- Email: [email protected]
Relationship Between Clinical Features and T2-Weighted Magnetic Resonance Images in Symptomatic Rathke Cleft Cysts
Original Article
Relationship Between Clinical Features and T2-Weighted Magnetic Resonance Images in Symptomatic Rathke Cleft Cysts Daisuke Wajima, Taiji Yonezawa, Katsuya Masui, Shuta Aketa
BACKGROUND: It is not known when surgery is appropriate for the treatment for incidental Rathke cleft cysts because knowledge of their natural history is lacking. In this study, we sought to determine whether symptomatic Rathke cleft cysts could be distinguished by their signal intensities in magnetic resonance (MR) images. We analyzed the relationship between these signal intensities and clinical manifestations of the cysts and their patterns of expansion.
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METHODS: MR signal intensities on T1-weighted (T1W) and T2-weighted (T2W) images for 52 cases were categorized into 3 types. Type 1 (20 cases) showed low signal intensities on T1W images and hyperintensity on T2W images. Type 2 (10 cases) showed hyperintensity on both T1W and T2W images. Type 3 (22 cases) showed hypointensity on T2W images.
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RESULTS: A significantly higher proportion of patients with type 1 signal intensities had large cysts compressing their third ventricle than patients with the other 2 types of signal intensities. Patients with type 1 signal intensities also frequently had visual disturbances. Anterior pituitary dysfunction was observed more often in patients with type 2 or 3 signal intensities than in patients with type 1 intensities.
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CONCLUSIONS: We conclude that Rathke cleft cysts that show an MR signal intensity similar to that of cerebrospinal fluid grow slowly and are frequently diagnosed
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as cysts associated with visual disturbance when they become large. It may be possible to predict the clinical progression of Rathke cleft cysts by assessing MR signal intensities.
INTRODUCTION
R
athke cleft cysts (RCCs) are nonneoplastic epithelial lesions of the sellar and suprasellar region. They are typically asymptomatic and have a slow growth rate. An asymptomatic RCC is most often diagnosed at autopsy, with a reported incidence of 5%e33%.1-4 Often, RCCs grow over time and can become sufficiently large to cause a compressive effect on surrounding structures, resulting in neurologic and endocrine abnormalities.5,6 Asymptomatic RCCs follow a variable natural history. In some cases, cysts undergo spontaneous resolution,7 and in others, treatment with glucocorticoids results in reduction of the size of the cyst and abatement of the symptoms.8 Numerous investigators have reported their experience in the management of RCCs and have speculated about an association between their regrowth and their various clinical or histopathologic features.9,10 Nonetheless, the factors that predict regrowth are still subject to debate.11 The present study was conducted to find correlations between the clinical characteristics of surgically treated symptomatic RCCs and the features of magnetic resonance imaging (MRI) of these cysts. Based on MRI results, we classified RCCs into 3 types, which we sought to use as predictors of the prognosis of the cysts.
Key words Clinical features - Cyst expansion - Magnetic resonance signal intensity - Rathke cleft cyst
Department of Neurosurgery, Osaka Police Hospital, Tennoji, Osaka, Japan
Abbreviations and Acronyms CT: Computed tomography MR: magnetic resonance MRI: Magnetic resonance imaging RCC: Rathke cleft cyst T1W: T1-weighted T2W: T2-weighted
Journal homepage: www.WORLDNEUROSURGERY.org
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WORLD NEUROSURGERY 88: 421-427, APRIL 2016
To whom correspondence should be addressed: Daisuke Wajima, M.D. [E-mail: [email protected]] Citation: World Neurosurg. (2016) 88:421-427. http://dx.doi.org/10.1016/j.wneu.2015.10.018
Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2016 Elsevier Inc. All rights reserved.
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RELATIONSHIP BETWEEN SYMPTOMATIC RATHKE CLEFT CYST AND MRI IMAGES
METHODS We performed a retrospective study of cases of symptomatic RCCs that were surgically treated at our institute. The institutional review board approved this study, and the requirement for informed consent was waived. Transsphenoidal procedures were performed with an endoscope after April 2013 and with a microscope before then. MR signal intensities on T1-weighted (T1W) and T2-weighted (T2W) images for 52 cases were categorized into 3 types. Type 1 showed low signal intensity on T1W images and hyperintensity on T2W images and was seen in 20 cases. Type 2 showed hyperintensity on both T1W and T2W images and was seen in 10 cases. Type 3 showed hypointensity on T2W images and was seen in the other 22 cases. We evaluated such clinical features as headache, visual disturbance (hemianopsia, etc.), hypopituitarism, and diabetes insipidus. In addition, we classified the expansion of cysts as intrasellar expansion (group A), intrasuprasellar expansion (group B), and suprasellar expansion to the floor of the third ventricle (group C). The mean, standard deviation, median, and range were calculated for patient demographics described with continuous variables. The frequency was calculated for discrete data. Univariate analysis using the c2 test for categorical variables and the MannWhitney U test or Kruskal-Wallis test for continuous variables was performed to evaluate the association between clinical parameters and the location of the RCC, the occurrence of squamous metaplasia, and the recurrence of the cyst. All variables with a P value 0.05 in the univariate analysis, in addition to age at the time of surgery and histology, were included as independent variables. All the analyses were tested at the 0.05 level of significance, and the analysis was performed using SPSS version 20 (IBM Corp., Armonk, New York, USA).
