Langerhans cell histiocytosis

Last updated
Langerhans cell histiocytosis
Langerhans cell histiocytosis - very high mag.jpg
Micrograph showing a Langerhans cell histiocytosis with the characteristic reniform Langerhans cells accompanied by abundant eosinophils. H&E stain.
Specialty Hematology

Langerhans cell histiocytosis (LCH) is an abnormal clonal proliferation of Langerhans cells, abnormal cells deriving from bone marrow and capable of migrating from skin to lymph nodes.

Contents

Symptoms range from isolated bone lesions to multisystem disease. [1] LCH is part of a group of syndromes called histiocytoses, which are characterized by an abnormal proliferation of histiocytes (an archaic term for activated dendritic cells and macrophages). [2] These diseases are related to other forms of abnormal proliferation of white blood cells, such as leukemias and lymphomas. [3]

The disease has gone by several names, including Hand–Schüller–Christian disease , 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. [4] [1]

Classification

Alternative names
Histiocytosis X

Histiocytosis X syndrome

Subordinate terms
Hand-Schüller-Christian disease

Letterer-Siwe disease
Histiocytosis X, unspecified
Eosinophilic Granulomatosis
Langerhans Cell granulomatosis
Langerhans Cell Histiocytosis, Hashimoto-Pritzker Type
Langerhans Cell Histiocytosis of lung
Langerhans Cell Histiocytosis, disseminated (clinical)
Langerhans Cell Histiocytosis, unifocal (clinical)

The disease spectrum results from clonal accumulation and proliferation of cells resembling the epidermal dendritic cells called Langerhans cells, sometimes called dendritic cell histiocytosis. These cells in combination with lymphocytes, eosinophils, and normal histiocytes form typical LCH lesions that can be found in almost any organ. [5] A similar set of diseases has been described in canine histiocytic diseases. [6]

LCH is clinically divided into three groups: unifocal, multifocal unisystem, and multifocal multisystem. [7]

Unifocal

Unifocal LCH, also called eosinophilic granuloma (an older term which is now known to be a misnomer), 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. [8] When found in the skin it is called cutaneous single system Langerhans cell LCH. This version can heal without therapy in some rare cases. [9] This primary bone involvement helps to differentiate eosinophilic granuloma from other forms of Langerhans Cell Histiocytosis (Letterer-Siwe or Hand-Schüller-Christian variant). [10]

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, often leading to diabetes insipidus. The triad of diabetes insipidus, exophthalmos, and lytic bone lesions is known as the Hand-Schüller-Christian triad . Peak onset is 2–10 years of age. [11]

Multifocal multisystem

Multifocal multisystem LCH, also called Letterer-Siwe disease , is an often rapidly progressing disease in which Langerhans 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%. [12]

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. PLCH develops when an abundance of monoclonal CD1a-positive Langerhans (immature histiocytes) proliferate the bronchioles and alveolar interstitium, and this flood of histiocytes recruits granulocytes like eosinophils and neutrophils and agranulocytes like lymphocytes further destroying bronchioles and the interstitial alveolar space that can cause damage to the lungs. [13] 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. [14] Some affected people recover completely after they stop smoking, but others develop long-term complications such as pulmonary fibrosis and pulmonary hypertension. [15]

Signs and symptoms

CT scan showing LCH infiltrating peri-orbital tissue (arrowed). CT of periorbital Langerhans cell histiocytosis.jpg
CT scan showing LCH infiltrating peri-orbital tissue (arrowed).
A patient with Hand-Schuller-Christian disease which is a subtype of Langerhans Cell Histiocytosis. Hans-Schuller-Christian.jpg
A patient with Hand–Schüller–Christian disease which is a subtype of Langerhans Cell Histiocytosis.

LCH provokes a non-specific inflammatory response, which includes fever, lethargy, and weight loss. Organ involvement can also cause more specific symptoms.

Pathophysiology

The pathogenesis of Langerhans cell histiocytosis (LCH) is a matter of debate. There are ongoing investigations to determine whether LCH is a neoplastic (cancerous) or reactive (non-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. [24] [25]

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. [26] [27] [28] 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. [29] 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. [30]

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%). [31] This study documented the first recurrent mutation in LCH samples. Two independent studies have confirmed this finding. [32] [33] Presence of this activating mutation could support the notion to characterize LCH as myeloproliferative disorder.

