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PubMed2003

[Study on the diagnostic significance of detecting the expression of AChR-gamma mRNA in rhabdomyosarcoma tissues].

OBJECTIVE: To detect over-expression of AChR-gamma mRNA in rhabdomyosarcoma tissues by duplex RT-PCR and discuss its potential in diagnosis of rhabdomyosarcoma. METHODS: Duplex RT-PCR was applied to the simultaneous detection of AChR-alpha and gamma subunit messenger RNA in 17 cases of rhabdomyosarcoma (9 ERMS, 6 ARMS, 2 PRMS). 20 cases of non-rhabdomyosarcomous small round cell tumors (6 poorly differentiated synovial sarcomas, 6 ES/PNET, 6 lymphomas, 2 neuroblastomas) and three normal muscle samples were also detected for AChR-alpha and gamma mRNA by the same method. RESULTS: AChR-alpha and AChR-gamma mRNA were expressed in all the cases of rhabdomyosarcoma. The rate of quantity in both transcripts was AChR-gamma/AChR-alpha >or= 1, but the rate for three normal muscle samples was < 1. Cases of non-rhabdomyosarcomous small round cell tumors were all negative for AChR-gamma. CONCLUSION: AChR-gamma mRNA expression detected by molecular genetic methods is useful in diagnosis and differential diagnosis of rhabdomyosarcoma.

Diagnosis, Differential↗
PubMed1987

Chordoma with a massive spindle-cell sarcomatous transformation. A light- and electron-microscopic and immunohistological study.

A 26-year-old woman was operated on for a bulky tumor in the sacral region; she died of massive local tumor recurrence and pulmonary metastases 3 months later. Most of the original tumor showed a highly cellular spindle-cell sarcoma compatible with a fibrosarcoma of a high grade of malignancy. In a few small areas of the tumor, a chordoma-like pattern surrounded by growth of spindle-cell sarcoma was found. The spindle-cell component exhibited vimentin positivity in all tumor cells, but many cells were also cytokeratin-positive. The chordoma-like areas showed cytokeratin in all tumor cells. The chordoma-like areas, but not the spindle-cell areas also were positive for epithelial membrane antigen and S-100 protein. This case indicates that the sarcomatous change associated with chordoma may contain keratins as a sign of epithelial differentiation, and may thus represent sarcomatous transformation of chordoma cells, rather than a coincidental soft-tissue sarcoma or collision tumor.

Adult↗
PubMed1991

Biochemical and genetic characterization of the HBA71 Ewing's sarcoma cell surface antigen.

Monoclonal antibody HBA71 detects a cell surface antigen of human Ewing's sarcomas and peripheral neuroepitheliomas that distinguishes these tumors from other small round cell tumors of childhood and adolescence. In the present study, we show that monoclonal antibody HBA71 reacts with polypeptides of Mr 32,000 and 30,000 and that the HBA71-coding gene segregates with human chromosomes X and Y in rodent-human hybrids. Therefore, we compared HBA71 to the T-cell leukemia antigen 12E7, which is encoded by the pseudoautosomal region of chromosomes X and Y. We show that monoclonal antibodies HBA71 and 12E7 (a) detect polypeptides of identical size, (b) react with mouse cells transfected with complementary DNA corresponding to the 12E7-coding gene, MIC2, and (c) give similar patterns of reactivity with human tumor cell lines and small round cell tumor tissues. Thus, HBA71 and 12E7 are identical or closely related antigens and the available MIC2 probes will facilitate analysis of the molecular mechanisms that determine differential HBA71 expression in small round cell tumors of childhood and adolescence.

12E7 Antigen↗
PubMed1997

Undifferentiated sarcomas of children: pathology and clinical behavior--an Intergroup Rhabdomyosarcoma study.

