Sentinel Lymph Node Biopsy: Comprehensive Guide Across Cancer Types
Overview and Fundamental Concept
Sentinel lymph node (SLN) biopsy identifies and removes the first lymph node(s) that directly drain a primary tumor, allowing accurate staging while avoiding the morbidity of complete lymph node dissection. 1, 2 The procedure requires coordination between nuclear medicine physicians, surgical oncologists, and pathologists to achieve optimal accuracy. 1
The technique involves three critical steps: pre-operative lymphoscintigraphy to identify sentinel nodes, intraoperative selective excision guided by blue dye and gamma probe, and meticulous histological examination using serial sections and immunohistochemistry. 1
Melanoma: The Most Established Application
Indications Based on Tumor Thickness
For intermediate-thickness melanomas (T2-T3: >1.0 to 4.0 mm Breslow thickness), SLN biopsy is strongly recommended as it provides critical staging information and guides treatment decisions. 3
Thin Melanomas (T1: <1.0 mm)
- Routine SLN biopsy is NOT recommended for T1a melanomas (non-ulcerated, ≤0.8 mm Breslow thickness). 3
- SLN biopsy may be considered for T1b melanomas (0.8-1.0 mm OR <0.8 mm with ulceration) only after thorough patient discussion of risks versus benefits. 3
- The overall risk of nodal involvement in thin melanomas is only approximately 5.1%, though subsets with ulceration and/or mitotic rate >1/mm² may have up to 20% positivity rates. 3
- High-risk features warranting consideration include ulceration and mitotic rate ≥1/mm², particularly in melanomas 0.75-0.99 mm thickness. 4
Thick Melanomas (T4: >4.0 mm)
- SLN biopsy may be recommended for thick melanomas after discussing potential benefits and risks, primarily for staging and regional disease control. 3
- Despite conventional wisdom suggesting high systemic disease risk, SLN biopsy provides important prognostic information, with seven of eight studies showing it as a significant predictor of overall survival. 3
- Approximately 30% of patients with thick melanomas have lymph node involvement, making regional disease control particularly important. 3
Management After Positive SLN Biopsy: Critical Paradigm Shift
For patients with positive SLN biopsy, either completion lymph node dissection (CLND) OR careful observation are acceptable options for low-risk micrometastatic disease, with clinicopathological factors guiding the decision. 3
This represents a major departure from older guidelines:
Low-Risk Features (Observation Acceptable)
- Absence of extracapsular spread/extension 3
- No concomitant microsatellitosis of primary tumor 3
- ≤3 involved nodes 3
- ≤2 involved nodal basins 3
- No immunosuppression 3
High-Risk Features (CLND Preferred, Observation Only After Extensive Discussion)
- Extracapsular spread/extension present 3
- Concomitant microsatellitosis 3
3 involved nodes 3
2 involved nodal basins 3
- Patient immunosuppression 3
Critical Evidence: The MSLT-II and DeCOG-SLT randomized controlled trials showed no difference in melanoma-specific survival between CLND and observation groups, but lymphedema incidence was significantly higher with CLND. 3 These trials included 66% of patients with sentinel node metastases >1.01 mm in size. 3
Important caveat: If CLND is not performed, the risk of regional nodal metastasis as first recurrence is approximately 15-20%. 3 However, CLND reduces regional nodal recurrence to approximately 4.2%. 3
Breast Cancer: Standard of Care
SLN biopsy has become standard surgical treatment in breast cancer patients without clinical evidence of nodal involvement. 2, 5
Technical Considerations
- Remove at least two sentinel nodes when possible, as false-negative rates are 31% with single-node sampling versus 12% with two nodes. 6
- Verify residual radioactivity in the lymphatic basin intraoperatively—it should be less than one-tenth that of the excised node with lowest radioactivity. 6
Management of Micrometastases and Isolated Tumor Cells
- Micrometastases are defined as tumor deposits >0.2 mm but ≤2.0 mm (classified as pN1mi). 6
- Isolated tumor cells (ITC) ≤0.2 mm are classified as pN0(i) and observation without completion ALND should be considered, as these have minimal clinical significance. 6
Axillary Dissection Technique
- During completion dissection, remove level I and II axillary lymph nodes while preserving the long thoracic nerve (C5-C7) and thoracodorsal nerve to prevent serratus anterior and latissimus dorsi dysfunction. 6
Other Cancers with Established SLN Biopsy Protocols
Vulvar and Cervical Cancer
SLN biopsy has become standard surgical treatment for vulvar and cervical cancers without clinical nodal involvement. 2, 5
Head and Neck Cancer
SLN biopsy procedures are used routinely for head and neck cancers, though specific indications vary by primary site. 5
Penile Cancer
Routine SLN biopsy procedures are established for penile cancer staging. 5
Gastrointestinal Cancers (Investigational)
- Gastric, esophageal, and colon cancers: SLN biopsy procedures are under investigation but not yet standard practice. 5
- The role remains undefined and should be considered investigational outside clinical trials. 5
Genitourinary Cancers
- Prostate cancer: SLN biopsy procedures are being investigated. 5
- Uterine and ovarian cancers: Under investigation but not standard practice. 5
Lung Cancer
SLN biopsy for lung cancer remains investigational after over 20 years of research and has not achieved the same impact as in melanoma or breast cancer. 7 The technique has not been validated sufficiently to recommend routine use. 7
Critical Technical and Pathological Requirements
Pathological Processing Standards
Sentinel nodes must be cut into perimeridianal slices ≤2 mm thick and examined with H&E staining at minimum. 6
- Perform step sections at 200-500 μm intervals rather than superficial serial sections alone, as this detects additional micrometastases more effectively. 6
- Submit each sentinel node in a separate cassette or mark with colored ink to permit accurate assessment of total node count and number of involved nodes. 6
- Immunohistochemistry with cytokeratin antibodies may be considered to facilitate detection of small tumor deposits, though not currently mandated by ASCO guidelines. 6
Pathology Report Requirements
The pathology report must document: 6
- Maximal size of the largest tumor cluster 6
- Pattern of metastasis (single cells, clusters, or confluent deposits) 6
- Accurate node counting with surgeon-pathologist coordination to avoid over-recording bisected or serially sectioned positive nodes as multiple positive nodes 6
Critical Pitfalls to Avoid
Failed Procedure Recognition
If only fat was submitted, a negative result should NOT be assumed—this represents a failed procedure requiring repeat sentinel node mapping or formal lymph node dissection if repeat mapping is not feasible. 6
Intraoperative Assessment Limitations
Do not rely solely on intraoperative assessment, as approximately 8-9 false-negative results occur per 100 patients evaluated intraoperatively, with only 16-17 true positives detected. 6
Incomplete Node Removal
Always verify residual radioactivity intraoperatively to confirm complete sentinel node removal. 6
Under-staging Risk
Removing only one sentinel node significantly increases false-negative rates compared to removing two or more nodes. 6
Emerging Technologies
New technologies including indocyanine green (ICG) fluorescent dye and near-infrared fluorescence (NIR) have increased SLN detection rates and decreased false-negative rates. 2 These adjuncts to traditional blue dye and radiotracer techniques may improve accuracy, particularly in challenging anatomical locations. 2