Category Archives: Cranial Base

Hyponatremia Following Transsphenoidal Surgery

Epidemiology

Delayed hyponatremia following transsphenoidal surgery is a known complication, with a peak incidence of 4-7 days post-operatively 1) 2) 3).

It is a common cause of hospital readmission, due to fluid retention resulting in reduction of plasma sodium concentration below physiologic levels 4).


In a database of 466 consecutive patients who underwent endoscopic transsphenoidal surgery at a tertiary care center between April 2006 and July 2014 was reviewed for 30-day causes for readmission, length of stay, level of care required, and average cost.

Twenty-nine readmissions were identified within the study period, indicating a 30-day readmission rate of 6.2%. Among all patients, rates of 30-day readmission were 2.1% for epistaxis, 1.5% for hyponatremia, 0.9% for cerebrospinal fluid leak, and 1.7% for other medical conditions. Average cost per readmission ranged from $6011 for hyponatremia to $24,613 for cerebrospinal fluid leak 5).

Etiology

The development of Delayed Symptomatic Hyponatremia (DSH) after transsphenoidal surgery has been ascribed mostly to elevations in the secretion of ADH following mechanical manipulation of the pituitary gland, or less frequently as a result of excessive urinary excretion of salt resulting in cerebral salt wasting syndrome (CSWS) 6).

Patients with Cushing’s disease were at a significantly higher risk than other patients to experience DSH 7) 8).

Clinical features

Patients can present with a range of symptoms, from minor nausea, vomiting headache to confusion, and in severe cases, seizures and death 9).

Management

Close symptom monitoring may be a reasonable alternative to routine screening 10).

Age, gender, tumor size, rate of decline of blood sodium, and Cushing disease are potential predictors of Delayed Symptomatic Hyponatremia (DSH) (defined as serum sodium level <135 mEq/L with associated symptoms) after postoperative day 3. By identifying patients at high risk for DSH, preventative efforts can be implemented in the perioperative setting to reduce the incidence of potentially catastrophic hyponatremia following transsphenoidal surgery 11).

Modern skull base surgeons suggest that improved visualization and identification provided by the endoscope can lead to greater visualization and reduced trauma to the posterior pituitary gland 12) 13) 14).

Systematic review

A systematic search of the literature was conducted using MEDLINE/PUBMED, EMBASE, and Cochrane databases. Inclusion criteria were 1) case series with at least 10 cases reported, 2) adult patients who underwent eTSS or mTSS for pituitary tumors, and 3) reported occurrence of Delayed Symptomatic Hyponatremia (DSH) (defined as serum sodium level <135 mEq/L with associated symptoms) after postoperative day 3. Data were analyzed using CMA V.3 Statistical Software (2014).

Ten case series satisfied the inclusion criteria for a total of 2947 patients. Various factors including age, gender, cerebrospinal fluid leak, and tumor size were investigated as potential predictors of DSH. DSH event rates for both mTSS and eTSS fell between around 4 and 12 percent and included a variety of proposed predictors.

Age, gender, tumor size, rate of decline of blood sodium, and Cushing disease are potential predictors of DSH. By identifying patients at high risk for DSH, preventative efforts can be implemented in the perioperative setting to reduce the incidence of potentially catastrophic hyponatremia following transsphenoidal surgery 15).

Case series

2017

Data from before and after delayed hyponatremia (DH) care pathway implementation were retrospectively reviewed. Patient demographics and clinical characteristics were compared. Readmission causes, clinical pathway failures, sodium trends, and symptoms were evaluated.

Before the DH care pathway implementation, 229 (55%) patients were treated (group 1); afterward, 188 (45%) were treated (group 2). Baseline characteristics were equivalent between groups, except for glucocorticoid supplementation, which was higher in group 2. The incidence of detected DH was significantly lower in group 1 (16/229, 7%) than group 2 (29/188, 15%) ( P = .006) likely due to the impact of routine screening in group 2. Ten group 1 patients (4%) were readmitted for hyponatremia and 6 (3%) were managed as outpatients. Eleven group 2 patients (6%) were readmitted and 17 (9%) were managed as outpatients. Readmission rates between groups were similar ( P = .49). Patients readmitted with severe hyponatremia experienced symptoms ≥24 h before presentation. The protocol failed to prevent readmission because outpatient management for mild or moderate DH (n = 4) failed, sodium levels precipitously declined after normal screening (n = 3), and severe hyponatremia developed after scheduled screenings were missed (n = 3).

Although more DH patients were identified after care pathway implementation, readmission rates were not reduced and clinical outcomes were not changed. Because DH onset timing varies, some patients have highly acute presentation, and most readmitted patients develop symptoms before reaching their sodium nadir, close symptom monitoring may be a reasonable alternative to routine screening 16).


Of 303 patients who had transsphenoidal surgery, 27 (8.9%) were readmitted within 30 days. Most of the 27 (15 [55.6%]) had delayed hyponatremia. Other causes were diabetes insipidus (4 [14.8%]), adrenal insufficiency (2 [7.4%]), and cerebrospinal fluid leak, epistaxis, cardiac arrhythmia, pneumonia, urinary tract infection, and hypoglycemia (1 each [3.7%]). Outpatient sodium screening was performed as needed. In cases of hyponatremia, the mean postoperative day of readmission was day 8 (range, 6-12 days) and the mean serum sodium was 119 mmol/L (range, 111-129 mmol/L). Numerous patient and surgical factors were examined, and no specific predictors of readmission were identified. We developed an outpatient care pathway for managing hyponatremia with the goal of improving readmission rates.

This study establishes a quality benchmark for readmission rates after transsphenoidal surgery for pituitary lesions and identifies delayed hyponatremia as the primary cause. Implementation of an outpatient care pathway for managing hyponatremia may improve readmission rates 17).

2013

A retrospective analysis of a single-institution prospective database was conducted; all patients undergoing TSS for lesions involving the pituitary gland were followed up in a multidisciplinary neuroendocrine clinic, and demographic, imaging, and clinical data were prospectively collected. Patients were examined preoperatively and followed up postoperatively in a standardized fashion, and their postoperative sodium levels were measured at Weeks 1 and 2 postoperatively. Levels of hyponatremia were rated as mild (serum sodium concentration 130-134 mEq/L), moderate (125-129 mEq/L), or severe (< 125 mEq/L). Routine clinical questionnaires were administered at all postoperative office visits. Postoperative hyponatremia was analyzed for correlations with demographic and clinical features and with immediate postoperative physiological characteristics. RESULTS: Over a 4-year interval, 373 procedures were performed in 339 patients who underwent TSS for sellar and parasellar lesions involving the pituitary gland. The mean (± SD) age of patients was 48 ± 18 years; 61.3% of the patients were female and 46.1% were obese (defined as a body mass index [BMI] ≥ 30). The overall prevalence of DPH within the first 30 days postoperatively was 15.0%; 7.2% of the patients had mild, 3.8% moderate, and 3.8% severe hyponatremia. The incidence of symptomatic hyponatremia requiring hospitalization was 6.4%. The Fisher exact test detected a statistically significant association of DPH with female sex (p = 0.027) and a low BMI (p = 0.001). Spearman rank correlation detected a statistically significant association between BMI and nadir serum sodium concentration (r = 0.158, p = 0.002) and an inverse association for age (r = -0.113, p = 0.031). Multivariate analyses revealed a positive correlation between postoperative hyponatremia and a low BMI and a trend toward association with age; there were no associations between other preoperative demographic or perioperative risk factors, including immediate postoperative alterations in serum sodium concentration. Patients were treated with standardized protocols for hyponatremia, and DPH was not associated with permanent morbidity or mortality. CONCLUSIONS: Delayed postoperative hyponatremia was a common result of TSS; a low BMI was the only clear predictor of which patients will develop DPH. Alterations in immediate postoperative sodium levels did not predict DPH. Therefore, an appropriate index of suspicion and close postoperative monitoring of serum sodium concentration should be maintained for these patients, and an appropriate treatment should be undertaken when hyponatremia is identified 18).

2011

Kinoshita et al. evaluated (i) the incidence of post-operative hyponatremia (serum Na levels ≤ 135 mEq/L) and the emergence of hyponatremic symptoms, and assessed (ii) the risk factors under a uniform protocol of i.v. infusion with steroid and electrolyte fluid. We examined 88 consecutive operated patients (female: 60; male: 28) with pituitary adenoma. Apart from reconfirming the effects of the purported risk factors, we focused on the degree of serum Na decline on post-operative hyponatremia. Although remained stable during early post-operative period (4 days after surgery), the serum Na levels subsequently decreased after post-operative day 4 in 81 of 88 cases (92.0%). Of 88 patients, 27 (30.7%) and 9 (10.2%) cases suffered from hyponatremia, and developed hyponatremic symptoms. Interestingly, the degree of serum Na levels decline (from pre-operative levels) indicated a useful independent risk factor for monitoring hyponatremic symptoms (p = 0.006) and the degree of decline tended to be greater in elder patients (> 60 years) (p = 0.0346). Serum Na levels should be monitored from, at least, post-operative day 7 to detect early development of hyponatremia. Special attention and recovery effort should be given to elder patients with marked serum Na level decline after surgery 19).

