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Lymphoscintigraphy

  • Author: Durre Sabih, MBBS, MSc, FRCP(Edin); Chief Editor: Gowthaman Gunabushanam, MD, FRCR  more...
 
Updated: Aug 28, 2015
 

Overview

Background

Lymphoscintigraphy (sentinel lymph node mapping) is an imaging technique used to identify the lymph drainage basin, determine the number of sentinel nodes, differentiate sentinel nodes from subsequent nodes, locate the sentinel node in an unexpected location, and mark the sentinel node over the skin for biopsy.

Sentinel node mapping is rapidly becoming an alternate staging procedure for the axilla in managing early breast cancer.[1] Several well-conducted studies have provided high-quality evidence for its usefulness.[2] Sentinel node scanning was initially studied in cutaneous melanomas to detect lymphatic drainage patterns prior to surgery. The procedure is applicable to almost all regions of the body, but the greatest impetus to the technique came with the application of the procedure to identify breast sentinel nodes.

The sentinel node is the first node to receive metastatic deposits in a malignancy. Lymphoscintigraphy is an important procedure because if the sentinel node is free of metastasis, subsequent nodes are also likely to be free of disease. The sentinel node is generally defined as follows:

  • The node closest to the primary lesion
  • The node with a radioactive channel leading to it
  • The node with the highest count rate on lymphoscintigraphic imaging and probe counting
  • The first node visible on lymphoscintigraphic imaging
  • The blue node on dye injection technique
  • The node with a blue channel leading to it

Lymphoscintigraphy allows the patient to avoid axillary clearance surgery (axillary lymph node dissection) if the sentinel node is negative for metastatic disease. Given the high prevalence of breast cancer worldwide, the possibility of avoiding axillary clearance surgery in a significant number of patients makes this an extremely valuable procedure.

Lymphoscintigraphy is the staging modality of choice for early breast cancer, and breast cancer trials with 5- to 10-year outcome data have shown no significant differences in disease-free survival rates or overall survival rates between lymphoscintigraphy and axial lymph node dissection but have shown significantly lower morbidity with lymphoscintigraphy.[3]

This topic is limited to lymphoscintigraphy in breast cancer. Applications for malignant melanoma will be introduced, but a detailed discussion is beyond the scope of this article. Both radionuclide and nonradionuclide methods (blue-dye methods) will be discussed.

Indications

Lymphoscintigraphy is indicated for proven palpable or nonpalpable invasive breast carcinoma for which removal of the primary tumor and axillary node dissection would be indicated.[4]

Contraindications

Absolute contraindications to lymphoscintigraphy include clinically positive (N1) axilla and allergy to component used.[1]

Relative contraindications to lymphoscintigraphy include the following[5] :

  • Prior biopsy (especially excisional biopsy)
  • Previous breast and axillary surgery
  • Advanced disease (associated with fatty degeneration of nodes with reduced function)
  • Neoadjuvant chemotherapy
  • Multicentric and multifocal disease
  • Ductal carcinoma in situ
  • High body mass index and old age
  • Pregnancy
  • Surgeon’s experience and skills

Other Applications

Lymphoscintigraphy has become widely accepted in several other applications besides breast cancer,[6, 7] including malignant melanoma (stage I and II disease).[8, 3, 9] Tc 99m tilmanocept is also approved for intradermal or SC injection for melanoma mapping.[10] The Multicenter Selective Lymphadenectomy Trial concluded that sentinel node scanning is a low-morbidity procedure for evaluating the regional nodal basin in early melanoma and should become the standard of care.[11] Other applications include head and neck cancer, thyroid cancer, non–small cell lung cancer, gastric cancer,[7] penile cancer,[12] and vulvar cancers.[13]

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Periprocedural Care

Equipment

Lymphoscintigraphy equipment includes the following:

