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

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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.

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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

References

  1. Haroche J, Arnaud L, Amoura Z (2012) Erdheim–Chester disease. Curr Opin Rheumatol 24(1):53–59

    Article  Google Scholar 

  2. Abdelfattah AM, Arnaout K, Tabbara IA (2014) Erdheim-Chester disease: a comprehensive review. Anticancer Res 34(7):3257–3261

    PubMed  Google Scholar 

  3. Haroche J, Arnaud L, Cohen-Aubart F et al (2013) Erdheim-Chester disease. Rheum Dis Clin N Am 39(2):299–311

    Article  Google Scholar 

  4. Campochiaro C, Tomelleri A, Cavalli G, Berti A, Dagna L (2015) Erdheim-Chester disease. Eur J int Med 26(4):223–229

    Article  CAS  Google Scholar 

  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):2375–2390

    Article  CAS  Google Scholar 

  6. Mazor RD, Manevich-Mazor M, Shoenfeld Y (2013) Erdheim-Chester Disease: a comprehensive review of the literature. Orphanet J Rare Dis 8(1):137

    Article  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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):483–492

    Article  CAS  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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):3607

    Article  Google Scholar 

  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 Haematol

  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):726–736

    Article  CAS  Google Scholar 

  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):411–418

    Article  CAS  Google Scholar 

  14. Brun A-L, Touitou-Gottenberg D, Haroche J et al (2010) Erdheim-Chester disease: CT findings of thoracic involvement. Eur Radiol 20(11):2579–2587

    Article  Google Scholar 

  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):473–482

    Article  Google Scholar 

  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):3504–3512

    Article  Google Scholar 

  17. Dion E, Graef C, Haroche J et al (2004) Imaging of thoracoabdominal involvement in Erdheim-Chester disease. AJR Am J Roentgenol 183(5):1253–1260

    Article  Google Scholar 

  18. Wittenberg KH, Swensen SJ, Myers JL (2000) Pulmonary involvement with Erdheim-Chester disease: radiographic and CT findings. AJR Am J Roentgenol 174(5):1327–1331

    Article  CAS  Google Scholar 

  19. Rush WL, Andriko JAW, Galateau-Salle F et al (2000) Pulmonary pathology of Erdheim-Chester disease. Mod Pathol 13(7):747–754

    Article  CAS  Google Scholar 

  20. Gianfreda D, Palumbo AA, Rossi E et al (2016) Cardiac involvement in Erdheim-Chester disease: an MRI study. Blood 128(20):2468–2471

    Article  CAS  Google Scholar 

  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):371–392

    Article  Google Scholar 

  22. Serratrice J, Granel B, De Roux C et al (2000) "Coated aorta": a new sign of Erdheim-Chester disease. J Rheumatol 27(6):1550–1553

    CAS  PubMed  Google Scholar 

  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

    Article  Google Scholar 

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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.

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Authors and Affiliations

  1. Radiology and Imaging Sciences, National Institutes of Health Clinical Center, 10 Center Dr, Bethesda, MD, 20892, USA

    S. Mojdeh Mirmomen, Moozhan Nikpanah, Rolf Symons, Anna K. Paschall & Ashkan A. Malayeri

  2. National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA

    Arlene Sirajuddin

  3. National Human Genome Research Institute, Medical Genetics Branch, Office of the Clinical Director, National Institutes of Health Clinical Center, Bethesda, MD, USA

    William A. Gahl, Kevin O’Brien & Juvianee I. Estrada-Veras

  4. Magnetic Resonance Imaging of Epirus (Magnitiki Tomografia Ipirou), Ioannina, Greece

    Ioannis Papageorgiou

Authors
  1. S. Mojdeh Mirmomen
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  2. Arlene Sirajuddin
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  3. Moozhan Nikpanah
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  4. Rolf Symons
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  5. Anna K. Paschall
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  6. Ioannis Papageorgiou
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  7. William A. Gahl
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  8. Kevin O’Brien
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  9. Juvianee I. Estrada-Veras
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  10. Ashkan A. Malayeri
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Corresponding author

Correspondence to Ashkan A. Malayeri.

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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

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Cite this article

Mirmomen, S.M., Sirajuddin, A., Nikpanah, M. et al. Thoracic involvement in Erdheim-Chester disease: computed tomography imaging findings and their association with the BRAFV600E mutation. Eur Radiol 28, 4635–4642 (2018). https://doi.org/10.1007/s00330-018-5421-3

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  • DOI: https://doi.org/10.1007/s00330-018-5421-3

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