Angiomyoid and follicular dendritic cell proliferative lesions in Castleman's disease of hyaline-vascular type: a study of 10 cases

Castleman's disease of hyaline-vascular type (HV CD) may rarely be associated with a confusing variety of stromal cell overgrowths and neoplasms. We report here on the pathologic and clinical findings of 10 such cases. In addition to the usual complex histoimmunophenotype of the stroma of HV CD and some unusual features that mimicked neoplasms, we observed focal proliferations of angiomyoid (five cases) and follicular dendritic cell type (five cases). The former were nonneoplastic growths featuring compact tangles of spindle cells, exhibiting immunoreactivity for smooth muscle actin and interpreted as vessel-related pericytes and myoid cells. The latter were neoplastic growths of oval to spindle cells intermixed with lymphocytes; the tumor cells grew in long, intersecting bundles, featured various degree of atypia, and expressed the markers of follicular dendritic cells (CD21, CD35, KiM4p). The two types were clinically distinct. Four of five patients with angiomyoid proliferations were young women, who presented with an abdominal mass and were cured by surgery; that is, they had a clinical profile similar to that of patients with the stroma-rich variant of HV CD. The follicular dendritic cell proliferations were in older patients of either gender presenting with masses at various sites, recapitulating the profile of follicular dendritic cell tumors arising independently from HV CD; in three patients with long-term follow-up, recurrences or metastases developed at various intervals from the initial diagnosis (1 1/6, 3 1/2, and 11 years), and one patient died as a result. This study confirms the potential for, and the variety of, stromal cell proliferations in HV CD. Because their biologic behavior differs, correct identification of these various proliferative lesions is clinically important.     

Ultrastructural identification of the splenic follicular dendritic cells in the chicken

BACKGROUND: There is a need to identify the follicular dendritic cells (FDC) of the chicken spleen at the ultrastructural level during a secondary immune response. METHODS: The cells were identified after intravenous priming BSA and boosting with biotinylated BSA conjugated to colloidal gold particles. Monoclonal antibodies raised specifically either to chicken IgG or IgM were used to characterize these immune complex-trapping cells. RESULTS: The FDC had an irregular morphology which varied through time, supporting the existence of two types of FDC in the chicken spleen, one showing filiform cell processes, the other provided with beaded dendrites. When the filiform dendrites were observed, the FDC bound the antigen on their surfaces. These dendrites showed an intrincate convoluted configuration, forming tightly wrapped networks near the cell body. The networks had the same features as those described in mammals as antigen retaining reticulum (ARR). In chickens, the ARR, which represents sites of antigen localization on FDC, reached maximum development on day 5 after the second injection of BSA and had disappeared by day 8. At this time FDC had beaded dendrites. CONCLUSIONS: Antigen is retained on FDC in the chicken spleen for long periods of time.     

Relation of follicular dendritic reticulum cells to Reed-Sternberg cells of Hodgkin's disease with emphasis on the expression of CD21 antigen

Based on observations of 66 cases, in which tissues were specially processed to optimize the simultaneous preservation of cell membrane antigens and morphology, we provide evidence in favor of a relationship between follicular dendritic reticulum cells (FDRC) and Reed-Sternberg (RS) cells of Hodgkin's disease (HD) other than the lymphocyte predominance subtype. RS cells were intimately related to the FDRC network (75% of cases), and the expression of CD21 antigen was frequent (41% of cases). Exclusive expression of CD21 antigen was found in 11 cases of HD, while the expression of other B-cell-associated markers (CD19, CD20, CD22) was both variable and inconsistent. The expression of T-cell antigens (CD3, CD4, CD8) was rare. Null phenotype of RS cells was observed in 27 of 66 cases (41%). Epstein-Barr virus (EBV) nucleic acids were found in 34 of 66 (51.5%) cases. Double labeling techniques showed the presence of EBV-positive RS cells within the FDRC network. A non-B-cell origin of RS cells was supported by the differential expression of EBV latent antigens in HD (latent membrane protein+, EB nuclear antigen 2-), which is unusual in EBV-driven lymphoblastoid cell lines and EBV-positive B-cell lymphomas. FDRC and RS cells are known to share morphological traits (binucleated cells), and both cell types possess Fc receptor for IgG. The hypothesis is further backed by the findings of CD15 antigen expression by occasional RS-like dysplastic FDRC in Castleman's disease (five cases), which is characterized by hyperplasia of FDRC. Whether FDRC might be the only cells involved in the conversion to RS cells by the loss or gain of antigens remains to be determined.     

