Chromosome translocation-mediated conversion of a tumor suppressor gene into a dominant oncogene: fusion of EWS1 to WT1 in desmoplastic small round cell tumors.
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Adolescent↗
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Results for “Sarcoma, Small Cell”
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Binarization of microarray data on the basis of a mixture model.
Although gathered as continuous data, expression measurements from gene microarrays may be quantized before downstream analysis and modeling. This is especially true for modeling gene prediction and genetic regulatory networks. Coarse quantization results in lower computational requirements, lower data requirements for model inference, and easier conceptualization. This paper proposes a mixture model for binarization. For each gene, the model, composed of a sum of two distributions, is fit to expression data for that gene, and data points are binarized according to the model. The mixture model is based on the assumption of multiplicative up-regulation. The proposed method is compared with mean and median binarization by comparing classification performance based on the binary data from the different methods. Classification is performed for simulated data generated from a microarray model studied previously and for cancer data arising from two studies involving hereditary breast cancer and small, round blue-cell tumors of childhood.
Breast Neoplasms↗
Synovial sarcoma mimicking desmoplastic small round-cell tumor: critical role for molecular diagnosis.
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Bone Neoplasms↗
Round cell sarcomas of possible myelomonocytic origin localized at the lip of aged dogs.
Four round cell tumors, situated at the lip of dogs older than 4 years of age, which could not be further classified, were examined light and electron microscopically, immunocytochemically and in part functionally and cytochemically. Immunocytochemically they were positive for vimentin, but negative for cytokeratin, desmin, neurofilament, synaptophysin, S-100 protein, neuron specific enolase, lysozyme, IgG and a pan-T-cell marker. Cell lines were established from two malignant neoplasms. In vitro, neoplastic cells had morphological, functional and cytochemical properties of myelomonocytic cells. A tumor cell-specific polyclonal rabbit antiserum reacted immunocytochemically positive with primary and recurrent tumors and metastases of the original and the three other round cell tumors. Immunoblotting demonstrated a main band with approximately 65-75 kDa. All four tumors were present in aged dogs and metastasized. They most likely represent a distinct group of malignant tumors among the canine round cell tumors.
Aging↗
[Chemotherapy for pulmonary metastases of soft tissue sarcoma].
The role and value of chemotherapy for soft tissue sarcomas remain unclear. Seventeen patients with pulmonary metastatic soft tissue sarcomas underwent treatment with chemotherapy, and the clinical efficacy and prognosis were studied. Six patients with synovial sarcomas, 4 with malignant fibrous histiocytomas, 4 with neurosarcomas, and the remaining 3 patients with leiomyosarcoma, extraskeletal osteosarcoma, and extraskeletal chondrosarcoma, were studied. Cases with small round cell sarcomas were excluded. The chemotherapy agents were ifosfamide in 10 cases, combination of ifosfamide and adriamycin in 5 cases, or cisplatin and adriamycin in 2 cases. Of the 17 patients, seven had partial responses radiographically and five had pulmonary metastases from synovial sarcoma. Eight patients underwent resection of pulmonary metastases following chemotherapy, and they were found to be residual tumor cells histologically. Twelve of the patients died of disease at 6-108 months (median, 30 months) from the time of the initial therapy, and five patients have survived from 1-53 months (median, 30 months). The absolute three-year survival rate, according to the Kaplan-Meier method, for all 17 patients was 39%. In the two cases with no change and progressive disease, all patients were dead within 2 years, while in the seven partial response cases, two patients were dead, four were alive with pulmonary metastases, and only one case was disease-free at this writing. The survival rate for patients with partial response was significantly higher than for patients with no response. Although the cure rate of pulmonary metastatic soft tissue sarcomas is still low, the combination of chemotherapy and surgery has been shown to result in prolonged survival.
Adult↗
Treatment of high-risk sarcomas in children and young adults: analysis of local control using intensive combined modality therapy.
