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PubMed2001

Primary Ewing sarcoma of the orbit.

PURPOSE: To report the clinicopathologic features of a 17-year-old patient with primary Ewing sarcoma of the orbit. METHODS: The patient was evaluated clinically before surgery with computed tomography scans of the orbit. After surgery, the patient was staged with computed tomography scans and bone scan and was treated with systemic chemotherapy and radiation therapy to the orbit. The orbital biopsy was evaluated with conventional light microscopy and immunohistochemistry. RESULTS: Clinical evaluation revealed proptosis and limited upgaze. Computed tomography scans disclosed a mass involving the superior orbit, anterior cranial fossa, and temporal fossa. Microscopic examination revealed small, poorly differentiated cells with medium-sized nuclei containing finely granular chromatin and small nucleoli. The cytoplasmic borders of the cells were indistinct. A PAS stain revealed modest glycogen in many of the tumor cells. The tumor stained positive for O-13 and vimentin and was negative for neural, skeletal, and lymphoid cell markers. Computed tomography scan, bone scan, and blood chemistries revealed no other site of involvement. After treatment, the clinical symptoms and signs resolved, and there has been no evidence of residual orbital tumor or metastasis. CONCLUSIONS: Primary Ewing sarcoma of the orbit should be considered in the differential diagnosis of children or young adults with proptosis, diplopia, or periorbital swelling. Immunohistochemistry is essential to distinguish Ewing sarcoma from other small round cell tumors.

Adolescent↗
PubMed2006

Interleukin-2 for the treatment of solid tumors other than melanoma and renal cell carcinoma.

Interleukin-2 (IL-2) is a lymphokine produced by T cells whose main function is to stimulate the growth and cytotoxic response of activated T lymphocytes. It has been used to stimulate the immune system for the treatment of multiples tumors. This article is intended to review the reports published from 1990 to 2004 on the IL-2 treatment of tumors other than melanoma and renal carcinoma. A literature search was made in various databases (MEDLINE, EMBASE and BioAssay), focused on IL-2 clinical efficacy in such tumors. A selection was made over 150 publications reporting on administration of IL-2 in multiple tumors: lung carcinoma (small cell and non-small cell), colorectal, gastric, pancreatic, ovarian and breast cancer, sarcomas, hepatocarcinoma, mesothelioma, and brain, urological, and head and neck tumors. IL-2 was mainly used in metastatic disease, associated with other immunotherapy or chemotherapy schedules. We conclude that adjuvant IL-2 may be of value in early stages combined with standard treatment for colon and pancreas cancers. In other neoplasms, the indication for adjuvant IL-2 has been sporadic and does not allow conclusions to be drawn. Assessment of the efficacy of IL-2 combined with chemotherapy as treatment for advanced stages is complex, due to the lack of a control, and the variety of dosages and schemes. The activity of IL-2 in monotherapy or in association with immunotherapy is clinically relevant in hepatocarcinoma, mesothelioma and in malignant overflows as palliative treatment. Randomized trials would be required in order to be able to draw conclusions about its indication in other tumors.

Antineoplastic Agents↗
PubMed1986

Fluoropyrimidine-mediated changes in small nuclear RNA.

Studies were completed to examine the effects of the antineoplastic agent 5-Fluorouridine (FUrd) on the metabolism of the small molecular weight nuclear RNA (snRNA). Cultured Sarcoma-180 murine tumor cells were exposed to FUrd concurrent with [3H]cytidine for 6 h, the drug was removed, and the RNA was isolated at 0, 24, or 48 h following the drug treatment. The results of these studies demonstrated that FUrd produced three dose-dependent changes in snRNA metabolism. The electrophoretic migration of the U4 and U6 snRNA was altered in nondenaturing 10% polyacrylamide slab gels. These results were not observed in denaturing gels or when RNA was extracted at temperatures exceeding 25 degrees C, suggesting that the incorporation of 5-fluorouracil induced secondary structural changes in these RNA. A dose- and time-dependent selective reduction in the turnover of the U1 snRNA synthesized in the presence of FUrd was observed as well, with levels over 100% higher than control cells at 48 h after exposure to 10 microM FUrd. These changes in snRNA metabolism may contribute to the reported alterations in large molecular weight RNA metabolism that also result in fluoropyrimidine-treated cells, or to cytotoxicity.

Animals↗
PubMed1989

[New aspects of nephroblastoma (Wilms tumor) and other metanephrogenic neoplasms].

