Touton giant cells are a type of multinucleated giant cell observed in a myriad of pathological disorders and conditions. Specifically, Touton giant cells are found in lipid rich lesions with high lipid content such as fat necrosis, xanthoma, xanthelasma and xanthogranulomas. With that being said, Touton giant cells are also referred to as Xanthelasmatic cells due to the fact they are found in lesions associated with xanthomas which are skin growths with yellow, lipid filled deposits. Touton giant cells are often frequently observed with granulomatous, which is a type of inflammation caused by the clustering of immune cells, or granulomas [1] . They are also found in dermatofibroma. [2] Touton giant cells are commonly characterized by their very unqiue histological appearance as well as their response to various stimuli associated with the body's immune system.
Touton giant cells are named for Karl Touton, a German botanist and dermatologist. [3] Karl Touton first observed these cells in 1885 and named them "xanthelasmatic giant cells", a name which has since fallen out of favor. [4] Karl Touton observed these giant cells when examining a biopsy or skin tissue sample from someone with a lesion under a microscope. He then classified and named these cells due to their strikingly unique appearance. Touton giant cells are still observed using these methods as well as staining with histological dyes such as hematoxylin and eosin (H&E) [5] .
Touton giant cells, being multinucleated giant cells, can be distinguished by the presence of several nuclei in a distinct pattern. This pattern is described as a ring-like or wreath-like in the center of a cell. These cells contain a ring of nuclei surrounding a central homogeneous cytoplasm, while foamy cytoplasm surrounds the nuclei. [6] [7] The cytoplasm is usually lipid-rich and has a foamy appearance. The cytoplasm is divided into two distic areas: the peripheral zone and the central zone. The central zone is the cytoplasm surrounded by the nuclei which is described as both amphophilic and eosinophilic. Meanwhile, the cytoplasm near the periphery of the cell, the peripheral zone, is pale and contains vacuoles due to the lipid content in this zone of the cell. [1] [8]
Touton giant cells are considered white blood cells due to their role in the immune system as well as where they are derived from. These multinucleated giant cells are formed by the fusion of macrophages, a type of white blood cell that has many functions such as removing dead cells and stimulating the action of other immune cells. Macrophages are derived from monocytes, white blood cells that aid in destroying bacteria and germs to prevent infection. These monocytes arise from the myeloid stem cell line. Touton giant cells aim to remove harmful substances in the tissue in which they are from. They do so by engulfing and degrading large foreign materials such as lipids in the lesions they are found in, most commonly in areas of fat necrosis [9] .
Touton giant cells are formed by the fusion of macrophage-derived foam cells. It has been suggested that cytokines (signaling molecules) such as interferon gamma, interleukin-3, interleukin-6 (IL-6) and M-CSF may be involved in the production of Touton giant cells. [10] [11] Specifically, Touton giant cells are said to be derived from macrophages that aid directly in reducing inflammation. They have reparative behavior and by using IL-6, a cytokine, these cells are activated and able to perform tissue repair. Although the specific fusion molecule associated with fusing macrophages to form Touton giant cells is not very well understood, it seems as though there is an association to the activated of Toll-like receptors (TLRs) [12] . Further proof that these Touton giant cells are histiocytic in origin, meaning they arise from a macrophage-lineage cell, are the fact they react positively to enzymes found in histiocytes such as lysozyme, alpha 1-anti-trypsin and alpha 1-anti-chymotrypsin. Touton giant cells are able to express these proteins which are involved in actions such as regulation of tissue damage, tissue breakdown, inflammation and more, which are common actions of a Touton giant cell [13] .
Conditions associated with Touton giant cells are ones that involve lipid metabolism or chronic inflammation. Some of these conditions include xanthomas: lesions that are seen in hyperlipidemia; xanthogranuloma: benign skin lesions; fat necrosis: areas of trauma where adipose tissue has been disrupted; dermatofibrosa: benign skin tumor characterized by fibrous components; granulomatous diseases such as sarcoidosis. [13]
Necrosis is a form of cell injury which results in the premature death of cells in living tissue by autolysis. The term "necrosis" came about in the mid-19th century and is commonly attributed to German pathologist Rudolf Virchow, who is often regarded as one of the founders of modern pathology. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated digestion of cell components. In contrast, apoptosis is a naturally occurring programmed and targeted cause of cellular death. While apoptosis often provides beneficial effects to the organism, necrosis is almost always detrimental and can be fatal.
Macrophages are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris, and foreign substances, which do not have proteins that are specific to healthy body cells on their surface. This process is called phagocytosis, which acts to defend the host against infection and injury.
A granuloma is an aggregation of macrophages that forms in response to chronic inflammation. This occurs when the immune system attempts to isolate foreign substances that it is otherwise unable to eliminate. Such substances include infectious organisms including bacteria and fungi, as well as other materials such as foreign objects, keratin, and suture fragments.
