Lymphoscintigraphy and Sentinel Node Mapping

Lymphoscintigraphy images the lymphatic drainage from a part of the body using a radiolabelled particle injected into the tissue or skin. It has two uses: mapping the first (sentinel) lymph node or nodes that drain a tumour, and assessing lymphatic flow in a swollen limb.

Sentinel node mapping allows removal of the one to three nodes most likely to hold metastases, and spares the patient a full node dissection if they are clear.

Technetium-99m tilmanocept or a technetium-99m labelled colloid (nanocolloid or sulphur colloid) is injected near the tumour or around the scar. The dose is 10 to 40 MBq for sentinel node mapping and 40 to 80 MBq for limb studies.

The tracer is carried by lymphatics to nodes, where it is retained. Planar images are taken at 15 to 30 minutes, with delayed images at 2 to 4 hours when needed.

Injection sites differ by cancer: peritumoural, subdermal, periareolar or intradermal injection in breast cancer, intradermal injection around the scar in melanoma, and peritumoural or submucosal injection in oral, cervical, vulval, penile and prostate cancer. SPECT-CT shows the position of nodes and helps surgery.

In the operating room, a handheld gamma probe finds the node, often with a blue dye or fluorescent dye.

The effective dose is low, about 0.5 to 1 mSv, with the injection site receiving the highest dose. Sentinel node detection rates exceed 95% in breast cancer and melanoma, and the false negative rate is about 5 to 10%.

Sentinel node status is the strongest predictor of prognosis in early melanoma and breast cancer.

Indications.

• Breast cancer: axillary staging in clinically node negative patients.
• Melanoma: staging of nodal basins in intermediate thickness and some thin tumours with adverse features.
• Squamous cell carcinoma of the vulva, penis and oral cavity, and Merkel cell carcinoma.
• Cervical, endometrial and prostate cancer: pelvic node mapping.
• Other tumours in selected centres (thyroid, gastric, colon, skin).
• Limb lymphoedema: confirmation, grading of severity, and exclusion of other causes of swelling.
• Chylous leaks, chylothorax and lymphatic malformations (to show the site of a leak).
• Lymph node transit time and function before lymphatic surgery.

Contraindications and precautions.

• Pregnancy: sentinel node mapping can be done when the benefit is clear, since the dose is low. Blue dye is avoided in pregnancy.
• Breast feeding: usually no interruption needed, or a brief one as the local rule requires.
• Allergy: blue dye can cause anaphylaxis in about 1% of patients. Indocyanine green is an alternative dye, but it contains iodide and is used with care in iodine allergy.
• Large tumours, extensive nodal disease and prior surgery in the area reduce accuracy.
• Palpable or biopsy proven metastatic nodes: the test is not needed and treatment is by dissection.
• Prior wide excision or flap surgery may change lymphatic drainage.
• The injection is painful, particularly for the intradermal route, and local anaesthetic cream may be used.

Preparation and technique.

No fasting is needed. The injection is given by an experienced operator, using sterile technique. In breast cancer, the dose is injected peritumourally, subdermally or periareolarly, and the area is massaged for a few minutes to speed up flow. In melanoma, four intradermal injections around the scar are given.

Dynamic images are taken for the first 5 to 20 minutes, to show lymphatic channels leading to the first node. Static images at 15 to 30 minutes and at 2 to 4 hours show the sentinel nodes.

Lateral and oblique views separate the nodes from the injection site. A marker pen is used to mark the skin over the node.

SPECT-CT is added when nodes are not seen or sit near the injection site, or when the anatomy is complex (head and neck, pelvis). Surgery is the same day or the next day.

During surgery the probe locates the nodes with counts of 10 times the background, and any remaining node with more than 10% of the hottest node is removed.

For limb lymphoscintigraphy, the tracer is injected subcutaneously in the first web space of both hands or feet, and images are taken at 15 to 30 minutes, 1 hour, and 2 to 4 hours. Exercise between images speeds up transit.

Normal appearances.

Sentinel node mapping: tracer moves along a lymphatic channel to one or a few nodes in a basin in 5 to 30 minutes, and is retained. Breast drainage is mostly to the axilla (level I) and sometimes to the internal mammary chain.

The injection site is bright and the liver may show a faint uptake.

