Posterior Pituitary and Hypothalamic Neuronal Tumors in the 5th WHO Classification: Molecular Insights, Diagnostic Markers, and Clinical Management

Posterior pituitary and hypothalamic neuronal tumors are uncommon sellar and suprasellar neoplasms that can mimic pituitary neuroendocrine tumors clinically and radiologically. The 5th edition World Health Organization classification (Endocrine and Neuroendocrine Tumors) reinforce a lineage-based framework that separates anterior pituitary tumors from posterior pituitary and hypothalamic neuronal lineages, which is particularly important in hormone-negative lesions and limited tissue samples. This narrative review provides a practical, pathology-centered approach to classification by integrating key anatomic and radiologic clues with histomorphology and targeted immunohistochemistry. We highlight the value and limitations of thyroid transcription factor 1, outline a stepwise workflow incorporating anterior pituitary transcription factors and neuronal differentiation markers, and discuss when vasopressin immunostaining is informative. We also summarize selected molecular insights and clinical management considerations relevant to surgical planning and follow-up.