  • Syringes with needles of appropriate gauge, usually 25-G insulin syringes (see the image below)
    Injecting syringe. Injecting syringe.
  • Syringe shields
  • Tc-99m radiopharmaceutical: antimony trisulphide, particle size 0.015-0.3 µm; nanocolloid, particle size 0.05-0.8 µm; sulfur colloid, particle size 0.22 µm; or tilmanocept (Lymphoseek) [14]
  • Alcohol swabs and other material used during and after injections (see the image below)
    Injection tray containing the radioactive dose in Injection tray containing the radioactive dose in a syringe shield, alcohol swabs, bandage, and dry cotton.
  • Gamma camera and imaging system
  • Gamma-detecting probe (see the image below)
    Gamma probe with a highly collimated handheld dete Gamma probe with a highly collimated handheld detecting wand, which is covered with a sterile cover for use within the surgical field.

The camera should be equipped with a low-energy, high-resolution collimator and should be peaked at 140 KeV with a 20% window centered over the peak. A small magnification (1.35) is often used.

Patient Preparation

Anesthesia

No anesthesia is required.

Positioning

The patient must be imaged in the same position used for surgery so that there is no shift when the sentinel node is marked on the skin. The patient is usually supine with the ipsilateral arm abducted at 90 degrees and suitably supported.

False-Positive and False-Negative Results

A false-positive result may be caused by contamination of the skin or residual activity from another nuclear medicine procedure done recently.

A false-negative result (absent or faint lymph node uptake) may be caused by a low radiopharmaceutical dose, poor radiopharmaceutical quality, insufficient radiocolloid particles, imaging time that is too early or too late, advanced patient age, or tumor replacement of nodes.

One way of reducing false-positive and false-negative results is to combine the visual assessment of nodes with intraoperative gamma counting and digital palpation through the surgical incision.[15]

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Technique

Approach Considerations

Injection techniques can be divided into superficial and deep methods. The superficial techniques include intradermal, subcutaneous, subareolar, and periareolar injections. Deep techniques include peritumoral or intratumoral injections. Subcutaneous, periareolar, and subareolar techniques are associated with a low yield of nonaxillary nodes and will not be discussed.

The combination of radiocolloid injection and blue-dye injection immediately before surgery gives the highest sensitivity and specificity of the technique.

Imaging and Interpretation

Imaging techniques must be meticulous and of a high standard. The camera should be equipped with a low-energy, high-resolution collimator and should be peaked at 140 KeV with a 20% window centered over the peak. Shielding of the injection site is usually not needed. A small magnification (1.35) is often used.

Imaging times for the various injection techniques are given in the table below.

Table. Acquisition Protocols and Imaging Times for Various Injection Types (Open Table in a new window)

  Computer Matrix Dynamic Phase Static Phase
Intradermal 128 x 128 x 16 (dynamic) or highest available



256 x 256 x 16 (static) or highest available



20 seconds for 15-20 minutes 20 minutes, 2-3 hours, 12-24 hours (immediately prior to surgery)
Subcutaneous 256 x 256 x 16 (static) or highest available   20-30 minutes, 2 hours, 4-6 hours, prior to surgery
Peritumoral or intratumoral 256 x 256 x 16 (static) or highest available   20-30 minutes, 2 hours, 4-6 hours, prior to surgery

An anterior oblique view with a 30-degree lateral tilt is used. If a dual-head camera is used, simultaneous lateral images are also acquired.

Transmission images, radioactive markers to identify the nipple, and flexible line sources to outline the breast contour may be used to provide additional anatomical localization.

Once a sentinel node is identified, a radioactive marker is moved over skin while the patient is under the gamma camera detector, keeping the sentinel node in the field of view. With real-time imaging mode, the marker is moved until the two sources coincide (the marker and sentinel node). This area is marked with waterproof ink.

It is useful to add late images before the patient is taken for surgery to ensure that the sentinel node identified is indeed retaining the radiopharmaceutical and also to see if subsequent tier nodes have appeared.

The sentinel node is the one that appears first, is closer to the injection, and/or has a lymphatic duct connecting the injection site with the node.

Axillary nodes are seen in almost all patients, but the appearance of nodes can take several patterns.

