The role of immunohistochemical analysis in improving the diagnosis accuracy of neuroendocrine tumors of the pituitary gland

BACKGROUND: The current clinical classification and treatment principles for pituitary adenomas are primarily based on the analysis of hormone levels in blood plasma. However, this approach does not account for the heterogeneity and plurihormonal nature of these tumors, which pose significant diagnostic challenges. Immunohistochemical (IHC) analysis is a crucial tool for studying the molecular characteristics of resected tumors, enabling the identification of features that may not be apparent through standard biochemical tests and clinical evaluation. AIM: To investigate the heterogeneity and hormone co-expression of pituitary adenomas through a comparative analysis of clinical, hormonal, and immunohistochemical data, aiming to optimize the diagnosis and classification of pituitary neuroendocrine tumors. MATERIALS AND METHODS: The study included 10 pituitary adenoma samples. A comprehensive immunohistochemical analysis was performed to evaluate the expression of transcription factors and pituitary hormones to detect tumor heterogeneity and potential plurihormonal pituitary adenomas. RESULTS: The analysis confirmed significant heterogeneity of pituitary adenomas and identified cases of hormone co-­expression in certain tumors, which may be overlooked when relying solely on clinical data and blood test results, or in the absence of IHC testing that covers all hormones and transcription factors in pituitary tissue. In our study, we identified heterogeneity in pituitary adenoma samples at the level of transcription factor and hormone expression. For example, in two hormonally active corticotropinomas, we observed not only the expression of standard IHC markers but also the unexpected expression of GH and PIT1. Notably, somatotropinomas exhibited distinct expression of SF1, a transcription factor typically specific to gonadotroph cells. Additionally, we identified signs of heterogeneity in hormone-inactive pituitary tumors — such as silent gonadotropinomas — where co-expression of both SF1 and TPIT was detected. CONCLUSION: The results of the study confirmed significant heterogeneity of pituitary adenomas and the presence of hormone co-expression, indicating the complexity of their diagnosis when relying solely on clinical and hormonal methods. Comprehensive immunohistochemical analysis plays a key role in the accurate classification of these tumors, which may contribute to the improvement of diagnostic and therapeutic approaches.