The Diagnostic Approach to Lymphedema: a Review of Current Modalities and Future Developments
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Purpose of Review
Breast cancer–related lymphedema (BCRL) is a chronic disease that results from a disruption or obstruction in the lymphatic system and affects 15 in 100 individuals in the USA with newly diagnosed breast cancer. As no curative therapy exists for lymphedema, early detection is crucial in order to reduce the risk of developing late stage symptoms, such as swelling, decreased limb flexibility, disfigurement, and impaired function of the extremity. The objective of this review is to discuss current modalities and devices as well as highlight promising advancements intended to aid in diagnosing secondary lymphedema in breast cancer patients.
Imaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) can offer high resolution of the lymphatics but are expensive and time-consuming. Single photon emission computed tomography (SPECT) is an alternative that reveals organ function as opposed to organ structure. Other imaging methods, such as color duplex ultrasound (CDU), laser scanner 3D (LS3D), and dual-energy X-ray absorptiometry (DXA), are relatively easy to use, reproducible, and fast to perform. However, the disadvantages of these techniques include lower sensitivity and specificity compared with CT and MRI. Of note, direct imaging techniques are highly effective for the diagnosis of lymphedema because they utilize dyes or radiotracers in order to directly visualize lymphatic vessels. Fluorescent microlymphography (FMLG) and near-infrared imaging (NIR) involve injection of fluorescent dyes that can be excited with light. Lymphoscintigraphy has effectively replaced lymphangiography as the method of choice for the diagnosis of lymphedema because it is safer, less invasive, and has no risk of causing an allergic reaction in patients. Novel approaches that are currently in development include bioimpedance spectroscopy, ultra-high-frequency ultrasound systems (UHFUS), and magnetic resonance lymphography (MRL).
The wide range of diagnostic methods for BCRL exhibit the tradeoff between simplicity and sensitivity; some techniques provide high resolution but are expensive and time consuming. On the other hand, other modalities are easy to use, reliable, and relatively fast in execution yet lack the ability to precisely visualize the lymphatic system. In review of these various techniques, lymphoscintigraphy serves as a clear gold standard for diagnosing secondary lymphedema while more advanced and promising techniques continue to emerge as newer alternatives in clinical practice.
KeywordsLymphedema Diagnostics Devices
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The authors declare that they have no conflict of interest.
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- 1.Group USCSW. U.S. Cancer Statistics Data Visualizations Tool, based on November 2018 submission data (1999-2016). U.S. Department of Health and Human Services, Centers for Disease Control and Prevention and National Cancer Institute. https://gis.cdc.gov/Cancer/USCS/DataViz.html. Accessed 6 Aug 2019.
- 4.McLaughlin S, Bagaria S, Gibson T, Arnold M, Diehl N, Crook J, et al. Trends in risk reduction practices for the prevention of lymphedema in the first 12 months after breast cancer surgery. J Am Coll Surg. 2013;216:380–9. https://doi.org/10.1016/j.jamcollsurg.2012.11.004.CrossRefPubMedGoogle Scholar
- 6.• Pamarthi V, Pabon-Ramos W, Marnell V, Hurwitz L. MRI of the central lymphatic system: indications, imaging, technique, and pre-procedural planning. Top Magn Reson Imaging. 2017;26:175–80. https://doi.org/10.1097/RMR.0000000000000130This review describes advances in magnetic resonance (MR) software that allow improved visualization of the lymphatics. In providing helpful visualization of central lymphatic system anatomy and pathology, this technology can be utilized for both lymphedema diagnosis and pre-procedural planning. CrossRefPubMedPubMedCentralGoogle Scholar
- 9.Padera T, Meijer E, Munn L. The lymphatic system in disease processes and cancer progression. Annu Rev Biomed Eng. 2016;18:125–58. https://doi.org/10.1146/annurev-bioeng-112315-031200.CrossRefPubMedPubMedCentralGoogle Scholar
- 10.Greene A. History and physical examination. In: Greene A, Slavin S, Brorson H, editors. Lymphedema. Cham: Springer; 2015.Google Scholar
- 11.Gerber L. A review of measures of lymphedema. Cancer. 1998;83:2803–4. https://doi.org/10.1002/(sici)1097-0142(19981215)83:12b+<2803::aid-cncr29>3.3.co;2-n.CrossRefPubMedGoogle Scholar
- 12.Lymphology ISo. The diagnosis and treatment of peripheral lymphedema: 2013 Consensus Document of the International Society of Lymphology. Lymphology. 2013;46:1–11.Google Scholar