Although combination chemotherapy and local irradiation are quite effective treatment for some children and young adults with small round cell sarcomas, high-risk patient groups, including patients with localized disease of the trunk and proximal extremity and those who present with metastases, continue to fare poorly with standard combined modality therapy. In an attempt to improve the local and systemic response of these tumors, an intensive treatment protocol was designed that integrates five cycles of chemotherapy with vincristine, doxorubicin, and cyclophosphamide (VADRIAC) plus radiation therapy to the primary tumor (55-60 Gy), bone, and soft tissue metastases (45-50 Gy). Patients achieving complete response to this induction therapy receive intensification treatment with total body irradiation (8.0 Gy), a cycle of VADRIAC, and autologous bone marrow transplantation. All treatment is completed within 6-7 months. From January 1983 to February 1986, 76 consecutive, previously untreated patients were entered in this study; 75 patients are evaluable. Twenty-five patients were diagnosed with rhabdomyosarcoma, 23 with Ewing's sarcoma, 15 with primitive neuroepithelioma, 12 with primitive sarcoma, and 1 patient with metastatic neuroblastoma. Forty-three patients (57%) had metastases at presentation. Overall, 68 of 75 patients (91%) achieved complete response. Fifty-eight of 61 patients with measurable soft tissue masses at the primary site had greater than or equal to 50% tumor reduction with two cycles of chemotherapy prior to local irradiation. Seven patients failed to have complete response at the primary site following five cycles of chemotherapy and local external beam irradiation, although 3 were subsequently rendered locally disease free by intraoperative radiotherapy (2 patients) or surgery (1 patient).(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
STUDIES ON IN VITRO GROWTH OF YOSHIDA SARCOMA CELLS. I. CULTURE OF A SMALL NUMBER OF CELLS WITH REFERENCES TO THE ROLE OF ERYTHROCYTES.
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Animals↗
Pitfalls in the detection of t(11;22) translocation by fluorescence in situ hybridization and RT-PCR: a single-blinded study.
The t(11;22) translocation is a diagnostic hallmark of various small round-cell tumors. This study correlates the performance of fluorescence in situ hybridization (FISH) and reverse transcription polymerase chain reaction (RT-PCR) in the detection of this translocation analyzing paraffin-embedded tissue specimens. As negative control samples, 10 cases of normal colon mucosa and 10 cases of colon carcinoma tissue were analyzed by FISH to determine a valid cutoff value for the diagnosis of a t(11;22) translocation. The mean number of false-positive nuclei differed significantly between disomic and polysomic control group cases (P=0.002). Therefore, the cutoff value was determined considering the pitfall polysomy. The analysis group consisted of 20 cases from the University of Düsseldorf and 10 cases from the University of Bonn. These cases were analyzed using PCR (Düsseldorf) and FISH (Bonn) using a single-blinded approach. Twenty-two cases (73.3%) were concordant in both methods. Five cases (16.7%) were discrepant, showing a positive result in FISH whereas PCR was negative. Three cases (10.0%) were analyzed by FISH, and PCR failed for nonoptimized tissue preparation. In conclusion, the detection of t(11;22) translocation is critically dependent on a thoroughly defined cutoff value for FISH and on appropriate tissue preparation for both methods. We recommend FISH as a sensitive screening tool in the detection of t(11;22) followed by subsequent PCR amplification of the specific chimeric transcript.
Adult↗
Experimental basis and clinical experience with non-cross-resistant combinations in solid tumours.
Experimental studies on anticancer drug resistance have shown that cisplatin and alkylating agents have a very low level of cross resistance towards heterocyclic agents such as anthracyclines, podophyllotoxins and vinca alkaloids. Based on this and on the model of Goldie and Coldman protocols using sequentially alternating non-cross-resistant combinations were given in testicular cancer, sarcomas and small cell bronchogenic carcinomas. Preliminary clinical results are presented here.
Animals↗
Diagnostic utility of MIC-2 immunocytochemical staining in the differential diagnosis of small blue cell tumors.
