Progressive transformation of germinal centers in children and adolescents: an intriguing cause of lymphadenopathy

Abstract

Background: The clinical implications of a diagnosis of progressive transformation of germinal centers (PTGC) in children are not well known.

Methods: To better understand this entity, we conducted a retrospective review of all patients aged 0-18 years diagnosed with PTGC at our center between 1998 and 2010.

Results: Twenty-nine patients were identified. Median age at diagnosis was 11.5 years, and median duration of follow-up was 2.8 years. Thirteen patients (45%) had a single episode of PTGC with no other associated features. Five patients (17%) had recurrent PTGC. Four patients (14%) had PTGC associated with Hodgkin lymphoma (HL): one preceding, two concurrent, and one subsequently developed HL. The most commonly associated HL was nodular lymphocyte-predominant HL. Seven patients (24%) had PTGC associated with immune disorders, including lupus, Castleman disease, and probable autoimmune lymphoproliferative syndrome. Overall, 15 patients (52%) had more than one lymph node biopsy. The cumulative incidence of a second biopsy after a diagnosis of PTGC was 42.3% ± 12.2% at 4 years. PTGC was PET-avid in all four patients tested.

Conclusions: PTGC is a nonspecific manifestation of a variety of associated conditions. There is a small risk of subsequent HL, and a larger risk of requiring multiple biopsies for recurrent PTGC. The presence of an immune disorder should be considered in patients who present with generalized lymphadenopathy, splenomegaly, immune cytopenias, and/or progression to HL. Routine surveillance imaging may not be required. Future research should determine the optimal surveillance strategy for patients with PTGC and the indications for repeat biopsies.