Skip to main content

Defining the role of modern imaging techniques in assessing lymph nodes for metastasis in cancer: evolving contribution of PET in this setting

European Journal of Nuclear Medicine and Molecular Imaging volume 38, pages 1353–1366 (2011)Cite this article

Abstract

Accurate characterization of lymph nodes in patients with cancer and in patients who present with unexplained lymphadenopathy is of major importance for appropriate treatment planning and determination of prognosis. Size measurements are still the most frequently used method for discriminating malignant from non-malignant lymph nodes, but are insufficiently accurate. In order to improve evaluation of lymph nodes, there is a need for imaging modalities that go beyond anatomical lymph node assessment and that allow visualization and quantification of physiological and biochemical processes at the cellular level. We review and discuss functional imaging techniques in the evaluation of lymph nodes.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

References

  1. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60:277–300.

    PubMed  Article  Google Scholar 

  2. Ioachim HL, Medeiros LJ. Ioachim's lymph node pathology, 4th.edn. Philadelphia, PA: Lippincott Williams and Wilkins; 2009.

  3. Allaf ME, Partin AW, Carter HB. The importance of pelvic lymph node dissection in men with clinically localized prostate cancer. Rev Urol. 2006;8:112–9.

    PubMed  Google Scholar 

  4. McLaughlin SA, Wright MJ, Morris KT, Giron GL, Sampson MR, Brockway JP, et al. Prevalence of lymphedema in women with breast cancer 5 years after sentinel lymph node biopsy or axillary dissection: objective measurements. J Clin Oncol. 2008;26:5213–9.

    PubMed  Article  Google Scholar 

  5. Del Bianco P, Zavagno G, Burelli P, Scalco G, Barutta L, Carraro P, et al. GIVOM. Morbidity comparison of sentinel lymph node biopsy versus conventional axillary lymph node dissection for breast cancer patients: results of the sentinella-GIVOM Italian randomised clinical trial. Eur J Surg Oncol. 2008;34:508–13.

    PubMed  Google Scholar 

  6. Schröder W, Baldus SE, Mönig SP, Beckurts TK, Dienes HP, Hölscher AH. Lymph node staging of esophageal squamous cell carcinoma in patients with and without neoadjuvant radiochemotherapy: histomorphologic analysis. World J Surg. 2002;26:584–7.

    PubMed  Article  Google Scholar 

  7. Mönig SP, Zirbes TK, Schröder W, Baldus SE, Lindemann DG, Dienes HP, et al. Staging of gastric cancer: correlation of lymph node size and metastatic infiltration. AJR Am J Roentgenol. 1999;173:365–7.

    PubMed  Google Scholar 

  8. Mönig SP, Baldus SE, Zirbes TK, Schröder W, Lindemann DG, Dienes HP, et al. Lymph node size and metastatic infiltration in colon cancer. Ann Surg Oncol. 1999;6:579–81.

    PubMed  Article  Google Scholar 

  9. Prenzel KL, Mönig SP, Sinning JM, Baldus SE, Brochhagen HG, Schneider PM, et al. Lymph node size and metastatic infiltration in non-small cell lung cancer. Chest. 2003;123:463–7.

    PubMed  Article  Google Scholar 

  10. Willard-Mack CL. Normal structure, function, and histology of lymph nodes. Toxicol Pathol. 2006;34:409–24.

    PubMed  Article  Google Scholar 

  11. Castenholz A. Architecture of the lymph node with regard to its function. In: Grundmann E, Vollmer E, editors. Reaction patterns of the lymph node. Part 1 Cell types and functions. Berlin Heidelberg: Springer-Verlag; 1990. p. 2–8.

    Google Scholar 

  12. Semeraro D, Davies JD. The arterial blood supply of human inguinal and mesenteric lymph nodes. J Anat. 1986;144:221–33.

    PubMed  CAS  Google Scholar 

  13. Yin T, Ji XL, Shen MS. Relationship between lymph node sinuses with blood and lymphatic metastasis of gastric cancer. World J Gastroenterol. 2003;9:40–3.

