Skip to main content

Advertisement

SpringerLink
Log in

The Diagnostic Approach to Lymphedema: a Review of Current Modalities and Future Developments

  • Hot Topics in Breast Cancer (K Hunt, Section Editor)
  • Published:
Current Breast Cancer Reports Aims and scope Submit manuscript

Abstract

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.

Recent Findings

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).

Summary

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  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.

  2. Lawenda B, Mondry T, Johnstone P. Lymphedema: a primer on the identification and management of a chronic condition in oncologic treatment. CA Cancer J Clin. 2009;59:8–24. https://doi.org/10.3322/caac.20001.

    Article  PubMed  Google Scholar 

  3. Mak S, Yeo W, Lee Y, Mo K, Tse K, Tse S, et al. Predictors of lymphedema in patients with breast cancer undergoing axillary lymph node dissection in Hong Kong. Nurs Res. 2008;57:416–25. https://doi.org/10.1097/NNR.0b013e31818c3de2.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  5. Morrell R, Halyard M, Schild S, Ali M, Gunderson L, Pockaj B. Breast cancer-related lymphedema. Mayo Clin Proc. 2005;80:1480–4. https://doi.org/10.4065/80.11.1480.

    Article  PubMed  Google 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.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Scallan J, Zawieja S, Castorena-Gonzalez J, Davis M. Lymphatic pumping: mechanics, mechanisms and malfunction. J Physiol. 2016;594:5749–68. https://doi.org/10.1113/JP272088.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Hancock D, Potezny T, White P. The peripheral lymphatics as an active player in the immune response. J Clin Cell Immunol. 2014;5:268. https://doi.org/10.4172/2155-9899.1000268.

    Article  Google 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.

    Article  CAS  PubMed  PubMed Central  Google 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.

    Article  CAS  PubMed  Google 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 

  13. Schook C, Mulliken J, Fishman S, Grant F, Zurakowski D, Greene A. Primary lymphedema: clinical features and management in 138 pediatric patients. Plast Reconstr Surg. 2011;127:2419–31. https://doi.org/10.1097/PRS.0b013e318213a218.

    Article  CAS  PubMed  Google Scholar 

  14. Shin S, Lee W, Park E, Shin C, Chung J, Park J. Comparison of characteristic CT findings of lymphedema, cellulitis, and generalized edema in lower leg swelling. Int J Card Imaging. 2013;29:135–43. https://doi.org/10.1007/s10554-013-0332-5.

    Article  Google Scholar 

  15. Liu N, Wang C, Sun M. Noncontrast three-dimensional magnetic resonance imaging vs lymphoscintigraphy in the evaluation of lymph circulation disorders: a comparative study. J Vasc Surg. 2005;41:69–75. https://doi.org/10.1016/j.jvs.2004.11.013.

    Article  PubMed  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 

  17. Nishiyama Y, Yamamoto Y, Mori Y, Satoh K, Takashamia H, Ohkawa M, et al. Usefulness of Technetium-99m human serum albumin lymphoscintigraphy in chyluria. Clin Nucl Med. 1998;23:429–31. https://doi.org/10.1097/00003072-199807000-00006.

    Article  CAS  PubMed  Google Scholar 

  18. Cavezzi A. Duplex ultrasonography. In: Lee B, Bergan J, Rockson S, editors. Lymphedema. London: Springer; 2011.

    Google Scholar 

  19. Cammarota T, Pinto F, Magliaro A, Sarno A. Current uses of diagnostic high-frequency US in dermatology. Eur J Radiol. 1998;27:S215–S23. https://doi.org/10.1016/S0720-048X(98)00065-5.

    Article  PubMed  Google Scholar 

  20. Matter D, Grosshans E, Muller J, Furderer C, Mathelin C, Warter S, et al. Sonographic imaging of lymphatic vessels compared to other methods. J Radiol. 2002;83:599–609.

    CAS  PubMed  Google Scholar 

  21. Suehiro K, Morikage N, Murakami M, Yamashita O, Samura M, Hamano K. Significance of ultrasound examination of skin and subcutaneous tissue in secondary lower extremity lymphedema. Ann Vasc Dis. 2013;6:180–8. https://doi.org/10.3400/avd.oa.12.00102.

