibited the two activities to a different extent, (b) adenine selectively protected the adenosine phosphorylase activity of Sarcoma 180 and rat liver extract against heat inactivation, while hypoxanthine selectively protected inosine-guanosine phosphorylase activity, (c) at nearly saturating substrate concentrations and using Sarcoma 180 extract, the rates of ribosylation of a mixture of adenine + hypoxanthine or adenine + guanine, but not of hypoxanthine + guanine, were found to be almost equal to the sum of their individual rates as measured separately, (d) inosine selectively inhibited the ribosylation of hypoxanthine and guanine catalysed by Sarcoma 180 and rat liver extract while 2-chloroadenosine selectively inhibited the ribosylation of adenine and N6-furfuryladenine, (e) pH vs. activity curves were similar with hypoxanthine or guanine as the substrate but they were markedly different from the curve with adenine as the substrate. The potential role of adenosine phosphorylase activity in vivo is discussed.

Adenine↗

PubMed1983

Reduced binding of epidermal growth factor by avian sarcoma virus-transformed rat cells.

Rat cells transformed by Rous sarcoma virus and Fujinami sarcoma virus bound 5-10% of the amount of epidermal growth factor (EGF) bound by normal cells. Scatchard plot analysis indicated that the reduction in binding by transformed cells was due to a decreased number of receptors rather than to altered binding affinity. In experiments with temperature sensitive mutants of Rous sarcoma virus and Fujinami sarcoma virus significant loss of EGF binding occurred within one hour of shift from non-permissive to permissive temperature. Conditioned media from various normal and transformed cell lines were examined for the ability to inhibit EGF binding to normal cells or to cause "down regulation" of EGF receptors. No activity of either type was found. EGF-dependent phosphorylation in isolated membrane preparations was also examined. Membranes from normal cells displayed EGF-dependent phosphorylation of a Mr 180,000 protein presumed to be the EGF receptor. This activity was absent in membranes from transformed cells. The data suggest a close correlation between activation of avian sarcoma virus transforming gene products and modulation of the EGF growth regulatory system.

Animals↗