Thyroid Eye Disease-Like Conditions Associated With Cancer and Immune Check Point Blockage: Systematic Literature...

To perform a systematic review of the literature on thyroid eye disease-like (TED-like) orbitopathy occurring as part of paraneoplastic syndromes or associated with immune checkpoint inhibitors and report a case of paraneoplastic TED-like orbitopathy.

A comprehensive literature search was conducted in PubMed, Embase, and Scopus databases up to July 2025 using predefined keywords related to orbitopathy, malignant neoplasms, paraneoplastic syndromes, and immune checkpoint inhibition. Only full-text articles were included. Eligible studies were independently screened, and data were extracted regarding patient demographics, oncologic diagnosis, immune checkpoint inhibitor exposure, clinical presentation, and imaging features.

Thirty-nine reports were retrieved in the literature; among those, 21 patients developed TED-like orbitopathy following immune checkpoint inhibitor therapy, most commonly with anticytotoxic T-lymphocyte-associated protein 4 or antiprogrammed cell death protein 1/programmed cell death protein ligand 1 agents. The clinical pattern was remarkably consistent, characterized by bilateral proptosis, inflammatory signs, and extraocular muscle enlargement, while upper eyelid retraction was present in only 16% of cases. In addition, 18 paraneoplastic cases mimicking TED were retrieved, mainly associated with seminomas, lymphomas, and pulmonary carcinomas. Imaging findings were similar to those seen in classic TED, yet thyroid autoimmunity was absent. We also present a patient with a hepatosplenic T-cell lymphoma who developed bilateral inflammatory orbitopathy and lateral rectus muscle hypertrophy.

TED-like orbitopathy represents a rare but increasingly recognized manifestation in oncology, occurring either as a paraneoplastic phenomenon or as an immune-related adverse event of checkpoint inhibition. The absence of TRAb positivity and thyroid dysfunction highlights a possible alternative immune mechanism underlying orbital inflammation mediated by cytotoxic T lymphocytes.