  • One sentinel node, with or without a visible lymphatic duct; no second-tier nodes
  • One sentinel and one or more second-tier nodes
  • The simultaneous appearance of two nodes with same uptake intensity (twin sentinel nodes)
  • A node closer to the injection site that appears later than other more distant nodes (the closer node is the sentinel node)

Differentiation of the sentinel node from second-tier nodes can be made by the following:

  • The presence of a lymphatic channel leading to the sentinel node
  • The sequence of appearance (the sentinel node appears first)
  • The intensity of uptake (the sentinel node has more activity)

Confirmation needs blue-dye corroboration.

Radiocolloid Injection Method

Intradermal Injection Technique

Many experts contend that this method offers the best results.[16] The injection is made 24 hours before the surgery, with 10-15 MBq (0.3-0.4 mCi) of the appropriate Tc-99m labeled radiopharmaceutical is used in a volume of 0.2 mL. Tc-99m tilmanocept dose is 0.5 mCi administered at least 15 minutes prior to initiating intraoperative lymphatic mapping and do not delay mapping more than 15 h following Tc-99m tilmanocept injection.

A 25-G needle is used and 0.2 mL of air bubble is drawn into the syringe behind the radiopharmaceutical. The air ensures that the whole radiopharmaceutical is injected and none of the dose is left behind in the needle; it also minimizes the risk of spillage as the syringe is withdrawn, which can lead to false-positive and false-negative results.

The injection is made in the skin overlying the tumor and the needle is inserted at an acute angle into the skin. Proper injection technique is confirmed by the appearance of a skin bleb at the injection site. See the image below.

Intradermal injection technique. Note that the nee Intradermal injection technique. Note that the needle tip is within the skin thickness and a bleb has formed on the skin. The cancer is represented by the black mass.

After the injection, dry cotton is applied over the injection site and the site is sealed with an adhesive bandage. The patient is asked to massage over the injection site with dry cotton wool. This massage should continue for 1-2 minutes. See the image below.

Intradermal injection technique. The needle is ins Intradermal injection technique. The needle is inserted at a very acute angle with the skin and the bleb forms when the radiocolloid is injected.

Peritumoral Injection Technique

In this technique, the injection is made deeper into the breast parenchyma around the mass. See the image below.

Intraparenchmal injections. Note the needle inject Intraparenchmal injections. Note the needle injects within the parenchyma around the lesion.

Usually four injections are made around the tumor. The volume of injectate is larger, with 1-2 mL injected at each injection site to make a total volume of 4-8 mL. The injections are made superior, inferior, lateral and medial to the mass. Another technique to inject in a semicircle along the axillary side of the mass.

If the mass is nonpalpable, ultrasound guidance can be used for needle placement.

The patient is asked to massage over the injection site and between the injection site and axilla for at least 1-2 minutes. See the image below.

Postinjection massage. Dry cotton is used to massa Postinjection massage. Dry cotton is used to massage the injection site to encourage lymph flow with the radiocolloid towards the sentinel node.

Intratumoral Injection Technique

Although some authors have advocated injection inside the tumor, there are concerns about tumor spread, especially along the needle track. Proponents claim 100% reproducibility and sentinel node visualization.[17] A small volume of radiopharmaceutical (0.2 mL), with 0.1 mL of air bubble behind it, is injected into the center of the tumor.

If the mass is nonpalpable, ultrasound guidance can be used for needle placement.

The patient is asked to massage over the injection site and between the injection site and axilla for at least 1-2 minutes.

Dye Injection Method

Methylene blue, patent blue, or isosulfan blue injections are used alone or in conjunction for sentinel node identification.[18] The injection is given in the operation theater, 5 minutes prior to the surgical incision. The injection is subdermal, peritumoral, or subareolar. See the image below.

Methylene blue is injected in the operating theate Methylene blue is injected in the operating theater. Note the larger volume and a deeper insertion angle.

A volume of approximately 1.5-2 mL is used for subdermal injections, whereas a larger volume of about 5 mL (divided into two aliquots) is used for peritumoral injections. The injection site is massaged as for the radiopharmaceutical injection.

