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Concept: Rathke's pouch

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The objective of this study was to evaluate outcomes of endoscopic transsphenoidal surgery using a single-surgeon technique as an alternative to the more commonly employed two-surgeon, three-hand method. Three hundred consecutive endoscopic transsphenoidal procedures performed over a 5 year period from 2006 to 2011 were reviewed. All procedures were performed via a binasal approach utilizing a single surgeon two handed technique with a pneumatic endoscope holder. Expanded enodnansal cases were excluded. Surgical technique, biochemical and surgical outcomes, and complications were analyzed. 276 patients underwent 300 consecutive surgeries with a mean follow-up period of 37 ± 22 months. Non-functioning pituitary adenoma (NFPA) was the most common pathology (n = 152), followed by growth hormone secreting tumors (n = 41) and Rathke’s cleft cysts (n = 30). Initial gross total cyst drainage based on radiologic criteria was obtained in 28 cases of Rathke’s cleft cyst, with 5 recurrences. For NFPA and other pathologies (n = 173) gross total resection was obtained in 137 cases, with a 92 % concordance rate between observed and expected extent of resection. For functional adenoma, remission rates were 30/41 (73 %) for GH-secreting, 12/12 (100 %) for ACTH-secreting, and 8/17 (47 %) for prolactin-secreting tumors. Post-operative complications included transient (11 %) and permanent (1.4 %) diabetes insipidus, hyponatremia (13 %), and new anterior pituitary hormonal deficits (1.4 %). CSF leak occurred in 42 cases (15 %), and four patients required surgical repair. Two carotid artery injuries occurred, both early in the series. Epistaxis and other rhinological complications were noted in 10 % of patients, most of which were minor and diminished as surgical experience increased. Fully endoscopic single surgeon transsphenoidal surgery utilizing a binasal approach and a pneumatic endoscope holder yields outcomes comparable to those reported with a two-surgeon method. Endoscopic outcomes appear to be better than those reported in microscope-based series, regardless of a one or two surgeon technique.

Concepts: Pituitary adenoma, Hospital, Surgery, Physician, Growth hormone, Common carotid artery, Anterior pituitary, Rathke's pouch

28

Diabetes insipidus (DI) after endoscopic transsphenoidal surgery (ETSS) can lead to increased morbidity, longer hospital stays, and increased medication requirements. Predicting which patients are at high risk for developing DI can help direct services to ensure adequate care and follow-up. The objective of this study was to review our institution’s experience with ETSS and determine which clinical/laboratory variables are associated with DI in this patient population. The authors wanted to see if there was an easily determined single value that would help predict which patients develop DI. This represents the largest North American series of this type. We retrospectively reviewed the charts of patients who had undergone ETSS for resection of sellar and parasellar pathology between 2006 and 2011. We examined patient and tumor characteristics and their relationship to postoperative DI. Out of 172 endoscopic transsphenoidal surgeries, there were 15 cases of transient DI (8.7 %) and 14 cases of permanent DI (8.1 %). Statistically significant predictors of postoperative DI (p < 0.05) included tumor volume and histopathology (Rathke's cleft cyst and craniopharyngioma). Significant indicators of development of DI were postoperative serum sodium, preoperative to postoperative change in sodium level, and urine output prior to administration of 1-deamino-8-D-arginine vasopressin. An increase in serum sodium of ≥2.5 mmol/L is a positive marker of development of DI with 80 % specificity, and a postoperative serum sodium of ≥145 mmol/L is a positive indicator with 98 % specificity. Identifying perioperative risk factors and objective indicators of DI after ETSS will help physicians care for patients postoperatively. In this large series, we demonstrated that there were multiple perioperative risk factors for the development of DI. These findings, which are consistent with other reports from microscopic surgical series, will help identify patients at risk for diabetes insipidus, aid in planning treatment algorithms, and increase vigilance in high risk patients.

