Langerhans cell histiocytosis (LCH) is an abnormal clonal proliferation of
Langerhans cell
A Langerhans cell (LC) is a tissue-resident macrophage of the skin. These cells contain organelles called Birbeck granules. They are present in all layers of the epidermis and are most prominent in the stratum spinosum. They also occur in the ...
s, abnormal
cell
Cell most often refers to:
* Cell (biology), the functional basic unit of life
Cell may also refer to:
Locations
* Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery ...
s deriving from
bone marrow
Bone marrow is a semi-solid tissue found within the spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It is composed of hematopoietic ce ...
and capable of migrating from skin to
lymph node
A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that inclu ...
s.
Symptoms range from isolated bone lesions to
multisystem disease
A systemic disease is one that affects a number of Organ (anatomy), organs and Tissue (biology), tissues, or affects the Human body, body as a whole.
Examples
* Mastocytosis, including mast cell activation syndrome and eosinophilic esophagitis
...
.
LCH is part of a group of syndromes called
histiocytoses, which are characterized by an abnormal proliferation of
histiocyte
A histiocyte is a vertebrate cell that is part of the mononuclear phagocyte system (also known as the reticuloendothelial system or lymphoreticular system). The mononuclear phagocytic system is part of the organism's immune system. The histiocyt ...
s (an archaic term for activated
dendritic cell
Dendritic cells (DCs) are antigen-presenting cells (also known as ''accessory cells'') of the mammalian immune system. Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system. ...
s and
macrophage
Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer cel ...
s). These diseases are related to other forms of abnormal proliferation of
white blood cell
White blood cells, also called leukocytes or leucocytes, are the cell (biology), cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and de ...
s, such as
leukemia
Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ' ...
s and
lymphoma
Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). In current usage the name usually refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enlar ...
s.
The disease has gone by several names, including
Hand–Schüller–Christian disease
Chronic multifocal Langerhans cell histiocytosis, previously known as Hand–Schüller–Christian disease, is a type of Langerhans cell histiocytosis (LCH), which can affect multiple organs. The condition is traditionally associated with a combina ...
,
Abt-Letterer-Siwe disease, Hashimoto-Pritzker disease (a very rare self-limiting variant seen at birth) and histiocytosis X, until it was renamed in 1985 by the
Histiocyte Society.
[
]
Classification
The disease spectrum results from clonal accumulation and proliferation of cells resembling the epidermal dendritic cell
Dendritic cells (DCs) are antigen-presenting cells (also known as ''accessory cells'') of the mammalian immune system. Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system. ...
s called Langerhans cell
A Langerhans cell (LC) is a tissue-resident macrophage of the skin. These cells contain organelles called Birbeck granules. They are present in all layers of the epidermis and are most prominent in the stratum spinosum. They also occur in the ...
s, sometimes called dendritic cell histiocytosis. These cells in combination with lymphocyte
A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include natural killer cells (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic ad ...
s, eosinophil
Eosinophils, sometimes called eosinophiles or, less commonly, acidophils, are a variety of white blood cells (WBCs) and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. A ...
s, and normal histiocyte
A histiocyte is a vertebrate cell that is part of the mononuclear phagocyte system (also known as the reticuloendothelial system or lymphoreticular system). The mononuclear phagocytic system is part of the organism's immune system. The histiocyt ...
s form typical LCH lesions that can be found in almost any organ. A similar set of diseases has been described in canine histiocytic diseases
Histiocytic diseases in dogs are a group of diseases in dogs which may involve the skin, and which can be difficult to differentiate from granulomatous, reactive inflammatory or lymphoproliferative diseases. The clinical presentation and behaviour ...
.
LCH is clinically divided into three groups: unifocal, multifocal unisystem, and multifocal multisystem.
Unifocal
Unifocal LCH, also called ''eosinophilic granuloma Humans
Human eosinophilic granuloma is characterized by abnormal proliferation of Langerhans cells (LCs). LCs are antigen-presenting cells derived from dendritic cells. In humans, eosinophilic granulomas are considered as a benign tumors that occ ...
'' (an older term which is now known to be a misnomer
A misnomer is a name that is incorrectly or unsuitably applied. Misnomers often arise because something was named long before its correct nature was known, or because an earlier form of something has been replaced by a later form to which the name ...
