Langerhans cell histiocytosis: a pathologist view

Czech version

Authors: R. Kodet; M. Mrhalová
Authors‘ workplace: Ústav patologie a molekulární medicíny 2. lékařské fakulty UK a FN Motol Praha, přednosta prof. MU Dr. Roman Kodet, CSc.
Published in: Vnitř Lék 2010; 56(Supplementum 2): 27-38
Category: Langerhans cell histiocytosis and some other Hematology rare diseases

Overview

Langerhans cell histiocytosis is a clinico- pathological entity with a wide spectrum of clinical and morphological findings. The disease was defined on the basis of recognition of three entities in medical history – Hand- Schüller- Christian disease, Letterer- Siwe disease and eosinophilic granuloma of bone. Later on in the past, these diseases were linked under a term histiocytosis X. With identification of a common cell of origin, the Langerhans cell, a name “Langerhans cell histiocytosis” (LCH) has been accepted. This review summarizes more than a hundred-year evolution of views on the disease. Langerhans cells are identified with the aid of histopathological investigations and an ultrastructural demonstration of specific membranous intracytoplasmic structures – Birbeck granules. At present the diagnosis of LCH utilizes immunohistochemical investigations to demonstrate positivity of S-100 protein, CD1a and langerin (CD207) in Langerhans cells. Characteristics of these molecules are briefly summarized. Further supportive laboratory methods may be used to demonstrate expression of proteins of the cell cycle, namely Ki- 67. The evaluation of the proliferation activity might support the estimation of a potential of the disease to progress or disseminate, especially in cases diagnosed at early stages or in situations they involve a single organ or tissue, and the progression might evolve secondarily. The histopathological differential diagnosis should separate LCH from reactive non-neoplastic Langerhans cell proliferations, histocytic diseases and a number of neoplastic diseases which are briefly reviewed.

Key words:
Langerhans cell histiocytosis – classification – histopathological and immunophenotypical findings – differential diagnosis

Sources

1. Adam Z, Pour L, Krejčí M et al. Histiocytóza z Langerhansových buněk u osob dospělého věku – nemoc s mnoha tvářemi. Zkušenosti jednoho pracoviště a přehled projevů nemoci. Vnitř Lék 2008; 54: 1063– 1080.

2. Swerdlow SH, Campo E, Harris NL et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 2nd ed. Lyon: IARC Press 2008.

3. Adam Z, Krejčí M, Pour L. Histiocytární choroby. Vnitř Lék 2009; 55: 109– 124.

4. Fraser J. Skeletal lipoid granulomatosis (Hand-Shüller-Cristian’s Disease). Br J Surg 1935; 22: 800– 824.

5. Abt AF, Denenholz EJ. Letterer-Siwe’s disease: Splenohepatomegaly associated with widespread hyperplasia of nonlipoid-stroing macrophages. Discussion of the so-called reticulo-endothelioses. Am J Dis Child 1936; 51: 499– 522.

6. Otani S, Ehrlich JC. Solitary granuloma of bone: simulating primary neoplasm. Am J Pathol 1940; 16: 479– 490.

7. Lichtenstein L, Jeffe HL. Eosinophilic granuloma of bone: with report of a case. Am J Pathol 1940; 16: 595– 604.

8. Wallgren A. Systemic reticuloendothelial granuloma: Nonlipod reticuloendotheliosis and Schuller-Christian disease. Am J Dis Child 1940; 60: 471– 500.

9. Farber S. The nature of “solitary eosinophilic granuloma” of bone. Am J Pathol 1941; 17: 625– 629.

10. Green WT, Farber S. “Eosinophilic or solitary granuloma” of bone. J Bone Joint Surg 1942; 24: 499– 526.

11. Mallory TB. Pathology: Diseases of Bone. N Engl J Med 1942; 227: 955– 960.

12. Laymon CW, Sevenants JJ. Systemic reticuloendothelial granuloma; comparison of Letterer-Siwe disease, Schueller-Christian disease and eosinophilic granuloma. Arch Derm Syphilol 1948; 57: 873– 890.

13. Dennis JW, Rosahn PD. The primary reticulo-endothelial granulomas, with report of an atypical case of Letterer-Siwe’s disease. Am J Pathol 1951; 27: 627– 653.

