Department of Biochemistry

Merkel cell carcinoma (MCC) is a rare but aggressive neuroendocrine skin cancer, driven by either Merkel cell polyomavirus (MCPyV) integration or ultraviolet (UV)-induced mutations. In MCPyV-positive tumors, viral T antigens inactivate tumor suppressors pRb and p53, while virus-negative MCCs harbor UV-induced mutations that activate similar oncogenic pathways. Key signaling cascades, including PI3K/AKT/mTOR and MAPK, support tumor proliferation, survival, and resistance to apoptosis. Histologically, MCC consists of small round blue cells with neuroendocrine features, high mitotic rate, and necrosis. The tumor microenvironment (TME) plays a central role in disease progression and immune escape. It comprises a mix of tumor-associated macrophages, regulatory and cytotoxic T cells, and elevated expression of immune checkpoint molecules such as PD-L1, contributing to an immunosuppressive niche. The extracellular matrix (ECM) within the TME is rich in proteoglycans, collagens, and matrix metalloproteinases (MMPs), facilitating tumor cell adhesion, invasion, and interaction with stromal and immune cells. ECM remodeling and integrin-mediated signaling further promote immune evasion and therapy resistance. Although immune checkpoint inhibitors targeting PD-1/PD-L1 have shown promise in treating MCC, resistance remains a major hurdle. Therapeutic strategies that concurrently target the TME—through inhibition of ECM components, MMPs, or integrin signaling—may enhance immune responses and improve clinical outcomes.

Objectives: Inflammatory fibroid polyps, also known as Vanek’s tumors, are rare benign lesions of the gastrointestinal tract. Although the exact cause remains unclear, several theories suggest an association with inflammatory processes and genetic factors. This study aims to present the largest cohort of inflammatory fibroid polyp cases to date, analyzing their clinical presentation, diagnostic methods, and treatment approaches. Materials and methods: A retrospective multicentric analysis was conducted on 67 patients diagnosed with inflammatory fibroid polyps between 2013 and 2023 across four hospitals. Clinical data regarding tumor location, size, symptoms, and treatment were collected. Non-parametric statistical tests, including the chi-square test, Cramér’s V coefficient, and the Mann–Whitney U test, were used to identify association between tumor characteristics, location, and treatment outcomes. Results: The cohort included 67 patients (58.2% female, median age 60 years). The stomach was the most common tumor site (47.8%), followed by the colon (32.8%), and small intestine (10.4%). The majority of patients (73.1%) were asymptomatic, while 9% experienced intestinal obstruction, all of which were located in the small intestine. Endoscopic resection was successful in 77.6% of cases, but surgical intervention was more frequently required for tumors in the small intestine. A significant association was found between larger tumor size, emergency presentation, intestinal location, and the need for surgery. Conclusions: Inflammatory fibroid polyps are commonly managed with endoscopic resection, particularly in gastric and colonic locations. However, small intestinal tumors more often need surgical treatment, especially when presenting with complications like intestinal obstruction.