Diagnosis

Micrograph showing Langerhans Cell Histiocytosis. H&E stain. Langerhans cell histiocytosis - high mag.jpg
Micrograph showing Langerhans Cell Histiocytosis. H&E stain.

Diagnosis is confirmed histologically by tissue biopsy. Hematoxylin-eosin stain of biopsy slide will show features of Langerhans Cell e.g. distinct cell margin, pink granular cytoplasm. [34] Presence of Birbeck granules on electron microscopy and immuno-cytochemical features e. g. CD1 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. [35]

Imaging may be evident in chest X-rays with micronodular and reticular changes of the lungs with cyst formation in advanced cases. MRI 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 with hypointense or hyperintense T1 signal extending from grey matter into the white matter. In the basal ganglia, MRI shows a hyperintense T1 signal in the globus pallidus. [36]

Assessment of endocrine function and bone marrow biopsy are also performed when indicated. [37]

Treatment

Guidelines for management of patients up to 18 years with Langerhans cell histiocytosis have been suggested. [44] [45] [46] [47] 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 for diabetes insipidus which can be applied as nasal drop. Chemotherapeutic agents such as alkylating agents, antimetabolites, vinca alkaloids either singly or in combination can lead to complete remission in diffuse disease.[ citation needed ]

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%. [48] A full recovery can be expected for people who seek treatment and do not have more lesions at 12 and 24 months. However, 50% of 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. [49] Although there is a general good prognosis for Langerhans cell histiocytosis, approximately 50% of patients with the disease are prone to various complications such as musculoskeletal disability, skin scarring and diabetes insipidus. [49]

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; [50] and in adults even rarer, in about 1 in 560,000. [51] It has been reported in elderly but is vanishingly rare. [52] It is most prevalent in Caucasians, and affects males twice as often as females. [53] In other populations too the prevalence in males is slightly more than in females. [54]

LCH is usually a sporadic and non-hereditary 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. [55]

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. [56]

Related Research Articles

<span class="mw-page-title-main">Multiple endocrine neoplasia type 1</span> Medical condition

Multiple endocrine neoplasia type 1 (MEN-1) is one of a group of disorders, the multiple endocrine neoplasias, that affect the endocrine system through development of neoplastic lesions in pituitary, parathyroid gland and pancreas. Individuals suffering from this disorder are prone to developing multiple endocrine and nonendocrine tumors. It was first described by Paul Wermer in 1954.

Malignant histiocytosis is a rare hereditary disease found in the Bernese Mountain Dog and humans, characterized by histiocytic infiltration of the lungs and lymph nodes. The liver, spleen, and central nervous system can also be affected. Histiocytes are a component of the immune system that proliferate abnormally in this disease. In addition to its importance in veterinary medicine, the condition is also important in human pathology.

<span class="mw-page-title-main">Letterer–Siwe disease</span> Medical condition

Letterer–Siwe disease, (LSD) or Abt-Letterer-Siwe disease, is one of the four recognized clinical syndromes of Langerhans cell histiocytosis (LCH) and is the most severe form, involving multiple organ systems such as the skin, bone marrow, spleen, liver, and lung. Oral cavity and gastrointestinal involvement may also be seen. LCH and all its subtypes are characterized by monoclonal migration and proliferation of specific dendritic cells.

<span class="mw-page-title-main">Erdheim–Chester disease</span> Medical condition

Erdheim–Chester disease (ECD) is an extremely rare disease characterized by the abnormal multiplication of a specific type of white blood cells called histiocytes, or tissue macrophages. It was declared a histiocytic neoplasm by the World Health Organization in 2016. Onset typically is in middle age, although younger patients have been documented. The disease involves an infiltration of lipid-laden macrophages, multinucleated giant cells, an inflammatory infiltrate of lymphocytes and histiocytes in the bone marrow, and a generalized sclerosis of the long bones.

<span class="mw-page-title-main">Idiopathic pulmonary fibrosis</span> Scarring of the lungs for no known reason

Idiopathic pulmonary fibrosis (IPF) synonymous with cryptogenic fibrosing alveolitis is a rare, progressive illness of the respiratory system, characterized by the thickening and stiffening of lung tissue, associated with the formation of scar tissue. It is a type of chronic pulmonary fibrosis characterized by a progressive and irreversible decline in lung function.

