Tertiary lymphoid structures with overlapping histopathologic features of cutaneous marginal zone lymphoma during...

The development of immune checkpoint inhibitor (ICI) therapy with anti-CTLA-4 and anti-PD-1/L1 monoclonal antibodies has led to a paradigm shift in cancer therapy. ICI neoadjuvant therapy followed by surgery has become the standard of care for several advanced-stage cancers. The pathology associated with ICI therapy is vast and includes neoadjuvant-associated tissue reactions and activation of tertiary lymphoid structures (TLSs) at the site of the tumor bed and off-target immune-related adverse events. TLSs are thought to recapitulate lymph node function and may act as localized immune machinery to mount an antitumor response. B-cell activation in TLSs during neoadjuvant ICI therapy has been correlated with antitumor response. We report a patient with a history of sarcomatoid squamous cell carcinoma treated with neoadjuvant ICI cemiplimab who developed clonal expansion of B-cells in the TLSs of the tumor bed. The TLSs morphologically mimicked a cutaneous marginal zone lymphoma with plasmacytic differentiation. Awareness of clonal expansion of B-cells in TLSs during neoadjuvant ICI therapy is critical to recognize a response to ICI therapy and to avoiding an incorrect diagnosis of low-grade B-cell lymphoma.