Oligodendrogliomas lacking O6-methylguanine-DNA-methyltransferase expression.

O6-Methylguanine-DNA-Methyltransferase (MGMT) is a DNA repair protein considered to be a chemosensitivity predictor. We evaluated the immunohistochemical MGMT expression in 28 consecutive oligodendroglial tumors (21 oligodendrogliomas, 5 mixed oligoastrocytomas, and 2 glioblastomas with prominent oligodendroglial features; 13 treated with CCNU) and compared it with that of 13 glioblastomas. Twenty-six (93%) oligodendroglial tumors were MGMT-negative, 2 (7%) were MGMT-positive. Twelve (92%) patients treated with CCNU had MGMT-negative lesions and their median survival was 73 months; 1 patient had an MGMT-positive oligodendroglioma and is alive at 28 months. Three (23%) glioblastomas were MGMT-negative and 10 (77%) MGMT-positive. The lower MGMT expression in oligodendroglial tumors compared to glioblastomas (P < 0.05), which have different chemosensitivity, suggests a possible role of MGMT in the determination of chemoresistance. Nevertheless, the heterogeneous outcome of our MGMT-negative oligodendroglial tumors treated with CCNU, indicates that MGMT expression alone is insufficient to predict the response to alkylating drugs, presumably because of the numerous mechanisms involved.

Ethanol-induced alterations of matrix network in the duodenal mucosa of chronic alcohol abusers.

Excessive consumption of alcoholic beverages may be associated with gastrointestinal symptoms, including dyspepsia and diarrhoea. It is not clear whether or not chronic alcohol ingestion damages the mucosa of the small intestine. We investigated the effect of chronic alcohol abuse on the duodenal mucosa, and particularly on its extracellular matrix (ECM) network. Duodenal biopsy specimens were obtained during upper gastrointestinal endoscopy from 50 chronic alcoholics without cirrhosis and 10 healthy subjects. Morphological studies were performed by routine histology, immunohistochemistry and electron microscopy. Morphometry of duodenal tissues was performed with a computerized image analyser. No significant duodenal epithelial changes were found in alcoholics, despite an evident reduction in the enterocyte turnover. Myofibroblast-like cells were significantly increased in the villus stroma of alcoholics in comparison to controls. These cells stained positively for desmin, alpha-smooth muscle actin and for several ECM components. In alcohol abusers the thickness of the mucosal basement membrane was greater and the staining for collagen I and III was enhanced both in the basement membrane and in the villus stroma. A higher expression of tenascin was also seen at the base of villi of alcoholics. Chronic alcohol abuse may induce fibrosis of duodenal villi which is associated with a transformation of villus juxta-parenchymal cells into active subepithelial myofibroblast-like cells able to produce different ECM components.

TGF-beta isoform and receptor expression in giant cell tumor and giant cell lesions of bone.

The authors examined the distribution of tumor growth factor-beta (TGF-beta) isoforms and receptors in 35 giant cell tumor (GCT) of bone in comparison with a group of benign giant cell-containing lesions of bone, including 5 aneurysmal bone cysts, 2 cases of brown tumor of hyperparathyroidism, 3 nonossifying fibromas, and 7 cases of giant cell reparative granuloma. The results of immunohistochemical analysis of GCT showed a complete absence of TGF-beta1 expression in both mononuclear tumor cells and giant cells. Only reactive bone present within the tumor showed an intense immunoreactivity. Transforming growth factor-beta2 and TGF-beta3 were detected in the majority of cases (97.1% and 82.8%, respectively), whereas TGF-beta receptor type I (TGF-beta RI) and type II (TGF-beta RII) were diffusely expressed in all cases. Reverse transcription-polymerase chain reaction (RT-PCR) analysis performed on 10 GCTs with specific oligonucleotide primers demonstrated the presence of mRNA transcripts for TGF-beta1, 2, 3, and for TGF-beta RI and RII. Quantitative measurements of TGF-beta1 in conditioned media from primary cultures of GCT showed undetectable or very low amounts of the cytokine (0-23 pg/mL). The results of immunohistochemical analysis showed that all giant cell-containing lesions of bone were at least focally positive for the 3 isoform of TGF-beta, with positivity present both in osteoclast-like giant cells and mononuclear cells, and diffusely positive for TGF-beta RI and RII. Reverse transcription-polymerase chain reaction analysis conducted on samples from 3 nonossifying fibromas and 1 giant cell reparative granuloma confirmed the expression of the corresponding mRNA. In conclusion, according to the current data, GCT of bone can be distinguished from other giant cell-containing lesions of bone on the basis of the absence of TGF-beta1 expression at the protein level, which appears to be the result of posttranslational regulation processes.

