Phase-Noise and Amplitude-Noise Measurement of DACs and DDSs.

This article proposes a method for the measurement of phase noise (PN, or PM noise) and amplitude noise (AN, or AM noise) of digital-to-analog converters (DACs) and direct digital synthesizers (DDSs) based on the modulation-index amplification. The carrier is first reduced by a controlled amount (30-40 dB) by adding a reference signal of nearly equal amplitude and opposite in phase. Then, residual carrier and noise sidebands are amplified and sent to a conventional PN analyzer. The main virtues of our method are: 1) the noise specs of the PN analyzer are relaxed by a factor equal to the carrier suppression ratio and 2) the capability to measure the AN using a PN analyzer with no need for the analyzer to feature AN measurement. An obvious variant enables AN and PN measurements using an AN analyzer with no PN measurement capability. Such an instrument is extremely simple and easy to implement with a power-detector diode followed by an FFT analyzer. Unlike the classical bridge (interferometric) method, there is no need for external line stretcher and variable attenuators because phase and amplitude controls are implemented in the device under test. In one case (AD9144), we could measure the noise over 10 decades of frequency. The flicker noise matches the exact 1/f law with a maximum discrepancy of ±1 dB over 7.5 decades. Due to the simplicity, reliability, and low background noise, this method has the potential to become the standard method for the AN and PN measurements of DACs and DDSs.

Noise characterization of analog to digital converters for amplitude and phase noise measurements.

Improvements on electronic technology in recent years have allowed the application of digital techniques in phase noise metrology, where low noise and high accuracy are required, yielding flexibility in system implementation and setup. This results in measurement systems with extended capabilities, additional functionalities, and ease of use. In most digital schemes, the Analog to Digital Converters (ADCs) set the ultimate performance of the system; therefore the proper selection of this component is a critical issue. Currently, the information available in the literature describes in depth the ADC features only at frequency offsets far from the carrier. However, the performance close to the carrier is a more important concern. As a consequence, the ADC noise is, in general, analyzed on the implemented phase measurement setup. We propose a noise model for ADCs and a method to estimate its parameters. The method retrieves the phase modulation and amplitude modulation noise by sampling around zero and maximum amplitude, a test sine-wave synchronous with the ADC clock. The model allows discriminating the ADC noise sources and obtaining the phase noise and amplitude noise power spectral densities from 10 Hz to one half of the sampling frequency. This approach reduces the data processing, allowing an efficient ADC evaluation in terms of hardware complexity and computational cost.

Peripheral neuroectodermal sarcoma of soft tissue (peripheral neuroepithelioma): a pathologic study of ten cases with differential diagnosis regarding other small, round-cell sarcomas.

Peripheral neuroepithelioma of soft tissue belongs to the group of peripheral neuroectodermal tumors (PNETs), but because of its clinical, biological, and morphological characteristics, it differs from other small, round-cell sarcomas that appear in children (neuroblastoma) or in the thoracopulmonary region (Askin's tumor) and bone (peripheral neuroectodermal sarcoma of bone). We report ten new cases of such PNET variety, based on their histologic, immunohistochemical, and electron microscopic findings. In all of these cases, the clinicopathologic correlations demonstrated high malignancy, with an ominous outcome in nine cases. The mean age of the patients was 32.6 years and there was a clear male predominance (eight men, two women). Histologically, the presence of Homer-Wright rosettes is mandatory for diagnosis, being complemented with positive immunohistochemistry for several neural immunomarkers using paraffin-embedded material. Neuron-specific enolase, E-36, HNK-1, and chromogranin neural markers proved to be positive in a high number of cases, but other markers (S-100 protein, synapto-physin, GFA protein, and neurofilaments [70 kilodalton]) were absent. Electron microscopy confirmed the presence of neural structures, both by scanning and transmission electron microscopy.

Bipolar (neural and myoblastic) phenotype in cell lines derived from human germ cell tumours of testis.

