Home Lymph node ultrasound in lymphoproliferative disorders: clinical characteristics and applications
Article
Licensed
Unlicensed Requires Authentication

Lymph node ultrasound in lymphoproliferative disorders: clinical characteristics and applications

  • Rita Tavarozzi ORCID logo , Anna Lombardi ORCID logo EMAIL logo , Ferdinando Scarano , Laura Staiano , Gerardo Trattelli , Michela Farro , Alessia Castellino and Carmine Coppola
Published/Copyright: June 3, 2025

Abstract

Introduction

Superficial lymph node (LN) enlargement is a common ultrasonographic finding and can be associated with a broad spectrum of conditions, from benign reactive hyperplasia to malignant lymphoproliferative disorders (LPDs). LPDs, which include various hematologic malignancies affecting lymphoid tissue, present with diverse immune-morphological and clinical features, making differentiation from other malignant causes of lymphadenopathy challenging. 

Content

Radiologic assessment is crucial in characterizing lymphadenopathy, with ultrasonography serving as a noninvasive and widely available imaging modality. High-resolution ultrasound allows the evaluation of key features such as LN size, shape, border definition, echogenicity, and the presence of abnormal cortical thickening, loss of the fatty hilum, or altered vascular patterns, which aid in distinguishing benign from malignant processes.

Summary

This review aims to describe the ultrasonographic characteristics of lymphadenopathy, offering essential diagnostic insights to differentiate malignant disorders, particularly LPDs. We will discuss standard ultrasound techniques, including grayscale imaging and Doppler ultrasound, and explore more advanced methods such as contrast-enhanced ultrasound (CEUS), elastography, and artificial intelligence–assisted imaging, which are gaining prominence in LN evaluation.

Outlook

By highlighting these imaging modalities, we aim to enhance the diagnostic accuracy of ultrasonography in lymphadenopathy assessment and improve early detection of LPDs and other malignant conditions.


Corresponding author: Anna Lombardi, Department of Translational Medical Sciences, Federico II University Hospital, Napoli, Italy, E-mail:
Rita Tavarozzi and Anna Lombardi contributed equally to this work.
  1. Research ethics: Not applicable.

  2. Informed consent: Not applicable.

  3. Author contributions: RT, AL: wrote the manuscript and collected figures. All the authors: approved the manuscript and revised literature.

  4. Use of Large Language Models, AI and Machine Learning Tools: None declared.

  5. Conflict of interest: The authors state no conflict of interest.

  6. Research funding: None declared.

  7. Data availability: Not applicable.

References

1. Swerdlow, SH, Campo, E, Pileri, SA, Harris, NL, Stein, H, Siebert, R, et al.. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 2016;127:2375–90. https://doi.org/10.1182/blood-2016-01-643569.Search in Google Scholar PubMed PubMed Central

2. Barrington, SF, Mikhaeel, NG, Kostakoglu, L, Meignan, M, Hutchings, M, Müeller, SP, et al.. Role of imaging in the staging and response assessment of lymphoma: consensus of the International Conference on Malignant Lymphomas Imaging Working Group. J Clin Oncol 2014;32:3048–58. https://doi.org/10.1200/jco.2013.53.5229.Search in Google Scholar

3. Cheson, BD, Fisher, RI, Barrington, SF, Cavalli, F, Schwartz, LH, Zucca, E, et al.. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol 2014;32:3059–68. https://doi.org/10.1200/jco.2013.54.8800.Search in Google Scholar PubMed PubMed Central

4. Pugliese, N, Di Perna, M, Cozzolino, I, Ciancia, G, Pettinato, G, Zeppa, P, et al.. Randomized comparison of power Doppler ultrasonography-guided core-needle biopsy with open surgical biopsy for the characterization of lymphadenopathies in patients with suspected lymphoma. Ann Hematol 2017;96:627–37. https://doi.org/10.1007/s00277-017-2926-9.Search in Google Scholar PubMed PubMed Central

