What are the guidelines for sentinel node biopsy in Merkel cell carcinoma?

Sentinel Lymph Node Biopsy Guidelines for Merkel Cell Carcinoma

Sentinel lymph node biopsy (SLNB) should be offered to all patients with clinically node-negative Merkel cell carcinoma, as it provides critical staging information that directly guides adjuvant treatment decisions and identifies the 26-33% of patients with occult nodal metastases. 1, 2

Indications for SLNB

• Perform SLNB in all patients with clinically node-negative (N0) disease to accurately stage nodal involvement and guide subsequent management 1, 3
• SLNB is typically performed concurrent with definitive wide local excision in clinical practice, though ideally it should be done before definitive excision to maximize accuracy 1
• The procedure identifies occult nodal metastases in approximately 26-33% of clinically node-negative patients 2, 4

Pathologic Evaluation Requirements

SLNB evaluation must include specialized immunohistochemistry to avoid missing micrometastases:

• Use an appropriate immunopanel including CK20 and pancytokeratins (AE1/AE3) based on the primary tumor's immunostaining pattern 1
• Perform immunohistochemistry even when hematoxylin and eosin sections appear negative, as 20% of metastases are identified only through immunohistochemical analysis 5
• Report tumor burden (% of node), location within the node (subcapsular sinus vs. parenchyma), and presence/absence of extracapsular extension 1

Management Based on SLNB Results

Negative SLNB

For extremity and torso locations:

• Regional nodal basins can be observed without radiation 1
• Radiation therapy is given to the primary site only in most instances 1
• False-negative rate is approximately 16%, justifying close observation 6

For head and neck locations (critical caveat):

• Higher risk of false-negative SLNB due to aberrant lymph node drainage and multiple sentinel node basins 1
• Consider radiation to nodal beds (46-50 Gy) if at risk for false-negative biopsy 1
• Alternative approach: perform wide local excision without SLNB and irradiate primary site, in-transit lymphatics, and regional nodal sites 1
• Consider radiation when there is potential for anatomic failure (previous surgery including WLE), operator failure, or histologic failure (inadequate immunohistochemistry on sentinel nodes) 1

Positive SLNB

Immediate actions:

• Multidisciplinary tumor board consultation is preferred 1
• Clinical trial participation should be considered when available 1

Treatment options:

• Most patients undergo completion lymph node dissection and/or radiation therapy 1
• For microscopic N+ on SLNB in axilla or groin: 50 Gy radiation 1
• For microscopic N+ on SLNB in head and neck: 50-56 Gy radiation 1
• Patients with positive SLNB have significantly higher risk of in-transit recurrence and may benefit from adjuvant radiation with inclusion of in-transit field 2
• Therapeutic lymph node dissection appears effective in preventing regional nodal recurrence in the short term 4

Prognostic Significance

• Sentinel lymph node positivity is strongly predictive of recurrence risk: patients with positive SLNB have a 19-fold greater risk of recurrence or metastasis compared to those with negative SLNB 4
• Disease recurrence occurs in approximately 30% of SLNB-positive patients versus only 3% of SLNB-negative patients 5
• When SLNB-positive patients receive additional treatment to the at-risk nodal basin, overall survival and disease-specific survival become similar to SLNB-negative patients 2
• Five-year disease-specific survival is 82.4% for SLNB-positive patients versus 86.8% for SLNB-negative patients when appropriately treated 2

Special Considerations

• If SLNB is not performed or is unsuccessful, consider irradiating nodal beds for subclinical disease (46-50 Gy) 1
• No tumor or patient characteristics (sex, age, tumor location, or size) reliably predict SLNB positivity, reinforcing the need to perform SLNB in all clinically node-negative patients 2
• Expeditious initiation of adjuvant radiation therapy after surgery is preferred, as delay has been associated with worse outcomes 1