The cell growth inhibitory transcription factor C/EBPdelta is expressed in human meningiomas in association with low histological grade and proliferation index.

CCAAT/enhancer binding protein (C/EBP) delta is a transcription factor which has been demonstrated to mediate the growth arrest of mammary and prostate cancer cell lines. It is induced by several stimuli including inflammatory cytokines. In this study, C/EBPdelta immunohistochemical expression was assessed in 49 meningiomas of different histotype and grade and correlated with a variety of clinico-pathological data and with the overall and recurrence-free survival of the patients. Positive staining was observed in the nuclei of neoplastic cells in 22 out of the 49 cases analyzed. C/EBPdelta expression was significantly associated with a low histological grade and proliferation index, reflected by low Ki-67 labeling index (LI) and mitotic activity, and with the presence of intra-tumoral inflammatory infiltrate and the absence of necrosis. In addition, the absence of C/EBPdelta was significantly correlated with a shorter disease-free interval. Our findings suggest that C/EBPdelta expression may prevent the development of recurrences by inhibition of neoplastic growth in meningiomas. If further studies confirm its induction by inflammatory mediators, this might be exploited in novel therapies to prevent recurrences in meningiomas.

CO2 efflux, CO2 concentration and photosynthetic refixation in stems of Eucalyptus globulus (Labill.).

In spite of the importance of respiration in forest carbon budgets, the mechanisms by which physiological factors control stem respiration are unclear. An experiment was set up in a Eucalyptus globulus plantation in central Portugal with monoculture stands of 5-year-old and 10-year-old trees. CO(2) efflux from stems under shaded and unshaded conditions, as well as the concentration of CO(2) dissolved in sap [CO(2)(*)], stem temperature, and sap flow were measured with the objective of improving our understanding of the factors controlling CO(2) release from stems of E. globulus. CO(2) efflux was consistently higher in 5-year-old, compared with 10-year-old, stems, averaging 3.4 versus 1.3 mumol m(-2) s(-1), respectively. Temperature and [CO(2)(*)] both had important, and similar, influences on the rate of CO(2) efflux from the stems, but neither explained the difference in the magnitude of CO(2) efflux between trees of different age and size. No relationship was found between efflux and sap flow, and efflux was independent of tree volume, suggesting the presence of substantial barriers to the diffusion of CO(2) from the xylem to the atmosphere in this species. The rate of corticular photosynthesis was the same in trees of both ages and only reduced CO(2) efflux by 7%, probably due to the low irradiance at the stem surface below the canopy. The younger trees were growing at a much faster rate than the older trees. The difference between CO(2) efflux from the younger and older stems appears to have resulted from a difference in growth respiration rather than a difference in the rate of diffusion of xylem-transported CO(2).

Central neurocytoma of the fourth ventricle. Case history.

Central neurocytomas are low-grade tumours of neuronal origin, affecting mainly young patients and usually located in the lateral or third ventricle. We report a rare case of central neurocytoma at the fourth ventricle level. Magnetic resonance imaging showed a homogeneously enhancing mass lesion at the fourth ventricle. Gross-total surgical removal was achieved. The histological diagnosis was of central neurocytoma but the lesion showed a fairly elevated Ki-67 index (6%). Given this finding, close neuroimaging monitoring was performed and at the moment the patient is free of recurrence.

Chordoid glioma of the third ventricle: an ultrastructural study of three cases with a histogenetic hypothesis.

Chordoid glioma is a rare neoplasm occurring in the third ventricle and, as the name implies, having a chordoid appearance. It is currently considered a glial neoplasm of uncertain histogenesis with distinct clinicopathologic features. We report three cases of chordoid glioma with a focus on the ultrastructural appearance. The patients were two men and one woman aged, respectively, 34, 40, and 43 years. Immunohistochemically, all tumors showed strong and diffuse reactivity for glial fibrillary acidic protein and vimentin, whereas immunoreactivity for epithelial membrane antigen and cytokeratin was focal. Ultrastructurally, they showed features of ependymal differentiation for the presence of an apical pole with microvilli and a basal pole characterized, as in normal ependyma, by many hemidesmosomelike structures connecting cell membranes to the underlying basal lamina. Constant features were a submicroscopic cell body zonation (i.e., perinuclear, intermediate, subapical, and apical regions) and the presence of secretory granules. These findings were similar to those described for the secretory ependymal cells of the subcommissural organ, a small structure located in a dorsocaudal region of the third ventricle that undergoes regression after birth in humans. Our observations suggest that chordoid glioma may represent a subtype of ependymoma whose cells resemble the highly specialized ependyma of the subcommissural organ.

Intracranial desmoplastic small-cell tumor. Report of a case.

