The hypothesis of tumor seeding in the pathogenesis of MF. Even in the early stages of the disease, patients have circulating neoplastic T-cell clones in peripheral blood. Early lesions are initiated by the pioneer clones and create a niche (blue-shaded area) that facilitates seeding of this area of the skin (lesion 1) with subsequent clones (lesion 2) (consecutive seeding model⁴³  and supplemental Figure 6). The clonal composition of different lesions may differ (lesion 3) due to the stochastic nature of cancer seeding. Some clones may have a higher proliferation capacity in the skin and may overgrow other clones (green clone in lesion 3), further mutate, reenter the circulation (orange arrow), and reseed another area of the skin (lesion 4). The figures represent symbolically the structure of the skin with the epidermis (Epi), dermis (Der), and a pink-shaded blood vessel (BV). Different clones of neoplastic T cells are marked with different colors.