Multicentric Castleman disease in an HHV8-infected child born to consanguineous parents with systematic review

Abstract

Childhood multicentric Castleman disease (MCD) is a rare and unexplained lymphoproliferative disorder. We report a human herpesvirus-8 (HHV-8)-infected child, born to consanguineous Comorian parents, who displayed isolated MCD in the absence of any known immunodeficiency. We also systematically review the clinical features of the 32 children previously reported with isolated and unexplained MCD. The characteristics of this patient and the geographic areas of origin of most previous cases suggest that pediatric MCD is associated with HHV-8 infection. Moreover, as previously suggested for Kaposi sarcoma, MCD in childhood may result from inborn errors of immunity to HHV-8 infection.

FIGURE 1

Histologic features of axillary lymph node sections from our patient. Pathologic analyses showed lymph nodes with abnormal germinal centers of variable size and shape, and atretic follicles with prominent hyalinization penetrating blood vessels in the germinal center. The lamination of the mantle cell layers led to a typical “onionskin” appearance of the follicle. Immunohistochemical staining of lymph node sections showed numerous plasma cells (anti-CD138 antibody staining) in the interfollicular region. Latent nuclear antigens (LANA) protein was detected in situ, in plasmacytes. A, Low magnification (×20) showing abnormal atretic hyaline-vascular germinal centers, “onionskin” cuffing of lymphocytes, and a central hyaline vascular region. B, High magnification (×40) revealing sheets of plasma cells in the interfollicular region (arrows). This biopsy showed features of both the hyaline vascular and plasma cell type types (mixed type) of Castleman disease. C, Immunohistochemistry with anti-CD138 antibody at high magnification (×40) confirming the presence of numerous plasma cells in the interfollicular region (arrows). D, Immunohistochemistry for LANA protein results in the staining of cells around the germinal center (arrows).