S-100 protein-positive dendritic cells in follicular lesions of the thyroid

To assess recall of childhood socioeconomic position for public health research, the authors conducted a cross-sectional study of 352 adult women twin pairs enrolled in Examination II of the Kaiser Permanente Women Twins Study carried out in 1989-1990 in Oakland, California. Among twin pairs, 91% (95% confidence interval (CI) 89-94%) agreed on their father's educational level and 81% (95% CI 77-85%) on their childhood social class. Recall did not differ by adult socioeconomic position, zygosity, race/ethnicity, or age. Thus, epidemiologic studies can validly use retrospective data on childhood socioeconomic position to study its relation to adult health status.     

Role of Langerhans cells and other dendritic cells in viral diseases

Langerhans cells are part of a vast system of potent antigen-presenting cells known under the name of dendritic cells. During the last decade, much has been learned on dendritic cell involvement in the immune response to infectious diseases. This review briefly summarizes our current understanding of the role played by Langerhans cells and other dendritic cells in the pathogenesis of DNA and RNA virus infections. These data may form the basis for the development of innovative approaches in the diagnosis, prevention, and treatment of viral diseases.     

Species barrier prevents an abnormal isoform of prion protein from accumulating in follicular dendritic cells of mice with Creutzfeldt-Jakob disease

The accumulation of abnormal prion protein in follicular dendritic cells did not occur in mice inoculated with materials from human Creutzfeldt-Jakob disease, whereas it always occurred in mice inoculated with mouse-adapted agents, suggesting an intense expression of the species barrier in the lymphoreticular system.     

Fibrillary glomerulonephritis in Castleman's disease

Castleman's disease is an uncommon lymph node disorder which can be associated with renal disease. In this report we describe a patient with fever, weight loss, anorexia, increase in inflammatory proteins, anemia and nephrotic syndrome. Castleman's disease, plasma cell type, was diagnosed by histologic analysis after surgical excision of a pelvic lymph node. The disease was considered localized, since further investigations did not show any other pathologic mass. After resection of the pelvic lymphoid mass, clinical remission of systemic symptoms and laboratory abnormalities was observed, with the exception of the nephrotic syndrome. Renal biopsy was performed and showed a pattern compatible with fibrillary glomerulonephritis. Progressive decline in renal function was observed, despite immunosuppressive therapy.     

Castleman's disease restricted to the infratemporal fossa

Giant lymph node hyperplasia (Castleman's disease) is usually reported as a solitary mediastinal tumour, although involvement of other anatomical sites and a multicentric form have been reported. We describe a rare case of Castleman's disease due to its localisation (the left infratemporal fossa) and histology (plasma-cell variant). A brief review of the main clinico-histological characteristics of Castleman's disease is also presented.     

Imaging of follicular dendritic cell tumours of the liver

Follicular dendritic cell tumour of the liver is a recently recognized entity. To date, only two cases have been described, both in the pathology literature. Histologically, it resembles an inflammatory pseudotumour and immunohistochemical and ultrastructural studies are required for its diagnosis. The ultrasound, computed tomography and angiographic features of two cases of follicular dendritic cell tumour of the liver are described in detail. One of the patients had multiple recurrences of this tumour. The imaging features are very similar to those of hepatocellular carcinoma. As follicular dendritic cell tumour is considered to be of low-grade malignant potential, in contrast to the dismal prognosis for hepatocellular carcinoma, it is important to be able to accurately distinguish between the two types of tumour prior to initiating definitive therapy.     

