7.4Pathology and Immunology

7.4.1Macroscopic Features

•Continuous involvement of directly connected lymph node regions or organs with lymphatic tissue (lung, liver, bone marrow). The spleen is often involved, being an important organ of the lymphatic system

•Staging system according to grade of involvement: I–IV, A, or B (see below)

7.4.2Microscopic Features

•Infiltration of the normal tissue structure of lymph nodes by lymphocytes, eosinophilic leukocytes, histiocytes, reticular cells, fibrocytes, and collagen tissue

•Pathognomonic: bito multinucleated giant cells, i.e., Reed–Sternberg cells: high cytoplasmic content, nuclei multilobulated, diameter of cells 15–45 mm, originally from B cell germinal center (with a lack of B-cell expression profile = aberrant B-cell development) and aberrant T-cell-specific gene expression. The exact mechanisms are unknown.

7.4.3Molecular Biology

•Cytokines (interleukins, IL). There are associations between:

–IL-2, -3, -5, and eosinophils

–Transforming growth factor-a (TGF-a), tumor necrosis factor (TNF), and fibrosis

–IL-1, -6, TNF, and B symptoms (see below)

–TGF-a, IL-10, and immunosuppression, especially by reduction of T regulatory cells

–IL-1, -6, -9, and expression of Reed–Sternberg cells

7.4.4Immunophenotype