Undifferentiated soft tissue sarcoma (UND-STS) is the most poorly defined tumor eligible for intergroup Rhabdomyosarcoma Studies (IRS). Recent IRS UND-STS experience was reviewed to assess the histologic characteristics and clinical behavior of undifferentiated sarcomas. Of the 1,527 patients entered on IRS-III and IRS pilot-IV, 96 had tumors classified by the IRS Pathology Committee as UND-STS. Of these, 52 had adequate histologic material for this study. After application of immunohistochemistry, 18 tumors were reclassified, mostly as embryonal rhabdomyosarcomas (RMS), primitive neuroectodermal tumors, and intraabdominal desmoplastic small found cell tumors. The remaining 34 UND-STS had a diffuse hypercellular histologic pattern made up of sheets of medium-sized cells. The tumor cells had a minimal to moderate amount of cytoplasm and a variable nuclear morphology, predominately vesicular with finely granular chromatin. Except for reactivity with antibodies against vimentin, most tumors had a negative immunohistochemical profile. The 5 year Kaplan-Meier survival estimate for patients with non-metastatic disease was 72%, a significant improvement when contrasted with patients diagnosed to have UND-STS in IRS-I and IRS-II.

Adolescent↗
PubMed1980

Non-T-cell-mediated cytotoxicity in mice with tumors induced by Moloney murine sarcoma virus (M-MuSV). II. Granulocyte-mediatd cytotoxicity against autochthonous target cells isolated from M-MuSV-induced tumors.

Experiments were performed in A/Sn and A/WySn mice to determine the specificity, organ distribution, and further characteristics of the small non-T-cells that infiltrate Moloney murine sarcoma virus (M-MuSV)-induced tumors and are capable of killing the autochthonous M-MuSV-infected tumor target cells. Continuous bovine serum albumin density gradient separation proved to be the most effective method of enriching the cytotoxic cells. Increase in cytotoxic activity, measured by both the 51Cr release assay and the microcytotoxicity test, paralleled the increase in the proportion of polymorphonuclear leukocytes in mice bearing M-MuSV-induced tumors also contained myeloperoxidas-positive cytotoxic effector cells. The cytotoxic activity appeared to be nonspecific. Various mouse tumor lines as well as allogeneic fibroblasts were sensitive to these effector cells. The only target cell type not affected was the syngeneic fibroblast. In addition to the tumor mass, cytotoxic cells were found in the bone marrow, blood, and spleens of mice bearing M-MuSV-induced tumors. Only bone marrow cells from normal mice exhibited cytotoxic activity. Thus cells of the myelopoietic series may be important in fighting M-MuSV-induced tumors by way of their direct cytotoxic effects on the infected cells.

Animals↗
PubMed1998

Monoclonal antibody NB84 in the differential diagnosis of neuroblastoma and other small round cell tumors.

Two hundred fifty-five well-characterized formaldehyde-fixed and paraffin-embedded small round cell tumors mainly from children and young adults including 105 neuroblastomas were immunohistochemically analyzed with the NB84 monoclonal antibody raised to neuroblastoma cells. Most of the undifferentiated neuroblastomas (21 of 22) and all 83 differentiated neuroblastomas reacted with NB84, but none of these tumors were CD99 positive. Compared with synaptophysin, NB84 was more sensitive, although less specific, in the identification of neuroblastoma in formaldehyde-fixed tissue. In addition to neuroblastoma, skeletal and extraskeletal Ewing's sarcoma and medulloblastoma showed NB84 reactivity in approximately 20% of cases, and 50% of desmoplastic small round cell tumors showed positive cells, usually in smaller numbers than the neuroblastomas. The NB84 reactivity was seen slightly more commonly in morphologically defined (rosette-positive) cases of peripheral primitive neuroectodermal tumors than in Ewing's sarcoma. However, the NB84 positivity did not correlate with the expression of other neural markers (neurofilament proteins, CD57, and synaptophysin) in these tumors. All other small round cell tumors including rhabdomyosarcomas, Wilms' tumors, and lymphomas were NB84 negative. In the case of NB84-positive tumors other than neuroblastoma, their specific reactivity for other markers was useful (Ewing's sarcoma CD99 positive, desmoplastic small round cell tumor desmin and keratin positive). The NB84 monoclonal antibody is a useful reagent to separate neuroblastoma from other small round cell tumors. In problem cases it is best used in a panel together with other markers that address the significant differential diagnostic alternatives.

Adolescent↗
PubMed1987

Small-cell osteosarcoma.