<span class="mw-page-title-main">Juvenile xanthogranuloma</span> Medical condition

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.

In medicine, histiocytosis is an excessive number of histiocytes, and the term is also often used to refer to a group of rare diseases which share this sign as a characteristic. Occasionally and confusingly, the term histiocytosis is sometimes used to refer to individual diseases.

<span class="mw-page-title-main">Chronic multifocal Langerhans cell histiocytosis</span> Medical condition

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 combination of three features; bulging eyes, breakdown of bone, and diabetes insipidus, although around 75% of cases do not have all three features. Other features may include a fever and weight loss, and depending on the organs involved there may be rashes, asymmetry of the face, ear infections, signs in the mouth and the appearance of advanced gum disease. Features relating to lung and liver disease may occur.

<span class="mw-page-title-main">Rosai–Dorfman disease</span> Medical condition

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.

<span class="mw-page-title-main">Desquamative interstitial pneumonia</span> Medical condition

Desquamative interstitial pneumonia (DIP) is a type of idiopathic interstitial pneumonia featuring elevated numbers of macrophages within the alveoli of the lung. DIP is a chronic disorder with an insidious onset. Its common symptoms include shortness of breath, coughing, fever, weakness, weight loss, and fatigue. In more severe cases, it may lead to respiratory failure, chest pain, digital clubbing, cyanosis, and hemoptysis. Asymptomatic cases are rare.

<span class="mw-page-title-main">Langerhans cell sarcoma</span> Medical condition

Langerhans cell sarcoma (LCS) is a rare form of malignant histiocytosis. It should not be confused with Langerhans cell histiocytosis, which is cytologically benign. It can present most commonly in the skin and lymphatic tissue, but may also present in the lung, liver, and bone marrow. Treatment is most commonly with surgery or chemotherapy.

Central diabetes insipidus, recently renamed arginine vasopressin deficiency (AVP-D), is a form of diabetes insipidus that is due to a lack of vasopressin (ADH) production in the brain. Vasopressin acts to increase the volume of blood (intravascularly), and decrease the volume of urine produced. Therefore, a lack of it causes increased urine production and volume depletion.

Progressive nodular histiocytosis is a cutaneous condition clinically characterized by the development of two types of skin lesions: superficial papules and deeper larger subcutaneous nodules. Progressive nodular histiocytosis was first reported in 1978 by Taunton et al. It is a subclass of non-Langerhans cell histiocytosis and a subgroup of xanthogranuloma.

Indeterminate cell histiocytosis(LCH) is an uncommon proliferative illness where the predominant cells have characteristics from both non-Langerhans cell histiocytosis (NLCH) and Langerhans cell histiocytosis (LCH) in terms of morphology and immunophenotypic characteristics. Wood et al. originally described ICH in 1985 as a neoplastic disease arising from dermal indeterminate cells that lack Birbeck granules but are characteristically positive for S-100 and CD1a.

Multifocal fibrosclerosis and idiopathic fibrosclerosis are disorders of unknown aetiology, characterised by fibrous lesions (co-)occurring at a variety of sites. Known manifestations include retroperitoneal fibrosis, mediastinal fibrosis and Riedel's thyroiditis.

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 as well as response to therapy vary greatly among the syndromes.

<span class="mw-page-title-main">History of diabetes</span>

The condition known today as diabetes is thought to have been described in the Ebers Papyrus. Ayurvedic physicians first noted the sweet taste of diabetic urine, and called the condition madhumeha. The term diabetes traces back to Demetrius of Apamea. For a long time, the condition was described and treated in traditional Chinese medicine asxiāo kě. Physicians of the medieval Islamic world, including Avicenna, have also written on diabetes. Early accounts often referred to diabetes as a disease of the kidneys. In 1674, Thomas Willis suggested that diabetes may be a disease of the blood. Johann Peter Frank is credited with distinguishing diabetes mellitus and diabetes insipidus in 1794.

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.