A positive test is when a node is coloured blue, often with a blue channel leading to it.

Note that there might be generalized blue coloration of the body and some patients might experience allergic reaction to the dye.

Intraoperative Sentinel Node Detection Technique

Imaging the sentinel node allows the surgeon to have an idea of where to explore to retrieve the sentinel node. However, the addition of radioguidance using a gamma probe is the true strength of the technique. This also introduces a multidisciplinary element to the procedure, with breast surgeons and nuclear medicine physicians operating in close cooperation.

By using sentinel node imaging, the surgeon can determine the area where the sentinel node lies. Complete excision can be confirmed by counting the area after removing the purported sentinel node to see if the counts have fallen to background levels. The probe also guides the surgeon into the right direction and allows removal of invisible non-blue nodes that are recognizable due to their radioactive signature.

The gamma probe is covered in sterile sheath that extends to cover the connecting wire up to the display console. The display console is placed where the surgeon can easily see the display. See the image below.

The sentinel node is located using the gamma count The sentinel node is located using the gamma counter probe in the area with the highest count rate. This is done after sterilization; note that the probe is covered with a sterile sheath.

The skin mark is confirmed to actually overlie the hottest node by placing the probe tip over the area and moving it to the surrounding areas. The hottest area is identified by the pitch of the audible signal as well as the count rate on the digital display. See the images below.

With the probe in the proper location, the area is With the probe in the proper location, the area is marked on the skin.
The incision is made over the area identified by t The incision is made over the area identified by the mark on the skin.
The incision leads to a blue lymph node. Note the The incision leads to a blue lymph node. Note the blue channel at 1 o'-clock position indicating that this is the sentinel node (to be corroborated by radiation counting).
The blue node is confirmed to be the sentinel node The blue node is confirmed to be the sentinel node by counting over it. It should be the "hottest" node.

Background is acquired. One practice is to acquire the background over the suprasternal notch.

The line of sight[19] is established by angling the probe at the site of maximum count to determine the angle that allows the shortest distance from the skin to the sentinel node. The node is approached along the line of sight, correcting the direction with periodic input from the probe. If a blue channel is seen, this reinforces the direction.

Once the node is exposed, the probe is applied to it again to ensure that this has a high count rate (in vivo counting). If a blue dye is used and the same node is colored, this corroborates the probe data.

Once the node is removed, it is placed on the probe surface to confirm the counts (ex vivo counting). See the image below.

The blue and hottest node is excised and ex vivo c The blue and hottest node is excised and ex vivo counts are checked. Note that the probe is directed towards the ceiling to avoid getting extraneous counts from the patient. Note the high counts (acquired over 2 seconds) at the top of the screen.

The probe is reapplied to the surgical field to confirm that the radioactive node(s) have been removed. If all radioactive nodes have been removed, the activity in the surgical bed should fall to 10% of the most active node.[19] See the images below.

After the sentinel node is excised, the nodal bed After the sentinel node is excised, the nodal bed is checked again for residual counts. If the sentinel node has been removed, the count rate should fall to the background level or 10% of the in vivo count rate.
Postexcision counts are acquired. In this image, t Postexcision counts are acquired. In this image, the counts have fallen to very low background rates.
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Contributor Information and Disclosures
Author

Durre Sabih, MBBS, MSc, FRCP(Edin) FRCP(Edin), Director, Multan Institute of Nuclear Medicine and Radiotherapy (MINAR), Nishtar Hospital, Pakistan

Disclosure: Nothing to disclose.

Coauthor(s)

Ali Nawaz Khan, MBBS, FRCS, FRCP, FRCR Consultant Radiologist and Honorary Professor, North Manchester General Hospital Pennine Acute NHS Trust, UK

Ali Nawaz Khan, MBBS, FRCS, FRCP, FRCR is a member of the following medical societies: American Association for the Advancement of Science, American Institute of Ultrasound in Medicine, British Medical Association, Royal College of Physicians and Surgeons of the United States, British Society of Interventional Radiology, Royal College of Physicians, Royal College of Radiologists, Royal College of Surgeons of England

Disclosure: Nothing to disclose.

