Expression of additional transcription factors is of prognostic value for aggressive behavior of pituitary adenomas.

OBJECTIVE: According to the latest WHO classification of tumors of endocrine organs in 2017, plurihormonal adenomas are subclassified by their transcription factor (TF) expression. In the group of plurihormonal adenomas with unusual immunohistochemical combinations (PAWUC), the authors identified a large fraction of adenomas expressing TFs for gonadotroph adenoma (TFGA) cells in addition to other TFs. The aim of this study was to compare clinicopathological parameters of PAWUC with TFGA expression to gonadotroph adenomas that only express TFGA. METHODS: This retrospective single-center series comprises 73 patients with TFGA-positive pituitary adenomas (SF1, GATA3, estrogen receptor α): 22 PAWUC with TFGA (TFGA-plus group) and 51 with TFGA expression only (TFGA-only group). Patient characteristics, outcome parameters, rate of invasiveness (assessed by direct endoscopic inspection), and MIB1 and MGMT status were compared between groups. RESULTS: Patients in the TFGA-plus group were significantly younger than patients in the TFGA-only group (age 46 vs 56 years, respectively; p = 0.007). In the TFGA-only group, pituitary adenomas were significantly larger (diameter 25 vs 18.3 mm, p = 0.002). Intraoperatively, signs of invasiveness were significantly more common in the TFGA-plus group than in the TFGA-only group (50% vs 16%, p = 0.002). Gross-total resection was significantly lower in the nonfunctioning TFGA-plus group than in the TFGA-only group (44% vs 86%, p = 0.004). MIB1 and MGMT status showed no significant difference between groups. CONCLUSIONS: These data suggest a more aggressive behavior of TFGA-positive adenomas if an additional TF is expressed within the tumor cells. Shorter radiographic surveillance and earlier consideration for retreatment should be recommended in these adenoma types.

Challenging Knosp high-grade pituitary adenomas.

OBJECTIVE: Parasellar growth is one of the most important prognostic variables of pituitary adenoma surgery, with adenomas regarded as not completely resectable if they invade the cavernous sinus (CS) but potentially curable if they displace CS structures. This study was conducted to correlate surgical treatment options and outcomes to the different biological behaviors (invasion vs displacement) of adenomas with parasellar extension into the superior or inferior CS compartments or completely encasing the carotid artery (Knosp high grades 3A, 3B, and 4). METHODS: This was a retrospective cohort analysis of 106 consecutive patients with Knosp high-grade pituitary adenomas with parasellar extension who underwent surgery via a primary endoscopic transsphenoidal approach between 2003 and 2017. Biological tumor characteristics (surgical status of invasiveness and tumor texture, 2017 WHO classification, proliferation rate), extent of resection, and complication rate were correlated with parasellar extension grades 3A, 3B, and 4 on preoperative MRI studies. RESULTS: Invasiveness was significantly less common in grade 3A (44%) than in grade 3B (72%, p = 0.037) and grade 4 (100%, p < 0.001) adenomas. Fibrous tumor texture was significantly more common in grade 4 (52%) compared to grade 3A (20%, p = 0.002), but not compared to grade 3B (28%) adenomas. Functioning macroadenomas had a significantly higher rate of invasiveness than nonfunctioning adenomas (91% vs 55%, p = 0.002). Mean proliferation rate assessed by MIB-1 was > 3% in all groups but without significant difference between the groups (grade 3A, 3.2%; 3B, 3.9%; 4, 3.7%). Rates of endocrine remission/gross-total resection were significantly higher in grade 3A (64%) than in grade 3B (33%, p = 0.021) and grade 4 (0%, p < 0.001) adenomas. In terms of complication rates, no significant difference was observed between grades. CONCLUSIONS: According to the authors' data, the biological behavior of pituitary adenomas varies significantly between parasellar extension patterns. Adenomas with extension into the superior CS compartment have a lower rate of invasive growth than adenomas extending into the inferior CS compartment or encasing the carotid artery. Consequently, a significantly higher rate of remission can be achieved in grade 3A than in grade 3B and grade 4 adenomas. Therefore, the distinction into grades 3A, 3B, and 4 is of importance for prediction of adenoma invasion and surgical treatment considerations.