RESULTS The mean age of the 52 patients included in this study was 41 14 years (range, 10e73 years). There were 37 female (71%) and 15 male (29%) patients. Nine patients (17%) had an entirely intrasellar RCC (Figure 1), 30 (58%) had an intrasuprasellar cyst (Figure 2), and 13 (25%) had a purely suprasellar lesion (Figure 3). The mean cyst volume was 2.4 0.9 cm3 (range, 0.36e4.9 cm3). Three recurrences of RCCs were observed in our study (5.7%). Here, we recount 3 typical cases of RCCs.
Case 1 A 50-year-old man presented at our hospital with a sudden onset headache (Figure 1). An examination of his head with computed tomography (CT) and of his brain with MRI showed an intrasellar mass lesion. The MRI of his brain showed that the cyst contents had relative hyperintensity on the T1W image and hypointensity on the T2W image. The cyst contents were not enhanced by gadolinium MRI. Emergent transsphenoidal surgery was performed because of a suspicion of pituitary apoplexy, but the intraoperative findings and the histologic findings were of an RCC. Intraoperative findings showed no apparent bleeding in the cystic lesion. The headache was relieved after fenestration of the cyst.
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Case 2 A 26-year-old woman visited our hospital to be checked for intracranial lesions that might account for her chronic headache (Figure 2). A CT examination of her head and an MRI examination of her brain showed an intrasellar and suprasellar cystic lesion, and the brain MRI showed that the cyst contents had relative hyperintensity on the T1W image and hypointensity on the T2W image. The cyst contents were not enhanced by Gd MRI. Transsphenoidal surgery was performed because of the suspicion of a pituitary tumor, but then the intraoperative findings and the histologic findings were of an RCC. The patient’s headache was relieved after fenestration of the cyst.
Case 3 A 61-year-old woman visited our hospital because of bilateral hemianopsia (Figure 3). A CT examination of her head and an MRI examination of her brain showed a suprasellar cystic lesion in the third ventricle, and the brain MRI showed that the contents of the cyst had relative hypointensity on the T1W image and hyperintensity on the T2W image. The cyst contents were not enhanced by Gd MRI. Transsphenoidal surgery was performed and the intraoperative findings and histologic findings were of an RCC. Her visual disturbance improved after fenestration of the cyst.
Preoperative Findings The contents of the cysts showed varying MR signal intensities. There were 20 cases of type 1, 10 cases of type 2, and 22 cases of type 3, respectively. The mean ages of the patients were 43 19.0 years for type 1, 45 16.3 years for type 2, and 40 20.2 years for type 3, respectively. Regarding expansion of the cysts, there were 8 cases in group A, 30 cases in group B, and 14 cases in group C. The mean ages of the patients were 37 16.4 years in expansion group A, 47 17.2 years in group B, and 53 10.2 years in group C, respectively (there was a significant difference between groups A and C (P < 0.01). The cases showed varying clinical features. Headache was the most frequent initial symptom, occurring in 16 cases (31%). Fourteen patients (27%) reported disturbances of vision. Preoperative hypopituitarism was found in 14 patients (27%) and diabetes insipidus in 8 patients (15%). Thirty-one patients had more than 1 of these presenting symptoms. The incidence of preoperative symptoms was not significantly associated with recurrence. In 14 patients with hypopituitarism, hypocortisolism was the most common dysfunction (40%), followed by hypothyroidism (30%), hypogonadism (20%), and growth hormone deficiency (10%). Four patients had hormonal deficiency in 2 or more hormonal axes. The mean duration of preoperative symptoms was 17 23 months (range, 1e108 months).
Relationship of MR Signal Intensity of Cyst Contents to Cyst Expansion Cases of type 1 were significantly lower in group B (P < 0.05) and significantly higher in group C (P < 0.05). Cases of type 2 were significantly lower in group C (P < 0.05) (Figure 4).
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ORIGINAL ARTICLE DAISUKE WAJIMA ET AL.
RELATIONSHIP BETWEEN SYMPTOMATIC RATHKE CLEFT CYST AND MRI IMAGES
Figure 1. A computed tomography examination of the head for case 1 showed an intrasellar cystic lesion (A). Magnetic resonance imaging of the brain showed that the cyst content had relative hyperintensity on the T1-weighted image (B) and hypointensity on the T2-weighted image (C).
Relationship of MR Intensity of Cyst Contents to Clinical Features Cases of type 1 were associated with visual disturbance and pituitary dysfunction, although there was no significant difference between them (Figure 5). Relationship of Cyst Expansion to Clinical Features Cases of group C were significantly more likely to involve visual disturbances (P < 0.05). DISCUSSION RCCs are believed to be derived from true remnants of the embryologic Rathke pouch.12,13 Regarding the development of RCC, theoretically, during the third or fourth week of gestation, a rostral out-pouching of the ectodermal primitive oral cavity meets a downward projection from the neuroectodermal diencephalon. These structures then give rise to the anterior lobe, pars tuberalis,
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The cyst content was not enhanced by gadolinium magnetic resonance imaging (D). The histologic finding was of a Rathke cleft cyst (E). HE, hematoxylin-eosin.
