- Email: [email protected]
Entirely Suprasellar Rathke Cleft Cysts: Clinical Features and Surgical Efficacy of Endoscopic Endonasal Transtuberculum Sellae Approach
Original Article
Entirely Suprasellar Rathke Cleft Cysts: Clinical Features and Surgical Efficacy of Endoscopic Endonasal Transtuberculum Sellae Approach Yasuhiko Hayashi1, Masaaki Kobayashi1, Yasuo Sasagawa1, Masahiro Oishi1, Osamu Tachibana2, Mitsutoshi Nakada1
BACKGROUND: Rathke cleft cysts (RCCs) arise from the remnant of Rathke pouch and are usually found in the intermediate lobe. In most cases, RCCs remain intrasellar and extend into the suprasellar region. Rarely, they emerge entirely into the suprasellar cistern—entirely suprasellar Rathke cleft cyst (ESSRCC).
-
METHODS: We retrospectively reviewed medical records of 7 patients (5.5%) with ESSRCC among 128 patients with a diagnosis of RCC from January 1994 to September 2018. Of RCC cases, 70 were treated surgically. Patient age and sex, symptoms, magnetic resonance imaging findings, cyst diameter, presence of preoperative or postoperative hypopituitarism, operative procedures and complications, and functional outcomes at the final follow-up were investigated.
treated effectively with the endoscopic endonasal transtuberculum sellae approach without recurrence of cysts or pituitary dysfunction.
-
RESULTS: All patients with ESSRCC were women with mean age 45.7 years (range, 29e69 years) at diagnosis. All patients experienced headache, mainly in the retro-orbital region. Mean ESSRCC diameter was 9.9 mm (range, 6e14 mm). Most cases exhibited hyperintensity on both T1weighted and T2-weighted imaging. The endoscopic endonasal transtuberculum sellae approach relieved headache effectively and safely in 5 patients. Postoperative endocrinologic functions were almost entirely preserved. No patient experienced recurrence during the follow-up period.
-
CONCLUSIONS: RCCs should be considered in the differential diagnosis of suprasellar cysts. The endoscopic endonasal transtuberculum sellae approach has an advantage in visualizing these lesions owing to the direction of light from the endoscope. Headache could be
-
Key words Endoscope - Entirely suprasellar - Headache - Magnetic resonance imaging - Rathke cleft cyst - Transtuberculum sellae approach -
Abbreviations and Acronyms DI: Diabetes insipidus EETSA: Endoscopic endonasal transtuberculum sellae approach ESSRCC: Entirely suprasellar Rathke cleft cyst MRI: Magnetic resonance imaging RCC: Rathke cleft cyst
WORLD NEUROSURGERY -: e1-e9, - 2019
INTRODUCTION
R
athke cleft cysts (RCCs) are the most common nonneoplastic cyst located entirely within the sellar turcica or within both intrasellar and suprasellar regions. The cyst walls are composed of epithelial cells, and the cysts contain fluid with a high protein concentration.1,2 RCCs arise from the remnant of the primitive craniopharyngeal duct, part of Rathke pouch, and usually are found at the pars intermedia of the pituitary gland between the adenohypophysis and neurohypophysis.3,4 Although RCCs are reported to be present in 3%e22% of routine autopsies, they are rarely symptomatic during life, especially when entirely suprasellar.5,6 The differential neuroimaging features of intrasellar and suprasellar cystic mass lesions, including RCCs, have been increasingly reported; however, there are still only a few reports regarding the correlation between clinical symptoms, neuroimaging findings, and characteristics of cyst contents.2,7-10 The most common clinical symptoms associated with RCCs are headache, impaired visual function, and endocrinologic insufficiency.11,12 The pathophysiology of RCCs is likely expansion due to the accumulation of fluid, leading to symptoms secondary to enlargement of the cyst, spread of cyst contents, and bleeding from the cyst wall. In most cases, RCCs remain intrasellar and extend into the suprasellar region. Rarely, they emerge entirely in the suprasellar
T1WI: T1-weighted imaging T2WI: T2-weighted imaging From the 1Department of Neurosurgery, Graduate School of Medical Science, and 2 Department of Neurosurgery, Kanazawa Medical University, Kanazawa, Japan To whom correspondence should be addressed: Yasuhiko Hayashi, M.D., Ph.D. [E-mail: [email protected]] Citation: World Neurosurg. (2019). https://doi.org/10.1016/j.wneu.2019.03.011 Journal homepage: www.journals.elsevier.com/world-neurosurgery Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2019 Elsevier Inc. All rights reserved.
www.journals.elsevier.com/world-neurosurgery
e1
ORIGINAL ARTICLE YASUHIKO HAYASHI ET AL.
ENTIRELY SUPRASELLAR RATHKE CLEFT CYST
patients (5.5%) with symptomatic ESSRCC among 128 patients with RCC seen in Kanazawa University Hospital between 1994 and 2018 were enrolled. All RCCs were clinically diagnosed based on magnetic resonance imaging (MRI) findings, and 70 patients received surgical treatment. We considered the following items obtained from the patients’ clinical charts: sex, age, symptoms, radiologic evaluation, endocrinologic insufficiencies, operative reports, pathologic findings, recurrence, outcomes, and follow-up periods. Postoperative outcomes were classified as improved with relief of preoperative symptoms, unchanged with continuation of symptoms, or worsening with deterioration of symptoms and/or occurrence of new postoperative symptoms.
Figure 1. Scheme of the surgical direction of endoscopic endonasal transtuberculum sellae approach. Arrow indicates the light direction of endoscope. ESSRCC, entirely suprasellar Rathke cleft cyst.
cistern with an intact diaphragm and intact sella; cysts of this type are referred to as entirely suprasellar Rathke cleft cyst (ESSRCC).13-15 Owing to their rarity, most studies of ESSRCCs have been case studies, and there are few studies describing clinical characteristics, such as symptoms, radiologic features, pathologic findings, operative approaches, recurrence rates, and functional outcomes. Chotai et al.16 reported the characteristics of RCCs based on cyst location and addressed purely suprasellar cysts. The present study discusses the clinical, radiologic, and endocrinologic features of ESSRCCs and treatment via an endoscopic endonasal transtuberculum sellae approach (EETSA).
MATERIALS AND METHODS Patients This study was approved by the Kanazawa University Institutional Review Board. In this retrospective clinical study, 7 Table 1. Demographics of Patients with Rathke Cleft Cysts and Patients with Entirely Suprasellar Rathke Cleft Cysts RCC
ESSRCC
Age, years, mean
46.9
45.7
Sex, male:female
24:66
0:7
53 (61.6)
7 (100)
Visual function disturbance
23 (26.7)
1 (14.3)
Hypopituitarism
14 (16.3)
0 (0)
Symptoms, number (%) Headache
RCC, Rathke cleft cyst; ESSRCC, entirely suprasellar Rathke cleft cyst.
e2
www.SCIENCEDIRECT.com
Diagnosis of RCC Preoperative diagnosis of RCCs was made on the basis of the following MRI findings that are characteristic of RCCs: cystic lesions in the suprasellar region only, absence of or faint cystic wall enhancement, normal pituitary gland and diaphragma sellae beneath the cyst, and absence of calcification. Radiologic evaluation included recording cyst diameter; signal intensities of cyst contents on both T1-weighted imaging (T1WI) and T2-weighted imaging (T2WI); areas of hyperintensity in the pituitary stalk and posterior lobe on T1WI; and presence of intracystic nodules, which were seen as very hypointense on T2WI. Contrast enhancement with gadolinium administration on T1WI was used for evaluating the cyst wall of the RCCs and the normal pituitary gland. MRI and computed tomography findings compatible with RCC were confirmed by at least 2 of 3 neurosurgeons (Y.H., Y.S., and O.T.). Intraoperative findings comparable to RCCs were considered when the cysts’ contents were white or yellow, with varying viscosities of mucinous liquid, and with no calcified nodules. Postoperatively, pathologic examination of the surgical specimen was routinely performed using hematoxylin and eosin staining and light microscopic analysis demonstrating the following pathologic findings: the epithelium lining of the cyst wall consisted of cuboidal or columnar cells, cilia on the cell surface inside the cyst, and goblet cells. CAM 5.2 (cytokeratin) was used for immunohistochemical staining for the diagnosis of RCC.17 Endocrinologic Evaluation A preoperative endocrinologic assessment was performed in each patient on hospital admission, including measurement of the plasma levels of the following hormones secreted from the pituitary gland and their target organs: growth hormone, insulin-like growth factor I, prolactin, adrenocorticotropic hormone, cortisol, thyroid-stimulating hormone, triiodothyronine, thyroxine, luteinizing hormone, and follicle-stimulating hormone. After removal of the cysts, corticotropin-releasing hormone, thyrotropin-releasing hormone, and luteinizing hormoneereleasing hormone loading tests were performed for evaluation of reserve capacity of each hormone tested preoperatively. Hypopituitarism was defined as the requirement of any hormone replacement. Regular follow-up endocrinologic assessment was performed at 3 and 6 months and annually thereafter.
WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2019.03.011
ORIGINAL ARTICLE YASUHIKO HAYASHI ET AL.
ENTIRELY SUPRASELLAR RATHKE CLEFT CYST
Figure 2. Coronal T1-weighted magnetic resonance imaging with contrast agent showing Rathke cleft cysts over the pituitary gland. (Upper row) Cases 1e4. (Lower row) Cases 5e7.
Figure 3. Sagittal T1-weighted magnetic resonance imaging with contrast agent showing Rathke cleft cysts over the pituitary gland and contact with the optic chiasm. (Upper row) Cases 1e4. (Lower row) Cases 5e7.
WORLD NEUROSURGERY -: e1-e9, - 2019
www.journals.elsevier.com/world-neurosurgery
e3
ORIGINAL ARTICLE YASUHIKO HAYASHI ET AL.
ENTIRELY SUPRASELLAR RATHKE CLEFT CYST
Figure 4. Coronal T2-weighted magnetic resonance imaging showing Rathke cleft cysts including hyperintense cyst contents over the pituitary
Diabetes Insipidus During the preoperative endocrinologic evaluation, diabetes insipidus (DI) was considered with presentations of polydipsia and polyuria and the requirement for 1-deamino-8-D-arginine vasopressin or desmopressin, synthetic forms of antidiuretic hormone, to control urine volume.18 In this study, central-type DI was diagnosed postoperatively if the following 2 conditions were met from viewing the patients’ clinical records: 1) total urine volume per day >2500 mL and 2) urine specific gravity of <1.005.19 In the assessment of preoperative and long-lasting postoperative DI after discharge, low levels of urine osmolality that did not increase with hypersaline loading were evaluated by endocrinologists.
gland and the diaphragm sellae delineated by linear hypointensity. (Upper row) Cases 1e4. (Lower row) Cases 5e7.
the diaphragm sellae inferiorly could be found after removal of the cyst. The anterior surface of the midbrain was found behind the location of the cyst. Therefore, the cystic lesion was considered to be within the suprasellar cistern. In this series, all operations were performed by 1 of the authors (Y.H.). After tumor removal, grafts of fat and fascia from the abdomen were placed into the cyst cavity, and autologous bone from the nasal septum was inserted in the epidural space. The surface of the bone was sealed with fibrin glue and then covered with a pedicled mucosal flap. A lumbar drain was placed for 3e4 days after the operation. RESULTS
Surgical Procedures All patients were treated using EETSA under general anesthesia, and total removal of the cyst was achieved. The procedure was performed as follows. First, the tuberculum sellae and upper half of the sella floor were drilled out, and the dura mater was incised vertically to expose the suprasellar cistern (Figure 1). The cyst wall was then found either in the front or behind the pituitary stalk just above the diaphragm sellae. Intraoperative exploration revealed the lesion to be a cyst containing mucinous fluid. After incision of the cyst wall and aspiration of as much of the contents as possible, the thin, fragile cyst wall was resected totally. Because the cyst wall did not adhere to the surrounding neural and vascular structures, it was easily removed without injury to the pituitary stalk. The optic chiasm and superior hypophyseal arteries superiorly; the internal carotid arteries, posterior communicating arteries, and oculomotor nerves laterally; and
e4
www.SCIENCEDIRECT.com
Patient Demographics The demographics of the 121 patients with RCCs (not including ESSRCCs) and 7 patients with ESSRCCs included in this study are summarized in Table 1. All patients with RCCs were identified from reviewing medical records. The patients with RCCs included 36 men and 86 women with a mean age of 45.4 years (range, 10e76 years). Symptoms included headache in 81 patients (66.9%), visual function disturbance in 30 patients (24.8%), and hypopituitarism in 25 patients (19.5%). All 7 patients with ESSRCCs were women with a mean age of 45.7 years (range, 29e69 years). Symptoms included headache in 7 patients (100%) and visual function disturbance in 1 patient (14.3%). The mean duration from onset of headache to radiologic diagnosis was 24.9 months (range, 2e91 months). The locations of headache were retro-orbital in 4 patients and across the whole
WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2019.03.011
ORIGINAL ARTICLE
WORLD NEUROSURGERY -: e1-e9, - 2019
MRI, magnetic resonance imaging; T1WI, T1-weighted imaging; T2WI, T2-weighted imaging; Preop, preoperative; Postop, postoperative; Hyper, hyperintense; EETSA, endoscopic endonasal transtuberculum sellae approach; Hypo, hypointense; Iso, isointense.
17
Resolved
6
12
þ Hyper
Hyper
Hyper
2
Pulsatile Whole 56/female
29/female
6
7
Retro-orbital
Pulsatile
Iso
EETSA
10 Hyper 34/female 5
Whole
Heaviness
Hyper
42
18
Resolved
Resolved
EETSA
þ
13
14
Hyper
Hypo
Hyper 2
2
Pulsatile
Whole
69/female
58/female
3
4
Retro-orbital
Heaviness
Hyper
EETSA
23
12
Resolved
Resolved
EETSA
EETSA
8
6
Hyper
Hyper Hyper
12
91 Pulsatile
Retro-orbital 44/female
30/female
1
2
Retro-orbital
Heaviness
Hyper
Outcomes Postop Preop Size (mm) Waxy Nodule Case
Location
Character
T1WI
T2WI
Hypopituitarism MRI
ENTIRELY SUPRASELLAR RATHKE CLEFT CYST
Onset to Surgery (Months) Headache
Age (Years)/ Sex
Table 2. Clinical and Radiologic Features of Patients with Entirely Suprasellar Rathke Cleft Cysts
Operation
Complication
Recurrence
Follow-Up (Months)
YASUHIKO HAYASHI ET AL.
head in 3 patients. The headaches were pulsatile in 4 patients and characterized by heaviness in 3 patients. Five of 7 patients felt that their quality of life was significantly disturbed. In the other 2 patients, 1 had anxiety regarding headache persistence despite light pain, and the other had visual function impairment. Although pain medications were administered after consultation with our department, headaches did not resolve in all patients. Neuroradiologic Evaluation The mean cyst diameter was 9.9 mm (range, 6e14 mm). The observed signals on MRI were hyperintensity in 6 patients and hypointensity in 1 patient on T1WI and hyperintensity in 6 patients and isointensity in 1 patient on T2WI. Five of 7 patients showed a pattern of hyperintensity on both T1WI and T2WI (Figures 2e4). Intracystic nodules, recognized as extreme hypointensities on T2WI, were found in only 1 patient (Table 2). Endocrinologic Evaluation The endocrinologic functions of the anterior lobe of the pituitary gland were not impaired in all patients preoperatively and were preserved in all patients except 1 postoperatively. In this patient, hormonal replacement of hydrocortisone was performed after surgery. The serum prolactin was 25.7 ng/mL preoperatively and increased to 50.8 ng/mL postoperatively. Hyperprolactinemia was initially recognized in 2 patients, which increased to 4 patients postoperatively. Although transient DI was found in 5 patients postoperatively, no patients developed permanent DI either preoperatively or postoperatively. Surgical Treatment and Pathologic Examination Five of 7 patients were operated via EETSA, and the other 2 patients received conservative treatment. No postoperative complications, including intracranial or massive intranasal hemorrhage or cerebrospinal fluid leakage, occurred in our series. Preoperative headache resolved in all patients. Recurrence was not observed during the postoperative follow-up period (mean 22.4 months range, 12e42 months). Two representative cases are shown in Figures 5 and 6. Pathologic examination showed a single layer of cuboidal or columnar epithelial cells filled with mucoid components and positive immunohistologic staining for CAM 5.2 in the specimens of all patients, resulting in the diagnosis of RCC. Moreover, the accumulation of lymphocytic cells and massive fibrosis in cyst walls were found in 5e patients, and squamous metaplasia was found in 3 patients. DISCUSSION RCCs arise from the remnant of Rathke pouch and usually are found in the intermediate lobe. However, rarely, they emerge entirely into the suprasellar cistern—ESSRCCs.3,4 The original site of ESSRCCs is assumed to be the pars tuberalis of the pituitary gland, which lies above the diaphragm sellae and is also derived from Rathke pouch.14,20 In the present study, 7 cases of ESSRCC were presented from radiological and clinical viewpoints. All patients with symptomatic ESSRCC were women, and their primary symptom was headache, mainly in the retro-orbital region or across the whole head. The ESSRCCs were small, with an average
www.journals.elsevier.com/world-neurosurgery
e5
ORIGINAL ARTICLE YASUHIKO HAYASHI ET AL.