), is a disease characterized by an expanding proliferation of Langerhans cells in one organ, where they cause damage called lesions. It typically has no extraskeletal involvement, but rarely a lesion can be found in the skin, lungs, or stomach. It can appear as a single lesion in an organ, up to a large quantity of lesions in one organ. When multiple lesions are scattered throughout an organ, it can be called a multifocal unisystem variety. When found in the lungs, it should be distinguished from Pulmonary Langerhans cell hystiocytosis—a special category of disease most commonly seen in adult smokers. When found in the skin it is called cutaneous single system Langerhans cell LCH. This version can heal without therapy in some rare cases. This primary bone involvement helps to differentiate eosinophilic granuloma from other forms of Langerhans Cell Histiocytosis (Letterer-Siwe or Hand-Schüller-Christian variant).
Multifocal unisystem
Seen mostly in children, multifocal unisystem LCH is characterized by fever, bone lesions and diffuse eruptions, usually on the scalp and in the ear canals. 50% of cases involve the pituitary stalk
The pituitary stalk (also known as the infundibular stalk, Fenderson's funnel, or simply the infundibulum) is the connection between the hypothalamus and the posterior pituitary. The floor of the third ventricle is prolonged downward as a funnel- ...
, often leading to diabetes insipidus
Diabetes insipidus (DI), recently renamed to Arginine Vasopressin Deficiency (AVP-D) and Arginine Vasopressin Resistance (AVP-R), is a condition characterized by large amounts of dilute urine and increased thirst. The amount of urine produce ...
. The triad of diabetes insipidus, exophthalmos
Exophthalmos (also called exophthalmus, exophthalmia, proptosis, or exorbitism) is a bulging of the eye anteriorly out of the orbit. Exophthalmos can be either bilateral (as is often seen in Graves' disease) or unilateral (as is often seen in ...
, and lytic bone lesions is known as the ''Hand-Schüller-Christian triad
Chronic multifocal Langerhans cell histiocytosis, previously known as Hand–Schüller–Christian disease, is a type of Langerhans cell histiocytosis (LCH), which can affect multiple organs. The condition is traditionally associated with a combina ...
''. Peak onset is 2–10 years of age.
Multifocal multisystem
Multifocal multisystem LCH, also called '' Letterer-Siwe disease'', is an often rapidly progressing disease in which Langerhans Cell cells proliferate in many tissues. It is mostly seen in children under age 2, and the prognosis is poor: even with aggressive chemotherapy, the five-year survival is only 50%.
Pulmonary Langerhans cell histiocytosis (PLCH)
Pulmonary Langerhans cell histiocytosis (PLCH) is a unique form of LCH in that it occurs almost exclusively in cigarette smokers. It is now considered a form of smoking-related interstitial lung disease
Interstitial lung disease (ILD), or diffuse parenchymal lung disease (DPLD), is a group of respiratory diseases affecting the interstitium (the tissue and space around the alveoli (air sacs)) of the lungs. It concerns alveolar epithelium, pulmo ...
. PLCH develops when an abundance of monoclonal CD1a-positive Langerhans (immature histiocytes) proliferate the bronchioles and alveolar interstitium, and this flood of histiocytes recruits granulocyte
Granulocytes are
cells in the innate immune system characterized by the presence of specific granules in their cytoplasm. Such granules distinguish them from the various agranulocytes. All myeloblastic granulocytes are polymorphonuclear. They ha ...
s like eosinophils and neutrophil
Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying in ...
s and agranulocyte
In immunology, agranulocytes (also known as nongranulocytes or mononuclear leukocytes) are one of the two types of leukocytes (white blood cells), the other type being granulocytes. Agranular cells are noted by the absence of Granule (cell biol ...
s like lymphocytes further destroying bronchioles and the interstitial alveolar space that can cause damage to the lungs. It is hypothesized that bronchiolar destruction in PLCH is first attributed to the special state of Langerhans cells that induce cytotoxic T-cell responses, and this is further supported by research that has shown an abundance of T-cells in early PLCH lesions that are CD4+ and present early activation markers. Some affected people recover completely after they stop smoking, but others develop long-term complications such as pulmonary fibrosis
Pulmonary fibrosis is a condition in which the lungs become scarred over time. Symptoms include shortness of breath, a dry cough, feeling tired, weight loss, and nail clubbing. Complications may include pulmonary hypertension, respiratory failu ...
and pulmonary hypertension.
Signs and symptoms
LCH provokes a non-specific inflammatory response
Inflammation (from la, inflammatio) 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 molecu ...
, which includes fever, lethargy
Lethargy is a state of tiredness, sleepiness, weariness, fatigue, sluggishness or lack of energy. It can be accompanied by depression, decreased motivation, or apathy. Lethargy can be a normal response to inadequate sleep, overexertion, overwo ...
