Correspondence

CD8+ T Lymphocytes in Bronchiolitis Obliterans, Paraneoplastic Pemphigus, and Solitary Castleman's Disease

N Engl J Med 2003; 349:407-408July 24, 2003

Article

To the Editor:

Paraneoplastic pemphigus has been reported in patients with Castleman's disease, and bronchiolitis obliterans in association with paraneoplastic pemphigus can eventuate in respiratory failure and death.1-4 Anatomically, there is a diffuse segmental constrictive bronchiolitis of small bronchioles.5 The cause of the bronchiolitis is obscure. Acantholysis of bronchial epithelium and linear deposition of IgG and complement along the lamina propria were observed on transbronchial biopsy in two patients,2 suggesting that autoantibodies may have a role.

A 52-year-old man presented with abdominal discomfort in December 1999. Computed tomography (CT) of the abdomen revealed a retroperitoneal mass, 12×8×6 cm, adjacent to the left kidney. A biopsy showed Castleman's disease of the hyaline vascular type. The tumor was unresectable because of its juxtaposition to the kidney and the aorta. The patient was treated with radiotherapy (3000 cGy), and follow-up CT revealed a 50 percent reduction in the size of the mass. In January 2001, oral, conjunctival, and penile erosions developed, cicatricial pemphigoid was diagnosed, and the patient was treated for this condition. Shortly thereafter, a dry cough and exertional dyspnea developed. The dyspnea rapidly worsened, necessitating 24-hour use of supplemental oxygen.

In September 2002, the diagnosis of paraneoplastic pemphigus and bronchiolitis obliterans, in association with solitary Castleman's disease, was made. Despite aggressive treatment with cyclosporine and two cycles of rituximab, cyclophosphamide, and dexamethasone, the patient died of hypercapneic respiratory failure in December 2002.

Autopsy revealed a spectrum of pathological changes in the small bronchioles, from detachment of columnar epithelial cells to panmural cellular infiltration, partial or complete obliteration of the bronchiolar lumen by fibrolymphocytic tissue, and replacement of the entire bronchiole by fibrosis. Immunohistochemical analysis revealed that the panmural infiltrate invading the bronchiolar walls consisted almost exclusively of CD8+ T lymphocytes (Figure 1Figure 1Section from a Small Bronchiole with Immunohistochemical Staining with Anti-CD8 Antibody (Panel A, ×100; Panel B, ×400), Showing Constrictive Bronchiolitis with Panmural Infiltration by CD8+ T Lymphocytes and the Partially Obliterated Bronchiolar Lumen.). B cells and natural killer cells were absent. Immunoglobulin and complement deposits were not detected in the bronchiolar lesions. Studies of rearrangements of T-cell receptor β and γ genes revealed no clonal rearrangement.

We postulate that although autoantibodies may play a part, CD8+ T lymphocytes may have a key role in the progression of the bronchiolitis. If so, immunosuppressive therapy directed against T cells might change the grim natural history of the disease.

Mark A. Hoffman, M.D.
Xiaoying Qiao, M.D., Ph.D.
Long Island Jewish Medical Center, New Hyde Park, NY 11040

Grant J. Anhalt, M.D.
Johns Hopkins University School of Medicine, Baltimore, MD 21205

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