Rathke's Cleft Research Articles

Xanthogranulomatous hypophysitis: a rare and often mistaken pituitary lesion.

SummaryXanthogranulomatous hypophysitis (XGH) is a very rare form of pituitary hypophysitis that may present both clinically and radiologically as a neoplastic lesion. It may either be primary with an autoimmune aetiology and can occur in isolation or as a part of autoimmune systemic disease or secondary as a reactive degenerative response to an epithelial lesion (e.g. craniopharyngioma (CP), Rathke's cleft cyst, germinoma and pituitary adenomas) or as a part of a multiorgan systemic involvement such as tuberculosis, sarcoidosis or granulomatosis. It may also present with a variation of symptoms in children and adults. Our case series compares the paediatric and adult presentations of XGH and the differential diagnoses considered in one child and two adult patients, highlighting the wide spectrum of this condition. Endocrine investigations suggested panhypopituitarism in all three patients and imaging revealed a suprasellar mass compressing the optic chiasm suggestive of CP or Rathke's cleft cyst in one patient and non-functioning pituitary macroadenoma in two patients. Magnetic resonance imaging (MRI) demonstrated mixed signal intensities on T1- and T2-weighted sequences. Following endoscopic transsphenoidal surgery, histological analysis revealed necrotic material with a xanthogranulomatous reaction confirming XGH in two patients and a necrobiotic granulomatous chronic inflammatory infiltrate with neutrophils in one patient, which is not typical of current descriptions of this disorder. This case series describes the wide spectrum of XGH disease that is yet to be defined. Mixed signal intensities on T1- and T2-weighted MRI sequences may indicate XGH and diagnosis is confirmed by histology. Histological variation may indicate an underlying systemic process.Learning points XGH is a rare form of pituitary hypophysitis with a wide clinical and histological spectrum and can mimic a neoplastic lesion.XGH primarily presents with growth arrest in children and pubertal arrest in adolescents. In adults, the presentation may vary.A combination of hypopituitarism and mixed signal intensity lesion on MRI is suggestive of XGH and should be considered in the differential diagnosis of sellar lesions.Radical surgery is the treatment of choice and carries an excellent prognosis with no recurrence.

GH-Producing Pituitary Adenoma and Concomitant Rathke's Cleft Cyst: A Case Report and Short Review.

Concomitant pituitary adenoma (PA) and Rathke's cleft cyst (RCC) are rare. In some cases, such PA is known to produce pituitary hormones. A 53-year-old man was admitted to our hospital with a diagnosis of lacunar infarction in the left basal ganglia. Magnetic resonance imaging (MRI) incidentally showed a suprasellar mass with radiographic features of RCC. When he consulted with a neurosurgical outpatient clinic, acromegaly was suspected based on his appearance. A diagnosis of growth hormone- (GH-) producing PA was confirmed from hormonal examinations and additional MRI. Retrospectively, initial MR images also showed intrasellar mass that is compatible with the diagnosis of PA other than suprasellar RCC. The patient underwent endonasal-endoscopic removal of the PA. Since we judged that the RCC of the patient was asymptomatic, only the PA was completely removed. The postoperative course of the patient was uneventful and GH levels gradually normalized. Only 40 cases of PA with concomitant RCC have been reported to date, including 13 cases of GH-producing PA. In those 13 cases, RCC tended to be located in the sella turcica, and suprasellar RCC like this case appears rare. In a few cases, concomitant RCCs were fenestrated, but GH levels normalized postoperatively as in the cases without RCC fenestration. If radiographic imaging shows typical RCC, and PA is not obvious at first glance, the possibility of concomitant PA still needs to be considered. In terms of treatment, removal of the RCC is not needed to achieve hormone normalization.