and pars intermedia of the pituitary gland. The residual lumen between the anterior and intermediate lobe constitutes the Rathke cleft. It is the persistence and enlargement of the Rathke cleft, with proliferation of the cell lining and accumulation of its secretions, that is said to be the cause of symptomatic RCCs. The persistence of a remnant of the Rathke cleft between the anterior lobe and the pars intermedia can result in an accumulation of fluid and cystic dilation. This leads to a purely intrasellar RCC or an intrasellar RCC with a suprasellar (intrasuprasellar) extension.14-16 The pars tuberalis lies above the diaphragm, and the Rathke pouch remnants in this location can give rise to an entirely suprasellar RCC. Biopsy of the cyst wall and drainage of the cyst contents proved to be an effective and safe treatment of symptomatic RCCs.17 Therefore, theoretically, preoperative diagnosis of RCCs is important to avoid pituitary tissue damage from attempted radical excision. The appearance of an RCC in CT scans varies,
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Figure 2. A computed tomography examination of the head for case 2 showed an intrasellar and suprasellar mass lesion (A). Magnetic resonance imaging of the brain showed that the cyst content had relative hyperintensity on the T1-weighted image (B) and hypointensity on the
but it is generally a homogeneous, low-density, nonenhancing lesion.18 These features do not reliably distinguish RCCs from other more common lesions in this area. The MRI features of RCCs are variable, depending on the components of the fluid and the location and size of the cysts. Previous reports15,19 have noted considerable variation in T1 and T2 image intensities for RCCs. It has been suggested that high cholesterol or mucopolysaccharide might influence the signals, possibly in combination with cell debris from the cyst wall.4 Other reports suggested that the wide variation in signal intensity for cysts imaged with MRI depends on their protein content and on cross-linking between protein molecules.17 However, molecular cyst contents have never been analyzed and quantified for a large series of cases. We believe that a smaller RCC with rich protein content will affect the
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T2-weighted image (C). The cyst content was not enhanced by gadolinium magnetic resonance imaging (D). The histologic finding was of a Rathke cleft cyst (E). HE, hematoxylin-eosin.
pituitary gland causing a pituitary deficiency. Pituitary apoplexy may in addition be caused by bleeding of the cyst components. With Gd-diethyltriaminepentaacetic acid administration, we showed that visualization of the pituitary gland was enhanced, allowing it to be differentiated from the cyst in all cases. Most often, the pituitary gland was displaced inferiorly or circumferentially. Although present in only 70% of our cases, such an aspect is suggestive of RCC. These findings are in accordance with previous descriptions,20 in which all cysts tended to displace the pituitary gland in an anterior-superior direction. A report of pathognomonic MR findings for RCCs showed that a posterior ledge of the diaphragma sellae occurred in 82% of cases in which a suprasellar extension was observed. We believe that it is important to identify the position of the pituitary gland preoperatively to better ensure that healthy pituitary tissue is preserved
WORLD NEUROSURGERY, http://dx.doi.org/10.1016/j.wneu.2015.10.018
ORIGINAL ARTICLE DAISUKE WAJIMA ET AL.
RELATIONSHIP BETWEEN SYMPTOMATIC RATHKE CLEFT CYST AND MRI IMAGES
Figure 3. A computed tomography examination of the head for case 3 showed a suprasellar mass lesion to the third ventricle (A). Magnetic resonance imaging of the brain showed that the cyst content had relative hypointensity on the T1-weighted image (B) and hyperintensity on the
during surgery. In our opinion, this pathologic association can be managed in the same fashion as for other types of pituitary adenomas. In most of our cases, expansion of the cyst was of the suprasellar type (group B or C). In addition, cases of type 1 in which the cyst had an MR signal intensity comparable with that of cerebrospinal fluid were significantly higher in group C and involved the occurrence of a visual disturbance. On the other hand, cases of type 2 were significantly lower in group C and involved pituitary dysfunction. This shows that for type 2 or 3 cases, various symptoms tend to occur before cyst growth of the sort seen in group B or C. In addition, the patients in group C were significantly older than those in the other groups. This showed that cysts of type 1 grow gradually to the point of inflicting chronic damage on surrounding tissue. Evaluations of the MR intensity of the contents of cysts may provide valuable information about the growth rates of
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T2-weighted image (C). The cyst content was not enhanced by gadolinium magnetic resonance imaging (D). The histologic finding was of a Rathke cleft cyst (E). HE, hematoxylin-eosin.
cysts. For the management of RCC, we recommend that symptomatic lesions should be removed by transsphenoidal surgery. However, our findings show that it is necessary to carefully observe asymptomatic type 1 lesions. Our flow chart indicates our recommended course of action when a pituitary cystic lesion is found on MRI (Figure 6). CONCLUSIONS We evaluated the MR signal intensities of symptomatic RCCs and analyzed the relationship of these intensities to manifestations of clinical symptoms and to patterns of suprasellar expansion. In our study, cysts of type 1 show gradual chronic expansion. This expansion tends to be of the sort we classified as group C and to involve the occurrence of visual disturbances. In general, evaluating the intensity of the contents of cysts in MRI may provide valuable information about their growth speed.
