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PubMed1998

Precursor B-Lymphoblastic lymphoma presenting as a solitary bone tumor and mimicking Ewing's sarcoma: a report of four cases and review of the literature.

Precursor B-lymphoblastic lymphoma (B-LBL) may present as a solitary bone tumor. Fewer than 10 cases with a proven precursor B-cell phenotype have been reported in the English literature. In this report, we describe four cases of B-lymphoblastic lymphoma presenting as a localized intraosseous mass, which clinically and histologically mimicked Ewing's sarcoma. Three tumors occurred in the tibia and one in the humerus. In all four cases, the initial diagnosis was either "Ewing's sarcoma" or "consistent with Ewing's sarcoma." All four patients were female. Three were children and one was an adult; mean age was 12.5 years (range, 4 to 31 years). All had extremity pain without significant constitutional symptoms. In three cases, the tumors were osteolytic on radiographic evaluation, and in one case, osteosclerotic. Immunohistochemical stains on paraffin-embedded tissue showed that the neoplastic cells expressed terminal deoxynucleotidyl transferase, CD43, vimentin, and CD99 (MIC2 gene product) in all cases. Three cases were negative for CD45. CD79a was positive in all four cases studied; however, CD20 (L26) was positive in only two of four cases. CD3 was negative in all cases. Two cases showed focal granular cytoplasmic staining for keratin. Two cases analyzed by polymerase chain reaction (PCR) revealed clonal rearrangement of the immunoglobulin heavy chain (IgH) gene. Follow-up revealed that the three pediatric patients, who received a high-dose multiagent chemotherapy regime for LBL, are disease free at follow-up intervals of more than 1, 11, and 12 years, respectively. The adult patient died two years after diagnosis with disseminated disease. Although rare, B-lymphoblastic lymphoma should be considered in the differential diagnosis of small round cell tumors of bone. A diagnosis of Ewing's sarcoma should be made only after complete immunophenotyping and, if necessary, molecular diagnostic tests to exclude lymphoblastic lymphoma. A limited panel of antibodies can lead to an erroneous diagnosis; B-lymphoblastic lymphoma may be negative for CD45 and CD20 but positive for CD99 and even for keratin, mimicking Ewing's sarcoma. Correct diagnosis is extremely important because LBL usually is curable in the pediatric age group with appropriate therapy.

Adult↗
PubMed1996

Embryonal rhabdomyosarcoma of the uterine corpus mistaken for small cell carcinoma: a case report.

Pure rhabdomyosarcomas of the female genital tract mostly occur in infancy and childhood, in the form of sarcoma botryoides (a variant of embryonal rhabdomyosarcoma), with vagina and cervix as typically involved sites. Such tumors rarely occur in the uterine corpus and cervix of adults. We would like to report a pure embryonal rhab-domyosarcoma of the uterine corpus that arose in a 31-year-old, gravida 1, para 1, female patient with widespread bony metastasis, and which was originally mistaken for metastatic small cell carcinoma to bone marrow.

Adult↗
PubMed2004

Targeting of EWS/FLI-1 by RNA interference attenuates the tumor phenotype of Ewing's sarcoma cells in vitro.

The defining cytogenetic abnormality of Ewing's sarcoma is the presence of a balanced t(11;22) translocation expressing the EWS/FLI-1 chimeric fusion protein. The effect of EWS/FLI-1 appears to be dominant negative since over-expression of EWS does not overcome the sarcoma phenotype. Previous studies have shown that EWS/FLI-1 as well as related sarcoma fusion proteins are necessary and sufficient to induce transformation both in vitro and in vivo. In this study we report that synthetic small interfering RNA (siRNA) specifically suppresses EWS/FLI-1 fusion gene expression in SK-ES Ewing's sarcoma cells. Knockdown of the EWS/FLI-1 fusion protein is correlated with decreased cell proliferation and increased apoptosis. We demonstrate that Ewing's sarcoma tumors as well as Ewing's sarcoma cell lines predominantly express the CXCR4 chemokine receptor. Using an in vitro invasion assay, the SDF-1 ligand of CXCR4 was shown to be a potent stimulus of invasion by SK-ES cells. Knockdown of EWS/FLI-1 by RNA interference abrogates the invasiveness of SK-ES cells. These experiments suggest that targeted silencing of the EWS/FLI-1 fusion gene by siRNA represents a promising strategy to study the loss of EWS/FLI-1 protein in Ewing's sarcoma cells of otherwise identical genetic background.

