Skip to main content
SpringerLink
Log in

Die pulmonale Langerhans-Zell-Histiozytose

Pulmonary Langerhans cell histiocytosis

  • Schwerpunkt: Histiozytäre Erkrankungen
  • Published:
Der Pathologe Aims and scope Submit manuscript

Zusammenfassung

Die pulmonale Langerhans-Zell-Histiozytose kann als reaktive Proliferation von Langerhans-Zellen auf chronischen Tabakrauchkonsum gesehen werden, kann aber auch besonders im Kindesalter als eine tumorartige systemische Erkrankung auftreten. Morphologisch können diese beiden Formen derzeit nicht unterschieden werden. In den Lungen kommt es zu einer nodulären Proliferation von Langerhans-Zellen in der Bronchialmukosa, aber auch peripher in den Alveolarsepten mit einer begleitenden Infiltration durch eosinophile Granulozyten und Zerstörung der Bronchialwand. Die Langerhans-Zellen lassen sich selektiv mithilfe von Antikörpern auf CD1a und Langerin nachweisen. In der reaktiven isoliert pulmonalen Form führt die Abstinenz von Tabakrauch bei den meisten Patienten zu einer Regression der Infiltrate und einer Besserung der Symptome. Radiologisch sind auch nach völliger Tabakrauchabstinenz die kleinen sternförmigen Narben zu erkennen.

Abstract

Pulmonary Langerhans cell histiocytosis is regarded as a reactive proliferation of the dendritic Langerhans cell population stimulated by chronic tobacco-derived plant proteins due to incomplete combustion but can also occur in childhood as a tumor-like systemic disease. Currently, both these forms cannot be morphologically distinguished. In the lungs a nodular proliferation of Langerhans cells occurs in the bronchial mucosa and also peripherally in the alveolar septa with an accompanying infiltration by eosinophilic granulocytes and destruction of the bronchial wall. Langerhans cells can be selectively detected with antibodies against CD1a and langerin. In the reactive isolated pulmonary form, abstinence from tobacco smoking in most patients leads to regression of infiltration and improvement of symptoms. In high-resolution computed tomography (HRCT) the small star-like scars can still be detected even after complete cessation of tobacco smoking.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Abb. 1
Abb. 2
Abb. 3
Abb. 4
Abb. 5
Abb. 6
Abb. 7
Abb. 8
Abb. 9
Abb. 10
Abb. 11

Literatur

  1. Ackerman AJ (1947) Eosinophilic granuloma of bones associated with involvement of the lungs and diaphragm. Am J Roentgenol Radium Ther 58(6):733–740

    CAS  PubMed  Google Scholar 

  2. Parkinson T (1949) Eosinophilic xanthomatous granuloma with honeycomb lungs. Br Med J 1(4614):1029

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Dickson DD (1948) Eosinophilic granuloma of bone with diffuse pulmonary involvement. Calif Med 69(1):51–53

    PubMed Central  CAS  PubMed  Google Scholar 

  4. Nadeau PJ, Ellis FH Jr, Harrison EG Jr, Fontana RS (1960) Primary pulmonary histiocytosis X. Dis Chest 37:325–339

    Article  CAS  PubMed  Google Scholar 

  5. Weiss W, Johnston DG (1957) Pulmonary histiocytosis X. Am Rev Tuberc 75(2):319–325

    CAS  PubMed  Google Scholar 

  6. Friedman PJ, Liebow AA, Sokoloff J (1981) Eosinophilic granuloma of lung. Clinical aspects of primary histiocytosis in the adult. Medicine (Baltimore) 60(6):385–396

    Article  CAS  Google Scholar 

  7. Knudson RJ, Badger TL, Gaensler EA (1966) Eosinophilic granuloma of the lung. Med Thorac 23(4):248–262

    CAS  PubMed  Google Scholar 

  8. Lichtenstein L (1964) Histiocytosis X (Eosinophilic Granuloma of Bone, Letterer-Siwe Disease, and Schueller-Christian Disease). Further observations of pathological and clinical importance. J Bone Joint Surg Am 46:76–90

