De novo lymph node formation in chronic inflammation of the human leg

Abstract

Organized lymphoid tissue is the first line of antigenic defense. Recruited by antigen located in the non-lymphoid tissues, the infiltrating lymphocytes often organize themselves as follicle-like structures that contain germinal centers, similar to those in secondary lymphoid follicles of lymph nodes. These extranodal tertiary lymphoid follicles are found in various autoimmune diseases. We investigated 153 patients with protracted lymph stasis of the lower limb, caused by lymphatic damage incurred through soft tissue bacterial inflammation or mechanical trauma of soft tissues and bones. In 10% of patients with post-inflammatory, and in 25% with post-traumatic lymph stasis, "newly-formed" lymph nodes were detected by means of lymphoscintigraphy. They were located along the large calf and thigh veins. Although scattered nodes are normally detected in these areas, the number and total mass of visualized nodes substantially exceeded those seen in healthy subjects. The calculated surface area of "newly formed" nodes attained 50-70% of the area of ipsilateral inguinal nodes. Histological evaluation of nodal biopsy specimens in three such patients revealed, in one, a lymph node structure without differentiation into cortical and medullary areas, and in a second, a follicle-like structure within a dilated lymph vessel. Lymph clot removed from another dilated vessel contained a lymphocyte/dendritic cell aggregate. The "newly formed" nodes likely originate from primordial lymphoid follicles and/or lymphoid cell aggregates formed in response to chronic stimulation by microbial products and self-antigens from the damaged tissues. Detection of "newly-formed" lymph nodes in the limb is evidence of an ongoing inflammatory process and requires appropriate therapy.