Continuing Education Activity

Lymphoscintigraphy is a nuclear medicine imaging technique for mapping the lymphatic system using radiopharmaceuticals or radiotracers. Lymphoscintigraphy is a critical evaluation tool for patients with various malignancies, including breast cancer and melanoma. Identifying sentinel lymph nodes via lymphoscintigraphy facilitates treatment planning and helps patients avoid unnecessary invasive procedures such as lymphadenectomy. Lymphoscintigraphy is a vital evaluation tool for patients with lymphedema unrelated to malignant disease.

Lymphoscintigraphy is noninvasive, apart from targeted radiotracer injections, and has a low complication rate while having few contraindications. Applications for lymphoscintigraphy continue to expand as clinicians seek to minimize invasive, sometimes disfiguring, therapies for malignancy. This activity reviews the pertinent anatomy, indications, contraindications, complications, necessary equipment, procedural steps, and clinical application of lymphoscintigraphy and highlights the critical role of the interprofessional team in improving outcomes for patients undergoing this imaging study.

Objectives:

• Identify appropriate candidates for lymphoscintigraphy based on their clinical history.

• Apply knowledge of lymphatic anatomy and physiology to interpret lymphoscintigraphy findings in the context of specific disease processes.

• Screen patients for contraindications to lymphoscintigraphy to mitigate potentially adverse outcomes.

• Develop and implement effective interprofessional team strategies to improve outcomes for patients undergoing lymphoscintography.

Introduction

Lymphoscintigraphy is a nuclear medicine imaging study for mapping the lymphatic system with scintigraphy. Attempts at understanding and mapping the lymphatic system began in the 1600s with the discovery of the cisterna chyli and thoracic duct.[1] The lymphatic drainage of the breast was first described in 1786 and identified 2 dominant drainage pathways of the breast: the axillary lymphatic basin and the internal mammary nodes.[2] Subsequently, intradermal or parenchymal injection of scintigraphic agents was found to be equivalent to an intralymphatic injection. In the late 20th century, protocols employing radiopaque contrast agents to visualize the first lymph node to receive the contrast agent, also termed the “sentinel lymph node,” were developed.[3] Several radioisotopes have been used for lymphoscintigraphy; current lymphoscintigraphic techniques utilize Technetium Tc 99m sulfur colloid.[4] The ideal radiotracer for lymphoscintigraphy will demonstrate rapid transfer to and prolonged stay within the lymph node.

Understanding the map of lymphatic drainage patterns of anatomical structures defines the clinical application of lymphoscintigraphy. A sentinel lymph node is the first node that accepts lymphatic drainage from an anatomical site. In cases of malignancy, such as malignant melanoma or breast cancer, the sentinel lymph node is most likely to harbor occult metastases. Sentinel lymph node histopathologic analysis, in the absence of overt metastases, can potentially preclude the need for adjuvant therapies, including lymphadenectomy, radiotherapy, chemotherapy, or more invasive surgical procedures. Lymphoscintigraphy has become the standard of care when managing select breast cancer and melanoma cases; other applications include the evaluation of lymphedema.[4]

Anatomy and Physiology

The lymphatic system drains lymph, which is water and other constitutive elements of the interstitial space with a composition similar to plasma, to the vascular system (see Image. Lymphoscintigraphy).[5][6] From descriptions as early as those of Sappey in 1874 and through ongoing lymphatic mapping, the predominant conceptual understanding of the lymphatic zones draining the skin are:

• Four zones of skin on the trunk drain to the axillary or groin lymphatic basins [7]
• Any region of skin along the borders of these zones has a less predictable drainage pattern [7]
• Postsurgical changes can often result in significant variability in lymphatic drainage patterns [8]

Under normal circumstances, most breast lymphatics drain to the ipsilateral axillary lymph nodes. Approximately 3% of breast lymphatics drain to the internal mammary chain nodes, and a smaller proportion drains to the posterior intercostal lymph nodes.[9] Given the infrequent and unlikely nodal basin of the posterior intercostal lymph nodes, this drainage pattern is considered less clinically relevant. The Sappey areolar plexus constitutes a complex network of lymphatics in and around the nipple-areolar complex. This plexus is clinically relevant; subareolar or periareolar radiotracer injection utilizes this lymphatic network to identify a sentinel lymph node.[10] 

Malignant melanoma frequently presents on the skin of the lower extremities and torso.[11] The ipsilateral axillary lymph nodes drain the upper extremities, and the inguinal lymph nodes drain the lower extremities. While the drainage of torso cutaneous melanomas is relatively predictable, aberrant drainage basins are frequently encountered, most notably from the longitudinal and horizontal midlines of the torso. Additional sites of potentially aberrant drainage include the long head of the triceps muscle and the triangular intermuscular space formed by the borders of the teres major and minor muscles. [12]

Indications

Lymphoscintigraphy is typically performed in the following circumstances:

• As an adjunct to clinical staging and preoperative planning in patients with breast cancer
• To identify sentinel lymph node drainage in patients with malignant melanoma as an adjunct to staging and treatment planning
• When diagnosing and evaluating lymphatic flow disorders such as chronic lymphedema (see Image. Lymphoscintigraphy, Lymphedema) [13]
• When evaluating chylous ascites or chylothorax [14]
• When evaluating patients with specific gynecologic cancers.[15][16][11]

Contraindications

Absolute contraindications to lymphoscintigraphy include but are not limited to clinically positive nodal disease. Relative contraindications to the procedure include allergies to radioisotopes or components of the radiotracer preparation, pregnancy, and significant alterations to normal anatomy, including those encountered after prior therapeutic interventions.