Sellar Masses That Present With Severe Hyponatremia

Hyponatremia is a known but underrecognized presentation of sellar lesions. Herein, we present a series of patients who presented with single or multiple episodes of hyponatremia. Over 5 years, patients undergoing endonasal surgery for a de novo sellar mass with hyponatremia as an initial presentation were included. Pathology, sodium levels, pituitary hormonal status, and treatment course were documented. Of 282 patients, 16 (5.7%) (9 males, 7 females, age 32 to 84 years) presented with severe hyponatremia, with a mean serum sodium level of 115 ± 6 mmol/L (range, 101 to 125 mmol/L), and 3 patients had 2 or more episodes. Severe hyponatremia was a presenting sign in 0, 4.1, 14.3, and 37.5% of patients with craniopharyngiomas (n = 10), pituitary adenomas (n = 243), Rathke's cleft cysts (RCCs) (n = 21), and sellar arachnoid cysts (n = 8), respectively (P<.01). Half of the patients presenting with hyponatremia, including 6 of 10 patients with adenomas and 2 of 3 patients with RCCs, had pituitary apoplexy or cyst rupture. All patients had anterior pituitary gland dysfunction, including 81% with hypoadrenalism and 69% with hypothyroidism. Following surgery, hormonal status was unchanged or improved in 15 patients (median follow-up, 14 months). No patient had tumor/cyst recurrence or recurrent hyponatremia. Severe hyponatremia was a presenting sign in 5.7% of patients with sellar pathology, most frequently in patients with arachnoid cysts, RCCs, and pituitary apoplexy. Patients with new-onset severe hyponatremia and no obvious pharmacologic or systemic cause should undergo pituitary hormonal evaluation and brain imaging. Surgical resection and correction of hormonal deficiencies are associated with resolution of recurrent hyponatremic episodes.

Extended endoscopic transsphenoidal approach infrachiasmatic corridor.

An extended endoscopic transsphenoidal approach is required for skull base lesions extending to the suprasellar area. Inferior approach using the infrachiasmatic corridor allows access to the lesions through the tumor growth that is favorable for the extended transsphenoidal approaches. Infrachiasmatic corridor is a safer route for the inferior approaches that is made up by basal arachnoid membrane and Liliequist's membrane with its leaves (diencephalic and mesencephalic leaf). This area extends from the optic canal and tuberculum sella to the corpus mamillare. We performed extended endoscopic approach using the infrachiasmatic corridor in 52 cases, including tuberculum sella meningiomas (n:23), craniopharyngiomas (n:16), suprasellar Rathke's cleft cyst (n:6), pituitary adenoma (n:2), fibrous dysplasia (n:1), infundibular granulosa cell tumor (n:2), and epidermoid tumor (n:2). Total resection was achieved in 17 of 23 (74%) with tuberculum sellae meningioma using infrachiasmatic approach. Twenty patients presented with visual disorders and 14 of them improved. There were two postoperative cerebrospinal fluid (CSF) leakages and one transient diabetes insipidus and one permanent diabetes insipidus. Sixteen patients were operated on by the infrachiasmatic approach for craniopharyngiomas. Improvement was reached in seven of eight patients presented with visual disorders. Complete tumor resection was performed in 10 of 16 cases and cyst aspiration in 4 cases, and there were remnants in two cases. Postoperative CSF leakage was seen in two patients. Infrachiasmatic corridor provides an easier and safer inferior route for the removal of middle midline skull base lesions in selected cases.

OTX2 mutations cause autosomal dominant pattern dystrophy of the retinal pigment epithelium

PurposeTo identify the genetic cause of autosomal-dominant pattern dystrophy (PD) of the retinal pigment epithelium (RPE) in two families.Methods and resultsTwo families with autosomal-dominant PD were identified. Eight members of...

Natural History of Pituitary Incidentalomas: A Canadian Tertiary Care Experience

Pituitary incidentalomas (PI) are frequently encountered during imaging studies. Few studies have examined the epidemiological trends. This retrospective analysis from Dalhousie University (2006 to 2012) includes all PI patients from the Province of Nova Scotia, Canada. One hundred seventy-five patients with PI were identified (99 [57%] females and 76 [43%] males). The mean age was 53.2 years (range 16 to 91 years). The most common indications for the initial diagnostic imaging were dizziness (24%), headache (19%), stroke or transient ischemic attack (15%), and head injury (14%). The initial imaging modalities included CT (38%) and MRI (62%). There were 85 non-functioning adenoma (48.6%), 21 Rathke's cleft cyst (12.0%), 18 prolactinoma (10.3%), 11 empty sella (6.3%), 10 enlarged normal pituitaries (5.7%), 7 craniopharyngiomas (4.0%), 6 acromegaly (3.4%), 6 pituitary cyst (3.4%), 5 Cushing's disease (2.9%), 3 meningioma (1.7%), 2 arachnoid cyst (1.1%) and 1 TSH producing adenoma (0.6%). There were 82 (71.3%) macroadenomas and 25 (21.7%) microadenomas. Size measurements were unavailable in 7.0%. Thirty (17%) of all PI were functioning adenomas. Thirty-nine (22%) patients on presentation had at least 1 hormonal deficiency. Of these, secondary hypogonadism occurred in 77%, secondary hypothyroidism in 46%, low IGF1 levels in 23%, secondary adrenal insufficiency in 23% and diabetes insipidus in 2.5%. Fifty-one (29%) patients underwent pituitary surgery. The most common indications for surgery were visual field abnormalities (29%), tumour growth (14%) and proximity to the optic chiasm (6%). Our data suggest that patients with PI require thorough hormonal workup at diagnosis and regular follow up.

