Granuloma

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Granuloma
Granuloma mac.jpg
Picture of a granuloma (without necrosis) as seen through a microscope on a glass slide. The tissue on the slide is stained with two standard dyes (hematoxylin: blue, eosin: pink) to make it visible. The granuloma in this picture was found in a lymph node of a patient with Mycobacterium avium infection
Specialty Pathology

A granuloma is a structure formed during inflammation that is found in many diseases. It is a collection of immune cells known as macrophages. [1] Granulomas form when the immune system attempts to wall off substances it perceives as foreign but is unable to eliminate. Such substances include infectious organisms including bacteria and fungi, as well as other materials such as keratin and suture fragments. [1] [2] [3] [4]

Inflammation signs of activation of the immune system

Inflammation is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molecular mediators. The function of inflammation is to eliminate the initial cause of cell injury, clear out necrotic cells and tissues damaged from the original insult and the inflammatory process, and initiate tissue repair.

Immune system A biological system that protects an organism against disease

The immune system is a host defense system comprising many biological structures and processes within an organism that protects against disease. To function properly, an immune system must detect a wide variety of agents, known as pathogens, from viruses to parasitic worms, and distinguish them from the organism's own healthy tissue. In many species, the immune system can be classified into subsystems, such as the innate immune system versus the adaptive immune system, or humoral immunity versus cell-mediated immunity. In humans, the blood–brain barrier, blood–cerebrospinal fluid barrier, and similar fluid–brain barriers separate the peripheral immune system from the neuroimmune system, which protects the brain.

Bacteria A domain of prokaryotes – single celled organisms without a nucleus

Bacteria are a type of biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a number of shapes, ranging from spheres to rods and spirals. Bacteria were among the first life forms to appear on Earth, and are present in most of its habitats. Bacteria inhabit soil, water, acidic hot springs, radioactive waste, and the deep portions of Earth's crust. Bacteria also live in symbiotic and parasitic relationships with plants and animals. Most bacteria have not been characterised, and only about half of the bacterial phyla have species that can be grown in the laboratory. The study of bacteria is known as bacteriology, a branch of microbiology.

Contents

Definition

In pathology, a granuloma is an organized collection of macrophages. [1] [5]

Pathology study and diagnosis of disease

Pathology is the study of the causes and effects of disease or injury. The word pathology also refers to the study of disease in general, incorporating a wide range of bioscience research fields and medical practices. However, when used in the context of modern medical treatment, the term is often used in a more narrow fashion to refer to processes and tests which fall within the contemporary medical field of "general pathology," an area which includes a number of distinct but inter-related medical specialties that diagnose disease, mostly through analysis of tissue, cell, and body fluid samples. Idiomatically, "a pathology" may also refer to the predicted or actual progression of particular diseases, and the affix path is sometimes used to indicate a state of disease in cases of both physical ailment and psychological conditions. A physician practicing pathology is called a pathologist.

Macrophage type of white blood cell

Macrophages are a type of white blood cell, of the immune system, that engulfs and digests cellular debris, foreign substances, microbes, cancer cells, and anything else that does not have the type of proteins specific to healthy body cells on its surface in a process called phagocytosis. These large phagocytes are found in essentially all tissues, where they patrol for potential pathogens by amoeboid movement. They take various forms throughout the body, but all are part of the mononuclear phagocyte system. Besides phagocytosis, they play a critical role in nonspecific defense and also help initiate specific defense mechanisms by recruiting other immune cells such as lymphocytes. For example, they are important as antigen presenters to T cells. In humans, dysfunctional macrophages cause severe diseases such as chronic granulomatous disease that result in frequent infections.

In medical practice, doctors occasionally use the term "granuloma" in it’s more literal meaning: "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 this use of the term granuloma are the lesions known as vocal cord granuloma (known as contact 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 (stained) tissue under a microscope.

In medicine, nodules are solid, elevated areas of tissue or fluid inside or under the skin with a diameter greater than 0.5 centimeters. Nodules may form on tendons and muscles in response to injury. The vocal cords may also develop nodules. Nodules are normally benign and often painless, although they can affect the functioning of the organ.

Nevus visible, circumscribed, chronic lesion of the skin or mucosa, either congenital or acquired

Nevus is a nonspecific medical term for a visible, circumscribed, chronic lesion of the skin or mucosa. The term originates from nævus, which is Latin for "birthmark", however, a nevus can be either congenital or acquired. Common terms, including mole, birthmark, and beauty mark, are used to describe nevi, but these terms do not distinguish specific types of nevi from one another.