Crystal-storing histiocytosis is a form of histiocytosis that mostly occurs in people with monoclonal gammopathies. Histiocytosis is an excessive number of histiocytes. In the vast majority of crystal-storing histiocytosis cases, immunoglobulins accumulate within the cytoplasm of histiocytes; in rare cases clofazimine, cystine, silica, or Charcot–Leyden crystals may be found in the histiocytes instead. Non-immunoglobulin crystal-storing histiocytosis is mostly associated with non-malignant disorders, such as chronic inflammation or autoimmune abnormality conditions such as rheumatoid arthritis, Crohn's disease, or Helicobacter pylori gastritis. It may be a localised or generalised disease. Examples of locations where histiocytosis may occur include the lungs, pleura, stomach, kidney, bone marrow, thyroid, thymus, and parotid gland. The disease is described as generalised if two or more unrelated sites are involved.

References

  1. 1 2 "Langerhans Cell Histiocytosis". NORD (National Organization for Rare Disorders). Retrieved 5 December 2020.
  2. ↑ "UpToDate". UpToDate. Retrieved October 18, 2023.
  3. ↑ Feldman, Andrew L; Berthold, Frank; Arceci, Robert J; Abramowsky, Carlos; Shehata, Bahig M; Mann, Karen P; Lauer, Stephen J; Pritchard, Jon; Raffeld, Mark; Jaffe, Elaine S (2005). "Clonal relationship between precursor T-lymphoblastic leukaemia/lymphoma and Langerhans-cell histiocytosis". The Lancet Oncology. 6 (6). Elsevier BV: 435–437. doi:10.1016/s1470-2045(05)70211-4. ISSN   1470-2045. PMID   15925822.
  4. ↑ The Writing Group of the Histiocyte Society (1987). "Histiocytosis syndromes in children. Writing Group of the Histiocyte Society". Lancet. 1 (8526): 208–9. doi:10.1016/S0140-6736(87)90016-X. PMID   2880029. S2CID   54351490.(subscription required)
  5. ↑ Makras P, Papadogias D, Kontogeorgos G, Piaditis G, Kaltsas G (2005). "Spontaneous gonadotrophin deficiency recovery in an adult patient with Langerhans cell Histiocytosis (LCH)". Pituitary. 8 (2): 169–74. doi:10.1007/s11102-005-4537-z. PMID   16379033. S2CID   7878051.
  6. ↑ Ettinger, Stephen J.; Feldman, Edward C. (2010). Textbook of Veterinary Internal Medicine (7th ed.). W.B. Saunders Company. ISBN   978-0-7216-6795-9.
  7. ↑ Cotran, Ramzi S.; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson; Robbins, Stanley L. (2005). Robbins and Cotran pathologic basis of disease . St. Louis, Mo: Elsevier Saunders. pp.  701–. ISBN   978-0-8089-2302-2.
  8. ↑ Kumar, Vinay; Abbas, Abul; Aster, Jon (2015). Robbins and Cotran Pathologic Basis of Disease (9th ed.). Philadelphia, PA: Elsevier. p. 622. ISBN   978-1-4557-2613-4.
  9. ↑ Afsar, Fatma Sule; Ergin, Malik; Ozek, Gulcihan; Vergin, Canan; Karakuzu, Ali; Seremet, Sila (2017). "Histiocitose de Células de Langerhans Autolimitada e de Início Tardio: Relato de Uma Entidade Raríssima". Revista Paulista de Pediatria. 35 (1): 115–119. doi:10.1590/1984-0462/;2017;35;1;00015. ISSN   0103-0582. PMC   5417814 . PMID   28977321.
  10. ↑ Ladisch, Stephan (2011). "Histiocytosis Syndromes of Childhood". In Kliegman, Robert M.; Stanton, Bonita F.; St. Geme, Joseph; Schor, Nina; Behrman, Richard E. (eds.). Nelson Textbook of Pediatrics (19th ed.). Saunders. pp. 1773–7. ISBN   978-1-4377-0755-7.
  11. ↑ Pushpalatha, G; Aruna, DR; Galgali, Sushma (2011). "Langerhans cell histiocytosis". Journal of Indian Society of Periodontology. 15 (3). Medknow: 276–279. doi: 10.4103/0972-124x.85675 . ISSN   0972-124X. PMC   3200027 . PMID   22028518.
