Clinical and prognostic implications of pituitary macroadenomas (PitNets) grading: a monocentric experience

Rationale: Pituitary neuroendocrine tumors (PitNets), also known as pituitary adenomas, are aggressive in 20% of cases, with local invasion, relapse/scarce response to conventional treatment, in the absence of reliable predictive parameters. In 2018, Trouillas et al. proposed a 5-tier clinicopathological classification, not widely validated yet. In the present study we investigated, in a PitNets monocentric series, the correlation between this classification system and features at diagnosis and medium-term clinical and biochemical outcomes. Materials & methods: we retrospectively evaluated 88 consecutive patients (51 M, 50.5±14.7 yrs) with functioning (FPA) or non-functioning pituitary macroadenomas (NFPA), referred to the Endocrine Unit of Messina University Hospital, and operated by the same neurosurgeon in the period 2015–2020. Of each patient we reviewed recorded demographic, clinical, radiological, biochemical data and visual field, both at diagnosis/last follow-up (median 3 ± 1.5 yrs), therapeutical history, and pathological data. Once classified PitNets according to Trouillas et al. grading system, we correlated it to clinico-pathological and hormonal features at diagnosis, and to clinical, biochemical and ophthalmological outcomes at 6 months after surgery and at last follow-up. Results: According to Trouillas grading system, 38.6% of patients were assigned the 1a grade, 7.9% the 1b, 48.9% and 4.5% the 2a and 2b, respectively. At diagnosis, panhypopituitarism and visual field alterations were more frequent among 2a grade tumors. GH-omas were significantly prevalent among 1a tumors, NFPA among 2a. PitNets with 1a and 2a grade had a better response to single surgery (p < 0.01), while cyberknife stereotactic radiotherapy was needed more frequently in 2a and 2b tumors. Panhypopituitarism/visual field alterations were more frequent among 2a PitNets even after surgery. Ki-67 was positively associated to persistent disease in FPA, while radiological invasion was associated to remnant presence among NFPA. Conclusions: Invasive and not-proliferating PitNets (2a) were more frequently associated to impaired pituitary function/visual field before and after surgery. Less proliferating tumors (1a and 2a) were more responsive to surgery. Ki-67 correlated to disease persistence in FPA, while adiuvant radiotherapy was more needed among invasive tumors. Thus, among ≥ 1 cm PitNets, tumor invasion seems to impact on clinico-biochemical outcomes, while Ki-67 proliferation index influences surgical outcomes.