Granuloma is an inflammation found in many diseases.
It is a collection of immune cells known as macrophages.
Granulomas form when the immune system attempts to wall off substances that it perceives as
foreign but is unable to eliminate.
Such substances include infectious organisms such as bacteria and fungi as well as other
materials such as keratin and suture fragments.
The adjective granulomatous means characterized by granulomas.
Definition In pathology, a granuloma is an organized
collection of macrophages.
In medical practice, doctors occasionally 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.
Examples of the inaccurate use of the term granuloma are the lesions known as vocal cord
granuloma, pyogenic granuloma and intubation granuloma, all of which are examples of granulation
tissue, not granulomas.
"Pulmonary hyalinizing granuloma" is a lesion characterized by keloid-like fibrosis in the
lung, and is not granulomatous.
Similarly, radiologists often use the term granuloma when they see a calcified nodule
on X-ray or CT scan of the chest.
They make this assumption since granulomas usually contain calcium, although the cells
that form a granuloma are too tiny to be seen by a radiologist.
The most accurate use of the term "granuloma" requires a pathologist to examine surgically
removed and specially colored tissue under a microscope.
Macrophages are the cells that define a granuloma.
They often, but not invariably, fuse to form multinucleated giant cells.
The macrophages in granulomas are often referred to 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.
They also have larger nuclei than ordinary macrophages and their cytoplasm is typically
more pink when stained with eosin.
These changes are thought to be a consequence of "activation" of the macrophage by the offending
antigen.
The other key term in the above definition is the word "organized" that 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.
All granulomas, regardless of cause, may contain additional cells and matrix.
These include lymphocytes, neutrophils, eosinophils, multinucleated giant cells, fibroblasts and
collagen.
The additional cells are sometimes a clue to the cause of the granuloma.
For example, granulomas with numerous eosinophils may be a clue to coccidioidomycosis or allergic
bronchopulmonary fungal disease, and granulomas with numerous neutrophils suggest blastomycosis,
Wegener's granulomatosis, aspiration pneumonia or cat-scratch disease.
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.
Granulomas are seen in a wide variety of diseases, both infectious and non-infectious.
Infections that are characterized by granulomas include tuberculosis, leprosy, histoplasmosis,
cryptococcosis, coccidioidomycosis, blastomycosis and cat scratch disease.
Examples of 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.
An important feature of granulomas is whether or not they contain necrosis.
Necrosis refers to dead cells that, under the microscope, appear as a mass of formless
debris with no nuclei present.
A related term, "caseation" refers to a form of necrosis that, to the unaided eye, appears
cheese-like, and is typically 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.
Necrosis in granulomas
Diseases characterized by granulomas Tuberculosis
The granulomas of tuberculosis tend to contain necrosis, but non-necrotizing granulomas may
also be present.
Multinucleated giant cells with nuclei arranged like a horseshoe are often present, but are
not specific for tuberculosis.
A definitive diagnosis of tuberculosis requires identification of the causative organism by
microbiologic cultures.
Leprosy In leprosy, granulomas are found in the skin
and tend to involve nerves.
The appearance of the granulomas differs according to the precise type of leprosy.
Schistosomiasis Some schistosome ova that are laid in intestinal
and urinary venules backwash into the liver via the portal vein causing granuloma formation
in the liver.
Histoplasmosis Granulomas are seen in most forms of histoplasmosis.
Histoplasma organisms can sometimes be demonstrated within the granulomas by biopsy or microbiological
cultures.
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.
Using a microscope and appropriate stains, organisms can be seen within the granulomas.
Cat-scratch disease Cat-scratch disease is an infection caused
by the bacterial organism Bartonella henselae, typically acquired by a scratch from a kitten
infected with the organism.
The granulomas in this disease are found in the lymph nodes draining the site of the scratch.
They are characteristically "suppurative", i.e., pus forming, containing large numbers
of neutrophils.
Organisms are usually difficult to find within the granulomas using methods routinely used
in pathology laboratories.
Rheumatic Fever Rheumatic fever is a systemic disease affecting
the peri-arteriolar connective tissue and can occur after an untreated Group A Beta
hemolytic streptococcal pharyngeal infection.
It is believed to be caused by antibody cross-reactivity.
Sarcoidosis
Sarcoidosis is a disease of unknown cause characterized by non-necrotizing granulomas
in multiple organs and body sites, most commonly the lungs and lymph nodes within the chest
cavity.
Other common sites of involvement include the 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 and are
surrounded by concentric scar tissue.
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 spontaneously without complications or heal with residual
scarring.
In the lungs, this scarring can cause a condition known as pulmonary fibrosis that impairs breathing;
in the heart, it can lead to rhythm disturbances, heart failure and even death.
Crohn's disease Crohn's disease is an inflammatory condition
of uncertain cause characterized by severe inflammation in the wall of the intestines
and other parts of the abdomen.
Within the inflammation in the gut wall, granulomas are often found, and are a clue to the diagnosis.
Listeria monocytogenes Listeria monocytogenes infection in infants
can cause potentially fatal disseminated granulomas, called granulomatosis infantiseptica, following
in utero infection.
Pneumocystis pneumonia Pneumocystis infection in the lungs is usually
not associated with granulomas, but rare cases are well documented to cause granulomatous
inflammation.
The diagnosis is established by finding Pneumocystis yeasts within the granulomas on lung biopsies.
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 lead to aspiration.
The resultant granulomas are typically found around the airways 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.
Rheumatoid arthritis Necrotizing granulomas can develop in patients
with rheumatoid arthritis, typically manifesting as bumps in the soft tissues around the joints
or in the lungs.
Granuloma annulare Granuloma annulare is a skin disease of unknown
cause in which granulomas are found in the dermis of the skin.
These granulomas typically have a central zone of mucin, which aids in the diagnosis
when a skin sample is viewed under the microscope.
Foreign-body granuloma A foreign-body granuloma occurs when a foreign
body penetrates the bodies soft tissue followed by acute inflammation and formation of a granuloma.
In some cases the foreign body can be found and removed even years after the precipitating
event.
Granulomas associated with vasculitis Certain inflammatory diseases are characterised
by a combination of granulomatous inflammation and vasculitis.
Both the granulomas as well as the vasculitis tend to occur in association with necrosis.
Classic examples of such diseases include granulomatosis with polyangiitis and Churg-Strauss
syndrome.
See also Lick granuloma, skin disorder in dogs that
results from dog's urge to lick the lower portion of its leg
Sperm granuloma Contact granuloma; i.e., "throat granuloma."
Notes
References
External links Atlas of Granulomatous Diseases Yale Rosen,
MD