Chief Editor

Gowthaman Gunabushanam, MD, FRCR Assistant Professor, Department of Diagnostic Radiology, Yale University School of Medicine

Gowthaman Gunabushanam, MD, FRCR is a member of the following medical societies: American Roentgen Ray Society, Connecticut State Medical Society

Disclosure: Nothing to disclose.

References
  1. Krontiras H, Bland KI. When is sentinel node biopsy for breast cancer contraindicated?. Surg Oncol. 2003 Nov. 12(3):207-10. [Medline].

  2. Kim T, Giuliano AE, Lyman GH. Lymphatic mapping and sentinel lymph node biopsy in early-stage breast carcinoma: a metaanalysis. Cancer. 2006 Jan 1. 106(1):4-16. [Medline].

  3. Moncayo VM, Aarsvold JN, Alazraki NP. Lymphoscintigraphy and sentinel nodes. J Nucl Med. 2015 Jun. 56 (6):901-7. [Medline].

  4. Keshtgar M, Waddington WA, Lakhani SR, Ell PJ. Injection Techniques. The Sentinel Node in Surgical Oncology. London: Springer-Verlag; 1999. 50-59.

  5. Filippakis GM, Zografos G. Contraindications of sentinel lymph node biopsy: are there any really?. World J Surg Oncol. 2007 Jan 29. 5:10. [Medline]. [Full Text].

  6. Keshtgar M, Zaknun JJ, Sabih D, Lago G, Cox CE, Leong SP. Implementing sentinel lymph node biopsy programs in developing countries: challenges and opportunities. World J Surg. 2011 Jun. 35(6):1159-68; discussion 1155-8. [Medline].

  7. Gipponi M, Solari N, Di Somma FC, Bertoglio S, Cafiero F. New fields of application of the sentinel lymph node biopsy in the pathologic staging of solid neoplasms: review of literature and surgical perspectives. J Surg Oncol. 2004 Mar. 85(3):171-9. [Medline].

  8. Bluemel C, Herrmann K, Giammarile F, Nieweg OE, Dubreuil J, Testori A, et al. EANM practice guidelines for lymphoscintigraphy and sentinel lymph node biopsy in melanoma. Eur J Nucl Med Mol Imaging. 2015 Jul 25. [Medline].

  9. Doepker MP, Zager JS. Sentinel lymph node mapping in melanoma in the twenty-first century. Surg Oncol Clin N Am. 2015 Apr. 24 (2):249-60. [Medline].

  10. Sondak VK, King DW, Zager JS, Schneebaum S, Kim J, Leong SP, et al. Combined analysis of phase III trials evaluating [??mTc]tilmanocept and vital blue dye for identification of sentinel lymph nodes in clinically node-negative cutaneous melanoma. Ann Surg Oncol. 2013 Feb. 20(2):680-8. [Medline]. [Full Text].

  11. Morton DL, Cochran AJ, Thompson JF, Elashoff R, Essner R, Glass EC. Sentinel node biopsy for early-stage melanoma: accuracy and morbidity in MSLT-I, an international multicenter trial. Ann Surg. 2005 Sep. 242(3):302-11; discussion 311-3. [Medline].

  12. Horenblas S, Jansen L, Meinhardt W, Hoefnagel CA, de Jong D, Nieweg OE. Detection of occult metastasis in squamous cell carcinoma of the penis using a dynamic sentinel node procedure. J Urol. 2000 Jan. 163(1):100-4. [Medline].

  13. Makar AP, Scheistroen M, van den Weyngaert D, Tropé CG. Surgical management of stage I and II vulvar cancer: the role of the sentinel node biopsy. Review of literature. Int J Gynecol Cancer. 2001 Jul-Aug. 11(4):255-62. [Medline].

