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.     

Clinical and histopathological findings of ''psoriatic neurodermatitis'' and of typical lichen simplex chronicus

BACKGROUND: We have seen several patients with itchy lichenified plaques located bilaterally on the elbows and/or knees and have named this condition 'psoriatic neurodermatitis' (PN). OBJECTIVE: The purpose of this study was to compare clinical and histopathological characteristics of these patients to those of patients with typical lichen simplex chronicus (LSC). METHODS: Nineteen patients with PN and 34 patients with typical LSC were included. Besides clinical dermatological evaluation, the prick test was carried out on 49 patients; the Phadiatop test on 40 patients; the patch test with European standard series on 47 patients; histopathological evaluation on 39 patients; and clinical psychiatric examination on 38 patients. RESULTS: Almost exclusively, PN was seen in females and was located on the extremities. It caused more plaques than typical LSC did. In PN, the plaques were smaller, sharper, more keratotic and less excoriated, and had fewer lichenoid papules around them. Itching was usually more severe in the evening, while resting and in a hot environment in typical LSC, but not in PN. In plaques of PN, microabscesses in the horny layer, hypogranulosis, regular acanthosis and thinning of the suprapapillary plates were more frequent, and hyperpigmentation in the basal layer was less. In patients with PN, depressive disorder was found more frequently; and generalized anxiety disorder or psychosomatic characteristics, less. There were no significant differences in the results of prick, Phadiatop and patch tests between patients with PN and those with typical LSC. CONCLUSION: In our opinion, it is most likely that the so-called PN is itchy psoriasis superimposed by LSC.     

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.     

Treatment of refractoriness to platelet transfusion by protein A column therapy

Ten thrombocytopenic patients (platelets < 10–24 × 10(9)/L) who were refractory to platelet transfusion were investigated for their responsiveness to staphylococcal protein A column therapy. Nine patients had previously been treated with steroids, intravenous immune globulin, and/or other forms of immunosuppressive therapy without improvement in their transfusion response. All patients were receiving multiple platelet transfusions without achieving 1-hour corrected count increments (CCIs) > or = 7500. Eight patients had antibodies that reacted with platelets and were directed against HLA class I antigens, ABO antigens, and/or platelet-specific alloantigens. Plasma (500-2000 mL) from each patient was passed over a protein A silica gel column and then returned to the patient. Patients received from 1 to 14 treatments. A positive response to protein A therapy was defined as at least a doubling of the pretreatment platelet count and/or two successive 10- to 120-minute posttransfusion CCIs > or = 7500. Following plasma treatments, 6 of 10 patients responded with daily platelet counts that averaged 48 +/− 11 × 10(9) per L as compared with counts of 16 +/− 7 × 10(9) per L (p < 0.0005) before treatment. Posttransfusion CCI values determined in four of these patients averaged 2480 +/− 810 and 10,010 +/− 3540 (p < 0.005) before and after treatment, respectively. In contrast, among the four unresponsive patients, platelet counts averaged 10 +/− 9 and 13 +/− 10 × 10(9) per L (p = NS), respectively, while posttransfusion CCIs were 700 +/− 1410 and 1520 +/− 2460 (p = NS), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Changes in cardiovascular function induced by verapamil in healthy subjects and in patients with ischemic heart disease

Alterations in cardiovascular function induced by the acute intravenous administration of verapamil (5 or 10 mg) in 52 patients (29 with ischemic heart disease and 23 without heart disease) were evaluated with use of invasive techniques (right and left heart catheterization, left ventricular cineangiography, and coronary arteriography). The most significant changes were represented by a decrease in systemic vascular resistance and systemic arterial pressure, and an increase in heart rate and cardiac output. Contractility indexes were not depressed in either group, and altered ventricular wall motion tended to improve to a slightly smaller degree than in patients treated with nitroglycerin. The use of verapamil in patients with ischemic heart disease appears to be safe, and concern about the negative inotropic influences in humans no longer seems justified.