    Article  PubMed  PubMed Central  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 

  23. Ohtake E, Matsui K. Lymphoscintigraphy in patients with lymphedema: a new approach using intradermal injections of technetium-99m human serum albumin. Clin Nucl Med. 1986;11:474–8.

    Article  CAS  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.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Allegra C, Bartolo M, Carlizza A. Fluorescent microlymphaniography. In: Lee B, Bergan J, Rockson S, editors. Lymphedema. London: Springer; 2011.

    Google Scholar 

  26. Mulasi U, Kuchnia A, Cole A, Earthman C. Bioimpedance at the bedside: current applications, limitations, and opportunitie. Nutr Clin Pract. 2015;30:180–93. https://doi.org/10.1177/0884533614568155.

    Article  PubMed  Google Scholar 

  27. Cornish B, Chapman M, Hirst C, Mirolo B, Bunce I, Ward L, et al. Early diagnosis of lymphedema using multiple frequency bioimpedance. Lymphology. 2001;34:2–11.

    CAS  PubMed  Google Scholar 

  28. Czerniec S, Ward L, Lee M, Refshauge K, Beith J, Kilbreath S. Segmental measurement of breast cancer-related arm lymphoedema using perometry and bioimpedance spectroscopy. Support Care Cancer. 2011;19:703–10. https://doi.org/10.1007/s00520-010-0896-8.

    Article  PubMed  Google Scholar 

  29. Ward L. Bioelectrical impedance analysis: proven utility in lymphedema risk assessment and therapeutic monitoring. Lymphat Res Biol. 2006;4:51–6. https://doi.org/10.1089/lrb.2006.4.51.

    Article  PubMed  Google Scholar 

  30. Cornish B, Thomas B, Ward L. Improved prediction of extracellular and total body water using impedance loci generated by multiple frequency bioelectrical impedance analysis. Phys Med Biol. 1993;38:337–46. https://doi.org/10.1088/0031-9155/38/3/001.

    Article  CAS  PubMed  Google Scholar 

  31. Cornish B, Bunce I, Ward L, Jones L, Thomas B. Bioelectrical impedance for monitoring the efficacy of lymphoedema treatment programmes. Breast Cancer Res Treat. 1996;38:169–76. https://doi.org/10.1007/BF01806671.

    Article  CAS  PubMed  Google Scholar 

  32. Ward L, Dylke E, Czerniec S, Isenring E, Kilbreath S. Confirmation of the reference impedance ratios used for assessment of breast cancer-related lymphedema by bioelectrical impedance spectroscopy. Lymphat Res Biol. 2011;9:47–51. https://doi.org/10.1089/lrb.2010.0014.

    Article  CAS  PubMed  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.

  34. Maus E, Tan I, Rasmussen J, Marshall M, Fife C, Smith L, et al. Near-infrared fluorescence imaging of lymphatics in head and neck lymphedema. Head Neck. 2012;34:448–53. https://doi.org/10.1002/hed.21538.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  36. Zhu B, Rasmussen J, Litorja M, Sevick-Muraca E. Determining the performance of fluorescence molecular imaging devices using traceable working standards with SI units of radiance. IEEE Trans Med Imaging. 2016;35:802–11. https://doi.org/10.1109/TMI.2015.2496898.

    Article  PubMed  Google Scholar 

  37. Deltombe T, Jamart J, Recloux S, Legrand C, Vandenbroeck N, Theys S, et al. Reliability and limits of agreement of circumferential, water displacement, and optoelectronic volumetry in the measurement of upper limb lymphedema. Lymphology. 2007;40:26–34.

    CAS  PubMed  Google Scholar 

  38. Stout Gergich N, Pfalzer L, McGarvey C, Springer B, Gerber L, Soballe P. Preoperative assessment enables the early diagnosis and successful treatment of lymphedema. Cancer. 2008;112:2809–19. https://doi.org/10.1002/cncr.23494.

    Article  PubMed  Google 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.

    Article  Google 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.

