PMC7686558_01
MRI of the upper left extremity: (A) Strong contrast enhancement of a 4.0 x 2.6 cm metastasis of the left deltoid muscle before initiation of immunotherapy. (B) Complete resolution of the tumor mass at three months after the first and only dose of ipilimumab plus nivolumab. Computed tomography of the chest: (C) Metastasis of the left upper lobe (arrow) before initiation of immunotherapy. (D) Complete resolution of the lung metastasis with residual dystelectasis (arrow) at three months after the first and only dose of ipilimumab plus nivolumab.
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March 2018 after presenting with a painless subcutaneous swelling of the left scapular region that had increased noticeably in size over the last few months. MRI scans revealed a tumor lesion of 4 cm in diameter within the left deltoid muscle ( Figure 1A ). Subsequent CT and FDG-PET scans detected multiple intramuscular, pulmonary, and bone lesions ( Figure 1C ). Three months after the first and only dose of ipilimumab plus nivolumab, CT and MRI scans showed no evidence of disease ( Figures 1B, D ), and the patient was classified as a complete responder.
Schematic timeline of immune checkpoint inhibition therapy and its immune-related adverse events.
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After interdisciplinary tumor board discussion, a combined immunotherapy with ipilimumab (3 mg/kg) plus nivolumab (1 mg/kg) Q3W was initiated (for timelines see  Figure 2 ).
Immune-related thyroiditis. (A) Time course of serum parameters reflecting the thyreoiditis after the application of ipilimumab plus nivolumab on 28.05.2018. Dotted lines represent the timepoint of initiation/discontinuation of thiamazole. TSH, thyroid stimulating hormone; fT4, free thyroxine; LLN, lower limit of normal; ULN, upper limit of normal. (B) Ultrasound showing hypoechoic, heterogeneous and hypervascular thyroid gland. (C) Tc99m scintigraphy showing proportional, slightly elevated tracer uptake (2.6%) throughout the thyroid gland.
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Four weeks after the first and only application of ipilimumab and nivolumab, the patient developed manifest hyperthyroidism (TSH 0.02 mU/L, normal range 0.3-3.0 mU/L; fT4 37.3 pmol/L, normal range 11.5-22.7 pmol/L) with negative TSH receptor antibodies;  Figure 3A .