ENTIRELY SUPRASELLAR RATHKE CLEFT CYST
Figure 5. Case 1. The patient presented with severe headache. (AeC) Intraoperative views of Rathke cleft cyst in the suprasellar cistern. (A) The cyst was located next to the pituitary stalk, and the cyst content was white. (B) The cyst wall was totally excised without
maximum diameter of 9.9 mm. EETSA relieved headache effectively and safely with preservation of endocrinologic functions. In our series, all patients experienced headache. Although there have been some reports describing the relationship between headaches and MRI and pathologic findings, the mechanisms causing these headaches remain unknown.10,21-23 In addition, some recent reports have suggested that sudden-onset episodic headaches resembled headaches seen in pituitary apoplexy, which suggests a potential new mechanism for RCC-induced headaches.24-26 The occurrence of headache due to RCCs has been suggested to be caused by the following mechanisms: compression or displacement of surrounding pain-sensitive structures, such as the diaphragma sellae27,28; chemicals spreading from cyst contents inducing inflammation in the adjacent adenohypophysis or neurohypophysis, leading to subsequent irreversible hypopituitarism and aggravated headache7,9,22,25,26,28,29; rupture of cyst wall
e6
www.SCIENCEDIRECT.com
severe adhesion to the surrounding structures. (C) No residual cyst wall was found at the suprasellar cistern. (D) Pathologic examination showed a cyst wall consisting of columnar cells, accumulation of massive inflammatory cells, and notable squamous metaplasia.
letting cyst contents into the subarachnoid space30,31; and intracystic hemorrhage from the cyst wall.10,23,32 In our study, the ESSRCC was located just above the diaphragm sellae and manifested with persistent headache. Therefore, this close colocalization between RCC and the diaphragm favors compression or spread of inflammation-inducing contents onto the diaphragm sellae as the underlying mechanism of headache. The diameters of cysts in this study were approximately 10 mm on average. In most cases, MRI exhibited hyperintensity on T1WI and T2WI. These findings suggest that ESSRCC tends to be symptomatic even if it is small and to have cyst contents primarily comprising highly concentrated protein. Two different mechanisms, mechanical compression of the surrounding structures and chronic spreading of an inflammatory reaction, were assumed to cause headache. The suprasellar cistern is usually a narrow space, leading to stretching stress across surrounding structures, such as
WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2019.03.011
ORIGINAL ARTICLE YASUHIKO HAYASHI ET AL.
Figure 6. Case 4. The patient presented with headache and bitemporal hemianopsia. (AeC) Intraoperative views of Rathke cleft cyst in the suprasellar cistern. (A) The cyst was located next to the pituitary stalk, and the cyst content was transparent. (B) The cyst wall was totally excised without severe adhesion to the
the diaphragm sellae, which is located below, and the spread of inflammatory agents from the cyst contents.16,33 Meanwhile, as the preoperative prolactin values (25.7 ng/mL) did not significantly exceed the normal range, the effect of sectioning the pituitary stalk by the cyst was not remarkable. However, the effect of intraoperative manipulation of the pituitary stalk elevated the postoperative prolactin values (50.8 ng/mL) significantly. As postoperative hypopituitarism requiring hormonal replacement was detected in only 1 patient, it was suggested that the sectioning effect after the cyst removal did not lead to the irreversible postoperative hypopituitarism. Chotai et al.16 reported the characteristics of purely suprasellar RCCs of 21 cases in their series; however, the transcranial route was used in the treatment for all of these cysts. Peng et al.34 reported the usefulness of the supraorbital keyhole approach
WORLD NEUROSURGERY -: e1-e9, - 2019
ENTIRELY SUPRASELLAR RATHKE CLEFT CYST
surrounding structures. (C) No residual cyst wall was found at the suprasellar cistern. (D) Pathologic examination revealed a cyst wall consisting of columnar and cuboidal cells, accumulation of inflammatory cells, and notable squamous metaplasia.
using an endoscope for suprasellar (8 cases) and supraintrasellar (5 cases) RCCs, and the cyst contents were removed in all cases. We used EETSA in our series and believe that it is a rational procedure to remove the cyst located just in the suprasellar cistern. The greatest advantage of this procedure is the ability to remove as much of the cyst wall as possible to prevent postoperative recurrence. In addition, dissection of the cyst wall and surrounding structures, including the pituitary stalk, internal carotid artery, posterior communicating artery, and oculomotor nerve, can be performed under direct visualization using the endoscope. Therefore, if reconstruction of tuberculum sellae with fascia and fat can be performed safely, this approach is considered to be the best strategy for effective relief of symptoms. Previously, postoperative recurrence rates of RCCs were reported to be 5%e27%, and risk factors for recurrence were
www.journals.elsevier.com/world-neurosurgery
e7
ORIGINAL ARTICLE YASUHIKO HAYASHI ET AL.
ENTIRELY SUPRASELLAR RATHKE CLEFT CYST
described by some authors as purely suprasellar location, squamous metaplasia of the cyst wall, cyst infection, and use of fat graft.16,35-37 Although 1 risk factor of suprasellar location was obviously present in all the cases in our study, no recurrences of RCC were recognized. We believe that total cyst removal can affect postoperative recurrence rates. As a differential diagnosis, it is important to take into consideration craniopharyngioma, owing to the cystic nature, suprasellar location, and pathologic findings.15,17,38 In our study, squamous metaplasia was recognized in 3 cases on the pathologic examination. Squamous metaplasia of the epithelial cells is considered to be a transitional form of progression from RCC to craniopharyngioma.17,39 Several explanations were proposed for the association between squamous metaplasia and recurrence.2,9,16,17,35 The presence of squamous metaplasia makes the distinction between papillary craniopharyngioma, which usually has extensive ciliation with mucin production, and RCC difficult.40,41 In addition, chronic inflammation may lead to metaplastic transformation from cuboidal and columnar to squamous epithelium.16 Therefore, in ESSRCC, it is suggested that chronic spreading of inflammatory content to the adjacent tissue can occur.
REFERENCES 1. Cohan P, Foulad A, Esposito F, Martin NA, Kelly DF. Symptomatic Rathke’s cleft cyst: a report of 24 cases. J Endocrinol Invest. 2004;27: 943-948. 2. Voelker JL, Campbell RL, Muller J. Clinical, radiographic, and pathological features of symptomatic Rathke’s cleft cysts. J Neurosurg. 1991;74: 535-544. 3. Fager CA, Carter H. Intrasellar epithelial cysts. J Neurosurg. 1966;24:77-81. 4. Yoshida J, Kobayashi T, Kageyama N, Kanzaki M. Symptomatic Rathke’s cleft cyst. Morphological study with light and electron microscopy and tissue culture. J Neurosurg. 1977;47:451-458. 5. Baskin DS, Wilson CB. Transsphenoidal treatment of non-neoplastic intrasellar cysts. A report of 38 cases. J Neurosurg. 1984;60:8-13. 6. Steinberg GK, Koenig GH, Golden JB. Symptomatic Rathke’s cleft cyst. Report of two cases. J Neurosurg. 1982;56:290-295. 7. Nishioka H, Hiraoka J, Izawa H, Ikeda Y. Magnetic resonance imaging, clinical manifestations, and management of Rathke’s cleft cyst. Clin Endocrinol (Oxf). 2006;64:184-188. 8. Madhok R, Prevedello DM, Gardner P, Carrau RL, Snyderman CH, Kassam AB. Endoscopic endonasal resection of Rathke cleft cysts: clinical outcomes and surgical nuances. J Neurosurg. 2010;112: 1333-1339. 9. Kim JE, Kim JH, Kim OL, et al. Surgical treatment of symptomatic Rathke cleft cysts: clinical features and results with special attention to recurrence. J Neurosurg. 2004;100:33-40.
e8
www.SCIENCEDIRECT.com
This study has some limitations. First, this study had a retrospective design. Second, the total number of patients with ESSRCC included (7 patients) was too small to provide significant statistical power. We believe accumulation of more cases would make the clinical and radiologic features of ESSRCC much clearer. Third, we performed surgery using only EETSA. Therefore, no comparisons between transnasal and transcranial approaches could be made. CONCLUSIONS Although ESSRCCs are rare, they should be considered in the differential diagnosis of suprasellar cysts. We present a rare case series of ESSRCCs from the radiologic and clinical viewpoints. All patients in this study were women, and their primary symptom was headache. Although the diameter of the cysts was small, the headaches were severe enough to disturb their activities of daily living to some extent. Surgery via EETSA relieved headache effectively and safely with the preservation of endocrinologic functions. Finally, it is important to discriminate ESSRCC from craniopharyngioma through radiologic and pathologic evaluation.
