IgG4-related disease (IgG4-RD) is a multi-organ fibroinflammatory condition often misdiagnosed due to its clinical similarities with other rheumatologic diseases such as Sjögren's syndrome (SS) and malignancy. This case highlights a 76-year-old woman with a complex medical history who presented with symptoms initially suggestive of SS but was ultimately diagnosed with IgG4-RD. The patient in our case report presented with bilateral, large, nontender submandibular lymphadenopathy. Initial serological tests were negative for SSA and SSB markers but revealed elevated immunoglobulin G levels of 2811 mg/dL. Imaging showed enlarged submandibular glands and lymphadenopathy. A core biopsy revealed a dense nodular lymphocytic infiltrate with variable parenchymal fibrosis and salivary gland acinar atrophy. The specimen was sent for further immunohistochemistry (IHC) testing as extended lab workup showed IgG4 levels of 843 mg/dL, raising concern for underlying IgG4-RD. IHC showed an increased number of IgG4 plasma cells, up to 50% in some areas, confirming the diagnosis of IgG4-RD. Treatment with prednisone led to rapid symptomatic improvement. Differentiating IgG4-RD from SS is challenging due to overlapping clinical and histological features. Elevated serum IgG4 levels (>135 mg/dL) are suggestive but not definitive for IgG4-RD; biopsy remains the gold standard for diagnosis. This case underscores the importance of considering IgG4-RD in patients presenting with SS-like symptoms, especially in the absence of anti-Ro/SSA and anti-La/SSB antibodies, and of initiating an extensive workup to fully delineate the extent of the disease in order to initiate timely treatment and prevent organ damage. This case report emphasizes the need for thorough evaluation in patients with SS-like symptoms to differentiate IgG4-RD, ensuring accurate diagnosis and effective treatment. Prompt recognition and management of IgG4-RD can improve patient outcomes and prevent long-term morbidity.

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.

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.