Concepts: Hospital, Developmental biology, Surgery, Prediction, Physician, Diabetes insipidus, Craniopharyngioma, Rathke's pouch

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BACKGROUND: Rathke’s cleft cyst (RCC) with significant squamous and/or stratified epithelium including smooth transition from single cuboidal to squamous epithelium (tRCC) is rare and possibly represents an intermediate form to craniopharyngioma. METHODS: Twelve patients with histologically confirmed tRCC were retrospectively investigated from a series of 167 cases of RCC and 96 cases of craniopharyngiomas. Clinical data were reviewed, and immunohistochemistry findings for cytokeratins and β-catenin were examined. RESULTS: All lesions were located in the sella turcica with marked extension to suprasellar cistern. Six of the 12 patients had suffered postoperative re-enlargement, and three of these six patients required more than two additional operations and irradiation. CAM5.2 was positive in the glandular epithelium in all tRCCs and focally positive in the squamous epithelium of all these tRCCs. 34βE12 was positive in the squamous epithelium in all tRCCs and focally positive in the glandular epithelium in all but one tRCC. The findings of cytokeratin expression of tRCCs were very similar to those of craniopharyngioma. β-Catenin showed nuclear translocation in five cases. All patients with nuclear translocation of β-catenin suffered postoperative re-enlargement. CONCLUSIONS: tRCC carries an extremely high risk of re-enlargement. Cytokeratin expression resembles that in craniopharyngioma, which might indicate a very close origin of these pathologies. Nuclear translocation of β-catenin may be related to the aggressive clinical course.

Concepts: Anatomical pathology, Squamous epithelium, Immunohistochemistry, Sella turcica, Empty sella syndrome, Craniopharyngioma, Rathke's pouch, Cytokeratin

26

Rathke’s cleft cysts (RCC) are benign lesions that originate from remnants of Rathke’s pouch. They can compress adjacent structures causing visual loss and endocrine dysfunction. The endoscopic endonasal transsphenoidal approach (EETA) has gained popularity in the surgical management of pituitary and parasellar tumors. However, postoperative cyst recurrence and endocrine dysfunction are still major concerns. A retrospective chart review was performed on 11 patients who underwent a purely EETA. Subtotal resection of the cyst wall with drainage of the intracystic contents followed by obliteration of the cyst with a fat graft was performed in all patients. Two patients underwent repeated surgeries for symptomatic cyst recurrence. One patient ultimately underwent extracapsular removal of the entire cyst wall because of multiple recurrences after simple drainage. There were no incidences of new permanent hypopituitarism, visual deficits, or postoperative cerebrospinal fluid leaks. All patients reported an improvement of initial preoperative symptoms. A non-aggressive strategy of partial cyst wall removal and simple drainage of cyst contents via EETA is a viable approach for surgical treatment of RCC with a low rate of postoperative endocrine and visual complications. A more aggressive strategy of extracapsular removal of the cyst wall may be indicated in patients with repeated recurrence.

Concepts: Neuroendocrinology, Sebaceous cyst, Anterior pituitary, Spontaneous cerebrospinal fluid leak, Rathke's pouch, Rathke's cleft cyst