We report a case of desmoplastic small-cell tumor occurring in the CNS in relation to the tentorium in a 24-year-old man. Morphologically, the neoplasm had the typical appearance of small, round tumor cells of primitive appearance growing as well-defined nests separated by abundant desmoplastic stroma. The diagnosis was confirmed through the demonstration of immunoreactivity for keratin, desmin, and neuron-specific enolase and the detection by Southern blot analysis of a unique gene resulting from the fusion of the WT1 gene in chromosome 11 and the EWS gene in chromosome 22. This is the first documented instance of the occurrence of this tumor type at a distance from a mesothelial-lined surface.

Extraventricular neoplasms with neurocytoma features. A clinicopathological study of 11 cases.

The clinicopathological features of a series of neuronal and mixed neuronal and astrocytic neoplasms of the CNS are described. Patients were aged 5 to 63 years. Six cases were composed predominantly of small round cells with clear cytoplasm resembling central neurocytoma but lacked the characteristic intraventricular location of that tumor. The remaining five cases had similar neurocytomatous features associated with a benign astrocytic component. Ganglion cells and hyalinization vessels were observed in both groups. The growth fraction evaluated with monoclonal antibody Ki67Mib1 was low, ranging from 1 to 1.5%. Immunohistochemical detection of synaptophysin played a crucial role in identifying the neuronal nature of these neoplasms and was instrumental in distinguishing them from oligodendrogliomas, with which they are readily confused. The neuronal nature of the oligodendroglial-like cells was confirmed ultrastructurally in one case. The present cases, together with others reported previously, suggest that neoplasms of the CNS with "neurocytic" components are more frequent than generally assumed and expand the morphologic spectrum of neuronal and mixed neuronal-glial tumors. Except for one patient who died postoperatively, all patients were alive at follow-up ranging from 6 to 80 months.

Nonrandom gain of chromosome 7 in central neurocytoma: a chromosomal analysis and fluorescence in situ hybridization study.

Central neurocytoma is a benign, slow-growing neoplasm with favourable prognosis. Biomolecular analysis has failed to demonstrate significant alterations, and no cytogenetic alterations have been reported. In this study we demonstrate chromosome 7 gain in three of nine neurocytomas (33%). Traditional cytogenetic analysis performed in four of the nine cases identified trisomy 7 as the sole chromosomal abnormality in one case. Interphase cytogenetics utilizing fluorescent in situ hybridization (FISH) on cell suspensions from formalin-fixed paraffin-embedded tumour tissue performed in all nine cases detected trisomy 7 in two more cases and tetrasomy in another. Our results suggest that chromosome 7 gain is a feature of neuroectodermal tumorigenesis, possibly conferring growth advantage on the neoplastic cells. FISH on interphase nuclei is a valuable adjunct in the genetic evaluation of rare central nervous system neoplasms with low baseline proliferative activity.

Unusual types of chondrosarcoma: chondrosarcoma arising in soft tissue and in non-skeletal cartilage.

Five cases of unusual chondrosarcomas of the soft tissue and of the skeletal cartilage are reported. A retrospective clinical study has been evaluated on ways to improve our knowledge of these rare neoplasms.

Chondrosarcoma--55 unreported cases: epidemiology, surgical treatment and prognostic factors.

Fifty-five cases of chondrosarcoma, seen at the Istituto Nazionale Tumori of Milan, were reviewed to collect epidemiological data in order to verify therapeutic effects and the validity of possible prognostic factors. Epidemiological data according to sex and age distribution and skeletal location were in accordance with the literature (male:female ratio, 1.8; mean age, 37 years, 62% of lesions located in the pelvic or scapular girdle). Of 52 cases operated on with the intent of radicality, 5 were intralesional operations, 20 marginal and 27 radical. The local recurrence rate was dependent upon the degree of surgical radicality (60%, 35% and 11% respectively for intralesional, marginal and radical surgery). Age, site, type of first symptom and pathological grading were significant as prognostic factors. The type of the first symptom was directly correlated to the site of the tumour. Sex, tumour size and degree of surgical radicality were not relevant.

Effects of partial defoliation on carbon and nitrogen partitioning and photosynthetic carbon uptake by two-year-old cork oak (Quercus suber) saplings.

At the end of the growing season in late July, 20-month-old cork oak (Quercus suber L.) saplings were partially defoliated (63% of leaf area) to evaluate their ability to recover leaf area after defoliation. At 18 and 127 days after defoliation, changes in starch and nitrogen pools were determined in leaves and perennial organs, and variations in photosynthetic carbon uptake were investigated. To determine the role of stored nitrogen in regrowth after defoliation, plant nitrogen was labeled in the previous winter by enriching the nutrient solution with 15N. Plants recovered the lost leaf area in 127 days. Although there was remobilization of starch and nitrogen from leaves and perennial organs, the availability of resources for growth in the following spring was not decreased by defoliation. On the contrary, starch concentration in coarse roots was higher in defoliated saplings than in control saplings, presumably as a result of the higher net CO2 exchange rate in newly developed leaves compared with pre-existing leaves.