10. Saeki N, Snami K, Sugaya Y, Yamaura A. MRI findings and clinical manifestations in Rathke’s cleft cyst. Acta Neurochir (Wien). 1991;141:1055-1061.
hyponatremia in the immediate course after transsphenoidal surgery for pituitary adenomas. Clin Endocrinol. 1999;50:431-439.
11. Zada G. Rathke cleft cysts: a review of clinical and surgical management. Neurosurg Focus. 2011;31:E1.
20. Larkin S, Karavitaki N, Ansorge O. Rathke’s cleft cyst. Handb Clin Neurol. 2014;124:255-269.
12. Wait SD, Garrett MP, Little AS, Killory BD, White WL. Endocrinopathy, vision, headache, and recurrence after transsphenoidal surgery for Rathke cleft cysts. Neurosurgery. 2010;67:837-843.
21. Aho CJ, Liu C, Zelman V, Couldwell WT, Weiss MH. Surgical outcomes in 118 patients with Rathke cleft cysts. J Neurosurg. 2005;102:189-193.
13. Barrow DL, Spector RH, Takei Y, Tindall GT. Symptomatic Rathke’s cleft cysts located entirely in the suprasellar region: review of diagnosis, management, and pathogenesis. Neurosurgery. 1985;6:766-772. 14. Itoh J, Usui K. An entirely suprasellar symptomatic Rathke’s cleft cyst: case report. Neurosurgery. 1992;30:581-585. 15. Wenger M, Simko M, Markwalder R, Taub E. An entirely suprasellar Rathke’s cleft cyst: case report and review of the literature. J Clin Neurosci. 2001;8: 564-567. 16. Chotai S, Liu Y, Pan J, Qi S. Characteristics of Rathke’s cleft cyst based on cyst location with primary focus on recurrence after resection. J Neurosurg. 2015;122:1380-1389. 17. Ogawa Y, Watanabe M, Tominaga T. Rathke’s cleft cysts with significant squamous metaplasia— high risk of postoperative deterioration and close origins to craniopharyngioma. Acta Neurochir (Wien). 2013;155:1069-1075. 18. Oishi M, Hayashi Y, Sasagawa Y, Kita D, Tachibana O, Nakada M. Outcome of diabetes insipidus in patients with Rathke’s cleft cysts. Clin Neurol Neurosurg. 2018;167:141-146. 19. Hensen J, Henig A, Fuhlbusch R, Meyer M, Boehnert M, Buchfelder M. Prevalence, predictors and patterns of postoperative polyuria and
22. Fukui I, Hayashi Y, Kita D, et al. Significant improvement in chronic persistent headaches caused by small Rathke cleft cysts after transsphenoidal surgery. World Neurosurg. 2017;99: 362-368. 23. Nishioka H, Haraoka J, Izawa H, Ikeda Y. Headaches associated with Rathke’s cleft cyst. Headache. 2006;46:1580-1586. 24. Chaiban JT, Abdelmannan D, Cohen M, Selman WR, Arafah BM. Rathke cleft cyst apoplexy: a newly characterized distinct clinical entity. J Neurosurg. 2011;114:318-324. 25. Nishioka H, Ito H, Miki T, Hashimoto T, Nojima H, Matsumura H. Rathke’s cleft cyst with pituitary apoplexy. Neuroradiology. 1999;41:832-834. 26. Pawar SJ, Sharma RR, Lad SD, Dev E, Devadas RV. Rathke’s cleft cyst presenting as pituitary apoplexy. J Clin Neurosci. 2002;9:76-79. 27. Suwanwela N, Phanthumchinda K, Kaoropthum S. Headache in brain tumor: a crosssectional study. Headache. 1994;34:435-438. 28. Hayashi Y, Oishi M, Kita D, Watanabe T, Tachibana O, Hamada J. Pure lymphocytic infundibuloneurohypophysitis caused by the rupture of Rathke’s cleft cyst: report of 2 cases and review of the literature. Turk Neurosurg. 2015;25:332-336. 29. Law ER, Kanter AS. Editorial: Rathke cleft cyst. J Neurosurg. 2004;101:571-572.
WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2019.03.011
ORIGINAL ARTICLE YASUHIKO HAYASHI ET AL.
30. McLaughlin N, Lavigne F, Kilty S, Berthelet F, Bojanowski MW. Hypophysitis secondary to a ruptured Rathke cleft cyst. Can J Neurol Sci. 2010;37: 402-405. 31. Neidert MC, Woernle CM, Leske H, et al. Ruptured Rathke cleft cyst mimicking pituitary apoplexy. J Neurol Surg A Cent Eur Neurosurg. 2013; 74(suppl 1):e229-e332. 32. 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. 33. Hayashi Y, Tachibana O, Muramatsu N, et al. Rathke cleft cyst: MR and biomedical analysis of cyst content. J Comput Assist Tomogr. 1999;23:34-38. 34. Peng Y, Fan J, Li Y, Qiu M, Qi S. The supraorbital keyhole approach to the suprasellar and supraintrasellar Rathke cleft cysts under pure endoscopic visualization. World Neurosurg. 2016;92: 120-125.
ENTIRELY SUPRASELLAR RATHKE CLEFT CYST
35. Han SJ, Rolston JD, Jahangiri A, Aghi MK. Rathke’s cleft cysts: review of natural history and surgical outcomes. J Neurooncol. 2014;7:197-203. 36. Mendelson ZS, Husain Q, Elmoursi S, Svider PF, Eloy JA, Liu JK. Rathke’s cleft cyst recurrence after transsphenoidal surgery: a meta-analysis of 1151 cases. J Clin Neurosci. 2014;21:378-385. 37. Frank G, Sciarretta V, Mazzatenta D, Farneti G, Modugno GC, Pasquini E. Transsphenoidal endoscopic approach in the treatment of Rathke’s cleft cyst. Neurosurgery. 2005;56:124-129.
relationship between Rathke cleft cyst and ciliated craniopharyngioma. Noshuyo Byori. 1995;12:97-103. 41. Wolfe SQ, Heros RC. A Rathke cleft cyst to craniopharyngioma: is there a spectrum? J Neurosurg. 2010;112:1322-1323.
Conflict of interest statement: The authors declare that the article content was composed on the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Received 13 January 2019; accepted 2 March 2019
38. Hayashi Y, Kita D, Fukui I, et al. Pediatric symptomatic Rathke cleft cyst compared with cystic craniopharyngioma. Childs Nerv Syst. 2016;32: 1625-1632.
Citation: World Neurosurg. (2019). https://doi.org/10.1016/j.wneu.2019.03.011
39. Sato K, Oka H, Utsuki S, Kondo K, Kurata A, Fujii K. Ciliated craniopharyngioma may arise from Rathke cleft cyst. Clin Neuropathol. 2006;25: 25-28.
Available online: www.sciencedirect.com
Journal homepage: www.journals.elsevier.com/worldneurosurgery 1878-8750/$ - see front matter ª 2019 Elsevier Inc. All rights reserved.
