Imaging is more sensitive than physical examination for nodal staging of cutaneous squamous cell carcinoma (cSCC), although its performance is reduced in immunosuppressed patients, according to a recent Spanish study.

Early detection of nodal metastases is critical in high-risk cSCC, where prognosis worsens markedly once regional spread occurs. However, the optimal approach to baseline nodal staging is still unclear.

The multicentre Longitudinal Appraisal of CT and Ultrasound for Node Assessment in cSCC (LACUNAS) diagnostic study, published in the journal JAMA Dermatology, compared the performance of physical examination, ultrasonography and contrast-enhanced computed tomography (CT) to address this gap.

The cohort comprised 155 adults enrolled across 13 tertiary dermato-oncology centres in Spain. Each had histologically confirmed high-risk cSCC, of whom 41.3% were immunosuppressed.

Patients had Brigham and Women’s Hospital (BWH) stage T2b/T3 or T2a tumours with additional high-risk features, and all underwent a baseline physical examination, high-resolution ultrasonography, and contrast-enhanced CT one month before and after surgery.

Ultrasonography sensitivity in high-risk cSCC

Sensitivity for detecting nodal metastases was the primary outcome. Specificity, predictive values and the area under the receiver operating characteristic curve (AUROC) were secondary measures, using histopathology or short-term follow-up as the reference standard.

Nodal metastases were seen in 12 patients within three months of surgery. Ultrasonography had the highest sensitivity for detection at 63.6% (95% CI 30.8–89.1%), followed by CT at 54.5% (95% CI 23.4–83.3%), whereas sensitivity for physical examination was only 8.3% (95% CI 0.2–38.5%). Specificity was high across all modalities.

Ultrasonography and CT showed strong agreement and had similar overall diagnostic performance, suggesting they can be used interchangeably depending on the clinical context. In contrast, imaging results and physical examination demonstrated low concordance.

Diagnostic performance varied by immune status

Both ultrasonography and CT had 100% sensitivity and demonstrated excellent discriminatory performance in immunocompetent patients (AUROC 0.98 for each), but accuracy declined sharply in individuals with cSCC who were immunosuppressed.

Sensitivity fell to 20.0% for ultrasonography and 16.7% for CT, with AUROC values of 0.57 and 0.55, respectively. In many of these patients, nodal metastases became clinically apparent within three months, despite negative baseline imaging, indicating rapid disease progression.

Physical examination showed consistently low sensitivity across both cSCC groups, reinforcing its limited utility as a standalone staging tool.

Limitations and clinical implications

The authors noted several limitations of the study, including the relatively small number of metastatic events, variability in the timing of the tests, and potential inter-centre variability. The absence of routine short-interval follow-up imaging may have further influenced detection, they added.

Overall, the findings supported the use of radiological imaging as part of baseline staging for high-risk cSCC. However, the markedly reduced diagnostic performance in immunosuppressed patients highlights an unmet need and spotlights the importance of close clinical follow-up and potentially tailored approaches in this population.

The authors highlighted that future research should assess whether earlier detection of subclinical nodal disease improves survival outcomes and explore optimised staging pathways, particularly in immunosuppression. They also noted that guideline recommendations may need to be stratified by immune status to optimise diagnostic outcomes.

Reference
Ferrándiz-Pulido C et al. Diagnostic modalities and nodal staging in high-risk cutaneous squamous cell carcinoma. JAMA Derm 2026;Apr 22:doi:10.1001/jamadermatol.2026.0803.