Rare Case of Severe Visual Compromise Due to a Symptomatic Rathke Cleft Cyst

Dear Editor, Rathke’s cleft cysts (RCCs) originate from Rathke’s pouch1, an epithelialized rostral invagination of the stomadeum. The Rathke’s pouch has an anterior and posterior wall in addition to a central embryonic cleft . The central lumen becomes the Rathke cleft , and normally regresses.2 However, this structure may persist and enlarge, resulting in the formation of a cyst. RCCs are usually asymptomatic, in rare cases secondary to lesional compression visual disturbances, hypopituitarism, headache and dizziness can occur.1 We present a patient with bilateral gross visual compromise, due to compression by a RCC; however the pituitary hormonal profi le was surprisingly normal.

Rathke's Cleft Cysts- Review of Two Cases

Rathke's Cleft Cysts- Review of Two Cases

English

Neonates may present with various causes of stridor. Nasopharyngeal cysts are rare congenital lesions causing difficulty in breathing. Differential diagnosis of nasopharyngeal cysts include thornwalds cyst, rathke cleft and craniopharyngioma, teratoma, epidemoid cysts, dermoid cyst, nasopharyngeal encephalocele, infected cyst and branchial cyst. Though branchial cysts are very rarely present in nasopharynx, they are easy to diagnose on MRI and fall under the category of preventable causes of neonatal stridor. Their surgical excision is the treatment of choice but sometimes owing to the other prematurities present the neonate period is not always the best time to operate. We report a case of a newborn child with nasopharyngeal branchial cyst presenting with stridor and managed conservatively with aspiration.

Morbidity of repeat transsphenoidal surgery assessed in more than 1000 operations.

OBJECT.: While transsphenoidal surgery is associated with low morbidity, the degree to which morbidity increases after reoperation remains unclear. The authors determined the morbidity associated with repeat versus initial transsphenoidal surgery after 1015 consecutive operations. The authors conducted a 5-year retrospective review of the first 916 patients undergoing transsphenoidal surgery at their institution after a pituitary center of expertise was established, and they analyzed morbidities. The authors analyzed 907 initial and 108 repeat transsphenoidal surgeries performed in 916 patients (9 initial surgeries performed outside the authors' center were excluded). The most common diagnoses were endocrine inactive (30%) or active (36%) adenomas, Rathke's cleft cysts (10%), and craniopharyngioma (3%). Morbidity of initial surgery versus reoperation included diabetes insipidus ([DI] 16% vs 26%; p = 0.03), postoperative hyponatremia (20% vs 16%; p = 0.3), new postoperative hypopituitarism (5% vs 8%; p = 0.3), CSF leak requiring repair (1% vs 4%; p = 0.04), meningitis (0.4% vs 3%; p = 0.02), and length of stay ([LOS] 2.8 vs 4.5 days; p = 0.006). Of intraoperative parameters and postoperative morbidities, 1) some (use of lumbar drain and new postoperative hypopituitarism) did not increase with second or subsequent reoperations (p = 0.3-0.9); 2) some (DI and meningitis) increased upon second surgery (p = 0.02-0.04) but did not continue to increase for subsequent reoperations (p = 0.3-0.9); 3) some (LOS) increased upon second surgery and increased again for subsequent reoperations (p < 0.001); and 4) some (postoperative hyponatremia and CSF leak requiring repair) did not increase upon second surgery (p = 0.3) but went on to increase upon subsequent reoperations (p = 0.001-0.02). Multivariate analysis revealed that operation number, but not sex, age, pathology, radiation therapy, or lesion size, increased the risk of CSF leak, meningitis, and increased LOS. Separate analysis of initial versus repeat transsphenoidal surgery on the 2 most common benign pituitary lesions, pituitary adenomas and Rathke's cleft cysts, revealed that the increased incidence of DI and CSF leak requiring repair seen when all pathologies were combined remained significant when analyzing only pituitary adenomas and Rathke's cleft cysts (DI, 13% vs 35% [p = 0.001]; and CSF leak, 0.3% vs 9% [p = 0.0009]). Repeat transsphenoidal surgery was associated with somewhat more frequent postoperative DI, meningitis, CSF leak requiring repair, and greater LOS than the low morbidity characterizing initial transsphenoidal surgery. These results provide a framework for neurosurgeons in discussing reoperation for pituitary disease with their patients.