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Figure 4. Bar graph showing percentages of the expansion groups AeC in the magnetic resonance imaging signal intensity groups types 1e3. We evaluated the expansion of cysts as intrasellar expansion (group A), intrasuprasellar expansion (group B), and suprasellar expansion to the floor of the third ventricle (group C).
Figure 5. Bar graph depicting percentages of magnetic resonance intensity types 1e3 associated with each sign or symptom. Magnetic resonance signal intensities on T1-weighted (T1W) and T2-weighted (T2W) images were categorized into 3 types in 52 cases, including our 5 cases. Type 1 involved low signal intensity on T1W images and hyperintensity on T2W images and was observed in 20 cases. Type 2 involved hyperintensity on both T1W and T2W images and was observed in 10 cases. Type 3 involved hypointensity on T2W images and was seen in the other 22 cases. We evaluated clinical features such as headache, visual disturbance (eg, hemianopsia), hypopituitarism, and diabetes insipidus.
Figure 6. Flow chart of the recommended course of action when an incidental pituitary cystic lesion is found on magnetic resonance imaging (MRI).
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REFERENCES 1. Baskin DS, Wilson CB. Transsphenoidal treatment of nonneoplastic intrasellar cysts. A report of 38 cases. J Neurosurg. 1984;60:8-13. 2. Shanklin WM. On the presence of cysts in the human pituitary. Anat Rec. 1949;104:379-407. 3. Shin JL, Asa SL, Woodhouse LJ, Smyth HS, Ezzat S. Cystic lesions of the pituitary: clinicopathological features distinguishing craniopharyngioma, Rathke’s cleft cyst, and arachnoid cyst. J Clin Endocrinol Metab. 1999;84:3972-3982. 4. Skjodt K, Loft Edal A, Nepper-Ramussen HJ. Rathke’s cleft cyst: two cases with uncommon MR signals. Acta Radiol. 1996;37:596-598. 5. Binning MJ, Liu JK, Gannon J, Osborn AG, Couldwell WT. Hemorrhagic and nonhemorrhagic Rathke cleft cysts mimicking pituitary apoplexy. J Neurosurg. 2008;108:3-8. 6. Komatsu F, Tsugu H, Komatsu M, Sakamoto S, Oshiro S, Fukushima T, et al. Clinicopathological characteristics in patients presenting with acute onset of symptoms caused by Rathke’s cleft cysts. Acta Neurochir (Wien). 2010;152:1673-1678. 7. Amhaz HH, Chamoun RB, Waguespack SG, Shah K, McCutcheon IE. Spontaneous involution of Rathke cleft cysts: is it rare or just underreported? J Neurosurg. 2010;112:1327-1332. 8. Ogawa Y, Watanabe M, Tominaga T. Prognostic factors of operated Rathke’s cleft cysts with spe-
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cial reference to reaccumulation and recommended surgical strategy. Acta Neurochir (Wien). 2011;153:2427-2433.
17. Ross DA, Norman D, Wilson CB. Radiologic characteristics and results of surgical management of Rathke’s cyst in 43 patients. Neurosurgery. 1992;30: 173-179.
9. Billeci D, Marton E, Tripodi M, Orvieto E, Longatti P. Symptomatic Rathke’s cleft cysts: a radiological, surgical and pathological review. Pituitary. 2004;7:131-137.
18. Byrd SE, Winter J, Takahashi M, Joyce P. Symptomatic Rathke’s cleft cyst demonstrated on computed tomography. J Comput Assist Tomogr. 1980;44:411-414.
10. Han SJ, Rolston JD, Jahangiri A, Aghi MK. Rathke’s cleft cysts: review of natural history and surgical outcomes. J Neurooncol. 2014;117:197-203.
19. Steinberg GK, Koenig GH, Golden JB. Symptomatic Rathke’s cleft cysts. Report of two cases. J Neurosurg. 1982;56:290-295.
11. Zada G. Rathke cleft cysts: review of clinical and surgical management. Neurosurg Focus. 2011;31:E1.
20. Sumida M, Uozumi T, Mukada K, Arita K, Kurisu K, Eguchi K. Rathke cleft cyst: correlation of enhanced MR and surgical findings. AJNR Am J Neuroradiol. 1994;15:525-532.
12. Frazier CH, Alpers BJ. Tumors of Rathke’s cleft (hithertocalled tumors of Rathke’s pouch). Arch Neurol Psychiatry. 1934;32:973-984. 13. Ikeda H, Yoshimoto T, Suzuki J. Immunohistochemical study of Rathke’s cleft cyst. Acta Neuropathol. 1988;77:33-38. 14. Potts MB, Jahangiri A, Lamborn KR, Blevins LS, Kunwar S, Aghi MK. Suprasellar Rathke cleft cysts: clinical presentation and treatment outcomes. Neurosurgery. 2011;69:1058-1068. 15. Rottenberg GT, Chong WK, Powell M, Kendall BE. Cyst formation of the craniopharyngeal duct. Clin Radiol. 1994;49:126-129. 16. Voelker JL, Campbell RL, Muller J. Clinical, radiographic, and pathological features of symptomatic Rathke’s cleft cysts. J Neurosurg. 1991;74:535-544.
