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Langerhans cell histiocytosis(LCH)

MedGen UID:
5568
Concept ID:
C0019621
Neoplastic Process
Synonyms: Eosinophilic granuloma (formerly); Histiocytosis X; LCH; Letterer-Siwe disease (formerly)
SNOMED CT: Histiocytosis X (65399007); Langerhans cell disease (65399007); Langerhans' cell histiocytosis (110450007); Differentiated progressive histiocytosis (65399007); LCH - Langerhan's cell histiocytosis (65399007); Langerhan's cell histiocytosis (65399007); Langerhans cell histiocytosis (65399007)
Modes of inheritance:
Unknown inheritance
MedGen UID:
989040
Concept ID:
CN307042
Finding
Source: Orphanet
Hereditary clinical entity whose mode of inheritance is unknown.
 
Monarch Initiative: MONDO:0018310
OMIM®: 604856
Orphanet: ORPHA389

Definition

Langerhans cell histiocytosis (LCH) is a rare disorder characterized by the dysregulated proliferation of Langerhans cells and subsequent organ infiltration. Clinical manifestations range from a spontaneously healing isolated osteolytic lesion to a lymphoma-like syndrome with fatal multiorgan failure, in the absence of any cellular evidence of malignancy. Although the disease can present at any age, the peak age at diagnosis is between 1 and 3 years (summary by Arico et al., 1999). Egeler and D'Angio (1995) presented a classification of histiocytosis syndromes in children: class I, Langerhans cell histiocytosis (LCH); class II, histiocytosis of mononuclear macrophages other than Langerhans cells, including familial hemophagocytic lymphohistiocytosis (267700); and class III, malignant histiocytic disorders, including histiocytic lymphoma. [from OMIM]

Additional description

From MedlinePlus Genetics
Langerhans cell histiocytosis is a disorder in which excess immune system cells called Langerhans cells build up in the body. Langerhans cells, which help regulate the immune system, are normally found throughout the body, especially in the skin, lymph nodes, spleen, lungs, liver, and bone marrow. In Langerhans cell histiocytosis, excess immature Langerhans cells usually form tumors called granulomas. Many researchers now consider Langerhans cell histiocytosis to be a form of cancer, but this classification remains controversial.

In approximately 80 percent of affected individuals, one or more granulomas develop in the bones, causing pain and swelling. The granulomas, which usually occur in the skull or the long bones of the arms or legs, may cause the bone to fracture.

Granulomas also frequently occur in the skin, appearing as blisters, reddish bumps, or rashes which can be mild to severe. The pituitary gland may also be affected; this gland is located at the base of the brain and produces hormones that control many important body functions. Without hormone supplementation, affected individuals may experience delayed or absent puberty or an inability to have children (infertility). In addition, pituitary gland damage may result in the production of excessive amounts of urine (diabetes insipidus) and dysfunction of another gland called the thyroid. Thyroid dysfunction can affect the rate of chemical reactions in the body (metabolism), body temperature, skin and hair texture, and behavior.

In 15 to 20 percent of cases, Langerhans cell histiocytosis affects the lungs, liver, or blood-forming (hematopoietic) system; damage to these organs and tissues may be life-threatening. Lung involvement, which appears as swelling of the small airways (bronchioles) and blood vessels of the lungs, results in stiffening of the lung tissue, breathing problems, and increased risk of infection. Hematopoietic involvement, which occurs when the Langerhans cells crowd out blood-forming cells in the bone marrow, leads to a general reduction in the number of blood cells (pancytopenia). Pancytopenia results in fatigue due to low numbers of red blood cells (anemia), frequent infections due to low numbers of white blood cells (neutropenia), and clotting problems due to low numbers of platelets (thrombocytopenia).

Other signs and symptoms that may occur in Langerhans cell histiocytosis, depending on which organs and tissues have Langerhans cell deposits, include swollen lymph nodes, abdominal pain, yellowing of the skin and whites of the eyes (jaundice), delayed puberty, protruding eyes, dizziness, irritability, and seizures. About 1 in 50 affected individuals experience deterioration of neurological function (neurodegeneration).

Langerhans cell histiocytosis is often diagnosed in childhood, usually between ages 2 and 3, but can appear at any age. Most individuals with adult-onset Langerhans cell histiocytosis are current or past smokers; in about two-thirds of adult-onset cases the disorder affects only the lungs.

The severity of Langerhans cell histiocytosis, and its signs and symptoms, vary widely among affected individuals. Certain presentations or forms of the disorder were formerly considered to be separate diseases. Older names that were sometimes used for forms of Langerhans cell histiocytosis include eosinophilic granuloma, Hand-Schüller-Christian disease, and Letterer-Siwe disease.

