Background: Although progressive transformation of germinal centers (PTGC) in lymph nodes was defined as an entity almost three decade ago, it is not well known to surgical and head and neck pathologists. PTGC may be mistaken for focal nodular lymphocyte predominant Hodgkin's Disease (NLPHD). Objective: To review the histopathologic and clinical features of PTGC, and PTGC's relationship with lymphoid neoplasia in pediatric and adult populations. Histopathologic features: PTGC occurs in 10-15% of enlarged lymph nodes with reactive follicular hyperplasia. PTGC is characterized as a nodule, which is three to five times the size of a typical reactive follicle, with mantle zone small B-cells infiltrating the residual germinal center. Epithelioid histiocytic clusters, immunoblasts, mononuclear cells, and eosinophils may also be present. Solitary or multiple nodules may be found. The immunophenotypes of both PTGC and NLPHD may be identical (CD45+, CD20+, CD15-, CD30-). The nodules in PTGC are relatively well defined, with those in NLPHD being more irregular. Clinical features: PTGC occurs in children (20%, mean age 11 years) and adults (80%, mean age 28 years), with a male predominance (3:1). PTGC is associated with Hodgkin's disease (HD) in 30-35% of patients. PTGC may precede, follow, or be concurrent with HD. Recurrent PTGC is more common in children (50 vs. 23%). Cervical lymph nodes account for almost 50% of cases, with oral cavity involvement also reported. Conclusion: PTGC occurs frequently in lymph nodes with reactive follicular hyperplasia, may resemble focal NLPHD, and has a nebulous association with NLPHD. PTGC is not considered a premalignant condition. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.