Sarcoidosis pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: :Roshan Dinparasti Saleh M.D.

Overview

Sarcoidosis is a multisystem disorder of unknown etiology characterized by noncaseating granulomas in involved tissues. The lungs are affected most commonly, and pulmonary disease accounts for the majority of the morbidity and mortality associated with this disease. Other tissues commonly involved include the skin, eyes, and lymph nodes.

Pathophysiology

Granuloma formation is a hallmark of sarcoidosis disease. The underlying immunologic events include (1) exposure to antigens, (2) activation of antigen-presenting cells (macrophages and/or dendritic cells), (3) a T cell response in an effort to eliminate the antigen, and (4) granuloma formation. macrophages differentiate into epithelioid cells, which gain secretory capability, lose phagocytic capacity, and fuse to form multinucleated giant cells which are cellular basis of granulomas. Th2 cells also contribute to granuloma formation. These cells secrete fibronectin and CCL18, which finally lead to macrophage-mediated collagen formation and fibrosis in 25% of patients with sarcoidosis . It is estimaed that two possible immunologic scenarios play role in sarcoidosis: an intense immune reaction in patients with active disease, finally resulting in antigen clearance, or chronic disease with less inflammation but the inability to eradicate the antigen and chronic stimulation of the immune response, resulting in organ damage such as lung fibrosis

Histopathological Findings

The first histopathological finding in the lung is a CD4+ T cell alveolitis, followed by the development of noncaseating granuloma Images courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology

This is a low-power photomicrograph of a lymph node. Note the rather pale-pink color of the tissue with dark-staining cells found in only a few scattered areas. These darker cells represent the original lymphocytes of this lymphoid organ.

This photomicrograph of lymph node tissue illustrates a paucity of lymphocytes as well as numerous small, pale-staining nodules (arrows) throughout the tissue.

This is a photomicrograph of the small nodules (arrows) seen in the previous image. Close examination reveals that they are composed of large macrophages (epithelioid macrophages). These small granulomas form multiple series of reaction centers throughout the lymph node. Note the remaining lymphocytes surrounding the granulomas.

This photomicrograph of a single granuloma illustrates the individual macrophages (arrows) which make up the bulk of this tissue. There is an absence of necrosis in the center of the lesions in this case.

This is a photomicrograph of a multinucleated giant cell (1). In the center of this foreign body-containing giant cell there is a small asteroid body (2). There is no functional significance to this asteroid body.

This is a higher-power photomicrograph of an asteroid body (arrow) inside of a multinucleated giant cell.