4

Cilia are highly conserved organelles, which serve critical roles in development and physiology. Motile cilia are expressed in a limited range of tissues, where they principally regulate local extracellular fluid dynamics. In contrast, primary cilia are expressed by many vertebrate cell types during interphase, and are intimately involved in the cell cycle and signal transduction. Notably, primary cilia are essential for vertebrate hedgehog pathway activity. Improved detection of motile cilia may assist in the diagnosis of some pathologic entities such as Rathke’s cleft cysts, whereas characterizing primary cilia in neoplastic tissues may implicate cilia-dependent signaling pathways as critical for tumorigenesis. We show that immunohistochemistry for the nuclear transcription factor FOXJ1, a master regulator of motile ciliogenesis, robustly labels the motile ciliated epithelium of Rathke’s cleft cysts. FOXJ1 expression discriminates Rathke’s cleft cysts from entities in the sellar/suprasellar region with overlapping histologic features such as craniopharyngiomas. Co-immunohistochemistry for FOXJ1 and markers that highlight motile cilia such as acetylated tubulin (TUBA4A) and the small GTPase ARL13B further enhance the ability to identify diagnostic epithelial cells. In addition to highlighting motile cilia, ARL13B immunohistochemistry also robustly highlights primary cilia in formalin-fixed paraffin-embedded sections. Primary cilia are present throughout the neoplastic epithelium of adamantinomatous craniopharyngioma, but are limited to basally oriented cells near the fibrovascular stroma in papillary craniopharyngioma. Consistent with this differing pattern of primary ciliation, adamantinomatous craniopharyngiomas express significantly higher levels of SHH, and downstream targets such as PTCH1 and GLI2, compared with papillary craniopharyngiomas. In conclusion, motile ciliated epithelium can be readily identified using immunohistochemistry for FOXJ1, TUBA4A, and ARL13B, facilitating the diagnosis of Rathke’s cleft cysts. Primary cilia can be identified by ARL13B immunohistochemistry in routine pathology specimens. The widespread presence of primary cilia in adamantinomatous craniopharyngioma implicates cilia-dependent hedgehog signaling in the pathogenesis of adamantinomatous craniopharyngioma.Modern Pathology advance online publication, 26 August 2016; doi:10.1038/modpathol.2016.153.

Concepts: Cell nucleus, Cell, Signal transduction, Eukaryote, Organelle, Epithelium, Cilium, Rathke's pouch

2

BACKGROUND: The pituitary gland is formed by the juxtaposition of two tissues: neuroectoderm arising from the basal diencephalon and oral epithelium, which invaginates towards the central nervous system from the roof of the mouth. The oral invagination that reaches the brain from the mouth is referred to as Rathke’s pouch (RP), with the tip forming the adenohypophysis and the stalk disappearing after the earliest stages of development. In tetrapods, formation of the cranial base establishes a definitive barrier between pituitary and oral cavity; however, numerous extinct and extant vertebrate species retain an open buccohypophyseal canal (BHC) in adulthood, which represents a vestige of the stalk of RP. Little is currently known about the formation and function of this structure. Here we have investigated molecular mechanisms driving formation of the BHC and their evolutionary significance. RESULTS: We show that RP is located at a boundary region delineated by endoderm, neural crest-derived oral mesenchyme and the anterior limit of the notochord, using CD1, R26R-Sox17-Cre and R26R-Wnt1-Cre mouse lines. As revealed by synchrotron x-ray microtomography after iodine staining in mouse embryos, the pouch has a lobulated three-dimensional structure that embraces the descending diencephalon during pituitary formation. Polarisfl/fl; Wnt1-Cre, Ofd1-/- and Kif3a-/- primary cilia mouse mutants have abnormal sonic hedghehog (Shh) signaling and all present with malformation of the anterior pituitary gland and midline structures of the anterior cranial base. Changes in the expressions of Shh downstream genes are confirmed in Gas1-/- mice. From an evolutionary perspective, persistence of the BHC is a basal character for all vertebrates and its maintenance in several groups is related to a specific morphology of the midline that can be related to modulation in Shh signaling. CONCLUSION: These results provide insight into a poorly understood ancestral vertebrate structure. It appears that the opening of the BHC depends upon Shh signaling and that modulation in this pathway most probably accounts for its persistence in phylogeny.

Concepts: Central nervous system, Nervous system, Hypothalamus, Brain, Growth hormone, Endocrine system, Sonic hedgehog, Rathke's pouch

