Continuing Education Activity

Lymphoscintigraphy is a powerful diagnostic imaging tool that can be obtained with little risk of adverse events. This activity reviews the applications of lymphoscintigraphy for current medicine and highlights the role of the interprofessional team in the management of patients with malignancy demonstrating concern for nodal involvement as well as lymphatic system flow pathology.

Objectives:

• Summarize the indications for lymphoscintigraphy.
• Describe the equipment, personnel, preparation, and technique for lymphoscintigraphy.
• Outline potential complications and their clinical significance of lymphoscintigraphy.
• Review interprofessional team strategies for improving care coordination to advance lymphoscintigraphy, thus improving outcomes.

Introduction

Lymphoscintigraphy is a method used to map the lymphatic system. Attempts at understanding and mapping the lymphatic system began in the 1600s upon discovery of the cisterna chyli and thoracic duct. In 1786 the first description of the lymphatic system in the breast was written containing information on two main drainage pathways; axillary and internal mammary. Later it was observed that intradermal or parenchymal injection would be an intralymphatic injection in theory. With this knowledge, the modern-day intralymphatic injection is via the intradermal route.

In the late 1900s, this method would be used to discover methods of imaging the lymphatic system through injection of radiopaque contrast agents for visualization, which subsequently allowed for visualization of the first lymph node to receive the agent, termed the “sentinel lymph node.”  A switch from radiopaque contrast agent to a radioactive isotope with labeled gold colloid was made with the addition of visual dye injections for the purposes of identifying sentinel lymph nodes for biopsy purposes. The most up-to-date lymphoscintigraphic technique is through the use of technetium 99m-labeled sulfur colloid as a tracer.

The sentinel lymph node idea, which is identified by either the radioisotope, visual dye, or both, is based on the principle that primary tumors drain to one or a few initial lymph nodes before spreading to the entire body. If the correctly identified sentinel lymph node is negative for metastasis, it is likely that the neoplasm is contained within the primary tumor location. This has many implications for the management of the neoplasm and can be of great importance and benefit for the patient and clinical decision making.[1][2][3][4][5][6][7][8]

Anatomy and Physiology

The lymphatic system is intimately connected to the vascular system and is made up of a large network of lymphatic vessels, lymphatic organs, and lymphoid tissues. The primary lymphoid organs include bone marrow and thymus, as these organs generate lymphocytes, integral to the immune system. The secondary lymphoid organs include lymph nodes and spleen. The cisterna chyli and thoracic duct are some of the largest vessels of the lymphatic system, located within the thorax.

The lymphatic system plays an important role in the regulation and maintenance of tissue fluid balance, immune system, and lipid transport from the alimentary tract. Neoplastic cells are spread to lymph nodes through lymphatic vessels resulting in the progression of cancer into distant tissues. Extracellular fluid enters the lymphatic system through the single layer of endothelial cells with a broken basement membrane, which functions as a one-way valve where increased extracellular fluid pressure will force fluid into the lymphatic system. Collective lymphatic vessels then have a more structured wall allowing lymph to stay within the vessel, which eventually flows through the regional lymph nodes and back into the blood circulation. Many factors result in the propulsion of the lymph through the lymphatic system, including pulsatile blood flow, muscle contraction, pressure gradients, and autonomous lymphatic vessel contractions. There are intraluminal valves within larger lymphatic vessels to help prevent backflow.

Tumors cause a local increase in surrounding lymphatic vasculature, which does not extend into the tumor itself. Instead, local fluid pressure gradients and active signaling from VEGF factors result in the passage of tumor cells into the increased adjacent lymphatic vasculature. The local infiltrating cancer cells will then travel through the collecting lymphatic vessels into the draining lymph nodes. Cancer laden lymph node will cause increased flow resistance, and subsequent rerouting of lymph flow will occur, allowing for a greater spread of metastasis.[9][10]

Indications

Lymphoscintigraphy is used as an adjunct to neoplasm staging workup and pre-operative planning in breast cancer diagnoses. Lymphoscintigraphy paired with axillary sentinel lymph node biopsy has replaced staging axillary lymph node dissection in early disease and is now considered the standard of care. If sentinel lymph node procedures demonstrate axillary metastasis, axillary lymph node dissection will then be performed.