Contact granuloma

Contact granuloma, also known as a contact ulcer, vocal fold contact ulcer or vocal process granuloma, is a condition that develops due to persistent tissue irritation in the posterior larynx. Benign granulomas, not to be confused with other types of granulomas, occur on the vocal process of the vocal folds, where the vocal ligament attaches. Signs and symptoms may include hoarseness of the voice, or a sensation of having a lump in the throat, but contact granulomas may also be without symptoms. There are two common causes associated with contact granulomas; the first common cause is sustained periods of increased pressure on the vocal folds, and is commonly seen in people who use their voice excessively, such as singers. Treatment typically includes voice therapy and changes to lifestyle factors. The second common cause of granulomas is gastroesophageal reflux and is controlled primarily through the use of anti-reflux medication. Other associated causes are discussed below.

Histiocytes (specifically macrophages) are the cells that define a granuloma. They often, but not invariably, fuse to form multinucleated giant cells (Langhans giant cell). [6] 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.

Langhans giant cell

Langhans giant cells are large cells found in granulomatous conditions.

Epithelioid histiocytes are activated macrophages resembling epithelial cells. Structurally, they are elongated, with finely granular, pale eosinophilic (pink) cytoplasm, and central, ovoid nuclei, which are less dense than that of a lymphocyte. They have indistinct shape and often appear to merge into one another, forming aggregates known as giant cells. Epithelioid cells are central in the formation of granulomas, which are associated with many serious diseases.

Eosin groups of chemical compound used as dyes

Eosin is the name of several fluorescent acidic compounds which bind to and form salts with basic, or eosinophilic, compounds like proteins containing amino acid residues such as arginine and lysine, and stains them dark red or pink as a result of the actions of bromine on fluorescein. In addition to staining proteins in the cytoplasm, it can be used to stain collagen and muscle fibers for examination under the microscope. Structures that stain readily with eosin are termed eosinophilic.

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 (fibrosis). 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, granulomatosis with polyangiitis, aspiration pneumonia or cat-scratch disease.

In biology, matrix is the material in animal or plant cells, in which more specialized structures are embedded, and a specific part of the mitochondrion. The internal structure of connective tissues is an extracellular matrix. Finger nails and toenails grow from matrices. It is found in various connective tissue. It is generally used as a jelly like structure instead of cytoplasm in connective tissue.

Collagen is the main structural protein in the extracellular space in the various connective tissues in the body. As the main component of connective tissue, it is the most abundant protein in mammals, making 25% to 35% of the whole-body protein content. Collagen consists of amino acids wound together to form triple-helices of elongated fibrils. It is mostly found in fibrous tissues such as tendons, ligaments, and skin.

Fibrosis formation of excess fibrous connective tissue in an organ or tissue in a reparative or reactive process

Fibrosis is the formation of excess fibrous connective tissue in an organ or tissue in a reparative or reactive process. This can be a reactive, benign, or pathological state. In response to injury, this is called scarring, and if fibrosis arises from a single cell line, this is called a fibroma. Physiologically, fibrosis acts to deposit connective tissue, which can interfere with or totally inhibit the normal architecture and function of the underlying organ or tissue. Fibrosis can be used to describe the pathological state of excess deposition of fibrous tissue, as well as the process of connective tissue deposition in healing. Defined by the pathological accumulation of extracellular matrix (ECM) proteins, fibrosis results in scarring and thickening of the affected tissue, it is in essence an exaggerated wound healing response which interferes with normal organ function.

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 sometimes the offending antigen is unknown (as in sarcoidosis).[ citation needed ]

Sarcoidosis hypersensitivity reaction type IV disease characterized by the growth of collections of inflammatory cells (granulomas) in multiple organs

Sarcoidosis is a disease involving abnormal collections of inflammatory cells that form lumps known as granulomas. The disease usually begins in the lungs, skin, or lymph nodes. Less commonly affected are the eyes, liver, heart, and brain. Any organ, however, can be affected. The signs and symptoms depend on the organ involved. Often, no, or only mild, symptoms are seen. When it affects the lungs, wheezing, coughing, shortness of breath, or chest pain may occur. Some may have Löfgren syndrome with fever, large lymph nodes, arthritis, and a rash known as erythema nodosum.

Granulomas are seen in a wide variety of diseases, both infectious and non-infectious. [1] [2] 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, granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, 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" (literally: turning to cheese) refers to a form of necrosis that, to the unaided eye (i.e., without a microscope), appears cheese-like ("caseous"), 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. [1] There are several exceptions to this general rule, but it nevertheless remains useful in day-to-day diagnostic pathology.