Specialization of mucosal follicular dendritic cells revealed by mucosal addressin-cell adhesion molecule-1 display

Follicular dendritic cells (FDC) in the mucosal lymphoid organs, Peyer's patches (PP), display mucosal vascular addressin-cell adhesion molecule-1 (MAdCAM-1). MAdCAM-1 decorates interlacing dendritic cells throughout PP follicles and is accentuated on FDC of the germinal center (GC) light zone and on "junctional" dendritic cells overlapping the B/T border and subepithelial dome region, sites associated with microenvironmental homing decisions. In contrast, MAdCAM-1 is rarely displayed by coronal or junctional FDC in peripheral lymph node follicles and is largely confined to the GC after lymph node immunization. FDC-associated MAdCAM-1 plays a prominent role in lymphocyte adhesion to GC in PP frozen sections and participates significantly in binding to GC in chronically stimulated lymph nodes and spleen, but not to GC in lymph nodes after primary immunization (where binding is dominated by vascular cell adhesion molecule-1). Differential display of MAdCAM-1 by FDC could contribute to the specialization of mucosal vs nonmucosal immune responses.     

Transduction of dendritic cells by DNA viral vectors directs the immune response to transgene products in muscle fibers

Immune responses to vector-corrected cells have limited the application of gene therapy for treatment of chronic disorders such as inherited deficiency states. We have found that recombinant adeno-associated virus (AAV) efficiently transduces muscle fibers in vivo without activation of cellular and humoral immunity to neoantigenic transgene products such as beta-galactosidase, which differs from the experience with recombinant adenovirus, where vibrant T-cell responses to the transgene product destroy the targeted muscle fibers. T cells activated following intramuscular administration of adenovirus expressing lacZ (AdlacZ) can destroy AAVlacZ-transduced muscle fibers, indicating a prior state of immunologic nonresponsiveness in the context of AAV gene therapy. Adoptive transfer of dendritic cells infected with AdlacZ leads to immune mediated elimination of AAVlacZ-transduced muscle fibers. AAVlacZ-transduced antigen-presenting cells fail to demonstrate beta-galactosidase activity and are unable to elicit transgene immunity in adoptive transfer experiments. These studies indicate that vector-mediated transduction of dendritic cells is necessary for cellular immune responses to muscle gene therapy, a step which AAV avoids, providing a useful biological niche for its use in gene therapy.     

Expression of MUC-1 glycoprotein in plasma cells, follicular dendritic cells, myofibroblasts and perineurial cells: immunohistochemical analysis using three monoclonal antibodies

Normal and malignant plasma cells (PC), follicular dendritic cells (FDC), myofibroblasts (MFB) and perineurial cells (PNC) were investigated for the expression of MUC-1 glycoprotein (MUC-1gp) by immunohistochemical and immunoelectron microscopic techniques using monoclonal antibodies E29, 115D8, DF3 and a combination of the three. MUC-1 glycoprotein-positive PC detected by the combined antibodies were frequently seen in a variety of pathological lesions tested, including chronic cervicitis, chronic synovitis, Hodgkin's disease, allergic rhinitis and sinusitis, tuberculous lymphadenitis, foreign body granuloma, multiple myeloma, and chronic tonsillitis. In the lesions containing MUC-1gp-positive PC, the infiltration of immunoglobulin (Ig) E PC and/or IgE-bound mast cells was significantly increased, but MUC-1gp-positive PC did not contain any specific immunoglobulin heavy or light chains. The findings suggest that the expression of MUC-1 gp in PC, although not restricted to IgE-class cells, may be induced in an allergic status. Plasma cells and PNC mainly reacted with the antibodies E29 and 115D8, while FDC and MFB were principally reactive with the antibody DF3. In some cases of multiple myeloma, the neoplastic PC were predominantly immunoreactive with DF3. The results indicate: (i) the epitopic variability of MUC-1gp molecules expressed on the non-epithelial cells; and (ii) the epitopic alterations during malignant transformation. It should also be noted that the expression of MUC-1gp in the non-epithelial cells represents a pitfall in histopathological diagnosis.     