1

Objective  The video stars orbitozygomatic resection of Rathke’s cleft cyst with suprasellar extension in a 37-year-old male patient presenting with severe headaches and bitemporal hemianopia. Clinical and radiological characteristics along with surgical technique (positioning, bony opening, surgical dissection and debulking, closure), histopathology, and postoperative course are described. Methods  Preoperative MRI demonstrated a noncontrast-enhancing cystic lesion in the sella with suprasellar extension causing compression of both optic nerves. A one-piece orbitozygomatic craniotomy was performed. The tumor was encountered in the interoptic space. First, the cyst was decompressed and fluid appearing like motor oil was aspirated. Both optic nerves were decompressed and dissected free from the cyst wall. Intraoperatively, the most challenging aspect was separating the tumor from surrounding vascular structures, including bilateral A1 arteries and the left carotid bifurcation. A combination of sharp and blunt dissection was utilized to free the tumor from adhesions to critical neurovascular structures. Once freed, the suprasellar aspect of the tumor was mobilized into the operative cavity and debulked. Finally, the sellar component of the tumor was removed all the way down to the sellar floor. Postoperative MRI demonstrated decompressed bilateral optic nerves with an intact pituitary stalk with preservation of normal pituitary gland. Histopathology identified pathognomonic features consistent with diagnosis of Rathke’s cleft cyst, including flattened ciliated epithelium and presence of Rathke’s cleft remnants. Results  Postoperatively, bilateral improvement in vision was noted with transient diabetes insipidus. Patient was discharged home on postoperative day 4. Conclusion  A one-piece orbitozygomatic craniotomy is an effective and safe strategy for resection of Rathke’s cleft cysts with suprasellar extension. The link to the video can be found at: https://youtu.be/-Yqtcd2gLSs .

Concepts: Pituitary gland, Common carotid artery, Vasopressin, Neuroendocrinology, Cyst, Diabetes insipidus, Sella turcica, Rathke's pouch

0

Craniopharyngiomas (CPs) are rare, benign tumors derived from Rathke’s pouch, known for their high recurrence rates and associated morbidity and mortality. Despite significant investigation on risk factors for recurrence, a lack of consensus persists. Recent research suggests that specific histopathological and molecular characteristics are prognostic for disease progression. In this systematic review, we analyzed and consolidated key features of CPs that contribute to increased recurrence rates. This systematic review was performed in accordance with PRISMA guidelines. A search string was created with the keywords “craniopharyngioma,” “histology,” “histopathology,” “molecular,” and “recurrence.” Literature was collected from 2006 to 2016 on the PubMed/Medline and Web of Science databases. The initial search resulted in 242 papers, examined with inclusion and exclusion criteria. The final review included a total of 37 studies, 36 primary studies covering a total of 1461 patients and 1 previous meta-analysis. Cystic lesions and whorl-like arrays were found to be associated with increased recurrence, while previously considered reactive gliosis and finger-shaped protrusions were not. The genetic elements found to be associated with increased risk of recurrence were Ki-67, Ep-CAM, PTTG-1, survivin, and certain RAR isotypes, as well as the glycoproteins osteonectin and chemokines CXCL12/CXCR4. The effects of VEGF, HIF-1α, and p53, despite extensive study, yielded conflicting results. Certain histopathological and molecular characteristics of CPs provide insight into their pathogenesis, likelihood of recurrence, and potential novel targets for therapy.

Concepts: Cancer, Pathology, Anatomical pathology, Histology, Histopathology, Benign tumor, Craniopharyngioma, Rathke's pouch

0

We present a case of a giant Rathke’s cleft cyst with significant superior extension into the third and right lateral ventricles and lateral extension into the left Sylvian fissure and over the anterior clinoid process. An extended modification of the frontotemporal approach was performed using a combined frontotemporal transbasal approach. This allowed wide exposure to both transsylvian and subfrontal corridors to the retrochiasmatic space. This video atlas demonstrates the operative technique and surgical nuances of the skull base approach, microdissection of the tumor, and safe handling of the neurovascular structures. A gross total resection was achieved and the patient was neurologically intact with improved visual acuity. In summary, the combined frontotemporal transbasal approach is an important strategy in the armamentarium for the surgical management of giant Rathke’s cleft cysts. The link to the video can be found at: https://youtu.be/UjhnUZVi03I .

Concepts: Brain, Skull, Cyst, Rathke's pouch, Rathke's cleft cyst

0

Lymphocytic hypophysitis (LH) is a rare inflammatory lesion in sellar region. LH secondary to ruptured Rathke’s cleft cyst (RCC) is even more rarely observed according to published case reports. The clinical characteristics, treatment strategies and prognosis of such lesions remain elusive.

Concepts: Medical terms, Neuroendocrinology, Rathke's pouch