  12. ↑ Langerhans Cell Histiocytosis at eMedicine
  13. ↑ Juvet, Stephan (2010). "Rare lung diseases III: Pulmonary Langerhans' cell histiocytosis". Canadian Respiratory Journal. 17 (3): e55–e62. doi: 10.1155/2010/216240 . PMC   2900147 . PMID   20617216.
  14. ↑ Tazi, A (2006). "Adult pulmonary Langerhans' cell histiocytosis". European Respiratory Journal. 27 (6): 1272–1285. doi: 10.1183/09031936.06.00024004 . PMID   16772390. S2CID   5626880.
  15. ↑ Juvet, Stephen C; Hwang, David; Downey, Gregory P (2010). "Rare lung diseases III: pulmonary Langerhans' cell histiocytosis". Canadian Respiratory Journal. 17 (3): e55–62. doi: 10.1155/2010/216240 . PMC   2900147 . PMID   20617216.
  16. ↑ Stull, MA; Kransdorf, MJ; Devaney, KO (July 1992). "Langerhans cell histiocytosis of bone". Radiographics. 12 (4): 801–23. doi:10.1148/radiographics.12.4.1636041. PMID   1636041.
  17. ↑ "Langerhans Cell Histiocytosis — Patient UK" . Retrieved 2007-05-10.
  18. ↑ Kaltsas, GA; Powles, TB; Evanson, J; Plowman, PN; Drinkwater, JE; Jenkins, PJ; Monson, JP; Besser, GM; Grossman, AB (April 2000). "Hypothalamo-pituitary abnormalities in adult patients with langerhans cell histiocytosis: clinical, endocrinological, and radiological features and response to treatment". The Journal of Clinical Endocrinology and Metabolism. 85 (4): 1370–6. doi: 10.1210/jcem.85.4.6501 . PMID   10770168.
  19. ↑ Grois, N; Pötschger, U; Prosch, H; Minkov, M; Arico, M; Braier, J; Henter, JI; Janka-Schaub, G; Ladisch, S; Ritter, J; Steiner, M; Unger, E; Gadner, H; DALHX- and LCH I and II Study, Committee (February 2006). "Risk factors for diabetes insipidus in langerhans cell histiocytosis". Pediatric Blood & Cancer. 46 (2): 228–33. doi:10.1002/pbc.20425. PMID   16047354. S2CID   11069765.
  20. ↑ Marchand, Isis; Barkaoui, Mohamed Aziz; Garel, Catherine; Polak, Michel; Donadieu, Jean (2011-09-01). "Central Diabetes Insipidus as the Inaugural Manifestation of Langerhans Cell Histiocytosis: Natural History and Medical Evaluation of 26 Children and Adolescents". The Journal of Clinical Endocrinology & Metabolism. 96 (9): E1352–E1360. doi:10.1210/jc.2011-0513. ISSN   0021-972X. PMID   21752883.
  21. ↑ Broadbent, V; Dunger, DB; Yeomans, E; Kendall, B (1993). "Anterior pituitary function and computed tomography/magnetic resonance imaging in patients with Langerhans cell histiocytosis and diabetes insipidus". Medical and Pediatric Oncology. 21 (9): 649–54. doi:10.1002/mpo.2950210908. PMID   8412998.
  22. ↑ Sholl, LM; Hornick, JL; Pinkus, JL; Pinkus, GS; Padera, RF (June 2007). "Immunohistochemical analysis of langerin in langerhans cell histiocytosis and pulmonary inflammatory and infectious diseases". The American Journal of Surgical Pathology. 31 (6): 947–52. doi:10.1097/01.pas.0000249443.82971.bb. PMID   17527085. S2CID   19702745.
  23. ↑ Cisternino A, Asa'ad F, Fusco N, Ferrero S, Rasperini G (Oct 2015). "Role of multidisciplinary approach in a case of Langerhans cell histiocytosis with initial periodontal manifestations". Int J Clin Exp Pathol. 8 (10): 13539–45. PMC   4680515 . PMID   26722570.
  24. ↑ Broadbent, V.; Davies, E.G.; Heaf, D.; Pincott, J.R.; Pritchard, J.; Levinsky, R.J.; Atherton, D.J.; Tucker, S. (1984). "Spontaneous remission of multi-system histiocytosis X". Lancet. 1 (8371): 253–4. doi:10.1016/S0140-6736(84)90127-2. PMID   6142997. S2CID   46217705.
