Rathke's cleft cyst apoplexy in a boy treated by endoscopic endonasal surgery: case report and literature review.

Rathke's cleft cyst (RCC) apoplexy is an uncommon lesion attributed to abnormal vascular supply to the fragile RCC epithelial wall. It is rare in children and very difficult to diagnose without pathologic confirmation. Here, we report an 8-year-old boy who presented with headache and visual deficit. MRI and CT showed a cystic mass in the sellar region. He underwent endoscopic endonasal surgery, and the cystic mass was resected completely via a trans-sphenoidal approach. The lesion was confirmed as RCC apoplexy by intraoperative observation and histopathological examination. Headache was completely relieved and the visual field deficit improved remarkably after the operation. The authors recommend surgical management for pediatric RCC apoplexy patients who present with severe neuro-ophthalmic signs or deterioration of consciousness, although there are at present no standardized management guidelines for pediatric RCC apoplexy.

The 1 µg Synacthen stimulation test in the diagnosis of secondary adrenal insufficiency in patients with Rathke's cleft cyst and empty sella syndrome.

INTRODUCTION: Rathke's cleft cyst (RCC) and primary empty sella syndrome (PESS) are usually incidental findings on magnetic resonance imaging (MRI) scans. In most cases, these lesions do not cause mass effect symptoms and do not require surgical intervention. In patients with RCC or PESS, it is important to exclude secondary adrenal insufficiency (SAI), which may be a life-threatening condition. MATERIAL AND METHODS: The incidence of SAI was assessed in patients with RCC or PESS detected by MRI, using the 1 µg Synacthen stimulation test. A total of 38 patients were analysed. Test results were linked to clinical symptoms and the type of cystic lesion. RESULTS: Assuming that cortisol levels < 14.6 µg/dL in Synacthen test are the criterion of SAI diagnosis, SAI was diagnosed only in 2 patients (5%). Adopting the traditional criterion of cortisol levels < 18 µg/dL, SAI would be diagnosed in 7 patients (18.4 %). Dizziness (Chi2 = 3.89; p = 0.049) and apathy (Chi2 = 3.87; p = 0.049) were significantly more frequent in the PESS group than in the RCC group. CONCLUSIONS: The incidence of SAI in the general patient population with empty sella syndrome and Rathke's cleft cysts is low. The 1 µg Synacthen test seems to be a valuable tool in the diagnosis of SAI among patients with RCC and PESS. Further studies are necessary to determine the sensitivity and specificity of the 1 µg Synacthen test with the standardization of test protocol and considering the cortisol level at the 20-minute timepoint. PESS patients report dizziness and apathy more frequently than RCC patients, which does not result from the disturbance of the hypothalamic-pituitary-adrenal axis, but probably from the different pathogenesis of these cystic lesions.

Rathke's cleft cyst discovered with ruptured anterior communicating artery aneurysm: a case report.

INTRODUCTION: Rathke's cleft cysts are thought to have a benign clinical outcome apart from associated hypopituitarism and visual defects. Synchronous central nervous system lesions, including pituitary adenoma and intracerebral aneurysms, are rarely reported. Diagnosis of Rathke's cleft cyst after presenting with a subarachnoid hemorrhage due to a ruptured arterial aneurysm is reported only once before. CASE PRESENTATION: A 33-year-old Sri Lankan female presented with a subarachnoid hemorrhage due to a ruptured anterior communication artery aneurysm. She underwent pterional craniotomy and aneurysm clipping. She was found to have partial cranial diabetes insipidus and hypogonadotropic hypogonadism. She had a cystic lesion occupying enlarged sella turcica with characteristics of a Rathke's cleft cyst. Subsequently, she underwent trans-sphenoidal excision of the sellar lesion. Histology confirmed the diagnosis of Rathke's cleft cyst. CONCLUSIONS: Rare co-occurrence of a Rathke's cleft cyst and an anterior communicating artery aneurysm would have been missed if subtle manifestations atypical for subarachnoid hemorrhage were not further pursued. This could have led to progressive visual deterioration and hypopituitarism.

Rapidly recurrent recalcitrant Rathke Cleft Cyst: Case report and review of the literature.