40. Oka H, Kawano N, Yagishita S, et al. Origin of ciliated craniopharyngioma: pathological
WORLD NEUROSURGERY -: e1-e9, - 2019
www.journals.elsevier.com/world-neurosurgery
e9
Entirely Suprasellar Rathke Cleft Cysts: Clinical Features and Surgical Efficacy of Endoscopic Endonasal Transtuberculum Sellae Approach Yasuhiko Hayashi1, Masaaki Kobayashi1, Yasuo Sasagawa1, Masahiro Oishi1, Osamu Tachibana2, Mitsutoshi Nakada1
BACKGROUND: Rathke cleft cysts (RCCs) arise from the remnant of Rathke pouch and are usually found in the intermediate lobe. In most cases, RCCs remain intrasellar and extend into the suprasellar region. Rarely, they emerge entirely into the suprasellar cistern—entirely suprasellar Rathke cleft cyst (ESSRCC).
-
METHODS: We retrospectively reviewed medical records of 7 patients (5.5%) with ESSRCC among 128 patients with a diagnosis of RCC from January 1994 to September 2018. Of RCC cases, 70 were treated surgically. Patient age and sex, symptoms, magnetic resonance imaging findings, cyst diameter, presence of preoperative or postoperative hypopituitarism, operative procedures and complications, and functional outcomes at the final follow-up were investigated.
treated effectively with the endoscopic endonasal transtuberculum sellae approach without recurrence of cysts or pituitary dysfunction.
-
RESULTS: All patients with ESSRCC were women with mean age 45.7 years (range, 29e69 years) at diagnosis. All patients experienced headache, mainly in the retro-orbital region. Mean ESSRCC diameter was 9.9 mm (range, 6e14 mm). Most cases exhibited hyperintensity on both T1weighted and T2-weighted imaging. The endoscopic endonasal transtuberculum sellae approach relieved headache effectively and safely in 5 patients. Postoperative endocrinologic functions were almost entirely preserved. No patient experienced recurrence during the follow-up period.
-
CONCLUSIONS: RCCs should be considered in the differential diagnosis of suprasellar cysts. The endoscopic endonasal transtuberculum sellae approach has an advantage in visualizing these lesions owing to the direction of light from the endoscope. Headache could be
-
Key words Endoscope - Entirely suprasellar - Headache - Magnetic resonance imaging - Rathke cleft cyst - Transtuberculum sellae approach -
Abbreviations and Acronyms DI: Diabetes insipidus EETSA: Endoscopic endonasal transtuberculum sellae approach ESSRCC: Entirely suprasellar Rathke cleft cyst MRI: Magnetic resonance imaging RCC: Rathke cleft cyst
WORLD NEUROSURGERY -: e1-e9, - 2019
INTRODUCTION
R
athke cleft cysts (RCCs) are the most common nonneoplastic cyst located entirely within the sellar turcica or within both intrasellar and suprasellar regions. The cyst walls are composed of epithelial cells, and the cysts contain fluid with a high protein concentration.1,2 RCCs arise from the remnant of the primitive craniopharyngeal duct, part of Rathke pouch, and usually are found at the pars intermedia of the pituitary gland between the adenohypophysis and neurohypophysis.3,4 Although RCCs are reported to be present in 3%e22% of routine autopsies, they are rarely symptomatic during life, especially when entirely suprasellar.5,6 The differential neuroimaging features of intrasellar and suprasellar cystic mass lesions, including RCCs, have been increasingly reported; however, there are still only a few reports regarding the correlation between clinical symptoms, neuroimaging findings, and characteristics of cyst contents.2,7-10 The most common clinical symptoms associated with RCCs are headache, impaired visual function, and endocrinologic insufficiency.11,12 The pathophysiology of RCCs is likely expansion due to the accumulation of fluid, leading to symptoms secondary to enlargement of the cyst, spread of cyst contents, and bleeding from the cyst wall. In most cases, RCCs remain intrasellar and extend into the suprasellar region. Rarely, they emerge entirely in the suprasellar
T1WI: T1-weighted imaging T2WI: T2-weighted imaging From the 1Department of Neurosurgery, Graduate School of Medical Science, and 2 Department of Neurosurgery, Kanazawa Medical University, Kanazawa, Japan To whom correspondence should be addressed: Yasuhiko Hayashi, M.D., Ph.D. [E-mail: [email protected]] Citation: World Neurosurg. (2019). https://doi.org/10.1016/j.wneu.2019.03.011 Journal homepage: www.journals.elsevier.com/world-neurosurgery Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2019 Elsevier Inc. All rights reserved.
www.journals.elsevier.com/world-neurosurgery
e1
ORIGINAL ARTICLE YASUHIKO HAYASHI ET AL.
ENTIRELY SUPRASELLAR RATHKE CLEFT CYST
patients (5.5%) with symptomatic ESSRCC among 128 patients with RCC seen in Kanazawa University Hospital between 1994 and 2018 were enrolled. All RCCs were clinically diagnosed based on magnetic resonance imaging (MRI) findings, and 70 patients received surgical treatment. We considered the following items obtained from the patients’ clinical charts: sex, age, symptoms, radiologic evaluation, endocrinologic insufficiencies, operative reports, pathologic findings, recurrence, outcomes, and follow-up periods. Postoperative outcomes were classified as improved with relief of preoperative symptoms, unchanged with continuation of symptoms, or worsening with deterioration of symptoms and/or occurrence of new postoperative symptoms.
Figure 1. Scheme of the surgical direction of endoscopic endonasal transtuberculum sellae approach. Arrow indicates the light direction of endoscope. ESSRCC, entirely suprasellar Rathke cleft cyst.
cistern with an intact diaphragm and intact sella; cysts of this type are referred to as entirely suprasellar Rathke cleft cyst (ESSRCC).13-15 Owing to their rarity, most studies of ESSRCCs have been case studies, and there are few studies describing clinical characteristics, such as symptoms, radiologic features, pathologic findings, operative approaches, recurrence rates, and functional outcomes. Chotai et al.16 reported the characteristics of RCCs based on cyst location and addressed purely suprasellar cysts. The present study discusses the clinical, radiologic, and endocrinologic features of ESSRCCs and treatment via an endoscopic endonasal transtuberculum sellae approach (EETSA).
MATERIALS AND METHODS Patients This study was approved by the Kanazawa University Institutional Review Board. In this retrospective clinical study, 7 Table 1. Demographics of Patients with Rathke Cleft Cysts and Patients with Entirely Suprasellar Rathke Cleft Cysts RCC
ESSRCC
Age, years, mean
46.9
45.7
Sex, male:female
24:66
0:7
53 (61.6)
7 (100)
Visual function disturbance
23 (26.7)
1 (14.3)
Hypopituitarism
14 (16.3)
0 (0)
Symptoms, number (%) Headache
RCC, Rathke cleft cyst; ESSRCC, entirely suprasellar Rathke cleft cyst.
e2
www.SCIENCEDIRECT.com
Diagnosis of RCC Preoperative diagnosis of RCCs was made on the basis of the following MRI findings that are characteristic of RCCs: cystic lesions in the suprasellar region only, absence of or faint cystic wall enhancement, normal pituitary gland and diaphragma sellae beneath the cyst, and absence of calcification. Radiologic evaluation included recording cyst diameter; signal intensities of cyst contents on both T1-weighted imaging (T1WI) and T2-weighted imaging (T2WI); areas of hyperintensity in the pituitary stalk and posterior lobe on T1WI; and presence of intracystic nodules, which were seen as very hypointense on T2WI. Contrast enhancement with gadolinium administration on T1WI was used for evaluating the cyst wall of the RCCs and the normal pituitary gland. MRI and computed tomography findings compatible with RCC were confirmed by at least 2 of 3 neurosurgeons (Y.H., Y.S., and O.T.). Intraoperative findings comparable to RCCs were considered when the cysts’ contents were white or yellow, with varying viscosities of mucinous liquid, and with no calcified nodules. Postoperatively, pathologic examination of the surgical specimen was routinely performed using hematoxylin and eosin staining and light microscopic analysis demonstrating the following pathologic findings: the epithelium lining of the cyst wall consisted of cuboidal or columnar cells, cilia on the cell surface inside the cyst, and goblet cells. CAM 5.2 (cytokeratin) was used for immunohistochemical staining for the diagnosis of RCC.17 Endocrinologic Evaluation A preoperative endocrinologic assessment was performed in each patient on hospital admission, including measurement of the plasma levels of the following hormones secreted from the pituitary gland and their target organs: growth hormone, insulin-like growth factor I, prolactin, adrenocorticotropic hormone, cortisol, thyroid-stimulating hormone, triiodothyronine, thyroxine, luteinizing hormone, and follicle-stimulating hormone. After removal of the cysts, corticotropin-releasing hormone, thyrotropin-releasing hormone, and luteinizing hormoneereleasing hormone loading tests were performed for evaluation of reserve capacity of each hormone tested preoperatively. Hypopituitarism was defined as the requirement of any hormone replacement. Regular follow-up endocrinologic assessment was performed at 3 and 6 months and annually thereafter.
WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2019.03.011
ORIGINAL ARTICLE YASUHIKO HAYASHI ET AL.
ENTIRELY SUPRASELLAR RATHKE CLEFT CYST
Figure 2. Coronal T1-weighted magnetic resonance imaging with contrast agent showing Rathke cleft cysts over the pituitary gland. (Upper row) Cases 1e4. (Lower row) Cases 5e7.
Figure 3. Sagittal T1-weighted magnetic resonance imaging with contrast agent showing Rathke cleft cysts over the pituitary gland and contact with the optic chiasm. (Upper row) Cases 1e4. (Lower row) Cases 5e7.
WORLD NEUROSURGERY -: e1-e9, - 2019
www.journals.elsevier.com/world-neurosurgery
e3
ORIGINAL ARTICLE YASUHIKO HAYASHI ET AL.
ENTIRELY SUPRASELLAR RATHKE CLEFT CYST
Figure 4. Coronal T2-weighted magnetic resonance imaging showing Rathke cleft cysts including hyperintense cyst contents over the pituitary
Diabetes Insipidus During the preoperative endocrinologic evaluation, diabetes insipidus (DI) was considered with presentations of polydipsia and polyuria and the requirement for 1-deamino-8-D-arginine vasopressin or desmopressin, synthetic forms of antidiuretic hormone, to control urine volume.18 In this study, central-type DI was diagnosed postoperatively if the following 2 conditions were met from viewing the patients’ clinical records: 1) total urine volume per day >2500 mL and 2) urine specific gravity of <1.005.19 In the assessment of preoperative and long-lasting postoperative DI after discharge, low levels of urine osmolality that did not increase with hypersaline loading were evaluated by endocrinologists.
gland and the diaphragm sellae delineated by linear hypointensity. (Upper row) Cases 1e4. (Lower row) Cases 5e7.
the diaphragm sellae inferiorly could be found after removal of the cyst. The anterior surface of the midbrain was found behind the location of the cyst. Therefore, the cystic lesion was considered to be within the suprasellar cistern. In this series, all operations were performed by 1 of the authors (Y.H.). After tumor removal, grafts of fat and fascia from the abdomen were placed into the cyst cavity, and autologous bone from the nasal septum was inserted in the epidural space. The surface of the bone was sealed with fibrin glue and then covered with a pedicled mucosal flap. A lumbar drain was placed for 3e4 days after the operation. RESULTS
Surgical Procedures All patients were treated using EETSA under general anesthesia, and total removal of the cyst was achieved. The procedure was performed as follows. First, the tuberculum sellae and upper half of the sella floor were drilled out, and the dura mater was incised vertically to expose the suprasellar cistern (Figure 1). The cyst wall was then found either in the front or behind the pituitary stalk just above the diaphragm sellae. Intraoperative exploration revealed the lesion to be a cyst containing mucinous fluid. After incision of the cyst wall and aspiration of as much of the contents as possible, the thin, fragile cyst wall was resected totally. Because the cyst wall did not adhere to the surrounding neural and vascular structures, it was easily removed without injury to the pituitary stalk. The optic chiasm and superior hypophyseal arteries superiorly; the internal carotid arteries, posterior communicating arteries, and oculomotor nerves laterally; and
e4
www.SCIENCEDIRECT.com
Patient Demographics The demographics of the 121 patients with RCCs (not including ESSRCCs) and 7 patients with ESSRCCs included in this study are summarized in Table 1. All patients with RCCs were identified from reviewing medical records. The patients with RCCs included 36 men and 86 women with a mean age of 45.4 years (range, 10e76 years). Symptoms included headache in 81 patients (66.9%), visual function disturbance in 30 patients (24.8%), and hypopituitarism in 25 patients (19.5%). All 7 patients with ESSRCCs were women with a mean age of 45.7 years (range, 29e69 years). Symptoms included headache in 7 patients (100%) and visual function disturbance in 1 patient (14.3%). The mean duration from onset of headache to radiologic diagnosis was 24.9 months (range, 2e91 months). The locations of headache were retro-orbital in 4 patients and across the whole
WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2019.03.011
ORIGINAL ARTICLE
WORLD NEUROSURGERY -: e1-e9, - 2019
MRI, magnetic resonance imaging; T1WI, T1-weighted imaging; T2WI, T2-weighted imaging; Preop, preoperative; Postop, postoperative; Hyper, hyperintense; EETSA, endoscopic endonasal transtuberculum sellae approach; Hypo, hypointense; Iso, isointense.
17
Resolved
6
12
þ Hyper
Hyper
Hyper
2
Pulsatile Whole 56/female
29/female
6
7
Retro-orbital
Pulsatile
Iso
EETSA
10 Hyper 34/female 5
Whole
Heaviness
Hyper
42
18
Resolved
Resolved
EETSA
þ
13
14
Hyper
Hypo
Hyper 2
2
Pulsatile
Whole
69/female
58/female
3
4
Retro-orbital
Heaviness
Hyper
EETSA
23
12
Resolved
Resolved
EETSA
EETSA
8
6
Hyper
Hyper Hyper
12
91 Pulsatile
Retro-orbital 44/female
30/female
1
2
Retro-orbital
Heaviness
Hyper
Outcomes Postop Preop Size (mm) Waxy Nodule Case
Location
Character
T1WI
T2WI
Hypopituitarism MRI
ENTIRELY SUPRASELLAR RATHKE CLEFT CYST
Onset to Surgery (Months) Headache
Age (Years)/ Sex
Table 2. Clinical and Radiologic Features of Patients with Entirely Suprasellar Rathke Cleft Cysts
Operation
Complication
Recurrence
Follow-Up (Months)
YASUHIKO HAYASHI ET AL.
head in 3 patients. The headaches were pulsatile in 4 patients and characterized by heaviness in 3 patients. Five of 7 patients felt that their quality of life was significantly disturbed. In the other 2 patients, 1 had anxiety regarding headache persistence despite light pain, and the other had visual function impairment. Although pain medications were administered after consultation with our department, headaches did not resolve in all patients. Neuroradiologic Evaluation The mean cyst diameter was 9.9 mm (range, 6e14 mm). The observed signals on MRI were hyperintensity in 6 patients and hypointensity in 1 patient on T1WI and hyperintensity in 6 patients and isointensity in 1 patient on T2WI. Five of 7 patients showed a pattern of hyperintensity on both T1WI and T2WI (Figures 2e4). Intracystic nodules, recognized as extreme hypointensities on T2WI, were found in only 1 patient (Table 2). Endocrinologic Evaluation The endocrinologic functions of the anterior lobe of the pituitary gland were not impaired in all patients preoperatively and were preserved in all patients except 1 postoperatively. In this patient, hormonal replacement of hydrocortisone was performed after surgery. The serum prolactin was 25.7 ng/mL preoperatively and increased to 50.8 ng/mL postoperatively. Hyperprolactinemia was initially recognized in 2 patients, which increased to 4 patients postoperatively. Although transient DI was found in 5 patients postoperatively, no patients developed permanent DI either preoperatively or postoperatively. Surgical Treatment and Pathologic Examination Five of 7 patients were operated via EETSA, and the other 2 patients received conservative treatment. No postoperative complications, including intracranial or massive intranasal hemorrhage or cerebrospinal fluid leakage, occurred in our series. Preoperative headache resolved in all patients. Recurrence was not observed during the postoperative follow-up period (mean 22.4 months range, 12e42 months). Two representative cases are shown in Figures 5 and 6. Pathologic examination showed a single layer of cuboidal or columnar epithelial cells filled with mucoid components and positive immunohistologic staining for CAM 5.2 in the specimens of all patients, resulting in the diagnosis of RCC. Moreover, the accumulation of lymphocytic cells and massive fibrosis in cyst walls were found in 5e patients, and squamous metaplasia was found in 3 patients. DISCUSSION RCCs arise from the remnant of Rathke pouch and usually are found in the intermediate lobe. However, rarely, they emerge entirely into the suprasellar cistern—ESSRCCs.3,4 The original site of ESSRCCs is assumed to be the pars tuberalis of the pituitary gland, which lies above the diaphragm sellae and is also derived from Rathke pouch.14,20 In the present study, 7 cases of ESSRCC were presented from radiological and clinical viewpoints. All patients with symptomatic ESSRCC were women, and their primary symptom was headache, mainly in the retro-orbital region or across the whole head. The ESSRCCs were small, with an average
www.journals.elsevier.com/world-neurosurgery
e5
ORIGINAL ARTICLE YASUHIKO HAYASHI ET AL.