    Article  Google Scholar 

  41. Gjorup C, Zerahn B, Juul S, Hendel H, Christensen K, Holmich L. Repeatability of volume and regional body composition measurements of the lower limb using dual-energy x-ray absorptiometry. J Clin Densitom. 2017;20:82–96. https://doi.org/10.1016/j.jocd.2016.08.009.

    Article  PubMed  Google 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.

    Article  PubMed  Google Scholar 

  43. Hayashi A, Yamamoto T, Yoshimatsu H, Hayashi N, Furuya M, Harima M, et al. Ultrasound visualization of the lymphatic vessels in the lower leg. Microsurgery. 2016;36:397–401. https://doi.org/10.1002/micr.22414.

    Article  PubMed  Google Scholar 

  44. Hayashi A, Hayashi N, Yoshimatsu H, Yamamoto T. Effective and efficient lymphaticovenular anastomosis using preoperative ultrasound detection technique of lymphatic vessels in lower extremity lymphedema. J Surg Oncol. 2018;117:290–8. https://doi.org/10.1002/jso.24812.

    Article  PubMed  Google 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.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Grassi R, Lagalla R, Rotondo A. Genomics, proteomics, MEMS and SAIF: which role for diagnostic imaging? Radiol Med. 2008;113:775–8. https://doi.org/10.1007/s11547-008-0309-y.

    Article  CAS  PubMed  Google Scholar 

  47. Grassi R, Cavaliere C, Cozzolino S, Mansi L, Cirillo S, Tedeschi G, et al. Small animal imaging facility: new perspectives for the radiologist. Radiol Med. 2009;114:152–67. https://doi.org/10.1007/s11547-008-0352-8.

    Article  CAS  PubMed  Google Scholar 

  48. Lux F, Mignot A, Mowat P, Louis C, Dufort S, Bernhard C, et al. Ultrasmall rigid particles as multimodal probes for medical applications. Angew Chem Int Ed Eng. 2011;50:12299–303. https://doi.org/10.1002/anie.201104104.

    Article  CAS  Google 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.

    Article  Google 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.

    Article  PubMed  PubMed Central  Google 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.

    Article  PubMed  PubMed Central  Google 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Mayrovitz H, Ryan S, Hartman J. Usability of advanced pneumatic compression to treat cancer-related head and neck lymphedema: a feasibility study. Head Neck. 2018;40:137–43. https://doi.org/10.1002/hed.24995.

    Article  PubMed  Google Scholar 

  54. Chang C, Cormier J. Lymphedema interventions: exercise, surgery, and compression devices. Semin Oncol Nurs. 2013;29:28–40. https://doi.org/10.1016/j.soncn.2012.11.005.

    Article  PubMed  Google Scholar 

  55. Melam G, Buragadda S, Alhusaini A, Arora N. Effect of complete decongestive therapy and home program on health- related quality of life in post mastectomy lymphedema patients. BMC Womens Health. 2016;16:23. https://doi.org/10.1186/s12905-016-0303-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Szuba A, Achalu R, Rockson S. Decongestive lymphatic therapy for patients with breast carcinoma-associated lymphedema: a randomized, prospective study of a role for adjunctive intermittent pneumatic compression. Cancer. 2002;95:2260–7. https://doi.org/10.1002/cncr.10976.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Plastic and Reconstructive Surgery, Department of Surgery, Keck School of Medicine, University of Southern California, 1510 San Pablo Street, Suite 415, Los Angeles, CA, 90033-4580, USA

    Anjali C. Raghuram, Roy P. Yu, Cynthia Sung, Sherry Huang & Alex K. Wong

Authors
  1. Anjali C. Raghuram
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Roy P. Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Cynthia Sung
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sherry Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Alex K. Wong
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alex K. Wong.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Hot Topics in Breast Cancer

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Raghuram, A.C., Yu, R.P., Sung, C. et al. The Diagnostic Approach to Lymphedema: a Review of Current Modalities and Future Developments. Curr Breast Cancer Rep 11, 365–372 (2019). https://doi.org/10.1007/s12609-019-00341-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12609-019-00341-3

Keywords

Search

Navigation