  25. ↑ Filippi, Paola; De Badulli, Carla; Cuccia, Mariaclara; Silvestri, Annalisa; De Dametto, Ennia; Pasi, Annamaria; Garaventa, Alberto; Prever, Adalberto Brach; del Todesco, Alessandra; Trizzino, Antonino; Danesino, Cesare; Martinetti, Miryam; Arico, Maurizio (2006). "Specific polymorphisms of cytokine genes are associated with different risks to develop single-system or multi-system childhood Langerhans cell histiocytosis". British Journal of Haematology. 132 (6): 784–7. doi: 10.1111/j.1365-2141.2005.05922.x . PMID   16487180.
  26. ↑ Steen, A.E.; Steen, K.H.; Bauer, R.; Bieber, T. (1 July 2001). "Successful treatment of cutaneous Langerhans cell histiocytosis with low-dose methotrexate". British Journal of Dermatology. 145 (1): 137–140. doi:10.1046/j.1365-2133.2001.04298.x. PMID   11453923. S2CID   34121488.
  27. ↑ Allen CE, Flores R, Rauch R, Dauser R, Murray JC, Puccetti D, Hsu DA, Sondel P, Hetherington M, Goldman S, McClain KL (2010). "Neurodegenerative central nervous system Langerhans cell histiocytosis and coincident hydrocephalus treated with vincristine/cytosine arabinoside". Pediatr Blood Cancer. 54 (3): 416–23. doi:10.1002/pbc.22326. PMC   3444163 . PMID   19908293.
  28. ↑ Minkov, M.; Grois, N.; Broadbent, V.; Ceci, A.; Jakobson, A.; Ladisch, S. (1 November 1999). "Cyclosporine A therapy for multisystem Langerhans cell histiocytosis". Medical and Pediatric Oncology. 33 (5): 482–485. doi:10.1002/(SICI)1096-911X(199911)33:5<482::AID-MPO8>3.0.CO;2-Y. PMID   10531573.
  29. ↑ Willman, Cheryl L.; Busque, Lambert; Griffith, Barbara B.; Favara, Blaise E.; McClain, Kenneth L.; Duncan, Marilyn H.; Gilliland, D. Gary (21 July 1994). "Langerhans'-Cell Histiocytosis (Histiocytosis X) -- A Clonal Proliferative Disease". New England Journal of Medicine. 331 (3): 154–160. doi: 10.1056/NEJM199407213310303 . PMID   8008029.
  30. ↑ Degar, Barbara A.; Rollins, Barrett J. (September 2, 2009). "Langerhans cell histiocytosis: malignancy or inflammatory disorder doing a great job of imitating one?". Disease Models & Mechanisms. 2 (9–10). The Company of Biologists: 436–439. doi: 10.1242/dmm.004010 . ISSN   1754-8411. PMC   2737054 . PMID   19726802.
  31. ↑ Badalian-Very G, Vergilio JA, Degar BA, MacConaill LE, Brandner B, Calicchio ML, Kuo FC, Ligon AH, Stevenson KE, Kehoe SM, Garraway LA, Hahn WC, Meyerson M, Fleming MD, Rollins BJ (2010). "Recurrent BRAF mutations in Langerhans cell histiocytosis". Blood. 116 (11): 1919–23. doi:10.1182/blood-2010-04-279083. PMC   3173987 . PMID   20519626.
  32. ↑ Satoh T, Smith A, Sarde A, Lu HC, Mian S, Mian S, Trouillet C, Mufti G, Emile JF, Fraternali F, Donadieu J, Geissmann F (2012). "B-RAF mutant alleles associated with Langerhans cell histiocytosis, a granulomatous pediatric disease". PLOS ONE. 7 (4): e33891. Bibcode:2012PLoSO...733891S. doi: 10.1371/journal.pone.0033891 . PMC   3323620 . PMID   22506009.
  33. ↑ Peters, Tricia L.; Tsz-Kwong Chris Man; Price, Jeremy; George, Renelle; Phaik Har Lim; Kenneth Matthew Heym; Merad, Miriam; McClain, Kenneth L.; Allen, Carl E. (10 December 2011). "1372 Frequent BRAF V600E Mutations Are Identified in CD207+ Cells in LCH Lesions, but BRAF Status does not Correlate with Clinical Presentation of Patients or Transcriptional Profiles of CD207+ Cells". Oral and Poster Abstracts presented at 53rd ASH Annual Meeting and Exposition{{cite journal}}: Cite journal requires |journal= (help)
