ABSTRACT
BACKGROUND AND AIM: About a third of Pituitary Neuroendocrine Tumors (PitNETs) may show aggressive behavior. Many efforts have been performed for identifying possible predictive factors to early determine the future behavior of PitNETs. Programmed cell death ligand 1 (PD-L1) expression was associated with a more aggressive biology in different solid tumors, but its role in PitNET is not well-established yet. Our study aims to analyze PD-L1 expression in a surgical cohort of PitNETs to determine its association with radiological invasion and pathology findings, as well as with long-term recurrence rates. METHODS: We performed a retrospective analysis in a series of 86 PitNETs. Clinical presentation and radiological features of the preoperative period were collected, as well as pathological data and follow-up data. The rate of PD-L1 expression was immunohistochemically evaluated and expressed as a tumor proportion score (TPS). We assessed its relationship with cavernous sinus invasion and Trouillas' classification as primary outcomes. Secondary outcomes included the TPS' relationship with histopathological markers of proliferation, hormonal expression, tumor size and long-term recurrence rates. We calculated the optimal cut-point for the primary outcomes while maximizing the product of the sensitivity and specificity and then we evaluated the significance of secondary outcomes with logistic regression analysis. RESULTS: Eighty-six patients were included in the analysis; 50 cases were non-functional PitNETs. The TPS for PD-L1 showed a highly right-skewed distribution in our sample, as 30.2% of patients scored 0. Using Trouillas' classification, we found that "proliferative" cases have a significantly higher probability to express PD-L1 in more than 30% of tumor cells (OR: 5.78; CI 95%: 1.80-18.4). This same cut-point was also associated with p53 expression. A positive association was found between PD-L1 expression and GH expression (p = 0.001; OR: 5.44; CI 95%: 1.98-14.98), while an inverse relationship was found with FSH/LH expression (p = 0.014; OR = 0.27, CI 95%: 0.10-0.76). No association was found with CS invasion, tumor size, bone erosion or dura invasion. We could not find any association between PD-L1 expression and recurrence. CONCLUSIONS: PD-L1 expression was associated with proliferative grades of Trouillas' classification and p53 expression. We also confirmed a higher expression of PD-L1 in somatotroph tumors. Larger studies are necessary to investigate the relationship between PD-L1 expression and aggressive behaviors.
ABSTRACT
Introduction: The optimal surgical treatment for giant pituitary neuroendocrine tumors(GPitNETs) is debated. Research question: The aim of this paper is to optimize the surgical management of these patients and to provide a consensus statement on behalf of the EANS Skull Base Section. Material and methods: We constituted a task force belonging to the EANS skull base committee to define some principles for the management of GPitNETs. A systematic review was performed according to PRISMA guidelines to perform a meta-analysis on surgical series of GPitNETs. Weighted summary rates were obtained for the pooled extent of resection and according to the surgical technique. These data were discussed to obtain recommendations after evaluation of the selected articles and discussion among the experts. Results: 20articles were included in our meta-analysis, for a total of 1263 patients. The endoscopic endonasal technique was used in 40.3% of cases, the microscopic endonasal approach in 34% of cases, transcranial approaches in 18.7% and combined approaches in 7% of cases. No difference in terms of gross total resection (GTR) rate was observed among the different techniques. Pooled GTR rate was 36.6%, while a near total resection (NTR) was possible in 45.2% of cases. Cavernous sinus invasion was associated with a lower GTR rate (OR: 0.061). After surgery, 35% of patients had endocrinological improvement and 75.6% had visual improvement. Recurrent tumors were reported in 10% of cases. Discussion and conclusion: After formal discussion in the working group, we recommend the treatment of G-PitNETs tumors with a more complex and multilobular structure in tertiary care centers. The endoscopic endonasal approach is the first option of treatment and extended approaches should be planned according to extension, morphology and consistency of the lesion. Transcranial approaches play a role in selected cases, with a multicompartmental morphology, subarachnoid invasion and extension lateral to the internal carotid artery and in the management of residual tumor apoplexy.
ABSTRACT
Objective: Large and giant pituitary adenomas (L- and G-PAs) continue to remain a surgical challenge. The diaphragm may have a role in determining the shape of the tumor and therefore influencing the extent of resection. Our study aims to analyze our surgical series of L- and G-PAs according to their relationship with the diaphragm and invasion of cavernous sinus (CS). Material and methods: We performed a retrospective analysis of our surgical series of patients operated for L- and G-PAs. We categorized the tumors into four grades according to their relationship with the diaphragm: grade 1 (supradiaphragmatic component with a wide incompetent diaphragm), grade 2 (purely infra-diaphragmatic tumor with a competent diaphragm), grade 3 (dumbbell-shape tumors), and grade 4 (multilobulated tumor with invasion of the subarachnoid space). Results: A total of 37 patients were included in our analysis. According to our classification, 43.3% of patients had grade 1 tumors, 27% had grade 2, 5.4% had grade 3, and 24.3% had grade 4 tumors. CS invasion was confirmed intraoperatively in 17 out of 37 patients (46%). The gross total resection (GTR) was obtained in 19% of the cases, near-total resection in 46%, and subtotal resection in 35%. All the patients who achieved GTR had grade 1 tumors and the lowest rate of CS invasion (p < 0.01). Conclusion: Radiological evaluation of the tumor relationship with the diaphragm, invasion of CS, and invasion of the subarachnoid space are crucial to plan the surgical strategy and maximize the possibilities of achieving GTR in L- and G-PAs.
