Beyond Binary Positivity: Spectrum of Nodal Tumor Burden in Sentinel Lymph Node Biopsy for High-Risk Cutaneous Squamous Cell Carcinoma

Background and Objectives: Sentinel lymph node biopsy (SLNB) is increasingly used for high-risk, clinically node-negative cutaneous squamous cell carcinoma (cSCC), yet pathological reporting remains binary, lacking morphological stratification. The prognostic relevance of nodal tumor burden subtypes—isolated tumor cells (ITC), micrometastases, and macrometastases—is well established in melanoma and breast cancer but remains uncharacterized in cSCC. We aimed to describe the morphological spectrum of sentinel lymph node involvement in a consecutive institutional cohort and determine whether primary tumor characteristics predict the extent of nodal colonization. Materials and Methods: We conducted a retrospective-observational study at Clinical Center Niš (Serbia) including 35 consecutive clinically N0 high-risk cSCC patients who underwent SLNB using a dual-tracer protocol (99mTc-labeled albumin and methylene blue). Sentinel nodes were processed by serial sectioning with hematoxylin-eosin and pancytokeratin (AE1/AE3) immunohistochemistry. Deposits were classified as ITC (≤0.2 mm), micrometastases (>0.2–2.0 mm), or macrometastases (>2.0 mm). Clinicopathologic predictors were evaluated using the Mann–Whitney U test, Fisher’s exact test, the Kruskal–Wallis test, and the Spearman rank correlation test. Results: SLN involvement was identified in 12 of 35 patients (34.3%). Among positive cases, ITC accounted for 6 patients (50.0%), micrometastases for 5 (41.7%), and macrometastasis for 1 (8.3%)—minimal nodal disease constituting 91.7% of positive findings. No primary tumor feature—including diameter, thickness, grade, perineural invasion, or lesion multiplicity—significantly distinguished ITC from overt metastatic deposits. Patients with ITC showed numerically higher median tumor thickness (8.0 mm) than those with micrometastases (4.0 mm), though this did not reach significance (Kruskal–Wallis p = 0.065). Conclusions: SLN positivity in high-risk cSCC is morphologically heterogeneous, with minimal nodal disease predominating. Primary tumor features do not reliably stratify the extent of nodal colonization. Structured tumor-burden reporting—distinguishing ITC, micrometastases, and macrometastases—should be adopted as standard practice to enable meaningful prognostic comparisons and inform individualized management.