  34. ↑ Padmanaban, Kamalakannan; Kamalakaran, Arunkumar; Raghavan, Priyadharshini; Palani, Triveni; Rajiah, Davidson (August 21, 2022). "Langerhans Cell Histiocytosis of the Mandible". Cureus. 14 (8). Cureus, Inc.: e28222. doi: 10.7759/cureus.28222 . ISSN   2168-8184. PMC   9486456 . PMID   36158441.
  35. ↑ Tillotson, Cara V.; Anjum, Fatima; Patel, Bhupendra C. (July 17, 2023). "Langerhans Cell Histiocytosis". StatPearls Publishing. PMID   28613635 . Retrieved October 18, 2023.
  36. ↑ Monsereenusorn, Chalinee; Rodriguez-Galindo, Carlos (October 2015). "Clinical Characteristics and Treatment of Langerhans Cell Histiocytosis". Hematology/Oncology Clinics of North America. 29 (5): 853–873. doi:10.1016/j.hoc.2015.06.005. PMID   26461147.
  37. ↑ Kaltsas, G. A.; Powles, T. B.; Evanson, J.; Plowman, P. N.; Drinkwater, J. E.; Jenkins, P. J.; Monson, J. P.; Besser, G. M.; Grossman, A. B. (2000). "Hypothalamo-Pituitary Abnormalities in Adult Patients with Langerhans Cell Histiocytosis: Clinical, Endocrinological, and Radiological Features and Response to Treatment". The Journal of Clinical Endocrinology & Metabolism. 85 (4). The Endocrine Society: 1370–1376. doi: 10.1210/jcem.85.4.6501 . ISSN   0021-972X. PMID   10770168.
  38. 1 2 Wilson, AJ; Maddox, PH; Jenkins, D (January 1991). "CD1a and S100 antigen expression in skin Langerhans cells in patients with breast cancer". The Journal of Pathology. 163 (1): 25–30. doi:10.1002/path.1711630106. PMID   2002421. S2CID   70911084.
  39. ↑ Coppola, D; Fu, L; Nicosia, SV; Kounelis, S; Jones, M (May 1998). "Prognostic significance of p53, bcl-2, vimentin, and S100 protein-positive Langerhans cells in endometrial carcinoma". Human Pathology. 29 (5): 455–62. doi:10.1016/s0046-8177(98)90060-0. PMID   9596268.
  40. ↑ McLelland, J; Chu, AC (October 1988). "Comparison of peanut agglutinin and S100 stains in the paraffin tissue diagnosis of Langerhans cell histiocytosis". The British Journal of Dermatology. 119 (4): 513–9. doi:10.1111/j.1365-2133.1988.tb03255.x. PMID   2461216. S2CID   32685876.
  41. ↑ Ye, F; Huang, SW; Dong, HJ (November 1990). "Histiocytosis X. S-100 protein, peanut agglutinin, and transmission electron microscopy study". American Journal of Clinical Pathology. 94 (5): 627–31. doi:10.1093/ajcp/94.5.627. PMID   2239828.
  42. ↑ Valladeau J, Ravel O, Dezutter-Dambuyant C, Moore K, Kleijmeer M, Liu Y, Duvert-Frances V, Vincent C, Schmitt D, Davoust J, Caux C, Lebecque S, Saeland S (2000). "Langerin, a novel C-type lectin specific to Langerhans cells, is an endocytic receptor that induces the formation of Birbeck granules". Immunity. 12 (1): 71–81. doi: 10.1016/S1074-7613(00)80160-0 . PMID   10661407.
  43. ↑ Lau, SK; Chu, PG; Weiss, LM (April 2008). "Immunohistochemical expression of Langerin in Langerhans cell histiocytosis and non-Langerhans cell histiocytic disorders". The American Journal of Surgical Pathology. 32 (4): 615–9. doi:10.1097/PAS.0b013e31815b212b. PMID   18277880. S2CID   40092500.
