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Cytoplasmic Pattern (cytoplasmic + pattern)
Selected AbstractsClusterin expression is associated with decreased disease-free survival of patients with colorectal carcinomasHISTOPATHOLOGY, Issue 7 2010Maximino Redondo Redondo M, Rodrigo I, Alcaide J, Tellez T, Roldan M J, Funez R, Diaz-Martin A, Rueda A & Jiménez E (2010) Histopathology,56, 932,936 Clusterin expression is associated with decreased disease-free survival of patients with colorectal carcinomas Aims:, It has been demonstrated that increased clusterin expression is involved in malignant progression and that anticlusterin treatment leads to selective apoptosis. The aim of this study was to determine the clinicopathological significance of clusterin expression in human colorectal carcinomas. Methods and results:, The expression of clusterin was examined in 31 adenomas and 103 colorectal carcinomas. Normal epithelial cells were always negative for clusterin expression, but clusterin expression was present in 16% (5/31) of adenomas and this percentage increased in colorectal carcinomas (30%, 31/103). Immunopositivity always presented an apical cytoplasmic pattern. The expression level of clusterin did not correlate with age, gender, grade or stage. However, its expression was significantly associated with a decrease in disease-free survival (P < 0.05). In a multivariate Cox proportional hazards model, clusterin expression remained a significant independent predictor. Conclusions:, Clusterin expression may have a role in colonic carcinogenesis and may help identify patients with more aggressive tumours who may benefit from targeted therapy. [source] Caveolin-1 is a novel immunohistochemical marker to differentiate epithelioid mesothelioma from lung adenocarcinomaHISTOPATHOLOGY, Issue 1 2009Vishwa Jeet Amatya Aims:, The incidence of mesothelioma is increasing in Europe, Japan and other developing countries. There is difficulty in the accurate diagnosis of mesothelioma and its differentiation from lung adenocarcinoma. Mesothelioma shows a complex immunohistochemical profile. Therefore, the use of a immunohistochemical panel that includes both positive and negative mesothelial markers has become a general rule for its accurate diagnosis. However, they are still not sufficient. The aim was to assess the diagnostic utility of caveolin-1 (Cav-1), which is expressed in endothelial cells, alveolar type I pneumocytes and mesothelial cells, as a novel positive marker of mesothelioma. Methods and results:, An immunohistochemical study of 80 cases of epithelioid mesothelioma and 80 cases of lung adenocarcinoma was performed for the analysis of the expression of Cav-1 and other markers. Cav-1 expression with a membranous and/or cytoplasmic pattern was found in all of the epithelioid mesothelioma. Of these, 42 cases (52.5%) showed Cav-1 expression in >50% of tumour cells, 34 cases (42.5%) in 6,50% of tumour cells, and four cases (5.0%) in <5% of tumour cells. In contrast, only six cases (7.5%) of lung adenocarcinoma showed focal Cav-1 expression in the cytoplasm of the tumour cells. The sensitivity and specificity of Cav-1 expression for the differentiation of epithelioid mesothelioma from lung adenocarcinoma were 100 and 92.5%, respectively. This is comparable or even superior to that of currently available positive markers such as calretinin or D2-40. Conclusions:, Cav-1 is a novel immunohistochemical marker for the differentiation of epithelioid mesothelioma from lung adenocarcinoma. [source] Nuclear and membrane expression of the angiogenesis regulator delta-like ligand 4 (DLL4) in normal and malignant human tissuesHISTOPATHOLOGY, Issue 5 2009Juan Carlos Martinez Aims:, Delta-like ligand 4 (DLL4) is one of five known Notch ligands in mammals and interacts predominantly with Notch 1. DLL4 is induced by vascular endothelial growth factor (VEGF) and acts downstream of VEGF as a ,brake' on VEGF-induced vessel growth, forming an autoregulatory negative feedback loop inactivating VEGF. This action was believed to occur only in vascular development, raising hopes that DLL4 could be a specific drug target for controlling vessel growth in tumours and other pathological conditions. Our aim was to pursue this by raising a monoclonal antibody to the internal domain of DLL4 and assess its distribution in normal and malignant tissues in comparison with antibodies against the external domain of DLL4. Methods and results:, The anti-DLL4 monoclonal antibody was raised using conventional mouse hybridoma techniques. The antibody has been fully characterized