Solitary left frontotemporal neuroendocrine metastasis mimicking a high-grade astrocytoma

Background: Brain metastases with neuroendocrine differentiation are rare but well-documented and may closely mimic primary intracranial neoplasms. Their radiological and clinical overlap with high-grade glial tumors can complicate the initial diagnostic approach, particularly in young patients without a known primary malignancy. Accurate diagnosis is critical, as neuroendocrine tumors (NETs) require systemic evaluation and management strategies distinct from those of primary brain tumors. Case Description: A 22-year-old man presented with a first-time generalized tonic–clonic seizure accompanied by severe headache, generalized weakness, malaise, and progressive right-sided facial paresis and paresthesias, later extending to the right upper extremity. Brain magnetic resonance imaging demonstrated a left frontotemporal lesion with imaging characteristics suggestive of a high-grade astrocytoma. The patient underwent surgical resection via an extended pterional approach, achieving gross total resection of the lesion. Initial histopathological evaluation suggested a high-grade glioma. However, further immunohistochemical analysis of the solid tumor component revealed positivity for pancytokeratin (AE1/AE3), MOC31 (polyclonal), and synaptophysin (polyclonal), with a Ki-67 (MIB-1) labeling index of 10–15%. These findings supported a diagnosis of carcinoma with neuroendocrine differentiation, contradicting the initial presumptive diagnosis of a primary glial tumor. A postoperative octreotide scintigraphy (octreoscan) failed to identify a primary NET. Conclusion: This case underscores the diagnostic challenge posed by brain metastases with neuroendocrine differentiation, particularly in young patients presenting with solitary intracranial lesions mimicking high-grade gliomas. It highlights the indispensable role of immunohistochemistry in establishing the correct diagnosis and guiding appropriate systemic evaluation and management. Awareness of this rare entity is essential, as misclassification may lead to suboptimal treatment strategies and delayed oncological workup.