, and weight loss. Organ involvement can also cause more specific symptoms.
* Bone: The most-frequently seen symptom in both unifocal and multifocal disease is painful bone swelling. The skull is most frequently affected, followed by the long bones of the upper extremities and flat bones. Infiltration in hands and feet is unusual. Osteolytic
Osteolysis is an active resorption of bone matrix by osteoclasts and can be interpreted as the reverse of ossification. Although osteoclasts are active during the natural formation of healthy bone the term "osteolysis" specifically refers to a path ...
lesions can lead to pathological fractures.
* Skin: Commonly seen are a rash which varies from scaly erythematous lesions to red papules pronounced in intertriginous In medicine, an intertriginous area is where two skin areas may touch or rub together. Examples of intertriginous areas are the axilla of the arm, the anogenital region, skin folds of the breasts and between digits. Intertriginous areas are known ...
areas. Up to 80% of LCH patients have extensive eruptions on the scalp.
* Bone marrow: Pancytopenia with superadded infection usually implies a poor prognosis. Anemia can be due to a number of factors and does not necessarily imply bone marrow infiltration.
* Lymph node: Enlargement of the liver in 20%, spleen in 30% and lymph nodes in 50% of Histiocytosis cases.
* Endocrine
The endocrine system is a messenger system comprising feedback loops of the hormones released by internal glands of an organism directly into the circulatory system, regulating distant target organs. In vertebrates, the hypothalamus is the neu ...
glands: Hypothalamic pituitary axis commonly involved. Diabetes insipidus
Diabetes insipidus (DI), recently renamed to Arginine Vasopressin Deficiency (AVP-D) and Arginine Vasopressin Resistance (AVP-R), is a condition characterized by large amounts of dilute urine and increased thirst. The amount of urine produce ...
is most common. Anterior pituitary
A major organ of the endocrine system, the anterior pituitary (also called the adenohypophysis or pars anterior) is the glandular, anterior lobe that together with the posterior lobe (posterior pituitary, or the neurohypophysis) makes up the p ...
hormone
A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are required ...
deficiency is usually permanent.
* Lungs: some patients are asymptomatic, diagnosed incidentally because of lung nodules on radiographs; others experience chronic cough and shortness of breath.
* Less frequently gastrointestinal tract
The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organ (biology), organs of the digestive syste ...
, central nervous system
The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...
, and oral cavity
In animal anatomy, the mouth, also known as the oral cavity, or in Latin cavum oris, is the opening through which many animals take in food and issue vocal sounds. It is also the cavity lying at the upper end of the alimentary canal, bounded on ...
.
Pathophysiology
The pathogenesis of Langerhans cell histiocytosis (LCH) is a matter of debate. There are ongoing investigations to determine whether LCH is a reactive (non-cancerous) or neoplastic (cancerous) process. Arguments supporting the reactive nature of LCH include the occurrence of spontaneous remissions, the extensive secretion of multiple cytokines by dendritic cells and bystander-cells (a phenomenon known as cytokine storm) in the lesional tissue, favorable prognosis and relatively good survival rate in patients without organ dysfunction or risk organ involvement.
On the other hand, the infiltration of organs by monoclonal population of pathologic cells, and the successful treatment of subset of disseminated disease using chemotherapeutic regimens are all consistent with a neoplastic process. In addition, a demonstration, using X chromosome–linked DNA probes, of LCH as a monoclonal proliferation provided additional support for the neoplastic origin of this disease. While clonality is an important attribute of cancer, its presence does not prove that a proliferative process is neoplastic. Recurrent cytogenetic or genomic abnormalities would also be required to demonstrate convincingly that LCH is a malignancy.
An activating somatic mutation of a proto-oncogene in the Raf family, the BRAF gene, was detected in 35 of 61 (57%) LCH biopsy samples with mutations being more common in patients younger than 10 years (76%) than in patients aged 10 years and older (44%). This study documented the first recurrent mutation in LCH samples. Two independent studies have confirmed this finding. Presence of this activating mutation could support the notion to characterize LCH as myeloproliferative disorder.
Diagnosis
Diagnosis is confirmed histologically
Histology,
also known as microscopic anatomy or microanatomy, is the branch of biology
Biology is the scientific study of life. It is a natural science with a broad scope but has several unifying themes that tie it together as a single ...
by tissue biopsy
A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a diseas ...