14. Lichtenstein L. Histiocytosis X, Integration of eosinophilic: granutoma of bone, “Letterer-Siwe disease”, and “Schüller-Christian disease” as related manifestations of a single nosologic entity. Arch Pathol 1953; 56: 84– 102.

15. Birbeck MS, Breathnach AS, Everall JD. An electron microscope study of nasal melanocytes and high‑level clear cells (Langerhans cells) in vitiligo. J Invest Dermat 1961; 37: 51– 63.

16. Basset F, Turiaf MJ. Identification par la microscopie electronique de particules de nature probablement virale dans les liaisons granulomateuses d’une histiocytose “X” pulmonaire. C R Acad Sci Hebd Seances Acad Sci D 1965; 261: 3701– 3703.

17. Basset F, Nezelof C, Turiaf J. Presence en microscopie electronique de structures filamenteuses originales dans les lesions pulmonaires et osseuses de l’histiocytose x. Etat actuel de la question. Bull Mem Soc Med Hop Paris 1966; 117: 413– 426.

18. Nezelof C, Basset F, Rousseau MF. Histiocytosis X histogenetic arguments for a Langerhans cell origin. Biomedicine 1973; 18: 365– 371.

19. Nezelof C, Barbey S. Histiocytosis: nosology and pathobiology. Pediatr Pathol 1985; 3: 1– 41.

20. Yu RC, Chu C, Buluwela L et al. Clonal proliferation of Langerhans cells in Langerhans cell histiocytosis. Lancet 1994; 343: 767– 768.

21. Willman CL, Busque L, Griffith BB et al. Langerhans’-cell histiocytosis (histiocytosis X) – a clonal proliferative disease. N Engl J Med 1994; 331: 154– 160.

22. Yousem SA, Colby TV, Chen YY et al. Pulmonary Langerhans’ cell histiocytosis: molecular analysis of clonality. Am J Surg Pathol 2001; 25: 630– 636.

23. Schouten B, Egeler RM, Leenen PJ et al. Expression of cell cycle‑related gene products in Langerhans cell histiocytosis. J Pediatr Hematol Oncol 2002; 24: 727– 732.

24. Betts DR, Leibundgut KE, Feldges A et al. Cytogenetic abnormalities in Langerhans cell histiocytosis. Br J Cancer 1998; 77: 552– 555.

25. Murakami I, Gogusev J, Fournet JC et al. Detection of molecular cytogenetic aberrations in Langerhans cell histiocytosis of bone. Hum Pathol 2002; 33: 555– 560.

26. Histiocytosis syndromes in children. Writing Group of the Histiocyte Society. Lancet 1987; 1: 208– 209.

27. da Costa CE, Annels NE, Faaij CM et al. Presence of osteoclast‑like multinucleated giant cells in the bone and nonostotic lesions of Langerhans cell histiocytosis. J Exp Med 2005; 201: 687– 693.

28. Kodet R, Elleder M, Šmelhaus V et al. Diseminovaná histiocytosis X. Česk Patol 1984; 20: 19– 26.

29. Williams JW, Dorfman RF. Lymphadenopathy as the initial manifestation of histiocytosis X. Am J Surg Pathol 1979; 3: 405– 421.

30. Favara B. Histopathology of the liver in histiocytosis syndromes. Pediatr Pathol Lab Med 1996; 16: 413– 433.

31. Kodet R, Zítková M. Morfologické a rentgenologické plicní nálezy pri diseminované histiocytóze X. Česk Pediatr 1985; 40: 634– 638.

32. Mierau GW, Favara BE, Brenman JM. Electron microscopy in histiocytosis X. Ultrastruct Pathol 1982; 3: 137– 142.

33. Elleder M. Activity of alpha-d-mannosidase in human Langerhans epidermal cells. Virchows Arch B Cell Pathol 1975; 19: 93– 96.

34. Novak N, Gros E, Bieber T et al. Human skin and oral mucosal dendritic cells as ‘good guys’ and ‘bad guys’ in allergic immune responses. Clin Exp Immunol 2010; 161: 28– 33.

35. Toebak MJ, Gibbs S, Bruynzeel DP et al. Dendritic cells: biology of the skin. Contact Dermatitis 2009; 60: 2– 20.

36. Salama I, Malone PS, Mihaimeed F et al. A review of the S-100 proteins in cancer. Eur J Surg Oncol 2008; 34: 357– 364.

37. Safran M, Dalah I, Alexander J et al. GeneCards Version 3: the human gene integrator. Database (Oxford) 2010: Print 2010.

