Differentiating malignant and nonmalignant T cells. (A) UMAP projection of CD3+ T-cell clusters. (B) Percent of cells expressing selected common markers for CTCL across the UMAP projection. (C) UMAP projection with proportion of total reads per sample of TCR V(D)J-based clonotype attached into the following grouping: hyperexpanded (0.1 < X ≤ 1), large (0.01 < X ≤ 0.1), medium (0.001 < X ≤ 0.01), small (1e−4 < X ≤ 0.001), and rare copies (0 < X ≤ 1e−4) using the scRepertoire R package22 with the percentage of cells in each clonotype category in the lower bar chart. Malignant T-cell clusters (C1, C2, C3, C6, C10, C12, and C15) had >50% of cells with hyperexpanded clonotypes. (D) Percent difference (Δ percent) between malignant and nonmalignant T cells vs log2-fold change with the top 10 significant (Bonferroni P value < .05) upregulated genes by both percentages and fold change labeled. (E) Violin plot of relative mRNA expression of the top 12 significant genes by Δ percent difference between malignant (M) and nonmalignant (NM) T cells. (F) Significantly upregulated genes in the single-cell (SC) cohort and a secondary SS cohort29 with the top 10 genes by a log-fold change in overlapping comparison and unique to the SC cohort. (G) Representative immunohistochemistry images for SS at 400× magnification. Representative images and data summary (bar graph) of 35 patients with MF, SS, or T-cell NHL. Black arrows indicate nuclear staining of AIRE, and the images displayed are at 200× magnification.