Antineoplastic Agents↗
PubMed1987

Synaptophysin--an immuno-histochemical marker for childhood neuroblastoma.

Synaptophysin, an integral membrane glycoprotein of presynaptic vesicles, was tested as an immuno-histochemical marker for childhood neuroblastoma. Synaptophysin immuno-reactivity was found in all neuroblastomas (6/6), but not in the other small round-cell tumors to be considered in its differential diagnosis. Thus, rhabdomyosarcomas (0/5), lymphomas (0/4), or Ewing's sarcomas (0/2) were negative for synaptophysin. The results suggest that synaptophysin is a useful marker for neuroblastoma, and it should belong to the marker panel used for the differential diagnosis of small round-cell tumors of childhood.

Adult↗
PubMed1991

Ewing's sarcoma.

Ewing's sarcoma and primitive neuroectodermal tumor are rare tumors of childhood, both considered to be small round blue cell tumors of childhood. Recent advances have been made regarding the histogenesis and biology of these tumors. Current thinking links Ewing's sarcoma and primitive neuroectodermal tumor by a shared chromosomal translocation and by evidence of neuroectodermal origin. Advances in chemotherapy have resulted in the cure of most patients presenting with Ewing's sarcoma. This review briefly outlines the year's literature on the histogenesis, biology, and treatment of this tumor.

Adolescent↗
PubMed1982

The number of nucleolar silver-stained granules of active nucleolus organizer regions in mitotic and interphase cells of rat Yoshida and Zajdela ascitic tumors.

To provide more information on the number of silver-stained granules (SSGs) of active mitotic nucleolus organizer regions (NORs) as well as interphase nucleoli, rat Yoshida ascitic sarcoma and Zajdela ascitic hepatoma cells were studied by means of standardized one-step and two-step silver-staining procedures. The number of SSGs of mitotic active NORs was relatively constant and corresponded to the number of active NORs of animals bearing the tumors investigated. Some anaphases and telophases were "asymmetric", i.e. chromosomal figures (future nuclei) in one and the same cell contained different number of SSGs (active NORs). The incidence of such asymetric anaphases and telophases was higher in aneuploid (hypoploid) Zajdela hepatoma than in euploid (diploid) Yoshida sarcoma cells. In the interphase, the number of SSGs was low in small or large cells with distinct chromocenters or chromosomes condensation presumably representing postmitotic and premitotic cells. In contrast, the highest number of SSGs was noted in nucleoli of large cells which were usually characterized by a fine chromatin structure.

Aneuploidy↗
PubMed1998

Detection of t(11;22)(q24;q12) translocation of Ewing's sarcoma in paraffin embedded tissue by nested reverse transcription-polymerase chain reaction.

Ewing's sarcoma is a poorly characterized malignant tumor with a relatively uniform histologic appearance, made up of densely packed small cells with round to oval nuclei, without distinct cell borders and without any structural differentiation. Often the diagnosis has to be made by exclusion. Recently, it has been made possible to identify characteristic chromosomal rearrangements associated with certain solid tumors. More than 85% of Ewing's sarcoma and peripheral neuroectodermal tumor present a specific t(11;22)(q24;q12) balanced translocation, resulting in the production of a novel chimerical EWS/FLI-1 message. Using oligonucleotide primers derived from EWS and FLI-1 complementary DNAs, we were able to use reverse transcription-polymerase chain reaction (RT-PCR) as a diagnostic tool. The described nested RT-PCR method as another supportive diagnostic method enables pathologists to differentiate small blue cell tumors not only to make correct diagnosis but also to investigate retrospective archival tumor samples, using formalin fixed paraffin embedded tissue as a source of RNA.