. Hematoxylin-eosin stain of biopsy slide will show features of Langerhans Cell e.g. distinct cell margin, pink granular cytoplasm
In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. The ...
. Presence of Birbeck granules
Birbeck granules, also known as Birbeck bodies, are rod shaped or "tennis-racket" cytoplasmic organelles with a central linear density and a striated appearance. First described in 1961 (where they were simply termed "characteristic granules"), the ...
on electron microscopy
An electron microscope is a microscope that uses a beam of accelerated electrons as a source of illumination. As the wavelength of an electron can be up to 100,000 times shorter than that of visible light photons, electron microscopes have a hi ...
and immuno-cytochemical features e. g. CD1
CD1 (cluster of differentiation 1) is a family of glycoproteins expressed on the surface of various human antigen-presenting cells. They are related to the class I MHC molecules, and are involved in the presentation of lipid antigens to T ...
positivity are more specific. Initially routine blood tests e.g. full blood count, liver function test, U&Es, bone profile are done to determine disease extent and rule out other causes.
Imaging may be evident in chest X-ray
A chest radiograph, 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 med ...
s with micronodular and reticular
In chemistry and biology a cross-link is a bond or a short sequence of bonds that links one polymer chain to another. These links may take the form of covalent bonds or ionic bonds and the polymers can be either synthetic polymers or natural ...
changes of the lungs with cyst formation in advanced cases. MRI
Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio waves ...
and High-resolution CT may show small, cavitated nodules with thin-walled cysts. MRI scan of the brain can show three groups of lesions such as tumourous/granulomatous lesions, nontumourous/granulomatous lesions, and atrophy. Tumourous lesions are usually found in the hypothalamic-pituitary axis with space-occupying lesions with or without calcifications. In non-tumourous lesions, there is a symmetrical hyperintense T2 signal
A hyperintensity or T2 hyperintensity is an area of high intensity on types of magnetic resonance imaging (MRI) scans of the human brain, brain of a human or of another mammal that reflect lesions produced largely by demyelination and axonal loss. ...
with hypointense or hyperintense T1 signal extending from grey matter into the white matter. In the basal ganglia
The basal ganglia (BG), or basal nuclei, are a group of subcortical nuclei, of varied origin, in the brains of vertebrates. In humans, and some primates, there are some differences, mainly in the division of the globus pallidus into an extern ...
, MRI shows a hyperintense T1 signal in the globus pallidus
The globus pallidus (GP), also known as paleostriatum or dorsal pallidum, is a subcortical structure of the brain. It consists of two adjacent segments, one external, known in rodents simply as the globus pallidus, and one internal, known in rod ...
.
Assessment of endocrine
The endocrine system is a messenger system comprising feedback loops of the hormones released by internal glands of an organism directly into the circulatory system, regulating distant target organs. In vertebrates, the hypothalamus is the neu ...
function and bonemarrow biopsy are also performed when indicated.
* S-100 protein
The S100 proteins are a family of low molecular-weight proteins found in vertebrates characterized by two calcium-binding sites that have helix-loop-helix ("EF-hand-type") conformation. At least 21 different S100 proteins are known. They are enc ...
is expressed in a cytoplasmic pattern
* peanut agglutinin
Peanut agglutinin (PNA) is plant lectin protein derived from the fruits of ''Arachis hypogaea''. Peanut agglutinin may also be referred to as ''Arachis hypogaea'' lectin. Lectins recognise and bind particular sugar sequences in carbohydrates; peanu ...
(PNA) is expressed on the cell surface and perinuclearly
* major histocompatibility (MHC) class II is expressed (because histiocytes are macrophages)
* CD1a #REDIRECT CD1A
{{R from different capitalization
...
* langerin
Langerin (CD207) is a type II transmembrane protein which is encoded by the ''CD207'' gene in humans. It was discovered by scientists Sem Saeland and Jenny Valladeau as a main part of Birbeck granules. Langerin is C-type lectin receptor on Langer ...
(CD207
Langerin (CD207) is a type II transmembrane protein which is encoded by the ''CD207'' gene in humans. It was discovered by scientists Sem Saeland and Jenny Valladeau as a main part of Birbeck granules. Langerin is C-type lectin receptor on Langer ...
), a Langerhans Cell–restricted protein that induces the formation of Birbeck granules
Birbeck granules, also known as Birbeck bodies, are rod shaped or "tennis-racket" cytoplasmic organelles with a central linear density and a striated appearance. First described in 1961 (where they were simply termed "characteristic granules"), the ...
and is constitutively associated with them, is a highly specific marker.
