Rathke's cleft cysts (RCCs) are nonneoplastic and benign cystic lesions in the sellar or suprasellar space. The pathogenesis of RCCs remains controversial, they are thought to originate from the remnant of an invagination of the dorsal oral ectoderm named Rathke's pouch, which usually regresses completely.1,2 Several other theories suggested that RCCs might arise from endodermal origin, neuroepithelial cells, or reverse metaplasia of pituitary cells,3–5 those seemed to be less plausible. The detection rate of RCCs is 12%-33% in autopsy.6–9 and almost all RCCs were small and clinically asymptomatic in lifetime, but if they are incidentally and persistently enlarged enough to cause compression for circumambient tissue such as pituitary gland or optic chiasm, and to increase intracranial pressure, they are exposed.10,11 Voelker et al12 presumed that the reason for an increase in the size of RCCs may be an imbalance between secretion and absorption of cyst content. And other reasons may be intracystic hemorrhage or infection.13 The development of modern medical imageology, especially magnetic resonance imaging (MRI), has encouraged the clinical diagnosis of RCCs.14–17 Because the signal intensities of RCCs are variable, the final diagnosis is more or less difficult before surgery. In this study, we retrospectively reviewed a series of 42 patients who underwent surgery resection because of RCCs, and analyzed the characteristics of surgical management and clinic outcomes.
Clinical numerical data came from the patients who were diagnosed as RCCs for the first time and underwent surgical treatment in the Department of Neurosurgery of the Affiliated Hospital of Medical College, Qingdao University between January 2005 and December 2010. The diagnosis was based on pathological, imageological, and intra-operative findings.
The comprehensive preoperative evaluation is necessary for every patient. All patients underwent brain MRI (routine scanning and enhancement scanning or only enhancement scanning) and sella turcica computed tomography (CT) examination.
The endocrinological laboratory examination such as thyrotropic stimulating hormone, growth hormone, prolactin, luteinizing hormone, and adrenocorticotropic hormone were performed for every patient preoperatively. The thyroid function tests and adrenal gland function tests were performed preoperatively additionally.
Visual field and acuteness of vision were examed for any patients with visual impairment or not.
The size of RCCs and the relation with circum-architecture were the evidence to decide which modus operandi was selected. Endonasal transsphenoidal microsurgery was done as described previously.18,19 A standard frontal craniotomy procedures was performed for suprasellar or metasellar lesions. The objective of surgical was to drain the contents of the cyst and to remove the capsule as much as possible under the precondition that do not increase the complications. The resection of the capsule should be gentle and prudent. The sellar floor was reconstructed following endonasal transsphenoidal surgery in order to prevent cerebrospinal rhinorrhea. Intranasal packing was performed after the operation and the bysma was removed on the 2nd or 3rd postoperative day. The suture lines were removed on the 7th or 8th postoperative day under transcranial surgery.
For the first day, the patients were monitored in neurosurgical intensive care unit (NICU) for vital sign and neurological observation. The specimens obtained in the operation were observed by pathological tissue analysis. The brain CT was performed on the 2nd postoperative day in order to get the information about operative region. The complication was surveilled, treated and recorded. No radiation therapy was given after surgery.
The routine follow-up includes physical, neuroimaging and hemadenology examinations, that were performed for all the patients, which were scheduled at 1-, 6-, and 12-month, and thereafter annually. The mean follow-up was 22 months (range 12-60 months). Medical history data reviews and direct contacts with the patients were used to derive the follow-up and outcome data. Recurrence was defined as neuroimaging evidence of re-appear or enlargement of the cysts mass postoperatively, with symptoms or not.
Totally 42 patients (19 males and 23 females; age range, 6-67 years, mean, 41.6 years) were enrolled in this study. Every patient was diagnosed and underwent surgical treatment for the first time in this serial. The duration of the symptoms ranged from 4 days to 10 years. The presenting isolated symptoms of the patients include simple headache (20 cases, 48%), simple visual impairment (7 cases, 17%) and simple hypopituitarism (1 case, 2%); seven patients (17%) presented with headache and also complained of visual disturbances, two patients (5%) presented with headache and pituitary dysfunction, one patient (2%) presented with visual disturbances and hypopituitarism. Four patients (10%) were discovered incidentally with no apparent clinical symptoms. Three of 4 patients who presented with pituitary dysfunction showed polydipsia and hyperdiuresis, the other one was amenorrhea and lactating. Headache was described as retroorbital, bitemporal and frontal; dull pain was common and acute headaches occurred in six patients; most of 20 patients with an simple headache symptom had a history no more than two months except one old woman who had headache for about ten years and aggravated in recent one month before surgery.
