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| Granuloma Classification and external resources |
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| H&E section of non-caseating granuloma seen in the colon of a patient with Crohn's disease | |
| ICD-9 | 686.1 |
| MeSH | D006099 |
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This article is written like a personal reflection or essay and may require cleanup. Please help improve it by rewriting it in an encyclopedic style. (November 2008) |
A granuloma is a medical term for a ball-like collection of immune cells trying to destroy a foreign substance. This represents a special type of inflammatory reaction common to a wide variety of diseases, both infectious and non-infectious. Most people other than medical professionals will hear the word "granuloma" from their doctor or read it on a biopsy report. The adjective "granulomatous" refers to diseases or inflammatory reactions that are characterized by granulomas.
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Definition
Doctors often use the term "granuloma" loosely to mean "a small nodule". Since a small nodule can represent anything from a harmless nevus to a malignant tumor, this usage of the term is not very specific. The correct use of the term "granuloma" requires a pathologist to examine surgically removed and specially colored (stained) tissue under a microscope. The following is a more technical definition of a granuloma.
In pathology, a granuloma (classical Latin plural granulomata; modern anglicized plural granulomas also accepted) is an organized collection of macrophages 1.
Macrophages (also known as histiocytes) are the cells that define a granuloma. The other key term in the above definition is the word "organized", which refers to a tight, ball-like formation. The macrophages in these formations are typically so tightly clustered that the borders of individual cells are difficult to appreciate. Loosely dispersed macrophages are not considered to be granulomas.
The macrophages in most granulomas have a special appearance that is described as "epithelioid". This term refers to the vague resemblance of these macrophages to epithelial cells. Epithelioid macrophages differ from ordinary macrophages in that they have elongated nuclei that often resemble the sole of a slipper or shoe. Epithelioid macrophages also have larger nuclei than ordinary macrophages and their cytoplasm is more pink. These changes are thought to be a consequence of "activation" of the macrophage by the offending antigen.
All granulomas, regardless of etiology, may contain additional cells and matrix. These include lymphocytes, neutrophils, eosinophils, multinucleated giant cells, fibroblasts and collagen (fibrosis). The additional cells are sometimes a clue to the cause of the granuloma. For example, granulomas with numerous eosinophils are a clue to coccidioidomycosis or allergic bronchopulmonary fungal disease, and granulomas with numerous neutrophils suggest blastomycosis, Wegener's granulomatosis or aspiration pneumonia.
In terms of the underlying cause, the difference between granulomas and other types of inflammation is that granulomas form in response to antigens that are resistant to "first-responder" inflammatory cells such as neutrophils and eosinophils. The antigen causing the formation of a granuloma is most often an infectious pathogen or a substance foreign to the body, but often the offending antigen is unknown (as in autoimmune disorders).
Granulomas are seen in a wide variety of diseases, both 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 both infection as well as non-infectious mechanisms may contribute in some diseases. For example, it has long been suspected that sarcoidosis might be caused by Propionibacterium acnes. On the other hand, the disease also displays autoimmune characteristics and is often accompanied by endocrine problems23.
An important feature of granulomas is whether they contain necrosis or not. Necrosis refers to dead cells, and, under the microscope, appears 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 (i.e., without a microscope), 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.
 Granuloma without necrosis in a lymph node of a person with sarcoidosis. |
 Granuloma with necrosis in a lung of a person with tuberculosis. |
Diseases Characterized By Granulomas
Tuberculosis
The granulomas of tuberculosis tend to contain necrosis ("caseating tubercule"), but non-necrotizing granulomas may also be present. Multinucleated giant cells with nuclei arranged like a horseshoe (Langhans giant cell) are often present, but are not specific for tuberculosis. The diagnosis of tuberculosis requires identification of the causative organism by special stains or culture.
Histoplasmosis
Granulomas are seen in most forms of histoplasmosis (acute histoplasmosis, histoplasmoma, chronic histoplasmosis). Histoplasma organisms can sometimes be demonstrated within the granulomas by biopsy or microbiological culture.
Cryptococcosis
When cryptococcus infection occurs in persons whose immune systems are intact, granulomatous inflammation is typically encountered. The granulomas can be necrotizing or non-necrotizing. The organisms can be seen within granulomas even without special stains.
Sarcoidosis
Sarcoidosis is a disease of unknown cause characterized by granulomas in multiple organs and body sites, most commonly the lungs, lymph nodes, liver, spleen, skin and eyes. The granulomas of sarcoidosis are similar to the granulomas of tuberculosis and other infectious granulomatous diseases. However, in most cases of sarcoidosis, the granulomas do not contain necrosis, are distributed along lymphatic pathways in the lung and are surrounded by concentric fibrosis. Sarcoid granulomas often contain star-shaped structures termed asteroid bodies or lamellar structures termed Schaumann bodies. However, these structures are not specific for sarcoidosis. Sarcoid granulomas can resolve without sequelae or heal with residual scarring. In the lungs, this scarring can cause pulmonary fibrosis; in the heart, it can impair function and lead to rhythm disturbances, heart failure and even death.
Chronic granulomatous disease
In the rare condition chronic granulomatous disease, neutrophil function is impaired and granulomas form in response to infection.
Rheumatic myocarditis
Rheumatic fever is a disease that affects heart tissue. Among all the pathologic changes, the only pathognomonic change is the formation of special granulomas termed Aschoff granulomas. They are often located around blood vessels and contain central fibrinoid necrosis. As in any other granuloma, they are surrounded by lymphocytes, plasma cells, fibroblasts and sometimes neutrophils.
Syphilis
A form of granuloma (gumma) may be formed in the third stage of syphilis. Gummas are of different sizes: smaller ones are miliary and more numerous, while larger ones (more common) are solitary. Gummas can develop in bones, brain, liver, skin, testis and elsewhere. Contrary to the granulomas of tuberculosis, a silhouette of the original tissue is visible within the necrosis. As with other granulomas, gummas can heal with scarring. In the liver, such scarring can result in a condition named hepar lobatum syphiliticum.
Aspiration pneumonia
Aspiration pneumonia is typically caused by aspiration of bacteria from the oral cavity into the lungs, and does not result in the formation of granulomas. However, granulomas may form when food particles or other particulate substances like pill fragments 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 4.
See also
References
- ^ Adams DO (1976). "The granulomatous inflammatory response. A review.". American Journal of Pathology 84 (1): 164–191. PMID 937513.
- ^ Inoue Y, Suga M (2008). "Granulomatous diseases and pathogenic microorganism" (in Japanese). Kekkaku 83 (2): 115–300. PMID 18326339.
- ^ Porter N, Beynon HL, Randeva HS (2003). "Endocrine and reproductive manifestations of sarcoidosis". QJM 96 (8): 553–61. PMID 12897340. http://qjmed.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=12897340.
- ^ Mukhopadhyay S, Katzenstein AL (2007). "Pulmonary disease due to aspiration of food and other particulate matter: a clinicopathologic study of 59 cases diagnosed on biopsy or resection specimens.". American Journal of Surgical Pathology 31 (5): 752–759. PMID 17460460.
External links
- Pathology Images of Granulomatous Diseases Yale Rosen, M.D.
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- This page was last modified on 10 December 2008, at 05:00.
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