Langerhans cell histiocytosis (overview) C96.0; C96,5; C96.6

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 19.07.2021

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Synonym(s)

Histiocytoses; Histiocytosis X; Histiocytosis X group; Langerhans cell histiocytosis; malignant histiocytosis

History
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Langerhans, 1868

Definition
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Generic term for a group of differently progressing systemic diseases, different dignities, with proliferation of dendritic cells of the Langerhans cell type and ontogenetically related cell variants. The proliferating cell, originally designated "X", has now been identified as a Langerhans cell, which shows Langerhans cell granules (Birbeck granules) under the electron microscope and stains itself immunohistologically with Langerhans cell markers ( CD1a), so that the term histiocytosis X (Lichtenstein) is no longer adequate.

Classification
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Langerhans cell histiocytoses are divided into: Classical Langerhans cell histiocytoses (CD1a+, Birbeck granula+):

Precursor Langerhans cell histiocytoses (CD1a+; Birbeck granula+/-):

Instead of the previously listed classification according to entities (probably these are not entities but only different manifestations and courses of a single underlying disease), a stratification for the classical Langerhans cell histiocytoses has proven useful, especially for therapy studies: "single-system-disease":

  • monoorganic affection of the skin. Unilocular skeletal infestation, infestation of a solitary lymph node .
  • Disseminated (organ) involvement: multilocular skeletal involvement; involvement of multiple lymph nodes.

"Multi-system disease":

  • Involvement of multiple organ systems
  • High risk: patient > 2 years; no involvement of hematopoietic system, liver, lung, or spleen.
  • Patient < 2 years, or patient > 2 years with involvement of the hematopoietic system, liver, lung, or spleen.

Occurrence/Epidemiology
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Incidence is 0.4 (0.2-1.0)/100,000 for children < 15 years of age; less common is adult onset.

Etiopathogenesis
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Unsolved. An intercellular communication defect with cytokine imbalance between T cells and Langerhans cells is being discussed.

Manifestation
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Age peak in the first three years of life. Later infestation possible at any age. m:w =1,3:1.

Clinical features
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The clinical picture is very variable and is characterized by the different organ manifestations (see under the different variants). In children in particular, the spectrum ranges from asymptomatic symptoms to discrete localised complaints to generalised symptoms such as weight loss, failure to thrive, restlessness and fever (see below Abt-Letterer-Siwe disease). The most frequent localization is the skeleton with about 80% (see below Eosinophilic granuloma of the bone - 34% skull -), followed by the skin manifestation (60%).

  • Skin involvement varies according to the acuity of the disease. Disseminated, small, flat, yellow-brownish papules with scaly to crusty surfaces are found. There is a tendency to necrotic disintegration and petechial haemorrhages, haemorrhagic-eczematoid ulcers and, in places, smaller ulcers. Especially affected in children are capillitium, intertriginous spaces, joint folds; furthermore, aphthous lesions of the oral mucosa; HV also hemorrhagic or xanthomatous.
  • In disseminated forms, one sees various combinations of rash, hepatosplenomegaly, generalized lymph node swelling, anemia or pancytopenia, pulmonary involvement, or bone involvement. Dysfunction of the liver (increased transaminases, hypoproteinemia, hypoalbuminemia, hyperbilirubinemia), lungs (dyspnea, pneumothorax), and hematopoiesis (cytopenia with or without bone marrow involvement).
  • General symptoms in osseous manifestations are local swelling, pain or limitation of movement. Depending on further organ involvement, other symptoms such as otitis media, otorrhea, loosening or loss of teeth, exophthalmos (see Hand-Schüller-Christian disease) or pathological fractures may be detectable.
  • CNS involvement, often with a chronic course, may occur [4]. Diabetes insipidus, as a sign of hypothalamic-pituitary CNS involvement, can often occur years before or after disease manifestations in other regions.

Histology
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Therapy
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  • Chemotherapy: Various study protocols are described. Involved cytostatics: 6-mercaptopurine; vinblastine; implementation by pediatric oncologists.
  • Salvage therapy: Immunosuppressive therapy (induction: ATG, prednisolone; maintenance: Ciclosporin A).
  • Allogeneic bone marrow transplantation in advanced stages.
  • Since about 50% of Langerhans cell histiocytoses have a BRAF V600E mutation (this also applies to systemic non-Langerhans cell histiocytoses ), very good therapeutic effects can be achieved with the BRAF inhibitor vemurafinib.

Progression/forecast
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With localized LCH the prognosis is very good. In multisystemic LCH, the prognosis depends on the age of the patient and especially on the involvement of risk organs and therapy response. Good initial response to systemic chemotherapy is a favourable prognosis criterion. In children under 2 years of age and especially in those with risk organ involvement, the course is often unfavourable. In older children, risk organs are less frequently affected and the prognosis is generally good, although chronic progression with recurrent skeletal involvement and development of late effects are possible. Most reactivations occur in the first three years after diagnosis, although reactivations more than 10 years after the initial illness are also described.

Literature
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  1. Birbeck MS et al (1961) An electron microscope study of basal melanocytes and high-level clear cells (Langerhans cells) in vitiligo. J Invest Derm 37: 51-64
  2. Goerdt S (1998) Histiocytic tumours. In: Garbe C, Rassner G Dermatology, guidelines and quality assurance for diagnostics and therapy. Springer Verlag, Berlin Heidelberg New York S 372-378
  3. Langerhans P (1868) On the nerves of human skin. Virchows Arch Catholic Anat 44: 325
  4. Leonidas JC et al (2003) Langerhans' cell histiocytosis. Lancet 361: 1293-1295
  5. Lichtenstein L (1953) Histiocytosis X. Integration of eosinophilic granuloma of bone, Letterer-Siwe Disease, and Schüller-Christian Disease as related manifestations of a single nosologic entity. Arch Catholic 56: 84-102
  6. Misery L (2003) Malignant Langerhans cell tumor: a case with a favorable outcome associated with the absence of blood dendritic cell proliferation. J Am Acad Dermatol 49: 527-529
  7. Petersen BL et al (2003) High expression of markers of apoptosis in Langerhans cell histiocytosis. Histopathology 42: 186-193
  8. Ruzicka T, Evers J (2003) Clinical course and therapy of Langerhans cell histiocytosis in children and adults. dermatologist 54: 148-155
  9. The writing Group of the Histiocyte Society (1987) Histiocytosis syndromes in children. Lancet I: 208-209

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Please ask your physician for a reliable diagnosis. This website is only meant as a reference.

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Last updated on: 19.07.2021