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European Radiology

, Volume 28, Issue 11, pp 4635–4642 | Cite as

Thoracic involvement in Erdheim-Chester disease: computed tomography imaging findings and their association with the BRAFV600E mutation

  • S. Mojdeh Mirmomen
  • Arlene Sirajuddin
  • Moozhan Nikpanah
  • Rolf Symons
  • Anna K. Paschall
  • Ioannis Papageorgiou
  • William A. Gahl
  • Kevin O’Brien
  • Juvianee I. Estrada-Veras
  • Ashkan A. Malayeri
Chest

Abstract

Objectives

To investigate the computed tomography (CT) thoracic findings in Erdheim-Chester disease (ECD) and evaluate the association of these findings with the BRAFV600E mutation.

Methods

This was a prospective study of patients with ECD (n=61, men=46) who underwent thoracic CT imaging. CT examinations were independently interpreted by two experienced radiologists. Association of imaging findings with BRAFV600E was achieved via the Chi-square or Fisher’s exact test and odds ratios (OR) with 95% confidence intervals (CI), as appropriate.

Results

Fifty-five ECD patients (90%) showed pulmonary findings, which included interlobular septal thickening (69%), pulmonary nodules (62%), airway thickening (13%) and ground glass opacities (36%). Pulmonary nodules were classified by the pattern of distribution: subpleural regions (36%), lung parenchyma (13%) and both regions (13%). Pleural and mediastinal involvement were present in 15% and 62% of cases, respectively. The most common mediastinal finding was sheathing of the right coronary artery (34%), followed by sheathing of the thoracic aorta (30%). The BRAFV600E mutation, positive in 31 patients, was associated with the frequency of sheathing of the coronary arteries (p = 0.01).

Conclusions

Of the thoracic findings reported in this study, we found a statistically significant positive association between the BRAFV600E mutation and presence of coronary artery sheathing.

Key Points

• To assess the degree of thoracic involvement in ECD with CT.

• BRAF V600E mutation has a high association with right coronary artery sheathing.

• BRAF V600E genetic testing detects patients at high risk of developing RCA sheathing.

Keywords

Erdheim-Chester disease Thorax Multidetector computed tomography Proto-oncogene proteins B-raf Genetic association study 

Abbreviations

CI

Confidence interval

CT

Computed tomography

ECD

Erdheim-Chester disease

ERK

Extracellular signal-regulated kinase

HIPPA

Health Insurance Portability and Accountability Act

LCH

Langerhans cell histiocytosis

MAP

Mitogen-activated protein

MDCT

Multi-detector computed tomography

NHGRI

National Human Genome Research Institute

OR

Odds ratio

RCA

Right coronary artery

SD

Standard deviation

WHO

World Health Organization

Notes

Funding

This work was supported by the Intramural Research programs of the National Human Genome Research Institute, the National Heart, Lung and Blood Institute, the Center for Cancer Research-National Cancer Institute and the National Institutes of Health Clinical Center, Bethesda, Maryland, USA.

Compliance with ethical standards

Guarantor

The scientific guarantor of this publication is Ashkan A. Malayeri.

Conflict of interest

The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article.

Statistics and biometry

Rolf Symons, MD, one of the authors, has significant statistical expertise.

Informed consent

Written informed consent was obtained from all patients prior to their participation in the study.

Ethical approval

This was a prospective study approved by the institutional review board at the National Human Genome Research Institute (NHGRI).

Study subjects or cohorts overlap

Clinical aspects of 60 patients of the present cohort were previously reviewed by Estrada-Veras et al. in the paper titled “The clinical spectrum of Erdheim-Chester disease: an observational cohort study” [7].

