Background Castleman's disease (CD) is a rare lymphoprolipherative mostly benign disorder presenting in two major forms: localized (unicentric) and systemic (multicentric). Based on pathomorphological finding it is classified as hyaline-vascular, plasma cell or mixed type. The age of onset can differ greatly from infancy to adulthood. Except for lymph node hyperplasia, patients with CD can also develop such symptoms as anemia, fatigue, hepatosplenomegaly, low-grade fevers and other systemic symptoms.
Objectives Analysis of clinical manifestations, pathomorphology and treatment efficiency in a group of pediatric patients.
Methods We conducted a retrospective analysis of 12 patients (11 boys and 1 girl) with histologically confirmed cases of Castleman's disease.
Results Age of onset varied from the moment of birth to 16 years (median 8,5 years) 8 patients had unicentric form of disease, 3 had multicentric form and one patient had two groups of lymph nodes affected, thus could not be precisely classified. The majority of the patients (9 patients) had hyaline-vascular variant of CD, one patient had plasma-cell type and two patients had the mixed pathomorphological type. The reason for seeking medical attention in three patients was visible unilateral enlargement of neck lymph nodes, four patients initially presented with anemia, fatigue, fever and laboratory signs of inflammation, and in 4 patients enlarged lymph nodes were incidentally visualized during control X-ray, and no other symptoms of CD were present. Interestingly, of 3 patients with multicentric form of CD, two had underlying primary immunodeficiency – Wiskott-Aldrich syndrome (WAS). They presented with plasma cell type and mixed type of CD, respectively. No immunodeficiency has been proven in other patients. We have conducted tests to indicate HHV VIII in affected lymph node biopsies and blood samples via PCR in half of the patients and none occurred to be positive.
Treatment: The affected lymph nodes were completely excised surgically in 7 patients with unicentric form, with no relapse of the disease on follow-up. Both patients with WAS received rituximab treatment followed by bone marrow transplantation, which was originally planned as a treatment of WAS, with remission on follow-up at 3 month and 2 years, respectively. Third patient with multicentric form received several courses of anti-cytokine and immunosuppressive treatment including tocilizumab, cyclophosphamide, vincristine and prednisolone (total of 5 blocks), rituximab (6 infusions) with partial effect, then surgical excision of large conglomerates of lymph nodes followed by bortezomib and bendamustine (total of 6 blocks) with positive effect. However at the one year follow-up patients demonstrated enlarged lymph nodes again, so she was started on JAK tyrosine kinase inhibitor ruxolitinib. Follow-up results are pending.
Conclusions Our analysis of a group of pediatric patients demonstrates great variability in symptoms and severity of the disease. Castleman's disease is a disorder with poorly studied pathogenesis. Based on our experience, the role of primary defects of immune system in development of CD requires further investigation.
Disclosure of Interest None declared