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Summary: 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 histiocytois in lymph nodes. Lymph node biopsy tissue was fixed in buffered formaldehyde, routinely processed to paraffin wax blocks, cut into 4-μm-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 imunoreactivity 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. [Copyright &y& Elsevier]