Solitary fibrous tumor of the meninges: two new cases and review of the literature.

BACKGROUND: Solitary fibrous tumor (SFT), a mesenchymal neoplasm originally described in the pleura has been more recently reported to arise in a number of other sites, including the meninges. Nowadays immunohistochemistry facilitates the otherwise problematic differential diagnosis with regard to other benign and malignant spindle cell neoplasms of the central nervous system. METHODS: Two recently treated cases of meningeal SFT (one craniospinal, one spinal) are presented and discussed in the light of the present knowledge and a review of the literature. RESULTS: Total resection was followed by complete recovery and both patients are presently asymptomatic and without evidence of disease. The microscopic and immunohistochemical profiles (CD 34, vimentin positive; S-100, EMA negative) were consistent with those of previously reported cases. CONCLUSIONS: The majority of SFTs behave in a benign fashion and do not recur unless subtotally resected. Malignant variants may account for up to 37% of SFTs in other locations but have never been reported to occur in the meninges. Meningeal SFTs are to be considered a new pathological entity. Wider use of immunohistochemical screening should enable the determination of their real incidence; larger series and longer follow-up will provide conclusions about their treatment and prognosis.

Hyalinizing trabecular adenoma of the thyroid. Report of two cases, with cytologic, immunohistochemical and ultrastructural studies.

The cytologic, histologic, immunocytochemical and ultrastructural features of 2 cases of hyalinizing trabecular adenoma (HTA) of the thyroid are described. The difficulty of a cytologic diagnosis and the need for an immunohistochemical profile of the lesions for a final histologic diagnosis are emphasized.

Relationship between pulmonary function tests and morphologic changes in the lung in bleomycin-treated patients.

The transfer factor of the lung for carbon monoxide (TLCO) and the respiratory response to moderate exercise were determined in 16 patients with pulmonary metastasis pretreated with bleomycin who underwent pulmonary partial resection. The results of pulmonary function tests were related to histologic findings. No significant correlation was found between pulmonary morphologic changes and the TLCO: this questions the usefulness of TLCO as a predictive method for detecting subclinical bleomycin pulmonary toxicity. No significant correlation was found between morphologic findings and cumulative dose of bleomycin: this confirms the limit of a dose limitation strategy. In contrast, evaluation of pulmonary response to exercise seemed to improve the sensitivity of monitoring such patients for clinical evidence of latent pulmonary toxicity; however, it seems that critical morphologic changes must occur before pulmonary performance begins to deteriorate.

Improvement of tumor cell detection using a pool of monoclonal antibodies.

It has been proven that monoclonal antibodies which are not strictly tumor specific may be useful in clinical oncology for diagnosis and in in vitro therapy. These applications, however, are hampered by the heterogeneous expression on tumor cells of the epitopes defined by the majority of monoclonal antibodies produced so far. The use of combined monoclonals could complement their antitumor specificity and solve the problem. In this perspective we selected nine monoclonal antibodies directed against different antigens of primary and metastatic breast cancer cells. The reactivity of the pool of these nine monoclonals versus a single antibody (MBr1) was determined by immunofluorescence on tumor cell lines, on frozen sections of various carcinomas, and on live cells obtained from malignant effusions. The results obtained with the pool, compared to those using MBr1 alone, showed a remarkable increase in the number of immunopositive breast and other carcinomas and the number of immunopositive cells within each positive tumor. In fact, the percentage of immunoreactive breast carcinomas increased from 79% to 100%, and the percentage of immunoreactive carcinomas of other sites from 61% to 89%. In addition, the number of positive breast carcinomas showing 100% immunoreactive cells increased from 5% with MBr1 to 71% when the pool was used.

CO2 fluxes and respiration of branch segments of sycamore (Platanus occidentalis L.) examined at different sap velocities, branch diameters, and temperatures.