Non-seminomatous germ cell tumours of the testis (NSGCT) form a heterogeneous group of neoplasms. Cell lines derived from NSGCT may provide useful data concerning the biology of neoplasic precursor germ cells, differentiation of tumour stem cells and the relationship between various tissue components of these tumours. Four NSGCT were studied, two mixed tumours composed of teratocarcinoma, yolk sac and trophoblastic elements, and two malignant teratomas with a massive neuroectodermal component, equivalent to primary neuroectodermal tumours (PNET) of the testis. The explanted tumours gave rise to various cell populations, including epitheloid cells, flattened large cells, spindle cells and tear drop cells of neuroblastic type. Ultrastructurally, cultured cells expressed various degrees of neural and muscular differentiation: neurosecretory granules, intermediate filaments of glial nature, and filaments resembling Z-bands. Cultured cells showed the expression of several neural and muscular markers, including neurofilaments, cytokeratin, actin, desmin, neuron-specific enolase, glial fibrillary acidic protein and HNK-1. In addition, three cases expressed HBA-71 antigen and two expressed MyoD1 protein. All cases were aneuploid, and an isochromosome 12p, i(12p), was detected in three cases. Myoblastic and neural cells are the predominant tumour cells that grow in vitro, independent of the nature and composition of the primary germ cell tumour. A histogenetic relationship between germ cell tumours and small round cell tumours of childhood is suggested.

Soft tissue Ewing sarcoma--peripheral primitive neuroectodermal tumor with atypical clear cell pattern shows a new type of EWS-FEV fusion transcript.

This study describes a new case of Ewing sarcoma (ES)-peripheral primitive neuroectodermal tumor (pPNET) with unusual phenotype and fusion gene structure. The tumor located in the inguinal area of a 15-year-old boy showed a highly aggressive behavior with hematogenous metastases after intensive chemotherapy and bone marrow transplant, causing death 28 months after diagnosis. The tumor displayed a clear cell pattern, and several neuroectodermal markers proved positive both in the original tumor and in xenografts. This neuroectodermal character was confirmed by electron microscopy. Moreover, cytogenetically the tumor has an unusual chromosomal rearrangement, t(2;22)(q13;q22,t(3;18)(p21;q23); representing a new EWS-FEV fusion type in which exon 7 of EWS gene is fused with exon 2 of FEV gene. This is the third published study of an ES-pPNET showing EWS-FEV fusion described, but it is the first study of a tumor with the aforementioned fusion points. These findings support the genetic and morphologic heterogeneity existing within the group of ES-pPNET tumors.

Translocation (X;18) in a biphasic synovial sarcoma with morphologic features of neural differentiation.

The authors report a recurred neoplasm showing distinctive histologic, immunophenotypic, and ultrastructural features characteristic of biphasic synovial sarcoma with neural differentiation. The features include areas with a growth pattern of densely packed spindle cells in irregularly intersecting, broad fascicles, diffuse vimentin and HBA 71 immunoreactivity, expression of S-100 protein, and other neural markers. Moreover, areas with glandular structures and cellular expression of cytokeratin and epithelial membrane antigen were noted. Additionally, areas of neural-like growth pattern were positive for neuron-specific enolase, HNK-1, and protein gene product 9.5. Furthermore, cytogenetic analysis, two-color interphase fluorescence in situ hybridization, and reverse transcription polymerase chain reaction demonstrated the reciprocal translocation between chromosomes X and 18 associated with the different subtypes of tumor cells. The establishment and characterization of the tumor cell line are detailed. This cell line retains the distinct morphologic and genetic characteristics of the original biphasic synovial sarcoma with neural differentiation.

Molecular alterations of the RB1, TP53, and MDM2 genes in primary and xenografted human osteosarcomas.