Small-cell osteosarcoma, a subtype of osteogenic sarcoma, consists of sheets of round cells that produce an osteoid matrix. It may be confused with Ewing sarcoma if the osteoid matrix is not included in the biopsy. The distinctive radiographic features of an osteoblastic tumor and a pattern of permeative destruction will confirm the histologic diagnosis or indicate the true nature if tumor osteoid is not included in the histological sections. We add 13 patients to the 32 previously reported in the literature. Fourteen (31%) of the 45 are living and well, though three have been followed for only 2 months (Tables 1 and 2). The treatments have been so varied that a statistically significant evaluation cannot be developed. The radiographic features are not distinctive, but the diagnosis may be suggested when a tumor has osteoblastic features in the metaphysis and extends well down into the shaft with a pattern of permeative destruction. The radiographic features are especially important when limited biopsies reveal only sheets of round cells, thus suggesting Ewing sarcoma. The presence of an osteoid-producing tumor as evidenced by osteoblastic new bone formation will lead to the correct diagnosis.

Adolescent↗
PubMed2002

[Musculoskeletal lymphomas].

Primary lymphomas of bone or skeletal muscle are rare entities. The most frequent among these diseases are primary non-Hodgkin's lymphomas of bone. They account for 3-5% of all bone tumors and 5% of all primary extranodal non-Hodgkin's lymphomas. Primary manifestations of Hodgkin's disease in bone or skeletal muscle are rarities. Primary non-Hodgkin's lymphomas of skeletal muscle are rarities as well. Primary non-Hodgkin's lymphomas of bone can be found in any patient age. A preference exists for the 3.-6. decade of life. The radiographic appearance of these entities resembles other aggressive bone tumors. Their differential diagnosis includes -- depending on the patient's age -- Ewing's sarcoma,malignant fibrous histiocytoma,metastases of small cell tumors and osteomyelitis.Further differential diagnoses are the peripheral primitive neuroectodermal tumor (PNET), osteosarcoma, eosinophilic granuloma and fibrosarcoma. Treatment of primary non-Hodgkin's lymphomas uses combinations of chemotherapy and radiation therapy. Operative treatment is reserved for the treatment of complications. The prognosis of primary non-Hodgkin's lymphomas is reflected by 10-year-survival-rates without recurrence of more than 80% in unifocal manifestations.

Bone Neoplasms↗
PubMed2003

Radical cystectomy for bladder cancer after definitive prostate cancer treatment.

OBJECTIVES: To review our perioperative experience with patients presenting with high-risk bladder cancer who had undergone prior therapy for prostate cancer. With the increase in diagnosis and subsequent treatment of prostate cancer, more patients presenting with high-risk bladder cancer have undergone prior therapy for prostate cancer. Radical cystectomy in these patients can be technically challenging and may be associated with added morbidity. METHODS: A retrospective review of 458 patients treated with radical cystectomy between January 1993 and January 2002 revealed 29 patients (mean age 72 years) who had received definitive treatment for prostate cancer prior to cystectomy for bladder carcinoma. The initial treatment in this cohort was radical prostatectomy or external beam radiotherapy in 12 (41%) and 17 (59%) men, respectively. Cystectomy was performed for transitional cell carcinoma in 25 (86%), small cell carcinoma in 2 (6%), and sarcoma in 2 (6%) patients. RESULTS: At the time of cystectomy, the mean blood loss was 1175 mL (range 275 to 3500), and the median length of hospitalization was 8 days (range 4 to 23). No intraoperative or perioperative deaths occurred in this cohort. Twenty-seven early complications were identified in 16 (55%) of 29 patients; no rectal injuries occurred. Patients with prior radiotherapy had a higher rate of extravesical bladder carcinoma (60%) than those patients treated with prior prostatectomy (33%). An orthotopic neobladder diversion was created in 5 patients (17%). CONCLUSIONS: Patients with bladder cancer previously treated for prostate cancer with external beam radiotherapy or radical prostatectomy have an increased risk of perioperative complications compared with patients undergoing cystectomy without prior therapy. This risk is not prohibitive, and radical cystectomy should remain the treatment of choice for high-risk bladder cancer in this population. Furthermore, orthotopic urinary diversion may be a reasonable option and should be considered in select patients.

Aged↗
PubMed1983

Granulocytic sarcoma (chloroma) of the uterine cervix: report of two cases.