2008

The incidence and risk factors of symptomatic and asymptomatic hyponatremia were investigated in 94 patients who underwent transsphenoidal surgery and serum sodium level monitoring between January 2002 and December 2006. The records were retrospectively reviewed to determine the incidence and risk factors (age and sex, tumor size, endocrinologic findings) of hyponatremia. Postoperatively, the serum sodium levels of the patients were measured at least once within 2 or 3 days. Hyponatremia was found in 17 of the 94 patients, of whom 7 became symptomatic. The mean sodium level of symptomatic patients with hyponatremia at diagnosis was 123.5 mEq/l, compared with 129.8 mEq/l of asymptomatic patients. The serum sodium levels began to fall on mean postoperative day 7 and reached nadir on mean day 8. All 17 patients with hyponatremia were treated with mild fluid restriction. Four symptomatic patients with severe hyponatremia were treated with 3% hypertonic saline infusion in addition to fluid restriction. One symptomatic patient with severe hyponatremia was treated with fluid restriction only. All patients recovered within 5 days of management. Sex, tumor type, and tumor size did not correlate with development of delayed hyponatremia, but patients aged >/=50 years were more likely to develop hyponatremia. Postoperative hyponatremia after transsphenoidal surgery is more common than previously reported and may lead to fatal complications. Therefore, all patients should undergo serum electrolyte level monitoring regularly for at least 1 or 2 weeks after transsphenoidal surgery 20).

2007

Patients who underwent transsphenoidal surgery at the University of Southern California University Hospital between 1997 and 2004 had serum sodium levels drawn on an outpatient basis on postoperative Day 7. Patient records were retrospectively reviewed to determine the incidence of, and risk factors for, symptomatic and asymptomatic hyponatremia. Two hundred forty-one patients had routine serum sodium levels drawn as outpatients on postoperative Day 7. Twenty-three percent of these patients were found to be hyponatremic (Na < or =135 mEq/L). The overall incidence rate of symptomatic hyponatremia in the 241 patients was 5%. The majority of hyponatremic patients (80%) remained asymptomatic, whereas 20% became symptomatic. In patients with symptomatic hyponatremia, the mean sodium level at diagnosis was 120.5 mEq/L, compared with 128.4 mEq/L in asymptomatic, hyponatremic patients (p < 0.0001). Female patients were more likely to develop hyponatremia than male patients (33% compared with 22%, p < 0.03). Fifty-two percent of patients who had transient diabetes insipidus (DI) early in their postoperative course subsequently developed hyponatremia, compared with 21% of those who did not have DI (p < 0.001). Patient age, tumor type, and tumor size did not correlate with development of delayed hyponatremia. Outpatients with moderately and severely low sodium levels were 5 and 12.5 times more likely, respectively, to be symptomatic than were patients with mild hyponatremia.

Delayed hyponatremia occurs more frequently than was previously suspected in patients who have undergone transsphenoidal surgery, especially in female patients and those who have previously had transient DI. The majority of hyponatremic patients remain asymptomatic. Obtaining a serum sodium value on an outpatient basis 1 week after pituitary surgery is helpful in recognition, risk stratification, and subsequent intervention, and may prevent potentially serious complications 21).

1999

1571 patients with pituitary adenomas (238 Cushing’s disease, 405 acromegaly, 534 hormonally inactive adenomas, 358 prolactinoma, 23 Nelson’s syndrome, and 13 thyrotropinoma) were daily examined within a 10-day postoperative inpatient observation period. Prevalence of patterns of polyuria (> 2500 ml) and oliguria/hyponatraemia (< 132 mmol/l) were surveyed as well as predictors of postoperative morbidity. RESULTS: 487 patients (31%) developed immediate postoperative hypotonic polyuria, 161 patients (10%) showed prolonged polyuria and 37 patients (2.4%) delayed hyponatraemia. A biphasic (polyuria-hyponatraemia) and triphasic (polyuria-hyponatraemia-polyuria) pattern was seen in 53 (3.4%) and 18 (1.1%) patients, respectively. Forty-one patients (2.6%) displayed immediate postoperative (day 1) hyponatraemia. Altogether, 8.4% of patients developed hyponatraemia at some time up to the 10th day postoperative, with symptomatic hyponatraemia in 32 patients (2.1%). Risk analysis showed that patients with Cushing’s disease had a fourfold higher risk of polyuria than patients with acromegaly and a 2.8-fold higher risk for postoperative hyponatraemia. Younger age, male sex, and intrasellar expansion were associated with a higher risk of hypotonic polyuria, but this was not considered clinically relevant.

The analysis illustrates that disturbances in osmoregulation resulting in polyuria and pertubations of serum sodium concentration are of very high prevalence and need observation even after selective transsphenoidal surgery for pituitary adenomas, especially in patients with Cushing’s disease22).

1995

To clarify the frequency, presentation, and outcome of this poorly understood complication, Taylor et al. reviewed the database of 2297 patients who underwent transsphenoidal pituitary surgery between February 1971 and June 1993. Of 53 patients (2.3%) treated for symptomatic hyponatremia, 11 were excluded (2 received arginine vasopressin within 24 hours, 1 had untreated hypothyroidism, 4 had untreated adrenal insufficiency, and 4 had incomplete records). The remaining 42 patients (1.8%), 11 men and 31 women aged 21 to 79 years, presented 4 to 13 days (mean, 8 d) postoperatively with nausea and vomiting (20 patients), headache (18 patients), malaise (12 patients), dizziness (4 patients), anorexia (2 patients), and seizures (1 patient). Hyponatremia was unrelated to sex, age, adenoma type, tumor size, or glucocorticoid tapering. Although the clinical picture in our patients is consistent with SIADH, this was not supported by the antidiuretic hormone levels, which were normal or low-normal in the two patients in whom they were measured, suggesting the possibility that low serum sodium may not reflect SIADH. In all patients, hyponatremia resolved within 6 days (mean, 2 d); treatment consisted of salt replacement and mild fluid restriction in 37 patients and fluid restriction only in 4 (treatment unknown in 1). Delayed hyponatremia after transsphenoidal resection of pituitary adenoma is not as rare as previously thought, nor is it necessarily associated with SIADH or with hypoadrenalism during glucocorticoid tapering 23).

1) , 21)

Zada G, Liu CY, Fishback D, Singer PA, Weiss MH. Recognition and management of delayed hyponatremia following transsphenoidal pituitary surgery. J Neurosurg. 2007 Jan;106(1):66-71. PubMed PMID: 17236489.

2) , 7) , 22)

Hensen J, Henig A, Fahlbusch R, Meyer M, Boehnert M, Buchfelder M. Prevalence, predictors and patterns of postoperative polyuria and hyponatraemia in the immediate course after transsphenoidal surgery for pituitary adenomas. Clin Endocrinol (Oxf). 1999 Apr;50(4):431-9. PubMed PMID: 10468901.

3) , 6)

Kelly DF, Laws ER, Jr., Fossett D. Delayed hyponatremia after transsphenoidal surgery for pituitary adenoma. Report of nine cases. J Neurosurg. 1995;83(2):363-367.

4)

Bohl MA, Ahmad S, Jahnke H, et al. Delayed Hyponatremia Is the Most Common Cause of 30-Day Unplanned Readmission After Transsphenoidal Surgery for Pituitary Tumors. Neurosurgery. 2015.

5)

Hendricks BL, Shikary TA, Zimmer LA. Causes for 30-Day Readmission following Transsphenoidal Surgery. Otolaryngol Head Neck Surg. 2016 Feb;154(2):359-65. doi: 10.1177/0194599815617130. Epub 2015 Nov 17. PubMed PMID: 26577772.

8)

Sane T, Rantakari K, Poranen A, Tahtela R, Valimaki M, Pelkonen R. Hyponatremia after transsphenoidal surgery for pituitary tumors. The Journal of clinical endocrinology and metabolism. 1994;79(5):1395-1398.

9)

Whitaker SJ, Meanock CI, Turner GF, et al. Fluid balance and secretion of antidiuretic hormone following transsphenoidal pituitary surgery. A preliminary series. Journal of neurosurgery. 1985;63(3):404-412.

10) , 16)

Bohl MA, Ahmad S, White WL, Little AS. Implementation of a Postoperative Outpatient Care Pathway for Delayed Hyponatremia Following Transsphenoidal Surgery. Neurosurgery. 2017 Apr 25. doi: 10.1093/neuros/nyx151. [Epub ahead of print] PubMed PMID: 28449052.

11) , 15)

Cote DJ, Alzarea A, Acosta MA, Hulou MM, Huang KT, Almutairi H, Alharbi A, Zaidi HA, Algrani M, Alatawi A, Mekary RA, Smith TR. Predictors and Rates of Delayed Symptomatic Hyponatremia after Transsphenoidal Surgery: A Systemastic Review. World Neurosurg. 2016 Apr;88:1-6. doi: 10.1016/j.wneu.2016.01.022. Epub 2016 Jan 22. PubMed PMID: 26805685.

12)

Ammirati M, Wei L, Ciric I. Short-term outcome of endoscopic versus microscopic pituitary adenoma surgery: a systematic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2013;84(8):843-849.

13)

Gao Y, Zhong C, Wang Y, et al. Endoscopic versus microscopic transsphenoidal pituitary adenoma surgery: a meta-analysis. World J Surg Oncol. 2014;12(94).

14)

Cavallo LM, Dal Fabbro M, Jalalod’din H, et al. Endoscopic endonasal transsphenoidal surgery. Before scrubbing in: tips and tricks. Surg Neurol. 2007;67(4):342-347.

17)

Bohl MA, Ahmad S, Jahnke H, Shepherd D, Knecht L, White WL, Little AS. Delayed Hyponatremia Is the Most Common Cause of 30-Day Unplanned Readmission After Transsphenoidal Surgery for Pituitary Tumors. Neurosurgery. 2016 Jan;78(1):84-90. doi: 10.1227/NEU.0000000000001003. PubMed PMID: 26348011.

18)

Hussain NS, Piper M, Ludlam WG, Ludlam WH, Fuller CJ, Mayberg MR. Delayed postoperative hyponatremia after transsphenoidal surgery: prevalence and associated factors. J Neurosurg. 2013 Dec;119(6):1453-60. doi: 10.3171/2013.8.JNS13411. Epub 2013 Sep 20. PubMed PMID: 24053496.

19)

Kinoshita Y, Tominaga A, Arita K, Sugiyama K, Hanaya R, Hama S, Sakoguchi T, Usui S, Kurisu K. Post-operative hyponatremia in patients with pituitary adenoma: post-operative management with a uniform treatment protocol. Endocr J. 2011;58(5):373-9. Epub 2011 Apr 5. PubMed PMID: 21467692.

