Angiofollicular lymph node hyperplasia (Castleman's disease) in an adolescent female. Clinical and immunologic...

Angiofollicular lymph node hyperplasia is a heterogeneous disorder of unclear etiology and has a wide spectrum of systemic symptoms. This report describes a case of this disorder in a 15-year-old girl and examines the response of the primary mass, systemic symptoms, and alterations of selected immune parameters at diagnosis, as a result of steroid therapy and radiation therapy (RT). The patient had a 1-year history of growth failure, delayed puberty, and refractory iron deficiency anemia. Computed tomography scan showed a posterior mediastinal mass. Biopsy revealed angiofollicular lymph node hyperplasia of mixed hyaline-vascular and plasma cell type histologic type. Immunoperoxidase studies showed polyclonal B-cells, predominance of T-helper cells (CD4) over cytotoxic/suppressor T-cells (CD8), and the presence of natural killer (NK) cells. Southern blot analysis demonstrated germ line gene configuration for the T-cell antigen receptor and Ig heavy chain. The patient clinically improved with RT after failing to respond to steroids. Immunophenotyping of peripheral blood lymphocytes before therapy revealed a CD4:CD8 ratio of 0.8 with decreased numbers of circulating T-cells; this increased to 1.4 after steroid therapy. The patient's T-lymphocytes had no proliferative response to phytohemagglutinin (PHA) or concanavalin A (Con A) before RT. After RT, a small but significant mitogenic response to these reagents was noticed. The proliferative response to recombinant interleukin-2 (rIL-2) remained similar to that of control lymphocytes. Induction of second messenger signals by activation of protein kinase C (PKC) and elevation of free cytosolic calcium through the use of the phorbol ester, phorbol 12, 13-dibutyrate (PDBu), and ionomycin (Io) resulted in a strong proliferative response at diagnosis and after RT. In vitro cytotoxicity assays revealed diminished NK activity before and after therapy. Lymphokine-activated killer (LAK) activity remained comparable with that of control cells and was not affected by therapy. Before RT patient lymphocytes maintained cytotoxic capabilities after coincubation with rIL-2 and PDBu plus Io, whereas coincubation with these reagents abrogated cytotoxic function of normal cells. This case demonstrates a clinical response to RT as well as improvement in immune parameters. Intact signal transduction mechanisms through PKC activation and elevation of cytosolic calcium were also demonstrated in the circulating lymphocytes.