Unique cytologic features of thyroiditis caused by immune checkpoint inhibitor therapy for malignant melanoma
Open accessAbstract
Blockade of immune checkpoint molecules to reverse cancer-induced immune suppression can improve anti-tumor immune responses in cancer patients. Monoclonal antibodies targeting two such molecules, Programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte associated protein 4 (CTLA-4) have shown clinical benefit in the treatment of advanced malignancies, including metastatic melanoma. Adverse effects of these immune checkpoint inhibitors include immune-related adverse events (irAE) and the inducing of new autoimmunity, of which one of the most common is autoimmune thyroiditis. Though thyroiditis is increasingly recognized, there are no reports of the pathological findings that occur in immunotherapy-induced thyroiditis. We present a case of immunotherapy-induced thyroiditis demonstrating its unique cytopathologic features. A 51-year-old woman with metastatic melanoma was found to have a suppressed TSH and elevated free thyroxine concentration 14 days after starting treatment with nivolumab (PD-1 antagonist) plus ipilimumab (CTLA-4 antagonist) therapy. A thyroid biopsy was performed based on ultrasound findings and cytopathology revealed unique features including abundant clusters of necrotic cells, lymphocytes and CD163-positive histiocytes. This case reports cytopathologic features found in immune checkpoint inhibitor related thyroiditis. These appear to be unique findings and may help inform future research regarding the pathophysiology and mechanisms of this condition.
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Histological and morphological analysis can demonstrate different pathophysiological mechanisms between autoimmune and ICPi-induced thyrotoxicosis.
“Histological and morphological analysis can demonstrate different pathophysiological mechanisms between autoimmune and ICPi-induced thyrotoxicosis [26,27].”
From Graves’ Disease during Immune Checkpoint Inhibitor Therapy (A Case Series and Literature Review) (2021) · cites this paper as [27]
The Case discussion reports a cytologic difference: necrotic cells appeared in checkpoint-inhibitor thyroiditis but are not present in autoimmune thyroid disease. It says these features may help explain mechanisms that remain to be elucidated; it does not demonstrate different pathophysiological mechanisms. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIn patients with immune checkpoint inhibitor-related hypophysitis, high-dose steroid treatment is associated with worse anti-tumor outcomes than replacement-dose steroid treatment.
“treated with high-dose steroids have inferior anti-tumor outcomes compared to those treated with replacement-dose steroids.62”
From Endocrine toxicities of immune checkpoint inhibitors (2021) · cites this paper as [62]
One study suggested that patients who developed ipilimumab-induced hypophysitis and were treated with high-dose steroids have inferior anti-tumor outcomes compared with those treated with replacement-dose steroids.
“One study suggested that patients who developed ipilimumab-induced hypophysitis treated with high-dose steroids have inferior anti-tumor outcomes compared to those treated with replacement-dose steroids.62”
From Endocrine toxicities of immune checkpoint inhibitors (2021) · cites this paper as [62]
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- Authors
- Angell, T. E., Min, L., Wieczorek, T. J., & Hodi, F. S.
- Affiliations
- Brigham and Women's Hospital (US)
- Dana-Farber Cancer Institute (US)
- Corresponding author
- Angell, Trevor E.
- Venue
- Genes & Diseases
- Publisher
- Elsevier BV
- Published
- 2018-03
- Volume
- 5
- Issue
- 1
- Pages
- 46-48
- ISSN
- 2352-3042 (ISSN-L)
- PMC
- PMC5879785
- OpenAlex
- W2769814019
- Cited by
- 69
- References
- 9
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 4 · 2023: 13 · 2022: 18 · 2021: 10 · 2020: 7 · 2019: 5
- FWCI
- 1.45
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Genes & Diseases (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- NIH (K08 HD070957)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Keywords
- autoimmune thyroiditis, metastatic melanoma, nivolumab, ipilimumab, anti-PD-1 therapy, CTLA-4 blockade, immune-related adverse events, thyroid cytopathology, necrotic cells, lymphocytic thyroiditis
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