In many people with Langerhans cell histiocytosis, the disorder eventually goes away with appropriate treatment. It may even disappear on its own, especially if the disease occurs only in the skin. However, some complications of the condition, such as diabetes insipidus or other effects of tissue and organ damage, may be permanent.  https://medlineplus.gov/genetics/condition/langerhans-cell-histiocytosis

Professional guidelines

PubMed

Goyal G, Tazi A, Go RS, Rech KL, Picarsic JL, Vassallo R, Young JR, Cox CW, Van Laar J, Hermiston ML, Cao XX, Makras P, Kaltsas G, Haroche J, Collin M, McClain KL, Diamond EL, Girschikofsky M
Blood 2022 Apr 28;139(17):2601-2621. doi: 10.1182/blood.2021014343. PMID: 35271698Free PMC Article
Abla O, Jacobsen E, Picarsic J, Krenova Z, Jaffe R, Emile JF, Durham BH, Braier J, Charlotte F, Donadieu J, Cohen-Aubart F, Rodriguez-Galindo C, Allen C, Whitlock JA, Weitzman S, McClain KL, Haroche J, Diamond EL
Blood 2018 Jun 28;131(26):2877-2890. Epub 2018 May 2 doi: 10.1182/blood-2018-03-839753. PMID: 29720485Free PMC Article
Di Iorgi N, Napoli F, Allegri AE, Olivieri I, Bertelli E, Gallizia A, Rossi A, Maghnie M
Horm Res Paediatr 2012;77(2):69-84. Epub 2012 Mar 16 doi: 10.1159/000336333. PMID: 22433947

Curated

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Histiocytic Neoplasms, 2024

Recent clinical studies

Etiology

Alarcon-Calderon A, Vassallo R, Yi ES, Ryu JH
Immunol Allergy Clin North Am 2023 May;43(2):273-287. Epub 2023 Mar 1 doi: 10.1016/j.iac.2023.01.007. PMID: 37055089
Cabeza Martínez B, Giménez Palleiro A, Mazzini Florindez SP
Radiologia (Engl Ed) 2022 Dec;64 Suppl 3:265-276. doi: 10.1016/j.rxeng.2022.09.005. PMID: 36737165
Fraitag S, Emile JF
Histopathology 2022 Jan;80(1):196-215. doi: 10.1111/his.14569. PMID: 34958507
Krooks J, Minkov M, Weatherall AG
J Am Acad Dermatol 2018 Jun;78(6):1035-1044. doi: 10.1016/j.jaad.2017.05.059. PMID: 29754885
Radzikowska E
Adv Respir Med 2017;85(5):277-289. Epub 2017 Oct 30 doi: 10.5603/ARM.a2017.0046. PMID: 29083024

Diagnosis

Kobayashi M, Tojo A
Cancer Sci 2018 Dec;109(12):3707-3713. Epub 2018 Oct 30 doi: 10.1111/cas.13817. PMID: 30281871Free PMC Article
Krooks J, Minkov M, Weatherall AG
J Am Acad Dermatol 2018 Jun;78(6):1035-1044. doi: 10.1016/j.jaad.2017.05.059. PMID: 29754885
Radzikowska E
Adv Respir Med 2017;85(5):277-289. Epub 2017 Oct 30 doi: 10.5603/ARM.a2017.0046. PMID: 29083024
Grana N
Cancer Control 2014 Oct;21(4):328-34. doi: 10.1177/107327481402100409. PMID: 25310214
Haupt R, Minkov M, Astigarraga I, Schäfer E, Nanduri V, Jubran R, Egeler RM, Janka G, Micic D, Rodriguez-Galindo C, Van Gool S, Visser J, Weitzman S, Donadieu J; Euro Histio Network
Pediatr Blood Cancer 2013 Feb;60(2):175-84. Epub 2012 Oct 25 doi: 10.1002/pbc.24367. PMID: 23109216Free PMC Article

Therapy

Alarcon-Calderon A, Vassallo R, Yi ES, Ryu JH
Immunol Allergy Clin North Am 2023 May;43(2):273-287. Epub 2023 Mar 1 doi: 10.1016/j.iac.2023.01.007. PMID: 37055089
Shaw B, Borchers M, Zander D, Gupta N
Semin Respir Crit Care Med 2020 Apr;41(2):269-279. Epub 2020 Apr 12 doi: 10.1055/s-0039-1700996. PMID: 32279297
Kobayashi M, Tojo A
Cancer Sci 2018 Dec;109(12):3707-3713. Epub 2018 Oct 30 doi: 10.1111/cas.13817. PMID: 30281871Free PMC Article
Radzikowska E
Adv Respir Med 2017;85(5):277-289. Epub 2017 Oct 30 doi: 10.5603/ARM.a2017.0046. PMID: 29083024
Vassallo R, Ryu JH, Colby TV, Hartman T, Limper AH
N Engl J Med 2000 Jun 29;342(26):1969-78. doi: 10.1056/NEJM200006293422607. PMID: 10877650