We report the status of the RB1, TP53, and MDM2 genes in human osteosarcomas and cell lines established from surgical specimens and transplanted into athymic naked mice. By using reverse transcriptase-polymerase chain reaction (RT-PCR) as a prescreening technique and posterior sequencing, we observe new mutations in the RB1 gene, notably a duplication in tandem of exons 3 through 6. TP53 mutations appear in codons most frequently mutated in osteosarcomas. We have not seen MDM2 gene amplification in any reported case. These molecular alterations appear in different osteosarcomas not simultaneously present in the same tumor sample. A link has been described between these three genes in the pathways that control the cell cycle and the tumoral progression, but their functions are probably independent in the development of osteosarcomas. TP53 mutations appear in adult patients, whereas RB1 alterations occur mostly in younger patients.

Case of meningioma with del(1)(p32) as sole anomaly.

We studied a case of typical syncytial meningioma. Cytogenetic analysis of the tumor cells showed a karyotype with normal chromosomes 22 and only one anomaly, del(1)(p32). Cases of meningiomas with normal chromosomes 22 and other anomalies are rare, and it is difficult to correlate their histologic characteristics and biologic behavior.

Near-haploidy in a malignant sacrococcygeal teratoma.

Cytogenetic analysis of a malignant sacrococcygeal teratoma in an adult patient revealed near-haploid (77%), near-diploid (19%), and polyploid (4%) cells. The near-haploid cells had a karyotype of 25,XX,der(5)t(5;7)(p15;p13),+7,der(9)t(6;9)(p21;q34),r(17)(p13q25) . In the near-diploid and polyploid cells identical copies of the structural chromosomal changes were found. Although some of the anomalies observed appear unique to this case, a common breakpoint in chromosome 6 was previously reported as specific in a subgroup of extragonadal germ cell tumors of adults.

Characterization of a new rat cell line established from 2'AAF-induced combined hepatocellular cholangiocellular carcinoma.

A rat cell line-nominated CC-62 derived from a combined hepatocellular and cholangiocellular carcinoma obtained by administration of 2-acetylaminofluorene to male Wistar rats, has been established. Using light and electron microscopy it was determined that morphologically the tumor consisted of a mixed population of hepatocytes and cholangiolar neoplastic cells, intermingled with small, undifferentiated oval-like cells. The CC-62 line has been maintained through 90 passages in culture adopting a paving stone arrangement. Doubling time at the 12th passage was 23 h. Immunostaining with a panel of antisera was performed to identify the cytological profiles of the cell line. There was no k-ras or p53 expression by immunohistochemistry, and molecular biology failed to detect mutations. Molecular analysis by reverse transcriptase-polymerase chain reaction revealed transcripts for c-met but no expression of HGF messenger ribonucleic acid. Three cell lines cloned from CC-62 showed the same immunohistochemical and molecular pattern as the parental line. Cytogenetic analysis revealed a chromosome number ranging from 74 to 82 with a modal number of 79 but no clonal structural abnormalities were found. Deoxyribonucleic acid ploidy analysis showed an aneuploid peak. CC-62 caused tumors 1 mo after subcutaneous transplantation into nude mice, with morphological patterns of mucosecretory solid and spindle-shaped carcinoma. This cell line is the first established from a primary rat combined hepatocellular and cholangiocellular neoplasm. The resulting cells expressed biological and morphological markers of hepatocytes and cholangiolar cells. Therefore this cell line may contribute to a better understanding of the histogenesis of liver cancer.

Ultrastructure of one Ewing's sarcoma of bone with endothelial character and a comparative review of the vessels in 27 cases of typical Ewing's sarcoma.

An atypical variant of Ewing's sarcoma, located in the left hip of a nine-year-old girl, is discussed at optical, histochemical and electron microscopical level. The endothelial appearing cells seem to play a main role in its histogenesis. Tumoral cells of an undifferentiated blastemic nature show round nuclei and bright lucent cytoplasm, being organized in solid sheets or vascular-like profiles. Alkaline and acid phosphatases are very prominent in all tumoral cells, and some of them also show PAS positive material. Its ultrastructure demonstrates an active pinocytic capacity, cytoplasmic filaments and Weibel-Palade bodies. Simultaneously a review is performed on 27 cases of typical Ewing's sarcoma of bone in order to compare its vessels of a reactive nature with this tumor. A differential diagnosis with hemangioendothelioma primary to bone is established.