Chromosomes, Human, Pair 11↗
PubMed2004

Expression of the RNA-binding protein CRD-BP in brain and non-small cell lung tumors.

The coding region determinant-binding protein (CRD-BP) is an RNA binding protein that recognizes c-myc and IGF-II leader 3 mRNAs as well as the oncofetal H19 RNA. CRD-BP exhibits an oncofetal pattern of expression and has been detected in the majority of colon (81%), breast (58.5%) and sarcoma (73%) tumors. The study of CRD-BP expression was extended in brain tumors and Non small cell lung (NSCL) carcinomas and 12/24 malignant, 2/5 benign neuroepithelial tumors and 4/15 of NSCL carcinomas were found positive. All normal matching tissues tested were found negative. The highest frequency (60%) of CRD-BP positive tumors was observed in meningiomas, either benign (11/18) or atypical (3/3). These findings confirm that CRD-BP expression is restricted in tumors; the frequency of its de novo expression may vary according to tumor type and appears to be an early event in the transformation process.

Adenocarcinoma↗
PubMed1994

Cytogenetic analyses of four solid tumours in dogs.

Four solid tumours (one haemangiopericytoma, one haemangioendothelioma, one spindle-cell sarcoma and one mammary carcinoma) in dogs were analysed cytogenetically. In the haemangiopericytoma, an additional small chromosomal segment was present. Very complex changes including centric fusions and symmetric meta-centrics 1, 6, 10 and 12 were conspicuous in the highly unbalanced karyotype of the haemangioendothelioma. Complex changes, particularly many centric fusions and a tandem translocation 4/14, were features of the spindle-cell sarcoma. One centric fusion and a symmetric metacentric 13 were present in the mammary carcinoma.

Adenocarcinoma, Papillary↗
PubMed1984

New procedure for DNA transfection with polycation and dimethyl sulfoxide.

A new procedure for DNA transfection has been developed in a system of chicken embryo fibroblast cells and cloned Rous sarcoma virus DNA by using a polycation reagent as a mediator to adsorb DNA to the cell surface and dimethyl sulfoxide as an agent to facilitate the uptake of adsorbed DNA by the cells. In this new, simple, and convenient polycation-dimethyl sulfoxide transfection, which requires no carrier DNA even with small amounts of DNA, the number of transformed cell foci induced by Rous sarcoma virus DNA was proportional to the dose of the transfecting DNA, and chicken embryo fibroblast cells were successfully transformed by v-src-containing subgenomic DNA as well.

Animals↗
PubMed2005

Spindle cells and their role in Kaposi's sarcoma.

Spindle cells represent the main cell type of the advanced final nodular stage of Kaposi's sarcoma lesions. Despite some clinical and epidemiological differences, the four Kaposi's sarcoma forms (classic, endemic, post-transplant and epidemic) display very similar histopathological features, with the proliferation of spindle cells (considered as the Kaposi's sarcoma tumor cells) associated with inflammation and neo-angiogenesis. Electron-microscopy and immuno-histochemistry studies have led to the consensus that the spindle cells originated from the endothelial lineage. However, only recently, studies that used specific lymphatic immunological markers (such as podoplanin) and molecular features (gene expression microarrays) strongly linked Kaposi's sarcoma spindle cells to the endothelium lymphatic cell lineage. Both hybridization and immuno-histochemistry techniques have demonstrated that human herpesvirus 8 also known as Kaposi's sarcoma associated herpesvirus was present in spindle cells at all stages of the disease (patch, plaque, nodule). Interestingly, while the human herpesvirus 8 latent genes are expressed in nearly all tumor spindle cells, only a small fraction of them expresses markers of viral lytic replication. Recent findings showing that nodular Kaposi's sarcoma lesions display all patterns of human herpesvirus 8 clonality support the model according to which this tumor begins as a polyclonal disease with a subsequent evolution to a mono/oligoclonal process involving infected spindle cells. Spindle cells appear to be the central masterpiece in KS tumorigenesis, however the exact respective role of each human herpesvirus 8 gene, in the initiation and the disease progression is still under investigation and the question of whether or not this tumor is a reactive process or a true malignant proliferation of spindle cells remains yet unclear.