Tropism of human herpesvirus 8 for peripheral blood lymphocytes in patients with Castleman's disease

Multicentric Castleman's disease (MCD), also called multicentric angiofollicular lymphoid hyperplasia, is a systemic lymphoproliferative disorder causing fever, lymphadenopathy and splenomegaly. Recently, Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 (KSHV/HHV-8) DNA sequences have been detected in cases of MCD. We examined HHV-8 DNA sequences in the peripheral blood mononuclear cells (PBMCs) of two HIV-negative patients with MCD and in PBMCs and the lymph node of a HIV-negative patient with localized Castleman's disease (LCD) by the polymerase chain reaction. The novel sequences were detected in all DNA samples. Furthermore, the sequences were detected in only the CD19+ B-lymphocyte fraction of the patient with LCD as previously reported. However, the sequences were detected in CD19+ B-lymphocyte and CD2+ T-lymphocyte fractions of two patients with MCD. These results suggest that HHV-8 has tropisms for both B lymphocytes and T lymphocytes in Castleman's disease.     

Detection of human herpesvirus 8 in patients with Kaposi's sarcoma or Castleman's disease associated with AIDS

A new herpesvirus provisionally termed as KSHV or HHV-8 has been detected in lesions from AIDS-based Kaposi's sarcoma (KS) and from other KS clinical forms, and also in other tumors such as body cavity-based lymphomas or Castleman's disease (CD). We have assessed the presence of this novel herpesvirus in specimens from patients diagnosed with either AIDS and KS or AIDS and CD. DNA samples from skin lesions and peripheral blood obtained from 8 patients diagnosed with AIDS, seven with KS and one with multicentric CD were analyzed; skin specimens and peripheral blood samples from volunteer blood donors or from KS and CD free HIV seronegative patients were used as controls. Detection of the virus was done by PCR amplification of KS330 region, one of the HHV-8 sequences first reported. All skin lesions analysed tested positive for KS330; peripheral blood samples from 5 of the patients, including the one diagnosed with CD, showed also the virus sequence. All skin specimens and peripheral blood samples from controls were negative. From our results it can be concluded that the novel herpesvirus HHV-8 can also be detected in patients with AIDS-associated KS and AIDS-associated CD in Spain.     

Dark and light zones of germinal centres of the human tonsil: an ultrastructural study with emphasis on heterogeneity of follicular dendritic cells

The cellular composition of the dark and light zones of germinal centres in human tonsils was quantitatively determined by electron microscopy. In addition to the well known germinal-centre B-cells, we defined the cleaved blast as a new distinct cell type in the germinal centre. The dark and the light zones clearly differed in their content of lymphoid and non-lymphoid germinal-centre cells. The dark zone was characterized by higher frequencies of cleaved blasts and small centroblasts, a higher blast-centrocyte ratio and a higher incidence of mitotic figures. In contrast, the light zone had higher frequencies of centrocytes, centroplasmacytoid cells, lymphocytes and follicular dendritic cells (FDC) and an inverted blast-centrocyte ratio. Seven distinct appearances of FDC (FDC.1-FDC.7) could be recognized on the basis of their ultrastructure. The distribution pattern of these subtypes differed between the dark and light zone. The undifferentiated subtypes FDC.2 and FDC.3 predominated in the dark zone. In contrast, the highly differentiated subtypes FDC.4 and FDC.5 were present at a much higher density in the light zone. These findings suggest that the dark and light zones are different compartments with regard to proliferation and differentiation of germinal-centre B-cells and that both compartments have a specific microenvironment influenced by FDC.     

Giant lymph node hyperplasia (Castleman's disease) presenting with chylous pleural effusion

A case of giant lymph node hyperplasia (Castleman's disease) with an original presentation of a chylous pleural effusion occurred in a female adolescent. CT scans showed mediastinal lymphadenopathy. Lymph node biopsy was consistent with the plasmacytic variant of Castleman's disease.