BACKGROUND: Rathke Cleft Cysts (RCC) are cystic sellar or suprasellar nonneoplastic lesions that are thought to originate from remnants of the rathke pouch. Postoperatively, RCCs have a tendency to reaccumulate, after which preoperative symptoms may recur. However, there exists very little evidence on which treatments are most effective in these patients. CASE-DESCRIPTION: In this report, we present a unique case of a symptomatic RCC that recurred four times after initial transsphenoidal surgery. Following each surgery, the patient had significant visual improvement with post-op imaging displaying decompression of the neural elements. However, RCC reaccumulated in strikingly rapid time intervals of 1.5 months, 0.5 months, 1.5 years, and 5 months after each respective prior surgery. Repeat interventions with transsphenoidal, pterional and supraorbital approaches were unsuccessful in providing a durable treatment response. The patient ultimately underwent radiotherapy after a final surgical marsupialization of the cyst and has since displayed stable imaging with improved vision. This patient represented a 'perfect storm' of factors that may contribute to cyst recurrence, including substantial visual field deficits, large cyst size, peripheral wall enhancements on MRI, an intraoperative CSF leak, use of a fat graft, subtotal resection of the portion of cyst wall that adhered to important suprasellar structures, squamous metaplasia noted in cyst wall, and suprasellar extension. CONCLUSIONS: We demonstrate that different surgical approaches through repeat surgeries may not assist in prevention of further recurrence; instead, we propose that radiotherapy should be offered early in the treatment course of recurrent cases that have additional risk factors for further reoccurrence.

Approach to the Patient: Differential Diagnosis of Cystic Sellar Lesions.

Cystic lesions arising in the sellar region are not uncommon and encompass cystic pituitary adenomas, Rathke cleft cysts, craniopharyngiomas, and arachnoid cysts. Their clinical presentation may be similar, including headache, visual field defects, and anterior pituitary hormone deficits, which makes differential diagnosis challenging. On the other hand, imaging features may indicate certain pathologies. In this approach to the patient, we describe the case of a patient who presented with right temporal hemianopsia and a sellar/suprasellar cystic lesion, which was determined to be Rathke cleft cyst. We discuss the imaging characteristics that may suggest a particular diagnosis between Rathke cleft cyst, cystic pituitary adenoma, craniopharyngioma, and arachnoid cyst and propose a flowchart for aiding in the imaging differential diagnosis.

Central Diabetes Insipidus after Syndrome of Inappropriate Antidiuretic Hormone Secretion with Severe Hyponatremia in a Patient with Rathke's Cleft Cyst.

A 49-year-old man developed severe hyponatremia associated with transient headache and was diagnosed with syndrome of inappropriate antidiuretic hormone secretion (SIADH). Fluid restriction and sodium supplementation corrected the hyponatremia. However, several days later, the patient exhibited hypernatremia with thirst and polyuria. A detailed examination indicated central diabetes insipidus (CDI) with an intrasellar cystic lesion indicative of Rathke's cleft cyst (RCC). A case of RCC exhibiting headache, hyponatremia, and subsequent hypernatremia has been reported. Our case shows that CDI may appear after SIADH in patients with RCC, especially in those with serum sodium levels that unexpectedly increase rapidly beyond the reference range.

Suprasellar Mature Cystic Teratoma Mimicking Rathke's Cleft Cyst: A Case Report and Systematic Review of the Literature.

In this article, we present a 31-year-old female who presented with intermittent headache and oligomenorrhea of over 10 years' duration. Imaging revealed a large suprasellar mass with sellar extension. The patient underwent an endoscopic endonasal trans-sphenoidal surgery to resection of the mass. Clinical, radiological, and operative findings from this patient were initially considered to be Rathke's cleft cyst (RCC). However, postoperative histological examinations revealed a mature cystic teratoma. No radiotherapy was performed after surgery. At the most recent follow-up, approximately 1 year later, the patient is doing well with no headache and no recurrence of the teratoma.

Novel compound heterozygous STN1 variants are associated with Coats Plus syndrome.

AIM: Coats plus syndrome (CP) is a rare autosomal recessive disorder, characterised by retinal telangiectasia exudates (Coats disease), leukodystrophy, distinctive intracranial calcification and cysts, as well as extra-neurological features including abnormal vasculature of the gastrointestinal tract, portal hypertension and osteopenia with a tendency to fractures. CP most frequently occurs due to loss-of-function mutations in CTC1. The encoded protein CTC1 constitutes part of the CST (CTC1-STN1-TEN1) complex, and three patients have been described with CP due to biallelic mutations in STN1. Together with the identification of homozygosity for a specific loss-of-function mutation in POT1 in a sibling pair, these observations highlight a defect in the maintenance of telomere integrity as the cause of CP, although the precise mechanism leading to the micro-vasculopathy seen at a pathological level remains unclear. Here, we present the investigation of a fourth child who presented to us with retinal exudates, intracranial calcifications and developmental delay, in keeping with a diagnosis of CP, and later went on to develop pancytopenia and gastrointestinal bleeding. Genome sequencing revealed compound heterozygous variants in STN1 as the likely genetic cause of CP in this present case. METHODS: We assessed the phenotype to be CP and undertook targeted sequencing. RESULTS: Whilst sequencing of CTC1 and POT1 was normal, we identified novel compound heterozygous variants in STN1 (previous gene symbol OBFC1): one loss-of-function--c.894dup (p.(Asp299Argfs*58)); and one missense--c.707T>C (p.(Leu236Pro)). CONCLUSION: Given the clinical phenotype and identified variants we suggest that this is only the fourth patient reported to date with CP due to mutations in STN1.