Kupffer cells, also known as stellate macrophages and Kupffer–Browicz cells, are specialized cells localized in the liver within the lumen of the liver sinusoids and are adhesive to their endothelial cells which make up the blood vessel walls. Kupffer cells comprise the largest population of tissue-resident macrophages in the body. Gut bacteria, bacterial endotoxins, and microbial debris transported to the liver from the gastrointestinal tract via the portal vein will first come in contact with Kupffer cells, the first immune cells in the liver. It is because of this that any change to Kupffer cell functions can be connected to various liver diseases such as alcoholic liver disease, viral hepatitis, intrahepatic cholestasis, steatohepatitis, activation or rejection of the liver during liver transplantation and liver fibrosis. They form part of the mononuclear phagocyte system.
A giant cell is a mass formed by the union of several distinct cells, often forming a granuloma.
In medicine, Aschoff bodies are nodules found in the hearts of individuals with rheumatic fever. They result from inflammation in the heart muscle and are characteristic of rheumatic heart disease. These nodules were discovered independently by Ludwig Aschoff and Paul Rudolf Geipel, and for this reason they are occasionally called Aschoff–Geipel bodies.
Foam cells, also called lipid-laden macrophages, are a type of cell that contain cholesterol. These can form a plaque that can lead to atherosclerosis and trigger myocardial infarction and stroke.
Monoblasts are the committed progenitor cells that differentiated from a committed macrophage or dendritic cell precursor (MDP) in the process of hematopoiesis. They are the first developmental stage in the monocyte series leading to a macrophage. Their myeloid cell fate is induced by the concentration of cytokines they are surrounded by during development. These cytokines induce the activation of transcription factors which push completion of the monoblast's myeloid cell fate. Monoblasts are normally found in bone marrow and do not appear in the normal peripheral blood. They mature into monocytes which, in turn, develop into macrophages. They then are seen as macrophages in the normal peripheral blood and many different tissues of the body. Macrophages can produce a variety of effector molecules that initiate local, systemic inflammatory responses. These monoblast differentiated cells are equipped to fight off foreign invaders using pattern recognition receptors to detect antigen as part of the innate immune response.
Interleukin 19 (IL-19) is an immunosuppressive protein that belongs to the IL-10 cytokine subfamily.
A foreign body reaction (FBR) is a typical tissue response to a foreign body within biological tissue. It usually includes the formation of a foreign body granuloma. Tissue encapsulation of an implant is an example, as is inflammation around a splinter. Foreign body granuloma formation consists of protein adsorption, macrophages, multinucleated foreign body giant cells, fibroblasts, and angiogenesis. It has also been proposed that the mechanical property of the interface between an implant and its surrounding tissues is critical for the host response.
Epithelioid cells are derivatives of activated macrophages resembling epithelial cells.
Rosai–Dorfman disease, also known as sinus histiocytosis with massive lymphadenopathy or sometimes as Destombes–Rosai–Dorfman disease, is a rare disorder of unknown cause that is characterized by abundant histiocytes in lymph nodes or other locations including the skin, sinuses, brain and heart. Individuals with the disorder often present with enlarged lymph nodes and a nodular red skin rash. The main causes of morbidity with the illness are systemic infection from impaired immune response and organ dysfunction from histiocyte deposition throughout the body.
Type IV hypersensitivity, in the Gell and Coombs classification of allergic reactions, often called delayed-type hypersensitivity, is a type of hypersensitivity reaction that can take a day or more to develop. Unlike the other types, it is not humoral but rather is a type of cell-mediated response. This response involves the interaction of T cells, monocytes, and macrophages.
A foreign-body giant cell is a collection of fused macrophages which are generated in response to the presence of a large foreign body. This is particularly evident with catheters, parasites, or biomaterials that are inserted into the body for replacement or regeneration of diseased or damaged tissues. Foreign body giant cells are also produced to digest foreign material that is too large for phagocytosis. The inflammatory process that creates these cells often leads to a foreign body granuloma.
White blood cells, also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. White blood cells are generally larger than red blood cells. They include three main subtypes: granulocytes, lymphocytes and monocytes.
Multinucleate cell angiohistiocytoma (MCAH) is a cutaneous condition that presents as slowly growing, multiple, discrete but grouped, red to violaceous papules
The xanthogranulomatous process (XP), is a form of acute and chronic inflammation characterized by an exuberant clustering of foamy macrophages among other inflammatory cells. Localization in the kidney and renal pelvis has been the most frequent and better known occurrence followed by that in the gallbladder but many others have been subsequently recorded. The pathological findings of the process and etiopathogenetic and clinical observations have been reviewed by Cozzutto and Carbone.
Karl Touton was a German dermatologist and amateur botanist.
Histopathology of dermatitis can be performed in uncertain cases of inflammatory skin condition that remain uncertain after history and physical examination.
Dermal macrophages are macrophages in the skin that facilitate skin homeostasis by mediating wound repair, hair growth, and salt balance. Their functional role in these processes is the mediator of inflammation. They can acquire an M1 or M2 phenotype to promote or suppress an inflammatory response, thereby influencing other cells' activity via the production of pro-inflammatory or anti-inflammatory cytokines. Dermal macrophages' ability to acquire pro-inflammatory properties also potentiates them in cancer defence. M1 macrophages can suppress tumour growth in the skin by their pro-inflammatory properties. However, M2 macrophages support tumour growth and invasion by the production of Th2 cytokines such as TGFβ and IL-10. Thus, the exact contribution of each phenotype to cancer defence and the skin's homeostasis is still unclear.
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