Do Indeterminate Cells Follow the Footsteps of Langerhans Cells and Migrate From the Skin to the Lymph Node?

Abstract

Indeterminate cells are considered by many to be pre-Langerhans cells as they mimic Langerhans cells in certain morphologic and immunophenotypic aspects. Indeterminate cells express CD1a and S-100 but lack Langerin expression (Langerin is used as an immunohistochemical substitute for electron microscopy for the detection of Birbeck granules). Migration of Langerhans cells to the lymph nodes through the dermal lymphatics to present skin antigens to T lymphocytes has been well defined before; however, the migration and the identification of indeterminate cells in lymph node has not been investigated before. In our study, we attempt to investigate the presence of indeterminate cells in normal lymph nodes and in lymph nodes with dermatopathic lymphadenitis and analyze their possible coexistence with Langerhans cells. We examined 9 cases of normal skin, 7 cases of normal lymph nodes (both normal skin and normal lymph nodes are obtained from mastectomy specimens), and 5 cases of reactive lymph nodes with dermatopathic lymphadenitis, for the presence of indeterminate cells. A set panel of immunostains was used that included CD1a, S-100, Langerin, CD3, and CD20. Indeterminate cells were defined as CD1a+, S-100+, and Langerin-, whereas Langerhans cells were defined as CD1a+, S-100+, and Langerin+. Scattered indeterminate cells were identified in most lymph nodes with dermatopathic lymphadenitis, but only in those normal lymph nodes that showed paracortical hyperplasia or expansion, whereas Langerhans cells were identified in both.