5. Guttikonda, R, Herts, BR, Dong, F, Baker, ME, Fenner, KB, Pohlman, B. Estimated radiation exposure and cancer risk from CT and PET/CT scans in patients with lymphoma. Eur J Radiol 2014;83:1011–15. https://doi.org/10.1016/j.ejrad.2014.02.015.Search in Google Scholar PubMed

6. Haar, GT. Ultrasonic imaging: safety considerations. Interface Focus 2011;1:686–97. https://doi.org/10.1098/rsfs.2011.0029.Search in Google Scholar PubMed PubMed Central

7. Cui, XW, Hocke, M, Jenssen, C, Ignee, A, Klein, S, Schreiber-Dietrich, D, et al.. Conventional ultrasound for lymph node evaluation, update 2013. Z Gastroenterol 2014;52:212–21. https://doi.org/10.1055/s-0033-1356153.Search in Google Scholar PubMed

8. Dudea, SM, Lenghel, M, Botar-Jid, C, Vasilescu, D, Duma, M. Ultrasonography of superficial lymph nodes: benign vs. malignant. Med Ultrason 2012;14:294–306.Search in Google Scholar

9. Yingb, M, Phil, M, Ahuja, A. Diagnostic accuracy of sonographic criteria for evaluation of cervical lymphadenopathy. J Ultrasound Med 1998;17:437–45. https://doi.org/10.7863/jum.1998.17.7.437.Search in Google Scholar PubMed

10. Regmi, D, Lohani, B, Kayastha, P, Shreevastav, S, Paudel, S, Jha, SK, et al.. Comparison of gray scale and color Doppler sonography with cytopathology findings in cervical lymphadenopathy in tertiary level hospital. Nepal J Radiol 2019;9:10–16. https://doi.org/10.3126/njr.v9i2.27414.Search in Google Scholar

11. Ahuja, AT, Ying, M, Ho, SY, Antonio, G, Lee, YP, King, AD, et al.. Ultrasound of malignant cervical lymph nodes. Cancer Imaging 2008;8:48–56. https://doi.org/10.1102/1470-7330.2008.0006.Search in Google Scholar PubMed PubMed Central

12. DePena, CA, Van Tassel, P, Lee, YY. Lymphoma of the head and neck. Radiol Clin 1990;28:723. https://doi.org/10.1016/s0033-8389(22)01257-x.Search in Google Scholar

13. Bruneton, JN, Normand, F, Balu-Maestro, C, Kerboul, P, Santini, N, Thyss, A, et al.. Lymphomatous superficial lymph nodes: US detection. Radiology 1987;165:233. https://doi.org/10.1148/radiology.165.1.3306785.Search in Google Scholar PubMed

14. Ho, SS, Ahuja, AT, Yeo, W, Chan, TC, Kew, J, Metreweli, C. Longitudinal colour Doppler study of superficial lymph nodes in non- Hodgkin’s lymphoma patients on chemotherapy. Clin Radiol 2000;55:110. https://doi.org/10.1053/crad.1999.0229.Search in Google Scholar PubMed

15. Solbiati, L, Rizatto, G, Bellotti, E, Montali, G, Cioffi, V, Croce, F. High resolution sonography of cervical lymph nodes in head and neck cancer: criteria for differentiation of reactive versus malignant nodes. Radiology 1988;169:113.Search in Google Scholar

16. Ahuja, AT, Ying, M. Sonographic evaluation of cervical lymph nodes. Am J Roentgenol 2005;184:1691–9. https://doi.org/10.2214/ajr.184.5.01841691.Search in Google Scholar PubMed

17. Khanna, R, Sharma, AD, Khanna, S, Kumar, M, Shukla, RC. Usefulness of ultrasonography for the evaluation of cervical lymphadenopathy. World J Surg Oncol 2011;9:29. https://doi.org/10.1186/1477-7819-9-29.Search in Google Scholar PubMed PubMed Central

18. Steinkamp, HJ, Hosten, N, Richter, C, Schedel, H, Felix, R. Enlarged cervical lymph nodes at helical CT. Radiology 1994;191:795–8. https://doi.org/10.1148/radiology.191.3.8184067.Search in Google Scholar PubMed