The maximum diameter of cysts ranged from 6.0 to 46.7 mm (mean, 20.07 mm). Signal intensities on T1 and T2 weighted images of the cysts were as follows: long-signal in 23 and 18 patients, iso-signal in 7 and 9 patients, and short-signal in 12 and 15 patients. No case showed homogeneous enhancement of the contents. And distinct rim enhancement was observed in 5 patients (Figure 1A). Nodulose long-signal intra-cyst on T1 weighted images was found in 3 patients (Figure 1B). Girdling signer was found in 8 patients whose lesions were located suprasellarly and intrasellarly (Figure 1C). Thirty-one (74%) RCCs were primarily located intrasellarly, ten (34%) RCCs were primarily located suprasellarly, and one case (2%) was located metasellarly. On CT, the cystic content was hyperdense in 6 patients, isodense in 21, hypodense in 15, and 11 of 42 RCCs were confirmed having encroached the sella turcica. One case was described as calcified on the rim (Figure 2).
Hyperprolactinemia was found in one woman whose presenting symptom was amenorrhea and lactating, and one man with headache. Adrenocorticotropic hormone and aldosterone were destitute in three patients who had polydipsia and hyperdiuresis. Other 37 patients were normal under endocrinological laboratory examination preoperatively.
Fifteen of the 42 patients (36%) had visual field deficits or/and vision deficits, and twelve of them (80%) had subjectively blurred vision, the other three had no any visual symptom.
Thirty-six of 42 patients underwent endonasal transsphenoidal microsurgery and the others underwent transcranial surgery. The cyst was identified and drained in all cases. Total resection was achieved in 12 patients, while the others underwent subtotal resection and decompression. The sellar floor was reconstructed following endonasal transsphenoidal surgery. Autologous bone from the vomer was used in 18 patients, and biomaterial was used in 18 others. All of the operations were successfully, and the average duration of hospitalization was 6 days. Decompression by partial removal of the cyst wall achieved satisfactory results in present series. The contents of the cysts were variable: the most common contents were mucoid, gelatinous, clear cerebrospinal fluid (CSF)-like, and xanthochromic fluid. Complete cyst resection was achieved in 6 patients and was defined by postoperative MRI. Twelve of 15 patients (80%) with visual deficits before surgery experienced an improvement in their vision after surgery. All the patients with hypopituitarism experienced an improved endocrine status including 3 patients with adrenocorticotropic hormone and aldosterone destitute, and two with hyperprolactinaemia. Twenty-seven of 29 patients (93%) with headache before the operation experienced a complete improvement after surgery.
The diagnosis of RCCs was confirmed by pathological tissue analysis: simple cuboidal or columnar epithelium was found in 28 patients, and RCCs filled with amorphous colloid material which is specific for RCCs were found in 34 patients. No pseudostratified epithelial lining or squamous metaplasia was diagnosed as RCCs.
Severe complication following surgery was not found. Perforation of the arachnoid and leakage of CSF were encountered in 17 patients during transsphenoidal surgery, and the autologous adipose tissue was used to repair it. The leakage of CSF occurred in 5 patients who underwent endonasal transsphenoidal microsurgery during the first 24 hours after operation, and was resolved after two days with lumbar catheter drainage. The endocrinological complication was usually diabetes insipidus, and postoperative transient diabetes insipidus occurred in 13 (31%) patients. No permanent diabetes insipidus was found. Two of 42 (5%) patients experienced transient hyponatremia. No post-discharge CSF leakage was observed in any of these cases. No perioperative deaths, vascular injuries, or complications leading to new neurological deficits in this series.
The recurrence rate was 7.1% in this series. Three of 42 patients had a recurrence within follow-up. Two of 30 patients who had a subtotal resection and decompression were identified relapsed in 6 months and 17 months postoperatively, respectively. One of 12 patients who had almost complete cyst resection was identified relapsed in 25 months postoperatively. One female patient died because of road accident in 19 months after surgery without relapse. The other 38 of 42 patients are all right nowadays. One symptomatic patient underwent re-transsphenoidal surgery, and the other two asymptomatic patients were required under clinical observation.
RCCs are benign cystic lesions in the sellar or suprasellar space, they are thought to originate from the Rathke's pouch which is a remnant of the embryological structure. The morbidity of RCCs is high but almost all of them are asymptomatic. RCCs are benign sellar cysts and nonfunctioning, but if they are persistently and incidentally untypically enlarged to cause compression for circumambient tissue such as the pituitary gland or optic chiasm, and to increase intracranial pressure, they can result in neurological or endocrine deficits.20 Symptomatic RCCs represented approximately 2%-9% of sellar and suprasellar lesions in previous series.21–24 Isono et al25 reported a series of 15 cases with RCCs about 14.7%. We experienced 968 cases with saddle area tumors by histological diagnosis during this period, the most lesions was pituitary adenomas, and the followed were craniopharyngioma, durosarcoma, and RCCs (4.3%), etc. The literature indicate that symptomatic patients are usually female, typically in their 4th or 5th decade of life.1,2,17,23,24,26–28 In our study, nineteen males (45%) and 23 females (55%) were confirmed as RCCs, and the sex difference was not significant, consistent with Xie et al.29 The mean age of females was 46.7 years, consistent with previous reports.