Prognosis

Barrios K, Patiño O, Muñoz N, Moneriz C
Biomedica 2020 Sep 1;40(3):464-471. doi: 10.7705/biomedica.5150. PMID: 33030824Free PMC Article
Krooks J, Minkov M, Weatherall AG
J Am Acad Dermatol 2018 Jun;78(6):1035-1044. doi: 10.1016/j.jaad.2017.05.059. PMID: 29754885
Grana N
Cancer Control 2014 Oct;21(4):328-34. doi: 10.1177/107327481402100409. PMID: 25310214
Margo CE, Goldman DR
Surv Ophthalmol 2008 Jul-Aug;53(4):332-58. doi: 10.1016/j.survophthal.2008.04.007. PMID: 18572052
Chu T
Australas J Dermatol 2001 Nov;42(4):237-42. doi: 10.1046/j.1440-0960.2001.00527.x. PMID: 11903153

Clinical prediction guides

Abla O
Hematology Am Soc Hematol Educ Program 2023 Dec 8;2023(1):386-395. doi: 10.1182/hematology.2023000439. PMID: 38066856Free PMC Article
Murakami I, Wada N, Nakashima J, Iguchi M, Toi M, Hashida Y, Higuchi T, Daibata M, Matsushita M, Iwasaki T, Kuwamoto S, Horie Y, Nagata K, Hayashi K, Oka T, Yoshino T, Imamura T, Morimoto A, Imashuku S, Gogusev J, Jaubert F
Cell Commun Signal 2018 Aug 22;16(1):49. doi: 10.1186/s12964-018-0261-y. PMID: 30134914Free PMC Article
Abla O, Jacobsen E, Picarsic J, Krenova Z, Jaffe R, Emile JF, Durham BH, Braier J, Charlotte F, Donadieu J, Cohen-Aubart F, Rodriguez-Galindo C, Allen C, Whitlock JA, Weitzman S, McClain KL, Haroche J, Diamond EL
Blood 2018 Jun 28;131(26):2877-2890. Epub 2018 May 2 doi: 10.1182/blood-2018-03-839753. PMID: 29720485Free PMC Article
Hyman DM, Puzanov I, Subbiah V, Faris JE, Chau I, Blay JY, Wolf J, Raje NS, Diamond EL, Hollebecque A, Gervais R, Elez-Fernandez ME, Italiano A, Hofheinz RD, Hidalgo M, Chan E, Schuler M, Lasserre SF, Makrutzki M, Sirzen F, Veronese ML, Tabernero J, Baselga J
N Engl J Med 2015 Aug 20;373(8):726-36. doi: 10.1056/NEJMoa1502309. PMID: 26287849Free PMC Article
Haroche J, Arnaud L, Cohen-Aubart F, Hervier B, Charlotte F, Emile JF, Amoura Z
Curr Rheumatol Rep 2014 Apr;16(4):412. doi: 10.1007/s11926-014-0412-0. PMID: 24532298

Recent systematic reviews

Steinhelfer L, Kühnel T, Jägle H, Mayer S, Karrer S, Haubner F, Schreml S
Orphanet J Rare Dis 2022 Mar 24;17(1):132. doi: 10.1186/s13023-022-02291-z. PMID: 35331271Free PMC Article
Chen T, Ashman PE, Bojrab DI 2nd, Johnson AP, Benson B, Hong RS, Svider PF
Otolaryngol Head Neck Surg 2022 Jan;166(1):48-59. Epub 2021 May 4 doi: 10.1177/01945998211004590. PMID: 33945752
Difloe-Geisert JC, Bernauer SA, Schneeberger N, Bornstein MM, Walter C
Clin Oral Investig 2021 Jun;25(6):3341-3349. Epub 2021 Mar 22 doi: 10.1007/s00784-021-03873-0. PMID: 33751219Free PMC Article
Miguel D, Lukacs J, Illing T, Elsner P
J Eur Acad Dermatol Venereol 2017 Feb;31(2):221-235. Epub 2016 Jul 19 doi: 10.1111/jdv.13786. PMID: 27436448
Howard JE, Dwivedi RC, Masterson L, Jani P
Cancer Treat Rev 2015 Apr;41(4):320-31. Epub 2015 Mar 9 doi: 10.1016/j.ctrv.2015.02.011. PMID: 25805533

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      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Curated

    • NCCN, 2024
      NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Histiocytic Neoplasms, 2024

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