19. Vassallo, P, Wernecke, K, Roos, N, Peters, PE. Differentiation of benign from malignant superficial lymphadenopathy: the role of high-resolution US. Radiology 1992;183:215–20. https://doi.org/10.1148/radiology.183.1.1549675.Search in Google Scholar PubMed

20. Sumi, M, Ohki, M, Nakamura, T. Comparison of sonography and CT for differentiating benign from malignant cervical lymph nodes in patients with squamous cell carcinoma of the head and neck. Am J Roentgenol 2001;176:1019–24. https://doi.org/10.2214/ajr.176.4.1761019.Search in Google Scholar PubMed

21. Saiag, P, Bernard, M, Beauchet, A, Bafounta, ML, Bourgault- Villada, I, Chagnon, S. Ultrasonography using simple di- agnostic criteria vs palpation for the detection of regional lymph node metastases of melanoma. Arch Dermatol 2005;141:183–9. https://doi.org/10.1001/archderm.141.2.183.Search in Google Scholar PubMed

22. Shozushima, M, Suzuki, M, Nakasima, T, Yanagisawa, Y, Sakamaki, K, Takeda, Y. Ultrasound diagnosis of lymph node metastasis in head and neck cancer. Dentomaxillofacial Radiol 1990;19:165–70. https://doi.org/10.1259/dmfr.19.4.2097226.Search in Google Scholar PubMed

23. Steinkamp, HJ, Beck, A, Werk, M, Rademaker, J, Felix, R. Extracapsular spread of cervical lymph node metastases: diagnostic relevance of ultrasound examinations. Ultraschall Med 2003;24:323–30. https://doi.org/10.1055/s-2003-42914.Search in Google Scholar PubMed

24. Som, PM. Lymph nodes of the neck. Radiology 1987;165:593–600. https://doi.org/10.1148/radiology.165.3.3317494.Search in Google Scholar PubMed

25. Abdelgawad, EA, Abu-samra, MF, Abdelhay, NM, Abdel-Azeem, HM. B-mode ultrasound, color Doppler, and sonoelastography in differentiation between benign and malignant cervical lymph nodes with special emphasis on sonoelastography. Egypt J Radiol Nucl Med 2020;51:157. https://doi.org/10.1186/s43055-020-00273-4.Search in Google Scholar

26. Ariji, Y, Kimura, Y, Hayashi, N, Onitsuka, T, Yonetsu, K, Hayashi, K, et al.. Power Doppler sonography of cervical lymphnodes in patients with head and neck cancer. Am J Neuroradiol 1998;19:303–7.Search in Google Scholar

27. Steinkamp, HJ, Wissgott, C, Rademaker, J, Felix, R. Current status of power Doppler and color Doppler sonography in the differential diagnosis of lymph node lesions. Eur Radiol 2002;12:1785–93. https://doi.org/10.1007/s003300101111.Search in Google Scholar PubMed

28. Steinkamp, HJ, Teichgraber, UK, Mueffelmann, M, Hosten, N, Kenzel, P, Felix, R. Differential diagnosis of lymph node lesions. A semiquantitative approach with power Doppler sonography. Investig Radiol 1999;34:509–15. https://doi.org/10.1097/00004424-199908000-00003.Search in Google Scholar PubMed

29. Ahuja, AT, Ying, M, Ho, SS, Metreweli, C. Distribution of intranodal vessels in differentiating benign from metastatic neck nodes. Clin Radiol 2001;56:197–201. https://doi.org/10.1053/crad.2000.0574.Search in Google Scholar PubMed

30. Ahuja, A, Ying, M, King, A, Yuen, HY. Lymph node hilus: gray scale and power Doppler sonography of cervical nodes. J Ultrasound Med 2001;20:987–92. https://doi.org/10.7863/jum.2001.20.9.987.Search in Google Scholar PubMed

