Extrathoracic investigation in adult patients with isolated pulmonary langerhans cell histiocytosis

Abdellatif Tazi, Constance de Margerie-Mellon, Laetitia Vercellino, Jean Marc Naccache, Stéphanie Fry, Stéphane Dominique, Stéphane Jouneau, Gwenaël Lorillon, Emmanuelle Bugnet, Raphael Chiron, Benoit Wallaert, Dominique Valeyre, Sylvie Chevret, Abdellatif Tazi, Constance de Margerie-Mellon, Laetitia Vercellino, Jean Marc Naccache, Stéphanie Fry, Stéphane Dominique, Stéphane Jouneau, Gwenaël Lorillon, Emmanuelle Bugnet, Raphael Chiron, Benoit Wallaert, Dominique Valeyre, Sylvie Chevret

Abstract

Background: An important objective on diagnosis of patients with Langerhans cell histiocytosis (LCH) is to determine the extent of disease. However, whether systematic extrathoracic investigation is needed in adult patients with clinically isolated pulmonary LCH (PLCH) has not been evaluated.

Methods: In this prospective, multicentre study, 54 consecutive patients with newly diagnosed clinically isolated PLCH were systematically evaluated at inclusion by bone imaging and blood laboratory testing to search for subclinical extrapulmonary LCH involvement. The patients were followed over a 2-year period. At each visit, they were asked about the presence of extrapulmonary manifestations of LCH.

Results: In the absence of bone symptoms, the skeletal X-ray survey results were normal for all but two patients who had a localised bone lesion consistent with possible LCH involvement, that remained unchanged over 2 years of follow-up. Whole-body bone scintigraphy did not add information to the plain radiography findings for the detection of asymptomatic bone involvement in isolated PLCH. Conversely, it showed nonspecific focal bone uptake in 18% of the patients, mainly corresponding to post-traumatic or degenerative abnormalities unrelated to LCH. Mild leucocytosis due to neutrophilia was observed in 22% of the patients and was not related to their smoking habits. Three patients had mild isolated lymphocytosis without haematological disease, whereas two patients had mild lymphopaenia. A mild inflammatory biological syndrome was observed in a minority of patients without infection or constitutional symptoms and was not associated with progressive disease. A substantial proportion (24.5%) of the patients had abnormal biological liver test results, including elevated liver enzymes and/or cholestasis, which were not linked to LCH involvement in this cohort.

Conclusions: Obtaining a thorough history and performing comprehensive physical examination are essential for staging patients diagnosed with PLCH. In the absence of symptoms or signs suggestive of extrapulmonary LCH involvement, the systematic performing of recommended bone imaging does not appear informative. Although the observed blood laboratory abnormalities were not specifically related to LCH, performing these tests in the diagnostic workup for PLCH is useful because some of these alterations may impact patient management.

Trial registration: ClinicalTrials.gov: No. NCT01225601; URL: www.clinicaltrials.gov.

