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      The sarcoid granuloma: ‘epithelioid’ or ‘lymphocytic-epithelioid’ granuloma?

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          Abstract

          Background

          This study aims to analyze the structure and quantities of cellular elements in sarcoid granulomas.

          Methods

          We investigated 34 transbronchial lung biopsy samples obtained from 34 sarcoid patients. The quantity and composition of the cellular elements inside a granuloma were determined by the quantitative stereometry method, employing the numerical density as a stereological method.

          Results

          A total of 102 sarcoid granulomas were analyzed. The central part of all granulomas was occupied by epithelioid cells. Besides these, giant cells, lymphocytes, macrophages and plasma cells were also seen. The mean numerical density of all the cells in the central part of a sarcoid granuloma was 111,751 mm -3. Lymphocytes prevailed in number, exceeding the total count of all other cells. With a mean numerical density of 74,321 mm -3, lymphocytes were twice as numerous as both epithelioid cells and macrophages with a mean numerical density of 37,193 mm -3.

          Conclusions

          Lymphocytes are the predominant cell type in the central part of a sarcoid granuloma, significantly exceeding both epithelioid cells and macrophages in number, raising the question if the term “epithelioid granuloma”, routinely used to designate sarcoid granulomas, is correct, or if it would be more logical to call them “lymphocytic-epithelioid granulomas” instead.

          Trial registration

          This study was supported by the Serbian Ministry of Science and Environmental Protection Grant Number 175006/2011.

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          Most cited references44

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          Statement on sarcoidosis. Joint Statement of the American Thoracic Society (ATS), the European Respiratory Society (ERS) and the World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) adopted by the ATS Board of Directors and by the ERS Executive Committee, February 1999.

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            Cytokine patterns in tuberculous and sarcoid granulomas: correlations with histopathologic features of the granulomatous response.

            Cytokines play an important role in granuloma formation, but the extent that cytokine profiles are similar in different granulomatous diseases and whether differences in the histopathologic features of the granulomatous response results from differences in cytokine production have not been evaluated. To investigate these questions, we used RT-PCR to quantify the expression of mRNAs coding for 16 cytokines in granulomatous lymph nodes from patients with tuberculosis and sarcoidosis and from control tissues, and we sought correlations between the level of expression of these cytokines and the histopathologic features of the granulomas. Expression of mRNAs coding for a number of cytokines (IL-1beta, IFN-gamma, TNF-alpha, granulocyte-macrophage (GM)-CSF, IL-12 (p40), and lymphotoxin-beta) was increased in tuberculous and sarcoid granulomas compared with that of control tissues. All sarcoid granulomas were shown to express a Th1 pattern of cytokine mRNAs, while tuberculous lymph nodes expressed either a Th1 or a Th0 profile. GM-CSF and lymphotoxin-beta mRNAs were more abundant in sarcoid than in tuberculous granulomas, whereas IL-8 mRNA was strongly expressed only in tuberculous lymph nodes. Strong expression of GM-CSF, TNF-alpha, and IL-8 by granulomas was shown to be correlated, respectively, with the presence of florid granulomatous lesions, the absence of central necrosis, and the presence of neutrophil infiltration. These results demonstrate that the formation of tuberculous and sarcoid granulomas in humans is associated with the expression of characteristic cytokine profiles and indicate that the expression of certain cytokines is associated with the development of specific pathologic features in the resulting granulomas.
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              Pathological studies on sarcoidosis autopsy. II. Early change, mode of progression and death pattern.

              Three hundred and twenty autopsy cases of sarcoidosis in Japan were analyzed to determine the pathological changes in the early stage, the mode of progression in each organ and the changes in the final stage of the disease. The lung and the mediastinal lymph nodes were affected in most of the cases, while the lesions were limited to the lung and intrathoracic nodes in some of the cases. It was suspected that early changes developed in the lung and in the hilar, and then in the mediastinal lymph nodes. The progression of sarcoid granulomas in the lung was classified into three patterns: (i) probably of a disseminated hematogenous nature; (ii) of an interstitial lymphogenous nature; and (iii) of a local expansive nature. These three patterns were observed also in the heart. In the brain, perivascular granuloma formation was a prominent feature. In the other organs in which sarcoid lesions were not malignant nor disseminated and conglomerated, no interstitial patterns were observed. In chronic cases, repeated dissemination and particularly the interstitial spread of granulomatous changes led to a prominent interstitial fibrosis and dysfunction of the organs, finally resulting in death of the individual. In such long-standing cases, the mediastinal nodes deteriorated by hyalinous degeneration of the granulomas, and many active granulomas were formed in the intra-abdominal or body surface lymph nodes. These lymph nodes were likely to continue supplying sensitized lymphocytes to the whole body. A persistence of active change in the lymph nodes and the lymphogenous spread of granulomas in organs would appear to be key factors in the prognosis of sarcoidosis.
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                Author and article information

                Journal
                Multidiscip Respir Med
                Multidiscip Respir Med
                Multidisciplinary Respiratory Medicine
                BioMed Central
                1828-695X
                2049-6958
                2012
                20 June 2012
                : 7
                : 1
                : 11
                Affiliations
                [1 ]Pathology Department, Institute for Lung Diseases of Vojvodina, 21234, Sremska Kamenica, Serbia
                [2 ]Bronchology Department, Institute for Lung Diseases of Vojvodina, 21234, Sremska Kamenica, Serbia
                [3 ]Pasteur Institute, Hajduk Veljkova 1, Novi Sad, Serbia
                [4 ]General Hospital, Sabac, Serbia
                [5 ]Dell’Angelo Hospital, via Paccagnella 11, Mestre (Venice), Italy
                Article
                2049-6958-7-11
                10.1186/2049-6958-7-11
                3436643
                22958359
                e115834b-c3f7-41a0-a6db-09774b0f4292
                Copyright ©2012 Kosjerina et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 17 May 2012
                : 20 June 2012
                Categories
                Original Research Article

                Respiratory medicine
                sarcoidosis,morphometry,epithelioid granuloma,lymphocytic-epithelioid granuloma

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