Supplementary Material for: Dermatofibroma associated with Lymphoid Follicles harboring Germinal Center. A Case Report.

Abstract
Introduction: Dermatofibroma (DF)s are common, benign firm dermal nodules. It is well known that their onsets often follow minor injuries including insect bites or arthropod assaults on-site. The frequency of DF cases associated with lymphoid follicles (LF) harboring germinal center (GC) amounts to around 1∼4%. The pathogenesis of this peculiar association is currently unknown, leaving a challenging topic for interpretation.
Case presentation: We present a case of a 55-year-old, otherwise healthy woman with a slightly erythematous flat nodule on the right side of her neck. It had occurred three months after a mosquito bite on the same site, and the lesion was tender. The nodule was eradicated completely from the right side of her neck as excisional biopsy after the treatment of secondary infection. Histopathological specimen revealed fibrocollagenous type of DF with well-organized multiple B-cell secondary lymphoid follicles. Their GCs indicated harboring bcl6-positive-CXCR5-positive-follicular helper T cells in the network of follicular dendritic cells. In addition, they were surrounded by CD163-positive-DC-SIGN (CD209)-positive macrophages expressing toll-like receptor (TLR) 4. We diagnosed the lesion as DF associated with LF harboring GC presumably driven by Th27/Th2 microenvironment.
Conclusion: Given GC associating LF in the present case is presumed to manifest Th27/Th2 microenvironment formation, the implication is that it plays a role in humoral immunity against extracellular pathogens. When miscellaneous pathogens bearing fucose-containing carbohydrate antigens happened to invade into the dermis through minor injuries, DC-SIGN, a pattern recognition receptor, and TLR4 on macrophages may have modulated Th differentiation into Th27/Th2 to generate follicular helper T cells and GC to induce humoral immunity. Accumulation of reports is required to check the validity of this speculation.