We differentiate (continuing the scheme of the National Wilms' Tumor Study) three groups of Wilms' tumors (WT), which for practical reasons also encompass WT variants: 1. a group of low-grade malignant tumors comprising 9.3% of cases (congenital mesoblasticnephroma; cystic, partially differentiated nephroblastoma); 2. the main group of tumors with histologically standard malignancy and constituting 77.7% of cases, against which a combined therapy is used depending upon age and stage of spread; and 3. a small group of tumors of high-grade malignancy (anaplastic WT, clear cell sarcoma of the kidney; malignant rhabdoid tumor of the kidney). This latter group constitutes only 13% of cases but is responsible for a high percentage of total deaths due to WT. To the tumor group with standard malignancy belong the classic triphasic WT (without anaplasia) as well as WT "with quantitative deviations", in which either the blastemic, the epithelial, or the stroma component dominates. In the differential diagnosis the relatively frequent blastemic WT must be differentiated from other so-called small, round, and blue cell tumors of childhood, especially the undifferentiated neuroblastomas. Pseudo-rosettes and cytokeratin expression are signs of an "early" epithelial differentiation. Anaplastic WT (comprising 6.1% of our cases) are diagnosed according to the criteria of BECKWITH and PALMER (1978). They are aneuploid tumors and occur predominantly in children over two years of age. By contrast, the histogenetic still undefined clear cell sarcomas and malignant rhabdoid tumors of the kidney occur chiefly in children under two. Both tumors are diploid, notwithstanding their high-grade malignancy. Clear cell sarcoma, which contains a high content of vessels and comprises 3.7% of our cases, consists of cells with weakly stained and partially vacuolized cytoplasm. In contrast to normal WT, clear cell sarcoma often progresses to bone metastases. Malignant rhabdoid tumor (2.7% of our cases) possesses cells with large, roundish nuclei, pale chromatin, very prominent nucleoli and characteristic spherical intermediate filament condensations. Cross striation and myoglobin are never present. Malignant rhabdoid tumor is not a genuine kidney tumor; it may also occur extrarenally. Low-grade congenital mesoblastic nephroma is a spindel cell tumor often exhibiting high cellularity and characterized by fingerlike projections extending into the adjacent kidney tissue. Nephroblastomatosis, with preferential perilobular localization, is a potential WT precursor found in 25% to 40% of all nephrectomy specimens containing WT and in all cases of bilateral and multifocal WT. Nevertheless, only a small proportion of the usually very small "nephrogenic remnants" lead by way of an adenomatous proliferation to manifestation of WT.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma↗
PubMed1992

Dermatopathologic findings in patients infected with HIV.

Several inflammatory, infectious, and neoplastic conditions in HIV-infected patients are distinctive or require a biopsy for diagnosis. Some differ subtly from similar conditions seen in noninfected patients. The exanthem of acute HIV infection cannot be diagnosed specifically on biopsy as its histologic appearance is similar to that of other viral exanthemata. A condition that closely resembles seborrheic dermatitis occurs in HIV-infected patients. Plasma cells, necrotic keratinocytes, and leukocytoclasis may be present, in contrast to findings in sporadic seborrheic dermatitis. Psoriasis and Reiter's disease also occur in HIV-infected patients and can be specifically diagnosed as such. The category "psoriasiform dermatitis of AIDS" thus seems to include several distinct entities and not to be a single disease. Bacillary angiomatosis is a treatable infection caused by a rickettsialike organism similar to Rochalimaea quintana, the agent of trench fever. Cutaneous lesions are characterized by lobules of capillaries with protuberant endothelial cells, neutrophils and their debris, and purplish-staining clumps of organisms, which can be demonstrated with silver stains or electron microscopy. An unusual reaction to atypical mycobacterial infection, in which spindle-shaped macrophages are seen, resembles histoid leprosy. Viral skin diseases that may challenge the dermatopathologist include unusual verrucous reactions to chronic varicella-zoster infection and flat warts caused by the human papillomavirus associated with epidermodysplasia verruciformis. Keratinocytes with foamy basophilic cytoplasm may be a marker for one of these viruses, human papillomavirus type 5. Neoplastic complications of HIV disease include Kaposi's sarcoma and mycosis fungoides. The earliest lesions of the patch stage of Kaposi's sarcoma show a slightly increased number of cells with small ovoid nuclei around preexistent structures, accompanied, in some cases, by sparse infiltrates of lymphocytes and plasma cells. Staining with antisera to type IV collagen may highlight the vascular spaces in these early lesions. Later lesions that resemble hemangiomas may also prove challenging and require level sections to demonstrate the presence of spindle cells and eosinophilic globules. Although HIV is cytotoxic to helper T cells, neoplastic proliferations of them may be seen in HIV-infected patients. These cases of mycosis fungoides do not seem to differ from sporadically occurring ones and occur in patients who seem not to be infected by HTLV-I.