    PubMed  Google Scholar 

  14. Hoshida T, Isaka N, Hagendoorn J, di Tomaso E, Chen YL, Pytowski B, et al. Imaging steps of lymphatic metastasis reveals that vascular endothelial growth factor-C increases metastasis by increasing delivery of cancer cells to lymph nodes: therapeutic implications. Cancer Res. 2006;66:8065–75.

    PubMed  Article  CAS  Google Scholar 

  15. Qian CN, Berghuis B, Tsarfaty G, Bruch M, Kort EJ, Ditlev J, et al. Preparing the "soil": the primary tumor induces vasculature reorganization in the sentinel lymph node before the arrival of metastatic cancer cells. Cancer Res. 2006;66:10365–76.

    PubMed  Article  CAS  Google Scholar 

  16. Harrell MI, Iritani BM, Ruddell A. Tumor-induced sentinel lymph node lymphangiogenesis and increased lymph flow precede melanoma metastasis. Am J Pathol. 2007;170:774–86.

    PubMed  Article  Google Scholar 

  17. Morgan-Parkes JH. Metastases: mechanisms, pathways, and cascades. AJR Am J Roentgenol. 1995;164:1075–82.

    PubMed  CAS  Google Scholar 

  18. Ohtake K, Shingaki S, Nakajima T. Histologic study on the metastatic process in the experimental model of lymph node metastasis. Oral Surg Oral Med Oral Pathol. 1993;75:472–8.

    PubMed  Article  CAS  Google Scholar 

  19. Naresh KN, Nerurkar AY, Borges AM. Angiogenesis is redundant for tumour growth in lymph node metastases. Histopathology. 2001;38:466–70.

    PubMed  Article  CAS  Google Scholar 

  20. Vermeulen PB. Sardari Nia P, Colpaert C, Dirix LY, Van Marck E. Lack of angiogenesis in lymph node metastases of carcinomas is growth pattern-dependent. Histopathology. 2002;40:105–7.

    PubMed  Article  CAS  Google Scholar 

  21. Thompson JF, Uren RF. Lymphatic mapping in management of patients with primary cutaneous melanoma. Lancet Oncol. 2005;6:877–85.

    PubMed  Article  Google Scholar 

  22. Benson JR, Jatoi I, Keisch M, Esteva FJ, Makris A, Jordan VC. Early breast cancer. Lancet. 2009;373:1463–79.

    PubMed  Article  Google Scholar 

  23. Ficarra V, Galfano A. Should the dynamic sentinel node biopsy (DSNB) be considered the gold standard in the evaluation of lymph node status in patients with penile carcinoma? Eur Urol. 2007;52:17–21.

    PubMed  Article  Google Scholar 

  24. Cheng G, Kurita S, Torigian DA, Alavi A. Current status of sentinel lymph-node biopsy in patients with breast cancer. Eur J Nucl Med Mol Imaging. doi:10.1007/s00259-010-1577-z.

  25. Czerniecki BJ, Bedrosian I, Faries M, Alavi A. Revolutionary impact of lymphoscintigraphy and intraoperative sentinel node mapping in the clinical practice of oncology. Semin Nucl Med. 2001;31:158–64.

    PubMed  Article  CAS  Google Scholar 

  26. Wasserberg N, Tulchinsky H, Schachter J, Feinmesser M, Gutman H. Sentinel-lymph-node biopsy (SLNB) for melanoma is not complication-free. Eur J Surg Oncol. 2004;30:851–6.

    PubMed  Article  CAS  Google Scholar 

  27. Leijte JA, Kroon BK. Valdés Olmos RA, Nieweg OE, Horenblas S. Reliability and safety of current dynamic sentinel node biopsy for penile carcinoma. Eur Urol. 2007;52:170–7.

    PubMed  Article  Google Scholar 

  28. Testori A, De Salvo GL, Montesco MC, Trifirò G, Mocellin S, Landi G, et al. Italian Melanoma Intergroup. Clinical considerations on sentinel node biopsy in melanoma from an Italian multicentric study on 1,313 patients (SOLISM-IMI). Ann Surg Oncol. 2009;16:2018–27.