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Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Received 8 June 2015; accepted 7 October 2015 Citation: World Neurosurg. (2016) 88:421-427. http://dx.doi.org/10.1016/j.wneu.2015.10.018 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2016 Elsevier Inc. All rights reserved.
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Relationship Between Clinical Features and T2-Weighted Magnetic Resonance Images in Symptomatic Rathke Cleft Cysts Daisuke Wajima, Taiji Yonezawa, Katsuya Masui, Shuta Aketa
BACKGROUND: It is not known when surgery is appropriate for the treatment for incidental Rathke cleft cysts because knowledge of their natural history is lacking. In this study, we sought to determine whether symptomatic Rathke cleft cysts could be distinguished by their signal intensities in magnetic resonance (MR) images. We analyzed the relationship between these signal intensities and clinical manifestations of the cysts and their patterns of expansion.
-
METHODS: MR signal intensities on T1-weighted (T1W) and T2-weighted (T2W) images for 52 cases were categorized into 3 types. Type 1 (20 cases) showed low signal intensities on T1W images and hyperintensity on T2W images. Type 2 (10 cases) showed hyperintensity on both T1W and T2W images. Type 3 (22 cases) showed hypointensity on T2W images.
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RESULTS: A significantly higher proportion of patients with type 1 signal intensities had large cysts compressing their third ventricle than patients with the other 2 types of signal intensities. Patients with type 1 signal intensities also frequently had visual disturbances. Anterior pituitary dysfunction was observed more often in patients with type 2 or 3 signal intensities than in patients with type 1 intensities.
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CONCLUSIONS: We conclude that Rathke cleft cysts that show an MR signal intensity similar to that of cerebrospinal fluid grow slowly and are frequently diagnosed
-
as cysts associated with visual disturbance when they become large. It may be possible to predict the clinical progression of Rathke cleft cysts by assessing MR signal intensities.
INTRODUCTION
R
athke cleft cysts (RCCs) are nonneoplastic epithelial lesions of the sellar and suprasellar region. They are typically asymptomatic and have a slow growth rate. An asymptomatic RCC is most often diagnosed at autopsy, with a reported incidence of 5%e33%.1-4 Often, RCCs grow over time and can become sufficiently large to cause a compressive effect on surrounding structures, resulting in neurologic and endocrine abnormalities.5,6 Asymptomatic RCCs follow a variable natural history. In some cases, cysts undergo spontaneous resolution,7 and in others, treatment with glucocorticoids results in reduction of the size of the cyst and abatement of the symptoms.8 Numerous investigators have reported their experience in the management of RCCs and have speculated about an association between their regrowth and their various clinical or histopathologic features.9,10 Nonetheless, the factors that predict regrowth are still subject to debate.11 The present study was conducted to find correlations between the clinical characteristics of surgically treated symptomatic RCCs and the features of magnetic resonance imaging (MRI) of these cysts. Based on MRI results, we classified RCCs into 3 types, which we sought to use as predictors of the prognosis of the cysts.
Key words Clinical features - Cyst expansion - Magnetic resonance signal intensity - Rathke cleft cyst
Department of Neurosurgery, Osaka Police Hospital, Tennoji, Osaka, Japan
Abbreviations and Acronyms CT: Computed tomography MR: magnetic resonance MRI: Magnetic resonance imaging RCC: Rathke cleft cyst T1W: T1-weighted T2W: T2-weighted
Journal homepage: www.WORLDNEUROSURGERY.org
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WORLD NEUROSURGERY 88: 421-427, APRIL 2016
To whom correspondence should be addressed: Daisuke Wajima, M.D. [E-mail: [email protected]] Citation: World Neurosurg. (2016) 88:421-427. http://dx.doi.org/10.1016/j.wneu.2015.10.018
Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2016 Elsevier Inc. All rights reserved.
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ORIGINAL ARTICLE DAISUKE WAJIMA ET AL.
RELATIONSHIP BETWEEN SYMPTOMATIC RATHKE CLEFT CYST AND MRI IMAGES
METHODS We performed a retrospective study of cases of symptomatic RCCs that were surgically treated at our institute. The institutional review board approved this study, and the requirement for informed consent was waived. Transsphenoidal procedures were performed with an endoscope after April 2013 and with a microscope before then. MR signal intensities on T1-weighted (T1W) and T2-weighted (T2W) images for 52 cases were categorized into 3 types. Type 1 showed low signal intensity on T1W images and hyperintensity on T2W images and was seen in 20 cases. Type 2 showed hyperintensity on both T1W and T2W images and was seen in 10 cases. Type 3 showed hypointensity on T2W images and was seen in the other 22 cases. We evaluated such clinical features as headache, visual disturbance (hemianopsia, etc.), hypopituitarism, and diabetes insipidus. In addition, we classified the expansion of cysts as intrasellar expansion (group A), intrasuprasellar expansion (group B), and suprasellar expansion to the floor of the third ventricle (group C). The mean, standard deviation, median, and range were calculated for patient demographics described with continuous variables. The frequency was calculated for discrete data. Univariate analysis using the c2 test for categorical variables and the MannWhitney U test or Kruskal-Wallis test for continuous variables was performed to evaluate the association between clinical parameters and the location of the RCC, the occurrence of squamous metaplasia, and the recurrence of the cyst. All variables with a P value 0.05 in the univariate analysis, in addition to age at the time of surgery and histology, were included as independent variables. All the analyses were tested at the 0.05 level of significance, and the analysis was performed using SPSS version 20 (IBM Corp., Armonk, New York, USA).