A 15-year-old adolescent with a rare pituitary lesion.

SummaryCystic sellar lesions are a rare cause of hypopituitarism and extremely rare in the pediatric age group. The differential diagnosis is large and includes both primary pituitary abscesses and cystic components on pre-existing lesions, such as adenoma, craniopharyngioma, Rathke's cleft cyst, leukemia, granulomatous disease and lymphocytic hypophysitis. In the absence of a definitive diagnosis, treatment can be challenging. We report a case of a 15-year-old female, who presented with headaches, altered consciousness and diplopia after a molar extraction, for which she had received oral antibiotics. Broad-spectrum i.v. antibiotics were given for presumed meningitis. Blood cultures failed to identify pathogens. Cerebral magnetic resonance imaging showed a pituitary cystic lesion. Endocrine studies revealed abnormal pituitary function. In the absence of a therapeutic response, the patient underwent a transsphenoidal biopsy of the pituitary gland, which yielded a purulent liquid, but cultures were negative. Histopathology showed lymphocytic infiltrates but no neutrophils, compatible with an inflammation of autoimmune or infectious origin. High-dose glucocorticoid therapy was started and pursued, along with i.v. antibiotics, for 6 weeks, leading to clinical and radiological improvement but with persistence of endocrine deficits. In conclusion, this is a case of secondary panhypopituitarism due to a cystic pituitary lesion, with a differential diagnosis of lymphocytic hypophysitis vs abscess in a context of decapitated meningitis. Combination therapy with antibiotics and glucocorticoids is a legitimate approach in the face of diagnostic uncertainty, given the morbidity, and even mortality, associated with these lesions.Learning points It is not always easy to differentiate primary cystic sellar lesions (such as a primary infectious pituitary abscess) from cystic components on pre-existing lesions (such as adenoma, craniopharyngioma, Rathke's cleft cyst, leukemia or lymphocytic hypophysitis).Because of the absence of specific symptoms and of immunohistochemical and serum markers, response to glucocorticoids can be the only way to differentiate lymphocytic hypophysitis from pituitary lesions of another origin. In addition, microbiological cultures are negative in 50% of cases of primary infectious sellar abscesses, thus the response to antibiotic treatment is often the key element to this diagnosis.A short course of high-dose glucocorticoids combined with antibiotics is not harmful in cases where there is no diagnostic certainty as to the origin of a cystic sellar mass, given the morbidity and mortality associated with these lesions.This approach may also diminish inflammation of either infectious or autoimmune origin while ensuring that the most likely pathogens are being targeted.

Cysto-Sphenoid Stenting for Rathke's Cleft Cysts

Objectives: To describe a technique to prevent reaccumulation of Rathke's Cleft Cysts (RCC) after endoscopic endonasal surgery.

A Case of Rathke's Cleft Cyst Associated with Transient Central Adrenal Insufficiency and Masked Diabetes Insipidus.

