Pilonidal sinus disease (PSD) is a chronic, recurrent inflammatory condition that persists in the sacrococcygeal region and often requires surgical excision for treatment. While its pathophysiology remains unclear, PSD is hypothesized to originate from infected hair follicles, triggering a foreign body granulomatous reaction. However, preliminary data provide a compelling case for further in-depth analysis investigating the presence of tertiary lymphoid structures (TLS)—aggregations of B and T cells in inflamed non-lymphoid tissues—in PSD: shifting the paradigm of PSD from an infectious disease to one with an immune-mediated component.

In this study, we examined skin samples from 10 PSD patients and 5 healthy controls. H&E staining revealed increased lymphoid aggregates and plasma cell infiltrates in PSD samples. Using immunofluorescence staining for CD3 (T cells), CD20 (B cells), and CD23 (follicular dendritic cells), we identified TLSs of varying maturity levels. Notably, a subset of PSD samples contained mature TLSs with germinal centers, which are defined by follicular dendritic cells (CD23+).

Our results highlight the presence of immune structures in most PSD tissue samples, as the combined density of these immune structures was significantly increased in PSD samples compared to healthy controls (p = 0.0197), and 30% of the samples contained highly organized germinal centers. Additionally, we found that TLS and germinal center formation often correlated with the presence of plasma cells (p = 0.0152).

These findings suggest that PSD may have an autoimmune component, since the presence of TLSs and plasma cells is similar to immune features seen in the inflammatory skin disease hidradenitis suppurativa (HS). Considering that 1-4% of HS patients have concomitant PSD, our study suggests immunomodulatory therapies approved for HS may also be beneficial in PSD patients, which is currently treated only with surgery. Future studies should explore whether TLS presence correlates with disease severity in PSD and whether biologic therapies targeting immune pathways could provide an alternative treatment strategy for PSD.