HIV Infections↗
PubMed2005

Efficacy of Wnt-1 monoclonal antibody in sarcoma cells.

BACKGROUND: Sarcomas are one of the most refractory diseases among malignant tumors. More effective therapies based on an increased understanding of the molecular biology of sarcomas are needed as current forms of therapy remain inadequate. Recently, it has been reported that Wnt-1/beta-catenin signaling inhibits apoptosis in several cancers. In this study, we investigated the efficacy of a monoclonal anti-Wnt-1 antibody in sarcoma cells. METHODS: We treated cell lines A-204, SJSA-1, and fresh primary cultures of lung metastasis of sarcoma with a monoclonal anti-Wnt-1 antibody. Wnt-1 siRNA treatment was carried out in A-204. We assessed cell death using Crystal Violet staining. Apoptosis induction was estimated by flow cytometry analysis (Annexin V and PI staining). Cell signaling changes were determined by western blotting analysis. RESULTS: We detected Wnt-1 expression in all tissue samples and cell lines. Significant apoptosis induction was found in monoclonal anti-Wnt-1 antibody treated cells compared to control monoclonal antibody treated cells (p < 0.02). Similarly, we observed increased apoptosis in Wnt-1 siRNA treated cells. Blockade of Wnt-1 signaling in both experiments was confirmed by analyzing intracellular levels of Dishevelled-3 and of cytosolic beta-catenin. Furthermore, the monoclonal anti-Wnt-1 antibody also induced cell death in fresh primary cultures of metastatic sarcoma in which Wnt-1 signaling was active. CONCLUSION: Our results indicate that Wnt-1 blockade by either monoclonal antibody or siRNA induces cell death in sarcoma cells. These data suggest that Wnt-1 may be a novel therapeutic target for the treatment of a subset of sarcoma cells in which Wnt-1/beta-catenin signaling is active.

Adaptor Proteins, Signal Transducing↗
PubMed1987

Leu-7 in small cell neoplasms. An immunohistochemical study with ultrastructural correlations.

In an effort to delineate the distribution of the Leu-7 antigen in small cell neoplasms, 283 paraffin-embedded examples of such tumors were studied immunohistochemically. These included 125 malignant lymphomas, 94 neuroendocrine carcinomas, 13 adenocarcinomas, 14 squamous carcinomas, four malignant melanomas, six neuroblastomas, four nephroblastomas (Wilms' tumors), six primitive neuroectodermal neoplasms, three "Askin" tumors, ten Ewing's sarcomas, and four embryonal rhabdomyosarcomas. Histologic diagnoses were verified by the use of electron microscopic study or independent immunostains. Overall, 44% of small cell neuroendocrine carcinomas expressed Leu-7, whereas nonendocrine carcinomas were uniformly nonreactive for this determinant. All neuroblastomas yielded immunopositivity, as did three primitive neuroectodermal tumors, three rhabdomyosarcomas, two "Askin" tumors, one nephroblastoma, one Ewing's sarcoma, and one malignant melanoma. None of the small cell lymphomas were Leu-7 positive. These results suggest that Leu-7 is a specific neuroendocrine marker in cases of small cell carcinoma, but its sensitivity is lower than that of other "endocrine" determinants. Reactivity patterns for Leu-7 in other small cell tumors demonstrate no specificity for any given line of cellular differentiation. However, the shared expression of this antigen by neuroblastomas, neuroectodermal tumors, Ewing's sarcomas, and Wilm's tumors contributes further to the hypothesis that these neoplasms may be related histogenetically.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1983

Transforming growth factors released from Kirsten sarcoma virus transformed cells do not compete for epidermal growth factor membrane receptors.

Kirsten murine sarcoma virus (KiMSV)-transformed rat kidney cells (KNRK) release small polypeptides (Mr 12,500-15,300) into the culture medium that are capable of stimulating normal rat kidney cells (NRK) to form colonies in soft agar. The transforming growth factors (TGFs) did not compete with epidermal growth factor (EGF) for its receptor and did not induce specific phosphorylation of EGF receptor on NRK cell membranes. These properties differ from the TGFs isolated by other investigators. Our data further establish the heterogeneity of the materials produced by transformed cells that induce transformation-specific changes in normal cells.

Animals↗
PubMed2003

Pediatric-type sarcomas in adult patients.