RESULTS The mean age of the 52 patients included in this study was 41 14 years (range, 10e73 years). There were 37 female (71%) and 15 male (29%) patients. Nine patients (17%) had an entirely intrasellar RCC (Figure 1), 30 (58%) had an intrasuprasellar cyst (Figure 2), and 13 (25%) had a purely suprasellar lesion (Figure 3). The mean cyst volume was 2.4 0.9 cm3 (range, 0.36e4.9 cm3). Three recurrences of RCCs were observed in our study (5.7%). Here, we recount 3 typical cases of RCCs.
Case 1 A 50-year-old man presented at our hospital with a sudden onset headache (Figure 1). An examination of his head with computed tomography (CT) and of his brain with MRI showed an intrasellar mass lesion. The MRI of his brain showed that the cyst contents had relative hyperintensity on the T1W image and hypointensity on the T2W image. The cyst contents were not enhanced by gadolinium MRI. Emergent transsphenoidal surgery was performed because of a suspicion of pituitary apoplexy, but the intraoperative findings and the histologic findings were of an RCC. Intraoperative findings showed no apparent bleeding in the cystic lesion. The headache was relieved after fenestration of the cyst.
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Case 2 A 26-year-old woman visited our hospital to be checked for intracranial lesions that might account for her chronic headache (Figure 2). A CT examination of her head and an MRI examination of her brain showed an intrasellar and suprasellar cystic lesion, and the brain MRI showed that the cyst contents had relative hyperintensity on the T1W image and hypointensity on the T2W image. The cyst contents were not enhanced by Gd MRI. Transsphenoidal surgery was performed because of the suspicion of a pituitary tumor, but then the intraoperative findings and the histologic findings were of an RCC. The patient’s headache was relieved after fenestration of the cyst.
Case 3 A 61-year-old woman visited our hospital because of bilateral hemianopsia (Figure 3). A CT examination of her head and an MRI examination of her brain showed a suprasellar cystic lesion in the third ventricle, and the brain MRI showed that the contents of the cyst had relative hypointensity on the T1W image and hyperintensity on the T2W image. The cyst contents were not enhanced by Gd MRI. Transsphenoidal surgery was performed and the intraoperative findings and histologic findings were of an RCC. Her visual disturbance improved after fenestration of the cyst.
Preoperative Findings The contents of the cysts showed varying MR signal intensities. There were 20 cases of type 1, 10 cases of type 2, and 22 cases of type 3, respectively. The mean ages of the patients were 43 19.0 years for type 1, 45 16.3 years for type 2, and 40 20.2 years for type 3, respectively. Regarding expansion of the cysts, there were 8 cases in group A, 30 cases in group B, and 14 cases in group C. The mean ages of the patients were 37 16.4 years in expansion group A, 47 17.2 years in group B, and 53 10.2 years in group C, respectively (there was a significant difference between groups A and C (P < 0.01). The cases showed varying clinical features. Headache was the most frequent initial symptom, occurring in 16 cases (31%). Fourteen patients (27%) reported disturbances of vision. Preoperative hypopituitarism was found in 14 patients (27%) and diabetes insipidus in 8 patients (15%). Thirty-one patients had more than 1 of these presenting symptoms. The incidence of preoperative symptoms was not significantly associated with recurrence. In 14 patients with hypopituitarism, hypocortisolism was the most common dysfunction (40%), followed by hypothyroidism (30%), hypogonadism (20%), and growth hormone deficiency (10%). Four patients had hormonal deficiency in 2 or more hormonal axes. The mean duration of preoperative symptoms was 17 23 months (range, 1e108 months).
Relationship of MR Signal Intensity of Cyst Contents to Cyst Expansion Cases of type 1 were significantly lower in group B (P < 0.05) and significantly higher in group C (P < 0.05). Cases of type 2 were significantly lower in group C (P < 0.05) (Figure 4).
WORLD NEUROSURGERY, http://dx.doi.org/10.1016/j.wneu.2015.10.018
ORIGINAL ARTICLE DAISUKE WAJIMA ET AL.
RELATIONSHIP BETWEEN SYMPTOMATIC RATHKE CLEFT CYST AND MRI IMAGES
Figure 1. A computed tomography examination of the head for case 1 showed an intrasellar cystic lesion (A). Magnetic resonance imaging of the brain showed that the cyst content had relative hyperintensity on the T1-weighted image (B) and hypointensity on the T2-weighted image (C).