Professor Rathke's gift to neurosurgery: the cyst, its diagnosis, surgical management, and outcomes.

PURPOSE: Rathke cleft cysts (RCC) are a target for transsphenoidal surgery when symptomatic; however, the surgical techniques and outcomes continue to be of interest. Our goal is to highlight nuances in diagnosis, surgical philosophy and techniques, and outcomes. METHODS: We retrospectively reviewed a single surgeon experience in a contemporary series of RCC from April 2008 through December 2019. The clinical presentation, radiographic studies, intraoperative findings, histopathological diagnosis, postoperative complications, and outcome data were recorded and analyzed. RESULTS: A total of 131 endoscopic endonasal operations were performed on 116 patients (30 male, 86 female), with an average age of 39 years. We identified 102 patients without prior surgery, and 14 patients with prior surgery elsewhere. Postoperative complications included transient diabetes insipidus (DI) (n = 23, 20%), permanent DI (n = 5, 4%), SIADH (n = 6, 5%), epistaxis (n = 6, 5%), postoperative infection (n = 3, 2.5%), postoperative CSF leak (n = 1, < 1%), intrasellar hematoma (n = 1, < 1%), and stroke (n = 1, < 1%). Visual improvement was observed in 74% (n = 31/42) of patients presenting with visual loss, and headache improvement in 86% (n = 80/93). Overall, the recurrence rate in our cohort was 11%, with a lower recurrence rate seen in males (p = 0.02). The median follow-up duration was 15.2 months (interquartile range 1.7-52.3) CONCLUSION: Our results reflect the philosophy of a conservative surgical approach, designed to preserve normal pituitary function, and avoid DI, while achieving the maximal feasible resection. Evacuation of the cyst contents and meticulous sampling of the cyst wall when possible for histopathological diagnosis are crucial. The postoperative relief of symptoms and signs is gratifying, as are the overall rates of recurrence and outcomes.

Rathke's cleft cyst infections and pituitary abscesses: case series and review of the literature.

PURPOSE: Pituitary abscesses (PAs) are a rare clinical entity which may arise from normal pituitary tissue or underlying lesions within the gland. Rathke's cleft cysts (RCCs) are not commonly associated with the development of PA. METHODS: Retrospective chart review of three patients with PAs within RCCs at a single university center and review of the literature. RESULTS: Three cases are reported. The first case presented with fever and headache and a history of prior surgery due to RCC and a recent respiratory tract infection. The second case had a history of recent skin infections and presented with sudden onset headache and hypopituitarism. In the third case, chronic visual field impairment prompted an ophthalmologic evaluation resulting in a diagnosis of an adenoma and an infected RCC. In all three cases, an endoscopic endonasal approach was performed to drain infected tissue and allowed microbiological identification of gram-positive cocci, followed by treatment with antibiotics for at least three weeks. Cases in the literature are scarce and the diagnosis is usually made intraoperatively due to non-specific manifestations and imaging. PAs arising from underlying pituitary lesions are less common than primary PAs. Differential diagnosis should include pituitary apoplexy, hypophysitis and other cystic lesions. CONCLUSION: PAs occurring in RCCs are infrequent. Clinical manifestations are commonly subacute, without septic symptoms. Imaging is usually non-specific. Preoperative diagnosis is infrequent and a broad differential diagnosis should be considered. Empirical antimicrobial therapy should be initiated and adjusted after obtaining cultures to reduce the rate of recurrence and improve clinical outcomes.

[Rathke's cleft cyst in a middle-aged man with chief complaint of depression : A case report and literature review].

