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A 35-year-old male with HIV infection underwent colonoscopy for a rectal lesion. The biopsy of the lesion showed extensive lymphoid proliferation involving the lamina propria and submucosa. The lymphoid proliferation comprised of large follicles of variable sizes and shapes (geographic hyperplasia) (figure A, 2x) composed of reactive appearing germinal centers with scattered immunoblasts and tingible body macrophages (figure B, 10x) surrounded by expansion of interfollicular zones by small lymphocytes. Immunohistochemistry revealed that the lymphoid proliferation predominantly consisted of CD20-positive (figure C, 2x) and PAX5-positive B-cells in the follicles as well as small monocytoid B-cells outside the follicles. CD3 highlighted few small T-cells.  The germinal centers expressed CD10 (figure D, 10x) and BCL6, and were negative for BCL2 (figure E, 10x). EBER in situ hybridization (ISH) was positive in scattered lymphoid cells (figure F, 10x) ranging from small to large in size, focally concentrated in the germinal centers, up to 20-30/40x (figure G, 40x). These B-cells were negative for CD15 (expressed in neutrophils), CD30 (highlighted few reactive immunoblasts), MUM1 (positive in plasma cells and some immunoblasts in the germinal centers), CD43 (highlighted small T-cells and plasma cells), HHV8, cyclin D1 and MNDA. Kappa and lambda ISH highlighted polytypic plasma cells and no expression on B-cells. The germinal centers showed appropriately high Ki-67 proliferative index (90%) with polarization. 

HIV-associated EBV-positive follicular proliferations are less commonly seen now due to advent of effective therapy for the management of HIV infection. Follicular hyperplasia, typically seen early on in the course of HIV infection in the lymph nodes and glandular tissue, is characterized by prominent hyperplastic follicles with enlarged germinal centers and monocytoid cell expansion in the interfollicular areas. Untreated patients may develop follicular lysis with attenuated mantle zones and relatively increased plasma cells. Later stages show sclerosis of the germinal centers that are small and hypocellular, and relative parafollicular expansion and vascular proliferation.