Relationship of MR Intensity of Cyst Contents to Clinical Features Cases of type 1 were associated with visual disturbance and pituitary dysfunction, although there was no significant difference between them (Figure 5). Relationship of Cyst Expansion to Clinical Features Cases of group C were significantly more likely to involve visual disturbances (P < 0.05). DISCUSSION RCCs are believed to be derived from true remnants of the embryologic Rathke pouch.12,13 Regarding the development of RCC, theoretically, during the third or fourth week of gestation, a rostral out-pouching of the ectodermal primitive oral cavity meets a downward projection from the neuroectodermal diencephalon. These structures then give rise to the anterior lobe, pars tuberalis,
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The cyst content was not enhanced by gadolinium magnetic resonance imaging (D). The histologic finding was of a Rathke cleft cyst (E). HE, hematoxylin-eosin.
and pars intermedia of the pituitary gland. The residual lumen between the anterior and intermediate lobe constitutes the Rathke cleft. It is the persistence and enlargement of the Rathke cleft, with proliferation of the cell lining and accumulation of its secretions, that is said to be the cause of symptomatic RCCs. The persistence of a remnant of the Rathke cleft between the anterior lobe and the pars intermedia can result in an accumulation of fluid and cystic dilation. This leads to a purely intrasellar RCC or an intrasellar RCC with a suprasellar (intrasuprasellar) extension.14-16 The pars tuberalis lies above the diaphragm, and the Rathke pouch remnants in this location can give rise to an entirely suprasellar RCC. Biopsy of the cyst wall and drainage of the cyst contents proved to be an effective and safe treatment of symptomatic RCCs.17 Therefore, theoretically, preoperative diagnosis of RCCs is important to avoid pituitary tissue damage from attempted radical excision. The appearance of an RCC in CT scans varies,
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Figure 2. A computed tomography examination of the head for case 2 showed an intrasellar and suprasellar mass lesion (A). Magnetic resonance imaging of the brain showed that the cyst content had relative hyperintensity on the T1-weighted image (B) and hypointensity on the
but it is generally a homogeneous, low-density, nonenhancing lesion.18 These features do not reliably distinguish RCCs from other more common lesions in this area. The MRI features of RCCs are variable, depending on the components of the fluid and the location and size of the cysts. Previous reports15,19 have noted considerable variation in T1 and T2 image intensities for RCCs. It has been suggested that high cholesterol or mucopolysaccharide might influence the signals, possibly in combination with cell debris from the cyst wall.4 Other reports suggested that the wide variation in signal intensity for cysts imaged with MRI depends on their protein content and on cross-linking between protein molecules.17 However, molecular cyst contents have never been analyzed and quantified for a large series of cases. We believe that a smaller RCC with rich protein content will affect the
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T2-weighted image (C). The cyst content was not enhanced by gadolinium magnetic resonance imaging (D). The histologic finding was of a Rathke cleft cyst (E). HE, hematoxylin-eosin.
pituitary gland causing a pituitary deficiency. Pituitary apoplexy may in addition be caused by bleeding of the cyst components. With Gd-diethyltriaminepentaacetic acid administration, we showed that visualization of the pituitary gland was enhanced, allowing it to be differentiated from the cyst in all cases. Most often, the pituitary gland was displaced inferiorly or circumferentially. Although present in only 70% of our cases, such an aspect is suggestive of RCC. These findings are in accordance with previous descriptions,20 in which all cysts tended to displace the pituitary gland in an anterior-superior direction. A report of pathognomonic MR findings for RCCs showed that a posterior ledge of the diaphragma sellae occurred in 82% of cases in which a suprasellar extension was observed. We believe that it is important to identify the position of the pituitary gland preoperatively to better ensure that healthy pituitary tissue is preserved
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Figure 3. A computed tomography examination of the head for case 3 showed a suprasellar mass lesion to the third ventricle (A). Magnetic resonance imaging of the brain showed that the cyst content had relative hypointensity on the T1-weighted image (B) and hyperintensity on the
during surgery. In our opinion, this pathologic association can be managed in the same fashion as for other types of pituitary adenomas. In most of our cases, expansion of the cyst was of the suprasellar type (group B or C). In addition, cases of type 1 in which the cyst had an MR signal intensity comparable with that of cerebrospinal fluid were significantly higher in group C and involved the occurrence of a visual disturbance. On the other hand, cases of type 2 were significantly lower in group C and involved pituitary dysfunction. This shows that for type 2 or 3 cases, various symptoms tend to occur before cyst growth of the sort seen in group B or C. In addition, the patients in group C were significantly older than those in the other groups. This showed that cysts of type 1 grow gradually to the point of inflicting chronic damage on surrounding tissue. Evaluations of the MR intensity of the contents of cysts may provide valuable information about the growth rates of
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T2-weighted image (C). The cyst content was not enhanced by gadolinium magnetic resonance imaging (D). The histologic finding was of a Rathke cleft cyst (E). HE, hematoxylin-eosin.
cysts. For the management of RCC, we recommend that symptomatic lesions should be removed by transsphenoidal surgery. However, our findings show that it is necessary to carefully observe asymptomatic type 1 lesions. Our flow chart indicates our recommended course of action when a pituitary cystic lesion is found on MRI (Figure 6). CONCLUSIONS We evaluated the MR signal intensities of symptomatic RCCs and analyzed the relationship of these intensities to manifestations of clinical symptoms and to patterns of suprasellar expansion. In our study, cysts of type 1 show gradual chronic expansion. This expansion tends to be of the sort we classified as group C and to involve the occurrence of visual disturbances. In general, evaluating the intensity of the contents of cysts in MRI may provide valuable information about their growth speed.
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Figure 4. Bar graph showing percentages of the expansion groups AeC in the magnetic resonance imaging signal intensity groups types 1e3. We evaluated the expansion of cysts as intrasellar expansion (group A), intrasuprasellar expansion (group B), and suprasellar expansion to the floor of the third ventricle (group C).