Respiration of stems and branches of trees (R(S)) has typically been estimated by measuring radial CO(2) efflux from woody tissue (E(A)) and rates of efflux are often scaled temporally using a temperature relationship (Q(10)). High concentrations of CO(2) in xylem sap ([CO(2)*]) have been shown to affect E(A), and the transport of CO(2) in the xylem stream has been suggested as a mechanism to explain field observations of temperature-independent fluctuations in E(A). Sap velocity and temperature were manipulated in detached branch segments of sycamore (Platanus occidentalis L.) under controlled conditions to quantify these effects. Within individual branches of similar size, E(A) and [CO(2)*] were greater at low sap velocity, while the amount of respired CO(2) transported in sap (transport flux, F(T)) was greater at high sap velocity. E(A) was linearly correlated with [CO(2)*]. In branches of three diameter classes (1, 2, and 3 cm), volume-based E(A), F(T), and R(S) did not differ, but surface-area based CO(2) fluxes increased with diameter class. Regardless of diameter, E(A) accounted for only 30% of respired CO(2) at high sap velocity, while at low sap velocity, E(A) accounted for 71% of respired CO(2). E(A), F(T), and R(S) measured at 5, 20, and 35 degrees C at the same sap velocity showed a typical exponential response to temperature. However, at the lowest temperature, E(A) accounted for only 18% of the CO(2) released from respiring cells compared with 44% at the highest temperature, perhaps due to the effect of temperature on the solubility of CO(2) in water. These results directly demonstrate the transport of respired CO(2) in the xylem stream and may help to explain inconsistencies in stem and branch respiration measurements made in situ.

Spinal intradural müllerianosis: a case report.

Müllerianosis is a term used to indicate lesions composed of an admixture of two or three types of müllerian-derivation glands in heterotopic sites. In this report we describe a case of spinal cord müllerianosis which occurred in a 42-year-old woman. The patient had suffered from catamenial lumbago and sciatica of three years duration before undergoing laminectomy of L2-L3 with excision of a polypoid mass that compressed nerve trunks. At histological examination, the lesion was composed of endocervical, endometrial and tubal glands within a smooth muscle nodule. These features were consistent with a diagnosis of müllerianosis. This is a very uncommon form of presentation of müllerianosis that must be correctly identified since patients can benefit from hormonal therapy.

Caveolin-1 in meningiomas: expression and clinico-pathological correlations.

Caveolin-1 (Cav-1) protein has been documented in several neoplasms with a controversial role in cell proliferation, tumour development and progression. The aim of the present study was to investigate the Cav-1 immunohistochemical expression in human meningiomas. Sixty-two cases, classified as 11 meningothelial (17%), 12 transitional (19%), 5 fibrous (8%), 3 microcystic (5%), 3 secretory (5%), 1 clear cell (2%), 1 chordoid (2%) and 26 (42%) atypical meningiomas, were selected from our pathological files. Clinico-pathological data, including Ki-67 values and survival data were also available. Ten leptomeningeal samples were utilized as normal tissue control. For each case, a polyclonal antibody against Cav-1 was applied and an intensity distribution (ID) score was determined. The Cav-1 immunoexpression was found in 95% of meningiomas with a variable ID score, while only minimal, not uniform, reactivity was noted in non-neoplastic meninges. Of note, higher Cav-1 ID score was significantly correlated with tumour site, Simpson's grade, histological type, higher histologic grade, Ki-67 labelling index > or = 4% and clinical course. Kaplan-Meier curves demonstrated a significantly worse survival in patients with higher Cav-1 ID score, Ki-67 > or = 4% and 2-3 Simpson grade. Multivariate analysis indicated that only Ki-67 was an independent prognostic factor. Increased immunoexpression of the Cav-1 seems to be associated with the biological aggressiveness of meningiomas, reflecting a worse prognosis.

DNA microspectrophotometric study in smear preparations from paraffin embedded tissue.

A DNA microspectrofluorimetric study on smears from cells detached from paraffin embedded tissue is presented. The cellular DNA values of these smears were compared with the cellular DNA values of fresh imprints and paraffin embedded sections obtained from the same tissue. The histograms were similar for fresh imprints and paraffin embedded smears while the DNA values in the sections were notably different. This method appears very suitable for retrospective studies of DNA using microspectrofluorimetry in routine histopathology.

Ultrastructural characterization of oligodendroglial-like cells in central nervous system tumors.

Cells with uniform, small-round nucleus and clear cytoplasm (oligodendroglial-like cell, OLC) are commonly observed in central nervous system (CNS) neoplasm of glial and neuronal lineage, such as oligodendroglioma, clear-cell ependymoma, and central neurocytoma. Immunohistochemistry does not always contribute to the characterization of OLC because of (1) loss of antigen expression; (2) lack of specific markers for oligodendrogliomas; and (3) occasional coexpression of neuronal and glial antigens. An ultrastructural analysis associated with an immunohistochemical study of 20 cases of CNS tumors largely constituted by OLCs has been performed. Neurocytomas (12 cases), medullocytomas (2 cases), cerebral neuroblastoma (1 case), and ganglioglioma (1 case) showed OLCs with ultrastructural features of neuronal differentiation (neuritic processes, dense-core granules, synaptic structures). Oligodendroglioma (3 cases) OLCs were characterized by mitochondrial-rich cytoplasm, and ependymoma (1 case) OLCs showed microrosettes and scattered cilia. The electron microscopic analysis can provide a more precise diagnosis of these OLC-containing tumors despite their uniform morphological appearance.