Touton Giant Cell
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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 Lipids are a broad group of organic compounds which include fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include storing ...
-rich lesions such as those of
fat necrosis Fat necrosis is necrosis affecting fat tissue (adipose tissue). The term is well-established in medical terminology despite not denoting a specific pattern of necrosis. Fat necrosis may result from various injuries to adipose tissue, including: p ...
,
xanthoma A xanthoma (pl. xanthomas or xanthomata) (condition: xanthomatosis) is a deposition of yellowish cholesterol-rich material that can appear anywhere in the body in various disease states. They are cutaneous manifestations of lipidosis in which lip ...
,
xanthelasma Xanthelasma is a sharply demarcated yellowish deposit of cholesterol underneath the skin. It usually occurs on or around the eyelids (''xanthelasma palpebrarum'', abbreviated XP). While they are neither harmful to the skin nor painful, these mino ...
and
xanthogranuloma Juvenile xanthogranuloma is a form of histiocytosis, classified as non-Langerhans cell histiocytosis. It is a rare skin disorder that primarily affects children under one year of age but can also be found in older children and adults. It was fi ...
s. 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 in
granulomatous A granuloma is an aggregation of macrophages (along with other cells) 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 subst ...
inflammation, which is a type of inflammation caused by the clustering of immune cells, or granulomas. They are also found in
dermatofibroma A dermatofibroma, or benign fibrous histiocytomas, is a benign nodule in the skin, typically on the legs, elbows or chest of an adult. It is usually painless. It usually ranges from 0.2 to 2 cm in size but larger examples have been reported. It ty ...
. 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.


History

Touton giant cells are named for Karl Touton, a German
botanist Botany, also called plant science, is the branch of natural science and biology studying plants, especially Plant anatomy, their anatomy, Plant taxonomy, taxonomy, and Plant ecology, ecology. A botanist or plant scientist is a scientist who s ...
and
dermatologist Dermatology is the branch of medicine dealing with the skin.''Random House Webster's Unabridged Dictionary.'' Random House, Inc. 2001. Page 537. . It is a speciality with both medical and surgical aspects. A dermatologist is a specialist medi ...
. Karl Touton first observed these cells in 1885 and named them "xanthelasmatic giant cells", a name which has since fallen out of favor. 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).


Appearance

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 The cytoplasm describes all the material within a eukaryotic or prokaryotic cell, enclosed by the cell membrane, including the organelles and excluding the nucleus in eukaryotic cells. The material inside the nucleus of a eukaryotic cell a ...
, while foamy cytoplasm surrounds the nuclei. 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 Eosinophilic (Greek suffix '' -phil'', meaning ''eosin-loving'') describes the staining of tissues, cells, or organelles after they have been washed with eosin, a dye commonly used in histological staining. Eosin is an acidic dye for stainin ...
. Meanwhile, the cytoplasm near the periphery of the cell, the peripheral zone, is pale and contains
vacuoles A vacuole () is a membrane-bound organelle which is present in plant and fungal cells and some protist, animal, and bacterial cells. Vacuoles are essentially enclosed compartments which are filled with water containing inorganic and organic mo ...
due to the lipid content in this zone of the cell.


Activation and macrophage relationship

Touton giant cells are formed by the fusion of
macrophage Macrophages (; abbreviated MPhi, φ, MΦ or MP) 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 ...
-derived foam cells. It has been suggested that
cytokines Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...
(signaling molecules) such as
interferon gamma Interferon gamma (IFNG or IFN-γ) is a dimerized soluble cytokine that is the only member of the type II class of interferons. The existence of this interferon, which early in its history was known as immune interferon, was described by E. F. ...
, interleukin-3,
interleukin-6 Interleukin 6 (IL-6) is an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine. In humans, it is encoded by the ''IL6'' gene. In addition, osteoblasts secrete IL-6 to stimulate osteoclast formation. Smoo ...
(IL-6) and
M-CSF The colony stimulating factor 1 (CSF1), also known as macrophage colony-stimulating factor (M-CSF), is a secreted cytokine which causes hematopoietic stem cells to differentiate into macrophages or other related cell types. Eukaryotic cells also ...
may be involved in the production of Touton giant cells. 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 with the activation of
Toll-like receptors Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system. They are single-pass membrane protein, single-spanning receptor (biochemistry), receptors usually expressed on sentinel cells such as macrophages ...
(TLRs). Further proof that these Touton giant cells are histiocytic in origin, meaning they arise from a macrophage-lineage cell, is the fact they react positively to enzymes found in histiocytes such as
lysozyme Lysozyme (, muramidase, ''N''-acetylmuramide glycanhydrolase; systematic name peptidoglycan ''N''-acetylmuramoylhydrolase) is an antimicrobial enzyme produced by animals that forms part of the innate immune system. It is a glycoside hydrolase ...
, 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.


Correspondence with immune system

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
monocyte Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and monocyte-derived dendritic cells. As a part of the vertebrate innate immune system monocytes also ...
s, 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.


Associated conditions

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 Hyperlipidemia is abnormally high levels of any or all lipids (e.g. fats, triglycerides, cholesterol, phospholipids) or lipoproteins in the blood. citing: and The term ''hyperlipidemia'' refers to the laboratory finding itself and is also use ...
; xanthogranuloma: benign skin lesions;
fat necrosis Fat necrosis is necrosis affecting fat tissue (adipose tissue). The term is well-established in medical terminology despite not denoting a specific pattern of necrosis. Fat necrosis may result from various injuries to adipose tissue, including: p ...
: areas of trauma where adipose tissue has been disrupted; dermatofibrosa: benign skin tumor characterized by fibrous components; granulomatous diseases such as
sarcoidosis Sarcoidosis (; also known as Besnier–Boeck–Schaumann disease) is a disease involving abnormal collections of White blood cell, inflammatory cells that form lumps known as granulomata. The disease usually begins in the lungs, skin, or lymph n ...
.


References


External links


Cytokines & Cells Online Pathfinder Encyclopaedia
Cell biology {{immunology-stub