Anaplastic thyroid carcinoma: diagnostic challenges,histopathologic features and ancillary testing

Anaplastic thyroid carcinoma (ATC) is an aggressive thyroid malignancy with high mortality rate. This malignancy arises in thyroid follicular cells either denovo or with an associated differentiated thyroid carcinoma component. Clinically, it usually presents as a rapidly enlarging mass, pain and locally compressive symptoms. Histopathologic variability and heterogeneity often pose diagnostic challenges, especially in scant and paucicellular specimens. This article describes the clinical, histopathologic and molecular features of ATC and also addresses the associated diagnostic limitations and challenges.     

Biochemical and biological activity of the anthracycline analog, 4-demethyl-6-0-methyl-doxorubicin

Summary The chromophore-modified derivative of doxorubicin, 4-demethyl-6-0-methyl-doxorubicin, has been tested for antitumor activity in a range of experimental murine tumor systems. In contrast to the inactive 6-0-methyl derivative of daunorubicin, 4-demethyl-6-0-methyl-doxorubicin provided antitumor effects comparable to that of the parent compound. In addition, detailed DNA-interaction studies showed that the doxorubicin derivative retains the ability to bind DNA by the intercalation mechanism. However, the binding affinity was appreciably reduced following structural modification in the anthraquinone chromophore. On the basis of the proposed models of intercalation, these results could be rationalized in terms of steric influence of the bulky methoxy group. The results of this study are in agreement with the correlation already observed between DNA binding and relative antitumor activity of anthracyclines.     

Human antibody against C domain of tenascin-C visualizes murine atherosclerotic plaques ex vivo.

Targeting proteins that are overexpressed in atherosclerotic plaques may open novel diagnostic applications. The C domain of tenascin-C is absent from normal adult tissues but can be inserted during tumor progression or tissue repair into the molecule by alternative splicing. We tested the ability of the human antibody G11, specific to this antigen, to reveal murine atherosclerotic plaques ex vivo. The antibody directed against the extra domain B of fibronectin (L19) was used as a reference. METHODS: We intravenously injected (125)I-labeled G11 or L19 antibodies into apolipoprotein E-deficient (ApoE(-/-)) mice and harvested the aortae 4 or 24 h later. En face analyses of distal aortae and longitudinal sections of the aortic arch were performed to compare antibody uptake using autoradiography with plaque staining using oil red O. Plaque macrophages were detected by immunohistochemistry (anti-CD68 staining). Biodistribution of injected antibodies was investigated in aortae and blood at 4 and 24 h. RESULTS: En face analyses revealed a significant correlation between radiolabeled G11 and fat-stained areas, increasing from 4 to 24 h, with a correlation coefficient of 0.92 (P < 0.0001) and an average signal-to-noise ratio of 104:1 at 24 h. Plaque imaging using L19 showed similar results (r = 0.86; P < 0.0001; signal-to-noise ratio, 72:1 at 24 h). Uptake of radiolabeled antibodies in histologic sections colocalized with fat staining and activated macrophages in aortic plaques. Biodistribution analyses confirmed specific accumulation in aortic plaques as well as rapid blood pool clearance of the antibodies 24 h after injection. Immunofluorescence analyses revealed increased expression of tenascin and fibronectin isoforms in macrophage-rich plaques. CONCLUSION: The antibody G11, specific to the C domain of tenascin-C, visualizes murine atherosclerotic plaques ex vivo. In conjunction with the increased expression of the C domain of tenascin-C in macrophage-rich plaques, the colocalization of G11 uptake with activated macrophages, and the favorable target-to-blood ratio at 24 h, this antibody may be useful for molecular imaging of advanced atherosclerotic plaques in the intact organism.     

Changes in pulmonary function test and cardio-pulmonary exercise capacity in COPD patients after lobar pulmonary resection.

