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Distribution of PD-1+ Lymphocytes in Reactive Lymphadenopathies

Objectives: Programmed death-1 (PD-1) is physiologically expressed by germinal center (GC)-associated helper T cells. It has been proposed that an increase in PD-1+ cells outside GC could indicate pattern I angioimmunoblastic T-cell lymphoma (AITL). Methods: We studied the distribution of PD-1+ cells in reactive lymphadenopathies (LA), including HIV-associated and dermatopathic LA (n = 5, each), Castleman (n = 3), Kikuchi (n = 2) and Rosai-Dorfman diseases (n = 1), sarcoidoses (n = 7) and follicular hyperplasias (n = 8). Results: The highest concentrations of PD-1+ cells in GC were found in Castleman and Rosai-Dorfman diseases (mean 57 and 50% of total cells, respectively), and the lowest in HIV-associated LA (mean 6%). The highest proportions in paracortices were found in Castleman disease, and in HIV-associated and dermatopathic LA (mean 7, 3 and 2%, respectively). PD-1+ cells predominated in the pale zones of GC in follicular hyperplasia. In HIV-associated LA, PD-1+ cells showed marked marginalization in the GC. No paracortical PD-1+ cells were found in sarcoidoses and Rosai-Dorfman disease. Conclusions: The varying distribution of PD-1+ cells in defined LA might indicate a functional relevance of these cells in the respective entities. Since increased numbers of PD-1+ cells outside GC are observed in various LA, this finding might not be entirely specific for pattern I AITL.