Fibroblast and myofibroblast participation in malignant fibrous histiocytoma (MFH) of bone. Ultrastructural study of eight cases with immunohistochemical support.

Eight malignant fibrous histiocytomas (MFH) of bone were studied with immunohistochemistry and electron microscopy. Ultrastructurally, fibroblasts and myofibroblasts were the main tumor cells in four cases and abundant in two other cases; these cells showed immunohistochemical positivity to alpha 1-antitrypsin, vimentin and anti-muscle antigen (HHF 35). Moreover, histiocytic-like tumor cells were electron-microscopically detected in four cases, being the main tumor cell type in two of the cases; immunohistochemically these cells expressed positivity to alpha-1-antichymotrypsin (A1ACT), alpha-1-antitrypsin (A1AT) and vimentin. Present results confirm the cellular heterogeneity of MFH of bone, in which fibroblasts and myofibroblasts transformed cells play a histogenetical role, suggesting the existence of close links with classic fibrosarcoma of bone.

Value of nude mice xenografts in the expression of cell heterogeneity of human sarcomas of bone and soft tissue.

Nude mice xenotransplants have been performed on human primary sarcomas of bone and soft tissues in order to delve into the cell heterogeneity of these neoplasms. Particular emphasis has been given to the group of small round blue cell sarcomas (Ewing's sarcomas and peripheral neuroectodermal tumors). Out of 31 xenotransplanted sarcomas, 16 cases have grown positively, and many of them continue to be transferred into nude mice on a regular time basis, being presently considered as fully established nude lines. Here we report the results of such a system, which has been followed with optical, electron microscopical, immunohistochemical and cytogenetic techniques. Osteosarcomas make up the group with the highest number of positivities taken (6 out of 9 transplanted cases). Diversity in growth rate, positive tumors and morphology are taken into consideration. Epithelial foci were seen in one of the transplanted neoplasms. Malignant fibrous histiocytoma and other mesenchymal sarcomas of bone and soft tissues are reviewed. Changes in immunohistochemical reactivity (alpha-1AT and alpha-1AQT) were observed in the transplanted neoplasms. Cytogenetic analysis performed on an undifferentiated (primitive) soft-tissue sarcoma provided clues to its synovial origin. Analysis of Ewing's sarcoma performed on nude mice transplanted tumors shows heterogeneous immunohistochemical response, with enhancement of cytokeratin positive cells, not previously seen in the primary neoplasms.

Nasal glioma or nasal glial heterotopia? Morphological, immunohistochemical and ultrastructural study of two cases.

The term nasal glioma has been used to describe a congenital benign tumor of the nasal region containing neural tissue. The nature of these lesions remains open to controversy, because of the different locations of the heterotopic neural tissue involved, the deficient development of the bony structures and the persistence or not of the structural relations with the central nervous system. More recent terms define these lesions as ectopic nervous tissue. A clinical, morphological, ultrastructural and immunohistochemical study is made of two cases of nasal glioma, one associated with agenesis of the corpus callosum. In this case, the mother had been treated with clomiphene. In such cases, morphological and immunohistochemical findings support that "nasal glioma" remain valid as a descriptive term defining a congenital benign tumor composed of heterotopic neural tissue within the nasal region and covered by skin, that may recur following incomplete surgical resection.

Histology, immunohistochemistry, and electron microscopy of small round cell tumors of bone.

