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In medicine (anatomical pathology), a granuloma (classical Latin plural granulomata; modern anglicized plural granulomas, also accepted) is a nodule consisting mainly of epithelioid macrophages and other inflammatory and immune cells as well as extracellular matrix. They are often surrounded by a lymphocyte cuff or fibrosis.

Broadly speaking, granulomas form when the immune system fends off and isolates an antigen but is unable to completely destroy it. The antigen is most often an infectious pathogen or a foreign body, but in many cases the offending antigen is not apparent (as in autoimmune disorders).

Granulomas are seen in a variety of diseases, infectious and non-infectious. Infections that are characterized by the presence of granulomas include tuberculosis, leprosy, histoplasmosis, cryptococcosis, blastomycosis, coccidioidomycosis and syphilis. The major non-infectious granulomatous diseases are sarcoidosis, Crohn's disease, berylliosis, Wegener's granulomatosis, Churg-Strauss syndrome, pulmonary rheumatoid nodules and aspiration of food and other particulate material into the lung. This classification of granulomas (infectious vs. non-infectious) should be used with caution as the both an infection and aberrant or inadequate immune response may contribute in some lesions. For example it has long been suspected that sarcoidosis might be caused by Propionibacterium acnes. On the other hand, the disease also clearly displays autoimmune characteristics and is often accompanied by endocrine problems.

An important feature of granulomas is whether they contain necrosis or not. Under the microscope, dead cells appear as a mass of formless debris. A related term, "caseation" (literally: turning to cheese) refers to a form of necrosis that, to the unaided eye, appears cheese-like, and is typically (but not uniquely) a feature of the granulomas of tuberculosis. The identification of necrosis in granulomas is important because granulomas with necrosis tend to have infectious causes. There are several exceptions to this general rule, but it nevertheless remains useful in day-to-day diagnostic pathology.


Tuberculous granuloma

The tuberculous granuloma (caseating tubercule): central caseous necrosis bordered by giant multinucleated cells (Langhans giant cell), and surrounded by epithelioid cells aggregates, lymphocytes and fibroblasts. Granulomatous tubercules tend to confluence. Multinucleated giant cell (Langhans giant cell): 50-100 micrometres, numerous small nuclei (over 20) disposed at the periphery of the cell (crown or horseshoe), abundant eosinophilic cytoplasm. It results when activated macrophages merge. Epithelioid cells are activated macrophages resembling epithelial cells: elongated, with finely granular, pale eosinophilic (pink) cytoplasm and central, ovoid nucleus. They have indistinct shape contour and form aggregates. At the periphery are the lymphocytes (T cells) and rare plasma cells and fibroblasts. Caseous necrosis is a central area, amorphous, finely granular, eosinophilic (pink). If recent, it may contain nuclear fragments. The caseum is the result of the accumulated destruction of giant cells and epithelioid cells.

Chronic granulomatous disease

In the rare condition chronic granulomatous disease, neutrophil granulocyte function is impaired and granulomas form in various organs in response to infection, as the infection is not being contained through normal means.

Granulomas of Sarcoidosis

Granulomas seen in Sarcoidosis are nodal aggregates of epithelioid cells, similar to epithelioid tubercules of tuberculosis. However, the quantity of necrosis is low and it is noncaseating. Multinucleated giant cells of Langhans cell type and foreign-body type giant cells are present, however they are less numerous and can be star-shaped (asteroid bodies) or lamellar (Schaumann bodies). These inclusions are not sarcoidose-specific. Some fibrous tissue and lymphocytes are present on the periphery.

These Boutrus granulomas can resorb or heal with a scar. In the lungs this can cause disseminated pulmonary fibrosis; in cardiac tissue they may cause impaired heart function and possibly death by heart failure.

Rheumatic myocarditis

Rheumatic fever affects all the heart tissue (rheumatic pancarditis). From all the pathological changes, only the granulomas, called Aschoff granulomas, are pathognomonic, often located perivascularly. In the centre, fibrinoid necrosis is visible. It is encompassed by lymphocytes, plasma cells, fibroblasts and individual neutrophils. Also mononuclear Anitschkow's cells (histiocytes) and characteristic Aschoff giant cells are present (these latter represent multinucleated macrophages). Anitschkow's cells appear like an owl's eye and have abundant pale eosinophilic cytoplasm with a characteristic "caterpillar" or lacy nucleole in the bright nucleus. They are often arranged in a palisade around the center. Aschoff cells have a single or multiple bean-shaped nuclei. Peripherally, fibroblasts and sclerotic fibrous tissue can be seen. The granuloma sometimes immediately borders partially fragmented muscle fibers. Ultimately, rheumatic heart disease results in a "fish mouth" appearing stenosis of the mitral valve, causing left atrial dilation, right ventricular hypertrophy, and mural thrombi. Patients are predisposed to endocarditis and CHF.

Gumma hepatitis

The less common form of the third stage of syphilis. Gummas are of different sizes: smaller ones are miliary and more numerous, while the larger ones that are more common, are solitary and elastic. Gumma can develop in different tissues and organs, especially in bones, brain, liver, skin, testis and elsewhere. Contrary to the tuberculous granuloma, in the elastic coagulative central necrosis of the gumma, which is eosinophilic and of grey yellowish colour, there is still some silhouette of the previous tissue visible. The granuloma is encompassed by the grey whitish fibrous envelope, that sometimes sends radial ribbons in the surrounding area. In between, there are lymphocytes, plasma cells and giant cells from capillaries and rare epitheloid cells, and on the periphery lymphocytes and plasma cells are present. By healing, gumma transforms in a large scar that can for example disfigure liver with deep furrows (hepar lobar syphiliticum).

Granulomas in Aspiration Pneumonia

Granulomas may form when food particles are aspirated into the lungs. Patients typically aspirate food because they have esophageal, gastric or neurologic problems. Intake of drugs that depress neurologic function may also be causal. The resultant granulomas are typically found around the airways (bronchioles) and are often accompanied by foreign-body-type multinucleated giant cells, acute inflammation or organizing pneumonia. The finding of food particles in lung biopsies is diagnostic ..

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