Pleomorphic adenoma of the lacrimal gland is a benign epithelial neoplasm and can rarely undergo cystic degeneration, mimicking other conditions with similar radiological findings. It commonly presents as a slow growing, painless mass in the outer upper eyelid, characterised by exophthalmos, ptosis, diplopia and reduced ocular movements. Here, we present one such case of a male in his mid-30s presenting with a painless, progressive fullness in the left upper eyelid with mild proptosis and restricted ocular movements which was initially suspected to be due to an underlying dermoid cyst owing to the cystic nature of the lesion on imaging. Surgical intervention involving complete excision was preferred, rendering no recurrence on follow-up. Histopathological examination however revealed microscopic features suggestive of a pleomorphic adenoma with cystic changes contrary to the initial diagnosis of a dermoid cyst. This case highlights the challenges faced in arriving at the right diagnosis with successful treatment outcomes.

Thyroid-associated ophthalmopathy (TAO) is an autoimmune orbital disorder associated with proptosis, ocular surface exposure, and corneal complications that may impair corneal repair. Transient receptor potential vanilloid 1 (TRPV1) is a calcium-permeable stress sensor involved in epithelial repair, inflammation, and stromal remodeling; however, its role in corneal wound healing under TAO-like ocular surface conditions remains unclear. In this study, a thyroxine (T4)-induced TAO-like condition was established in rats, followed by standardized alkali corneal injury to evaluate healing responses under this condition. Rats received topical H89 (20 μM), a protein kinase A (PKA) inhibitor, or saline for 17 days. Corneal healing was evaluated by fluorescein staining, anterior-segment optical coherence tomography, histology, immunohistochemistry for p-PKA, TRPV1, p-PI3K, p-AKT, p-CREB, MPO, and α-SMA, and quantitative PCR for IL-1β and TRPV1. Rats with the TAO-like condition exhibited marked exophthalmos and showed delayed epithelial closure with increased corneal opacity and edema after injury. TRPV1 expression was increased in the basal epithelium and stroma, accompanied by enhanced MPO and α-SMA expression. Topical H89 was associated with improved epithelial healing, reduced inflammation and fibrosis, and lower IL-1β and TRPV1 mRNA expression. These changes were accompanied by altered expression of PKA/TRPV1-related signaling molecules. Collectively, these findings suggest that TRPV1-associated signaling is involved in inflammatory and fibrotic responses during corneal wound healing under TAO-like ocular surface conditions, and that pharmacologic modulation with H89 may help improve corneal repair in this setting.

Guillain-Barré syndrome (GBS) is an acute immune-mediated peripheral neuropathy typically characterized by a monophasic course; however, atypical or relapsing presentations suggest that sustained immune dysregulation contribute to disease heterogeneity. We report a 33-year-old man with progressive limb weakness diagnosed as motor-predominant acute inflammatory demyelinating polyradiculoneuropathy (AIDP), supported by albuminocytologic dissociation and demyelinating features on nerve conduction studies with preserved sensory conduction. Immunological evaluation revealed B lymphocyte expansion, elevated interleukin-6 and interleukin-8 levels, and strong thyroid autoantibody positivity consistent with Graves' disease, while anti-ganglioside and paraneoplastic antibodies were negative. The clinical course was marked by immune-triggered relapses and the patient responded well to intravenous immunoglobulin (IVIg) and FcRn inhibition with efgartigimod. Further investigation identified papillary thyroid carcinoma harboring a BRAF V600E mutation, after which neurological symptoms stabilized following thyroidectomy. This case illustrates a rare concurrence of relapsing AIDP, Graves' disease, and papillary thyroid carcinoma, and supports the hypothesis that persistent systemic immune activation underlies relapsing GBS, rather than a chronic demyelinating process. Clinically, it highlights the importance of considering underlying autoimmune and neoplastic conditions in atypical or relapsing GBS to guide individualized management.

