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

Abstract

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.

The management of unicentric and multicentric Castleman's disease

“…Low dose radiotherapy (2700 -4500 cGy) administered to involved sites has been reported to result in remission of disease in isolated cases 33,[42][43][44][45][46][47][48][49] but has failed in others. 3,8,51 Keller et al 3 reported on four patients with unicentric-HV disease who were treated with 1800 -4300 cGy with no response.…”

Treatment of castleman’s disease

“…Hematologic-Anemia of chronic disease; Pure red cell aplasia [70]; Autoimmune hemolytic anemia [71], Autoimmune thrombocytopenia [72]; Acquired hemophilia [69]; Osteosclerotic myeloma (POEMS syndrome) [2,73]71 Oncologic-Non-Hodgkin's lymphoma [22•]; Hodgkin's disease [22]; Follicular dendritic cell sarcoma [23]; Kaposi's sarcoma [74]; Mesenchymal spindle-cell neoplasm [75] Dermatologic-Pemphigus [8,9]; Bechet's disease [10] Renal-Membroproliferative glomerulonephritis [69]; Fibrillary glomerulonephritis [19]; Secondary (SAA) amyloidosis Neurologic-Demyelinating polyneuropathy (POEMS syndrome) [2,73] Pulmonary-Bronchiolitis obliterans [15][16][17]; Lymphoid interstitial pneumonia [14]; Pulmonary fibrosis [16] Rheumatologic-Systemic lupus erythematosus [76] Endocrine-Growth failure, delayed puberty [77]; Adrenal insufficiency [78] POEMS-peripheral neuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes.…”

Iron-Deficiency Anemia in Castleman Disease: Implication of the Interleukin 6/Hepcidin Pathway

“…In addition to occasional autoimmune hemolytic anemia, mild inflammatory anemia is common with CD, but unexplained irondeficiency anemia may also be observed, particularly in children. [6][7][8][9][10] With overproduction of IL-6 as a hallmark, 11 CD could be an interesting human model for studying the contribution of the IL-6/hepcidin pathway in the pathogenesis of ACD.…”