Small round cell tumors (SRCTs) of the bone make up a family of primary bone sarcomas with morphologically, biologically, and clinically specific features. Among them, Ewing's sarcoma (ES) is the most common entity, but several varieties such as atypical ES, large cell ES, and ES with neuroectodermal differentiation (peripheral primitive neuroectodermal tumor of the bone or neuroepithelioma of the bone) have been identified recently. Histology and electron microscopy together with the variable expression of several epitopes (as shown by immunohistochemistry, mainly HBA/71 [Mic2 antigen]) provide the basis for characterizing the group within the context of neuroectodermal-derived neoplasms. A number of other ES-like tumors with small round cells, mimicking those previously described, have been characterized; Askin's tumor of the thoracopulmonary region will be considered as an ES similar to those already described, but within a particularly anatomic location. On the other hand, the presence of an endothelial appearance within a poorly differentiated neoplasm may be present in some ES-like SRCTs (atypical ES with endothelial features). The differential diagnosis with other sarcomas defined by small round to spindle cell contours might prove difficult. Particular attention must be paid to small cell osteosarcoma and mesenchymal chondrosarcoma. Likewise, "primitive sarcoma of bone" is considered in this study because it is a very rare neoplasm differing from the formerly discussed types; its pluripotentiality provides this tumor a blastemic character and a multiphenotypic expression. Malignant non-Hodgkin's lymphoma is an unusual presentation when primary to the bone, previous to any other anatomic location. Several subtypes have been considered within a histology that encompasses that seen in lymph nodes.

[Determination of copper in hepatic tissue for the diagnosis of Wilson's disease]. / Determinación de cobre en tejido hepático para el diagnóstico de la enfermedad de Wilson.

Three young patients had clinical data compatible with Wilson's disease (WD); all of them had high serum levels of ceruloplasmin without Kayser-Fleischer rings (K-F), the urinary copper level being very low, not supporting the Wilson's disease diagnosis. This reason was why we decided to detect the amount of copper in the liver tissue, which was very high in all patients, confirming the disease. We would comment that WD of abdominal type does not usually have the K-F rings, which made the diagnosis difficult. An algorithm is proposed to be applied in each case were WD is suspected.

[Biopathology of Ewing's sarcoma]. / Biopatologiia sarkomy Iuinga.

The paper presents the history of Ewing's sarcoma studies; the results of light- and electron microscopy, immunohistochemistry of its variants; criteria of prognosis and differential diagnosis with osteosarcoma, undifferentiated bone sarcoma, malignant ectomesenchymoma, lymphoma, neuroblastoma and rhabdomyosarcoma metastases.

Synovial sarcoma (SS): new perspectives supported by modern technology.

Based upon the experience of 256 cases of synovial sarcoma (SS), the present review analyzes structural, biological and molecular pathology of this poorly known sarcoma. The histology displays a multiphenotype with two major components: biphasic and monophasic SS. In addition, a number of variants have been described: undifferentiated Ewing's like, myoxid and predominantly epithelial (monophasic epithelial sarcoma). Microcalcifications and squamous metaplasia are often seen in the tumor. Immunohistochemistry with EMA and cytokeratin in the epithelial or epithelioid component is diagnostic for SS together with vimentin positivity in the spindle cells. Several other epitopes are also expressed (CD99, CD56, C-MET, HGF/SF, CD44). The ultrastructure confirms the variegated pattern of the neoplasm demonstrating the epithelial component and the epithelioid or spindle cell type closely associated with each other. Transition of epithelial cells to epithelioid and spindle-like mesenchymal component is seen. Nude-mice xenografts and cell lines after in vitro culture confirm heterogeneity of this sarcoma. Molecular histology of the SS has provided high utility not only for their differential diagnosis due to a specific chromosomal translocation: t(X;18)(p11.2;q11.2) but also after cloning these breakpoints resulting in the fusion of two genes: SYT at 18q11 and SSX at Xp11. Further observations have lead to distinguish the existence of two related genes: SSX1 and SSX2, that provide a highly specific and sensitive diagnostic marker for SS. Moreover, clinical correlations have demonstrated that SYT-SSX1 leads to a poor clinical outcome while the fusion SYT-SSX2 provides survival advantages to the patients.