Figure 5. Bar graph depicting percentages of magnetic resonance intensity types 1e3 associated with each sign or symptom. Magnetic resonance signal intensities on T1-weighted (T1W) and T2-weighted (T2W) images were categorized into 3 types in 52 cases, including our 5 cases. Type 1 involved low signal intensity on T1W images and hyperintensity on T2W images and was observed in 20 cases. Type 2 involved hyperintensity on both T1W and T2W images and was observed in 10 cases. Type 3 involved hypointensity on T2W images and was seen in the other 22 cases. We evaluated clinical features such as headache, visual disturbance (eg, hemianopsia), hypopituitarism, and diabetes insipidus.
Figure 6. Flow chart of the recommended course of action when an incidental pituitary cystic lesion is found on magnetic resonance imaging (MRI).
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REFERENCES 1. Baskin DS, Wilson CB. Transsphenoidal treatment of nonneoplastic intrasellar cysts. A report of 38 cases. J Neurosurg. 1984;60:8-13. 2. Shanklin WM. On the presence of cysts in the human pituitary. Anat Rec. 1949;104:379-407. 3. Shin JL, Asa SL, Woodhouse LJ, Smyth HS, Ezzat S. Cystic lesions of the pituitary: clinicopathological features distinguishing craniopharyngioma, Rathke’s cleft cyst, and arachnoid cyst. J Clin Endocrinol Metab. 1999;84:3972-3982. 4. Skjodt K, Loft Edal A, Nepper-Ramussen HJ. Rathke’s cleft cyst: two cases with uncommon MR signals. Acta Radiol. 1996;37:596-598. 5. Binning MJ, Liu JK, Gannon J, Osborn AG, Couldwell WT. Hemorrhagic and nonhemorrhagic Rathke cleft cysts mimicking pituitary apoplexy. J Neurosurg. 2008;108:3-8. 6. Komatsu F, Tsugu H, Komatsu M, Sakamoto S, Oshiro S, Fukushima T, et al. Clinicopathological characteristics in patients presenting with acute onset of symptoms caused by Rathke’s cleft cysts. Acta Neurochir (Wien). 2010;152:1673-1678. 7. Amhaz HH, Chamoun RB, Waguespack SG, Shah K, McCutcheon IE. Spontaneous involution of Rathke cleft cysts: is it rare or just underreported? J Neurosurg. 2010;112:1327-1332. 8. Ogawa Y, Watanabe M, Tominaga T. Prognostic factors of operated Rathke’s cleft cysts with spe-
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cial reference to reaccumulation and recommended surgical strategy. Acta Neurochir (Wien). 2011;153:2427-2433.
17. Ross DA, Norman D, Wilson CB. Radiologic characteristics and results of surgical management of Rathke’s cyst in 43 patients. Neurosurgery. 1992;30: 173-179.
9. Billeci D, Marton E, Tripodi M, Orvieto E, Longatti P. Symptomatic Rathke’s cleft cysts: a radiological, surgical and pathological review. Pituitary. 2004;7:131-137.
18. Byrd SE, Winter J, Takahashi M, Joyce P. Symptomatic Rathke’s cleft cyst demonstrated on computed tomography. J Comput Assist Tomogr. 1980;44:411-414.
10. Han SJ, Rolston JD, Jahangiri A, Aghi MK. Rathke’s cleft cysts: review of natural history and surgical outcomes. J Neurooncol. 2014;117:197-203.
19. Steinberg GK, Koenig GH, Golden JB. Symptomatic Rathke’s cleft cysts. Report of two cases. J Neurosurg. 1982;56:290-295.
11. Zada G. Rathke cleft cysts: review of clinical and surgical management. Neurosurg Focus. 2011;31:E1.
20. Sumida M, Uozumi T, Mukada K, Arita K, Kurisu K, Eguchi K. Rathke cleft cyst: correlation of enhanced MR and surgical findings. AJNR Am J Neuroradiol. 1994;15:525-532.
12. Frazier CH, Alpers BJ. Tumors of Rathke’s cleft (hithertocalled tumors of Rathke’s pouch). Arch Neurol Psychiatry. 1934;32:973-984. 13. Ikeda H, Yoshimoto T, Suzuki J. Immunohistochemical study of Rathke’s cleft cyst. Acta Neuropathol. 1988;77:33-38. 14. Potts MB, Jahangiri A, Lamborn KR, Blevins LS, Kunwar S, Aghi MK. Suprasellar Rathke cleft cysts: clinical presentation and treatment outcomes. Neurosurgery. 2011;69:1058-1068. 15. Rottenberg GT, Chong WK, Powell M, Kendall BE. Cyst formation of the craniopharyngeal duct. Clin Radiol. 1994;49:126-129. 16. Voelker JL, Campbell RL, Muller J. Clinical, radiographic, and pathological features of symptomatic Rathke’s cleft cysts. J Neurosurg. 1991;74:535-544.
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Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Received 8 June 2015; accepted 7 October 2015 Citation: World Neurosurg. (2016) 88:421-427. http://dx.doi.org/10.1016/j.wneu.2015.10.018 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2016 Elsevier Inc. All rights reserved.
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