ENTIRELY SUPRASELLAR RATHKE CLEFT CYST
Figure 5. Case 1. The patient presented with severe headache. (AeC) Intraoperative views of Rathke cleft cyst in the suprasellar cistern. (A) The cyst was located next to the pituitary stalk, and the cyst content was white. (B) The cyst wall was totally excised without
maximum diameter of 9.9 mm. EETSA relieved headache effectively and safely with preservation of endocrinologic functions. In our series, all patients experienced headache. Although there have been some reports describing the relationship between headaches and MRI and pathologic findings, the mechanisms causing these headaches remain unknown.10,21-23 In addition, some recent reports have suggested that sudden-onset episodic headaches resembled headaches seen in pituitary apoplexy, which suggests a potential new mechanism for RCC-induced headaches.24-26 The occurrence of headache due to RCCs has been suggested to be caused by the following mechanisms: compression or displacement of surrounding pain-sensitive structures, such as the diaphragma sellae27,28; chemicals spreading from cyst contents inducing inflammation in the adjacent adenohypophysis or neurohypophysis, leading to subsequent irreversible hypopituitarism and aggravated headache7,9,22,25,26,28,29; rupture of cyst wall
e6
www.SCIENCEDIRECT.com
severe adhesion to the surrounding structures. (C) No residual cyst wall was found at the suprasellar cistern. (D) Pathologic examination showed a cyst wall consisting of columnar cells, accumulation of massive inflammatory cells, and notable squamous metaplasia.
letting cyst contents into the subarachnoid space30,31; and intracystic hemorrhage from the cyst wall.10,23,32 In our study, the ESSRCC was located just above the diaphragm sellae and manifested with persistent headache. Therefore, this close colocalization between RCC and the diaphragm favors compression or spread of inflammation-inducing contents onto the diaphragm sellae as the underlying mechanism of headache. The diameters of cysts in this study were approximately 10 mm on average. In most cases, MRI exhibited hyperintensity on T1WI and T2WI. These findings suggest that ESSRCC tends to be symptomatic even if it is small and to have cyst contents primarily comprising highly concentrated protein. Two different mechanisms, mechanical compression of the surrounding structures and chronic spreading of an inflammatory reaction, were assumed to cause headache. The suprasellar cistern is usually a narrow space, leading to stretching stress across surrounding structures, such as
WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2019.03.011
ORIGINAL ARTICLE YASUHIKO HAYASHI ET AL.
Figure 6. Case 4. The patient presented with headache and bitemporal hemianopsia. (AeC) Intraoperative views of Rathke cleft cyst in the suprasellar cistern. (A) The cyst was located next to the pituitary stalk, and the cyst content was transparent. (B) The cyst wall was totally excised without severe adhesion to the
the diaphragm sellae, which is located below, and the spread of inflammatory agents from the cyst contents.16,33 Meanwhile, as the preoperative prolactin values (25.7 ng/mL) did not significantly exceed the normal range, the effect of sectioning the pituitary stalk by the cyst was not remarkable. However, the effect of intraoperative manipulation of the pituitary stalk elevated the postoperative prolactin values (50.8 ng/mL) significantly. As postoperative hypopituitarism requiring hormonal replacement was detected in only 1 patient, it was suggested that the sectioning effect after the cyst removal did not lead to the irreversible postoperative hypopituitarism. Chotai et al.16 reported the characteristics of purely suprasellar RCCs of 21 cases in their series; however, the transcranial route was used in the treatment for all of these cysts. Peng et al.34 reported the usefulness of the supraorbital keyhole approach
WORLD NEUROSURGERY -: e1-e9, - 2019
ENTIRELY SUPRASELLAR RATHKE CLEFT CYST
surrounding structures. (C) No residual cyst wall was found at the suprasellar cistern. (D) Pathologic examination revealed a cyst wall consisting of columnar and cuboidal cells, accumulation of inflammatory cells, and notable squamous metaplasia.
using an endoscope for suprasellar (8 cases) and supraintrasellar (5 cases) RCCs, and the cyst contents were removed in all cases. We used EETSA in our series and believe that it is a rational procedure to remove the cyst located just in the suprasellar cistern. The greatest advantage of this procedure is the ability to remove as much of the cyst wall as possible to prevent postoperative recurrence. In addition, dissection of the cyst wall and surrounding structures, including the pituitary stalk, internal carotid artery, posterior communicating artery, and oculomotor nerve, can be performed under direct visualization using the endoscope. Therefore, if reconstruction of tuberculum sellae with fascia and fat can be performed safely, this approach is considered to be the best strategy for effective relief of symptoms. Previously, postoperative recurrence rates of RCCs were reported to be 5%e27%, and risk factors for recurrence were
www.journals.elsevier.com/world-neurosurgery
e7
ORIGINAL ARTICLE YASUHIKO HAYASHI ET AL.
ENTIRELY SUPRASELLAR RATHKE CLEFT CYST
described by some authors as purely suprasellar location, squamous metaplasia of the cyst wall, cyst infection, and use of fat graft.16,35-37 Although 1 risk factor of suprasellar location was obviously present in all the cases in our study, no recurrences of RCC were recognized. We believe that total cyst removal can affect postoperative recurrence rates. As a differential diagnosis, it is important to take into consideration craniopharyngioma, owing to the cystic nature, suprasellar location, and pathologic findings.15,17,38 In our study, squamous metaplasia was recognized in 3 cases on the pathologic examination. Squamous metaplasia of the epithelial cells is considered to be a transitional form of progression from RCC to craniopharyngioma.17,39 Several explanations were proposed for the association between squamous metaplasia and recurrence.2,9,16,17,35 The presence of squamous metaplasia makes the distinction between papillary craniopharyngioma, which usually has extensive ciliation with mucin production, and RCC difficult.40,41 In addition, chronic inflammation may lead to metaplastic transformation from cuboidal and columnar to squamous epithelium.16 Therefore, in ESSRCC, it is suggested that chronic spreading of inflammatory content to the adjacent tissue can occur.
REFERENCES 1. Cohan P, Foulad A, Esposito F, Martin NA, Kelly DF. Symptomatic Rathke’s cleft cyst: a report of 24 cases. J Endocrinol Invest. 2004;27: 943-948. 2. Voelker JL, Campbell RL, Muller J. Clinical, radiographic, and pathological features of symptomatic Rathke’s cleft cysts. J Neurosurg. 1991;74: 535-544. 3. Fager CA, Carter H. Intrasellar epithelial cysts. J Neurosurg. 1966;24:77-81. 4. Yoshida J, Kobayashi T, Kageyama N, Kanzaki M. Symptomatic Rathke’s cleft cyst. Morphological study with light and electron microscopy and tissue culture. J Neurosurg. 1977;47:451-458. 5. Baskin DS, Wilson CB. Transsphenoidal treatment of non-neoplastic intrasellar cysts. A report of 38 cases. J Neurosurg. 1984;60:8-13. 6. Steinberg GK, Koenig GH, Golden JB. Symptomatic Rathke’s cleft cyst. Report of two cases. J Neurosurg. 1982;56:290-295. 7. Nishioka H, Hiraoka J, Izawa H, Ikeda Y. Magnetic resonance imaging, clinical manifestations, and management of Rathke’s cleft cyst. Clin Endocrinol (Oxf). 2006;64:184-188. 8. Madhok R, Prevedello DM, Gardner P, Carrau RL, Snyderman CH, Kassam AB. Endoscopic endonasal resection of Rathke cleft cysts: clinical outcomes and surgical nuances. J Neurosurg. 2010;112: 1333-1339. 9. Kim JE, Kim JH, Kim OL, et al. Surgical treatment of symptomatic Rathke cleft cysts: clinical features and results with special attention to recurrence. J Neurosurg. 2004;100:33-40.
e8
www.SCIENCEDIRECT.com
This study has some limitations. First, this study had a retrospective design. Second, the total number of patients with ESSRCC included (7 patients) was too small to provide significant statistical power. We believe accumulation of more cases would make the clinical and radiologic features of ESSRCC much clearer. Third, we performed surgery using only EETSA. Therefore, no comparisons between transnasal and transcranial approaches could be made. CONCLUSIONS Although ESSRCCs are rare, they should be considered in the differential diagnosis of suprasellar cysts. We present a rare case series of ESSRCCs from the radiologic and clinical viewpoints. All patients in this study were women, and their primary symptom was headache. Although the diameter of the cysts was small, the headaches were severe enough to disturb their activities of daily living to some extent. Surgery via EETSA relieved headache effectively and safely with the preservation of endocrinologic functions. Finally, it is important to discriminate ESSRCC from craniopharyngioma through radiologic and pathologic evaluation.