20)

Lee JI, Cho WH, Choi BK, Cha SH, Song GS, Choi CH. Delayed hyponatremia following transsphenoidal surgery for pituitary adenoma. Neurol Med Chir (Tokyo). 2008;48(11):489-92; discussion 492-4. PubMed PMID: 19029775.

23)

Taylor SL, Tyrrell JB, Wilson CB. Delayed onset of hyponatremia after transsphenoidal surgery for pituitary adenomas. Neurosurgery. 1995 Oct;37(4):649-53; discussion 653-4. Review. PubMed PMID: 8559292.

Update Cerebellopontine angle epidermoid cyst

The cerebellopontine angle epidermoid cyst is a posterior fossa epidermoid cyst.

It account for 3-6% of cerebellopontine angle tumors. Comparatively, vestibular schwannomas, the most common CPA angle tumor, account for 85%.

Men and women are equally affected and the symptoms usually arise between the mid-20’s and early 50’s 1) with a mean age of 38.8 years at presentation 2).

Pathophysiology

Although several mechanisms for cranial nerve dysfunction due to these tumors have been proposed.

Hasegawa et al. report the first direct evidence of etiology of cranial nerve dysfunction caused by cerebellopontine angle epidermoid tumors. Young age and rapidly progressive neurological deficit might be the characteristics for strangulation of the affected nerves by the cyst capsule 3).

Clinical features

CPA epidermoid cysts can compress the surrounding cranial nerves, brainstem, and cerebellum. Ataxia and cranial nerve palsies often result 4).Thirty cases of cerebellopontine angle epidermoid cysts treated over a period of 20 years werw reviewed with regard to their clinical features, the pathophysiology of their symptoms and their management. The predominating symptoms were related to the 7th and 8th cranial nerves and headaches. The signs and symptoms were present for an average period of 4 months. It was not always possible to determine if the signs and symptoms were due to local involvement by the epidermoid, increased intracranial pressure, or both 5).

Diagnosis

Diagnostic procedures evolved from angiography and ventriculography to non-invasive computed tomography and MRI 6).


cerebelloponineangleepidermoidcyst.jpg

Treatment

The posterior cranial fossa approach was used in 27 cases in the case series of deSouza et al. Total excision of the epidermoid was the aim and was carried out in five (18%) patients but concern regarding the preservation of nearby important neurovascular structures forced partial removal in 22 patients. To minimise reformation, the residual epidermoid was carefully coagulated with the aid of the operating microscope and bipolar cautery without damaging surrounding neurovascular structures 7).


The characteristics of epidermoid cysts make them amenable to whole course neuroendoscopic resection. Use of physiologic/pathologic interspaces and neuroendoscopic angulations decreases traction on the brain, improves complete resection rates, and decreases postoperative complications 8).

Case series

2016

Twenty-two cases with epidermoid cysts of CPA micro-neurosurgically treated since 2005 were reviewed. Clinical status of the patients before the surgery and post-operative functional outcome were recorded. Available data from the English literature were summarized for comparison. Mass reduction of cyst contents in most cases was usually associated with prompt and marked improvement of the symptoms suggesting neuroapraxia caused by compression of the tumor content and/or mild ischemia. Among them, two cases showed strangulation of the affected nerves by the tumor capsule whose preoperative dysfunction did not improve after surgery in spite of meticulous microsurgical removal of the lesion. Involved facial and abducent nerves in these two cases showed distortion of nerve axis and nerve atrophy distal to the strangulation site.

Hasegawa et al. report the first direct evidence of etiology of cranial nerve dysfunction caused by cerebellopontine angle epidermoid tumors. Young age and rapidly progressive neurological deficit might be the characteristics for strangulation of the affected nerves by the cyst capsule. Even though the number of cases might be limited, immediate decompression and release of the strangulating band might be urged in such patients to prevent irreversible deficits 9).


17 patients, including 7 with tumor limited to the cerebellopontine angle, 7 with cerebellopontine angle tumor penetrating supratentorially, and 3 with cerebellopontine angle tumor extending along skull base to contralateral cerebellopontine angle. All patients were followed-up for the mean duration of 126 months.

On admission cranial nerve symptoms predominated. Total tumor removal was achieved in 5 patients, and incomplete removal (with small tumor remnants left on vessels, nerves, or brainstem) in 12 patients. Postoperatively, preoperative deficits worsened in 2 and new postoperative deficits occurred in 10 patients. The extent of tumor expansion had no effect on postoperative morbidity and risk of recurrence. During long-term follow-up, improvement or resolution of preoperative deficits was seen in 11 of 17 patients, and new postoperative deficits in 8 of 10 patients. Symptomatic recurrences after an average of more than 9 years were noted in 5 patients, 3 of whom were reoperated. Recurrences occurred in some younger patients and always in area of primary tumor. No effect of extent of tumor removal on risk of recurrence was found.

The extent of tumor removal had no effect on the risk of recurrence, and thus it may be acceptable to leave tumor capsule fragments adhering closely to nerves, vessels, or brainstem. During long-term follow-up, resolution or improvement of present preoperatively and new postoperative neurological deficits may be expected in most patients 10).

2015

In a case series, pathophysiology of cranial nerve dysfunction in CPA epidermoid cysts was evaluated with special attention to a new mechanism of capsule strangulation caused by stratified tumor capsule. Twenty-two cases since 2005 were reviewed. Clinical status of the patients before the surgery and post-operative functional outcome were recorded. Available data from the English literature were summarized for comparison. Mass reduction of cyst contents in most cases was usually associated with prompt and marked improvement of the symptoms suggesting neurapraxia caused by compression of the tumor content and/or mild ischemia. Among them, two cases showed strangulation of the affected nerves by the tumor capsule whose preoperative dysfunction did not improve after surgery in spite of meticulous microsurgical removal of the lesion. Involved facial and abducent nerves in these two cases showed distortion of nerve axis and nerve atrophy distal to the strangulation site. Hasegawa et al. report the first direct evidence of etiology of cranial nerve dysfunction caused by cerebellopontine angle epidermoid tumors. Young age and rapidly progressive neurological deficit might be the characteristics for strangulation of the affected nerves by the cyst capsule. Even though the number of cases might be limited, immediate decompression and release of the strangulating band might be urged in such patients to prevent irreversible deficits 11)


Hu et al. performed a retrospective analysis of clinical data of 13 male and 17 female patients (mean age: 42.4 ± 11.4 years) who presented with a CPA epidermoid cyst and underwent whole course neuroendoscopy. Complications and tumor recurrence were assessed at follow-up. Results Clinical manifestations included an initial symptom of headache (n = 21), gait instability (n = 6), intracranial hypertension (n = 13), posterior cranial nerve symptoms (n = 6), ataxia (n = 5), and hydrocephalus (n = 1). All patients tolerated tumor resection with subsequent symptomatic improvement, and the results of the postoperative magnetic resonance imaging scan did not show any remnants of tumor. Mean duration of surgery was 2.61 ± 0.47 hours, mean loss of blood was 96.8 ± 35.4 mL, and the mean duration of hospitalization was 7.5 ± 2.25 days. Postoperative complications (8 of 30 [26.7%]) included fever (n = 5), communicating hydrocephalus (n = 1), facial nerve paralysis (n = 1), and abducens nerve palsy (n = 1). Tumor recurrence was observed in two patients (6.7%). No deaths or intracranial hemorrhage was reported.

The characteristics of epidermoid cysts make them amenable to whole course neuroendoscopic resection. Use of physiologic/pathologic interspaces and neuroendoscopic angulations decreases traction on the brain, improves complete resection rates, and decreases postoperative complications 12).

2010

Between 1996 and 2004, 10 patients with typical symptoms of trigeminal neuralgia were found to have cerebellopontine angle epidermoids and treated surgically.

Total resection was done in 6 patients (60%). Surgical removal of tumor and microvascular decompression of the trigeminal nerve were performed simultaneously in one case. One patient died due to postoperative aseptic meningitis. The others showed total relief from pain. During follow-up, no patients experienced recurrence of their trigeminal neuralgia (TN).

The clinical features of TN from CPA epidermoids are characterized by symptom onset at a younger age compared to TN from vascular causes. In addition to removal of the tumor, the possibility of vascular compression at the root entry zone of the trigeminal nerve should be kept in mind. If it exists, a microvascular decompression (MVD) should be performed. Recurrence of tumor is rare in both total and subtotal removal cases, but long-term follow-up is required 13).

1989

Thirty cases of cerebellopontine angle epidermoid cysts treated over a period of 20 years are reviewed with regard to their clinical features, the pathophysiology of their symptoms and their management. The predominating symptoms were related to the 7th and 8th cranial nerves and headaches. The signs and symptoms were present for an average period of 4 months. It was not always possible to determine if the signs and symptoms were due to local involvement by the epidermoid, increased intracranial pressure, or both. Diagnostic procedures evolved from angiography and ventriculography to non-invasive computed tomography and MRI. The posterior cranial fossa approach was used in 27 cases. Total excision of the epidermoid was the aim and was carried out in five (18%) patients but concern regarding the preservation of nearby important neurovascular structures forced partial removal in 22 patients. To minimise reformation, the residual epidermoid was carefully coagulated with the aid of the operating microscope and bipolar cautery without damaging surrounding neurovascular structures 14).

Case reports

2016

Malignant transformation of a residual cerebellopontine angle epidermoid cyst 15).

2015

Guan et al. the case of a 13-year-old female with a newly diagnosed cerebellopontine angle EC who presented with worsening headaches, photophobia, and emesis. Magnetic resonance imaging demonstrated significant pericystic brainstem edema and mass effect with effacement of the fourth ventricle. Refractory symptoms prompted repeat imaging, revealing cyst enlargement and dense rim enhancement. Resection of the EC resolved both her symptoms and the brainstem edema. This case documents the radiographic evolution of EC rupture and subsequent clinical course 16).


