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.