    CAS  PubMed  Google Scholar 

  9. Cline MJ (1994) Histiocytes and histiocytosis. Blood 84(9):2840–2853

    CAS  PubMed  Google Scholar 

  10. Nezelof C, Basset F (1998) Langerhans cell histiocytosis research. Past, present, and future. Hematol Oncol Clin North Am 12(2):385–406

    Article  CAS  PubMed  Google Scholar 

  11. Chikwava KR, Hunt JL, Mantha GS, Murphy JE, Jaffe R (2007) Analysis of loss of heterozygosity in single-system and multisystem Langerhans’ cell histiocytosis. Pediatr Dev Pathol 10(1):18–24

    Article  CAS  PubMed  Google Scholar 

  12. Badalian-Very G, Vergilio JA, Degar BA et al (2010) Recurrent BRAF mutations in Langerhans cell histiocytosis. Blood 116(11):1919–1923

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. van Nieuwenhuijze AE, Coghill E, Gray D et al (2014) Transgenic expression of GM-CSF in T cells causes disseminated histiocytosis. Am J Pathol 184(1):184–199

    Article  PubMed  Google Scholar 

  14. Chilosi M, Facchetti F, Calio A et al (2014) Oncogene-induced senescence distinguishes indolent from aggressive forms of pulmonary and non-pulmonary Langerhans cell histiocytosis. Leuk Lymphoma 55(11):2620–2626

    Article  CAS  PubMed  Google Scholar 

  15. Sundar KM, Gosselin MV, Chung HL, Cahill BC (2003) Pulmonary Langerhans cell histiocytosis: emerging concepts in pathobiology, radiology, and clinical evolution of disease. Chest 123(5):1673–1683

    Article  PubMed  Google Scholar 

  16. Attili AK, Kazerooni EA, Gross BH et al (2008) Smoking-related interstitial lung disease: radiologic-clinical-pathologic correlation. Radiographics 28(5):1383–1396 (discussion 96–98)

    Article  PubMed  Google Scholar 

  17. Popper HH (2000) Bronchiolitis, an update. Virchows Arch 437(5):471–481

    Article  CAS  PubMed  Google Scholar 

  18. Egeler RM, Favara BE, van Meurs M, Laman JD, Claassen E (1999) Differential In situ cytokine profiles of Langerhans-like cells and T cells in Langerhans cell histiocytosis: abundant expression of cytokines relevant to disease and treatment. Blood 94(12):4195–4201

    CAS  PubMed  Google Scholar 

  19. Uebelhoer M, Bewig B, Sternberg K et al (1995) Alveolar macrophages from bronchoalveolar lavage of patients with pulmonary histiocytosis X: determination of phenotypic and functional changes. Lung 173(3):187–195

    Article  CAS  PubMed  Google Scholar 

  20. Costabel U, Guzman J, Bonella F, Oshimo S (2007) Bronchoalveolar lavage in other interstitial lung diseases. Semin Respir Crit Care Med 28(5):514–524

    Article  PubMed  Google Scholar 

  21. Dziegiel P, Dolilnska-Krajewska B, Dumanska M et al (2007) Coexpression of CD1a, langerin and Birbeck’s granules in Langerhans cell histiocytoses (LCH) in children: ultrastructural and immunocytochemical studies. Folia Histochem Cytobiol 45(1):21–25

    PubMed  Google Scholar 

  22. Wilejto M, Abla O (2012) Langerhans cell histiocytosis and Erdheim-Chester disease. Curr Opin Rheumatol 24(1):90–96

    Article  CAS  PubMed  Google Scholar 

  23. Badalian-Very G, Vergilio JA, Degar BA, Rodriguez-Galindo C, Rollins BJ (2012) Recent advances in the understanding of Langerhans cell histiocytosis. Br J Haematol 156(2):163–172