31. Ying, M, Ahuja, A, Brook, F, Metreweli, C. Vascularity and grey-scale sonographic features of normal cervical lymph nodes: variations with nodal size. Clin Radiol 2001;56:416–19. https://doi.org/10.1053/crad.2000.0680.Search in Google Scholar PubMed

32. Grtizmann, N. Sonography of the neck: current potentials and limitations. Ultraschall Med 2005;26:185–96. https://doi.org/10.1055/s-2005-858271.Search in Google Scholar PubMed

33. Dangore, SB, Degwekar, SS, Bhowate, RR. Evaluation of the efficacy of colour Doppler ultrasound in diagnosis of cervical lymphadenopathy. Dentomaxillofacial Radiol 2008;37:205–12. https://doi.org/10.1259/dmfr/57023901.Search in Google Scholar PubMed

34. Tzankov, A, Heiss, S, Ebner, S, Sterlacci, W, Schaefer, G, Augustin, F, et al.. Angiogenesis in nodal B cell lymphomas: a high throughput study. J Clin Pathol 2007;60:476–82. https://doi.org/10.1136/jcp.2006.038661.Search in Google Scholar PubMed PubMed Central

35. Farinha, P, Kyle, AH, Minchinton, AI, Connors, JM, Karsan, A, Gascoyne, RD. Vascularization predicts overall survival and risk of transformation in follicular lymphoma. Haematologica (Roma) 2010;95:2157–60. https://doi.org/10.3324/haematol.2009.021766.Search in Google Scholar PubMed PubMed Central

36. Na, DG, Lim, HK, Byun, HS, Kim, HD, Ko, YH, Baek, JH. Differential diagnosis of cervical lymphadenopathy: usefulness of color Doppler sonography. Am J Roentgenol 1997;168:1311–16. https://doi.org/10.2214/ajr.168.5.9129432.Search in Google Scholar PubMed

37. Cardesa-Salzmann, TM, Colomo, L, Gutierrez, G, Chan, WC, Weisenburger, D, Climent, F, et al.. High microvessel density determines a poor outcome in patients with diffuse large B-cell lymphoma treated with rituximab plus chemotherapy. Haematologica (Roma) 2011;96:996–1001. https://doi.org/10.3324/haematol.2010.037408.Search in Google Scholar PubMed PubMed Central

38. Xin, L, Yan, Z, Zhang, X, Zang, Y, Ding, Z, Xue, H, et al.. Parameters for contrast-enhanced ultrasound (CEUS) of enlarged superficial lymph nodes for the evaluation of therapeutic response in lymphoma: a preliminary study. Med Sci Monit 2017;23:5430–8. https://doi.org/10.12659/msm.907293.Search in Google Scholar PubMed PubMed Central

39. Lee, YLP, Antonio, GE, Ho, SSY. Serial dynamic sonographic contrast enhancement changes in cervical lymph nodes: before and after treatment for lymphoma. International & 9th National Head and Neck Cancer Conference; 7–11 September 2007; Urumqi, China. 2007.Search in Google Scholar

40. Nie, J, Ling, W, Yang, Q, Jin, H, Ou, X, Ma, X. The value of CEUS in distinguishing cancerous lymph nodes from the primary lymphoma of the head and neck. Front Oncol 2020;10:473. https://doi.org/10.3389/fonc.2020.00473.Search in Google Scholar PubMed PubMed Central

41. Ma, X, Ling, W, Xia, F, Zhang, Y, Zhu, C, He, J. Application of contrast-enhanced ultrasound (CEUS) in lymphomatous lymph nodes: a comparison between PET/CT and contrast-enhanced CT. Contrast Media Mol Imaging 2019;7:5709698. https://doi.org/10.1155/2019/5709698, 2019.Search in Google Scholar PubMed PubMed Central

42. Sigrist, RMS, Liau, J, El Kaffas, A, Cristina Chammas, M, Willmann, JK. Ultrasound elastography: review of techniques and clinical applications. Theranostics 2017;7:1303-29, https://doi.org/10.7150/thno.18650.Search in Google Scholar PubMed PubMed Central