    PubMed  Article  Google Scholar 

  29. Van der Ploeg IM, Nieweg OE, van Rijk MC. Valdés Olmos RA, Kroon BB. Axillary recurrence after a tumour-negative sentinel node biopsy in breast cancer patients: A systematic review and meta-analysis of the literature. Eur J Surg Oncol. 2008;34:1277–84.

    PubMed  Google Scholar 

  30. Leijte JA, Hughes B, Graafland NM, Kroon BK, Olmos RA, Nieweg OE, et al. Two-center evaluation of dynamic sentinel node biopsy for squamous cell carcinoma of the penis. J Clin Oncol. 2009;27:3325–9.

    PubMed  Article  Google Scholar 

  31. Lam TK, Uren RF, Scolyer RA, Quinn MJ, Shannon KF, Thompson JF. False-negative sentinel node biopsy because of obstruction of lymphatics by metastatic melanoma: the value of ultrasound in conjunction with preoperative lymphoscintigraphy. Melanoma Res. 2009;19:94–9.

    PubMed  Article  Google Scholar 

  32. Goyal A, Douglas-Jones AG, Newcombe RG, Mansel RE. Effect of lymphatic tumor burden on sentinel lymph node biopsy in breast cancer. Breast J. 2005;11:188–94.

    PubMed  Article  Google Scholar 

  33. Leijte JA, van der Ploeg IM. Valdés Olmos RA, Nieweg OE, Horenblas S. Visualization of tumor blockage and rerouting of lymphatic drainage in penile cancer patients by use of SPECT/CT. J Nucl Med. 2009;50:364–7.

    PubMed  Article  Google Scholar 

  34. Padhani AR, Liu G, Koh DM, Chenevert TL, Thoeny HC, Takahara T, et al. Diffusion-weighted magnetic resonance imaging as a cancer biomarker: consensus and recommendations. Neoplasia. 2009;11:102–25.

    PubMed  CAS  Google Scholar 

  35. Glazer GM, Orringer MB, Chenevert TL, Borrello JA, Penner MW, Quint LE, et al. Mediastinal lymph nodes: relaxation time/pathologic correlation and implications in staging of lung cancer with MR imaging. Radiology. 1988;168:429–31.

    PubMed  CAS  Google Scholar 

  36. Ranade SS, Trivedi PN, Bamane VS. Mediastinal lymph nodes: relaxation time/pathologic correlation and implications in staging of lung cancer with MR imaging. Radiology. 1990;174:284–5.

    PubMed  CAS  Google Scholar 

  37. De Bondt RB, Hoeberigs MC, Nelemans PJ, Deserno WM, Peutz-Kootstra C, Kremer B, et al. Diagnostic accuracy and additional value of diffusion-weighted imaging for discrimination of malignant cervical lymph nodes in head and neck squamous cell carcinoma. Neuroradiology. 2009;51:183–92.

    PubMed  Article  Google Scholar 

  38. Vandecaveye V, De Keyzer F, Vander Poorten V, Dirix P, Verbeken E, Nuyts S, et al. Head and neck squamous cell carcinoma: value of diffusion-weighted MR imaging for nodal staging. Radiology. 2009;251:134–46.

    PubMed  Article  Google Scholar 

  39. Nakayama J, Miyasaka K, Omatsu T, Onodera Y, Terae S, Matsuno Y, et al. Metastases in mediastinal and hilar lymph nodes in patients with non-small cell lung cancer: quantitative assessment with diffusion-weighted magnetic resonance imaging and apparent diffusion coefficient. J Comput Assist Tomogr. 2010;34:1–8.

    PubMed  Article  Google Scholar 

  40. Sakurada A, Takahara T, Kwee TC, Yamashita T, Nasu S, Horie T, et al. Diagnostic performance of diffusion-weighted magnetic resonance imaging in esophageal cancer. Eur Radiol. 2009;19:1461–9.