Diseases with granulomas

Tuberculosis

The granulomas of tuberculosis tend to contain necrosis ("caseating tubercules"), but non-necrotizing granulomas may also be present. Multinucleated giant cells with nuclei arranged like a horseshoe (Langhans giant cell) and foreign body giant cells [7] are often present, but are not specific for tuberculosis. A definitive diagnosis of tuberculosis requires identification of the causative organism by microbiologic cultures. [8]

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 (acute histoplasmosis, histoplasmoma, chronic histoplasmosis). Histoplasma organisms can sometimes be demonstrated within the granulomas by biopsy or microbiological cultures. [1]

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. [8]

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

Two asteroid bodies in sarcoidosis. H&E stain. Asteroid bodies high mag cropped.jpg
Two asteroid bodies in sarcoidosis. H&E stain.

Sarcoidosis is a disease of unknown cause characterized by non-necrotizing ("non-caseating") granulomas in multiple organs and body sites, [9] 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 (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. [8] 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. [10]

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. [11]

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 (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. [12]

Rheumatoid arthritis

Necrotizing granulomas can develop in patients with rheumatoid arthritis, typically manifesting as bumps in the soft tissues around the joints (so-called rheumatoid nodules) or in the lungs. [8]

Granuloma annulare

Granuloma annulare is a skin disease of unknown cause in which granulomas are found in the dermis of the skin. However, it is not a true granuloma. Typically there is a central zone of necrobiotic generation of collagen with surrounding inflammation and mucin deposition on pathology.

Foreign-body granuloma

A foreign-body granuloma occurs when a foreign body (such as a wood splinter, piece of metal, glass etc.) penetrates the body's soft tissue followed by acute inflammation and formation of a granuloma. [13] In some cases the foreign body can be found and removed even years after the precipitating event. [14]

Childhood granulomatous periorificial dermatitis

Childhood granulomatous periorificial dermatitis is a rare granulomatous skin disorder of unknown cause. It is temporary and tends to affect children, usually of African descent.

Granulomas associated with vasculitis

Certain inflammatory diseases are characterised by a combination of granulomatous inflammation and vasculitis (inflammation of the blood vessels). Both the granulomas as well as the vasculitis tend to occur in association with necrosis. Classic examples of such diseases include granulomatosis with polyangiitis (GPA; previously referred to by the eponym Wegener's granulomatosis [15] ) and eosinophilic granulomatosis with polyangiitis (EGPA; formerly known as Churg-Strauss syndrome).

Etymology

The term is from granule + -oma. The plural is granulomas or granulomata. The adjective granulomatous means characterized by granulomas.

See also

Related Research Articles

Berylliosis pneumoconiosis that involves allergic response located in lungs caused by inhalation of beryllium compounds

Berylliosis, or chronic beryllium disease (CBD), is a chronic allergic-type lung response and chronic lung disease caused by exposure to beryllium and its compounds, a form of beryllium poisoning. It is distinct from acute beryllium poisoning, which became rare following occupational exposure limits established around 1950. Berylliosis is an occupational lung disease.

Hemoptysis is the coughing up of blood or blood-stained mucus from the bronchi, larynx, trachea, or lungs. This can occur with lung cancer, infections such as tuberculosis, bronchitis, or pneumonia, and certain cardiovascular conditions. Hemoptysis is considered massive at 300 mL. In such cases, there are always severe injuries. The primary danger comes from choking, rather than blood loss.

Histoplasmosis human disease

Histoplasmosis is a disease caused by the fungus Histoplasma capsulatum. Symptoms of this infection vary greatly, but the disease affects primarily the lungs. Occasionally, other organs are affected; this is called disseminated histoplasmosis, and it can be fatal if left untreated.

Vasculitis vascular disease that is characterized by inflammation of the blood vessels

Vasculitis is a group of disorders that destroy blood vessels by inflammation. Both arteries and veins are affected. Lymphangitis is sometimes considered a type of vasculitis. Vasculitis is primarily caused by leukocyte migration and resultant damage.