OBJECTIVE: To present a case of Rathke's cleft cyst (RCC) in a middle-aged man complaining of depression and review the relevant literature. METHODS: A 51-year-old man firstly visited the outpatient clinic of neurology in our hospital due to 4 years of low mood. The patient was found normal in physical and thyroid function laboratory examinations and achieved a total score of 19 in Hamilton Depression Scale, which indicated depression. After failure to respond to antidepressant medication, the patient again came to the clinic of andrology and was found with sexual dysfunction and aspermia. With the serum FSH, LH, PRL, T and fasting blood glucose levels of 0.88 IU/L, 0.25 IU/L, 30.8 nmol/L, <0.24 nmol/L and 3.9 nmol/L respectively, it was considered to be a case of hypogonadotropic hypogonadism. Pituitary MRI indicated RCC but the adreno-cortico-tropic hormone and growth hormone were normal. All the data obtained led to the final diagnosis of RCC, acquired hypogonadotropic hypogonadism, depression and acquired aspermia and therefore the patient was referred to the department of neurosurgery and underwent navigation- and endoscopy-guided microsurgical resection of the Rathke cleft cyst via the nasopharynx and sella region in 2018. RESULTS: RCC was pathologically confirmed postoperatively. At 3 months after surgery, the patient was found with a serum T level of 0.72 nmol/L and received the testosterone replacement therapy. After 3 months of treatment, the serum T was increased to 10.3 nmol/L, the patient's symptoms of depression, hyposexuality and sexual dysfunction were significantly improved, and a little semen was observed in the ejaculate. CONCLUSIONS: RCC is one of causes of hypogonadism in middle-aged men, causing the clinical symptoms mainly by pressing the pituitary gland and inducing gonadotropin deficiency. It is hard for RCC patients with depression and sexual dysfunction to restore gonadotropin to normal even after surgical removal of the cyst and therefore testosterone replacement therapy is necessitated postoperatively.

Cushing's Syndrome in a Patient With Rathke's Cleft Cyst and ACTH Cell Hyperplasia Detected by 11C-Methionine PET Imaging-A Case Presentation.

Background: Adrenocorticotropic Hormone (ACTH)-dependent Cushing's Syndrome (CS) is most often caused by a pituitary adenoma. Although rarely, it can also result from pituitary corticotroph cell hyperplasia (CH). Reports on concomitant pituitary lesions including ACTH-producing adenomas and Rathke's cleft cysts (RCCs) have been published. Positron emission tomography (PET), using 11C-labelled-methionine (MET) as a tracer and co-registered with magnetic resonance imaging (MRI) has been shown to be useful in the diagnosis of pituitary collision lesions, however, its role is still under investigation. In this work we present the case of a patient in whom CS was caused by non-adenomatous CH within the wall of an RCC. Case Summary: In 2015 a patient with signs and symptoms of CS was referred to our Department. Biochemical studies repeatedly showed elevated midnight serum cortisol and ACTH levels. Magnetic resonance imaging of the sellar region revealed an RCC and MET-PET/MR showed heterogeneous labelled-methionine metabolism in the vicinity of the cyst's wall. Transsphenoidal surgery resulted in rapid, complete and lasting relief of symptoms. Histopathological examination demonstrated an RCC and CH. Conclusions: Concomitance of pituitary focal lesions is a rare phenomenon. Methionine-labelled PET/MR may be useful in the diagnosis of collision sellar lesions, including CH. Corticotroph cell hyperplasia can present as mild and fluctuating hypercortisolaemia.

Sellar Pathologies Mimicking Pituitary Tumors.

The most common sellar pathology that merits neurosurgical attention is the pituitary adenoma. However, some developmental, inflammatory, and neoplastic lesions may primarily or secondarily involve the sella, mimicking pituitary tumors. Advances in imaging and endocrinological assessment have helped in the recognition of these less common sellar, supra sellar pathologies, which may occasionally create confusion in management. The most common developmental anomaly is the Rathke's cleft cyst and an increasingly recognized inflammatory pathology is the spectrum of hypophysitis. Neoplasms, viz. Craniopharyngioma, Germinoma, Langerhans's cell histiocytosis or metastasis, have more distinctive features in various age groups and are more likely to be correctly diagnosed on current imaging and managed accordingly. This review looks at mainly intraparenchymal pathologies, namely Rathke's Cleft Cyst and various hypophysitides, and will discuss their management strategies.

Sellar Tumors.

Sellar region lesions include a broad range of benign and malignant neoplastic as well as non-neoplastic entities, many of which are newly described or have recently revised nomenclature. In contrast to other intracranial sites, imaging features are relatively less specific, and the need for histopathological diagnosis is of paramount importance. This review will describe pituitary adenomas, inflammatory lesions, and tumors unique to the region (craniopharyngioma) as well as tumors which may occur in but are not exclusively localized to the sellar location (schwannoma, metastasis, etc.).

Rathke's cleft cyst presenting as incomplete cavernous sinus syndrome and disc edema: a case report with literature review.