38. Marenholz I, Heizmann CW, Fritz G. S-100 proteins in mouse and man: from evolution to function and pathology (including an update of the nomenclature). Biochem Biophys Res Commun 2004; 322: 1111– 1122.

39. Park HR, Min SK. Expression of S-100A2 and S-100B proteins in epithelial tumors of the skin. J Cutan Pathol 2003; 30: 373– 378.

40. Nishikawa Y, Sato H, Oka T et al. Immunohistochemical discrimination of plasmacytoid dendritic cells from myeloid dendritic cells in human pathological tissues. J Clin Exp Hematop 2009; 49: 23– 31.

41. Shrestha P, Muramatsu Y, Kudeken W et al. Localization of Ca(2+)‑binding S-100 proteins in epithelial tumours of the skin. Virchows Arch 1998; 432: 53– 59.

42. Krenács L, Tiszalvicz L, Krenács T et al. Immunohistochemical detection of CD1a antigen in formalin‑fixed and paraffin‑embedded tissue sections with monoclonal antibody. J Pathol 1993; 171: 99– 104.

43. Salamero J, Bausinger H, Mommaas AM et al. CD1a molecules traffic through the early recycling endosomal pathway in human Langerhans cells. J Invest Dermatol 2001; 116: 401– 408.

44. Salio M, Silk JD, Cerundolo V. Recent advances in processing and presentation of CD1 bound lipid antigens. Curr Opin Immunol 2010; 22: 81– 88.

45. Varki A, Cummings RD, Esko JD et al. eds. Essentials of Glycobiology, Cold Spring Harbor. 2nd ed. New York: Cold Spring Harbor Laboratory Press 2009.

46. Valladeau J, Duvert-Frances V, Pin JJ et al. The monoclonal antibody DCGM4 recognizes Langerin, a protein specific of Langerhans cells, and is rapidly internalized from the cell surface. Eur J Immunol 1999; 29: 2695– 2704.

47. Valladeau J, Ravel O, Dezutter-Dambuyant C et al. Langerin, a novel C‑type lectin specific to Langerhans cells, is an endocytic receptor that induces the formation of Birbeck granules. Immunity 2000; 12: 71– 81.

48. Thépaut M, Valladeau J, Nurisso A et al. Structural studies of langerin and Birbeck granule: a macromolecular organization model. Biochemistry 2009; 48: 2684– 2698.

49. Gerdes J, Schwab U, Lemke H et al. Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int J Cancer 1983; 31: 13– 20.

50. Egeler RM, van Halteren AG, Hogendoorn PC et al. Langerhans cell histiocytosis: fascinating dynamics of the dendritic cell-macrophage lineage. Immunol Rev 2010; 234: 213– 232.

51. Amir G, Weintraub M. Association of cell cycle‑related gene products and NF-kappaB with clinical parameters in Langerhans cell histiocytosis. Pediatr Blood Cancer 2008; 50: 304– 307.

52. Bohn OL, Ruiz-Argüelles G, Navarro L et al. Cutaneous Langerhans cell sarcoma: a case report and review of the literature. Int J Hematol 2007; 85: 116– 120.

53. Bank MI, Rengtved P, Carstensen H et al. p53 expression in biopsies from children with Langerhans cell histiocytosis. J Pediatr Hematol Oncol 2002; 24: 733– 736.

54. Kodet R, Elleder M, De Wolf-Peeters C et al. Congenital histiocytosis: a heterogeneous group of diseases, one presenting as so-called congenital self-healing histiocytosis. Pathol Res Pract 1991; 187: 458– 466.

55. Safali M, McCutcheon JM, Wright DH. Langerhans cell histiocytosis of lymph nodes: draining a papillary carcinoma of the thyroid. Histopathol 1997; 30: 599– 603.

56. Kodetová D, Kodet R, Syrůček M et al. Sinusová histiocytóza s masivní lymfadenopatií – diseminovaná forma syndromu Rosai-Dorfman. Česk Patol 1996; 32: 53– 59.

57. Abbott GF, Rosado-de-Christenson ML, Franks TJ et al. From the archives of the AFIP: pulmonary Langerhans cell histiocytosis. Radiographics 2004; 24: 821– 841.

58. Tazi A. Adult pulmonary Langerhans’ cell histiocytosis. Eur Respir J 2006; 27: 1272– 1285.