Ewing's sarcoma (ES) and peripheral neuroectodermal tumor (PNET) are considered in the differential diagnosis of small round blue cell tumors of infancy and childhood which includes neuroblastoma, rhabdomyosarcoma and malignant lymphoma. Fine-needle aspiration diagnosis of these neoplasms can be particularly difficult when the neoplasms are composed of poorly differentiated cells or fail to produce a stroma. MIC-2 is a highly sensitive and specific marker for the PNET/ES group of neoplasms and has been studied extensively in surgical pathology. Other small blue cell neoplasms including rhabdomyosarcoma, blastemal Wilm's tumor, and lymphoblastic lymphoma have also shown positivity, but the staining reactions are usually weak and focal. The utility of this marker in the differential of small blue cell neoplasms in cytologic material has not been examined. Twenty cases of small blue cell neoplasms obtained by fine-needle aspiration (FNA) were studied. MIC-2 antibody was applied retrospectively to formalin-fixed cell block material and destained alcohol-fixed and air-dried cytologic preparations. These cases include primitive neuroectodermal tumor (five cases), Ewing's sarcoma (two cases), neuroblastoma (four cases), Wilms's tumor (four cases), lymphoblastic lymphoma (two cases), and small-cell carcinoma (three cases). The cases were judged positive when the majority of the cells showed cytoplasmic staining. Diffuse cytoplasmic staining was observed in all seven cases of PNET/ES. Staining could be seen on the destained air-dried smears (three cases), fixed smears (two cases), or the cell block material (two cases). None of the other 13 small blue cell neoplasms showed positive staining. We conclude that MIC-2 is a sensitive and specific marker for the PNET/ES group of neoplasms in specimens from formalin-fixed cell block, air-dried, and alcohol-fixed cytologic material and is useful in the differential diagnosis of small blue cell tumors.
12E7 Antigen↗
High-dose chemotherapy with stem cell reinfusion and growth factor support for solid tumors.
With the help of stem cell reinfusion and hematopoietic growth factors, it is possible to get up to a ten-fold dose increase for certain chemotherapeutic drugs. A number of reasons may have made high-dose chemotherapy less dangerous and therefore more acceptable in a more upfront treatment setting. One of these is the addition of peripheral stem cell harvest obtained after mobilization with a hematopoietic growth factor alone or after chemotherapy followed by a hematopoietic growth factor, which seems to result in a faster recovery of neutrophils and platelets compared to bone marrow reinfusion alone. The combination of various hematopoietic growth factors could potentially improve hematopoietic recovery of the high-dose chemotherapy regimen. The relevance of tumor cells sometimes present in the reinfused hematopoietic stem cells is as yet unknown. High-dose chemotherapy may be interesting for a number of solid tumors such as nonseminomatous testicular carcinoma, breast carcinoma in the metastatic and adjuvant setting, ovarian carcinoma, tumors of young adults such as Ewing sarcoma and small cell lung carcinoma. In patients with refractory nonseminomatous testicular cancer there have been a number of studies performed with high-dose chemotherapy showing a 15% complete and prolonged remission. For other tumor types and settings it will be necessary to perform randomized studies before firm conclusions can be drawn. For example, this is especially important for patients with breast carcinoma with more than three positive axillary lymph nodes. Preliminary data from various groups compared to historical controls treated with standard adjuvant chemotherapy show favorable results of adjuvant chemotherapy containing high-dose chemotherapy. Many relatively small nonrandomized studies are performed in various stages of disease for ovarian carcinoma. Although there are long-term survivors reported it is currently difficult to draw firm conclusions. The potentially safer therapy of high-dose chemotherapy may reveal in the near future the role of high-dose chemotherapy in solid tumors.
Adult↗
Desmoplastic small round cell tumour in children and adolescents.
BACKGROUND: Desmoplastic small round cell tumour (DSRCT) is a rare highly aggressive neoplasm, and clinical studies are scarce. PROCEDURE: We report six cases of children and adolescents (median age 14 years, range 6.9-17.5) with DSRCT (5 abdominal, 1 paratesticular) registered by the Italian Cooperative Group (ICG) for soft tissue sarcoma over a 9-year period. Patients received a multidisciplinary treatment, including aggressive initial or delayed surgery and radiotherapy. Chemotherapy regimen was based on the use of ifosfamide, vincristine, dactinomycin, and a few doses of antharacyclines (doxorubicin or epirubicin). RESULTS: Complete surgical resection was possible only for the paratesticular tumour. Among the patients with abdominal lesions, macroscopically radical excision was possible in only one case. All patients received multidrug chemotherapy, and tumour reduction was obtained in the 4 evaluable patients. No relapses were evident in the irradiated fields in the 4 patients who received radiotherapy. Two patients remained progression-free 22 and 63 months after diagnosis, one is in third complete remission, whereas three died 10-25 months after diagnosis. CONCLUSIONS: DSRCT is a chemosensitive tumour, but survival rates remain disappointing despite aggressive multimodality therapy. Our results support surgical tumour removal and radiotherapy to achieve local control. Our experience and a review of the literature suggest that patients with localised abdominal tumours or a paratesticular primary may have a better prognosis.