A 73-year-old woman admitted to our hospital because of headache, poor appetite, malaise, weight loss, and vomiting was found to have central adrenal insufficiency and thyrotoxicosis due to silent thyroiditis. Polyuria developed after replacement with glucocorticoid (masked diabetes insipidus), which was controlled with nasal administration of desmopressin. Magnetic resonance imaging of the brain showed a large cystic pituitary mass (18 × 18 × 12 mm) extending suprasellarly to the optic chiasm. Transsphenoidal surgery revealed that the pituitary tumor was Rathke's cleft cyst. Following surgery, replacement with neither glucocorticoid nor desmopressin was needed any more. Therefore, it is suggested that Rathke's cleft cyst is responsible for the masked diabetes insipidus and the central insufficiency. Furthermore, it is speculated that thyrotoxicosis with painless thyroiditis might induce changes from subclinical adrenal insufficiency to transiently overt insufficiency.

Bilateral acute visual loss from Rathke's cleft cyst apoplexy in a patient with dengue fever.

Hemorrhagic complications of optic pathway diseases are extremely rare causes of acute visual loss associated with dengue fever. In this paper we report a patient presenting with dengue fever and bilateral acute visual loss caused by chiasmal compression due to Rathke's cleft cyst apoplexy. Considering the importance of early diagnosis and treatment to visual recovery, apoplexy of sellar and suprasellar tumors should be considered in the differential diagnosis of patients with acute visual loss and dengue fever.

Clinical and radiological findings of incidental Rathke's cleft cysts in children and adolescents.

PurposeIn the pediatric population, Rathke's cleft cysts (RCCs) are known to be an infrequent cause of headaches, visual disturbances, and pituitary dysfunction. We investigated the clinical characteristics of children in whom RCCs were incidentally discovered and evaluated whether RCCs influence the treatment response of patients with proven endocrinopathy.MethodsA retrospective analysis was conducted in 34 patients with RCCs who were diagnosed between 2006 and 2013 at Hallym University Medical Center. Their clinical, hormonal, and imaging findings were reviewed. We evaluated the clinical outcomes of the patients with concomitant RCCs and endocrinopathy compared to matched controls.ResultsTwenty-six of 34 patients with radiologically proven RCCs had endocrine disorders. They were 9 boys and 17 girls, with ages ranging from 4.8 to 17.4 years at the time of the diagnosis. Of these, 7 (27%) had idiopathic short stature, 7 (27%) had growth hormone deficiency (GHD), and 12 (46%) had central precocious puberty (CPP). Nineteen of 26 patients (73.1%) showed low signal intensities on T1-weighted images (T1WI) and high signal intensities on T2-weighted images. The incidence of hypointensity on T1WI was higher in the patients with RCCs accompanied by endocrinopathy than in those without endocrinopathy (P=0.033). The treatment outcomes of the patients with CPP and GHD with and without RCCs were similar.ConclusionCPP and GHD patients with a small RCC (less than 20 mm) expressing cystic magnetic resonance intensity can be managed with medical treatment, although the RCCs need to be closely monitored in radiological studies to observe their growth.

Optic Neuritis Caused by Rathke's Cleft Cyst in Young Adult.

We report a case of right optic neuritis caused by Rathke's cleft cyst (RCC) in a young adult. A 15-year-old boy presented with reduced visual acuity in the right eye. He was diagnosed with optic neuritis in the right eye 4 years earlier at other clinics before he was referred to our department. During our one-year examinations, the cause of the reduced vision in his right eye could not be determined conclusively. At the age of 17 years, a RCC was detected by a neurosurgeon who specialized in hypophyseal diseases. He underwent microscopic transsphenoidal resection of the cyst, and his vision recovered to 1.2 and he has had no recurrence for at least 9 months. We suggest that repeated rupturing of the RCC was the cause of the optic neuritis, and a RCC can be successfully treated by surgery even after 3 years of optic neuritis.