- 16.Bourgeois P. Combined role of lymphoscintigraphy, x-ray computed tomography, magnetic resonance imaging, and positron emission tomography in the management of lymphedematous disease. In: Lee B, Bergan J, Rockson S, editors. Lymphedema. London: Springer; 2011.Google Scholar
- 18.Cavezzi A. Duplex ultrasonography. In: Lee B, Bergan J, Rockson S, editors. Lymphedema. London: Springer; 2011.Google Scholar
- 22.Krasnow A, Elgazzar A, Kazem N. Lymphoscintigraphy. In: Elgazzar A, editor. The pathophysiologic basis of nuclear medicine. Berlin, Heidelberg: Springer; 2006.Google Scholar
- 24.•• O’Donnell T, Rasmussen J, Sevick-Muraca E. New diagnostic modalities in the evaluation of lymphedema. J Vasc Surg Venous Lymphat Disord. 2017;5:261–73. https://doi.org/10.1016/j.jvsv.2016.10.083This review examines new diagnostic modalities for evaluating lymphedema and evaluates the utility of each modality. The strength of the literature in support of each modality offers helpful context for physicians to decide which modality to apply in individual patient cases. CrossRefPubMedPubMedCentralGoogle Scholar
- 25.Allegra C, Bartolo M, Carlizza A. Fluorescent microlymphaniography. In: Lee B, Bergan J, Rockson S, editors. Lymphedema. London: Springer; 2011.Google Scholar
- 33.• Qin E, Bowen M, James S, Chen W. Multi-segment bioimpedance can assess patients with bilateral lymphedema. J Plast Reconstr Aesthet Surg. 2019. https://doi.org/10.1016/j.bjps.2019.06.041This single institution study examined the role of bioimpedance spectroscopy as a lymphedema diagnostic modality. Single-segment bioimpedance (SSB) was more sensitive than multi-segment impedance (MSB) for diagnosing unilateral lymphedema, while MSB had greater sensitivity and specificity for diagnosing bilateral lymphedema. Moreover, MSB was found to be easier to perform and therefore adapted in the authors’ department practice.
- 35.Rasmussen J, Aldrich M, Tan I, Darne C, Zhu B, O’Donnell TJ, et al. Lymphatic transport in patients with chronic venous insufficiency and venous leg ulcers following sequential pneumatic compression. J Vasc Surg Venous Lymphat Disord. 2016;4:9–17. https://doi.org/10.1016/j.jvsv.2015.06.001.CrossRefPubMedGoogle Scholar
- 39.Cau N, Galli M, Cimolin V, Grossi A, Battarin I, Puleo G, et al. Quantitative comparison between the laser scanner three-dimensional method and the circumferential method for evaluation of arm volume in patients with lymphedema. J Vasc Surg Venous Lymphat Disord. 2017;6:96–103. https://doi.org/10.1016/j.jvsv.2017.08.014.CrossRefGoogle Scholar
- 40.Cau N, Galli M, Cimolin V, Aranci M, Caraceni A, Balzarini A. Comparative study between circumferential method and laser scanner 3D method for the evaluation of arm volume in healthy subjects. J Vasc Surg: Venous and Lymphat Disord. 2016;4:64–72. https://doi.org/10.1016/j.jvsv.2015.05.005.CrossRefGoogle Scholar
- 42.Gjorup C, Zerahn B, Hendel H. Assessment of volume measurement of breast cancer-related lymphedema by three methods: circumference measurement, water displacement, and dual energy X-ray absorptiometry. Lymphat Res Biol. 2010;8:111–9. https://doi.org/10.1089/lrb.2009.0016.CrossRefPubMedGoogle Scholar
- 45.Hayashi A, Giacalone G, Yamamoto T, Belva F, Visconti G, Hayashi N, et al. Ultra high-frequency ultrasonographic imaging with 70 MHz scanner for visualization of the lymphatic vessels. Plast Reconstr Surg Glob Open. 2019;7:e2086. https://doi.org/10.1097/GOX.0000000000002086.CrossRefPubMedPubMedCentralGoogle Scholar
- 49.Muller A, Fries P, Jelvani B, Lux F, Rube C, Kremp S, et al. Magnetic resonance lymphography at 9.4T using a gadolinium-based nanoparticle in rats: investigations in healthy animals and in a hindlimb lymphedema model. Investig Radiol. 2017;52:725–33. https://doi.org/10.1097/RLI.0000000000000398.CrossRefGoogle Scholar
- 50.Taradaj J, Rosinczuk J, Dymarek R, Halski T, Schneider W. Comparison of efficacy of the intermittent pneumatic compression with a high- and low-pressure application in reducing the lower limbs phlebolymphedema. Ther Clin Risk Manag. 2015;11:1545–54. https://doi.org/10.2147/TCRM.S92121.CrossRefPubMedPubMedCentralGoogle Scholar
- 51.Adams K, Rasmussen J, Darne C, Tan I, Aldrich M, Marshall M, et al. Direct evidence of lymphatic function improvement after advanced pneumatic compression device treatment of lymphedema. Biomed Opt Express. 2010;1:114–25. https://doi.org/10.1364/BOE.1.000114.CrossRefPubMedPubMedCentralGoogle Scholar
- 52.Brayton K, Hirsch A, O Brien P, Cheville A, Karaca-Mandic P, Rockson S. Lymphedema prevalence and treatment benefits in cancer: impact of a therapeutic intervention on health outcomes and costs. PLoS One. 2014;9:e114597. https://doi.org/10.1371/journal.pone.0114597.CrossRefPubMedPubMedCentralGoogle Scholar