by Western blotting and transfectant immunostaining. It has also been comprehensively compared with other antibodies against both the internal and external domains of DLL4. The antigen is widely expressed on human tissues not only on endothelium but also on epithelium and stromal cells. Indeed, in our comprehensive survey only pulmonary alveoli failed to express DLL4. Of a wide range of malignancies, most also expressed DLL4 on tumour cells with a predominantly cytoplasmic pattern, although a number also displayed nuclear positivity. Conclusions:, Contrary to previous beliefs, DLL4 is widely distributed in tissues other than vessels including many malignancies. Furthermore, the molecule is internalized on binding its receptor and often transported to the nucleus. These findings raise many interesting possibilities for further study of DLL4 and its potential as a therapeutic target. [source] Cutaneous sarcoid-like granulomas with alveolar hemorrhage and c-ANCA PR-3INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 9 2004Natividade Rocha MD A 28-year-old woman, employed as a leather factory worker, noted asymptomatic, well-delimited plaques on both knees, 6 years ago. The plaques were violaceous with a smooth surface. One appeared over a post-traumatic scar from childhood (Fig. 1). Two years later, she began to complain of symptoms suggestive of polyarthritis, first of the small joints of the hands (proximal interphalanges) and then of the larger joints (wrists, elbows, and knees). She was diagnosed with rheumatoid arthritis and began treatment with nonsteroidal anti-inflammatory drugs for 1 month without any change. Deflazacort, 12 mg/day, and hydroxychloroquine, 400 mg/day, were administered for 3 months, with improvement of her articular complaints, but not her skin lesions. Figure 1. Well-delimited, violaceous plaques with a smooth surface on the knees, one over an old post-traumatic scar One year later, she complained of dysphonia, which remitted spontaneously after some weeks. After one additional year, she noted papules, with similar characteristics to the plaques, on the elbows, and two well-delimited orange-to-brown plaques on the forehead (Fig. 2). Figure 2. Orange,brown plaques symmetrically placed on the forehead During the fifth year of the disease, she was referred for the first time to a dermatologist, who biopsied one of the knee lesions. The histologic result was compatible with "sarcoid granuloma." At that time, she presented with skin lesions as her only complaint. Sarcoidosis was suspected based on a chest X-ray, which revealed hilar lymphadenopathy and diffuse accentuation of the interstitium. In November 2000, she suddenly developed fever (40 °C), cough with hemoptysis, dysphonia, and subcutaneous nodules on the palmar surface of the fingers of both hands that were painless, well-delimited, 5 mm in diameter, and firm (Fig. 3). She reported a weight loss of 12 kg in the previous 3 months. Pulmonary condensation was found on auscultation, and she had palpable hepatomegaly. Peripheral lymphadenopathy was not present. Figure 3. Painless, well-delimited, firm subcutaneous nodules on the palmar surface of the fingers Laboratory investigations revealed normochromic, normocytic anemia (hemoglobin, 7.7 g/dL), iron deficit, a white blood cell count of 16,000/µL with neutrophilia, an erythrocyte sedimentation rate of 130 mm/h, elevation of liver enzymes, a slight increase in angiotensin-converting enzyme (ACE) level (72 U/L), hypergammaglobulinemia (IgG, 3350 mg/dL), antinuclear antibody (ANA) of 1 : 320, and a slight increase in CD4 and decrease in CD8 lymphocytes with normal cellular morphology in blood. Renal function, urine sediment, urine and serum calcium, complement (C4), dsDNA, antimitochondrial antibody, direct and indirect Coombs test, antineutrophil cytoplasmic antibody (ANCA), tuberculin skin tests, viral markers of hepatitis B, C, and human immunodeficiency virus (HIV), electrocardiogram (ECG), ophthalmic examinations, and culture for infectious agents in blood and sputum were all normal or negative. Computed tomography (CT) scan showed an infiltrate in the upper right pulmonary lobule with a central cavity and bilateral hilar lymphadenopathy (Fig. 4). Homogeneous hepatosplenomegaly was present. The bronchoalveolar lavage (BAL) showed a slight lymphocytic increase predominantly of CD8 cells and hemosiderosis. Stains for infectious agents, including acid-fast bacillus, fungi, Mycoplasma, and Legionella, were negative. Three biopsies from the forehead, elbows, and knees showed well-formed noncaseating epithelioid