Oligodendroglioma: HMB-45 positivity using catalyzed signal amplification method: an immunohistochemical (HMB-45, CD31, p53, Mib-1) and ultrastructural study.

Although melanin synthesis and the presence of melanosomes are exceptionally reported in nervous system tumors, there is no record of melanotic oligodendrogliomas in the literature. The purpose of the current study was to evaluate whether melanosomes are immunohistochemically and ultrastructurally detectable in nonmelanotic oligodendrogliomas and to verify whether these data are related to prognosis. Thirty surgical specimens (19 primary lesions and 11 recurrences) from 19 patients were examined. Median survival was 80 months. Immunohistochemical studies were performed using the monoclonal antibodies HMB-45, CD31. Mib-1, and p53. Using catalyzed signal amplification (CSA), HMB-45 positivity was noticed in 3 (10%) of the oligodendrogliomas being studied. No correlation with survival was found. Ultrastructural examination displayed the presence of melanosomelike structures. Tumor vascularization, estimated by means of CD31 antibody, was increased in 6 of 19 primary lesions but there was no significant correlation with survival. Nine of the19 primary lesions were p53 negative. In these cases, survival was longer than in p53-positive tumors (P = 0.0213). Proliferation rate, evaluated with Mib-1, was unrelated to survival, but proved greater in recurrences (10 of 11 cases) than in primary tumors (7 of 19 lesions; P = 0.007).

Oligodendroglioma: CD44 as a possible prognostic opportunity.

CD44, in its standard form as well in its isoforms, is a cell surface adhesion glycoprotein which occurs in a wide variety of non-neoplastic and neoplastic cells. CD44 has been considered to be implicated in tumoral growth and in metastatic potential. We studied the immunohistochemical expression of CD44 standard in 30 oligodendrogliomas (19 primary lesions and 11 recurrences) in order to verify its possible prognostic role. Twelve primary oligodendrogliomas (63%) and 8 recurrences (73%) were CD44-positive. Three of 9 (33%) primary oligodendrogliomas with a Smith grade A-B and 9 of 10 (90%) primary oligodendrogliomas with a Smith grade C-D were found to be in CD44H-positive (p = 0.020). Three of 9 (33%) primary oligodendrogliomas that had not relapsed and 9 of 10 (90%) successively relapsed primary lesions were found to be CD44H-positive (p = 0.020). Median survival of the patients with a CD44H-positive lesion was 84 months; median survival of the patients with a CD44H-negative lesion was 91 months. We conclude that CD44H could have prognostic value regarding the occurrence of relapses.

Hodgkin's disease associated with sarcoidosis: case report.

Coexistence of true systemic sarcoidosis and Hodgkin's disease has been reported as a very exceptional occurrence. In this paper a case observed at the Institute of Radiology of Florence is described of which the most interesting features were 1) sarcoidosis appeared 5 years earlier than Hodgkin's disease; 2) at staging lymphography the paraortic nodes appeared extensively enlarged and showed multiple filling defects; 3) at laparotomy the nodes removed were histologically affected by sarcoidosis only; 4) multiple foci of sarcoidosis were found also in the spleen and liver; 5) this feature led us to refrain from irradiating the abdomen; 6) one year later a further enlargement of paraortic nodes was observed; 7) a second laparotomy revealed Hodgkin's infiltration in the removed nodes; 8) irradiation of the inverted "y" field was followed by complete regression of the nodes and the patient is alive and well 2.5 years after the relapse.

Primary cutaneous B-cell lymphoma: a unique type of low-grade lymphoma. Clinicopathologic and immunologic study of 83 cases.