A case of an unusual epidermoid cyst of the cerebellopontine angle extending into the upper cervical canal that appeared hyper-dense on computed tomography scanning, hyper-intense on T1-weighted magnetic resonance (MR) images, and hypo-intense on T2-weighted MR images 17).

1)

Fleming JF, Botterell EH. Cranial dermoid and epidermoid tumors. Surg Gynecol Obstet. 1959;109:403–411.
2)

Fawcitt RA, Isherwood I. Radiodiagnosis of intracranial pearly tumours with particular reference to the value of computer tomography. Neuroradiology. 1976;11:235–242.
3) , 11)

Hasegawa M, Nouri M, Nagahisa S, Yoshida K, Adachi K, Inamasu J, Hirose Y, Fujisawa H. Cerebellopontine angle epidermoid cysts: clinical presentations and surgical outcome. Neurosurg Rev. 2015 Nov 14. [Epub ahead of print] PubMed PMID: 26566990.
4)

Berger M, Wilson C. Epidermoid cysts of the posterior fossa. J Neurosurg. 1985;62:214–219.
5) , 6) , 7) , 14)

deSouza CE, deSouza R, da Costa S, Sperling N, Yoon TH, Abdelhamid MM, Sharma RR, Goel A. Cerebellopontine angle epidermoid cysts: a report on 30 cases. J Neurol Neurosurg Psychiatry. 1989 Aug;52(8):986-90. PubMed PMID: 2795068; PubMed Central PMCID: PMC1031839.
8) , 12)

Hu Z, Guan F, Kang T, Huang H, Dai B, Zhu G, Mao B, Kang Z. Whole Course Neuroendoscopic Resection of Cerebellopontine Angle Epidermoid Cysts. J Neurol Surg A Cent Eur Neurosurg. 2015 Aug 24. [Epub ahead of print] PubMed PMID: 26302403.
9)

Hasegawa M, Nouri M, Nagahisa S, Yoshida K, Adachi K, Inamasu J, Hirose Y, Fujisawa H. Cerebellopontine angle epidermoid cysts: clinical presentations and surgical outcome. Neurosurg Rev. 2016 Apr;39(2):259-66; discussion 266-7. doi: 10.1007/s10143-015-0684-5. PubMed PMID: 26566990.
10)

Czernicki T, Kunert P, Nowak A, Wojciechowski J, Marchel A. Epidermoid cysts of the cerebellopontine angle: Clinical features and treatment outcomes. Neurol Neurochir Pol. 2016;50(2):75-82. doi: 10.1016/j.pjnns.2015.11.008. PubMed PMID: 26969562.
13)

Son DW, Choi CH, Cha SH. Epidermoid tumors in the cerebellopontine angle presenting with trigeminal neuralgia. J Korean Neurosurg Soc. 2010 Apr;47(4):271-7. doi: 10.3340/jkns.2010.47.4.271. PubMed PMID: 20461167; PubMed Central PMCID: PMC2864819.
15)

Pikis S, Margolin E. Malignant transformation of a residual cerebellopontine angle epidermoid cyst. J Clin Neurosci. 2016 Nov;33:59-62. doi: 10.1016/j.jocn.2016.04.008. Review. PubMed PMID: 27519146.
16)

Guan Z, Hollon T, Bentley JN, Garton HJ. Ruptured pediatric cerebellopontine angle epidermoid cyst: a case report detailing radiographic evolution and clinical course. J Neurosurg Pediatr. 2015 Aug 21:1-5. [Epub ahead of print] PubMed PMID: 26295366.
17)

Lim J, Cho K. Epidermoid cyst with unusual magnetic resonance characteristics and spinal extension. World J Surg Oncol. 2015 Aug 7;13:240. doi: 10.1186/s12957-015-0651-1. PubMed PMID: 26245481; PubMed Central PMCID: PMC4527251.

Update: Intracanalicular vestibular schwannoma

The current practitioner is more often managing intracanalicular vestibular schwannomas than in the past, as improved imaging and heightened awareness leads to earlier diagnosis of these tumors.

Case courtesy of Dr Ian Bickle, <a href=“https://radiopaedia.org/”>Radiopaedia.org</a>. From the case <a href=“https://radiopaedia.org/cases/48853”>rID: 48853</a>

Differential diagnosis

Intracanalicular meningioma


Pantopaque (iophendylate) is an oily contrast medium historically used during spine imaging. Due to its persistence in the subarachnoid space and the potential to lead to severe arachnoiditis, it is no longer used today. Deep et al., present a 40-year-old male with new-onset headaches, imbalance, and vertigo. Brain magnetic resonance imaging revealed a 2-mm T1 -hyperintense intracanalicular lesion. Numerous hyperdense foci were scattered throughout the subarachnoid space on computed tomography. Further history revealed the patient received Pantopaque 30 years prior, after sustaining spinal trauma. Remnant Pantopaque contrast is an important differential when evaluating a patient with a suspected intracranial tumor in order to avoid unwarranted surgical intervention 1).


A 46-year-old man with venous compression of the vestibulocochlear nerve inside the internal auditory canal (IAC). The patient presented with a 2-year history of recurrent attacks of disabling vertigo and intermittent high-frequency tinnitus on the right side. Magnetic resonance images showed a small, contrast-enhancing lesion in the fundus of the right IAC, which was suspicious for vestibular schwannoma. During surgical exploration, a large venous loop was found extending into the IAC and compressing the vestibulocochlear nerve. The vessel was mobilized and rerouted out of the IAC. The presumed vestibular schwannoma at the cochlear fossa was left in situ. The patient’s symptoms resolved immediately after surgery. Hearing was unchanged postoperatively. On follow-up, there has been no growth of the contrast-enhancing lesion in the IAC for 3 years so far.Disabling vertigo can also be caused by venous microvascular compression of the vestibulocochlear nerve inside the IAC and may be treated successfully by microvascular decompression. A sensitive, conservative approach to lesions in the fundus may be justified in the presence of an additional, more prominent pathology that causes compression of the vestibulocochlear nerve 2).

Treatment

The role of observation, microsurgery, and radiation treatment in the management of intracanalicular tumors continues to evolve.

Watchful waiting is an important management option for patients with minimal symptoms. The literature on the natural history of small vestibular schwannomas continues to expand, with particular emphasis on the expected hearing outcomes.

Microsurgical techniques also focus on hearing preservation. Presence of fundal fluid and good or normal hearing preoperatively are positive predictors of hearing preservation after surgery. Long-term follow-up after radiation therapy for vestibular schwannomas continues to demonstrate excellent tumor control rates, although hearing preservation rates are modest.

Multiple factors, including status of hearing, presence of vestibular symptoms, patient age, medical comorbidities, institutional outcomes, and patient preferences, help determine the management strategy for patients with an intracanalicular vestibular schwannoma 3).


Complete surgical removal of intracanalicular vestibular schwannomas with nerve VII and VIII sparing and without worsening patient’s status is challenging. Also the choice of an optimal surgical technique, which is usually limited to selection between retrosigmoid transmeatal (RT) and middle fossa (MF) approach, can be a challenge. Although many previous studies documented superiority of RT to MF approach and vice versa, still no consensus has been reached regarding an optimal approach to intracanalicular vestibular schwannomas. In a technical note, Turek et al., present RT approach with an endoscopic assistance and highlight its advantages over MF approach in surgical management of pure intracanalicular vestibular schwannomas.

RT approach with an endoscopic assistance is presented as an optimal surgical treatment for intracanalicular vestibular schwannomas, and its advantages are compared to those offered by MF approach.

Under an endoscopic guidance, they found a residual tumor in the fundus of the inner acoustic canal and performed its gross total resection.

RT approach is an excellent technique suitable for safe radical surgical treatment of T1 vestibular schwannomas; this technique is associated with lower morbidity risk than MF approach 4).


A longitudinal study of a series of consecutive patients operated on with the 2 techniques by the same surgeon was conducted. Selection criteria included tumor confined to the internal auditory canal (IAC) with a length ranging from 4 to 12 mm and hearing class A or B. Patients were alternately assigned to 1 of the 2 groups regardless of auditory class and distance of the tumor from the IAC fundus. Thirty-five subjects were operated on with the RS-TM technique and 35 via the MF route.

No significant differences in auditory and facial nerve function results between the 2 techniques were observed. The RS-TM approach, however, showed better facial nerve results at discharge. VS size, IAC enlargement, and, particularly, the distance from the IAC fundus were found to influence the postoperative results more than the type of approach itself.

The MF approach has been described as being the better technique for VS surgery in terms of auditory results. However, this claim lacks statistical substantiation because no prospective studies are to be found in the literature. The present longitudinal investigation shows that the MF approach does not afford any particular advantages over the RS-TM route in terms of auditory results in intracanalicular VS, with the exception of tumors reaching the IAC fundus 5).

Case series

2016

A retrospective study was done in 14 patients who underwent MFA for vestibular schwannoma in Asan Medical Center.

The median age at diagnosis was 46.3 years. At initial presentation, 57% of the patients had vertigo, 43% hearing disturbance, and 64% tinnitus. The mean tumor size was 9.7 mm. The tumors were completely resected in 86% of the patients. Hearing was post-operatively preserved in 12 patients and two patients lost their hearing following surgery. Facial nerve function post-operatively remained unchanged in 12 patients (86%) 6).