Cell Lineage↗
PubMed1991

Lymphadenopathic tumor exhibiting intermingled features of Kaposi's sarcoma, malignant lymphoma, and angiofollicular hyperplasia.

A 56-year-old man presented with an inguinal lymph node enlargement. Histologic study of the tumor revealed three intermingled pathologic lesions: a nodular small cell lymphoma, an angiofollicular hyperplasia of vasculohyaline type, and a vascular neoplasia closely resembling Kaposi's sarcoma. The patient was immunocompetent and denied any homosexual relationships, transfusions, or drug use. The serum was negative for the presence of human immunodeficiency virus antibody. Computed tomographic scan and ultrasound examination revealed no other lymphadenopathies. This case shows that both hyperplastic and neoplastic lymphoid proliferations can occur simultaneously with vascular neoplasia. It thereby suggests that the neoplastic populations might interact to favor the tumor growth, the sequence and the nature of the stimulating events remaining unclear.

Castleman Disease↗
PubMed2000

Value of A103 (melan-A) immunostaining in the differential diagnosis of ovarian sex cord stromal tumours.

AIMS: To assess A103 (melan-A) immunoreactivity in a range of ovarian sex cord stromal tumours and to evaluate it for the differential diagnosis of other neoplasms. METHODS: Paraffin embedded tissue sections from 45 sex cord stromal tumours and 44 potential histological mimics were examined immunohistochemically using the antibody A103. The sex cord stromal group included 21 adult granulosa cell tumours (AGCT), two juvenile granulosa cell tumours (JGCT), eight tumours showing Sertoli cell or Sertoli-Leydig cell differentiation, two unclassified tumours, two gonadoblastomas, one sex cord tumour with annular tubules, two steroid cell tumours, five thecomas/fibrothecomas, and two sclerosing stromal tumours. The histological mimics include 14 primary ovarian carcinomas, 13 metastatic carcinomas, four carcinoid tumours, four lymphomas, three endometrioid stromal sarcomas, two ovarian tumours of probable Wolffian origin, and one case each of small cell carcinoma, desmoplastic small round cell tumour, melanoma, and primitive neuroectodermal tumour. RESULTS: A103 immunoreactivity was identified in 25 sex cord stromal tumours including 10 AGCT, two JGCT, six Sertoli/Sertoli-Leydig cell tumours, two steroid cell tumours, three thecomas/fibrothecomas, and two sclerosing stromal tumours. Of the potential histological mimics, staining was present only in the two ovarian tumours of probable Wolffian origin and the melanoma. Immunoreactive stromal cells were noted in a minority of cases. Normal hilus cells and rete ovarii epithelium also expressed A103. CONCLUSIONS: A103 is a moderately sensitive and specific marker of sex cord stromal differentiation within the range of tumours examined in this study and as such is a valuable adjunct to other immunocytochemical markers in the assessment of diagnostically problematic ovarian tumours. The staining of normal and neoplastic Wolffian elements merits further investigation.

Adult↗
PubMed1999

Melanotic peritoneal sarcomatosis originating from clear cell sarcoma.

Peritoneal sarcomatosis was found in a 53-year-old male who had a history of resection of clear cell sarcoma (CCS) of the right wrist 7 years previously. Both the previous wrist tumor and the peritoneal disseminants consisted of small, spindle-shaped cells occasionally containing melanophages. Histologic features, histochemical demonstration of argentaffin granules, immunohistochemical reaction with HMB 45, and the demonstration of a chimeric transcript of EWS-ATF-1 established the diagnosis of CCS in the peritoneal tumors. As far as we are aware, this is the first case of a peritoneal sarcomatosis associated with CCS.