43. Cui, XW, Jenssen, C, Saftoiu, A, Ignee, A, Dietrich, CF. New ultrasound techniques for lymph node evaluation. World J Gastroenterol [Internet] 2013;19:4850–60. https://doi.org/10.3748/wjg.v19.i30.4850.Search in Google Scholar PubMed PubMed Central

44. Wojcinski, S, Dupont, J, Schmidt, W, Cassel, M, Hillemanns, P. Real-time ultrasound elastography in 180 axillary lymph nodes: elasticity distribution in healthy lymph nodes and prediction of breast cancer metastases. BMC Med Imag 2012;12:35. https://doi.org/10.1186/1471-2342-12-35.Search in Google Scholar PubMed PubMed Central

45. Wing-Han, YQ, Zheng, YP, Huang, YP, He, JF, Chung-Wai Cheung, J, Ying, M. In-vitro strain and modulus measurements in porcine cervical lymph nodes. Open Biomed Eng J 2011;5:39–46. https://doi.org/10.2174/1874120701105010039.Search in Google Scholar PubMed PubMed Central

46. Herman, J, Sedlackova, Z, Vachutka, J, Furst, T, Salzman, R, Vomacka, J. Shear wave elastography parameters of normal soft tissues of the neck. Biomed Pap [Internet] 2017;161:320–5. https://doi.org/10.5507/bp.2017.024.Search in Google Scholar PubMed

47. Bhatia, KS, Cho, CC, Tong, CS, Yuen, EH, Ahuja, AT. Shear Wave elasticity imaging of cervical lymph nodes. Ultrasound Med Biol 2011;38:195–201. https://doi.org/10.1016/j.ultrasmedbio.2011.10.024.Search in Google Scholar PubMed

48. Teng, DK, Wang, H, Lin, YQ, Sui, GQ, Guo, F, Sun, LN. Value of ultrasound elastography in assessment of enlarged cervical lymph nodes. Asian Pac J Cancer Prev APJCP 2012;13:2081–5. https://doi.org/10.7314/apjcp.2012.13.5.2081.Search in Google Scholar PubMed

49. Alam, F, Naito, K, Horiguchi, J, Fukuda, H, Tachikake, T. Accuracy of sonographic elastography in the differential diagnosis of enlarged cervical lymph nodes: comparison with conventional B-mode sonography. Am J Roentgenol 2008;191:604–10. https://doi.org/10.2214/ajr.07.3401.Search in Google Scholar PubMed

50. Arda, K, Ciledag, N, Gumusdag, P. Differential diagnosis of malignant cervical lymph nodes at real-time ultrasonographic elastography and Doppler ultrasonography. Magyar Radiol Online 2006;6:10–13.Search in Google Scholar

51. Ying, L, Hou, Y, Zheng, H-M, Lin, X, Xie, ZL, Hu, YP. Real-time elastography for the differentiation of benign and malignant superficial lymph nodes: a meta-analysis. Eur J Radiol 2012;81:2576–84. https://doi.org/10.1016/j.ejrad.2011.10.026.Search in Google Scholar PubMed

52. Lo, W-C, Cheng, P-W, Wang, C-T, Liao, LJ. Real-time ultrasound elastography: an assessment of enlarged cervical lymph nodes. Eur Radiol 2013;23:2351–7. https://doi.org/10.1007/s00330-013-2861-7.Search in Google Scholar PubMed

53. Shibashi, N, Yamagata, K, Sasaki, H, Seto, K, Shinya, Y, Ito, H, et al.. Realtime tissue elastography for the diagnosis of lymph node metastasis in oral squamous cell carcinoma. Ultrasound Med Biol 2012;38:389–95. https://doi.org/10.1016/j.ultrasmedbio.2011.12.004.Search in Google Scholar PubMed

54. Furukawa, MK, Kubota, A, Hanamura, H. Clinical application of real-time tissue elastography to head and neck cancer--evaluation of cervical lymph node metastasis with real-time tissue elastography. Nihon Jibiinkoka Gakkaikaiho 2007;110:503–5. https://doi.org/10.3950/jibiinkoka.110.503.Search in Google Scholar PubMed

