Jod-Basedow phenomenon (JBP) is a rare thyrotoxic condition due to increased exogenous iodine exposure, also known as iodine-induced hyperthyroidism (IIH). Historically JBP was typically seen in iodine-deficient patients when exposed to increased amounts of iodine. However, in today's era, the most common cause of JBP is exposure to iodinated contrast media commonly used in various radiological examinations and interventional procedures, resulting in massive iodine exposure. Patients with normal thyroid function usually experience no ill effects. There has been increasing use of iodinated contrast in imaging and procedures over recent decades. Deposition of iodine in the thyroid in a person with normal functioning thyroid glands would usually be autoregulated and inhibited by the Wolff Chaikoff effect. However, a small albeit a significant portion of patients, particularly those with pre-existing thyroid conditions, can escape this auto-regulatory effect and be subject to life-threatening conditions, such as arrhythmias, heart failure, pulmonary arterial hypertension, cerebrovascular and pulmonary embolism, and cardiomyopathy. We present a case of a 59-year-old female with pre-existing goiter who presented with altered mentation and seizures, requiring endotracheal intubation for airway protection. She underwent a CT angiogram of the head and neck for a suspected stroke, receiving iodinated IV contrast in the process. Thyroid function tests on admission showed a thyroid-stimulating hormone (TSH) of 0.974 mIU/L (reference range 0.465-4.650 mIU/L) and free T4 of 0.46 ng/dL (reference range 0.75-2.19 ng/dL). The ensuing ICU course was complicated by thyrotoxicosis eight days after contrast administration with a surge of free T4 from 0.46 ng/dL on admission to 4.07 ng/dL and a TSH suppression to <0.015 mIU/L. She subsequently required three sessions of emergent plasmapheresis to remove excess free T4 before undergoing partial thyroidectomy and cardiac catheterization. Iodine-induced hyperthyroidism solidifies the need for awareness of a potential JBP following contrast administration, especially in an aging population and undiagnosed thyroid conditions, and timely diagnosis and intervention can greatly influence outcomes.

SMARCA4-deficient undifferentiated tumors (SMARCA4-dUT) are infrequently occurring aggressive neoplasms found predominantly in young male smokers. These tumors are distinguished by the loss of expression of Brahma-related gene 1 (BRG1) due to a deactivating mutation of SMARCA4. Immunophenotype can be variable but characteristically lack the expression of BRG1. SMARCA4-dUT has a poor prognosis and generally progresses or recurs. The median survival is around 6 months. Here, we report a case of a 36-year-old male smoker who presents with multiple right-sided lung masses. The patient was found to have a loss of SMARAC4 and SMARCA2 along with the absence of markers of vascular, melanocytic, lymphoid, keratin, or myogenic origin. Tumor size was reduced significantly after 3 cycles of carboplatin and 1 cycle of pembrolizumab. From reviewing the literature and the clinical course in our case, we suggest combination chemotherapy plus immune checkpoint inhibitor (ICI) therapy to be the first choice of therapy for treating SMARCA4-dUT of lungs. Further research and studies are needed to evaluate the response to ICI therapy alone or combination therapy (chemotherapy plus ICI).

Background: Poorly differentiated neuroendocrine tumors of the pancreas (pd-PNETs) are very rare tumors. Differentiating primary pd-PNET from neuroendocrine carcinomas, which metastasize to the pancreas, can be difficult. We will refer to any neuroendocrine carcinoma with pancreatic metastasis as secondary pd-PNETs. This study evaluates the differences in incidence, clinical picture, outcomes, and treatment between primary and secondary pd-PNETs. Methods: A comprehensive search of the pd-PNET database was performed to gather data on incidence, race, age, gender, clinical picture, and outcomes for primary and secondary pd-PNETs. The emphasis was on small-cell lung cancer (SCLC) and Merkel cell carcinoma (MCC) due to their associations with secondary pd-PNET. Additional data from the PubMed database were analyzed, and 12 case reports of primary pd-PNETs were added for clinical characteristic analysis. Results: Primary and secondary pd-PNETs exhibit highly similar profiles in terms of age, gender, race, and clinical features. However, treatment strategies are significantly different. Primary pd-PNETs are managed with tumor resection and platinum-based chemotherapy. Primary tumors usually have poor prognosis, with a median survival of 12 months. Treatment for secondary pd-PNETs varies based on the primary tumor. The treatment strategy for metastatic MCC was changed to immune checkpoint inhibitors (ICIs), and survival improved. Tarlatamab also recently showed a good response in the management of SCLC. These findings highlight the need for accurate and timely diagnosis to provide correct treatment. Conclusions: Patients with primary and secondary pd-PNETs exhibit similar clinical presentations and epidemiological characteristics. However, when a poorly differentiated neuroendocrine pancreatic mass is identified, it is critical to exclude MCC or small-cell lung carcinoma metastasis, as treatments may be different and prognosis may also be different.

Conclusion: Patients with primary and secondary pd-PNETs exhibit similar clinical presentations and epidemiological characteristics. However, when a poorly differentiated neuroendocrine pancreatic mass is identified, it is critical to exclude MCC or Small cell lung carcinoma metastasis, as treatments may be different and prognosis may also be different.

Toll-like receptor 2 (TLR2) is a versatile pattern-recognition receptor of the innate immune system that recognizes both pathogen-associated molecular patterns (PAMPs) and endogenous danger-associated molecular patterns (DAMPs). Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs)—clonal hematopoietic stem-cell disorders that include essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF)—are characterized by persistent inflammation and an increased risk of thrombosis. Dysregulated TLR2 signaling has emerged as a potentially important mediator of this chronic thrombo-inflammatory state. Findings from our group and others suggest that TLR2 may have a particularly prominent role in promoting inflammatory cytokine production, platelet–leukocyte interactions, endothelial dysfunction, and thrombotic complications in MPNs. Our findings are also consistent with evidence that NF-κB-mediated proinflammatory signaling, in addition to constitutive JAK/STAT activation, contributes substantially to MPN pathogenesis. In this review, we provide a comprehensive overview of TLR2 biology and examine its contribution to the thrombo-inflammatory milieu of MPNs, with particular emphasis on its potential utility as a biomarker and a therapeutic target. Ruxolitinib, a JAK1/2 inhibitor, markedly reduces symptom burden and splenomegaly in JAK2-mutant MPNs, particularly PV and MF; however, it has limited efficacy in CALR-mutant or triple-negative ET. This differential therapeutic response may reflect divergent downstream signaling pathways and may also be related to dysregulated TLR2 signaling. Furthermore, hyperactive TLR2 signaling in MPNs may help explain the incomplete ability of ruxolitinib to suppress thrombo-inflammatory responses. Therefore, combined TLR2-targeted therapy and ruxolitinib may represent a more effective therapeutic strategy for future MPN trials. Overall, however, we consider the TLR2-mediated thrombo-inflammatory response in MPNs to be an amplifier of inflammation rather than a primary disease driver.