Sarcomas included in the broad group of small round-cell tumors (SRCT) and some non-SRCT lesions that typically are seen in pediatric-age patients can rarely occur in adults. However, there are differences in the anatomic sites that are involved and the prognosis in these two patient groups. The diagnosis of pediatric-type sarcomas in adults is often challenging because of the unusual contextual clinical setting and morphologic features. Immunohistochemical studies have greatly facilitated this process. Moreover, limited biomolecular studies that have been conducted have demonstrated comparable cytogenetic alterations in adults and children with pediatric-type tumors. They also have raised interesting questions concerning possible biological bases for differences in clinical behavior in the two cohorts. This review focuses on the morphological, immunohistochemical, and molecular characteristics of childhood-type sarcomas that affect adults, with emphasis on possible pitfalls in differential diagnosis.

Adult↗
PubMed1982

Sarcomas of the mouth and jaws--a study of 16 autopsy cases.

Sixteen autopsy cases of the primary sarcomas of the mouth and jaws were reviewed, which included 1 chondrosarcoma, 3 osteosarcomas, 1 leiomyosarcoma, 7 rhabdomyosarcomas and 4 histiocytic lymphoma (reticulum cell sarcoma). Although the case materials studied were too small, the pattern of the spread of the sarcomas of the mouth and jaw was likely to be divided into two groups, localized and generalized. The former is comprised of chondrosarcoma osteosarcoma, leiomyosarcoma and pleomorphic rhabdomyosarcoma. The latter is comprised of alveolar rhabdomyosarcoma and histiocytic lymphoma. Embryonal rhabdomyosarcoma belongs to either depending on the case. The former, being resistant to local therapy, tended to recur with a contiguous spread but was slow to metastasize. Metastases were limited to the lung and pleura through the hematogenous route. The primary sarcoma of the latter group were not so extended in local spread and occasionally cured with therapy. However, metastases, both hematogenous and lymphogenous, were generalized.

Adolescent↗
PubMed1993

Ewing sarcoma of bone in infants and toddlers. A clinicopathologic report from the Intergroup Ewing's Study.

BACKGROUND: Nineteen patients with Ewing sarcoma of bone, each younger than 3 years of age at the time of initial presentation, are reported. These children represent an unusually young age group for documented Ewing sarcoma and represent 2.6% of all patients registered in the Intergroup Ewing's Sarcoma Study (IESS). METHODS: The diagnosis was made on combined histologic, clinical, and radiographic grounds and was supported by immunohistochemistry in nine patients and electron microscopic study in eight patients. Immunohistochemical studies showed no staining against neuro-specific enolase, chromogranin, or S-100 in any patients, and in only one in nine patients were results of such studies focally positive against Leu-7. RESULTS: The most marked clinical variation between this group of infants and the general IESS patient population was a striking predominance of female patients in the younger age group (P < 0.001). There was a trend toward more rib, pelvis, and proximal long bone tumors in the infants and toddlers. The overall survival rate of the infants was 56%, almost identical to the survival rates of the older children. All of the infants who died of disease did so within 4 years. Extended follow-up as long as 9.9 years has found no late deaths attributable to tumor. The most significant late complications of therapy included cardiotoxicity with cerebral embolization from the heart and a short lower limb secondary to radiation therapy. CONCLUSIONS: Ewing sarcoma must be considered in the differential diagnosis of small cell, round cell, and blue cell tumors in bone, even in infants and toddlers.

Bone Neoplasms↗
PubMed1991

Sarcomatoid tumours of lymph nodes showing follicular dendritic cell differentiation.

Putative sarcomas of follicular dendritic cells are extremely uncommon and only small case numbers have been clearly documented. A major difficulty in their delineation has been the persistent controversy over the phenotype and ontogeny of normal follicular dendritic cells. Two new cases arising in adult females are presented herein, both of which had initially been mistaken for metastases from a true soft tissue sarcoma. Their morphology, immunophenotype, and ultrastructure (in one case) are described in order to aid their wider recognition. In the light of these findings, the nature and origin of follicular dendritic cells are discussed.

Adult↗
PubMed1989

Ifosfamide in small cell lung cancer.

Ifosfamide, an analogue of cyclophosphamide, has been proven to be of value in numerous malignancies, including testicular cancer, sarcoma, and lymphoma. Furthermore, ifosfamide is more suitable for combination chemotherapy than its parent compound because it causes less myelosuppression than cyclophosphamide. There have been only a few studies evaluating single-agent ifosfamide in small cell lung cancer (SCLC). In patients who have had little or no prior chemotherapy, ifosfamide appears as active as any single agent. Combination chemotherapy regimens employing cisplatin (or carboplatin) plus etoposide plus ifosfamide are currently under way on both sides of the Atlantic. A Hoosier Oncology Group (HOG) study will evaluate this three-drug regimen v cisplatin plus etoposide, and this protocol will establish or refute the value of ifosfamide as first-line therapy in extensive SCLC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Primitive neuroectodermal tumor of the head and neck: incidence, diagnosis, and management.

