Is there a need to diagnose Rathke's cleft cyst pre operatively?
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.60402
Source of Support: None, Conflict of Interest: None
Background: Rathke's cleft cyst is a rare benign sellar lesion. The exact preoperative diagnosis of this lesion by clinical and radiological features is difficult. Hence it is often misdiagnosed as craniopharyngioma. Aim: To identify the radiological pointers for pre operative diagnosis of Rathke's cleft cyst. Materials and Methods: This study presents the details of nine patients who were operated in our institution between 1998 and 2008. Radiological and histopathological variations were studied. Results: The possibility of Rathke's cleft cyst was considered pre operatively in one patient only. On reviewing the images, characteristic imaging findings were observed in a few cases. Conclusion: As minimally invasive trans-sphenoidal approach is sufficient for treating these lesions, pre operative diagnosis is important.
Keywords: Rathke′s cleft cyst, sellar lesions, trans sphenoidal approach
Rathke's cleft cysts are benign, single cell layered intrasellar cysts containing mucoid material, derived from the true remnants of embryonic Rathke's pouch. 1n 1913, Goldzieher described the first case. These cystes are found in pars intermedia or pars distalis of pituitary gland in 2% to 26% of routine autopsy series. , However, very few symptomatic lesions are reported in literature.  With the advent of computed tomography (CT) scan and magnetic resonance imaging (MRI), the lesions in the sellar region are more commonly diagnosed or detected incidentally. Rathke's cleft cyst may, however, go undiagnosed preoperatively and are often considered as cystic craniopharyngioma, which are the more common lesions of this region. A pre-operative diagnosis is important because aspiration and partial removal of Rathke's cleft cyst by transsphenoidal route is considered sufficient since these cysts are non-neoplastic and the cyst wall is supposed to have no cell proliferating ability  unlike craniopharyngioma. We have reviewed our total experience over the last 10 years focusing on radiological and pathological correlates to find out diagnostic criteria based on radiology.
Nine patients with Rathke's cleft cyst who were operated upon at National Institute of Mental Health and Neurological Sciences (NIMHANS) during 1998 to 2008 were selected for the study. Clinical characteristics of these patients were analyzed from the case records. Original radiological images and histopathological slides were reviewed. Five patients underwent transcranial surgery, two patients had endoscopic transventricular surgery and the remaining two patients underwent transsphenoidal surgery. Statistical analysis of the data was done using SPSS 15.0 software.
Mean age of the patients was 28.4 + 16.5 years. Seven of the nine patients were males. All the nine patients were symptomatic. Mean duration of symptoms was 18.3 + 30 months. Seven patients had complained of headache, six had visual disturbances, and one each had endocrine dysfunction, diabetes insipidus and hypopituitarism. Four patients had exhibited altered behavior in the form of irrelevant talk, agitation or drowsiness. Summary of these findings is presented in [Table 1].
Imaging included MRI in six patients and CT scan in three. All the lesions had sellar and suprasellar components. Three patients had associated hydrocephalus. On T1 weighted imaging, all the six lesions showed low signal intensity. On T2 weighted imaging, five lesions were of high intensity and one showed low intensity. Intracystic nodule with hyper intensity on T1weighted imaging and hypo intensity on T2 weighted imaging was seen in one patient [Figure 1]. Contrast MRI showed rim-enhancement in four patients [Figure 2] and no enhancement in the remaining two. CT showed rim enhancement in two patients. Calcifications were noted in three patients by CT scans. Summary of the radiological findings with a review of literature is given in [Table 2].
Transsphenoidal drainage of the cyst was performed on two patients, two patients underwent transventricular endoscopic decompression, and five patients had transcranial approach. During surgery, significant adhesions to surrounding tissues were seen in three cases. Thick paste like material which was whitish, yellowish or greenish in color was noted in three lesions, clear fluid in two, xanthochromic in three, and machine oil like in one. Summary of the operative findings with the imaging correlation is presented in [Table 3].
In six patients, the lining epithelium of the cyst was predominantly stratified squamous even though they contained islands of characteristic cuboidal/columnar epithelium. Of the remaining three, two cysts were lined by columnar and one by collagenized tissue. Cilia were noted in two patients and calcification in one patient. Summary of these findings with a review of literature is presented in [Table 4]. Selected histopathological slides are showed in [Figure 3].
Outcome following surgery and follow-up
Six patients made good recovery following surgery. Visual improvement was noted in two patients and was unchanged in three patients. Visual deterioration occurred in two patients of which one had normal vision preoperatively. Both of them had mild improvement on follow-up. One patient developed transient diabetes insipidus. Post operative CT scan showed no residue in three cases and residual lesion in six cases. One patient developed uncontrolled seizures in the postoperative period. He subsequently expired following aspiration pneumonia with septicemia. Summary of the surgical approach and outcome is presented in [Table 5]. Follow up was available for five patients (out of the eight patients). Mean follow-up duration was 8.8 + 8.6 months.None had any symptomatic recurrence.