Graves' orbitopathy (GO) is a progressive autoimmune disorder of visual organ, mostly associated with Graves' disease (GD). Although rituximab has been used as an off-label therapy for steroid-resistant GO, paradoxical immune reactivation has also been reported. We present a rare case of GO that developed after bendamustine-rituximab (BR) therapy for chronic lymphocytic leukemia (CLL). A 73-year-old male with a 3-year history of GD, presented with new onset of bilateral proptosis, diplopia, and decreased visual acuity, that happened two weeks after his second BR cycle for CLL. The anamnesis was negative for both smoking, and radioiodine therapy. Laboratory studies showed persistently elevated thyrotropin receptor antibodies levels in plasma, and extraocular muscle enlargement on orbital MRI. The active phase (CAS 6/6) of moderate-to-severe (EUGOGO) GO was diagnosed. Despite two courses of intravenous methylprednisolone (cumulative dose - 12.2 g) and 10 retrobulbar dexamethasone injections, the patient progressed to dysthyroid optic neuropathy. Although the patient had a predisposing autoimmune background, the close temporal association with BR therapy, progressive disease course, and glucocorticoid resistance suggest that chemotherapy-induced immune dysregulation played a critical role in triggering GO. Rituximab-related B-cell depletion and cytokine release syndrome may have facilitated T-cell-mediated orbital inflammation, while bendamustine-induced lymphopenia further disrupted immune tolerance. This case illustrates the potential for paradoxical autoimmune activation following BR therapy in a predisposed patient. Clinicians should monitor for GO signs, and symptoms before, during, and after BR therapy in patients with underlying thyroid autoimmunity. Further clinical trials are needed to verify this phenomenon.

While immune checkpoint inhibitors (ICIs) have revolutionised cancer treatment, they can cause immune-related adverse events, including thyroid dysfunction and rarely, thyroid storm. Here, we present a rare case of thyroid storm occurring during ICI therapy, in which clinical and immunological findings strongly suggested Graves' disease. A man in his 80s with advanced lung cancer was hospitalised for multiple rib fractures. During admission, he developed fever, delirium, atrial fibrillation and marked thyrotoxicosis, leading to a diagnosis of thyroid storm. Given his prior treatment with nivolumab and ipilimumab, destructive thyroiditis was initially suspected, as this is the most common mechanism of ICI-associated thyrotoxicosis. However, marked thyroid-stimulating antibody positivity was more suggestive of Graves' disease than destructive thyroiditis. This case highlights that ICI therapy-associated thyroid storm can arise not only from destructive thyroiditis but also from Graves' disease. Therefore, careful clinical evaluation is essential to determine the underlying pathophysiology and guide optimal management.

Graves' disease (GD) is a classical autoimmune disorder caused by interactions between genetic susceptibility and immune dysregulation. However, the transcriptomic mechanisms underlying disease relapse and remission, particularly those involving alternative splicing (AS), remain poorly understood.

Thyroid eye disease (TED) is the most common extra-thyroidal complication of Graves' disease, but its molecular pathogenesis is not fully understood. This study explored the mechanism associated with methyltransferase like 3 (METTL3), NOP2/Sun RNA methyltransferase 4 (NSUN4), and solute carrier family 2 member 3 (SLC2A3) in an in vitro TED model. Human normal orbital fibroblasts were stimulated with platelet-derived growth factor BB (PDGF-BB) to establish in vitro TED model. Differentially expressed genes were screened using online databases. Western blotting was performed for protein detection, and qPCR was used for mRNA quantification. CCK-8 assay and EdU assay were conducted to examine metabolic viability and proliferation, respectively. Hyaluronan (HA) production and glycolysis metabolism were assessed via commercial kits. Methylated RNA immunoprecipitation (MeRIP), RIP, dual-luciferase reporter assay, and RNA-protein pull-down assay were utilized for interaction analysis. Bioinformatics screening obtained 1139 differential genes and 45 glycolytic genes, yielding 2 overlapping genes that were considered as glycolysis-related genes in TED. SLC2A3 was highly expressed in TED and PDGF-BB-stimulated orbital fibroblasts, and silencing SLC2A3 suppressed PDGF-BB-induced cell proliferation, HA production and glycolysis. NSUN4 mediated the m5C methylation modification to increase SLC2A3 expression in an YBX1-dependent manner. NSUN4 inhibition restrained PDGF-BB-induced effects via downregulating SLC2A3. METTL3 mediated m6A methylation modification to reduce NSUN4 expression, with YTHDF2 as a reader protein. The influences of PDGF-BB on human orbital fibroblasts were significantly alleviated by METTL3 overexpression to down-regulate NSUN4. NSUN4 downregulation caused by METTL3-induced m6A modification of NSUN4 mRNA regulated m5C modification of SLC2A3 mRNA, thereby ameliorating PDGF-BB-induced proliferation, HA generation and glycolysis of human orbital fibroblasts in TED. The evidence uncovered the specific molecular mechanism underlying TED pathogenesis.