Two cases of granulocytic sarcoma in the cervix are described, adding to the six previously reported cases. Both our cases were primarily misdiagnosed as other types of small-cell malignant tumors. Misdiagnosis often occurs in granulocytic sarcomas, especially for those in extraskeletal sites or when the tumor precedes development of frank leukemia. A conclusive diagnosis of granulocytic sarcoma depends upon the demonstration of granulocytic differentiation of the tumor cells. For this purpose, special staining methods like the Leder stain and the antilysozyme immunoperoxidase stain are particularly useful.

Adult↗
PubMed2004

Inhibin alpha and beta expression in ovarian stromal tumors and their histological equivalences.

Inhibin is a heterodimeric protein hormone that appears to be a sensitive immunohistochemical marker of sex cord-stromal tumors. Although sex cord-stromal tumors can usually be distinguished from ovarian epithelial tumors or their metastases by morphology or by using antibodies against intermediate filaments, the diagnosis remains difficult in rare situations in such cases as sarcomatoid granulosa-theca cell tumors, ovarian small cell carcinomas, or soft-tissue sarcomas. The purposes of this study were to examine inhibin alpha and beta immunoreactivity in a wide range of gonadal stromal neoplasms and to assess its value in the differential diagnosis of problematic tumors. A total of 108 paraffin-embedded ovarian and extraovarian tumors were examined immunohistochemically by using anti-alpha inhibin and anti-beta inhibin. Inhibin alpha immunostaining was identified in 46 (81%) of 57 gonadal stromal tumors, one (14%) of seven endometrial stromal tumors, and one (50%) of two primary ovarian carcinoid tumors. Inhibin beta immunostaining was detected in 55 (96%) of 57 gonadal stromal tumors, two (29%) of seven endometrial stromal tumors, one (50%) of two dysgerminomas, and in all of two (100%) primary ovarian carcinoid tumors. Inhibin alpha expression was not detected in any ovarian surface epithelial tumor cells. Some surface epithelial tumors showed stromal inhibin alpha (15% of cases) and inhibin beta (48% of cases) positivity. Weak immunoreactivity for inhibin beta was found in most (83% of cases) ovarian surface epithelial tumors. Two ovarian Burkitt lymphomas were negative for inhibin alpha and beta. Inhibin alpha is a sensitive immunohistochemical marker of gonadal stromal tumors and is of value in the differential diagnosis of ovarian neoplasia. Inhibin beta is a nonspecific marker for ovarian neoplasms, showing expression on tumor and stromal cells of different epithelial or stromal tumors.

Biomarkers, Tumor↗
PubMed2005

A practical approach to the clinical diagnosis of Ewing's sarcoma/primitive neuroectodermal tumour and other small round cell tumours sharing EWS rearrangement using new fluorescence in situ hybridisation probes for EWSR1 on formalin fixed, paraffin wax embedded tissue.

BACKGROUND: Over 90% of Ewing's sarcoma/primitive neuroectodermal tumour (ES/PNET) cases have the t(11;22) chromosomal rearrangement, which is also found in other small round cell tumours, including desmoplastic small round cell tumour (DSRCT) and clear cell sarcoma (CCS). Although this rearrangement can be analysed by fluorescence in situ hybridisation (FISH) using routinely formalin fixed, paraffin wax embedded (FFPE) tissues when fresh or frozen tissues are not available, a sensitive and convenient detection method is needed for routine clinical diagnosis. AIMS: To investigate the usefulness of newly developed probes for detecting EWS rearrangement resulting from chromosomal translocations using FISH and FFPE tissue in the clinical diagnosis of ES/PNET, DSRCT, and CCS. METHODS: Sixteen ES/PNETs, six DSRCTs, and six CCSs were studied. Three poorly differentiated synovial sarcomas, three alveolar rhabdomyosarcomas, and three neuroblastomas served as negative controls. Interphase FISH analysis was performed on FFPE tissue sections with a commercially available EWSR1 (22q12) dual colour, breakapart rearrangement probe. RESULTS: One fused signal and one split signal of orange and green, demonstrating rearrangement of the EWS gene, was detected in 14 of 16 ES/PNETs, all six DRSCTs, and five of six CCSs, but not in the negative controls. CONCLUSIONS: Interphase FISH using this newly developed probe is sensitive and specific for detecting the EWS gene on FFPE tissues and is of value in the routine clinical diagnosis of ES/PNET, DSRCT, and CCS.