Abdominal Neoplasms↗
Small round cell tumor with biphenotypic differentiation and variant of t(21;22)(q22;q12).
A 14-year-old boy presented with a soft tissue swelling on the outer aspect of his left upper arm. Examination of the tumor by light microscopy showed a small round cell tumor with a rare focus of myogenic differentiation. Myogenic differentiation was confirmed on ultrastructural examination by immunohistochemistry and reverse transcriptase polymerase chain reaction (RT-PCR). Conventional G-banding and fluorescent in situ hybridization (FISH) demonstrated a complex variant of t(21;22)(q22;q12). By RT-PCR, the EWS-ERG fusion transcript was defined as type 9e. This tumor was unusual in that it showed characteristics of myogenic and neural differentiation, and contained a rearrangement of the EWS gene consistent with a diagnosis of Ewing's sarcoma. This supports the hypothesis that a class of biphenotypic childhood sarcomas, with features of myogenic and neural differentiation, exists that may be related to the Ewing's sarcoma family of tumors.
Adolescent↗
Fine needle aspiration cytologic findings in malignant small cell tumor of the thoracopulmonary region (Askin tumor).
From 1980 to 1992, five cases of Askin tumor were diagnosed by fine needle aspiration cytology at the Shiraz University Hospitals, Namazi, Faghihi and Beheshti, Iran. All patients were female, their ages ranging between 15 and 22 years. Three of them had a mass on the right side and two on the left side of the chest. Chest roentgenography revealed no bone involvement. Two tumors involved the lungs and pleura. Urinary catecholamine levels were within normal limits. The fine needle aspiration smears revealed many small, round malignant cells with indistinct cytoplasm, a high nuclear/cytoplasmic ratio and prominent, multiple nucleoli. Homer-Wright rosettes were seen frequently. The cells were often arranged in rows simulating rouleaux formation. They were positively stained by periodic acid-Schiff stain. The histologic sections confirmed the cytologic diagnosis of Askin tumor. Four of the patients died within 7-11 months after treatment began.
Adolescent↗
Ca125 and neuron-specific enolase (NSE) as tumour markers for intra-abdominal desmoplastic small round-cell tumours.
Seven consecutive patients with intra-abdominal desmoplastic small round-cell tumours were screened at presentation for carcinoembryonic antigen (CEA), Ca19-9, Ca15-3, Ca125, alpha-fetoprotein (AFP), human chorionic gonadotrophin (hCG) and neuron-specific enolase (NSE). Initially elevated tumour markers were used to monitor therapy and follow-up. Tumour marker assays were all in the normal range, with the exception of Ca125 and NSE. The Ca125 level was initially high in six of the seven patients (86%) with a median value of 200 U ml-1 and a range of 22-735 U ml-1. The NSE value was elevated before therapy in three of the five patients (60%) for whom assay results were available, with a median of 19 ng ml-1 and a range of 6.8-37.5 ng ml-1 . Ca1 25 normalized in five out of six cases and NSE always normalized during chemotherapy, but neither of these two tumour markers correlated specifically with response, as only one patient experienced a partial response, five tumour stabilization and the remaining patient tumour progression. At progression, Ca125 was again elevated in two out of four cases several weeks before clinical relapse and NSE in only one out of three cases. Ca125 and NSE are frequently raised in the serum of patients with intra-abdominal desmoplastic small round-cell tumours before therapy, but are not reliable monitors of the course of the disease. However, normalization is frequently associated with an improvement of symptoms or a moderate clinical response.
Adolescent↗
Use of reverse transcriptase polymerase chain reaction for diagnosis and staging of alveolar rhabdomyosarcoma, Ewing sarcoma family of tumors, and desmoplastic small round cell tumor.