There are several indications for lymphoscintigraphy, including diagnosis and workup of metastatic diseases as well as diagnosis of lymphatic flow disorders such as lymphatic dysplasia or chylous leaks such as chylous ascites or chylothorax. Lymphoscintigraphy can be used for initial diagnosis as well as outcome monitoring after an intervention.[11]

Contraindications

There are a number of contraindications of lymphoscintigraphy, with most of them being relative contraindications. A patient with clinically positive lymph nodes should not obtain lymphoscintigraphy imaging. The examination should also not be performed or avoided if there is a history of hypersensitivity or allergy to the radiotracer. Pregnant or breastfeeding females need to consider the risks and benefits and take extra precautions when considering the examination because of the small amount of exposure to radiation.

If there is a recent surgical intervention within the region of concern, waiting two weeks is recommended for minor procedures and six weeks for major procedures because of concern for false positives from post-surgical reactive tissues. If a patient has a difficult time maintaining a certain position for a long period of time, the test will be less accurate, and the performance of the examination may not provide reliable results. Also, regarding the accuracy of the examination, patients with high body mass index may result in low-quality examinations.[12]

Equipment

The ideal radiotracer for lymphoscintigraphy would be one that demonstrates rapid uptake into the lymph nodes with prolonged retention. The most commonly used radiotracer currently is technetium 99 sulfur colloid. A scintillation gamma camera is also needed to acquire the images produced by the radiation the radiotracer emits, and a dedicated computerized workstation is used to calculate and produce the images.[11]

Preparation

Radiologists, nuclear medicine physicians and technicians, cyclotron engineers, surgeons, and scheduling departments are required personnel to set up and perform lymphoscintigraphy.

There is no specific preparation for a patient receiving lymphoscintigraphy imaging. A nuclear medicine technologist should be present to assist, explain, and execute the examination. Additionally, a physical examination should be performed before injection to further confirm that no recent surgical intervention has been performed. All prior imaging and medical records should be reviewed by the radiologist or nuclear medicine physician. Certain questions should be asked prior to image acquisition, including if the patient is able to maintain a position of lying on a hard surface for an extended period of time as well as inquiring about pregnancy status or current breastfeeding. The patient should remove all clothing and jewelry and wear a hospital gown if available.

Quality control on the equipment should be routinely performed including the imaging system, display, and gamma probes. The Society of Nuclear Medicine has provided general guidelines for quality control, which should be referred to often to ensure proper adherence.[13]

Technique or Treatment

For melanoma or other cutaneous lesions, radiotracer should be injected intradermally around the lesion with a fine gauge needle, tangential with the skin. Two to four injections around the site with 0.1 to 0.2 mL of technetium 99 deposited each time. The total activity of around 200-1,000 microCuries will be injected.

For breast malignancy, there are several techniques that could be performed with the most common technique being perilesional injection (whether superficial or deep) with 3-4 mL injected with a total activity of 200 to 3,000 microCuries. Another method includes intradermal or subcutaneous injection superficial to the lesion with 0.2 to 1 mL of technetium 99 injected with a total activity of 150-2,000 microCuries. Other methods include periareolar region injection and intralesional injection.

For lymphatic flow pathology, the interdigital space of the affected extremity should be injected with 0.05 mL of technetium 99 with a total activity of 500 microCuries.

The planar scintillation camera is then set appropriately for technetium 99 with a large field-of-view detector and parallel-hole collimator. Image acquisition should occur immediately after injection until 45 minutes to an hour after the injection, and a cobalt-57 flood source can be utilized to outline the body for better localization. If anatomy is more complex, SPECT-CT can be used for cross-sectional analysis. Status (planar) imaging should be obtained at 15 to 30 minutes, 1 hour, and 2 to 4 hours after injection and as needed, according to the radiologist, up to 24 hours after injection. The three planes that should be obtained include anterior, anterior oblique, and lateral. Image acquisition time takes up to 5 minutes to obtain sufficient counts. The number of counts within a sentinel lymph node has not been shown to correspond to the severity of the disease; therefore identification of the sentinel lymph node is the most important factor and purpose. Dynamic imaging can be obtained if desired according to the interpreter’s request.

