Immunohistopathology of lymph node, skin, and thymus. (A) Lymph node biopsy from patient P shows preserved nodal architecture with well-formed secondary B follicles and multiple epithelioid granulomas with multinucleated giant cells in the paracortical area. In contrast, lymph node at autopsy from patient's sister showed no secondary B follicles and marked polyclonal plasmacytosis (B). (C) Skin biopsy (heel) shows dense granulomatous inflammation involving mid dermis around vessels, clusters of epithelioid cells, and multinucleated giant cells. (D) Thymic biopsy shows abnormal thymic architecture with loss of corticomedullary demarcation (CMD), fat replacement and absence of Hassal bodies (HBs); moderate number of thymocytes, mostly of a blastic immature phenotype, and are admixed with TECs (top left). Immunostains highlight a diffuse epithelial network mostly composed of cytokeratin-5⁺cytokeratin-8⁻ (CK5⁺CK8⁻) double-positive immature TECs and no expression of Cld4 and AIRE (middle left). In contrast, normal thymus shows defined CMD and presence of HBs (top right and inset) with normal distribution of CK5⁺CK8⁻ and CK5⁻CK8⁺ single-positive cortical (c) and medullary (m) TECs, with expression of claudine-4 (Cld4) and AIRE (middle right). Severe depletion of thymic S-100⁺ DCs and Foxp3⁺ regulatory T cells (Tregs) are seen in patient (bottom left), whereas normal distribution of medullary S-100⁺ DCs and Foxp3⁺ Tregs were present in control thymus (bottom right; Foxp3⁺ cells are indicated by arrows). Hematoxylin and eosin (H&E) staining, 4×, 40× (inset), and 60× original magnification; immunostains for CK5, CK8, S-100, and Foxp3, 20× magnification; immunostains for Cld4 and AIRE, 40× magnification.