    PubMed  Article  Google Scholar 

  41. Yasui O, Sato M, Kamada A. Diffusion-weighted imaging in the detection of lymph node metastasis in colorectal cancer. Tohoku J Exp Med. 2009;218:177–83.

    PubMed  Article  CAS  Google Scholar 

  42. Kim JK, Kim KA, Park BW, Kim N, Cho KS. Feasibility of diffusion-weighted imaging in the differentiation of metastatic from nonmetastatic lymph nodes: early experience. J Magn Reson Imaging. 2008;28:714–9.

    PubMed  Article  Google Scholar 

  43. Park SO, Kim JK, Kim KA, Park BW, Kim N, Cho G, et al. Relative apparent diffusion coefficient: determination of reference site and validation of benefit for detecting metastatic lymph nodes in uterine cervical cancer. J Magn Reson Imaging. 2009;29:383–90.

    PubMed  Article  Google Scholar 

  44. Eiber M, Beer AJ, Holzapfel K, Tauber R, Ganter C, Weirich G, et al. Preliminary results for characterization of pelvic lymph nodes in patients with prostate cancer by diffusion-weighted MR-imaging. Invest Radiol. 2010;45:15–23.

    PubMed  Article  Google Scholar 

  45. Nakai G, Matsuki M, Inada Y, Tatsugami F, Tanikake M, Narabayashi I, et al. Detection and evaluation of pelvic lymph nodes in patients with gynecologic malignancies using body diffusion-weighted magnetic resonance imaging. J Comput Assist Tomogr. 2008;32:764–8.

    PubMed  Article  Google Scholar 

  46. Lin G, Ho KC, Wang JJ, Ng KK, Wai YY, Chen YT, et al. Detection of lymph node metastasis in cervical and uterine cancers by diffusion-weighted magnetic resonance imaging at 3 T. J Magn Reson Imaging. 2008;28:128–35.

    PubMed  Article  Google Scholar 

  47. Kwee TC, Takahara T, Luijten PR, Nievelstein RA. ADC measurements of lymph nodes: Inter- and intra-observer reproducibility study and an overview of the literature. Eur J Radiol. 2010;75:215–20.

    PubMed  Article  Google Scholar 

  48. Weissleder R, Elizondo G, Wittenberg J, Lee AS, Josephson L, Brady TJ. Ultrasmall superparamagnetic iron oxide: an intravenous contrast agent for assessing lymph nodes with MR imaging. Radiology. 1990;175:494–8.

    PubMed  CAS  Google Scholar 

  49. Guimaraes R, Clément O, Bittoun J, Carnot F, Frija G. MR lymphography with superparamagnetic iron nanoparticles in rats: pathologic basis for contrast enhancement. AJR Am J Roentgenol. 1994;162:201–17.

    PubMed  CAS  Google Scholar 

  50. Wunderbaldinger P, Josephson L, Bremer C, Moore A, Weissleder R. Detection of lymph node metastases by contrast-enhanced MRI in an experimental model. Magn Reson Med. 2002;47:292–7.

    PubMed  Article  Google Scholar 

  51. Will O, Purkayastha S, Chan C, Athanasiou T, Darzi AW, Gedroyc W, et al. Diagnostic precision of nanoparticle-enhanced MRI for lymph-node metastases: a meta-analysis. Lancet Oncol. 2006;7:52–60.

    PubMed  Article  Google Scholar 

  52. Koh DM, George C, Temple L, Collins DJ, Toomey P, Raja A, et al. Diagnostic accuracy of nodal enhancement pattern of rectal cancer at MRI enhanced with ultrasmall superparamagnetic iron oxide: findings in pathologically matched mesorectal lymph nodes. AJR Am J Roentgenol. 2010;194:W505–13.

    PubMed  Article  Google Scholar 

  53. Torchia MG, Nason R, Danzinger R, Lewis JM, Thliveris JA. Interstitial MR lymphangiography for the detection of sentinel lymph nodes. J Surg Oncol. 2001;78:151–6.

