Development of thoracic sarcoid reactions associated with complete response to anti‐PD‐1 therapy in a patient with advanced cutaneous squamous cell carcinoma

In patients with advanced cutaneous squamous cell carcinoma (cSCC), positive efficacy data were reported for anti-PD-1 antibodies. However, anti-PD-1 treatment is associated with a wide range of immune-related adverse events (irAEs). Here, we report on a 78-year-old woman with a huge cSCC on the right cheek spanning from the temporal to the cervical region with evidence for infiltration of the parotid gland, right masseter muscle and right auditory canal. Ultrasound revealed cervical, submandibular and supraclavicular lymph node metastases on patient's right side. On the basis of a medical hardship application, treatment with pembrolizumab was initiated. After two applications, a dramatic regression of the tumour was observed. At this point, the patient was switched to cemiplimab, which, in the meantime, had become available in Germany. After 3 months on cemiplimab, the tumour-related ulcer on the right cheek showed almost complete regression and all previously affected lymph nodes displayed no evidence for malignancy. Thoracic computed tomography (CT) scans revealed enlarged mediastinal and bilateral hilar lymph nodes assessed as primarily reactive. Three months later, however, mediastinal and bilateral hilar lymph nodes further increased in size, accompanied by radiological alterations of the lung parenchyma. Lymph node biopsies revealed sarcoid reactions (SRs) including fibrotic non-caseating epitheloid cell granulomas surrounded by lymphocytes. Since the patient did not display any clinical symptoms, cemiplimab treatment was continued following a 4-week break. Three months later, CT showed significant regression of the described enlarged lymph nodes and parenchymal lung changes. Twenty months after anti-PD-1 treatment, the patient was still in complete remission. In conclusion, we describe, for the first time, the case of a patient with advanced cSCC who developed disseminated thoracic SRs which were associated with dramatic regression of tumour masses. Thus, as with other irAEs, development of SRs might be indicative of an anti-tumour response to anti-PD-1 therapy.