Equipment

The equipment to perform lymphoscintigraphy typically includes:

• Collimator: low-energy, all-purpose, parallel (LEAP) collimator
• Gamma camera
• Gamma probe; an instrument typically utilized in the operating room
• Radiotracer: the most commonly utilized radiotracer is filtered or unfiltered technetium Tc 99m sulfur colloid; other radiotracers are available
  • Filtered tracer typically requires a 22-μ millipore filter
  • A pH-balanced 1% lidocaine additive can be considered based on institutional preference.

Preparation

In preparation for lymphoscintigraphy, a comprehensive medical history should be obtained, prior imaging studies should be thoroughly reviewed, and pregnancy status should be definitively identified and adequately documented. The indications, risks, benefits, and alternatives to the procedure should be thoroughly explained to the patient before informed consent to proceed is obtained. The possibility of pain during injection of the radiotracer should be explicitly discussed. Jewelry or overlying objects that may result in photo attenuation should be removed; this includes necklaces that may obscure visualization of the internal mammary lymph nodes. The injection site should be examined, marked, and cleansed.

Lymphoscintigraphy is typically performed with the patient either supine or prone. Patients undergoing lymphoscintigraphy for the evaluation of breast cancer should position their arms in a position mimicking that held intraoperatively.

Technique or Treatment

Radiotracer activities vary and depend on the institution. The activity typically utilized for lymphoscintigraphy ranges from 0.1 to 10 mCi; doses are often adjusted depending on the timing of the injection with planned surgery. The injection technique and the number of injections will vary among institutions and may include peritumoral, intradermal, periareolar, and subareolar techniques; the chosen technique has demonstrated little effect on sentinel lymph node identification. 

Considerable institutional variation exists for lymphoscintigraphy procedures. However, the following generalities typically persist:

• When evaluating melanoma or other cutaneous lesions, radiotracer can be injected intradermally around the lesion using a fine-gauge needle tangential to the skin.
• A combination of deep and superficial radiotracer injections may decrease the number of false-positive lymphoscintigraphic results in patients being evaluated for breast malignancies.[17]
• A synchronous injection of the affected and contralateral extremities is preferred when evaluating patients with lymphedema.

Following radiotracer injection, sequential or continuous imaging is performed for 30 to 60 minutes; the routine field of view includes the expected drainage direction. Intense activity at the site of radiotracer administration may need to be attenuated with lead. Massaging the injection area may improve radiotracer distribution. Transmission images with a Cobalt-57 source are often utilized, and oblique views may also be useful in node identification. 

Complications

Lymphoscintigraphy is relatively noninvasive and has few adverse effects. One of the most common complications associated with lymphoscintigraphy is radiopharmaceutical extravasation into perivascular tissues; no long-term adverse effects have been reported. Another common complication of lymphoscintigraphy is an allergic reaction to the radiotracer or its preparation. Allergic reactions to radiotracers are rare; reactions to the preparation contents, such as lidocaine, are more common.

Clinical Significance

The identification of a sentinel lymph node in patients undergoing evaluation for breast cancer or melanoma has a critical role in guiding treatment strategies. A sentinel lymph node provides diagnostic information regarding the presence or absence of metastases and predicts the metastatic potential for the evaluated malignancy. The decision to employ surgical techniques that include more extensive interventions is also guided by the presence or absence of metastases in a sentinel lymph node (see Image. Lymphoscintigraphy, Breast Cancer).

The morbidity associated with axillary lymph node dissection, namely lymphedema, has furthered the role of lymphoscintigraphy. The added advantage of histopathologic sectioning of a single lymph node and the ability to use staining in a more targeted manner can promote better detection of isolated tumor cells.[18] Observations on the limitations of lymph node dissection, its effect on overall survival, and the lack of survival benefit of lymphadenectomy following the identification of a positive sentinel lymph node underscore the need for effective lymphoscintigraphic methods.[19][20][21]

Sentinel lymph node identification and biopsy as a staging tool in intermediate-thickness melanoma has similarly precluded the need for lymph node dissection in patients for whom such a surgical intervention would yield little benefit (see Image. Lymphoscintigraphy, Melanoma).[22] Lymphadenectomy following positive sentinel lymph node identification in patients with melanoma offers little benefit.[23]

Enhancing Healthcare Team Outcomes

Lymphoscintigraphy is a diagnostic nuclear medicine imaging modality that employs radiotracers to identify neoplastic lymph node involvement and lymphatic system flow issues. The most effective way to enhance patient outcomes is through coordination of care to smoothly execute the examination, interpret the results, and relay those results to the pertinent parties. This coordination of care begins before the patient arrives at the imaging facility. Accurate and timely scheduling of the examination facilitates patient satisfaction. Once the study is scheduled, the ordering physician should be informed; some patients must proceed immediately to sentinel lymph node biopsy.

A comprehensive preimaging questionnaire should be completed with the assistance of clinical nursing or scheduling staff. This questionnaire should include inquiries about recent surgical procedures, imaging studies with radiopharmaceuticals, and a general medical history. Particular attention must be paid to any history of allergic reactions, particularly to radiopharmaceuticals; while rare, such an allergy may require modifications to the radiotracer preparation or alternate imaging methods.

The nuclear medicine technician must perform scintillation camera quality control measures according to the general guidelines of the Society of Nuclear Medicine. The chosen radiotracers should be prepared and shipped when necessary within an appropriate timeframe to avoid radioactive decay.