Clinical and neuroradiological red flags in differential diagnosis of pituitary metastases and PitNETs (adenomas): a surgeon's experience and systematic literature review

Introduction: Pituitary metastases (PMs) are rare malignancy manifestations, generally deemed to have an extremely poor prognosis. Differential diagnosis from primary pituitary lesions is often difficult, as their features can mimic those of pituitary neuroendocrine tumours (PitNETs). This study aimed to report a single surgeon's experience in managing PMs and to gather the existing evidence on their clinical and neuroradiological presentation to build a model of 'red flags' that help raise the suspicion of PMs in the context of sellar lesions. Material and methods: We retrieved an original 10-year surgical series of patients undergoing endoscopic transsphenoidal (TNS) surgery for suspected PitNETs, and we additionally conducted a systematic review of case reports or series of patients with PMs. Results: The local series consisted of n = 6 PMs. The literature review yielded n = 149 works reporting n = 340 PMs. Overall, the clinical presentation and neuroradiological features of n = 346 PMs were analysed and compared to data retrieved from n = 361 PitNETs from our original cohort. Primary features associated with PMs were: the presence of headaches (OR 1.24, p = 0.001), visual field deficits (OR 1.19, p = 0.02), extraocular nerve palsies (OR 1.23, p = 0.001), diabetes insipidus (OR 2.13, p < 0.001), MRI features of pituitary stalk/infundibular involvement (OR 1.98, p = 0.001), cavernous sinus invasion (OR 1.57, p = 0.004), and T2w flow voids (OR 1.13, p = 0.001). An incidental diagnosis (OR 0.49, p < 0.001) and cystic changes (OR 0.77, p = 0.02) were less common among PMs. Secondary features involved an acute onset of symptoms (OR 1.25, p = 0.001), the presence of oncological history (OR 1.89, p = 0.001), sellar walls erosion (OR 1.55, p = 0.002), and gross appearance of a firm (OR 2.01, p < 0.001) and easily bleeding lesion (OR 1.99, p < 0.001). Sellar enlargement predicted a lower risk of PMs (OR 0.54, p = 0.001). Conclusion: We have compiled a list of primary and secondary red flags, including clinical and neuroradiological features, to serve as a guiding tool for clinicians to raise suspicion of PMs and aid in the differential diagnosis of various lesions centered in the sella.