PURPOSE: To report a Rathke's cleft cyst (RCC) presenting as unilateral incomplete cavernous sinus syndrome and disc edema METHOD: Case report with literature review RESULTS: We present an 18-year-old girl who has been experiencing intermittent binocular diplopia for 1 month. Upon examination, the best corrected visual acuity was 20/20 (OU). Pronounced limitation of ocular motility with ptosis in her right eye was noted. Her pupil constricted normally. However, a relative afferent pupillary defect in the right eye was observed. Fundus examination showed disc edema in the right eye without peripapillary hemorrhage. Moreover, her thyroid function and acetylcholine receptor antibody levels were normal. Brain magnetic resonance imaging revealed a 1.6-cm mass at the suprasellar fossa and optic nerve sheath of right eye enhancement. She underwent transsphenoidal surgery, and pus-like formation was noted. Pathological findings were consistent with RCCs. After the cyst was removed, her ocular motility remarkably improved and ptosis subsided. CONCLUSION: A case of RCC presenting as multiple cranial nerve palsy was reported. RCCs are benign and usually asymptomatic. Symptomatic RCCs often manifest as headache or visual problems, such as reduced visual acuity and visual field defect. Multiple cranial nerve involvement is uncommon and indicates inflammation or compression of the cavernous sinus and optic nerve. Neuropathy may resolve after surgery; therefore, surgery is indicated for symptomatic RCCs. Further, RCC should be included in the differential diagnosis of patients with disc edema.

Cystic sellar salivary gland-like lesions.

INTRODUCTION: Cystic sellar salivary gland-like lesions (CSSLs) are exceedingly rare, with fewer than a dozen case reports. They contain amorphous colloid identical to Rathke cleft cyst contents, but the cyst wall additionally shows cohesive aggregates of benign salivary glands. We report three new examples. MATERIALS AND METHODS: Two cases were seen at University of Colorado Denver and one at Memorial Sloan Kettering (MSK). Molecular testing was attempted on two of three. RESULTS: Case 1 is a 20-year-old female who presented with panhypopituitarism and was found to have a suprasellar mass that proved to be a CSSL. She received no postoperative adjuvant therapy, but recurrence of headaches and blurred vision 2 years later prompted return to medical attention. A much smaller local cyst recurrence was now accompanied by a thickened, bulbous infundibular stalk. Second resection yielded a gliotic infundibular stalk and amorphous mucin, but no residual salivary-like glands. She is without further recurrence on 6-year follow-up. Case 2 is a 29-year-old female with headache; while seen initially at a tertiary care center, diagnosis was only made after consultation at MSK. Case 3 is 68-year-old female who had originally presented with apoplexy to an outside hospital 7 years prior to surgery and diagnosis. Molecular testing was uninformative on case 1 and negative for mutations or fusions on case 3. CONCLUSION: Few pathologists or neuropathologists have encountered CSSLs in their practices; case 1 produced recurrence and significant infundibular stalk damage, and case 3 originally manifested apoplexy, features not previously reported.

Leukoencephalopathy with calcifications and cysts (LCC): 5 cases and literature review.

INTRODUCTION: Leukoencephalopathy with calcifications and cysts (LCC) is a rare autosomal recessive cerebral angiomatous-like microangiopathy characterized by diffuse and asymmetric white-matter lesions associated with multiple calcifications and cysts. The disease is caused by SNORD118 mutations. The entire clinical spectrum of LCC is not yet fully determined. MATERIAL AND METHODS: To define the clinical spectrum of LCC, we analyzed data from recently diagnosed cases and from the litterature. Both clinical and imaging features from our five LCC cases harboring compound heterozygous SNORD118 mutations were presented and all cases reported in the litterature reviewed. RESULTS: Ninety-two LCC cases including our five patients were identified. Consanguinity was rare (4%), and 97% of cases were symptomatic. Mean age of first clinical manifestations was 16.1±16.1 years (range 1 month-71 years) and was earlier in men (10.3±14.3 years) than in women (20.2±22.8 years) (P=0.02). The main inaugural symptoms were seizures (36%; mean age at onset: 5.2±9.5 years) and progressive neurological symptoms including ataxia, dystonia and spasticity (26%; 27.8±23.6 years). Intracranial hypertension was less frequently observed (14%), mostly in adults (mean age 31.5±13.2 years). Ischemic or hemorrhagic strokes were inaugural symptoms in two adults (2%). During follow-up, most patients developed progressive extrapyramidal, cerebellar and pyramidal signs (83%), cognitive decline (56%), seizures (37%), intracranial hypertension (30%) or stroke (2%). CONCLUSION: In LCC, the clinical spectrum is largely heterogeneous and the course of the disease appears highly variable in contrast to other hereditary cerebral small vessel diseases.