  44. ↑ Haupt, Riccardo; Minkov, Milen; Astigarraga, Itziar; Schäfer, Eva; Nanduri, Vasanta; Jubran, Rima; Egeler, R. Maarten; Janka, Gritta; Micic, Dragan; Rodriguez-Galindo, Carlos; Van Gool, Stefaan; Visser, Johannes; Weitzman, Sheila; Donadieu, Jean (February 2013). "Langerhans cell histiocytosis (LCH): Guidelines for diagnosis, clinical work-up, and treatment for patients till the age of 18 years". Pediatric Blood & Cancer. 60 (2): 175–184. doi:10.1002/pbc.24367. PMC   4557042 . PMID   23109216.
  45. ↑ Girschikofsky, Michael; Arico, Maurizio; Castillo, Diego; Chu, Anthony; Doberauer, Claus; Fichter, Joachim; Haroche, Julien; Kaltsas, Gregory A; Makras, Polyzois; Marzano, Angelo V; de Menthon, Mathilde; Micke, Oliver; Passoni, Emanuela; Seegenschmiedt, Heinrich M; Tazi, Abdellatif; McClain, Kenneth L (2013). "Management of adult patients with Langerhans cell histiocytosis: recommendations from an expert panel on behalf of Euro-Histio-Net". Orphanet Journal of Rare Diseases. 8 (1): 72. doi: 10.1186/1750-1172-8-72 . PMC   3667012 . PMID   23672541.
  46. ↑ "Langerhans cell histiocytosis — Histiocyte Society Evaluation and Treatment Guidelines". April 2009. Archived from the original on 2018-01-21. Retrieved 2015-04-28.{{cite journal}}: Cite journal requires |journal= (help)
  47. ↑ PDQ Pediatric Treatment Editorial Board (2002). "Langerhans Cell Histiocytosis Treatment (PDQ®): Health Professional Version". Langerhans Cell Histiocytosis Treatment (PDQ®). National Cancer Institute (US). PMID   26389240. and 1
  48. ↑ Komp D, El Mahdi A, Starling K, Easley J, Vietti T, Berry D, George S (1980). "Quality of survival in Histiocytosis X: a Southwest Oncology Group study". Med. Pediatr. Oncol. 8 (1): 35–40. doi:10.1002/mpo.2950080106. PMID   6969347.
  49. 1 2 Tillotson CV, Anjum F, Patel BC. Langerhans Cell Histiocytosis. [Updated 2022 Jul 18]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430885/
  50. ↑ "MedlinePlus Medical Encyclopedia: Histiocytosis" . Retrieved 2007-05-10.
  51. ↑ "Histiocytosis Association of Canada". Archived from the original on 2007-05-14. Retrieved 2007-05-16.
  52. ↑ Gerlach, Beatrice; Stein, Annette; Fischer, Rainer; Wozel, Gottfried; Dittert, Dag-Daniel; Richter, Gerhard (1998). "Langerhanszell-Histiozytose im Alter" [Langerhans cell histiocytosis in the elderly]. Der Hautarzt (in German). 49 (1): 23–30. doi:10.1007/s001050050696. PMID   9522189. S2CID   20706403.
  53. ↑ Sellari-Franceschini, S.; Forli, F.; Pierini, S.; Favre, C.; Berrettini, S.; Macchia, P.A. (1999). "Langerhans' cells histiocytosis: a case report". International Journal of Pediatric Otorhinolaryngology. 48 (1): 83–7. doi:10.1016/S0165-5876(99)00013-0. PMID   10365975.
  54. ↑ Aricò, M.; Girschikofsky, M.; Généreau, T.; Klersy, C.; McClain, K.; Grois, N.; Emile, J.-F.; Lukina, E.; De Juli, E.; Danesino, C. (2003). "Langerhans cell histiocytosis in adults: Report from the International Registry of the Histiocyte Society". European Journal of Cancer. 39 (16): 2341–8. doi:10.1016/S0959-8049(03)00672-5. PMID   14556926.
  55. ↑ Kapur, Payal; Erickson, Christof; Rakheja, Dinesh; Carder, K. Robin; Hoang, Mai P. (2007). "Congenital self-healing reticulohistiocytosis (Hashimoto-Pritzker disease): Ten-year experience at Dallas Children's Medical Center". Journal of the American Academy of Dermatology. 56 (2): 290–4. doi:10.1016/j.jaad.2006.09.001. PMID   17224372.
  56. ↑ Jolles, S. (April 2002). "Paul Langerhans". Journal of Clinical Pathology. 55 (4): 243. doi:10.1136/jcp.55.4.243. PMC   1769627 . PMID   11919207.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.