The most common presenting symptoms are headache, visual impairment, and pituitary dysfunction. Previous reports indicated that headache was present in the vast majority of patients with RCCs, followed with visual impairment and pituitary dysfunction.13,24,28,30 Headache is described as retroorbital, bitemporal, frontal or whole head. Continuous, dull pain was common and could be sudden and severe if bleeding occurred. There are no distinguishing characteristics to discriminate RCCs from other diseases which could augment the intracranial pressure. The majority of patients presented with a simple headache, and 93% of this group experienced a complete improvement after surgery in our series, that was consistent with previous reports.9,17,24,31
The other published reports indicated that pituitary dysfunction was the major symptom in most of patients with RCCs.23,25,30,32 The common pituitary dysfunction displayed as menstrual irregularity, sexual dysfunction, growth hormone deficiency, and etc.12 However, only 4 of 42 patients had pituitary dysfunction in our series. The difference in the symptom of pituitary dysfunction may be concerned with the ethnic of people, and need lucubrating about this phenomenon.
More than 30% of patients who had visual impairment were followed by headache. Twelve of 15 patients with presenting symptom was visual impairment had been resolved after surgery. The reasons may be the mass effect of RCCs that induces compression of chiasm opticum to cause visual impairment.
Modern medical imageology especially MRI has encouraged the clinical diagnosis of RCCs preoperatively. It is well known that the signal intensity of RCCs is variable and directly depend on its contents, and attribute to different compositions of the cyst.17,31,33 So neuroimaging diagnosis of RCC is usually difficult. Intracystic nodules show characteristic intensity on MRI if present,34,35 and 3 cases we met in clinic, nodulose high intensity intra-cyst on T1-weighted images was observed. Nishioka et al31 suggested that the presence of waxy nodules was the most reliable diagnostic indicator of RCCs, although not found in every case. The nodules may represent a diff-homogeneous intensity within the cyst. Saeki et al36 reported that the cyst with iso- to long-signal on T1-weighted images may cause clinical symptoms even if a smaller size than those of the low-intensity cyst, that was consistent with our series. The reason was unknown, may be related to chronic bleeding in some cases. The features of RCCs on MRI may include a smooth contour, girdling signer, and the lack of internal enhancement, verge enhancement, nodules and cyst wall enhancement.
Surgical operation is the fundamental treatment for symptomatic RCCs. Transsphenoidal approach resection is a classic modus operandi, and be used frequently nowadays,17,32 especially in the intrasellar lesions and even in the suprasellar lesions.1,24 The size of RCCs and relationship with circum-architecture are the evidence to decide which modus operandi was selected. Craniotomy is recommended for RCCs which located entirely in the suprasellar or metasellar region. The objective of surgery is to drain the contents of the cyst and to remove the capsule as much as possible under the precondition that does not increase the complications, so the resection of the capsule should be gentle and prudent. The sellar floor should be reconstructed following endonasal transsphenoidal surgery in order to prevent cerebrospinal rhinorrhea. A gross-total resection, a subtotal resection or only a simple drainage of the cysts is alive with argument.1,17 Some experts have recommended biopsy and decompression procedures because the gross-total resection did not decrease the probability of relapse and could likely lead to endocrinological complications after operation.11,24,25,29,32 The higher risks of complications such as diabetes insipidus and pituitary dysfunction experienced in total resection must be weighed against the benefits of removal of symptoms in each patient.13
CSF leakage, transient diabetes insipidus, and delayed hyponatremia are the most common complications.12,24 The endocrinological complication is usually transient diabetes insipidus. The rate of transient diabetes insipidus was 31% in our study. The rate of transient hyponatremia in this series was 5%, consistent with previous reports.37 The reason of delayed hyponatremia and diabetes insipidus after sella region surgery is inappropriate secretion of neurohypophysis during or after operation. The inappropriate secretion of neurohypophysis may be ascribing to the pressurization intraoperative management. CSF leak was due to that the subarachnoid dissepiment was violated. The rate of postoperative complication is higher if an aggressive resection was employed, especially the cyst's tenacious adhesions to the surrounding tissue and structures. Biopsy and decompression procedures remarkably degrade the rate of complication.
The recurrence rate was variable in previous reports. Frank et al32 reported a recurrence rate of 4.5% in 22 patients followed up for 8-60 months. Benveniste et al24 reported a recurrence rate of 16.1% in 62 patients followed up for 1-166 months. In addition, Lillehei et al23 reported a recurrence rate of 10.7% in 75 patients followed up for 43 months. The recurrence rate was 7% in our study. There is no significant difference between a gross-total resection and a subtotal resection or only a simple drainage of the capsule in the recurrence rate. Biopsy and decompression procedures did not increase the recurrence rate. The varied recurrence rates may account for different factors such as diagnostic criteria, the number of patients, duration of follow-up, surgical technique, and etc. Multi-centre studies with long-time clinical and neuroimaging follow-up should be performed to analyze the high-risk factors of RCCs relapse.
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