Rathke's cleft cysts are thought to be derived from Rathke's pouch, which appears in the 3 rd or 4 th week of embryonic life as an outgrowth of stomodeum which elongates dorsally to form the craniopharyngeal duct. Proximal end obliterates by 11 th week and the cranial end comes in contact with infundibulum. Anterior wall proliferates to form anterior lobe of pituitary and posterior wall forms pars intermedia. The residual lumen is reduced to a narrow cleft and regresses later. Persistence and enlargement of this cleft causes symptomatic Rathke's cleft cysts. ,
On MR imaging, Rathke's cleft cyst is seen as an ovoid mass lesion in the sella, sometimes extending to suprasellar cistern, sharply demarcating itself from the surrounding tissue without remarkable mass effect or invasion.  It is usually homogenous in appearance. On T1 weighted imaging, two-third of lesions are hyper intense and one third of it hypo intense. On T2 weighted imaging one fourth are iso intense, one fourth are hypo intense and rest hyper intense.  But in the present study, all the cases who underwent MRI had hypo intense lesions on T1 weighted imaging. Five out of six were hyper intense in T2 weighted imaging. These intensity variations can be explained by varying concentration of mucopolysaccharides, bleed, cholesterol content, and cellular debris , A few imaging characteristics/variations have been described in the literature which can help the neurosurgeon in the pre- operative period to keep the diagnosis of Rathke's cleft cyst high in the priority list. They are the following: 1. Based on signal intensity-signal intensities in these lesions are variable depending on biochemical content, with most of them exhibiting T2 high signal intensity. , Diagnosis based on signal intensity is not possible as pointed out by numerous previous studies. ,,, A homogenous T2 hypo intensity in a nonenhancing midline sellar cyst continues to be highly suggestive of Rathke's cleft cyst, , whereas most of the craniopharyngiomas are hyper intense on T2 weighted images and cyst wall enhances on contrast. In our study one Rathke's cleft cyst had this feature [Table 3]. N. Kunni et al. investigated the usefulness of single-shot fast spin-echo (SSPE) diffusion-weighted MR imaging (DWI) in the diagnosis of Rathke cleft cyst. Rathke's cleft cysts are hypointense and craniopharyngiomas exhibits iso to hyperintense signals relative to brain parenchyma in DWI-SSPE. Apparent diffusion coefficient (ADC) and relative ADC in Rathke's cleft cyst were higher than those in cystic craniopharyngiomas. 
2. Intracystic nodules, which are hyper intense on T1 weighted Images and hypo intense on T2 weighted Images are considered a diagnostic indicator for Rathke's cleft cyst. Woo Mok Byun et al.  detected the existence of such a nodule in 10 out of 13 patients. In this study we were able to detect the same in one patient.
3. Egg in cup appearance had been described by Brassier. G et al.  It is characteristically made out in sagittal images when the nonenhancing cyst (egg) displaces enhancing pituitary (cup) inferiorly. None of the images in our study showed this finding. Displacement of normal pituitary gland may also be a diagnostic clue. 
4. Calcifications are uncommon in CT. [7,9] Calcifications are uncommon in Rathke's cleft cyst but more common in craniopharyngioma. However, in the present study, CT showed calcification in three patients. Cyst wall enhancement is uncommon in Rathke's cleft cyst. Rim enhancement, when compared to previous studies ,, is more commonly seen in the present study. Rim enhancement in Rathke's cleft cyst (usually seen in one third of the cases) suggests perilesional inflammation due to leakage of contents, squamous metaplasia of the wall, or displaced rim of pituitary gland. , There has been an attempt correlate rim enhancement with surgical observation and the ease of dissection. Adherence to surrounding structures was seen in three patients with rim enhancement and also in one patient with out rim enhancement. All three patients (3/9) in whom total decompression was achieved had rim enhancement. On analysis, rim enhancement was not found to have any correlation with adherence ( P = 0.79) or total excision ( P = 0.54) in our series. The fluid of the cyst with low intensity on T1 weighted images and high intensity on T2 weighted images was clear or xanthochromic in four, and greenish thick in one. The only one lesion, which had hypo intensity on T2 weighted images, yielded yellowish thick paste like material. Machine oil like fluid was obtained in one patient. Even though this is characteristically seen in craniopharyngioma, Rathke's cleft cysts also can yield similar fluid occasionally. ,,
Rathke's cleft cysts are usually lined by a single layer of cuboidal or columnar epithelium on basement membrane in 92% of cases and 58% of them are ciliated.  In this study predominant epithelium is squamous in 66.6% of the patients, suggestive of a higher incidence of squamous metaplasia in these lesions. Pituitary adenoma and concomitant Rathke's cleft cyst have been observed rarely. Rathke's cleft cyst may be observed with 0.51% to 1.7% of pituitary adenomas. We observed adenohypophyseal cells found to be entrapped in two cysts, even though there was no characteristic pituitary adenoma.
In our study, preoperative diagnosis in almost all the patients was craniopharyngioma, and not Rathke's cleft cyst. Hence the transcranial approach was done in majority of the patients with its attendant morbidity. According to the largest surgical series, aggressive resection is not justified in the management of Rathke's cleft cysts. In conclusion, characteristic findings need not be visualized in all cases of Rathke's cleft cyst. But when the cyst shows low signal intensity on T2 weighted images without cyst wall enhancement with or without other features mentioned above, the possibility of Rathke's cleft cyst should be considered and treated by the transsphenoidal route, which is what is recommended for the management of these simple cysts.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]