Clinicopathologic Analysis of Pituitary Adenoma: A Single Institute Experience

Pituitary adenoma (PA) is a common benign neuroendocrine tumor; however, the incidence and proportion of hormone-producing PAs in Korean patients remain unknown. Authors analyzed 506 surgically resected and pathologically proven pituitary lesions of the Seoul National University Hospital from 2006 to 2011. The lesions were categorized as: PAs (n = 422, 83.4%), Rathke's cleft cysts (RCCs) (n = 54, 10.6%), inflammatory lesions (n = 8, 1.6%), meningiomas (n = 4), craniopharyngiomas (n = 4), granular cell tumors (n = 1), metastatic renal cell carcinomas (n = 2), germinomas (n = 1), ependymomas (n = 1), and unsatisfactory specimens (n = 9, 1.8%). PAs were slightly more prevalent in women (M: F = 1:1.17) with a mean age of 48.8 yr (9-80 yr). Immunohistochemical analysis revealed that prolactin-producing PAs (16.6%) and growth hormone-producing adenomas (9.2%) were the most common functional PAs. Plurihormonal PAs and nonfunctioning (null cell) adenomas were found in 14.9% and 42.4% of patients with PAs, respectively. The recurrence rate of PAs was 11.1%, but nearly 0% for the remaining benign lesions such as RCCs. 25.4% of patients with PAs were treated by gamma-knife after surgery due to residual tumors or regrowth of residual tumor. In conclusion, the pituitary lesions and the proportions of hormone-producing PAs in Korean patients are similar to those of previous reports except nonfunctioning (null cell) PAs, which are unusually frequent.

A modified combined transseptal/transnasal binostril approach for pituitary lesions in patients with a narrow nasal space: technical note.

We describe a modification of the combined transseptal/transnasal binostril approach using a two-surgeon, four-handed technique (modified Stamm's approach) for pituitary lesions in patients with narrow nasal spaces. This approach comprises of a transseptal route through one nostril and a transnasal route without harvesting a pedicled nasoseptal flap (NSF) through the other. On the transseptal side, the nasal septum was removed using an endoscopic septoplasty technique. On the transnasal side, the mucosa containing the septal branch of the sphenopalatine artery over the face of the sphenoid and nasal septum was preserved for harvesting the NSF if an intraoperative cerebrospinal fluid leak was encountered. This approach was performed in six patients with pituitary lesions, including four nonfunctioning macroadenomas, one growth hormone-producing macroadenoma, and one Rathke's cleft cyst, all of which were associated with a severe deviation of the nasal septum and/or narrow nasal space. The meticulous and comfortable manipulation of an endoscope and instruments were achieved in all six patients without surgical complications. Our findings, although obtained in a limited number of cases, suggest that the modified Stamm's approach may be useful for selected patients, particularly those with a severe deviation of the nasal septum, without considerable damage to the nasal passages.

Dynamics of the dynamic enhancement in a suprasellar lesion: Diagnostic dilemmas and literature review

Brain tumors with high vascularity show dynamic enhancement on magnetic resonance contrast imaging owing to their rapid blood flow. This principle is used to differentiate highly vascular lesions in sellar/suprasellar area from the non-vascular or mildly vascular ones. We report a case of suprasellar lesion affecting a 35-year-old female, lesion exhibiting dynamic enhancement on contrast magnetic resonance imaging. The imaging and intra-operative findings have created a diagnostic dilemma about the nature of the lesion and the histopathology revealed it to be a Rathke's cleft cysts (R.C.C). R.C.C have varied imaging manifestations. They can create diagnostic dilemma in a surgeon's mind when they present with such extremes of variations including dynamic contrast enhancement. One should be aware of these atypical imaging findings before approaching these lesions at surgery for an optimal outcome.

A Case of Presumably Rathke’s Cleft Cyst Associated with Postoperative Cerebrospinal Fluid Leakage through Persisting Embryonal Infundibular Recess

Persisting embryonal infundibular recess (PEIR) is a rare anomaly of the third ventricular floor. Only eight cases have been published. In this report, a case of presumably Rathke's cleft cyst associated with cerebrospinal fluid leakage caused by PEIR is described. An 81-year-old woman underwent endoscopic transsphenoidal surgery for the intra- and supra-sellar cystic lesion. Intraoperatively a hole was confirmed over the sella turcica connecting the sellar cyst and the infundibular recess. Liquorrhea did not occur throughout the procedure. A computed tomography (CT) scan obtained immediately after surgery disclosed accumulation of air in the third and lateral ventricles, in addition to the intra- and supra-sellar region. Air accumulation resolved spontaneously after bed rest for 11 days and she was discharged without neurological deficits. However, she required the second transsphenoidal surgery to repair the sellar floor because of bacterial meningitis caused by liquorrhea on the postoperative day 23. A postoperative 3-tesla magnetic resonance image revealed a deep infundibular recess connecting the sella turcica and the third ventricle, which was considered to be PEIR. To the best our knowledge, this is the first reported case describing the intraoperative findings of PEIR.