Background/Objectives: High-frequency ultrasonography (HFUS) has gained increasing attention in dermatology as a non-invasive imaging technique capable of visualizing cutaneous structures with high resolution. In cutaneous T-cell lymphomas (CTCL), including mycosis fungoides (MF)/Sézary syndrome (SS), HFUS may provide an objective method for assessing disease activity and monitoring treatment response. This study aimed to evaluate the clinical utility of HFUS in detecting therapy-induced changes in subepidermal low-echogenic band (SLEB) thickness. Methods: We conducted a prospective, single-center study between May 2021 and May 2025. Thirty-three patients with histologically confirmed MF (n = 31) or SS (n = 2) underwent HFUS at baseline and after 4–8 weeks of treatment. SLEB thickness was measured before (E1) and after early treatment (E2). Patients received systemic agents, phototherapy, or topical regimens. Statistical analysis included mixed-model ANOVA with repeated measures to assess SLEB changes, and post hoc tests were applied to explore the influence of therapy type, age, and gender. Results: Among 31 evaluable patients with MF, HFUS revealed a significant reduction in SLEB thickness after treatment (0.90 ± 1.10 mm vs. 0.69 ± 0.89 mm; F(1,29) = 8.88, p = 0.006, η² = 0.23). The type of early therapy (systemic vs. topical) did not significantly affect outcomes (p = 0.452). Age emerged as a relevant factor: patients ≥ 66 years exhibited higher baseline SLEB values and a significant reduction post-treatment (p < 0.001), whereas no comparable effect was observed in younger patients. Gender did not significantly influence SLEB changes. Conclusions: HFUS is a sensitive and clinically applicable imaging tool for monitoring treatment response in MF/SS. Reductions in SLEB thickness were observed across therapeutic modalities and aligned with early clinical improvement. HFUS may serve as a valuable adjunct to standard clinical and histopathological evaluation in the routine management of MF/SS.

Background/Objectives: Cutaneous T-cell lymphoma (CTCL), including Mycosis fungoides (MF) and Sézary syndrome (SS), is a challenging-to-diagnose lymphoproliferative malignancy characterized by T-cell dysfunction and progressive cutaneous and extra cutaneous involvement. Disease severity assessment in CTCL is crucial for guiding treatment. This study aims to evaluate the interrater agreement and interrater reliability of mSWAT among dermatology residents and identify lesion types most prone to scoring variability. Methods: Sixteen dermatology residents with varied experience levels assessed 14 patients with confirmed MF/SS diagnoses. Using mSWAT, residents independently scored lesions severity on a standardized set of patient’s photos. The results were compared with reference mSWAT scores provided by an experienced clinician. Descriptive statistics and the Shapiro–Wilk test were applied to evaluate data distributions, while Student’s t-test assessed score deviations from reference values. Furthemore, we conducted a pilot the high frequency ultrasound (HFUS) study on a single patient, whose mSWAT score and photographs are also presented in the manuscript. Results: Significant discrepancies were observed in 64.29% of cases (9/14), with tumors and infiltrative lesions in erythrodermic SS patients posing particular scoring challenges. Misclassification of tumors as patches or plaques was a frequent issue, leading to underestimations in mSWAT scores. Residents’ assessments of infiltrative lesions were also notably inconsistent. Conclusions: This study highlights significant interobserver variability in mSWAT scoring among less experienced dermatology residents, particularly with tumor and erythrodermic lesions. Findings underscore the need for enhanced training and standardized scoring protocols to improve mSWAT reliability. Similar to other comparable indices, such as PASI, the mSWAT should be employed consistently by the same physician during each assessment to systematically monitor and evaluate the skin condition of a patient under observation. However, broader application requires the acquisition of sufficient experience. The study suggests the use of the HFUS as an objective method of assessment of the skin lesion infiltration in MF/SS patients.