55. Choi, JJ, Kang, BJ, Kim, SH, Lee, JH, Jeong, SH, Yim, HW, et al.. Role of sonographic elastography in the differential diagnosis of axillary lymph nodes in breast cancer. J Ultrasound Med 2011;30:429–36. https://doi.org/10.7863/jum.2011.30.4.429.Search in Google Scholar PubMed

56. E Squillaci, M Antonicoli, G Manenti, F Bolacchi. Real-time ultrasound elastography for assessment of response to brentuximab vedotin treatment in relapsed and refractory Hodgkin lymphoma. Eur Rev Med Pharmacol Sci 2016;20:1628–35.Search in Google Scholar

57. Suh, CH, Choi, YJ, Baek, JH, Lee, JH. The diagnostic performance of shear wave elastography for malignant cervical lymph nodes: a systematic review and meta-analysis. Eur Radiol 2017;27:222–30. https://doi.org/10.1007/s00330-016-4378-3.Search in Google Scholar PubMed

58. Bayramoglu, Z, Caliskan, E, Karakas, Z, Karaman, S, Tugcu, D, Somer, A, et al.. Diagnostic performances of superb microvascular imaging, shear wave elastography and shape index in pediatric lymph nodes categorization: a comparative study. Br J Radiol 2018;91:20180129. https://doi.org/10.1259/bjr.20180129.Search in Google Scholar PubMed PubMed Central

59. Łasecki, M, Olchowy, C, Sokołowska-Dąbek, D, Biel, A, Chaber, R, Zaleska-Dorobisz, U. Modified sonoelastographic scale score for lymph node assessment in lymphoma – a preliminary report. Journal of Ultrasonography 2015;15:45–55. https://doi.org/10.15557/jou.2015.0004.Search in Google Scholar PubMed PubMed Central

60. Chae, SY, Jung, HN, Ryoo, I, Suh, S. Differentiating cervical metastatic lymphadenopathy and lymphoma by shear wave elastography. Sci Rep 2019;9:12396. https://doi.org/10.1038/s41598-019-48705-0.Search in Google Scholar PubMed PubMed Central

61. Cosgrove, D, Piscaglia, F, Bamber, J, Bojunga, J, Correas, JM, Gilja, OH, et al.. EFSUMB Guidelines and Recommendations on the clinical use of ultrasound elastography part 2: clinical applications. Ultraschall Med 2013;34:238–53. https://doi.org/10.1055/s-0033-1335375.Search in Google Scholar PubMed

62. Kurt, A, Gunes Tatar, I, Ipek, A, Hekimoglu, B. B-mode and elastosonographic evaluation to determine the reference Elastosonography values for cervical lymph nodes. ISRN Radiol 2013;2013:1–4. https://doi.org/10.5402/2013/895287.Search in Google Scholar PubMed PubMed Central

63. Christensen-Jeffries, K, Couture, O, Dayton, PA, Eldar, YC, Hynynen, K, Kiessling, F, et al.. Super-resolution ultrasound imaging. Ultrasound Med Biol 2020;46:865–91. https://doi.org/10.1016/j.ultrasmedbio.2019.11.013.Search in Google Scholar PubMed PubMed Central

64. Zhu, J, Zhang, C, Christensen-Jeffries, K, Zhang, G, Harput, S, Dunsby, C, et al.. Super-resolution ultrasound localization microscopy of microvascular structure and flow for distinguishing metastatic lymph nodes - an initial human study. Ultraschall Med 2022;43:592–8. https://doi.org/10.1055/a-1917-0016.Search in Google Scholar PubMed

Received: 2025-05-07
Accepted: 2025-05-13
Published Online: 2025-06-03

© 2025 Walter de Gruyter GmbH, Berlin/Boston

Downloaded on 20.10.2025 from https://www.degruyterbrill.com/document/doi/10.1515/jbcpp-2025-0089/html
Scroll to top button