    PubMed  Article  CAS  Google Scholar 

  54. Thoeny HC, Triantafyllou M, Birkhaeuser FD, Froehlich JM, Tshering DW, Binser T, et al. Combined ultrasmall superparamagnetic particles of iron oxide-enhanced and diffusion-weighted magnetic resonance imaging reliably detect pelvic lymph node metastases in normal-sized nodes of bladder and prostate cancer patients. Eur Urol. 2009;55:761–9.

    PubMed  Article  Google Scholar 

  55. Rohren EM, Turkington TG, Coleman RE. Clinical applications of PET in oncology. Radiology. 2004;231:305–32.

    PubMed  Article  Google Scholar 

  56. Fletcher JW, Djulbegovic B, Soares HP, Siegel BA, Lowe VJ, Lyman GH, et al. Recommendations on the use of 18F-FDG PET in oncology. J Nucl Med. 2008;49:480–508.

    PubMed  Article  Google Scholar 

  57. Kyzas PA, Evangelou E, Denaxa-Kyza D, Ioannidis JP. 18F-fluorodeoxyglucose positron emission tomography to evaluate cervical node metastases in patients with head and neck squamous cell carcinoma: a meta-analysis. J Natl Cancer Inst. 2008;100:712–20.

    PubMed  Article  Google Scholar 

  58. Peare R, Staff RT, Heys SD. The use of FDG-PET in assessing axillary lymph node status in breast cancer: a systematic review and meta-analysis of the literature. Breast Cancer Res Treat. 2010;123:281–90.

    PubMed  Article  Google Scholar 

  59. Kang S, Kim SK, Chung DC, Seo SS, Kim JY, Nam BH, et al. Diagnostic value of 18F-FDG PET for evaluation of paraaortic nodal metastasis in patients with cervical carcinoma: a metaanalysis. J Nucl Med. 2010;51:360–7.

    PubMed  Article  Google Scholar 

  60. Gould MK, Kuschner WG, Rydzak CE, Maclean CC, Demas AN, Shigemitsu H, et al. Test performance of positron emission tomography and computed tomography for mediastinal staging in patients with non-small-cell lung cancer: a meta-analysis. Ann Intern Med. 2003;139:879–92.

    PubMed  Google Scholar 

  61. Hustinx R, Smith RJ, Benard F, Rosenthal DI, Machtay M, Farber LA, et al. Dual time point fluorine-18 fluorodeoxyglucose positron emission tomography: a potential method to differentiate malignancy from inflammation and normal tissue in the head and neck. Eur J Nucl Med. 1999;26:1345–8.

    PubMed  Article  CAS  Google Scholar 

  62. Kumar R, Dhanpathi H, Basu S, Rubello D, Fanti S, Alavi A. Oncologic PET tracers beyond [(18)F]FDG and the novel quantitative approaches in PET imaging. Q J Nucl Med Mol Imaging. 2008;52:50–65.

    PubMed  CAS  Google Scholar 

  63. Basu S, Kung J, Houseni M, Zhuang H, Tidmarsh GF, Alavi A. Temporal profile of fluorodeoxyglucose uptake in malignant lesions and normal organs over extended time periods in patients with lung carcinoma: implications for its utilization in assessing malignant lesions. Q J Nucl Med Mol Imaging. 2009;53:9–19.

    PubMed  CAS  Google Scholar 

  64. Sanz-Viedma S, Torigian DA, Parsons M, Basu S, Alavi A. Potential clinical utility of dual time point FDG-PET for distinguishing benign from malignant lesions: implications for oncological imaging. Rev Esp Med Nucl. 2009;28:159–66.

    PubMed  Article  CAS  Google Scholar 

  65. Suga K, Kawakami Y, Hiyama A, Sugi K, Okabe K, Matsumoto T, et al. Differential diagnosis between (18)F-FDG-avid metastatic lymph nodes in non-small cell lung cancer and benign nodes on dual-time point PET/CT scan. Ann Nucl Med. 2009;23:523–31.

    PubMed  Article  Google Scholar 

  66. Shinya T, Rai K, Okumura Y, Fujiwara K, Matsuo K, Yonei T, et al. Dual-time-point F-18 FDG PET/CT for evaluation of intrathoracic lymph nodes in patients with non-small cell lung cancer. Clin Nucl Med. 2009;34:216–21.