Granulomatosis with polyangiitis autoimmune disease affecting blood vessels in the lungs, kidneys, and skin

Granulomatosis with polyangiitis (GPA), formerly known as Wegener's Granulomatosis (WG), is a long-term systemic disorder that involves both granulomatosis and polyangiitis. It is a form of vasculitis that affects small- and medium-size vessels in many organs but most commonly affects the upper respiratory tract and the kidneys. Therefore, the signs and symptoms of GPA are highly varied and reflect which organs are supplied by the affected blood vessels. Typical signs and symptoms include nosebleeds, stuffy nose and crustiness of nasal secretions, and inflammation of the uveal layer of the eye. Damage to the heart, lungs and kidneys can be fatal.

Eosinophilic granulomatosis with polyangiitis vasculitits that is systemic vasculitis realized as blood vessel inflammation and has_symptom asthma along with hay fever, rash and gastrointestinal bleeding.

Eosinophilic granulomatosis with polyangiitis (EGPA), also known as allergic granulomatosis, is an extremely rare autoimmune condition that causes inflammation of small and medium-sized blood vessels (vasculitis) in persons with a history of airway allergic hypersensitivity (atopy).

Uveitis human disease

Uveitis is the inflammation of the uvea, the pigmented layer that lies between the inner retina and the outer fibrous layer composed of the sclera and cornea. The uvea consists of the middle layer of pigmented vascular structures of the eye and includes the iris, ciliary body, and choroid. Uveitis is an ophthalmic emergency and requires a thorough examination by an optometrist or ophthalmologist and urgent treatment to control the inflammation. It is often associated with other ocular problems.

Chest radiograph

A chest radiograph, colloquially called a chest X-ray (CXR), or chest film, is a projection radiograph of the chest used to diagnose conditions affecting the chest, its contents, and nearby structures. Chest radiographs are the most common film taken in medicine.

Tuberculous lymphadenitis

Tuberculous lymphadenitis is the most common form of tuberculosis infections that appears outside the lungs. Tuberculous lymphadenitis is a chronic, specific granulomatous inflammation of the lymph node with caseation necrosis, caused by infection with Mycobacterium tuberculosis or related bacteria.

Caseous necrosis

Caseous necrosis is a form of cell death in which the tissue maintains a cheese-like appearance. The dead tissue appears as a soft and white proteinaceous dead cell mass.

Lung abscess lung disease characterized by microbial infection which causes a type of liquefactive necrosis of the pulmonary tissue and formation of cavities containing necrotic debris or fluid

Lung abscess is a type of liquefactive necrosis of the lung tissue and formation of cavities containing necrotic debris or fluid caused by microbial infection.

Scleritis Human disease

Scleritis is a serious inflammatory disease that affects the white outer coating of the eye, known as the sclera. The disease is often contracted through association with other diseases of the body, such as granulomatosis with polyangiitis or rheumatoid arthritis. There are three types of scleritis: diffuse scleritis, nodular scleritis, and necrotizing scleritis. Scleritis may be the first symptom of onset of connective tissue disease.

Giant cell Wikimedia disambiguation page

A giant cell is a mass formed by the union of several distinct cells, often forming a granuloma. It can arise in response to an infection, such as from tuberculosis, herpes, or HIV, or foreign body. These multinucleate giant cells (MGCs) are cells of monocyte or macrophage lineage fused together.

Mediastinitis inflammatory process affecting the mediastinum

Mediastinitis is inflammation of the tissues in the mid-chest, or mediastinum. It can be either acute or chronic. It is thought to be due to four different etiologies:

Orofacial granulomatosis (OFG) is a condition characterized by persistent enlargement of the soft tissues of the mouth, lips and the area around the mouth on the face. The enlargement does not cause any pain, but the best treatment and the prognosis are uncertain. The mechanism of the enlargement is granulomatous inflammation. The underlying cause of the condition is not completely understood, and there is disagreement as to how it relates to Crohn's disease and sarcoidosis.

Cavitary pneumonia is a disease in which the normal lung architecture is replaced by a cavity. In a healthy lung, oxygen transport occurs at the level of the alveoli, each of which has an average size of 0.1 mm. These air spaces can become enlarged by a number of processes: bacterial infection (tuberculosis), fungal infection, vasculitis, collagen vascular disease or granulomatous disease (sarcoidosis).

Necrotizing vasculitis also called Systemic necrotizing vasculitus (SNV) is a category of vasculitis, comprising vasculitides that present with necrosis.

Granulomatous mastitis can be divided into idiopathic granulomatous mastitis and granulomatous mastitis occurring as a rare secondary complication of a great variety of other conditions such as tuberculosis and other infections, sarcoidosis and granulomatosis with polyangiitis. Special forms of granulomatous mastitis occur as complication of diabetes. Some cases are due to silicone injection or other foreign body reactions.

References

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