10. Saeki N, Snami K, Sugaya Y, Yamaura A. MRI findings and clinical manifestations in Rathke’s cleft cyst. Acta Neurochir (Wien). 1991;141:1055-1061.
hyponatremia in the immediate course after transsphenoidal surgery for pituitary adenomas. Clin Endocrinol. 1999;50:431-439.
11. Zada G. Rathke cleft cysts: a review of clinical and surgical management. Neurosurg Focus. 2011;31:E1.
20. Larkin S, Karavitaki N, Ansorge O. Rathke’s cleft cyst. Handb Clin Neurol. 2014;124:255-269.
12. Wait SD, Garrett MP, Little AS, Killory BD, White WL. Endocrinopathy, vision, headache, and recurrence after transsphenoidal surgery for Rathke cleft cysts. Neurosurgery. 2010;67:837-843.
21. Aho CJ, Liu C, Zelman V, Couldwell WT, Weiss MH. Surgical outcomes in 118 patients with Rathke cleft cysts. J Neurosurg. 2005;102:189-193.
13. Barrow DL, Spector RH, Takei Y, Tindall GT. Symptomatic Rathke’s cleft cysts located entirely in the suprasellar region: review of diagnosis, management, and pathogenesis. Neurosurgery. 1985;6:766-772. 14. Itoh J, Usui K. An entirely suprasellar symptomatic Rathke’s cleft cyst: case report. Neurosurgery. 1992;30:581-585. 15. Wenger M, Simko M, Markwalder R, Taub E. An entirely suprasellar Rathke’s cleft cyst: case report and review of the literature. J Clin Neurosci. 2001;8: 564-567. 16. Chotai S, Liu Y, Pan J, Qi S. Characteristics of Rathke’s cleft cyst based on cyst location with primary focus on recurrence after resection. J Neurosurg. 2015;122:1380-1389. 17. Ogawa Y, Watanabe M, Tominaga T. Rathke’s cleft cysts with significant squamous metaplasia— high risk of postoperative deterioration and close origins to craniopharyngioma. Acta Neurochir (Wien). 2013;155:1069-1075. 18. Oishi M, Hayashi Y, Sasagawa Y, Kita D, Tachibana O, Nakada M. Outcome of diabetes insipidus in patients with Rathke’s cleft cysts. Clin Neurol Neurosurg. 2018;167:141-146. 19. Hensen J, Henig A, Fuhlbusch R, Meyer M, Boehnert M, Buchfelder M. Prevalence, predictors and patterns of postoperative polyuria and
22. Fukui I, Hayashi Y, Kita D, et al. Significant improvement in chronic persistent headaches caused by small Rathke cleft cysts after transsphenoidal surgery. World Neurosurg. 2017;99: 362-368. 23. Nishioka H, Haraoka J, Izawa H, Ikeda Y. Headaches associated with Rathke’s cleft cyst. Headache. 2006;46:1580-1586. 24. Chaiban JT, Abdelmannan D, Cohen M, Selman WR, Arafah BM. Rathke cleft cyst apoplexy: a newly characterized distinct clinical entity. J Neurosurg. 2011;114:318-324. 25. Nishioka H, Ito H, Miki T, Hashimoto T, Nojima H, Matsumura H. Rathke’s cleft cyst with pituitary apoplexy. Neuroradiology. 1999;41:832-834. 26. Pawar SJ, Sharma RR, Lad SD, Dev E, Devadas RV. Rathke’s cleft cyst presenting as pituitary apoplexy. J Clin Neurosci. 2002;9:76-79. 27. Suwanwela N, Phanthumchinda K, Kaoropthum S. Headache in brain tumor: a crosssectional study. Headache. 1994;34:435-438. 28. Hayashi Y, Oishi M, Kita D, Watanabe T, Tachibana O, Hamada J. Pure lymphocytic infundibuloneurohypophysitis caused by the rupture of Rathke’s cleft cyst: report of 2 cases and review of the literature. Turk Neurosurg. 2015;25:332-336. 29. Law ER, Kanter AS. Editorial: Rathke cleft cyst. J Neurosurg. 2004;101:571-572.
WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2019.03.011
ORIGINAL ARTICLE YASUHIKO HAYASHI ET AL.
30. McLaughlin N, Lavigne F, Kilty S, Berthelet F, Bojanowski MW. Hypophysitis secondary to a ruptured Rathke cleft cyst. Can J Neurol Sci. 2010;37: 402-405. 31. Neidert MC, Woernle CM, Leske H, et al. Ruptured Rathke cleft cyst mimicking pituitary apoplexy. J Neurol Surg A Cent Eur Neurosurg. 2013; 74(suppl 1):e229-e332. 32. 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. 33. Hayashi Y, Tachibana O, Muramatsu N, et al. Rathke cleft cyst: MR and biomedical analysis of cyst content. J Comput Assist Tomogr. 1999;23:34-38. 34. Peng Y, Fan J, Li Y, Qiu M, Qi S. The supraorbital keyhole approach to the suprasellar and supraintrasellar Rathke cleft cysts under pure endoscopic visualization. World Neurosurg. 2016;92: 120-125.
ENTIRELY SUPRASELLAR RATHKE CLEFT CYST
35. Han SJ, Rolston JD, Jahangiri A, Aghi MK. Rathke’s cleft cysts: review of natural history and surgical outcomes. J Neurooncol. 2014;7:197-203. 36. Mendelson ZS, Husain Q, Elmoursi S, Svider PF, Eloy JA, Liu JK. Rathke’s cleft cyst recurrence after transsphenoidal surgery: a meta-analysis of 1151 cases. J Clin Neurosci. 2014;21:378-385. 37. Frank G, Sciarretta V, Mazzatenta D, Farneti G, Modugno GC, Pasquini E. Transsphenoidal endoscopic approach in the treatment of Rathke’s cleft cyst. Neurosurgery. 2005;56:124-129.
relationship between Rathke cleft cyst and ciliated craniopharyngioma. Noshuyo Byori. 1995;12:97-103. 41. Wolfe SQ, Heros RC. A Rathke cleft cyst to craniopharyngioma: is there a spectrum? J Neurosurg. 2010;112:1322-1323.
Conflict of interest statement: The authors declare that the article content was composed on the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Received 13 January 2019; accepted 2 March 2019
38. Hayashi Y, Kita D, Fukui I, et al. Pediatric symptomatic Rathke cleft cyst compared with cystic craniopharyngioma. Childs Nerv Syst. 2016;32: 1625-1632.
Citation: World Neurosurg. (2019). https://doi.org/10.1016/j.wneu.2019.03.011
39. Sato K, Oka H, Utsuki S, Kondo K, Kurata A, Fujii K. Ciliated craniopharyngioma may arise from Rathke cleft cyst. Clin Neuropathol. 2006;25: 25-28.
Available online: www.sciencedirect.com
Journal homepage: www.journals.elsevier.com/worldneurosurgery 1878-8750/$ - see front matter ª 2019 Elsevier Inc. All rights reserved.
40. Oka H, Kawano N, Yagishita S, et al. Origin of ciliated craniopharyngioma: pathological
WORLD NEUROSURGERY -: e1-e9, - 2019
www.journals.elsevier.com/world-neurosurgery
e9