Pregranutomatous phase of sarcoidosis: Immunohistochemical diagnosis
ABSTRACT Histopathological confirmation of clinical suspicion of sarcoidosis is based on the finding of non-caseating granulomas in biopsy material, usually in prescalene lymph nodes or in transbronchial lung biopsies. Lymph node reactive sinus histiocytosis (RSH) seen in relation to various inflammatory and non-inflammatory diseases can mimic the pregranulomatous phase of sarcoidosis (PSH). Differentiation of sinus histiocytosis based on histopathological features alone is limited. The purpose of this study is immunohistochemical determination of lymph node cellular response in granulomatous sarcoidosis, the PSH and RSH using a immunohistochemistry employing a panel of antibodies. Patient groups under study each contained 25 patients and included: those with clinical picture of sarcoidosis and non-caseating granulomatous lymphadenitis; those with confirmed sarcoidosis and with sinus histiocytosis without granuloma formation in lymph nodes; and finally, those without sarcoidosis and with "reactive" sinus histiocytosis in lymph nodes. Lymph node biopsy tissue was fixed in buffered formaldehyde, routinely processed to paraffin wax blocks, cut into 4-microm-thick sections, stained with hematoxylin and eosin and immunohistochemically labelled using a triple-layer APAAP protocol with purified polyclonal antibodies directed against SP 70 and SP90 from Mycobacterium tuberculosis and monoclonal antibodies against CD22, CD4, CD8, CD56, and CD68. Intensity of immunolabelling was assessed semiquantitatively by two independent observers. An increased CD4:CD8 ratio, moderate increase of immunolabelling for CD68 and slight decrease in immunolabelling for CD20, CD56, and SP90 was indicative of PSH when compared with RSH. The most notable difference between the studied groups was a difference in immunoreactivity to SP70 and CD4 antibodies. Lymph nodes with pregranulomatous sinus histiocytosis labelled with both antibodies. This profile of immunolabelling can be used in the differentiation of this condition from reactive sinusoidal lesions.
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ABSTRACT: Sarcoidosis (SA) is a granulomatous disorder of an unknown etiology. Mycobacterium tuberculosis heat shock proteins (Mtb-hsp), considered as causative agents, play an important role in apoptosis. A role for apoptosis has been proposed in pathogenesis of SA and tuberculosis (TB) granuloma formation but results remain controversial. Differences in Mtb-hsp-induced apoptosis between SA, TB, and healthy subjects found in this study might put some light on the etiology of SA. Early apoptotic peripheral blood mononuclear cells (PBMC) were determined in 22 SA patients, 20 TB patients, and 20 healthy volunteers by flow cytometry (Annexin-V-FITC). Our results revealed that spontaneous apoptosis of monocytes and CD8+ T-cells was comparable between tested groups. Apoptosis of unstimulated CD4+ T-cells was significantly lower in TB versus controls and insignificantly lower versus SA. Mtb-hsp- and PHA (Phytohemagglutinin)-induced monocytes apoptosis was significantly lower in TB versus controls and SA. Mtb-hsp-induced CD4+ T-cell apoptosis was significantly lower in TB versus controls and SA. There were no differences of PHA-induced CD4+ T-cell and CD8+ T-cell apoptosis between tested groups. Apoptosis of Mtb-hsp-induced CD8+ T-cells was significantly lower in TB and SA versus controls. Analysis of PBMC apoptosis before and after stimulation in each tested group revealed that, in contrast to TB, sarcoid monocytes were resistant to Mtb-hsp- and PHA-induced apoptosis and CD4+ T-cells were resistant to PHA- but not Mtb-hsp-induced apoptosis. CD8+ T-cell apoptosis, before and after Mtb-hsp or PHA stimulation, was significantly increased in all tested groups. It seems likely that dysregulated apoptosis of CD4+ T-cells and resistant apoptosis monocytes may be involved in pathogenesis of SA.Journal of Clinical Immunology 06/2006; 26(3):243-50. DOI:10.1007/s10875-006-9011-9 · 3.18 Impact Factor
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ABSTRACT: We present an uncommon case of sudden cardiac death in a 34-year-old white woman. She was found lifeless at home by her parents. Three months before death she was recovered at the Emergency Room for chest pain, palpitation and loss of consciousness. Subsequent cardiological evaluation with ECG showed sinusal rhythm, QRS deviation to the left, QS aspect, asymmetric and rounded T waves and slight length of QT. During hospitalization she presented some episodes of supraventricular paroxysmal tachycardia and non-sustained ventricular tachycardia. No echocardiography alterations were found. An anti-arrhythmic treatment was prescribed. Autopsy revealed some fibrotic scarring in the myocardium of left ventricle. The histological examination of the heart revealed diffuse and extensive fibrosis with non-caseating sarcoid granulomas. The lungs, kidneys and lymph node also showed the same non-caseating granulomas. The diagnosis of sarcoidosis with massive and extensive cardiac involvement was established as cause of death.Forensic science international 12/2008; 183(1-3):e1-5. DOI:10.1016/j.forsciint.2008.09.020 · 2.14 Impact Factor
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ABSTRACT: Neurosarcoidosis carries a mortality of 10%, over twice that of sarcoidosis overall, although it has been rarely reported as a cause of sudden death. The current evidence suggests that sarcoidosis results from an enhanced immune reaction to a variety of antigens, non-self or self which causes CD4 (helper-inducer) T-cell accumulation with a ratio of helper-inducer T cells to suppressor-cytotoxic T cells usually high in affected organs, activation and release of inflammatory cytokines, and formation of granulomatous lesions. Numerous cytokines and other mediators are produced by both activated macrophages and T lymphocytes bearing the CD4-helper phenotype during the granuloma responses. A number of data suggest that interferon-gamma (IFN-gamma) and cytokines such as TNF-α, IL-2, and IL-18 play a critical role in the formation of granulomas. In this article, we describe the clinical and pathological characteristics of a patient who suddenly died due to acute respiratory failure. Neurosarcoidosis with massive and extensive involvement of the brainstem was established as the cause of death. Western blot analysis in the patient demonstrated the TNF-α presence as a 51-kDa protein in the brain tissue. The immunohistochemical analysis showed a poor positiveness for CD4 in all samples around the granulomas, as well as moderate positiveness for CD8, CD15, and CD20; CD45 and CD68 showed a strong positiveness in all the brain samples. Histological findings, immunohistochemical analysis, and proteomic studies addressed the diagnosis of neurosarcoidosis with involvement of the nucleus of the solitary tract in the brainstem and central hypoventilation as the cause of death.Forensic science international 02/2011; 208(1-3):e1-5. DOI:10.1016/j.forsciint.2011.01.021 · 2.14 Impact Factor