Adolescent↗
PubMed1988

Immunohistochemical analysis of nerve growth factor receptor expression in normal and malignant human tissues.

Nerve growth factor (NGF) is a polypeptide important for normal development of the nervous system and promotion of survival and differentiation of sensory and sympathetic neurons in culture. The cellular effects of NGF are mediated by a specific cell surface molecule, nerve growth factor receptor (NGF-R). In the present study we have used a monoclonal antibody against human NGF-R to examine, by the avidin-biotin-immunoperoxidase method, the receptor distribution in a wide range of normal tissues and in more than 200 malignant tumors. Our results show that (a) human NGF-R is expressed in the peripheral nervous system but not in any of the central nervous system areas tested; (b) NGF-R expression is not restricted to neural tissues but is also found in a number of normal epithelial, mesenchymal, and lymphoid tissues; (c) NGF-R expression changes during normal development; and (d) NGF-R expression in malignant tumors generally parallels its normal tissue distribution. Thus, NGF-R is detected in a proportion of neuroectoderm-derived tumors, carcinomas, and lymphomas, and also in a characteristic group of small round-cell tumors (Ewing's sarcomas and embryonal rhabdomyosarcomas). These findings suggest a normal regulatory role for NGF in both neuronal and non-neuronal cells and identify a range of human tumors in which the NGF/NGF-R system may contribute to the malignant phenotype.

Aging↗
PubMed1998

Malignant mixed Müllerian tumor (homologous type) of the adnexa with neuroendocrine differentiation: a case report.

Malignant mixed müllerian tumors (MMMT) are unusual neoplasms occurring mostly in the uterus. In the ovary, they are very rare and represent fewer than 1% of all ovarian malignancies; in the salpinx, they are even rarer than those of the ovary. We report a carcinosarcoma of the left adnexa having features of neuroendocrine differentiation in a 69-year-old female. The tumor contained both adenocarcinoma and squamous cell carcinoma having dear cell change admixed with an undifferentiated malignant mesenchymal component. The sarcoma components consisted of spindle cells, small-round cells and bizarre giant cells mimicking rhabdomyoblast. Almost all of the carcinomatous glandular components and some foci of the squamous cell and undifferentiated carcinomatous components were focal positive for S-100 protein, chromogranin, neuron specific enolase, synaptophysin and Leu-7. Electron microscopy revealed membrane-bound neurosecretory granules in the cytoplasm of some glandular epithelial cells. Histologically, the tumor involved the left adnexa, abdominal peritoneum, surface of the bladder dome, omentum and left external iliac lymph node (stage IIIc).

Adnexa Uteri↗
PubMed2003

Tyrosine kinase inhibitor imatinib mesylate as anticancer agent for advanced ocular melanoma expressing immunoistochemical C-KIT (CD 117): preliminary results of a compassionate use clinical trial.

Imatinib mesylate (IM), is a selective and competitive inhibitor of tyrosine kinases, including BCR-ABL, ABL, KIT, and the platelet-derived growth factor receptors (PDGF-R). It binds to the ATP-binding site of the target kinase and prevents the transfer of phosphate from ATP to the tyrosine residues of various substrates. At oral doses of 200-600 mg, the majority of patients with chronic myeloid leukaemia, Philadelphia chromosome-positive acute lymphoblastic leukemia expressing the BCR-ABL fusion protein and gastrointestinal stromal tumours (GIST) achieve a bio-molecular and clinical response, frequently complete, associated with limited toxicity. Several other human cancers, as small-cell lung carcinoma, melanoma, seminoma, some sarcomas, and adenoid cystic carcinomas may over-express KIT or PDGF-R, and clinical trials to evaluate the role of IM in the treatment of such cancers are currently ongoing. We determined c-KIT with Dako CD 117 antibody in 5 cases of advanced ocular melanoma (OM) and we found positive immuno-reactivity for CD 117 in three patients. We treated all patients with palliative-use IM at the oral dose of 400 mgr daily. We obtained in expressing positive immuno-reactivity for CD 117 patients: a reduction of malignant ascites in one, a partial remission in the neck nodes in another, and progression of liver metastases in the third. Evidences of progression has been reported in the other two patients expressing negative immuno-reactivity for CD 117. We conclude that the effect of IM should be assessed only in OM with positive immuno-histochemical c-kit (CD 117) expression. IM might be a potential therapeutic strategy for these patients.