    Article  CAS  PubMed  Google Scholar 

  24. Routy B, Hoang J, Gruber J (2015) Pulmonary langerhans cell histiocytosis with lytic bone involvement in an adult smoker: regression following smoking cessation. Case Rep Hematol 2015:201536

    PubMed Central  CAS  PubMed  Google Scholar 

  25. Yousem SA, Dacic S, Nikiforov YE, Nikiforova M (2013) Pulmonary Langerhans cell histiocytosis: profiling of multifocal tumors using next-generation sequencing identifies concordant occurrence of BRAF V600E mutations. Chest 143(6):1679–1984

    Article  CAS  PubMed  Google Scholar 

  26. Roden AC, Hu X, Kip S et al (2014) BRAF V600E expression in Langerhans cell histiocytosis: clinical and immunohistochemical study on 25 pulmonary and 54 extrapulmonary cases. Am J Surg Pathol 38(4):548–551

    Article  PubMed  Google Scholar 

  27. Shahla A, Parvaneh V, Hossein HD (2004) Langerhans cells histiocytosis in one family. Pediatr Hematol Oncol 21(4):313–320

    Article  PubMed  Google Scholar 

  28. Arceci RJ (2014) Biological and therapeutic implications of the BRAF pathway in histiocytic disorders. Am Soc Clin Oncol Educ Book 2014:e441–e445

    Article  Google Scholar 

  29. Wei R, Wang Z, Li X, Shu Y, Fu B (2013) Frequent mutation has no effect on tumor invasiveness in patients with Langerhans cell histiocytosis. Biomed Rep 1(3):365–368

    PubMed Central  CAS  PubMed  Google Scholar 

  30. Hutter C, Kauer M, Simonitsch-Klupp I et al (2012) Notch is active in Langerhans cell histiocytosis and confers pathognomonic features on dendritic cells. Blood 120(26):5199–5208

    Article  CAS  PubMed  Google Scholar 

  31. Murakami I, Morimoto A, Oka T et al (2013) IL-17A receptor expression differs between subclasses of Langerhans cell histiocytosis, which might settle the IL-17A controversy. Virchows Arch 462(2):219–228

    Article  CAS  PubMed  Google Scholar 

  32. Coury F, Annels N, Rivollier A et al (2008) Langerhans cell histiocytosis reveals a new IL-17A-dependent pathway of dendritic cell fusion. Nat Med 14(1):81–87

    Article  CAS  PubMed  Google Scholar 

  33. Nelson DS, van Halteren A, Quispel WT et al (2015) MAP2K1 and MAP3K1 mutations in Langerhans cell histiocytosis. Genes Chromosomes Cancer 54(6):361–368

    Article  CAS  PubMed  Google Scholar 

  34. Kawauchi Y, Kuroda Y, Kojima N (2012) Preferences for uptake of carbohydrate-coated liposomes by C-type lectin receptors as antigen-uptake receptors. Glycoconj J 29(7):481–490

    Article  CAS  PubMed  Google Scholar 

  35. Chabrol E, Nurisso A, Daina A et al (2012) Glycosaminoglycans are interactants of Langerin: comparison with gp120 highlights an unexpected calcium-independent binding mode. PLoS One 7(11):e50722

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. Salazar F, Ghaemmaghami AM (2013) Allergen recognition by innate immune cells: critical role of dendritic and epithelial cells. Front Immunol 4:356

    Article  PubMed Central  PubMed  Google Scholar 

  37. Lambrecht BN, Hammad H (2014) Allergens and the airway epithelium response: gateway to allergic sensitization. J Allergy Clin Immunol 134(3):499–507

    Article  CAS  PubMed  Google Scholar 

  38. Santiago-Schwarz F (1999) Positive and negative regulation of the myeloid dendritic cell lineage. J Leukoc Biol 66(2):209–216