Antigens, Neoplasm↗
PubMed1986

Antibodies against small nuclear ribonucleoproteins immunoprecipitate complexes containing ts110 Moloney murine sarcoma virus genomic and messenger RNAs.

Small nuclear ribonucleoproteins (snRNPs) are believed to play a role in processing premessenger RNAs. In this study, snRNPs were immunoprecipitated from extracts of cells infected with ts110 Moloney murine sarcoma virus (ts110 MoMuSV). Both the unspliced 4.0 kb and the spliced 3.5-kb ts110 MoMuSV specific RNA species were found in the immunoprecipitates obtained with monoclonal antibody anti-Sm and polyclonal anti-Sm, anti-(U1) RNP and anti-La sera. Although only a portion of the total ts110 RNAs was present in these immunoprecipitates, immune recognition by the anti-snRNPs was specific and not due to contaminating anti-RNA (at least for the anti-Sm sera) or, to anti-viral protein activities. Genomic 8.3-kb RNA and subgenomic 3.0-kb spliced env mRNA from Moloney murine leukemia virus (MoMuLV) infected cells as well as the cellular actin mRNA were also detected in immunoprecipitates obtained with the same antisera. The fact that pre-mRNAs and mature mRNAs of different origin can be recovered from immunoprecipitates formed with anti-snRNP sera establishes their tight association and confirms the role of snRNPs in mRNA processing.

Actins↗
PubMed1981

Differential synthesis of methotrexate polyglutamates in normal proliferative and neoplastic mouse tissues in vivo.

Synthesis of poly-gamma-glutamyl metabolites of methotrexate was demonstrated in mouse small intestine, liver, and bone marrow and in L1210 leukemia, Sarcoma 180, and Ehrlich tumor cells after s.c. injections of [3H]methotrexate to tumor-bearing mice. Ion-exchange chromatography of tissue extracts resolved six peaks of radioactivity believed to represent methotrexate and metabolites with up to five additional glutamyl residues. Polyglutamate formation in L1210 cells and small intestine was shown to be independent of dose at least to 400 mg/kg as long as intracellular levels of drug in excess of the dihydrofolate reductase-binding capacity (exchangeable) were maintained. Both the total amount of polyglutamates and the average length of the polyglutamyl chain increased with time as long as exchangeable level of drug was present intracellularly. The results also showed differences in the extent of metabolism of methotrexate polyglutamates among the tissues examined. Although these differences were at times very large, there was no consistent correlation between these differences and other pharmacological parameters or cytotoxicity. Tumor cells appeared to synthesize more polyglutamates than did the normal tissues examined. However, differences in total drug persistence and sensitivity to drug among tumor cells and among normal tissues did not reflect the relative extent of polyglutamate synthesis in each group. It is concluded that the extent of polyglutamate synthesis per se may not be a determinant of drug sensitivity in murine tissues. However, the accumulation of these metabolites may contribute in some way to overall therapeutic response or relative cytotoxicity.

Animals↗
PubMed1987

A monoclonal antibody (FMG25) that can differentiate neuroblastoma from other small round-cell tumours of childhood.

The monoclonal antibody (MAb), FMG25, raised following immunization of mice with the human T cell line HUT 78, binds to human neuroblastoma but not to other small round-cell tumours of childhood (rhabdomyosarcoma and Ewing's sarcoma). The specificity of the reagent is paralleled on normal tissues binding to brain but not frozen sections of thymus, tonsil, lymph node and spleen. Of the 15 T-cell malignancies examined, only 3, belonging to the large T-cell type, were positive. This represents only 50% of this type examined. Only one early case of pre-B ALL was found to be positive for FMG25 binding out of 27 non-T-cell malignancies. The pattern of reactivity of FMG25 makes the MAb useful as a diagnostic reagent in paediatric pathology. In addition, the antibody may be useful as one of a panel of reagents applied to detect and remove tumour cells from bone marrow harvested for autologous transplantation.

Antibodies, Monoclonal↗