A retrospective analysis of 19 patients with intracanalicular VS and disabling vestibular dysfunction as the main or only symptom (Group A). All of the patients reported having had disabling vertigo attacks. Subjective evaluation of the impairment of patients was performed before surgery, 3 weeks after surgery, 3 months after surgery, and 1 year after surgery, using the Dizziness Handicap Inventory (DHI). The main outcome measures were improvement in quality of life as measured using the DHI, and general and functional outcomes, in particular facial function and hearing. Patient age, preoperative tumor size, preoperative DHI score, and preservation of the nontumorous vestibular nerve were tested using a multivariate regression analysis to determine factors affecting the postoperative DHI score. The Mann-Whitney U-test was used to compare the postoperative DHI score at 3 weeks, 3 months, and 1 year after surgery with a control group of 19 randomly selected patients with intracanalicular VSs, who presented without vestibular symptoms (Group B). The occurrence of early postoperative discrete vertigo attacks was also compared between groups. RESULTS The preoperative DHI score was ≥ 54 in all patients. All patients reported having had disabling rotational vertigo before surgery. The only significant factor to affect the DHI outcome 3 weeks and 3 months after surgery was the preoperative DHI score. The DHI outcome after 1 year was not affected by the preoperative DHI score. Compared with the control group, the DHI score at 3 weeks and 3 months after surgery was significantly worse. There was no significant difference between the groups after 1 year. Vertigo was improved in all patients and completely resolved after 1 year in 17 patients.

Disabling vestibular dysfunction that affects quality of life should be considered an indication for surgery, even in otherwise asymptomatic patients with intracanalicular VS. Surgical removal of the tumor is safe and very effective in regard to symptom relief. All patients had excellent facial nerve function within 1 year after surgery, with a very good chance of hearing preservation 7).


156 patients diagnosed with an intracanalicular VS managed conservatively.

After a follow-up of 9.5 years, tumor growth had occurred in 37% and growth into the cerebellopontine angle had occurred in 23% of patients. Conservative treatment failed in 15%. The pure tone average had increased from 51- to 72-dB hearing level, and the speech discrimination score (SDS) had decreased from 60% to 34%. The number of patients with good hearing (SDS > 70%) was reduced from 52% to 22%, and the number of patients with American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) class A hearing was reduced from 19% to 3%. Hearing was preserved better in patients with 100% SDS at diagnosis than in patients with even a small loss of SDS. Serviceable hearing was preserved in 34% according to AAO-HNS (class A-B) and in 58% according to the word recognition score (class I-II). Rate of hearing loss was higher in patients with growing tumors.

Tumor growth occurred in only a minority of patients diagnosed with an intracanalicular VS during 10 years of observation. The risk of hearing loss is small in patients with normal discrimination at diagnosis. Serviceable hearing is preserved spontaneously in 34% according to AAO-HNS and in 58% according to the word recognition score 8).

2014

31 patients who were followed up for more than 1 year among patients diagnosed as having VS limited to the internal auditory canal. The median follow-up period was 31 months (range, 12-84 mo). We analyzed the patients’ clinical features, clinical courses, and audiologic changes.

The most frequent initial presenting symptom in patients with ICVS was hearing loss, and one-half of the patients (8 of 16) had a history of sudden hearing loss. Seven patients (22.5%) showed tumor growth during the follow-up period. When we considered the initial tumor size in ICVS, the patients larger in size than the median showed a significantly higher rate of tumor growth. In terms of the initial hearing levels of ICVS according to the Consensus Meeting Guidelines, five patients were classified as Class A (normal hearing) and six patients were classified as Class B. Only one patient among patients with useful hearing (Classes A and B) showed tumor growth. The follow-up hearing levels of all Class A patients were preserved; however, all Class B patients deteriorated to Class C.

Patients with ICVS showed favorable results with conservative management. Among them, patients with small tumors and normal hearing showed a good prognosis 9).

2011

47 patients with a unilateral intracanalicular vestibular schwannoma. Evaluation of growth was monitored by repeat MRI scanning. Repeated pure-tone and speech audiometry results were evaluated for subgroups of patients showing growth or no growth and by subsite location of tumor in the internal auditory canal.

Patients had a mean follow-up of 3.6 years. Over the entire population, the pure-tone average thresholds at 0.5, 1, 2, and 3 kHz and the word recognition scores both significantly deteriorated from 38 to 51 dB HL, and from 66% to 55%, respectively. Overall, 74% of subjects with good hearing, according to the 50/50 rule, maintained hearing above this rule. There were no significant differences in hearing loss by subsite in the internal auditory canal (porus, fundus, central) or by growth status (stable, growing, shrinking). Only 6 patients showed a large hearing change. This happened early during follow-up, with relatively stable hearing after this.

Hearing will deteriorate in some intracanalicular vestibular schwannomas, regardless of tumor growth. Hearing deterioration, if on a large scale, most likely occurs early in follow-up. The present results using conservative management in these tumors appear similar to those reported for stereotactic radiotherapy or microsurgery 10).

2008

Forty-seven patients (22 men and 25 women) harboring an intracanalicular vestibular schwannoma were followed prospectively. Mean age at the time of inclusion was 54.4 (20-71) years. The mean follow-up period was 43.8 months (+/-40 months) ranging from 9 to 222 months. Failure was defined as significant tumor growth and/or hearing deterioration that required a microsurgical or radiosurgical treatment. Failure was observed in 35 cases while a conservative treatment is still ongoing in 12 patients. Ten patients kept an unchanged tumor size (21.3%), while 36 patients experienced a tumor growth (76.6%), and 1 patient experienced a mild decreased tumor size (2.1%). Among the 40 patients who where available for hearing level study, 24 patients (60%) did not change their Gardner and Robertson hearing class. Fifteen patients (37.5%) experienced a >10-dB hearing loss and 2 of them became deaf. One patient (2.5%) improved her hearing level from 56.3 to 43.8 dB over a 39.5-month follow-up period. These data suggest that the wait and see policy exposes the patient to degradation of hearing and tumor growth. Both events may occur in an independent way in the middle-term period. This information has to be given to the patient, and a careful sequential follow-up may be adopted when the wait and see strategy is chosen 11).


Between 1987 and 2003, 96 patients (65 men and 31 women) underwent gamma knife stereotactic radiosurgery (SRS) for intracanalicular tumors. The median patient age was 54 years (range, 22-80 years). Hearing was graded using the Gardner-Robertson (GR) and the American Academy of Otolaryngology-Head and Neck Surgery classifications. Dose planning was performed on intraoperative stereotactic images using multiple 4-mm isocenters. The median tumor volume was 0.112 mm3 (range, 0.05-0.447 mm3), and the median margin dose was 13 Gy (range, 10-18 Gy).

The mean and median audiologic follow-up periods were 42 months and 28 months (range, 12-144 months), respectively. Serviceable hearing was preserved in 31 of 40 (77.5%) patients with initial American Academy of Otolaryngology-Head and Neck Surgery Class A hearing. Serviceable hearing was preserved in 40 of 79 (64.5%) patients with GR Grade I or II pre-SRS hearing. Ninety-two patients had GR Grade I, II, or III hearing before SRS, and GR Grade I, II, or III hearing was maintained in 78 patients (85%). Hearing grades improved in 7 patients. Facial and trigeminal nerve function was preserved in all patients. The tumor control rate (freedom from additional intervention) was 99.0% (95 of 96) at a median follow-up of 28 months (range, 12-144 months). One patient underwent tumor resection 18 months after radiosurgery.

SRS is a minimally invasive first-line management option for patients with intracanalicular tumors and provides high rates of hearing preservation with minimal morbidity 12).

2000

40 patients with 40 unilateral VS in the period 1973 to 1996 (mean 3.6 years). Twenty-seven tumours (67.5%) revealed growth and 13 tumours (32%) had no measurable growth. Four growth patterns were observed: (i) 15 tumours (37.5%) exhibited constant growth; (ii) 13 tumours (32.5%) had no measurable growth; (iii) 8 tumours (20%) revealed growth subsequent to a no-growth period; and (iv) 4 tumours (10%) manifested different growth patterns during the observation period. The mean diameter growth per year was 3.2 mm. The findings of the present study, especially those achieved in groups B (the non-growing tumours) and C (tumour growth subsequent to a silent period), question the reliability of the results achieved by radiosurgery, as no tumour growth may occur with no intervention13).

Case reports

2008

A unique case of unilateral widening of the internal auditory canal (IAC) with no significant contact with an ipsilateral intracanalicular vestibular schwannoma (VS), raising the issue of the cause(s) of this IAC widening.

The medical record and radiologic data were reviewed of a patient presenting an enlarged unilateral IAC, which led to the diagnosis of an intracanalicular VS that could not account for the dilation.

The patient had a unilateral dilation of the IAC that did not match the ipsilateral VS he had. As a result, this case motivated discussion of whether such dilation of the IAC was congenitally asymmetrical or the result of the mechanisms involved in the widening of the IAC.

Although asymmetry of IAC is a current notion, this case demonstrates a contrario that increased pressure exerted on the walls of the IAC cannot be the only mechanism in such widening 14).

2004

The first reported case of hemifacial spasm responsive to gamma knife radiosurgery in a patient with an intracanalicular vestibular schwannoma. Both the resolution of the spasm as well as tumor growth control were achieved with a single session of gamma knife radiosurgery. We report a 49-year-old male patient with a 6-month history of right-sided hearing loss and hemifacial spasm. MR examination revealed an intracanalicular vestibular schwannoma. The patient was treated with radiosurgery and received 13 Gy to the 50 % isodose line. Tumor growth control was achieved and no change in the tumor volume was present at the last follow-up at 22 months. The hemifacial spasm completely resolved after one year. Surgical removal of the presumably causative mass lesion has been reported to be the sole treatment in secondary hemifacial spasm. This case report indicates that it may be responsive to gamma knife radiosurgery. Whether or not this might be a treatment option in selected refractory cases of hemifacial spasm remains to be defined 15).

