Nuclear translocation of beta catenin in patients with Rathke cleft cysts—clinical and imaging characteristics and risk of recurrence

Abstract

Purpose Although Rathke cleft cysts (RCC) are benign lesions of the sellar region, recurrence is frequent after surgical treatment. Nuclear translocation of ß-catenin (NTßC), a key effector of the wnt-signaling pathway that is responsible for cell renewal, has been shown to act as a proto-oncogene and is considered to be a potential risk factor for increased recurrence in RCC. In this study, we analyzed a surgically treated cohort into patients with and without NTßC expression in order to identify clinical and imaging differences and further evaluate the risk of recurrence. Methods Patients with resection of RCC between 04/2001 and 11/2020 were included. Histological specimens were immunohistochemically stained for ß-catenin. Study endpoints were time to cyst recurrence (TTR) and functional outcome. Functional outcome included ophthalmological and endocrinological data. Furthermore, MRI data were assessed. Results Seventy-three patients (median age 42.3 years) with RCC underwent mainly transsphenoidal cyst resection (95.9%), 4.1% via transcranial approach. Immunohistochemical staining for ß-catenin was feasible in 61/73 (83.6%) patients, with nuclear translocation detected in 13/61 cases (21.3%). Patients with and without NTßC were equally likely to present with endocrine dysfunction before surgery (p = 0.49). Postoperative new hypopituitarism occurred in 14/73 (19.2%) patients. Preoperative visual impairment was equal in both groups (p = 0.52). Vision improved in 8/21 (33.3%) patients and visual field deficits in 22/34 (64.7%) after surgery. There was no difference in visual and perimetric outcome between patients with and without NTßC (p = 0.45 and p = 0.23, respectively). On preoperative MRI, cyst volume (9.9 vs. 8.2 cm3; p = 0.4) and evidence of hemorrhage (30.8% vs. 35.4%; p = 0.99) were equal and postoperative cyst volume decreased significantly in both groups (0.7 vs. 0.5 cm3; p < 0.0001 each). Cyst progression occurred in 13/73 (17.8%) patients after 39.3 ± 60.3 months. Cyst drainage with partial removal of the cyst wall resulted in improved recurrence-free survival without increasing the risk of complications compared with cyst fenestration alone. Patients with postoperative diabetes insipidus had an increased risk for recurrence according to multivariate analysis (p = 0.005). NTßC was evident in 4/15 patients (26.7%) and was not associated with a higher risk for recurrence (p = 0.67). Conclusion Transnasal transsphenoidal cyst drainage with partial removal of the cyst wall reduces the risk of recurrence without increasing the risk of complications compared with fenestration of the cyst alone. Patients with postoperative diabetes insipidus seem to have an increased risk for recurrence. In contrast, NTßC was not associated with a higher risk of recurrence and did not provide stratification for clinically distinct patients.

Long-term outcome of surgically treated and conservatively managed Rathke cleft cysts

“…In 65 patients (89.0%), fenestrations with an augmented cyst wall resection were conducted. In the remaining patients, only cyst fenestration was performed as previously described by our group [ 21 ]. Demographic data are shown in Table 1 .…”

“…The aggressiveness of the resection of the cyst wall appears to have a crucial influence on the rate of pituitary dysfunction [ 1 ]. Patients in this study were treated with a rather conservative surgical approach with cyst fenestration or augmented cyst wall resection as previously described [ 21 ]. The rate of surgical complications was lower in the secondary surgery group, indicating the safety of the surgical procedure after the initial WWS.…”

“…Surgery is indicated in space-occupying cysts that lead to worsening visual acuity and visual field loss due to compression of the optic apparatus and may lead to a significant improvement of these symptoms in up to 80% [ 3 , 11 , 21 ]. Surgical complications such as a new hormone deficiency of the anterior or posterior pituitary or leakage of cerebrospinal fluid may occur in about 5–43% of cases [ 1 , 5 , 17 ].…”

“…While risk factors for recurrence/progression in surgically treated patients such as preoperative cyst size or squamous metaplasia in the cyst wall and new-onset diabetes insipidus postoperatively have been identified [ 13 , 21 , 24 ], the literature on risk factors for progression in nonsurgical RCC is sparse. Only Kinoshita et al could show that patients older than 57 years are at an increased risk for cyst progression [ 12 ].…”