Methodology

• observational

• single-centre

• prospective

References

  1. 1.
    Haroche J, Arnaud L, Amoura Z (2012) Erdheim–Chester disease. Curr Opin Rheumatol 24(1):53–59CrossRefGoogle Scholar
  2. 2.
    Abdelfattah AM, Arnaout K, Tabbara IA (2014) Erdheim-Chester disease: a comprehensive review. Anticancer Res 34(7):3257–3261PubMedGoogle Scholar
  3. 3.
    Haroche J, Arnaud L, Cohen-Aubart F et al (2013) Erdheim-Chester disease. Rheum Dis Clin N Am 39(2):299–311CrossRefGoogle Scholar
  4. 4.
    Campochiaro C, Tomelleri A, Cavalli G, Berti A, Dagna L (2015) Erdheim-Chester disease. Eur J int Med 26(4):223–229CrossRefGoogle Scholar
  5. 5.
    Swerdlow SH, Campo E, Pileri SA et al (2016) The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 127(20):2375–2390CrossRefGoogle Scholar
  6. 6.
    Mazor RD, Manevich-Mazor M, Shoenfeld Y (2013) Erdheim-Chester Disease: a comprehensive review of the literature. Orphanet J Rare Dis 8(1):137CrossRefGoogle Scholar
  7. 7.
    Estrada-Veras JI, O’Brien KJ, Boyd LC et al (2017) The clinical spectrum of Erdheim-Chester disease: an observational cohort study. Blood Adv 1(6):357–366.  https://doi.org/10.1182/bloodadvances.2016001784 CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Diamond EL, Dagna L, Hyman DM et al (2014) Consensus guidelines for the diagnosis and clinical management of Erdheim-Chester disease. Blood 124(4):483–492CrossRefGoogle Scholar
  9. 9.
    Haroche J, Charlotte F, Arnaud L et al (2012) High prevalence of BRAF V600E mutations in Erdheim-Chester disease but not in other non-Langerhans cell histiocytoses. Blood 120(13):2700–2703.  https://doi.org/10.1182/blood-2012-05-430140 CrossRefPubMedGoogle Scholar
  10. 10.
    Janku F, Vibat CRT, Kosco K et al (2014) BRAF V600E mutations in urine and plasma cell-free DNA from patients with Erdheim-Chester disease. Oncotarget 5(11):3607CrossRefGoogle Scholar
  11. 11.
    Cohen Aubart F, Emile JF, Maksud P, et al (2016) Efficacy of the MEK inhibitor cobimetinib for wild-type BRAF Erdheim-Chester disease. B J HaematolGoogle Scholar
  12. 12.
    Hyman DM, Puzanov I, Subbiah V et al (2015) Vemurafenib in multiple nonmelanoma cancers with BRAF V600 mutations. N Engl J Med 373(8):726–736CrossRefGoogle Scholar
  13. 13.
    Haroche J, Cohen-Aubart F, Emile J-F et al (2014) Reproducible and sustained efficacy of targeted therapy with vemurafenib in patients with BRAF(V600E)-mutated Erdheim-Chester disease. J Clin Oncol 33(5):411–418CrossRefGoogle Scholar
  14. 14.
    Brun A-L, Touitou-Gottenberg D, Haroche J et al (2010) Erdheim-Chester disease: CT findings of thoracic involvement. Eur Radiol 20(11):2579–2587CrossRefGoogle Scholar
  15. 15.
    Antunes C, Graça B, Donato P (2014) Thoracic, abdominal and musculoskeletal involvement in Erdheim-Chester disease: CT, MR and PET imaging findings. Insights Into imaging 5(4):473–482CrossRefGoogle Scholar
  16. 16.
    Arnaud L, Pierre I, Beigelman-Aubry C et al (2010) Pulmonary involvement in Erdheim-Chester disease: A single-center study of thirty-four patients and a review of the literature. Arthritis Rheum 62(11):3504–3512CrossRefGoogle Scholar
  17. 17.
    Dion E, Graef C, Haroche J et al (2004) Imaging of thoracoabdominal involvement in Erdheim-Chester disease. AJR Am J Roentgenol 183(5):1253–1260CrossRefGoogle Scholar
  18. 18.
    Wittenberg KH, Swensen SJ, Myers JL (2000) Pulmonary involvement with Erdheim-Chester disease: radiographic and CT findings. AJR Am J Roentgenol 174(5):1327–1331CrossRefGoogle Scholar
  19. 19.
    Rush WL, Andriko JAW, Galateau-Salle F et al (2000) Pulmonary pathology of Erdheim-Chester disease. Mod Pathol 13(7):747–754CrossRefGoogle Scholar
  20. 20.
    Gianfreda D, Palumbo AA, Rossi E et al (2016) Cardiac involvement in Erdheim-Chester disease: an MRI study. Blood 128(20):2468–2471CrossRefGoogle Scholar
  21. 21.
    Haroche J, Amoura Z, Dion E et al (2004) Cardiovascular involvement, an overlooked feature of Erdheim-Chester disease: report of 6 new cases and a literature review. Medicine 83(6):371–392CrossRefGoogle Scholar
  22. 22.
    Serratrice J, Granel B, De Roux C et al (2000) "Coated aorta": a new sign of Erdheim-Chester disease. J Rheumatol 27(6):1550–1553PubMedGoogle Scholar
  23. 23.
    Nikpanah M, Kim L, Mirmomen SM et al (2018) Abdominal involvement in Erdheim-Chester disease (ECD): MRI and CT imaging findings and their association with BRAFV600E mutation. Eur Radiol :1–9.  https://doi.org/10.1007/s00330-018-5326-1 CrossRefGoogle Scholar

Copyright information

© This is a U.S. government work and its text is not subject to copyright protection in the United States; however, its text may be subject to foreign copyright protection 2018

Authors and Affiliations

  • S. Mojdeh Mirmomen
    • 1
  • Arlene Sirajuddin
    • 2
  • Moozhan Nikpanah
    • 1
  • Rolf Symons
    • 1
  • Anna K. Paschall
    • 1
  • Ioannis Papageorgiou
    • 4
  • William A. Gahl
    • 3
  • Kevin O’Brien
    • 3
  • Juvianee I. Estrada-Veras
    • 3
  • Ashkan A. Malayeri
    • 1
  1. 1.Radiology and Imaging SciencesNational Institutes of Health Clinical CenterBethesdaUSA
  2. 2.National Heart, Lung, and Blood InstituteNational Institutes of HealthBethesdaUSA
  3. 3.National Human Genome Research Institute, Medical Genetics Branch, Office of the Clinical DirectorNational Institutes of Health Clinical CenterBethesdaUSA
  4. 4.Magnetic Resonance Imaging of Epirus (Magnitiki Tomografia Ipirou)IoanninaGreece

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