Primitive neuroectodermal tumors are in the Ewing's sarcoma family of tumors and are composed of small round cells. Because of their rare occurrence, optimal therapy is challenging, particularly if they occur in the head and neck. Diagnosis is based on history, immunostaining with at least 2 neural markers, ultrastructural examination, and evidence of an abnormal t(11;22)(q24;q12) translocation as the hallmark for the Ewing's sarcoma family. The prognosis in general is poor because of overt metastasis at the time of diagnosis. Of 27 reported patients with primitive neuroectodermal tumors of the head and neck, 23 were less than 20 years of age. Most patients presented with a tumor in the nasal cavity, paranasal sinuses, or neck. Symptoms developed rapidly (3.6 months, on average), and a lethal outcome occurred in 9 patients. This highly malignant tumor requires an aggressive combination of radical resection, chemotherapy, and radiotherapy. A close follow-up with regular radiographic examination for at least 5 years is mandatory.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2007

Discovering biomarkers from gene expression data for predicting cancer subgroups using neural networks and relational fuzzy clustering.

BACKGROUND: The four heterogeneous childhood cancers, neuroblastoma, non-Hodgkin lymphoma, rhabdomyosarcoma, and Ewing sarcoma present a similar histology of small round blue cell tumor (SRBCT) and thus often leads to misdiagnosis. Identification of biomarkers for distinguishing these cancers is a well studied problem. Existing methods typically evaluate each gene separately and do not take into account the nonlinear interaction between genes and the tools that are used to design the diagnostic prediction system. Consequently, more genes are usually identified as necessary for prediction. We propose a general scheme for finding a small set of biomarkers to design a diagnostic system for accurate classification of the cancer subgroups. We use multilayer networks with online gene selection ability and relational fuzzy clustering to identify a small set of biomarkers for accurate classification of the training and blind test cases of a well studied data set. RESULTS: Our method discerned just seven biomarkers that precisely categorized the four subgroups of cancer both in training and blind samples. For the same problem, others suggested 19-94 genes. These seven biomarkers include three novel genes (NAB2, LSP1 and EHD1 - not identified by others) with distinct class-specific signatures and important role in cancer biology, including cellular proliferation, transendothelial migration and trafficking of MHC class antigens. Interestingly, NAB2 is downregulated in other tumors including Non-Hodgkin lymphoma and Neuroblastoma but we observed moderate to high upregulation in a few cases of Ewing sarcoma and Rabhdomyosarcoma, suggesting that NAB2 might be mutated in these tumors. These genes can discover the subgroups correctly with unsupervised learning, can differentiate non-SRBCT samples and they perform equally well with other machine learning tools including support vector machines. These biomarkers lead to four simple human interpretable rules for the diagnostic task. CONCLUSION: Although the proposed method is tested on a SRBCT data set, it is quite general and can be applied to other cancer data sets. Our scheme takes into account the interaction between genes as well as that between genes and the tool and thus is able find a very small set and can discover novel genes. Our findings suggest the possibility of developing specialized microarray chips or use of real-time qPCR assays or antibody based methods such as ELISA and western blot analysis for an easy and low cost diagnosis of the subgroups.

Biomarkers, Tumor↗
PubMedDate not supplied

Exfoliative cytology of invasive neuroendocrine small cell carcinoma in a cervical cytologic smear. A case report.

BACKGROUND: Neuroendocrine small cell carcinoma of the cervix (NSC) is cytologically identical to its counterparts at other sites, such as the lung, and can be suspected on a cervical cytologic smear. It has to be distinguished from poorly differentiated nonkeratinizing squamous small cell carcinoma, adenocarcinoma with carcinoid features, embryonal neuroblastoma, embryonal rhabdomyosarcoma, stromal sarcoma and non-Hodgkin's lymphoma. CASE: An 18-year-old woman had invasive NSC. Exfoliative cytology of the cervix showed tumor cells, single or in small clusters and files, with darkly staining nuclei. The chromatin pattern was coarse, with small, prominent chromocenters, and the nuclei were often invisible. The cytoplasm was so reduced as to be barely discernible. Mutual molding of adjacent nuclei was frequent. Immunohistochemistry showed positive staining for pancytokeratin and neuron-specific enolase. Flow cytometry showed aneuploidy, with a DNA index of 1.93. CONCLUSION: The cytologic appearance of NSC in a cervical cytologic smear is characteristic. The diagnosis, nevertheless, has to be proven by the identification of neuroendocrine differentiation.

Adolescent↗