[T follicular helper cell lesions and mimics in dermatopathology: From theory to practice]

Interpreting follicular helper T cell (Tfh) markers in the skin is challenging, raising the question of whether their expression is physiological or pathological. This review has two objectives: (1) to summarize current knowledge on Tfh lymphocytes, including circulating Tfh (cTfh) and peripheral helper T cells (Tph), and (2) to propose a practical approach for analyzing Tfh-rich skin infiltrates. Our method consists of two complementary entry points: histological and clinical. The histological approach classifies infiltrates into three patterns: (1) predominantly T-cell proliferation, suggesting a reactive infiltrate or hematodermia, (2) mixed B- and T-cell populations with a diffuse architecture, raising suspicion of a primary cutaneous CD4-positive small/medium T-cell lymphoproliferative disorder or Tfh lymphoma (primary or secondary), (3) B-cell nodules within a diffuse T-cell infiltrate, characteristic of reactive lymphoid hyperplasia, marginal zone B-cell lymphoproliferative disorders, or marginal zone lymphomas. In these cases, anti-IgM and anti-IgD immunolabeling is useful. Beyond Tfh-associated lymphocytes, the expression patterns and intensity of some Tfh markers (e.g., PD-1 in Sézary syndrome) help in reaching a diagnosis. The clinical algorithm categorizes presentations into three groups: (1) a solitary nodule or plaque, (2) multiple lesions (papules, plaques, or nodules/tumors), and (3) diffuse plaques or erythroderma. These histological and clinical algorithms are intertwined and complementary, providing a structured approach to evaluate Tfh-rich infiltrates in the skin.