2002

A 68-year-old man with complete deafness of the left ear since childhood, who developed sudden, profound sensorineural hearing loss in the right ear. Magnetic resonance imaging revealed a small right-sided intracanalicular tumor. Treatment with high-dose corticosteroids produced only minimal improvement in hearing. Subsequent emergency decompression and resection of a VS resulted in rapid improvement and restoration of hearing, with facial nerve preservation. Although most neurotologic lesions in patients with hearing in only one ear are managed nonsurgically, resection of small tumors in the setting of sudden hearing loss should be considered in selected cases. This finding indicates that a therapeutic window may exist during which sudden hearing loss caused by intracanalicular tumors is reversible 16).

1998

An unusual case in which they recognized an additional branch arising from the jugular bulb. Three-dimensional computed tomography (3-D CT) revealed this anomaly beforehand, enabling us to avert excessive bleeding upon resection of the tumour. The abnormal vein was thought to be a remnant of the petrosquamosal sinus in the embryonic stage 17).


1) Deep NL, Patel AC, Hoxworth JM, Barrs DM. Pantopaque contrast mimicking intracanalicular vestibular schwannoma. Laryngoscope. 2016 Oct 11. doi: 10.1002/lary.26340. [Epub ahead of print] PubMed PMID: 27726152.
2) Wuertenberger CJ, Rosahl SK. Vertigo and tinnitus caused by vascular compression of the vestibulocochlear nerve, not intracanalicular vestibular schwannoma: review and case presentation. Skull Base. 2009 Nov;19(6):417-24. doi: 10.1055/s-0029-1220209. PubMed PMID: 20436843; PubMed Central PMCID: PMC2793889.
3) Quesnel AM, McKenna MJ. Current strategies in management of intracanalicular vestibular schwannoma. Curr Opin Otolaryngol Head Neck Surg. 2011 Oct;19(5):335-40. doi: 10.1097/MOO.0b013e32834a3fa7. Review. PubMed PMID: 22552696.
4) Turek G, Cotúa C, Zamora RE, Tatagiba M. Endoscopic assistance in retrosigmoid transmeatal approach to intracanalicular vestibular schwannomas – An alternative for middle fossa approach. Technical note. Neurol Neurochir Pol. 2017 Jan 19. pii: S0028-3843(16)30222-5. doi: 10.1016/j.pjnns.2016.12.005. [Epub ahead of print] PubMed PMID: 28162791.
5) Colletti V, Fiorino F. Is the middle fossa approach the treatment of choice for intracanalicular vestibular schwannoma? Otolaryngol Head Neck Surg. 2005 Mar;132(3):459-66. PubMed PMID: 15746862.
6) Kang WS, Kim SA, Yang CJ, Nam SH, Chung JW. Surgical outcomes of middle fossa approach in intracanalicular vestibular schwannoma. Acta Otolaryngol. 2016 Nov 25:1-4. [Epub ahead of print] PubMed PMID: 27885877.
7) Samii M, Metwali H, Gerganov V. Efficacy of microsurgical tumor removal for treatment of patients with intracanalicular vestibular schwannoma presenting with disabling vestibular symptoms. J Neurosurg. 2016 Jun 17:1-6. [Epub ahead of print] PubMed PMID: 27315031.
8) Kirchmann M, Karnov K, Hansen S, Dethloff T, Stangerup SE, Caye-Thomasen P. Ten-Year Follow-up on Tumor Growth and Hearing in Patients Observed With an Intracanalicular Vestibular Schwannoma. Neurosurgery. 2016 Aug 26. [Epub ahead of print] PubMed PMID: 27571523.
9) Lee JD, Park MK, Kim JS, Cho YS. The factors associated with tumor stability observed with conservative management of intracanalicular vestibular schwannoma. Otol Neurotol. 2014 Jun;35(5):918-21. doi: 10.1097/MAO.0000000000000338. PubMed PMID: 24686291.
10) Pennings RJ, Morris DP, Clarke L, Allen S, Walling S, Bance ML. Natural history of hearing deterioration in intracanalicular vestibular schwannoma. Neurosurgery. 2011 Jan;68(1):68-77. doi: 10.1227/NEU.0b013e3181fc60cb. PubMed PMID: 21099722.
11) Roche PH, Soumare O, Thomassin JM, Régis J. The wait and see strategy for intracanalicular vestibular schwannomas. Prog Neurol Surg. 2008;21:83-8. doi: 10.1159/000156710. PubMed PMID: 18810203.
12) Niranjan A, Mathieu D, Flickinger JC, Kondziolka D, Lunsford LD. Hearing preservation after intracanalicular vestibular schwannoma radiosurgery. Neurosurgery. 2008 Dec;63(6):1054-62; discussion 1062-3. doi: 10.1227/01.NEU.0000335783.70079.85. PubMed PMID: 19057318.
13) Thomsen J, Charabi S, Tos M, Mantoni M, Charabi B. Intracanalicular vestibular schwannoma–therapeutic options. Acta Otolaryngol Suppl. 2000;543:38-40. PubMed PMID: 10908971.
14) Kania RE, Herman P, Guichard JP, Tran Ba Huy P. [Dilation of the internal auditory canal and intracanalicular vestibular schwannoma: what are the mechanisms involved?]. Ann Otolaryngol Chir Cervicofac. 2008 Nov;125(5):256-60. doi: 10.1016/j.aorl.2008.07.006. French. PubMed PMID: 18786666.
15) Peker S, Ozduman K, Kiliç T, Pamir MN. Relief of hemifacial spasm after radiosurgery for intracanalicular vestibular schwannoma. Minim Invasive Neurosurg. 2004 Aug;47(4):235-7. PubMed PMID: 15346321.
16) Meiteles LZ, Liu JK, Couldwell WT. Hearing restoration after resection of an intracanalicular vestibular schwannoma: a role for emergency surgery? Case report and review of the literature. J Neurosurg. 2002 Apr;96(4):796-800. PubMed PMID: 11990824.
17) Tsutsumi T, Tsunoda A, Shimamoto K, Komatsuzaki A. Aberrant jugular bulb vein obstructing approach to intracanalicular vestibular schwannoma. J Laryngol Otol. 1998 Aug;112(8):772-4. PubMed PMID: 9850321.

Update: Cerebellopontine angle lipoma

Characteristically lipomas of the CPA have the facial nerve and vestibulocochlear nerve coursing through it on their way to the IAM. They are associated with intravestibular lipomas and sensorineural hearing loss.

Epidemiology

They account for ~10% of all intracranial lipomas.

Diagnosis

Radiographic features

MRI brain Signal characteristics are those of a lipoma

T1: high signal

images.radiopaedia.org_images_2107232_e3e8537790364cc8a2404efc00cdd4_gallery.jpg

https://images.radiopaedia.org/images/2107232/e3e8537790364cc8a2404efc00cdd4_gallery.jpg

T2: high signal

true FISP/FIESTA: low signal margin due to chemical shift artefact fat saturated sequences: shows signal dropout.

http://www.otosurgery.org/DJL_NEWSITE%20images/MRI_cpa-lipoma.gif

Differential diagnosis

Cerebellopontine angle tumors (CPA) are frequent; vestibular schwannomas and cerebellopontine angle meningiomas represent the great majority of such tumors. However, a large variety of unusual lesions can also be encountered in the CPA. The site of origin is the main factor in making a preoperative diagnosis for an unusual lesion of the CPA. In addition, it is essential to analyze attenuation at computed tomography (CT), signal intensity at magnetic resonance (MR) imaging, enhancement, shape and margins, extent, mass effect, and adjacent bone reaction. CPA masses can primarily arise from the cerebellopontine cistern and other CPA structures (arachnoid cyst, nonacoustic schwannoma, aneurysm, melanoma, miscellaneous meningeal lesions) or from embryologic remnants (epidermoid cyst, dermoid cyst, lipoma). Tumors can also invade the CPA by extension from the petrous bone or skull base (cholesterol granuloma, paraganglioma, chondromatous tumors, chordoma, endolymphatic sac tumor, pituitary adenoma, apex petrositis). Finally, CPA lesions can be secondary to an exophytic brainstem or ventricular tumor (glioma, choroid plexus papilloma, lymphoma, hemangioblastoma, ependymoma, medulloblastoma, dysembryoplastic neuroepithelial tumor). A close association between CT and MR imaging findings is very helpful in establishing the preoperative diagnosis for unusual lesions of the CPA 1).


The differential for lesions with high T1 signal includes:

haemorrhagic vestibular schwannoma

neurenteric cyst

thrombosed berry aneurysm

white epidermoid

ruptured intracranial dermoid

Treatment

They are not associated with malformations and can become symptomatic in a slowly progressive way by affecting the more susceptible of the cranial nerves in this region. As a result of the rare occurrence, the experience in treating and managing these tumors is limited. Consequently, the recommendations for treatment and for the role of surgery are very variable 2).

Free article https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1656654/pdf/skullbasesurg00018-0039.pdf

Resections are considered in symptomatic patients who are refractory to targeted medical therapies, but at those stages the lipomas have often reached considerable sizes and encompass critical neurovascular structures.

Scoring system

The objective of a study is to develop and to evaluate the utility of a scoring system for CPA lipomas. The hypothesis is that CPA lipomas with lower scores are probably best managed with early surgery.

The PubMed database was searched using relevant terms. Data on patient and lipoma characteristics were extracted and used to design a scoring system. CPA lipomas were stratified by scores with corresponding managements and outcomes analyzed.

One hundred and seventeen patients with CPA lipomas were identified and 40 CPA lipomas were scored. The remaining CPA lipomas were deficient in data and not scored. No lipomas were scored as 1. Score 2 lipomas (n = 12; 30%) most often underwent serial surveillances (n = 5; 41.6%), with the majority of symptoms remaining unimproved (n = 2; 40%). Patients with score 2 CPA lipomas treated with medical therapies (n = 3; 25%) often experienced symptom resolution (n = 2; 66.6%) (p = 0.0499). Patients with score 2 CPA lipomas undergoing surgical resections (n = 3; 25%) all experienced symptom resolution (n = 3; 100%) (p = 0.0499). Score 3 was most common (n = 16; 40%) and these lipomas were often surgically resected (n = 10; 62.5%). The majority of patients with score 3 CPA lipomas having undergone surgical resections (n = 10; 62.5%) experienced symptom improvement (n = 1; 10%) or resolution (n = 4; 40%).

