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Ultrasound outperformed baseline clinical assessment for detection of lymph node metastasis in patients with high-risk cutaneous squamous cell carcinoma (SCC) of the head and neck, a retrospective Dutch study showed.

Imaging achieved 91% sensitivity and 78% specificity for metastasis as compared with 50% and 96% for clinical examination. Among patients with lymph node metastasis but a negative baseline clinical exam, ultrasound identified the metastasis in nine of 11 cases.

Ultrasound had a high false-positive rate that led to unnecessary biopsies, which should be weighed against the potential to identify metastasis in clinically negative patients, according to Marlies Wakkee, MD, PhD, of Erasmus Medical Center Cancer Institute in Rotterdam, The Netherlands, and colleagues.

"We found that relying on clinical examination only, which comprises the observation and palpation of often visible lymph node swellings, can result in missed diagnosis for approximately one half of all metastatic disease," the group wrote in . "This finding is similar to that of previous research on the detection of subclinical disease among patients with high-risk cutaneous SCC, which mainly used computed tomography, positron emission tomography, and magnetic resonance imaging."

"Future studies are needed to identify which subsets of patients with high-risk cutaneous SCC would benefit most from baseline ultrasonographic examination in the setting of a negative result at clinical examination," they added. "The European consensus-based recommends ultrasonography for all patients with high-risk cutaneous SCC. However, despite the present population having a greater risk of metastasis, baseline ultrasonography had a high rate of false-positive findings, which may limit its usefulness for routine screening."

The study included 233 patients with 246 high-risk (T2 or higher, T1 with localization on an ear or lip, or recurrent T1) cutaneous SCC tumors of the head and neck referred to Erasmus Medical Center from January 2015 through December 2017. All patients had ultrasound of the head and neck as part of their workup.

A total of 22 metastases were cytologically confirmed, 20 at baseline and two during 6 months of follow-up, resulting in a 9% metastasis rate. Clinical examination detected only half of the metastases while ultrasonography detected all but two (91% sensitivity). Additionally, ultrasonography detected nine of 11 clinically negative metastases for a sensitivity of 82%.

Clinical examination detected clinically suspicious lymphadenopathy in association with 8.1% (n=20) of the 246 high-risk tumors. Fine needle aspiration cytology (FNAC) confirmed metastases in 11 of 20 cases. Baseline ultrasonography identified suspicious lymph nodes in 28.5% of cases (n=70), and FNAC confirmed nodal metastasis in 20 of those cases.

Overall, clinical examination had a specificity of 96%, positive predictive value (PPV) of 55%, and negative predictive value (NPV) of 95%. Baseline ultrasonography had a specificity of 78%, PPV of 29%, and NPV of 99%.

Among those patients who had negative baseline clinical examinations, 54 SCC tumors had a suspicious ultrasonographic result at 6 months, and FNAC confirmed nodal metastasis in nine of those cases. This yielded a specificity of 79% while the NPV remained high at 99%. However, the 45 false-positive results led to a PPV of 17%.

"This low PPV means that, although ultrasonographic examination is highly sensitive for the detection of both clinically visible and occult lymph node metastasis, this sensitivity needs to be evaluated against the consequences of many false-positive ultrasonographic results," the authors cautioned.

Limiting the analysis to primary tumors would have resulted in a metastasis rate of 2.3% (four of 177 tumors), lower than what would be expected for a high-risk cohort, noted Emily S. Ruiz, MD, of Brigham and Women's Hospital in Boston, in an . More than half of the tumors included in the study were low stage and had a very low metastatic risk. Restricting the analysis to recurrent tumors would have resulted in a metastasis rate exceeding 10%.

Additionally, the authors evaluated ultrasonography at diagnosis, Ruiz continued. Not all nodal metastases are present at initial presentation, with many more being identified on surveillance imaging.

"There is no predefined risk level in cancer staging and surveillance when nodal staging should be considered," the editorialist acknowledged.

Also, data are limited on the optimal imaging modality for nodal evaluation in cutaneous SCC. The current study does suggest ultrasonography has promise in this regard and is less expensive than other imaging modalities and safe, involving no radiation or contrast exposure. Ultrasound also can be combined with a routine clinical exam.

"Although ultrasonography is a potential valuable imaging modality, there is a need for further study on which patients benefit from imaging and the optimal imaging modality," Ruiz wrote, agreeing with the authors' final assessment of the study.

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