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Case Reports
. 2021 Jun 18:12:606056.
doi: 10.3389/fimmu.2021.606056. eCollection 2021.

Pembrolizumab-Induced Thyroiditis Shows PD-L1Expressing Histiocytes and Infiltrating T Cells in Thyroid Tissue - A Case Report

Affiliations
Case Reports

Pembrolizumab-Induced Thyroiditis Shows PD-L1Expressing Histiocytes and Infiltrating T Cells in Thyroid Tissue - A Case Report

Jörg Jabkowski et al. Front Immunol. .

Abstract

Context: Immune-related adverse events frequently take place after initiation of immune checkpoint inhibitors (ICI) therapy. The thyroid gland is the endocrine organ most commonly affected by ICI therapy, the pathological mechanism is still poorly understood.

Case description: A 60-year old Upper Austrian male melanoma patient under pembrolizumab therapy received thyroidectomy because of a suspicious FDG avid thyroid nodule. Histopathology showed a pattern comparable with thyroiditis de Quervain. The inflammatory process consisted predominantly of T lymphocytes with a dominance of CD4+ T helper cells. In addition CD68+ histiocytes co-expressing PD-L1 were observed.

Conclusion: Clusters of perifollicular histiocytes expressing PD-L1 were observed in this case of pembrolizumab induced thyroiditis - probably induced by the former ICI therapy. This finding might indicate the initial target for the breakdown of self tolerance. In context with other data the immunological process seems to be driven by CD3+ lymphocytes infiltrating the thyroid.

Keywords: FDG; PET; melanoma; pembrolizumab; thyroiditis.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
FDG-PET (A) shows a marked focal uptake with an SUV=14, corresponding to left thyroid lobe at PET/CT (B).
Figure 2
Figure 2
(A–F) Pembrolizumab induced thyroiditis: (A) H&E 200x: thyroid tissue with follicle partially destucted by histiocytes. (B) CD3 100x: thyroid tissue densely infiltrated by CD3 reactive T-lymphocytes. (C) CD 4 200x: thyroid tissue densely infiltrated by T helper cells (CD4 reactive). (D) CD 20 100x: thyroid tissue sparsely infiltrated by CD20 reactive B-lymphocytes. (E) CD 68 200x: thyroid tissue densely infiltrated and partially destructed by CD68 reactive histiocytes. (F) PD-L1 (SP263 hemalum2 8min) 400x: thyroid follicle partially destructed by histiocytes with coexpression of PD-L1 (clone SP263). (G) Regular thyroid tissue: PD-L1 (SP263 hemalum2 8min) 400x: normal thyroid tissue without PD-L1 (clone SP263) reactive cellular elements. (H, I) Graves´ Disease: (H) CD68 reactive histiocytes in the stroma and in thyroid follicles. (I) Histiocytes in the stroma and in thyroid follicles showing coexpression of PD-L1 (clone SP263).

References

    1. Akturk HK, Alkanani A, Zhao Z, Yu L, Michels AW. Pd-1 Inhibitor Immune-Related Adverse Events in Patients With Preexisting Endocrine Autoimmunity. J Clin Endocrinol Metab (2018) 103:3589–92. 10.1210/jc.2018-01430 - DOI - PMC - PubMed
    1. Imblum BA, Baloch ZW, Fraker D, LiVolsi VA. Pembrolizumab-Induced Thyroiditis. Endocr Pathol (2019) 30:163–7. 10.1007/s12022-019-9579-2 - DOI - PubMed
    1. Nogueira E, Newsom-Davis T, Morganstein D. Immunotherapy-Induced Endocrinopathies: Assessment, Management and Monitoring. Ther Adv Endocrinol Metab (2019) 10:2042018819896182. 10.1177/2042018819896182 - DOI - PMC - PubMed
    1. Khan M, Arooj S, Wang H. NK Cell-Based Immune Checkpoint Inhibition. Front Immunol (2020) 11:167. 10.3389/fimmu.2020.00167 - DOI - PMC - PubMed
    1. El El Sabbagh R, Azar NS, Eid AA, Azar ST. Thyroid Dysfunctions Due to Immune Checkpoint Inhibitors: A Review. Int J Gen Med (2020) 13:1003–9. 10.2147/IJGM.S261433 - DOI - PMC - PubMed

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