If the patient is undergoing the examination for identification of the sentinel lymph node during surgery, a gamma probe will be utilized to identify the area of highest activity.

The technical success rate of lymphoscintigraphy is close to 100%.[11][14][15]

Complications

Lymphoscintigraphy is relatively noninvasive and has very few adverse effects. The most common complications would include extravasation of radiopharmaceuticals and an allergic reaction to the radiotracer. Extravasation of technetium 99 into the perivascular soft tissues has not been shown to cause significant adverse effects. Allergic reactions to radiotracers are rare; however, they do occur, and the American College of Radiology has provided appropriate steps for patients who are at risk and those with minor to severe reactions. Preparatory medication includes corticosteroids and antihistamine, while the emergent medications after the development of symptoms (ranging from a mild skin rash to anaphylaxis and hypotension) include epinephrine and labetalol.

Lymphoscintigraphy is used for identifying sentinel lymph nodes and the flow of lymph through the body. There have been reports of non-sentinel lymph node metastasis, and when an identified sentinel lymph node is proven negative by pathology, there is a chance that there is metastasis to other lymph nodes not biopsied. This suggests in some rare cases that the examination cannot be fully relied upon for determining the extent of nodal metastasis. Additionally, sentinel lymph node non-visualization on imaging occurs. If the patient is going to surgery after the examination, intraoperative gamma probes will often detect radiotracer in the sentinel lymph node.

Small lymphatic leaks will not be identified and produce a false negative because of the inherent low spatial resolution of nuclear medicine imaging. If a lymphatic leak occurs into the peritoneal or thoracic cavity, the water-soluble radiotracer will dilute quickly and will be difficult to evaluate on the imaging.[12][16]

Clinical Significance

Lymph nodes are the most common location for metastasis. There is a strong correlation between the presence of metastasis within the lymphatic system and prognosis. Given this, the treatment of neoplastic cells within the lymphatic system is essential for the prevention of distant metastatic locations. Once a distant metastatic location is identified, it is more likely that the patient will be treated with systemic therapy.

Lymphoscintigraphy has a benefit and clinical significance, most commonly utilized in the identification of sentinel lymph nodes for breast cancer to determine the extent of disease metastasis. When a sentinel lymph node is identified and shown to be negative for metastasis, there can be higher confidence that the disease has not metastasized distally. It has a relatively low exposure to radiation and is non-invasive with a high impact on clinical decision making, therefore, adding value to the field of medicine. The field of lymphatic system imaging has been growing recently with many large advances, including MR lymphangiography and intranodal lymphangiogram, for interventional procedures with research published frequently, indicating the growing field.[1][11][17]

Enhancing Healthcare Team Outcomes

Lymphoscintigraphy is a diagnostic imaging modality that uses radiotracers to identify lymph node extent of neoplasm as well as lymphatic system flow issues. With limited complications, including extravasation of radiotracer during injection and allergic reaction, the most effective way to enhance healthcare team outcomes occurs through coordination of care to smoothly execute the examination. Prior to the patient arriving at the imaging facility for their examination, the following items should be completed:

• Accurate and appropriate scheduling should occur for optimal patient satisfaction.
• Screening for patient history should be done, including interrogation for recent surgeries, recent imaging with radiotracers, allergies, and personal medical history. If a history of prior radiotracer reaction is present, the radiologist should oversee the appropriate pre-scan medication preparation and/or cancellation of the examination.
• Quality control on the scintillation camera should be performed by the nuclear medicine technician according to the general guidelines by the Society of Nuclear Medicine.
• Image and chart review should be performed by the radiologist for a better understanding of the case and ensuring that the examination will answer the desired questions of the consulting physician.
• The chosen radiotracers should be prepared (and shipped if necessary) within the appropriate timeframe to avoid radioactive decay.
• The surgeon should be informed of the schedule for the examination in case they would like to take the patient to surgery for immediate post-examination sentinel lymph node biopsy.

When all the steps and scheduling has taken place with all involved parties appropriately, high-value care is provided. The patient, as well as the entire healthcare team, will have an overall better experience with more associated positive outcomes. Current Oxford CEBM levels of evidence would be at level 1.