Tertiary lymphoid structures with overlapping histopathologic features of cutaneous marginal zone lymphoma during neoadjuvant cemiplimab therapy are associated with antitumor response

Keith J. Sweeney, Michael T. Tetzlaff, Francisco Vega, Ann Gillenwater, Zhuang Zuo, Neil Gross, Priyadharsini Nagarajan, Jennifer Wargo, Kelly Nelson, Victor G. Prieto, Carlos A. Torres-Cabala, Jonathan L. Curry

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
JournalJournal of Cutaneous Pathology
DOIs
StateAccepted/In press - 2021
Externally publishedYes

Keywords

  • cemiplimab anti-PD-1 therapy
  • marginal zone lymphoma
  • sarcomatoid squamous cell carcinoma
  • tertiary lymphoid structures
  • tumor response

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Dermatology

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