Suprabasal acantholytic dermatologic toxicities associated checkpoint inhibitor therapy: A spectrum of immune reactions from paraneoplastic pemphigus-like to Grover-like lesions

Wei Shen Chen, Michael T. Tetzlaff, Hafeez Diwan, Richard Jahan-Tigh, Adi Diab, Kelly Nelson, Isabella C. Glitza, Genevieve J. Kaunitz, Daniel Johnson, Carlos Torres-Cabala, Omar Pacha, Janis M Taube, Kudakwashe Maloney, Victor G. Prieto, Jonathan L. Curry

Research output: Contribution to journalArticle

Abstract

Checkpoint inhibitors (CPIs) restore the function of effector immunocytes to target and destroy cancer cells. Immune-related adverse events (irAEs) are a consequence of immune reactivation, with unpredictable inflammatory response, loss of self-tolerance, and development of autoimmunity. Adverse events from CPIs that present as dermatologic toxicities have diverse clinical and histopathologic features. CPI-associated dermatologic toxicities may exhibit histopathologic features of lichenoid dermatitis, bullous pemphigoid, and granulomatous/sarcoid-like reactions. Suprabasal acantholytic dermatologic toxicities associated with CPIs are particularly rare but represent an emerging histopathologic pattern and include lichenoid dermatitis with suprabasal acantholysis/vesicle formation to Grover disease (transient acantholytic dermatosis). Here, we report two patients who developed suprabasal acantholytic dermatologic toxicities during CPI therapy. One patient exhibited a CPI-associated autoimmune blistering disease with paraneoplastic pemphigus (PNP)-like features restricted to histopathology and immunofluorescence, while the other patient had Grover-like lesions. A review of the literature revealed a spectrum of suprabasal acantholytic dermatologic toxicities associated CPIs that may present as lichenoid dermatitis with acantholysis/vesicle formation, Grover-like eruptions, and lesions with PNP-like features restricted to histopathology and immunofluorescence. It is important for clinicians and pathologists to recognize the types of dermatologic toxicities associated with CPIs to direct appropriate therapeutic strategies.

Original languageEnglish (US)
JournalJournal of Cutaneous Pathology
DOIs
StateAccepted/In press - Jan 1 2018

Keywords

  • Acantholysis
  • Dermatologic toxicities
  • Immune checkpoint
  • Lichenoid
  • Paraneoplastic pemphigus

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Dermatology

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    Chen, W. S., Tetzlaff, M. T., Diwan, H., Jahan-Tigh, R., Diab, A., Nelson, K., Glitza, I. C., Kaunitz, G. J., Johnson, D., Torres-Cabala, C., Pacha, O., Taube, J. M., Maloney, K., Prieto, V. G., & Curry, J. L. (Accepted/In press). Suprabasal acantholytic dermatologic toxicities associated checkpoint inhibitor therapy: A spectrum of immune reactions from paraneoplastic pemphigus-like to Grover-like lesions. Journal of Cutaneous Pathology. https://doi.org/10.1111/cup.13312