    CAS  PubMed  Google Scholar 

  39. Bartlett JA, Fischer AJ, McCray PB Jr (2008) Innate immune functions of the airway epithelium. Contrib Microbiol 15:147–163

    Article  CAS  PubMed  Google Scholar 

  40. Karo JM, Sun JC (2015) Novel molecular mechanism for generating NK-cell fitness and memory. Eur J Immunol 45(7):1906–1915

    Article  CAS  PubMed  Google Scholar 

  41. Satpathy AT, Chang HY (2015) Long noncoding RNA in hematopoiesis and immunity. Immunity 42(5):792–804

    Article  CAS  PubMed  Google Scholar 

  42. Haniffa M, Bigley V, Collin M (2015) Human mononuclear phagocyte system reunited. Semin Cell Dev Biol 41:59–69

    Article  CAS  PubMed  Google Scholar 

  43. Fischer A (2015) Recent advances in understanding the pathophysiology of primary T cell immunodeficiencies. Trends Mol Med 21(7):408–416

    Article  CAS  PubMed  Google Scholar 

  44. Egeler RM, van Halteren AG, Hogendoorn PC, Laman JD, Leenen PJ (2010) Langerhans cell histiocytosis: fascinating dynamics of the dendritic cell-macrophage lineage. Immunol Rev 234(1):213–232

    Article  CAS  PubMed  Google Scholar 

  45. Koethe SM, Kuhnmuench JR, Becker CG (2000) Neutrophil priming by cigarette smoke condensate and a tobacco anti-idiotypic antibody. Am J Pathol 157(5):1735–1743

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  46. Youkeles LH, Grizzanti JN, Liao Z, Chang CJ, Rosenstreich DL (1995) Decreased tobacco-glycoprotein-induced lymphocyte proliferation in vitro in pulmonary eosinophilic granuloma. Am J Respir Crit Care Med 151(1):145–150

    Article  CAS  PubMed  Google Scholar 

  47. Popper HH (1999) Epithelioid cell granulomatosis of the lung: new insights and concepts. Sarcoidosis Vasc Diffuse Lung Dis 16(1):32–46

    CAS  PubMed  Google Scholar 

  48. Fisher GM, Iqball S, Knight SC (1999) Gene expression during differentiation of human dendritic cells from cord blood cd34 stem cells. Cytokine 11(2):111–117

    Article  CAS  PubMed  Google Scholar 

  49. Popper HH (2013) Interstitial lung diseases-can pathologists arrive at an etiology-based diagnosis? A critical update. Virchows Arch 462(1):1–26

    Article  PubMed  Google Scholar 

  50. Hyman DM, Diamond EL, Vibat CR et al (2015) Prospective blinded study of BRAFV600E mutation detection in cell-free DNA of patients with systemic histiocytic disorders. Cancer Discov 5(1):64–71

    Article  CAS  PubMed  Google Scholar 

  51. Emile JF, Diamond EL, Helias-Rodzewicz Z et al (2014) Recurrent RAS and PIK3CA mutations in Erdheim-Chester disease. Blood 124(19):3016–3019

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  52. Park HJ, Jeon YK, Lee AH et al (2012) Use of the JL1 epitope, which encompasses the nonglycosylation site of CD43, as a marker of immature/neoplastic Langerhans cells. Am J Surg Pathol 36(8):1150–1117

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Forschungseinheit Molekulare Lungen- & Pleurapathologie, Institut für Pathologie, Medizinische Universität Graz, Auenbruggerplatz 25, 8036, Graz, Österreich

    H.H. Popper

Authors
  1. H.H. Popper
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to H.H. Popper.

Ethics declarations

Interessenkonflikt

H.H. Popper gibt an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

Additional information

Schwerpunktherausgeber

F. Fend, Tübingen

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Popper, H. Die pulmonale Langerhans-Zell-Histiozytose. Pathologe 36, 451–457 (2015). https://doi.org/10.1007/s00292-015-0052-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00292-015-0052-9

Schlüsselwörter

Keywords

Search

Navigation