Score 2 CPA lipomas are smaller and would be deemed non-surgical in general practice. However, the data of Lagman et al., suggest that these lipomas may benefit from either medical therapies or early surgical resections. The advantages of early surgery are maximal resection, decreased surgical morbidity, and improved symptom relief 3).

Case series

2014

Of 15 patients with CPA lipomas, six were female and nine were male, with an average age at presentation of 50.2 years (range, 31.7-76.4 yr) and an average follow-up time of 51.7 months (range, 6-216 mo). The lipomas were unilateral in all cases, nine on the right (60%) and six on the left (40%) side. None of the lipomas increased in size. All patients were treated conservatively. Sensorineural hearing loss was the main presenting symptom (80%) followed by tinnitus (46.7%) and vertigo (20%). None of the patients suffered from facial nerve dysfunction. There was no correlation between weight gain and tumor growth.

CPA lipomas can be diagnosed accurately with appropriate magnetic resonance imaging techniques and be managed conservatively with safety. Cochleovestibular are the most common presenting symptoms, whereas facial nerve involvement is rare. CPA lipomas do not tend to grow and can be monitored on a less regular basis 4).

2013

Between 1996 and 2012, 15 patients were diagnosed with a CPA or IAC lipoma at the authors’ institution and were included in the analysis. The mean duration of radiological and clinical follow-up was 3.4 years and 5.1 years, respectively. Eight lesions were confined to the IAC, while seven involved the CPA. The median tumor size at diagnosis was 7.2 mm; one patient demonstrated tumor growth on serial MRI while the remaining subjects did not have radiological progression. The most common presenting symptoms were sensorineural hearing loss (40%) and tinnitus (33%); five patients were diagnosed after incidental discovery on MRI. Fourteen patients were managed with observation, while one subject underwent subtotal resection. None of the observed patients reported worsening symptoms at last follow-up.

While rare, lipomas should be included in the differential diagnosis of CPA and IAC lesions. Owing to a generally benign clinical course and high morbidity associated with resection, microsurgery should only be considered in cases of definite tumor enlargement with intractable symptoms from mass effect. Careful radiological evaluation is critical for establishing an accurate diagnosis in order to prevent unnecessary morbidity associated with resection 5).

2006

A healthy 42-year-old woman who presented with left-sided hearing loss and facial synkinesis. T1-weighted magnetic resonance imaging revealed an enhancing lesion of the left CPA with no signal on fat suppression sequences. Despite conservative therapy, the patient developed progressive hemifacial spasm, and a suboccipital craniotomy approach was used to debulk the tumor, which encased cranial nerves V, VII, VIII, IX, X, and XI. Surgical histopathology demonstrated mature adipocytes, consistent with lipoma. Two years after surgery, the patient remains free of facial nerve symptoms. Cerebellopontine angle lipomas are rare lesions of the skull base and are reliably diagnosed with T1-weighted and fat suppression magnetic resonance sequences, which we recommend in the routine radiologic workup of CPA tumors. Accurate preoperative diagnosis is crucial because most CPA lipomas should be managed conservatively. Partial surgical resection is indicated only to alleviate intractable cranial neuropathies or relieve brainstem compression 6).

2002

Tankéré et al., report four new cases of CPA lipomas diagnosed in the Department of Otorhinolaryngology-Head and Neck Surgery of Hôpital Pitié-Salpêtrière and review 94 cases reported previously in the literature.

Lipomas represented 0.14% of CPA and internal acoustic meatus tumors. Localization was on the left side in 59.9%, on the right side in 37%, and bilateral in 3.1% of the patients. The diagnosis was confirmed radiologically in 33 of 98 patients, surgically in 60 patients, and by autopsy in 5 patients. The most frequent associated symptoms were of cochleovestibular origin, such as hearing loss (62.2%), dizziness (43.3%), and unilateral tinnitus (42.2%). Other associated symptoms involved the facial nerve (9%) or the trigeminal nerve (14.4%). Complete resection was performed in only 32.8% of the patients with frequent cranial nerve involvement. Frequent cranial nerve involvement was seen in 95.4% of all patients. After surgery, patient symptomatology was unchanged in 9.2% of the patients, and 50% were improved; however, new postoperative deficits occurred in two-thirds of the patients. Overall, 72.2% of the patients experienced new postoperative deficits such as hearing loss (64.8%). Preservation of hearing was possible in only 26% of the patients. Only 18% of patients were improved after surgery without any new postoperative deficits.

Preoperative diagnosis of internal acoustic meatus/CPA lipomas is based on magnetic resonance imaging. The aim of surgery in these cases is not tumor removal but cranial nerve decompression or vestibular transection, and surgery is performed only in patients with disabling and uncontrolled symptoms 7).

1998

17 IAC/CPA lipomas, bringing the total number of documented cases to 84 in 1998. There appears to be a nearly 2:1 male to female predominance. Sixty percent were left-sided lesions, and three were bilateral. Hearing loss, dizziness, and tinnitus were the most common presenting symptoms. Surgical resection was performed in 52 (62%) of these lesions; however, total tumor removal was accomplished in only 17 (33%), which is most likely because of the fact that these tumors tend to have a poorly defined matrix and a dense adherence to neurovascular structures. Sixty-eight percent of patients experienced a new deficit postoperatively, 11% were unchanged, and only 19% improved with no new deficit. Only one documented case of tumor growth was identified; however, the reported follow-up was short (average, less than 3 years).

With the magnetic resonance imaging techniques now available, lipomas can be reliably differentiated from other masses within the CPA and IAC, so histopathologic diagnosis is rarely necessary. Because of the potential for significant morbidity with resection of these lesions, we believe that conservative follow-up is the best treatment option for patients with these rare lesions. Surgery is indicated only when significant progressive or disabling symptoms are present 8).

Case reports

2012

A 5-year-old boy was evaluated for recurrent primary generalized seizures of 20 days duration. He had preceding headache, vomiting for which he was subjected to a Magnetic resonance imaging (MRI) scan of the brain. Imaging studies revealed a hyperintense mass in the right CPA suggestive of lipoma/epidermoid. He was referred to us for further management.

Basic routine blood investigations were essentially normal. His vital parameters were stable. He was conscious, oriented, and obeying commands. Child was active and had no motor/sensory/cranial nerve deficits. Plantars were bilaterally flexor with normal deep tendon reflexes. MR imaging has now achieved a very high sensitivity and specificity for detecting lipomas. On T1-weighted MR images, lipomas typically appear hyperintense compared with brain tissue and hyperintense on T2-weighted MR images. MRI scan of the brain was done and the findings is given below.

Multiplanar, multisequences, MR imaging, including SE T1 axial, flair axial, FSE T2 axial were done. Postcontrast T1-weighted multiplanar sequences were also performed.

A 17mm (trans) ×15mm (AP) × 15mm (CC) well-encapsulated mass lesion noted in the right CP angle which was hyperintense on T1, T2, and FLAIR with inversion on fat suppression sequence. The lesion was situated inferior to the right Vth nerve and indenting upon right lower pons and medulla. The right VIIth and VIIIth nerves and superior cerebellar artery were encased by the lesion. No evidence of tumor extension into IAC was noted. There was neither significant shift nor hydrocephalus. Right cerebello pontine angle tumor–lipoma/epidermoid.

A right retro sigmoid suboccipital approach was chosen to expose the tumor. The lesion was extra-axial, yellowish and surrounding the seventh and eighth nerve complex. Branches of the AICA were embedded in the tumor. The lesion was partially decompressed. Neurovascular structures were preserved. There were no postoperative deficits.

Histopathological evaluation revealed it to be lipoma-right CP angle

These tumors can cause symptoms related to the VIII nerve involvement, such as hearing loss, tinnitus, and vertigo. However, trigeminal symptoms such as neuralgia, paresthesia or headache, can also occur with CPA lipomas extending to the trigeminal cisterns.

This patient presented with headache, and seizures. Neuroimaging revealed a hypodense mass in the right CPA suggestive of lipoma/epidermoid. He underwent surgical exploration and decompression of the tumor. Histopathology confirmed it as lipoma 9).

2009

A 13-year-old female patient was evaluated due to a 1-year history of headache and hearing loss. The physical examination was unremarkable. The audiometric evaluation demonstrated a discrete sensorineural hearing loss on the right side. The CT scan revealed a markedly hypodense non-enhancing mass in the right CPA. The MR imaging showed a lesion measuring 2.1 × 2.0 × 1.7 cm in the right CPA cistern. The mass was hyperintense on T1-weighted images and isointense with hypointense halo (chemical-shift) on T2-weighted images, with very low signal on T1-weighted images with fat suppression (Figs 1 and 2). The VII and VIII cranial nerves were seen as linear images with low signal inside the CPA mass. The diagnosis of CPA lipoma was suggested and the surgical treatment was chosen once the patient was young and the chance of lesion growing and future complications was considerable. A craniotomy with posterior fossa approach was performed, the lesion was partially removed, and the histological examination confirmed the diagnosis of lipoma. Six months after the surgery the patient remains asymptomatic. The parent signed the informed consent agreeing with the study.

Case 2

A 35-year-old woman presented with a six-month history of vertigo, without significant abnormalities on physical examination. A CT scan revealed a left-sided hypodense non-enhancing CPA mass. The MR imaging showed a left CPA cistern hyperintense lesion on T1-wheighted images and isointense with hypointense halo (chemical-shift) on T2-weighted images, measuring 1.4 × 1.3 cm and showing no enhancement after contrast administration (Fig 3). The diagnosis of CPA lipoma was suggested and the patient was managed conservatively. The symptoms were controlled with medical therapy. The follow-up MR imaging performed one year later showed no significant modifications 10).

