Expression patterns of transcription factors in progressively transformed germinal centers and Hodgkin lymphoma

The World Health Organization (WHO) classification of Hodgkin lymphoma (HL) distinguishes two types: Classical Hodgkin lymphoma (CHL) and nodular lymphocyte predominant Hodgkin lymphoma (NLPHL). Both groups have in common that they mostly derive from B cells with rare classical cases originating from T cells. They differ in their histomorphology, immunophenotype, and clinical behavior. One of the subtypes of CHL, designated as lymphocyte-rich classical Hodgkin lymphoma (LRCHL), shares some morphological features with NLPHL. The transcription factors BSAP, BOB.1, Oct2 and MUM1 are sequentially expressed in normal B-cell development. In order to investigate the relationship between the CHL subgroups and NLPHL, we examined the protein expression of these transcription factors using immunohistochemistry in 15 reactive processes and 4 different subtypes of 58 HL cases. Our findings underline the B-cell origin of HL, without evidence, that reactive processes like progressively transformed germinal centers (PTGCs) are precursor lesions of HL. Furthermore, they demonstrate that LRCHL is distinct from NLPHL and that it is closely related to the mixed cellularity CHL (MCHL) in respect of BSAP, BOB.1, and Oct2 expression. It therefore occupies an intermediate position between MCHL and NLPHL. Based on MUM1 staining, LRCHL exhibits a more mature phenotype than NLPHL.