Background Despite reducing pneumonia and other infections, antibody replacement does not appear to treat pulmonary lymphoid hyperplasia (PLH) in patients with common variable immunodeficiency (CVID). The pathogenesis and optimal treatments remain to be clarified. Objective We aimed to better understand the pathology of CVID-associated lung disease. Tertiary lymphoneogenesis, although a component of interstitial lung disease associated with autoimmune diseases, has not previously been explored in patients with CVID. Methods We examined the clinical characteristics and pathologic findings of 6 patients with CVID with nodular/infiltrative lung disease who had biopsy specimens demonstrating PLH. Results In these subjects regions of PLH contained distinct Band T-cell zones, with B-cell predominance in 1 patient and T-cell predominance in the others. Colocalization of Ki67, Bcl6, and CD23 within this ectopic lymphoid architecture demonstrated tertiary lymphoneogenesis with active centers of cellular proliferation. One patient received rituximab with improved pulmonary radiologic findings. Conclusion Ectopic lymphoid tissue forming germinal centers suggest tertiary lymphoneogenesis in CVID-associated lung disease. B cell–targeted therapy might disrupt CVID-associated lymphoid hyperplasia.

Eight cases are reported of an unusual breast lesion consisting of dense intralobular, perilobular, and perivascular lymphocytic infiltrates associated with lobular atrophy and sclerosis. Immunologic studies on paraffin-embedded tissue (seven cases) and frozen tissue (two cases) demonstrated a predominance of B-cells and expression of HLA-DR antigen in involved lobular epithelium. The immunologic features of this lesion are reminiscent of lymphoepithelial lesions of salivary glands and other sites. A possible autoimmune pathogenesis is suggested.

Kaposi's sarcoma-associated herpesvirus (KSHV or HHV8) sequences are present in primary effusion lymphomas (PEL). KSHV+cell lines have been established from such lymphomas. Here we report the first description of the establishment of a KSHV+, EBV− cell line (BCP-1) from the peripheral blood of a patient with PEL. Using this cell line and a KSHV+, EBV+ PEL cell line (HBL-6) previously established from ascitic fluid, we investigated whether in nonobese diabetic/severe combined immunodeficiency disease (Nod/SCID) mice tumors representing PEL can be established. When injected intravenously (IV) into Nod/SCID mice, BCP-1 and HBL-6 infiltrated organs, with only occasional macroscopic tumor formation. Intraperitoneal injections (ip) led to the development of ascites and diffuse infiltration of organs, without obviously solid lymphoma formation, resembling the diffuse nature of human PEL. To investigate a possible mechanism for the peculiar phenotype of PEL, we examine the presence of adhesion molecules and homing markers on PEL cells before and after growing in mice. Both BCP-1 and HBL-6 cells lack expression of important cytoadhesion molecules including CD11a and CD18 (LFA1 α and β chains), CD29, CD31, CD44, CD54 (ICAM-1), and CD62L and E (L and E selectins).

Common variable immunode®ciency (CVID) is a primary immunode®ciency disease characterized by low serum immunoglobulins IgG, IgA, and usually IgM. The central immune de®ciency is impaired secretion of immunoglobulins and lack of antibody production; however, T cell dysfunction and a variety of in¯ammatory complications suggest global immune dysregulation. A number of reports have documented the association of primary immunode®ciency diseases with the development of non-Hodgkin's lymphoma (NHL). In CVID, the risk has been estimated to lie between 1.4% and 7%. As for NHL arising in other immunode®ciency states, the lymphomas in CVID are extranodal and are usually B cell in type. Of 22 B cell lymphomas that have appeared over a period of 25 years in a cohort of subjects with CVID, ®ve lymphomas, appearing in more recently studied subjects, that arose in mucosal sites would be classi®ed as mucosaassociated lymphoid tissue (MALT) lymphomas. MALT lymphomas are low-grade B cell lymphomas that result from a proliferation of neoplastic marginal-zone related cells of lymphoid tissue and tend to occur in organs that have acquired lymphoid tissue due to long-term infectious or autoimmune stimulation. Lymphomas of this kind have not been described in patients with congenital immunode®ciency, although chronic mucosal antigen stimulation is an integral part of these immune de®ciency states. Am.