Limb studies: symmetrical flow along the limb lymphatics, with nodes in the groin or axilla seen by 1 to 2 hours, and the liver also visible after 2 hours. There is no dermal tracer outside the channels.

Interpretation.

• Sentinel nodes: the first nodes that take up tracer (hot nodes), which may be one to three, sometimes in different basins. Their location and number are reported, with the relation to the injection site and to nodal basins.
• In transit nodes: nodes along the lymphatic channel between the primary and the basin are recorded, since they can hold metastases.
• Non-visualisation: no node is seen. Causes are a blocked channel from tumour, prior surgery, an injection that went wrong, or a node hidden by the injection site. Repeat injection, delayed images or SPECT-CT help.
• Unexpected drainage: to another basin (for example, the internal mammary chain or contralateral axilla) is common in breast and trunk melanoma, and directs surgery.
• Second echelon nodes appear on delayed images and are not regarded as sentinel nodes.
• Histology: the node is examined with serial sections. Metastases are classed as macrometastasis, micrometastasis, or isolated tumour cells, which direct decisions on further surgery and systemic treatment.
• Limb lymphoedema: delayed or absent transit of tracer, dermal backflow (diffuse tracer in the skin), few or absent nodes, and asymmetry between sides. The degree is judged from the transit time and the node uptake.
• Lymphatic leak: tracer collects at the site of leak, such as the pleural space or peritoneum.
• Primary lymphoedema: hypoplasia of lymphatic channels. Secondary lymphoedema follows surgery, radiotherapy, infection or tumour.

Critical values and findings needing immediate action.

• Anaphylaxis to blue dye: stop, give adrenaline and resuscitate. This can occur after the intradermal injection.
• Hot node in an unexpected location (internal mammary, interval node): report to the surgeon before the operation.
• Non-visualisation in a patient with suspected metastatic obstruction: the surgeon decides on full dissection.
• Radioactive node or tissue handling: surgical team follows the local radiation safety rules.

Limitations and artefacts.

• Injection site activity can hide a node near the primary (for example, a tumour in the upper outer breast). Shielding, lateral views or SPECT-CT help.
• Tumour blocking the lymphatics gives non-visualisation or diversion to other nodes.
• Prior surgery, radiotherapy, or a large biopsy cavity changes drainage and lowers detection.
• Contamination of the skin or clothes by tracer mimics a node.
• A false negative sentinel node (5 to 10%) occurs when metastases lie in a non-sentinel node, or when the sentinel node is replaced by tumour. Accuracy depends on the surgeon and the number of nodes removed.
• Late images can show second echelon nodes and confuse the picture.
• Tilmanocept and colloid differ in particle size and flow speed, and the injection depth changes the drainage.
• Limb lymphoscintigraphy needs the same technique at each study for comparison. Early and delayed images are needed.
• The scan does not show the nodal content. Histology decides.

Special groups.

• Breast cancer: sentinel node biopsy is the usual staging method, and the extent of axillary surgery depends on the findings and the planned treatment.
• Melanoma: sentinel node status is the strongest predictor of outcome, and the pattern of drainage is unpredictable in head, neck and trunk lesions.
• Pregnant patients: low dose mapping can be done, with tracer only and no blue dye.
• Children: melanoma, sarcoma and lymphatic malformations. Weight based dose.
• Patients with lymphoedema: the scan helps in choosing between conservative and surgical treatment.
• Regions: breast cancer and melanoma (acral) present late, and filariasis is a common cause of lymphoedema. Mapping is available in few centres, so blue dye alone or axillary surgery is used, and lymphoedema is diagnosed clinically.

Follow up tests.

• Histology of the sentinel node with serial sections and immunohistochemistry.
• Completion node dissection or radiotherapy of the basin, as the pathology and the treatment plan require.
• Ultrasound of nodal basins, with fine needle aspiration of abnormal nodes.
• Staging imaging (PET-CT, CT or MRI) for higher risk tumours.
• Tumour markers and blood tests for specific cancers.
• Lymphoedema measurement, compression therapy and physiotherapy.
• Magnetic resonance lymphangiography or indocyanine green lymphography before lymphatic surgery.
• Referral to surgical oncology, oncology, plastic surgery or lymphoedema services.