The clinical presentation and course, and the morphoimmunologic features of primary cutaneous B-cell lymphoma (CBCL) were investigated in a series of 83 patients. Fifty-one patients were male and 32 were female (male-to-female ratio of 1.6:1); CBCL primarily involved the elderly (median age, 58 years). A locoregional extension of the disease was quite frequent (86.7%). The neoplastic cells showed a range of appearances reminiscent of the whole spectrum of follicular/parafollicular cells. The antigenic phenotype of tumor cells (CD19+, CD20+, CD22+, CD28+, CD10-, CD5-, MB2+, CD74+/-, CDw75+/-, MT2+/-, surface immunoglobulin + monoclonal/-) plus the presence of admixed CD14- dendritic reticulum cells suggest a mantle-zone nature for CBCL. The nonaggressive clinical behavior with a substantial tendency to remain localized to a limited area of the skin, the quite good response to nonaggressive treatment, and the dichotomy existing between the enhancement of morphoimmunologic atypism--which parallels the increasing age and growth rate of lesions--and the constant benign overall prognosis on long-term follow-up make CBCL a unique type of lymphoma of low-grade malignancy. Proper recognition of CBCL is mandatory to avoid possible undertreatment or overtreatment of the patients affected.

Prognostic significance of histologic subdivision of Hodgkin's disease nodular sclerosis.

Sixty-seven patients with nodular sclerosis (Hodgkin's disease stages I and II) have been subclassified according to the cellular composition and the amount of fibrosis. Predominance of mature lymphocytes and rarity of Reed Sternberg cells were associated with less extensive disease at presentation and more favourable outcome. A less definite correlation to the amount of fibrosis was found.

[CT-guided percutaneous fine-needle biopsy in the histological characterization of mediastinal-pulmonary lesions]. / La biopsia percutanea con ago sottile TC-guidata nella tipizzazione istologica delle lesioni mediastino-polmonari.

CT-guided percutaneous fine-needle biopsy (FNB) is the method of choice in the histological characterization of mediastinum and lung lesions in which a diagnosis could not be reached through noninvasive methods such as cytology of the sputum, or biopsy during bronchoscopy. FNB represents an alternative to diagnostic thoracotomy: it is, in fact, less invasive, it can be carried out with no need for hospitalization, and has a low incidence of complications. FNB diagnostic accuracy is very high, as our results prove: accuracy 89.6%, sensitivity 87.6% and specificity 98%. Our series includes 419 percutaneous fine-needle biopsies.

Endogenous splenic colonies and megakaryopoiesis in methylcellulose treated irradiated mice.

Endogenous splenic colonies are increased in methylcellulose-treated irradiated mice, 10 days after sublethal irradiation (450 R). The spleen shows an enhancement of megakaryopoiesis, especially localized around foam-cell foci. This suggests that the macrophage system, activated through phagocytic activity against methylcellulose, affects megakaryopoiesis by a microenvironmental mechanism.

[CT-guided thoracic biopsy. Personal experience with DBNH Haaga 20 G needles]. / Biopsia toracica TC-guidata. Esperienza personale con ago tipo DBNH 20 G.

CT-guided fine-needle biopsy of the chest is nowadays a conventional diagnostic procedure, which can be furtherly improved so as to increase its diagnostic sensitivity and to reduce complications. We studied a series of possible improvements over a 2-year period (1990-1992). In our radiology department 164 CT-guided biopsies were performed in 130 men and 34 women. DBNH Haaga 20-G (15 cm) needles (Cook, Denmark) were used. This kind of needle is a coaxial cutting-edge needle used for simultaneous cytological and histological sampling. Exams were performed with a Philip Tomoscanner CX-S (scanning time: 2.8 seconds). Of 164 tissue samples, 153 (93.4%) were adequate for histological diagnosis. As for suspected neoplastic disease, our results demonstrated 108 true positives, 27 true negatives, 18 false negatives and no false positive. Sensitivity, specificity and diagnostic accuracy were 85.7%, 100% and 88.2%, respectively. In 24 cases there were minor complications--i.e., 5 cases of parenchymal hemorrhage and 19 cases of minor pneumothorax. In one case only there was major pneumothorax which required surgical drainage. On the basis of our experience, we suggest the use of such coaxial catheters as the DBNH Haaga type for the collection of both histological and cytological material because this needle reduces the need for repeated invasive and potentially dangerous maneuvers.

