Fig. 3.22 ), the activated macrophages in granulomas have pink granular cytoplasm with indistinct cell boundaries and are called epithelioid cells. A collar of lymphocytes surrounds the aggregates of epithelioid macrophages. Older granulomas may have a rim of fibroblasts and connective tissue. Frequently, but not invariably, multinucleated giant cells 40 to 50 µm in diameter are found in granulomas; these are called Langhans giant cells.They consist of a large mass of cytoplasm and many nuclei. Granulomas associated with certain infectious organisms (classically Mycobacterium tuberculosis) often contain a central zone of necrosis. Grossly, this has a granular,cheesy appearance and is therefore called caseous necrosis. Microscopically, this necrotic material appears as amorphous, structureless, eosinophilic, granular debris, with loss of cellular details.The granulomas in Crohn disease, sarcoidosis, and foreign body reactions tend to not have necrotic centers and are said to be noncaseating. Healing of granulomas is accompanied by fibrosis that may be extensive.
Fig. 3.22 Typical tuberculous granuloma showing an area of central necrosis surrounded by multiple multinucleate giant cells, epithelioid cells, and lymphocytes.
Granulomas are encountered in certain specific pathologic states; recognition of the granulomatous pattern is important because of the limited number of conditions (some life threatening) that cause it (
Table 3.9 ). In the setting of persistent T cell responses to certain microbes (e.g., M. tuberculosis, Treponema pallidum, or fungi), T cell– derived cytokines are responsible for chronic macrophage activation and granuloma formation. Granulomas may also develop in some immune-mediated inflammatory diseases, notably Crohn disease, which is one type of inflammatory bowel disease and an important cause of granulomatous inflammation in the United States, and in a disease of unknown etiology called sarcoidosis. Tuberculosis is the prototype of a granulomatous disease caused by infection and should always be excluded as the cause when granulomas are identified. In this disease the granuloma is referred to as a tubercle. The morphologic patterns in the various granulomatous diseases may be sufficiently different to allow a reasonably accurate diagnosis ( 3.9 ), but it is always necessary to identify the specific etiologic agent by special stains for organisms (e.g., acid-fast stains for tubercle bacilli), by culture methods (e.g., in tuberculosis and fungal diseases), by molecular techniques (e.g., the polymerase chain reaction in tuberculosis), and by serologic studies (e.g., in syphilis).
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Table 3.9 Examples of Diseases With Granulomatous Inflammation
Tuberculosis Mycobacterium tuberculosis Caseating granuloma (tubercle): focus of activated macrophages (epithelioid cells), rimmed by fibroblasts, lymphocytes, histiocytes, occasional Langhans giant cells; central necrosis with amorphous granular debris; acid-fast bacilli
Syphilis Treponema pallidum Gumma: microscopic to grossly visible lesion, enclosing wall of macrophages; plasma cell infiltrate; central cells are necrotic without loss of cellular outline; organisms difficult to identify in tissue
Sarcoidosis Unknown etiology Noncaseating granulomas with abundant activated macrophages
Chronic inflammation is a prolonged host response to persistent stimuli that may follow unresolved acute inflammation or be chronic from the outset.
It is caused by microbes that resist elimination, immune responses against self and environmental antigens, and some toxic substances (e.g., silica); underlies many medically important diseases.