Tumour Microenvironment: The General Principles of Pathogenesis and Implications in Diffuse Large B Cell Lymphoma.

Diffuse large B cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma worldwide, constituting around 30-40% of all cases. Almost 60% of patients develop relapse of refractory DLBCL. Among the reasons for the therapy failure, tumour microenvironment (TME) components could be involved, including tumour-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), tumour-associated neutrophils (TANs), cancer-associated fibroblasts (CAFs), and different subtypes of cytotoxic CD8+ cells and T regulatory cells, which show complex interactions with tumour cells. Understanding of the TME can provide new therapeutic options for patients with DLBCL and improve their prognosis and overall survival. This review provides essentials of the latest understanding of tumour microenvironment elements and discusses their role in tumour progression and immune suppression mechanisms which result in poor prognosis for patients with DLBCL. In addition, we point out important markers for the diagnostic purposes and highlight novel therapeutic targets.

Immunohistochemical Profile of Parathyroid Tumours: A Comprehensive Review.

Immunohistochemistry remains an indispensable tool in diagnostic surgical pathology. In parathyroid tumours, it has four main applications: to detect (1) loss of parafibromin; (2) other manifestations of an aberrant immunophenotype hinting towards carcinoma; (3) histogenesis of a neck mass and (4) pathogenetic events, including features of tumour microenvironment and immune landscape. Parafibromin stain is mandatory to identify the new entity of parafibromin-deficient parathyroid neoplasm, defined in the WHO classification (2022). Loss of parafibromin indicates a greater probability of malignant course and should trigger the search for inherited or somatic CDC73 mutations. Aberrant immunophenotype is characterised by a set of markers that are lost (parafibromin), down-regulated (e.g., APC protein, p27 protein, calcium-sensing receptor) or up-regulated (e.g., proliferation activity by Ki-67 exceeding 5%) in parathyroid carcinoma compared to benign parathyroid disease. Aberrant immunophenotype is not the final proof of malignancy but should prompt the search for the definitive criteria for carcinoma. Histogenetic studies can be necessary for differential diagnosis between thyroid vs. parathyroid origin of cervical or intrathyroidal mass; detection of parathyroid hormone (PTH), chromogranin A, TTF-1, calcitonin or CD56 can be helpful. Finally, immunohistochemistry is useful in pathogenetic studies due to its ability to highlight both the presence and the tissue location of certain proteins. The main markers and challenges (technological variations, heterogeneity) are discussed here in the light of the current WHO classification (2022) of parathyroid tumours.