The plasmablasts in Castleman disease.

To the Editor In their article, Hsi et al 1 described the broad spectrum of histopathologic features of Castleman disease (CD). We would like to report one additional peculiar case, rich in human herpesvirus-8 (HHV-8)–infected plasmablasts (PBs), which we recently observed in our institution. The normal PB is a short-lived, very mobile B cell that can secrete antibodies but retains characteristics of an activated and proliferating cell. 2 The PB could be considered the precursor of the more mature noncycling plasma cell (PC). Both naive and memory B cells can differentiate into PBs when activated with or without T-cell help, with or without antigen. 3 The maturation of PBs in PCs is characterized by the cessation of proliferation and loss of mobility. B-lymphocyte–induced maturation protein 1 (Blimp-1)/PR domain zinc finger protein (PRdm-1) is essential for PC maturation, repressing the expression of genes that maintain B-cell identity (Pax5) and others that promote B-cell proliferation, such as Bcl6 and MYC. 3 The PB is characterized by the following phenotype: CD19+, CD27++, CD38–/+, CD20–/+, cIgM+. 4 The PBs are rare in normal lymph nodes; they probably live around the mantle zone of the germinal centers, and then they exit into peripheral blood and may survive for a short period only unless they are recruited into mucosa or bone marrow niches by chemokine receptor expression. 5,6 In pathology, PBs characterize only rare human disorders, most notably the multicentric, HHV-8–related variant of CD. HHV-8, which uses host cell division as a means of propagation, targets the rapidly proliferating, antibody-secreting PBs. 7 HHV-8– infected PBs express the permissive phenotype IgM+, l+. 8,9 Our case of multicentric CD had an unusual primitive mesenteric involvement ❚Image 1A❚. 10 Because of the absence of interfering lymph nodal populations (extranodal site) and the very high amount of clustered HHV-8–infected cells, the case was particularly useful for the study of PB characteristics. The mesentery was infiltrated by a nodular lymphoid proliferation organized in neoformed germinal centers with peculiar " lollipop " features ❚Image 1B❚ and ❚Image 1C❚. In the perifollicular areas, immunohistochemistry (IHC) and immunofluorescence (IF) revealed a significant (CD138+, IgA+, CD56–, cyclin D1–) mature PC population ❚Image 1D❚ and ❚Image 1E❚, polyclonal for the k/l immunoglobulin (Ig) light chain. Neoformed germinal centers were colonized by a second, exceptionally abundant, HHV-8–infected PB population (CD138–, IgA–, IgM+) (Image 1D) ❚Image 1F❚. Double staining for HHV-8/CD20 showed only very rare double-stained cells ❚Image …