cell granulomas with giant cells of the Langhans type in the dermis, suggestive of sarcoidosis (Figs 5 and 6). A fourth biopsy from a finger nodule demonstrated inflammatory infiltration of the dermis and necrosis with cellular debris. Vasculitis was not seen (Fig. 7). Figure 4. Computed tomography scan showing an infiltrate in the upper right pulmonary lobule with a central cavity Figure 5. Beneath a flattened epidermis, several sarcoid granulomas composed of epithelioid histiocytes and several multinucleated giant cells of Langhans type can be seen (hematoxylin and eosin, ×10) Figure 6. Less well-formed sarcoid granulomas in a hyperkeratotic area, surrounded by a sparse rim of lymphocytes (hematoxylin and eosin, ×20) Figure 7. Foci of necrosis and fibrinoid degeneration with some neutrophil infiltration and nuclear dusting (hematoxylin and eosin, ×40) The patient was treated with a broad-spectrum empirical antimicrobial (levofloxacin, 500 mg daily intravenously) over 12 days, with prompt improvement in her symptoms and remission of the forehead and finger lesions. Nevertheless, on the first evaluation after hospitalization, the CT scan showed persistence of the pulmonary cavity (Fig. 8). A repeat ANCA determination was positive (cytoplasmic pattern, c-ANCA) at 1 : 640 by indirect immunofluorescence (IIF). Antiproteinase-3 antibody was demonstrated at 78 by enzyme-linked immunosorbent assay (ELISA). Figure 8. Computed tomography scan showing persistence of the pulmonary cavity She underwent an open lung biopsy which revealed intra-alveolar hemorrhage and scanty noncaseating epithelioid cell granulomas of the sarcoidosis type in the peripheral blood vessels without vasculitis. A diagnosis of Wegener's granulomatosis was made and she began prednisolone (1 mg/kg/day) and oral cyclophosphamide (2 mg/kg/day). One year later, she is asymptomatic, the skin lesions have completely remitted, c-ANCA is negative, and the CT scan shows partial regression of the pulmonary cavity. [source] Expression of growth hormone receptor in benign and malignant cutaneous proliferative entities ,JOURNAL OF CUTANEOUS PATHOLOGY, Issue 6 2000Manuel Ginarte The skin has the necessary elements to respond to growth hormone (GH) and suffers clinical changes in the pathological circumstances of excess and deficiency of GH. The GH has been involved in the development of different types of human neoplasms. Based on these data, we have studied the GH receptor (GHR) expression in acrochordons, seborrheic keratosis, melanocytic nevi, histiocytomas, squamous cell carcinomas, basal cell carcinomas, and malignant melanomas by means of the immunohistochemistry with the monoclonal antibody MAb 263. All the entities showed immunoreactivity for GHR. In the histiocytomas, the expression of GHR in the keratinocytes of the hyperplastic epidermis coating the lesion showed a strong nuclear pattern, but the non-hyperplastic epidermis of the edges of the histiocytomas expressed GHR with a cytoplasmic pattern. In the basal cell carcinoma and squamous cell carcinoma, the immunoreactivity was weaker than in normal skin. In the squamous cell carcinoma, the intensity of immunostaining correlated directly with the grade of cellular differentation. In conclusion, the GH may be involved in the development of different kinds of cutaneous neoplasms, and the intracellular localization of GHR may imply a functional significance, at least in the histiocytomas. [source] Cerebral and Oculorhinal Manifestations of a Limited Form of Wegener's Granulomatosis With c-ANCA,Associated VasculitisJOURNAL OF NEUROIMAGING, Issue 1 2001Peterus Thajeb MD ABSTRACT The authors report on cerebral and oculorhinal manifestations in a patient with a cytoplasmic pattern of antineutrophil cytoplasmic autoantibody (c-ANCA),associated vasculitis. Recurrent Tolosa-Hunt syndrome, cavernous sinus syndrome, Raeder's paratrigeminal neuralgia, and seizures were the major clinical manifestations. Brain MRI showed localized enhancing lesions initially in the cavernous sinus and later in the convexity pachymeninges. The lesions disappeared following 9 months of oral prednisolone (15 mg/day) and cyclophosphamide (100 mg/day) therapy. The presence of c-ANCA, demonstration of vasculitis, and depositions of immunoglobulin G (IgG) and fibrinogen in the vessel walls of pachymeninges of the patient confirmed an immune-mediated cause of the vasculitis. Cranial pathology without renal and pulmonary involvement suggests a variant of Wegener's granulomatosis, which is called the "limited" form of Wegener's granulomatosis. [source] | ||||||||||