Prognostic impact of immune microenvironment in laryngeal and pharyngeal squamous cell carcinoma: Immune cell subtypes, immuno-suppressive pathways and clinicopathologic characteristics

Angiogenesis has long been considered to facilitate and sustain cancer growth, making the introduction of anti-angiogenic agents that disrupt the vascular endothelial growth factor/receptor (VEGF/VEGFR) pathway an important milestone at the beginning of the 21st century. Originally research on VEGF signaling focused on its survival and mitogenic effects towards endothelial cells, with moderate so far success of anti-angiogenic therapy. However, VEGF can have multiple effects on additional cell types including immune and tumor cells, by directly influencing and promoting tumor cell survival, proliferation and invasion and contributing to an immunosuppressive microenvironment. In this review, we summarize the effects of the VEGF/VEGFR pathway on non-endothelial cells and the resulting implications of anti-angiogenic agents that include direct inhibition of tumor cell growth and immunostimulatory functions. Finally, we present how previously unappreciated studies on VEGF biology, that have demonstrated immunomodulatory properties and tumor regression by disrupting the VEGF/VEGFR pathway, now provide the scientific basis for new combinational treatments of immunotherapy with anti-angiogenic agents.

Adenomatoid tumors have been described almost a century ago, and their nature has been the subject of debate for decades. They are tumors of mesothelial origin usually involving the uterus, the Fallopian tubes, and the paratesticular region. Adenomatoid tumors of the adrenal gland, the liver, the extragenital peritoneum, the pleura, and the mediastinum have been rarely reported. They are usually small incidental findings, but large, multicystic and papillary tumors, as well as multiple tumors have been described. Their pathogenesis is related to immunosuppression and to TRAF7 mutations. Despite being benign tumors, there are several macroscopic or clinical aspects that could raise diagnostic difficulties. The aim of this review was to describe the microscopic and macroscopic aspects of adenomatoid tumor with a special focus on its differential diagnosis and pathogenesis and the possible link of adenomatoid tumor with other mesothelial lesions, such as the well-differentiated papillary mesothelioma and the benign multicystic mesothelioma, also known as multilocular peritoneal cysts.