Stage-dependent activation of mTORC1 signaling pathway in tissues involved by CTCL. Representative H&E stains of CTCL patch (A) and tumor (D) stage and lymph node involved by CTCL with large cell transformation (G). Immunohistochemical staining for the phosphorylated S235/236-S6rp (B) and S65-4E-BP1 (C) in the patch stage is negative in the majority of atypical lymphocytes with many of the positive cells representing plasma cells and macrophages (B). The stains are positive for the phospho-S235/236-S6rp and phospho-S65-4E-BP1 in a large subset of the atypical lymphocytes cells at the tumor stage (E and F, respectively). The percentage of positive cells was the highest among the malignant-appearing cells in lymph nodes involved by CTCL that has undergone large cell transformation with the positive cells representing a majority in some cases (H,I). The main images represent 200X magnification ×200 and the insets are magnification ×400.