P07.17.A WHEN THE TUMOR DISAPPEARS: CLINICAL RELEVANCE OF NEGATIVE HISTOLOGY IN PITUITARY NEUROENDOCRINE TUMORS (PITNETS)

Abstract BACKGROUND Pituitary Neuroendocrine Tumors (PitNETs) with paradoxically negative pathology (NP) have been well described in ACTH adenomas and, more rarely, in PRL and GH adenomas. NP cases are characterized by suggestive clinical, hormonal, and radiological evidence of a PitNET, yet lack histopathological confirmation. Their true prevalence, underlying causes, and prognostic implications remain unclear. This study aims to characterize NP across subtypes of functioning PitNET and assess its clinical significance. MATERIAL AND METHODS We included all patients who underwent a first-time surgery for a PitNET between January 1996 and December 2023. Cases without histological reports or interpretable biopsies were excluded, as were patients lost before a first follow-up. RESULTS A total of 666 patients were included (mean age: 48.5 years; F/M ratio = 1.3). NP findings were observed in 30% of ACTH-, 28% of PRL-, 12% of GH- and 9% of multi-secreting tumors. Most NP cases (76%) were microadenomas (or non visible). Pre-treatment hormonal levels were similar between NP and histologically confirmed PitNETs. Cure rates were comparable between NP and confirmed PitNETs for PRL, higher for GH, and slightly lower in ACTH cases. While reoperation for NP adenomas with unfavorable outcomes was rare in GH and PRL cases, it was systematic in ACTH cases. The unfavorable outcomes in ACTH-NP cases are partly explained by a high rate of radiological mislocalization (60%), resulting in incorrect surgical targeting. Such mislocalization has not been described in GH and PRL cases. Higher postoperative morning cortisol levels were found in mislocalized cases compared to both cured and recurrent cases. CONCLUSION Negative pathology is a frequent finding in functioning PitNET and is generally associated with favorable outcomes, particularly in PRL- and GH-secreting tumors. In contrast, ACTH adenomas with negative histology appear to have poorer outcomes, likely due to radiological mislocalization leading to suboptimal surgical targeting. Elevated postoperative cortisol levels may serve as an early biomarker for such cases. Other instances of negative pathology may be explained by technical limitations, including specimen loss or misdiagnosis of focal hyperplasia. Recognizing these patterns is essential to avoid diagnostic doubt and ensure appropriate postoperative management.