Comparison with other studies
In keeping with the literature, the majority of the patients that underwent transsphenoidal surgery for Rathke’s cleft cysts in our cohort presented with headache, visual loss, and endocrine dysfunction [
1,
4,
7,
15,
18,
19,
28]. Our finding that pre-operative endocrine dysfunction related to the anterior pituitary was present in over two thirds of patients (42/61; 68.9%) was considerably higher than other groups, with a large meta-analysis reporting a weighted average of 46% [
23]. We speculate this may be the result of our joint management of such patients with endocrinologists that are more likely to investigate and report deficiency.
In our cohort, cysts were typically greater than 10 mm in maximal diameter (54/61; 88.5%) and were located within sellar and suprasellar regions or the sellar region alone (55/61; 90.2%). These findings are comparable with the literature, with the aforementioned meta-analysis reporting a weighted average cyst diameter of 15 mm, and a location within the sellar and suprasellar region or the sellar region alone in 94% of cases [
23]. Entirely suprasellar Rathke’s cleft cysts are uncommon and, where they occur, are thought to arise from Rathke’s pouch remnants within the pars tuberalis, which lies above the diaphragm [
3]. It has been suggested that entirely suprasellar cysts have a greater propensity for recurrence, but we could not find data to support this in our study [
7].
The signal characteristics of Rathke’s cleft cysts on T1-weighted MRI were characteristically variable in our cohort; cysts were most commonly hypointense (29/61; 47.5%), but were hyperintense in 22 cases (22/61; 36.1%) and isointense in 10 cases (16.4%). These variable signal characteristics are thought to reflect number and type of secretory cells, the presence or absence of chronic inflammation and the rate of cell desquamation [
7,
26]. A number of studies have sought to associate signal characteristics with recurrence but most fail to do so, as is the case with our study [
16]. Chotai et al. found that characteristics on T1-weighted MRI were associated with squamous metaplasia but not recurrence and that hypointensity on T2-weighted MRI was associated with recurrence but not squamous metaplasia [
7].
Transsphenoidal surgery remains the gold-standard treatment for symptomatic Rathke’s cleft cysts, but a wide range of operative strategies have been described in the literature [
1,
4‐
6,
10,
15,
18‐
20,
23,
24]. Both microscopic and endoscopic transsphenoidal surgical approaches are reported as being safe and effective options, but the latter has gained popularity in recent years due to technological advances [
1,
8,
9,
13,
14,
17,
21,
22,
28‐
31]. In an meta-analysis of 1151 patients, Mendelson et al. found that the endoscopic approach was associated with a reduced rate of recurrence when compared with the microscopic approach (weighted average of 8 and 14% respectively) [
23]. However, the authors acknowledged considerable confounders including the fact that there were far fewer studies reporting the use of an endoscopic approach and that these were more recent.
The optimal extent of surgical resection of Rathke’s cleft cysts is also contentious in the literature; with some surgeons advocating simple cyst fenestration and others complete resection [
20,
23]. In a recent meta-analysis of 655 patients, Lu et al. found that complete resection was associated with a reduced rate of recurrence when compared with partial resection or simple fenestration (pooled incidence of 14% and 20% respectively), but also an increased rate of post-operative diabetes insipidus (pooled incidence of 27 and 10% respectively). [
20]
We were not able to find data to support a difference in outcomes between the microscopic and endoscopic approach or between simple cyst fenestration and complete resection. However, an important potential confounder in our study was the fact that one surgeon favoured use of a microscope and complete resection where possible and the other favoured the use of an endoscope and simple cyst drainage.
Interestingly, squamous metaplasia and inflammation identified in the cyst wall was an infrequent finding in our study (14.8 and 27.9% respectively) and was not associated with recurrence. This is in contrast to the literature, and Kinoshita et al. suggested that squamous metaplasia may be the most important factor associated with cyst recurrence [
16]. The reasons for this discrepancy are unclear and may reflect inconsistent reporting of pathological features.
The rate of post-operative CSF leak in this study (13/61; 21.3%) was rather higher than reported in the literature, and indeed higher than we have found following transsphenoidal surgery for pituitary adenoma (ca. 5%). We speculate that this is because if no obvious CSF leak is identified intra-operatively, we often attempt to establish free drainage of the cyst with the sphenoid sinus. In cases where there is a breach in the arachnoid, either unrecognized intra-operatively or later post-operatively, this can result in a CSF fistula. To address this complication, we have now modified our technique to include an intraoperative Valsalva manoeuvre to check for a CSF leak and a lower threshold for placing an abdominal fat graft and a lumbar drain.
In patients presenting with visual loss, most patients experienced stabilization or improvement of visual symptoms following transsphenoidal surgery for Rathke’s cleft cyst (21/22; 95.4%).
As with other studies, we found that the majority of patients with pre-operative endocrine dysfunction required on-going replacement post-operatively [
12,
15]. In particular, patients with ACTH and TSH deficiency, as well as central DI, had no significant improvement post-operatively [
25]. It is thought that this limited recovery of endocrine function is due to capsular wall inflammation resulting in chronic hypophysitis or prolonged compression of the gland, leading to irreversible damage.
The rate of new post-operative diabetes insipidus (10/53; 18.9%) was also rather higher than is generally reported in the literature. However, other groups have reported similar findings where resection of the cyst wall is attempted. In a study of 188 patients with Rathke’s cleft cysts treated surgically, Aho et al. found that 17.8% (21/118) exhibited symptoms of diabetes insipidus that had not been present pre-operatively.
The overall rate of regrowth and re-operation in our study was 19.7 and 11.5% respectively. Although these findings are comparable to the literature, few studies explicitly distinguish between radiological regrowth and symptomatic recurrence that requires re-operation [
20,
23]. In a recent study of 100 patients undergoing transsphenoidal surgery for Rathke’s cleft cyst, Lin et al. found regrowth in 26.6% of cases and re-operation in 9.2% of cases. As with our study, they found that residual cystic disease on post-operative MRI was most strongly associated with recurrence.
Limitations
The present study has several limitations. The sample size of 61 patients was small because symptomatic Rathke’s cleft cyst is rare and may have been underpowered to detect more subtle associations. Nonetheless, we met our a priori minimum of 50 patients, and our principle finding that residual cystic disease on post-operative MRI was most strongly associated with recurrence is likely valid.
More generally, although the cases were recorded on a prospectively maintained database, the data was drawn from a retrospective case note review. There was therefore the possibility of incomplete or inaccurate data, selection bias and lack of control.