Adhesion, growth, and matrix production by osteoblasts on collagen substrata.

A number of studies have demonstrated the pivotal role of collagen molecules in modulating cell growth and differentiation. In order to analyze the direct effects of collagen type I on the osteoblastic phenotype, we have devised an in vitro culture system for studying the interactions between bovine collagen type I and Saos-2 cells, a human osteoblastic cell line. Saos-2 cells were cultured both on top of collagen-coated culture dishes as well as inside a three-dimensional collagen network. Plating on dishes treated with collagen induced maximal adhesion of Saos-2 cells after 24-hour incubation. Cells cultured on collagen gel matrix expressed about 2.5-fold more alkaline phosphatase when compared with untreated plastic dishes. On collagen-coated dishes the responsiveness of Saos-2 cells to parathyroid hormone was decreased, whereas no modifications were observed in the effect of vasoactive intestinal peptide on these cells. Using a microfluorimetric measurement of DNA, an increase of proliferation was observed in Saos-2 cells cultured on collagen gel. Saos-2 cells were also able to colonize collagen sponges and in this three-dimensional network they were able to synthesize osteocalcin, as assessed both by immunocytochemistry and radioimmunoassay. In this study we have demonstrated that bovine collagen type I exhibits favorable effects on attachment and functional and growth activities of a human osteoblastic cell line, encouraging its use as a bone graft material.

Expression of transforming growth factor beta isoforms in osteosarcoma variants: association of TGF beta 1 with high-grade osteosarcomas.

Studies on osteosarcoma cell lines point to the potential importance of transforming growth factor beta (TGF beta) as an autocrine factor which controls the growth of human osteosarcomas. To define further the role of TGF beta isoforms in these neoplasms, a series of 27 osteosarcomas was studied using immunohistochemical, mRNA in situ hybridization, and reverse transcriptase-polymerase chain reaction (RT-PCR) techniques. All 14 central high-grade osteosarcomas, two telangiectatic osteosarcomas, and one high-grade surface osteosarcoma showed cytoplasmic immunoreactivity for TGF beta 1, -2, and -3. The expression of TGF beta 1 was moderate or diffuse in 14 cases (82.3 per cent), while low expression was detected in only three cases (17.7 per cent). For TGF beta 2 and -3, only moderate or diffuse staining was observed. Low-grade parosteal and periosteal osteosarcomas showed low or undetectable levels of TGF beta 1, while TGF beta 2 and -3 were moderately or diffusely expressed. Finally, three dedifferentiated parosteal osteosarcomas were diffusely positive for TGF beta 1, -2, and -3 in the high-grade component, while in the low-grade component, available for analysis in two of these cases, TGF beta 1 was demonstrated in a few neoplastic cells, and TGF beta 2 and -3 maintained a diffuse distribution. Statistical analysis of these data showed that high-grade osteosarcomas had a significantly higher expression of TGF beta 1 than low-grade osteosarcomas, while levels of TGF beta 2 and -3 were comparable in the two groups (p < 0.001; p = 0.3; p = 0.3, respectively; Fisher's exact test). Similarly, mRNA levels of TGF beta 1 detected by in situ hybridization were significantly higher (p = 0.04, Fisher's exact test) in high-grade osteosarcoma variants, while no differences were found for TGF beta 2 and -3 mRNA (p = 1.0; p = 0.2, respectively; Fisher's exact test). In addition, mRNA analysis performed by RT-PCR in seven cases (five high-grade and two low-grade osteosarcomas) confirmed the presence of high levels of TGF beta 1 in high-grade osteosarcomas, while low-grade tumours had low or absent mRNA expression. In conclusion, this positive association suggests that TGF beta 1 may be involved in determining the aggressive clinical behaviour of high-grade osteosarcomas.