PURPOSE: To compare the use of reverse transcriptase polymerase chain reaction (RT-PCR) with that of morphology-based methods for diagnosis, staging, and detection of metastatic disease in pediatric alveolar rhabdomyosarcoma (ARMS), Ewing sarcoma family of tumors (ESFT), and desmoplastic small round cell tumors (DSRCT). MATERIALS AND METHODS: RT-PCR assays for the EWS-FLII, EWS-ERG, PAX3-FKHR, PAX7-FKHR, and EWS-WTI fusion transcripts were performed on RNA extracted from the primary tumor tissue, bone marrow, and body fluids obtained at initial presentation and relapse. Molecular findings were compared with original histologic diagnoses and results of staging procedures. RESULTS: Eighty-eight samples from 47 patients with ARMS (n = 13), ESFT (n = 31), or DSRCT (n = 3) were analyzed. The detection rate of metastatic disease was significantly higher with RT-PCR (95%) as compared with the morphologic methods (70%) for the three pediatric sarcomas studied. In primary tumors with characteristic fusion transcript, RT-PCR was positive in all cases with morphologic evidence of metastatic disease. Moreover, in six patients (3 with ARMS, 2 with DSRCT, and 1 with ESFT) with metastatic disease, micrometastases in bone marrow (4) and other sites (2) were detected by RT-PCR alone. Importantly, none of the patients with localized disease diagnosed had micrometastases detected by RT-PCR in bone marrow. CONCLUSIONS: The high sensitivity and specificity of RT-PCR for the characteristic fusion transcripts of pediatric sarcomas make it an ideal method to aid in the routine staging of these patients. In addition, the 100% sensitivity of RT-PCR in detection of micrometastasis makes it useful for follow-up and detection of minimal residual disease. However, the clinical significance of molecularly-detectable disease remains unknown. Further studies should aim to elucidate the therapeutic and prognostic implications of micrometastases detected by RT-PCR alone.
Biomarkers, Tumor↗
Disseminated intrathoracic desmoplastic small round-cell tumor: a case report.
PURPOSE: Recently recognized as a distinct clinicopathologic entity, desmoplastic small round-cell tumors typically affect young men. These aggressive tumors usually arise in the abdomen; other sites of primary disease have been described only rarely. We report the case of an extraabdominal primary tumor with widespread dissemination, including the subcutaneous tissue, a previously unrecognized metastatic site. PATIENT AND METHODS: We describe the case of a 16-year-old boy with a primary extraabdominal metastatic desmoplastic small round-cell tumor. RESULTS: Our patient had a primary intrathoracic desmoplastic small round-cell tumor and widespread dissemination involving the subcutaneous tissue, kidney, liver, bone, and lymph nodes. Histopathologic analysis found intense desmoplasia and polyphenotypic expression of neural, muscle, and epithelial markers. Reverse transcriptase-polymerase chain reaction analysis of fresh tumor tissue confirmed the characteristic EWS-WT1 transcript. CONCLUSIONS: Broader than originally anticipated, the clinical spectrum of desmoplastic small round-cell tumors continues to evolve. Primary intrathoracic tumors with soft-tissue dissemination and polyphenotypic expression should prompt suspicion of this malignancy. Molecular analysis of fresh tumor tissue is an important adjunct to diagnosing this rare neoplasm.
Adolescent↗
Development of B-cell lymphoma in homosexual men. Clinical and immunologic findings.
Serious infections, neoplasms, and immunologic abnormalities have been found in homosexual men. We describe the development of malignant lymphoma in six such patients, three of whom had persistent, generalized lymphadenopathy. In biopsies done before the lymphoma developed, the lymphadenopathy was characterized morphologically by a distinctive pattern of B-cell follicular hyperplasia. All lymphomas were of B-lymphocytic origin, including B-cell immunoblastic sarcoma; small noncleaved, Burkitt-like lymphoma; and plasmacytoid lymphocytic lymphoma. Extranodal presentation with B symptoms occurred in five patients. Median age of our patients was 33 years. Three patients had histories of repeated systemic infections. The peripheral blood lymphocyte count was depressed in four, with depression of OKT 4+ (helper phenotype) cell levels and reversal of the T-helper: T-suppressor ratio in all. We conclude that these patients are at risk for the development of abnormalities of the B-lymphocytic system, manifested by abnormal hyper-B-cell response in enlarged reactive lymph nodes and aggressive, extranodal B-cell lymphomas.
Adult↗