    PubMed  Article  Google Scholar 

  67. Uesaka D, Demura Y, Ishizaki T, Ameshima S, Miyamori I, Sasaki M, et al. Evaluation of dual-time-point 18F-FDG PET for staging in patients with lung cancer. J Nucl Med. 2008;49:1606–12.

    PubMed  Article  Google Scholar 

  68. Nishiyama Y, Yamamoto Y, Kimura N, Ishikawa S, Sasakawa Y, Ohkawa M. Dual-time-point FDG-PET for evaluation of lymph node metastasis in patients with non-small-cell lung cancer. Ann Nucl Med. 2008;22:245–50.

    PubMed  Article  Google Scholar 

  69. So Y, Chung JK, Jeong JM, Lee DS, Lee MC. Usefulness of additional delayed regional F-18 fluorodeoxy-glucose positron emission tomography in the lymph node staging of non-small cell lung cancer patients. Cancer Res Treat. 2005;37:114–21.

    PubMed  Article  Google Scholar 

  70. Hu Q, Wang W, Zhong X, Yuan S, Fu Z, Guo H, et al. Dual-time-point FDG PET for the evaluation of locoregional lymph nodes in thoracic esophageal squamous cell cancer. Eur J Radiol. 2009;70:320–4.

    PubMed  Article  Google Scholar 

  71. Ma SY, See LC, Lai CH, Chou HH, Tsai CS, Ng KK, et al. Delayed (18)F-FDG PET for detection of paraaortic lymph node metastases in cervical cancer patients. J Nucl Med. 2003;44:1775–83.

    PubMed  Google Scholar 

  72. Kasai T, Motoori K, Horikoshi T, Uchiyama K, Yasufuku K, Takiguchi Y, et al. Dual-time point scanning of integrated FDG PET/CT for the evaluation of mediastinal and hilar lymph nodes in non-small cell lung cancer diagnosed as operable by contrast-enhanced CT. Eur J Radiol. 2010;75:143–6.

    PubMed  Article  Google Scholar 

  73. Yen RF, Chen KC, Lee JM, Chang YC, Wang J, Cheng MF, et al. 18F-FDG PET for the lymph node staging of non-small cell lung cancer in a tuberculosis-endemic country: is dual time point imaging worth the effort? Eur J Nucl Med Mol Imaging. 2008;35:1305–15.

    PubMed  Article  Google Scholar 

  74. Yen TC, Chang YC, Chan SC, Chang JT, Hsu CH, Lin KJ, et al. Are dual-phase 18F-FDG PET scans necessary in nasopharyngeal carcinoma to assess the primary tumour and loco-regional nodes? Eur J Nucl Med Mol Imaging. 2005;32:541–8.

    PubMed  Article  Google Scholar 

Download references

Conflicts of interest

None.

Author information

Affiliations

  1. Department of Radiology, University Medical Center Utrecht, Utrecht, The Netherlands

    Thomas C. Kwee

  2. Radiation Medicine Center (Bhabha Atomic Research Center), Tata Memorial Center Annexe, Bombay, India

    Sandip Basu

  3. Division of Nuclear Medicine, Hospital of the University of Pennsylvania, 3400 Spruce St., 110 Donner Bldg, Philadelphia, PA, 19104, USA

    Sandip Basu, Drew A. Torigian, Babak Saboury & Abass Alavi

Authors
  1. Thomas C. Kwee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sandip Basu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Drew A. Torigian
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Babak Saboury
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Abass Alavi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Abass Alavi.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Kwee, T.C., Basu, S., Torigian, D.A. et al. Defining the role of modern imaging techniques in assessing lymph nodes for metastasis in cancer: evolving contribution of PET in this setting. Eur J Nucl Med Mol Imaging 38, 1353–1366 (2011). https://doi.org/10.1007/s00259-010-1717-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00259-010-1717-5

Keywords

  • Lymph node imaging
  • Lymph node metastasis
  • Sentinel lymph node
  • MRI
  • PET