Treatment
Guidelines for management of patients up to 18 years with Langerhans cell histiocytosis have been suggested. Treatment is guided by extent of disease. Solitary bone lesion may be amenable through excision or limited radiation, dosage of 5-10 Gy for children, 24-30 Gy for adults. However systemic diseases often require chemotherapy. Use of systemic steroid is common, singly or adjunct to chemotherapy. Local steroid cream is applied to skin lesions. Endocrine deficiency often require lifelong supplement e.g. desmopressin
Desmopressin, sold under the trade name DDAVP among others, is a medication used to treat diabetes insipidus, bedwetting, hemophilia A, von Willebrand disease, and high blood urea levels. In hemophilia A and von Willebrand disease, it should on ...
for diabetes insipidus which can be applied as nasal drop. Chemotherapeutic
Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs ( chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemothera ...
agents such as alkylating agents
Alkylation is the transfer of an alkyl group from one molecule to another. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion, or a carbene (or their equivalents). Alkylating agents are reagents for effecting al ...
, antimetabolites, vinca alkaloids
''Vinca'' alkaloids are a set of anti-mitotic and anti-microtubule alkaloid agents originally derived from the periwinkle plant ''Catharanthus roseus'' (basionym ''Vinca rosea'') and other ''vinca'' plants. They block beta-tubulin polymerizatio ...
either singly or in combination can lead to complete remission in diffuse disease.
Prognosis
There is a general excellent prognosis for the disease as those with localized disease have a long life span. With multi-focal disease 60% have a chronic course, 30% achieve remission and mortality is up to 10%.A full recovery can be expected for people who seek treatment and do not have more lesions at 12 and 24 months. With that being said, 50% children under 2 with disseminated Langerhans cell histiocytosis die of the disease. The prognosis rate decreases for patients who experience lung involvement. Whereas patients with skin and a solitary lymph node involvement generally have a good prognosis.
Although there is a general good prognosis for Langerhans cell histiocytosis, approximately 0% of patients with the disease are prone to various complications such as musculoskeletal disability, skin scarring and diabetes insipidus.
Prevalence
LCH usually affects children between 1 and 15 years old, with a peak incidence between 5 and 10 years of age. Among children under the age of 10, yearly incidence is thought to be 1 in 200,000; and in adults even rarer, in about 1 in 560,000. It has been reported in elderly but is vanishingly rare. It is most prevalent in Caucasians, and affects males twice as often as females. In other populations too the prevalence in males is slightly more than in females.
LCH is usually a sporadic and non-hereditary
Heredity, also called inheritance or biological inheritance, is the passing on of traits from parents to their offspring; either through asexual reproduction or sexual reproduction, the offspring cells or organisms acquire the genetic inform ...
condition but familial clustering has been noted in limited number of cases. Hashimoto-Pritzker disease is a congenital self-healing variant of Hand-Schüller-Christian disease.
Culture
In the 10th episode of season 3 of ''House
A house is a single-unit residential building. It may range in complexity from a rudimentary hut to a complex structure of wood, masonry, concrete or other material, outfitted with plumbing, electrical, and heating, ventilation, and air condi ...
'' entitled "Merry Little Christmas", the primary patient is a girl with dwarfism
Dwarfism is a condition wherein an organism is exceptionally small, and mostly occurs in the animal kingdom. In humans, it is sometimes defined as an adult height of less than , regardless of sex; the average adult height among people with dw ...
who has a variety of symptoms, who is ultimately diagnosed with Langerhans cell histiocytosis. Also in the 5th episode, season 1 of "The Good Doctor", Dr. Murphy tries to diagnose Langerhans cell histiocytosis in a boy with a previously diagnosed osteosarcoma.In an episode of ''Mystery Diagnosis
''Mystery Diagnosis'' is a television docudrama series that aired on OWN: Oprah Winfrey Network. Each episode focuses on two or more individuals who have struggled with obscure medical ailments, and their quest for a diagnosis. The program deta ...
'', "The Woman Who Saw Pink", Brooke Rohrer has experiencing symptoms of abdominal pain, was diagnosed with Langerhans cell histiocytosis.
Nomenclature
Langerhans cell histiocytosis is occasionally misspelled as "Langerhan" or "Langerhan's" cell histiocytosis, even in authoritative textbooks. The name, however, originates back to its discoverer, Paul Langerhans.
References
External links
{{Histiocytosis
Histiocytosis
Monocyte- and macrophage-related cutaneous conditions
Rare diseases