Adult↗
PubMed1984

Two new monoclonal antibodies (LN-1, LN-2) reactive in B5 formalin-fixed, paraffin-embedded tissues with follicular center and mantle zone human B lymphocytes and derived tumors.

Two monoclonal antibodies (LN-1, LN-2) reactive with B lymphocytes in B5 formalin-fixed, paraffin-embedded tissue sections have been produced by utilizing cell extracts from pokeweed mitogen-stimulated peripheral blood lymphocytes and diffuse histiocytic lymphoma SU-DHL-4 cells, respectively. Both monoclonal antibodies were initially identified by indirect immunofluorescence screening techniques on paraformaldehyde-acetone-fixed cell preparations. Specificity screens with 36 well-characterized human lymphoma and leukemia cell lines showed that both LN-1 and LN-2 stained cell lines of B cell lineage but were unreactive with those of T cell or, with one exception, myeloid derivation. Null cell acute lymphoblastic leukemia cell lines were found to be LN-2+ but LN-1-. The B cell specificity of these reagents was confirmed on 15 lymphoma and 17 leukemia biopsy specimens by using indirect immunofluorescence techniques. Immunoperoxidase staining of sections from B5-fixed, paraffin-embedded human lymphoid tissues showed that LN-1 bound to the cell membrane and cytoplasm of germinal center cells whereas LN-2 stained the nuclear membrane and cytoplasm of germinal center and mantle zone B lymphocytes as well as interfollicular histiocytes and thymic medullary dendritic cells. Both monoclonal antibodies failed to stain cortical thymocytes, lymph node T cells, and peripheral blood T and myeloid cells. Immunoperoxidase staining of 20 nonlymphoid human organs and tissues revealed that LN-1 reacted positively with red blood cell precursors of the bone marrow, ciliated epithelial cells of the bronchus, distal tubular cells of the kidney, and ductal cells from several organs including the breast and prostate. In contrast, LN-2 was unreactive with all human nonlymphoid organs and tissues including the bone marrow. Indirect immunofluorescence staining of a panel of 26 solid tumor cells lines showed that LN-1 was reactive with the majority of epithelium-derived cell lines, glioblastomas, and astrocytomas but was unreactive with neuroblastomas, small cell carcinoma of the lung, and sarcomas. LN-2 was unreactive with 25 of 26 of the solid tumor cell lines by these techniques. Immunobiochemical studies have shown that LN-1 recognizes a cell surface sialoantigen whereas LN-2 is directed against a 35,000 dalton nuclear membrane protein. Because of their high specificity for B cell tumors and their ability to stain B5-fixed, paraffin-embedded tissues, LN-1 and LN-2 are useful reagents for the diagnosis and classification of the human lymphomas and leukemias.

Antibodies, Monoclonal↗
PubMedDate not supplied

[Small cell-sarcomatoid carcinoma of the urinary bladder].

OBJECTIVES: Oat cell carcinoma of the urinary bladder is extremely uncommon. To date, 87 cases have been reported in the literature. Histologically, these tumors are similar to oat cell carcinoma of the lung and in slightly more than half of the cases the tumor is associated with another carcinomatous component: urothelial, squamous carcinoma, adenocarcinoma or, more rarely, sarcomatoid carcinoma. A case of sarcomatoid small cell carcinoma is described herein. METHODS/RESULTS: We report a case of sarcomatoid small cell carcinoma of the urinary bladder in a 79-year-old female patient. The tumor was in the advanced stages and was unamenable to resection. The patient was treated with multi-drug systemic chemotherapy, but she died five months after diagnosis. Light microscopy disclosed a carcinomatous component similar to oat cell carcinoma of the lung that stained with epithelial and neuroendocrine markers. The sarcomatoid component was histologically nondescript and showed extensive immunoreactivity to mesenchymal and epithelial markers. CONCLUSIONS: Sarcomatoid small cell carcinoma of the bladder is rare. To our knowledge, only five cases have been previously reported. It is aggressive, metastasizes early and has a poor diagnosis. Surgical resection with adjuvant multidrug systemic chemotherapy is currently the best available treatment.

Aged↗