References

    1. Suri H, Yi ES, Nowakowski GS, Vassallo R. Pulmonary langerhans cell histiocytosis. Orphanet J Rare Dis. 2012;7(1):16. doi: 10.1186/1750-1172-7-16.
    1. Tazi A. Adult pulmonary Langerhans’ cell histiocytosis. Eur Respir J. 2006;27(6):1272–85. doi: 10.1183/09031936.06.00024004.
    1. Arico M, Girschikofsky M, Genereau T, Klersy C, McClain K, Grois N, et al. Langerhans cell histiocytosis in adults. Report from the International Registry of the Histiocyte Society. Eur J Cancer. 2003;39(16):2341–8. doi: 10.1016/S0959-8049(03)00672-5.
    1. Howarth DM, Gilchrist GS, Mullan BP, Wiseman GA, Edmonson JH, Schomberg PJ. Langerhans cell histiocytosis: diagnosis, natural history, management, and outcome. Cancer. 1999;85(10):2278–90. doi: 10.1002/(SICI)1097-0142(19990515)85:10<2278::AID-CNCR25>;2-U.
    1. Stockschlaeder M, Sucker C. Adult Langerhans cell histiocytosis. Eur J Haematol. 2006;76(5):363–8. doi: 10.1111/j.1600-0609.2006.00648.x.
    1. Girschikofsky M, Arico M, Castillo D, Chu A, Doberauer C, Fichter J, et al. Management of adult patients with Langerhans cell histiocytosis: recommendations from an expert panel on behalf of Euro-Histio-Net. Orphanet J Rare Dis. 2013;8:72. doi: 10.1186/1750-1172-8-72.
    1. Tazi A, de Margerie C, Naccache JM, Fry S, Dominique S, Jouneau S, et al. The natural history of adult pulmonary Langerhans cell histiocytosis: a prospective multicentre study. Orphanet J Rare Dis. 2015;10(1):30. doi: 10.1186/s13023-015-0249-2.
    1. Crausman RS, Jennings CA, Tuder RM, Ackerson LM, Irvin CG, King TE., Jr Pulmonary histiocytosis X: pulmonary function and exercise pathophysiology. Am J Respir Crit Care Med. 1996;153(1):426–35. doi: 10.1164/ajrccm.153.1.8542154.
    1. Schonfeld N, Frank W, Wenig S, Uhrmeister P, Allica E, Preussler H, et al. Clinical and radiologic features, lung function and therapeutic results in pulmonary histiocytosis X. Respiration. 1993;60(1):38–44. doi: 10.1159/000196171.
    1. Travis WD, Borok Z, Roum JH, Zhang J, Feuerstein I, Ferrans VJ, et al. Pulmonary Langerhans cell granulomatosis (histiocytosis X). A clinicopathologic study of 48 cases. Am J Surg Pathol. 1993;17(10):971–86. doi: 10.1097/00000478-199310000-00002.
    1. Vassallo R, Ryu JH, Schroeder DR, Decker PA, Limper AH. Clinical outcomes of pulmonary Langerhans’-cell histiocytosis in adults. N Engl J Med. 2002;346(7):484–90. doi: 10.1056/NEJMoa012087.
    1. Watanabe R, Tatsumi K, Hashimoto S, Tamakoshi A, Kuriyama T. Clinico-epidemiological features of pulmonary histiocytosis X. Intern Med. 2001;40(10):998–1003. doi: 10.2169/internalmedicine.40.998.
    1. Friedman PJ, Liebow AA, Sokoloff J. Eosinophilic granuloma of lung. Clinical aspects of primary histiocytosis in the adult. Medicine (Baltimore) 1981;60(6):385–96. doi: 10.1097/00005792-198111000-00001.
    1. Schonfeld N, Dirks K, Costabel U, Loddenkemper R. A prospective clinical multicentre study on adult pulmonary Langerhans’ cell histiocytosis. Sarcoidosis Vasc Diffuse Lung Dis. 2012;29(2):132–8.
    1. Elia D, Torre O, Cassandro R, Caminati A, Harari S. Pulmonary Langerhans cell histiocytosis: A comprehensive analysis of 40 patients and literature review. Eur J Intern Med. 2015;26(5):351–6. doi: 10.1016/j.ejim.2015.04.001.
    1. Baumgartner I, von Hochstetter A, Baumert B, Luetolf U, Follath F. Langerhans’-cell histiocytosis in adults. Med Pediatr Oncol. 1997;28(1):9–14. doi: 10.1002/(SICI)1096-911X(199701)28:1<9::AID-MPO3>;2-P.
    1. Howarth DM, Mullan BP, Wiseman GA, Wenger DE, Forstrom LA, Dunn WL. Bone scintigraphy evaluated in diagnosing and staging Langerhans’ cell histiocytosis and related disorders. J Nucl Med. 1996;37(9):1456–60.
    1. Meyer JS, Harty MP, Mahboubi S, Heyman S, Zimmerman RA, Womer RB, et al. Langerhans cell histiocytosis: presentation and evolution of radiologic findings with clinical correlation. Radiographics. 1995;15(5):1135–46. doi: 10.1148/radiographics.15.5.7501855.
    1. Schaub T, Ash JM, Gilday DL. Radionuclide imaging in histiocytosis X. Pediatr Radiol. 1987;17(5):397–404. doi: 10.1007/BF02396617.
    1. Phillips M, Allen C, Gerson P, McClain K. Comparison of FDG-PET scans to conventional radiography and bone scans in management of Langerhans cell histiocytosis. Pediatr Blood Cancer. 2009;52(1):97–101. doi: 10.1002/pbc.21782.
    1. Yanbaeva DG, Dentener MA, Creutzberg EC, Wesseling G, Wouters EF. Systemic effects of smoking. Chest. 2007;131(5):1557–66. doi: 10.1378/chest.06-2179.
    1. Egeler RM, Neglia JP, Arico M, Favara BE, Heitger A, Nesbit ME, et al. The relation of Langerhans cell histiocytosis to acute leukemia, lymphomas, and other solid tumors. The LCH-Malignancy Study Group of the Histiocyte Society. Hematol Oncol Clin North Am. 1998;12(2):369–78. doi: 10.1016/S0889-8588(05)70516-5.
    1. Feuillet S, Louis L, Bergeron A, Berezne A, Dubreuil ML, Polivka M, et al. Pulmonary Langerhans cell histiocytosis associated with Hodgkin’s lymphoma. Eur Respir Rev. 2010;19(115):86–8. doi: 10.1183/09059180.00007509.
    1. Abdallah M, Genereau T, Donadieu J, Emile JF, Chazouilleres O, Gaujoux-Viala C, et al. Langerhans’ cell histiocytosis of the liver in adults. Clin Res Hepatol Gastroenterol. 2011;35(6-7):475–81. doi: 10.1016/j.clinre.2011.03.012.
    1. Araujo B, Costa F, Lopes J, Castro R. Adult langerhans cell histiocytosis with hepatic and pulmonary involvement. Case Rep Radiol. 2015;2015:536328.
    1. Konno S, Hizawa N, Betsuyaku T, Yasuo M, Yamamoto H, Koizumi T, et al. Adult Langerhans cell histiocytosis with independently relapsing lung and liver lesions that was successfully treated with etoposide. Intern Med. 2007;46(15):1231–5. doi: 10.2169/internalmedicine.46.6433.
    1. Grobost V, Khouatra C, Lazor R, Cordier JF, Cottin V. Effectiveness of cladribine therapy in patients with pulmonary Langerhans cell histiocytosis. Orphanet J Rare Dis. 2014;9(1):191. doi: 10.1186/s13023-014-0191-8.
    1. Lorillon G, Bergeron A, Detourmignies L, Jouneau S, Wallaert B, Frija J, et al. Cladribine is effective against cystic pulmonary Langerhans cell histiocytosis. Am J Respir Crit Care Med. 2012;186(9):930–2. doi: 10.1164/ajrccm.186.9.930.
    1. Robak T, Korycka A, Robak E. Older and new formulations of cladribine. Pharmacology and clinical efficacy in hematological malignancies. Recent Pat Anticancer Drug Discov. 2006;1(1):23–38. doi: 10.2174/157489206775246467.

Source: PubMed

Patrocinadores y Colaboradores

Condiciones médicas

Intervenciones de drogas

3
Suscribir