  14. Wallace AM, Han LK, Povoski SP, Deck K, Schneebaum S, Hall NC, et al. Comparative Evaluation of [99mTc]Tilmanocept for Sentinel Lymph Node Mapping in Breast Cancer Patients: Results of Two Phase 3 Trials. Ann Surg Oncol. 2013 Mar 17. [Medline].

  15. Mathelin C, Croce S, Brasse D, Gairard B, Gharbi M, Andriamisandratsoa N, et al. Methylene blue dye, an accurate dye for sentinel lymph node identification in early breast cancer. Anticancer Res. 2009 Oct. 29(10):4119-25. [Medline].

  16. Lin KM, Patel TH, Ray A, Ota M, Jacobs L, Kuvshinoff B, et al. Intradermal radioisotope is superior to peritumoral blue dye or radioisotope in identifying breast cancer sentinel nodes. J Am Coll Surg. 2004 Oct. 199(4):561-6. [Medline].

  17. Tanis PJ, Valdés Olmos RA, Muller SH, Nieweg OE. Lymphatic mapping in patients with breast carcinoma: reproducibility of lymphoscintigraphic results. Radiology. 2003 Aug. 228(2):546-51. [Medline].

  18. East JM, Valentine CS, Kanchev E, Blake GO. Sentinel lymph node biopsy for breast cancer using methylene blue dye manifests a short learning curve among experienced surgeons: a prospective tabular cumulative sum (CUSUM) analysis. BMC Surg. 2009 Jan 27. 9:2. [Medline]. [Full Text].

  19. Krag DN, Weaver DL, Alex JC, Fairbank JT. Surgical resection and radiolocalization of the sentinel lymph node in breast cancer using a gamma probe. Surg Oncol. 1993 Dec. 2(6):335-9; discussion 340. [Medline].

 
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Injecting syringe.
Gamma probe with a highly collimated handheld detecting wand, which is covered with a sterile cover for use within the surgical field.
Injection tray containing the radioactive dose in a syringe shield, alcohol swabs, bandage, and dry cotton.
Intradermal injection technique. Note that the needle tip is within the skin thickness and a bleb has formed on the skin. The cancer is represented by the black mass.
Intradermal injection technique. The needle is inserted at a very acute angle with the skin and the bleb forms when the radiocolloid is injected.
Intraparenchmal injections. Note the needle injects within the parenchyma around the lesion.
Postinjection massage. Dry cotton is used to massage the injection site to encourage lymph flow with the radiocolloid towards the sentinel node.
Methylene blue is injected in the operating theater. Note the larger volume and a deeper insertion angle.
The sentinel node is located using the gamma counter probe in the area with the highest count rate. This is done after sterilization; note that the probe is covered with a sterile sheath.
With the probe in the proper location, the area is marked on the skin.
The incision is made over the area identified by the mark on the skin.
The incision leads to a blue lymph node. Note the blue channel at 1 o'-clock position indicating that this is the sentinel node (to be corroborated by radiation counting).
The blue node is confirmed to be the sentinel node by counting over it. It should be the "hottest" node.
The blue and hottest node is excised and ex vivo counts are checked. Note that the probe is directed towards the ceiling to avoid getting extraneous counts from the patient. Note the high counts (acquired over 2 seconds) at the top of the screen.
After the sentinel node is excised, the nodal bed is checked again for residual counts. If the sentinel node has been removed, the count rate should fall to the background level or 10% of the in vivo count rate.
Postexcision counts are acquired. In this image, the counts have fallen to very low background rates.
Table. Acquisition Protocols and Imaging Times for Various Injection Types
  Computer Matrix Dynamic Phase Static Phase
Intradermal 128 x 128 x 16 (dynamic) or highest available



256 x 256 x 16 (static) or highest available



20 seconds for 15-20 minutes 20 minutes, 2-3 hours, 12-24 hours (immediately prior to surgery)
Subcutaneous 256 x 256 x 16 (static) or highest available   20-30 minutes, 2 hours, 4-6 hours, prior to surgery
Peritumoral or intratumoral 256 x 256 x 16 (static) or highest available   20-30 minutes, 2 hours, 4-6 hours, prior to surgery
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