OBJECTIVE: Pulmonary Function Tests (PFT) and Cardio-Pulmonary Exercise Testing (C-PET) are useful to evaluate operability in functionally compromised patients. Although modifications of PFT and C-PET after lung surgery have been widely explored, little information exists as to modifications of exercise capacity in COPD patients undergoing lung resection. We prospectively analyzed the changes in PFT and C-PET in patients with COPD after a pulmonary lobar resection. METHODS: From January 2003 to March 2004 all patients scheduled for lung resection were considered for participation in the study protocol. Those patients with a preoperative diagnosis of COPD on PFT were explored through a C-PET. Only patients who had undergone a lobar pulmonary resection were subsequently considered; these patients had a new complete cardio-respiratory evaluation 3 months after surgery. The pre- and postoperative values compared were those of FEV1, TLC, DLCO, VO2max, and VE/VCO2. Data are expressed as mean +/- standard deviation (SD). Statistic evaluation was made using the Wilcoxon test. RESULTS: During this period 11 patients completed the study protocol. Ten patients underwent surgery for NSCLC and one for a pulmonary aspergilloma. Nine lobectomies and two bilobectomies were performed. In the study population, the preoperative mean value of FEV1 resulted as being 53% (SD+/-20) of the predicted mean value, that of TLC 120% (SD+/-35) and that of DLCO 65% (SD+/-27). The preoperative mean value of VO2max resulted as being 17.8 ml/Kg/min (SD+/-3.25) and mean VE/VCO2 resulted as being 35.7 (SD+/-4). Three months after surgery the measured mean value of FEV1 was 53% (SD+/-18), that of TLC was 99% (SD+/-24) and that of DLCO 52% (SD+/-18). The mean value of VO2max resulted as being 14.1 ml/Kg/min (SD+/-3.04) and that of VE/VCO2 was 42.5 (SD+/-12.8). Statistical analysis of PFT values showed that FEV1 and DLCO were not significantly modified (P > 0.05); in contrast, TLC had significantly decreased (P = 0.008). VO2max had significantly decreased (P = 0.004) and VE/VCO2 had significantly increased (P = 0.018). CONCLUSIONS: Three months after a lobar pulmonary resection, patients with COPD were found to have a significant decrease in exercise tolerance. PFT alone can underestimate the postoperative loss of exercise capacity through exercise.     

Significance of cyclin D1 expression in meningiomas: a preliminary study.

Forty-four evaluable patients with intracranial meningiomas were assessed for the expression of the cell-cycle regulator cyclin D1 and of proteins involved in proliferation and apoptosis such as PCNA, MIB-1, p53 and bcl-2. Analyses were carried out by western blot and immunohistochemistry after immediate processing of fresh tumor specimens. By western blot, expression of cyclin D1 significantly correlated with p53 (p=0.02) and with proliferative activity, as assessed by PCNA expression (p=0.0009). By immunohistochemistry, a significant relationship between cyclin D1 and the proliferation marker MIB-1 was confirmed (p=0.05), whereas significance with bcl-2 expression was not found (p=0.01). Moreover, although the association with tumor grade appeared of borderline statistical significance (p=0.07), all the grade II/III meningiomas showed increased expression of cyclin D1 and high proliferative activity. In conclusion, data from this preliminary study seem to suggest a potential value of the combined expression of cyclin D1 and proliferation indicators in defining subgroups of meningiomas with a more aggressive biological behavior.     

Immunohistochemical study of colonic mucosa macrophages in children with Crohn's disease and ulcerative colitis]

In this research the histological characteristics of the macrophages on the colonic mucosa in Crohn's disease and ulcerative colitis were quantified and analysed. Twelve Crohn's disease, 19 ulcerative colitis and 10 specimen of the rectal mucosa, representing the control group according to the followed model, were studied: I period (PI) = pre-treatment, II period (PII) = up two years of evolution and III period (PIII) = more than two years of evolution. The macrophages were identified in a colonic mucosa by the monoclonal CD68 through the immunoperoxidase method. The macrophages quantification was done by chromatic computer images analysis, that express the area (mm2) used by the CD68 positive cells, in percentage. The percentage of the area used by the macrophages was increased in both diseases, in all the studied periods, when compared with the control group, but without statistic significance. The macrophages' distribution inside the control group mucosa was subepithelial, while in the illness group, it reached all the mucosa that was concentrated on the basis of ulcers and all long the fissures. On the Crohn's disease the CD68 positive cells facilited the identification of the microgranulomas, sometimes unnoticed in the hematoxiline-eosine. Although there was no difference between patients and control group in the macrophages area, the difference in the distribution could suggest the macrophages' participation on the injure in both diseases although they do not permit a differential diagnosis because of the variety of the values. The CD68 did not identify the different functional status of the macrophages, but their position in the mucosa suggest that, in terms of fissures and ulcers, their mainly function should be the phagocitosis and in the other cases, they have been the cells that should show the antigens and that recruit the other inflammatory cells.