1997

The case of an extensive lipoma of the cerebellopontine angle (CPA) represents 0.05% of all CPA tumors operated on in a department from 1978 to 1996. The lipoma constitutes an important differential diagnosis because the clinical management differs significantly from other CPA lesions. The clinical presentation and management of the presented case are analyzed in comparison to all previously described cases of CPA lipomas. The etiology and the radiological features of CPA lipomas are reviewed and discussed. CPA lipomas are maldevelopmental lesions that may cause slowly progressive symptoms. Neuroradiology enables a reliable preoperative diagnosis. Attempts of complete lipoma resection usually result in severe neurological deficits. Therefore, we recommend a conservative approach in managing these patients. Limited surgery is indicated if the patient has an associated vascular compression syndrome or suffers from disabling vertigo 11).

1994

Two patients with cerebellopontine angle (CPA) lipoma were studied. They were submitted to surgical treatment. Available literature was reviewed and 29 cases with same lesion were identified which had been treated by surgery. Clinical manifestations, possibility of diagnostic methods, surgical indications and treatment strategies are discussed. Attention is called to the peculiarities of CPA lipomas and the doubtful validity of attempting complete excision in all cases12).


1) Bonneville F, Sarrazin JL, Marsot-Dupuch K, Iffenecker C, Cordoliani YS, Doyon D, Bonneville JF. Unusual lesions of the cerebellopontine angle: a segmental approach. Radiographics. 2001 Mar-Apr;21(2):419-38. PubMed PMID: 11259705.
2) , 11) Schuhmann MU, Lüdemann WO, Schreiber H, Samii M. Cerebellopontine angle lipoma: a rare differential diagnosis. Skull Base Surg. 1997;7(4):199-205. PubMed PMID: 17171031; PubMed Central PMCID: PMC1656654.
3) Lagman C, Voth BL, Chung LK, Bui TT, Lee SJ, Barnette NE, Gopen Q, Yang I. Evaluating the utility of a scoring system for lipomas of the cerebellopontine angle. Acta Neurochir (Wien). 2017 Jan 21. doi: 10.1007/s00701-017-3076-5. [Epub ahead of print] PubMed PMID: 28110401.
4) Kontorinis G, Freeman SR, Potter G, Rutherford SA, Siripurapu R, King AT, Lloyd SK. Management of cerebellopontine angle lipomas: need for long-term radiologic surveillance? Otol Neurotol. 2014 Jun;35(5):e163-8. doi: 10.1097/MAO.0000000000000395. PubMed PMID: 24691513.
5) White JR, Carlson ML, Van Gompel JJ, Neff BA, Driscoll CL, Lane JI, Link MJ. Lipomas of the cerebellopontine angle and internal auditory canal: Primum Non Nocere. Laryngoscope. 2013 Jun;123(6):1531-6. doi: 10.1002/lary.23882. PubMed PMID: 23401141.
6) Brodsky JR, Smith TW, Litofsky S, Lee DJ. Lipoma of the cerebellopontine angle. Am J Otolaryngol. 2006 Jul-Aug;27(4):271-4. PubMed PMID: 16798407.
7) Tankéré F, Vitte E, Martin-Duverneuil N, Soudant J. Cerebellopontine angle lipomas: report of four cases and review of the literature. Neurosurgery. 2002 Mar;50(3):626-31; discussion 631-2. Review. PubMed PMID: 11841733.
8) Bigelow DC, Eisen MD, Smith PG, Yousem DM, Levine RS, Jackler RK, Kennedy DW, Kotapka MJ. Lipomas of the internal auditory canal and cerebellopontine angle. Laryngoscope. 1998 Oct;108(10):1459-69. Review. PubMed PMID: 9778284.
9) Venkataramana N, Rao SA, Naik AL, Chaitanya K, Murthy P. Cerebello pontine angle lipoma in a child. J Pediatr Neurosci. 2012 Jan;7(1):75-7. doi: 10.4103/1817-1745.97635. PubMed PMID: 22837790; PubMed Central PMCID: PMC3401666.
10) Borges RS, Brito CC, Carvalho GA, Domingues RC, Gasparetto EL. Cerebellopontine angle lipomas: magnetic resonance imaging findings in two cases. Arq Neuropsiquiatr. 2009 Jun;67(2B):496-8. PubMed PMID: 19623450.
12) Ferreira MP, Ferreira NP, Lenhardt R. Lipoma of the cerebellopontine angle. Case reports and literature review. Arq Neuropsiquiatr. 1994 Mar;52(1):58-63. Review. PubMed PMID: 8002809.

Update: Craniopharyngioma malignant transformation

Epidemiology

Sofela et al., conducted in 2014 conducted a PUBMED, SCOPUS, OVID SP, and INFORMA search with a combination of key words: craniopharyngioma, malignancy, transformation, neoplasm, radiation therapy, and anaplastic. They identified 23 cases relevant to our study.

Median age at the time of diagnosis of malignant craniopharyngiomas was 31 years (range, 10-66 years); 52.6% of the patients were female. Histologically, the most common tumor types were squamous cell carcinoma (80.96%), with adamantinomatous cell type being the most common morphology (89.47%).

Sofela et al., found that 21.7% of the cases were diagnosed as malignant craniopharyngioma at first biopsy. Of the rest, the median time from initial benign diagnosis to MT was 8.5 years (range, 3-55 years). Median overall survival after MT was 6 months (range, 2 weeks-5 years). Using the Spearman rank correlation, we found no correlation between the use of radiation therapy (correlation coefficient, -0.25; P < .05) or its dosage (correlation coefficient, -0.26; P < .05) and MT 2).

Pathogenesis

The exact cause and pathogenesis of this MT are unknown, although the literature has suggested a possible correlation with radiotherapy 3).

Radiation therapy and p53 mutations could be involved in malignant transformation in craniopharyngioma 4).

Histology

It assumes varied histologic appearances, usually after multiple recurrences and radiation therapy, and has a near uniformly fatal outcome. De novo malignancy in odontogenic tumors of the sella is even more unusual, but also has an ominous prognosis 5).

Outcome

Malignant craniopharyngiomas are associated with a poor prognosis. MTs occur years after the initial benign craniopharyngioma diagnosis and are associated with multiple benign craniopharyngioma recurrence. Results also show that, contrary to widespread belief, there is a poor correlation between radiotherapy and MT 6).

Case reports

2017

Jeong et al., report the case of a 26-year-old male patient who underwent suprasellar mass excision via an interhemispheric transcallosal approach. Histopathological examination indicated that the craniopharyngioma was of the adamantinomatous subtype. The patient received postoperative medical treatment for endocrine dysfunction and diabetes mellitus without radiation treatment. Two years after the operation, he presented with progressive visual disturbance and altered mentality. Magnetic resonance imaging revealed a huge mass in the suprasellar cistern and third ventricle. He underwent a second operation via the same approach. The histopathological examination showed an adamantinomatous craniopharyngioma with sheets of solid proliferation in a spindled pattern, indicating malignant transformation 7).

2015

A 29-year-old male patient was admitted into hospital with the main complaint of progressive visual disturbance. Both CT SCAN and MRI demonstrated a cystic-solid contrast-enhancing sellar-suprasellar mass with obvious calcification. Histopathological examination of the first resected specimen showed a typical appearance of adamantinomatous craniopharyngioma. The patient received gamma knife therapy after his first operation because of partial tumor removal. He experienced two relapses in the subsequent 2 years, for which only surgical resection was performed. The later histopathology presented malignant appearance with tumor cells moderate to severe pleomorphism, hyperchromasia, increased nuclear cytoplastic ratio, high mitotic activity (30/10 high power fields) and focal coagulative necrosis. The patient died 9 months after identification of histologic malignancy. Clinical and histopathological features, biological behavior of one case of malignant craniopharyngioma were discussed, with a brief review of the relevant literature 8).

2014

Malignant transformation of craniopharyngioma in an infradiaphragmatic case 9).

2011

A 66-year-old female who presented with visual disturbance and radiological evidence of a sellar and suprasellar tumor. The patient underwent transsphenoidal biopsy followed by pterional craniotomy with partial tumor removal. Histological diagnosis documented a malignant adamantinomatous type craniopharyngioma. The patient received adjuvant radiotherapy with a significant tumor reduction. She remained in good clinical conditions for 10 months; she deteriorated and died, due to tumor progression, 15 months after diagnosis.

This is the first case of de novo malignant craniopharyngioma with significant follow-up 10).


Gao et al., report a case of ameloblastic carcinoma arising from a previously benign craniopharyngioma in a 42-year-old woman. The patient was diagnosed with craniopharyngioma in August 2004 and underwent surgical resection of a typical craniopharyngioma, the pathological result was craniopharyngioma, papillary and adamantinomatous types. During the subsequent 5 years, this patient experienced two recurrences, for which surgical resections were performed without radiotherapy. The last two pathologic diagnoses were malignant craniopharyngiomas and there was more apparent sign of malignancy in the third pathologic section 11).

2010

Aquilina et al., describe 2 additional pediatric cases. Treatment in both of these cases consisted of multiple resections and external beam radiation therapy (EBRT). Malignant transformation occurred 7 and 8 years after EBRT. The authors also review another 6 cases in adults. A possible causative association with radiation therapy is discussed. As radiation is currently an important option in the management of craniopharyngiomas, this association requires further study 12).


A 32-year-old man presented with malignant craniopharyngioma associated with moyamoya syndrome manifesting as right visual disturbance. Magnetic resonance (MR) imaging revealed a parasellar mass lesion diagnosed as adamantinomatous craniopharyngioma. He underwent three surgical procedures and repeated courses of radiotherapy, and was able to resume his daily life. MR imaging demonstrated tumor regrowth and bilateral occlusions of the internal carotid arteries (ICAs) with basal moyamoya phenomenon, which might have been induced by irradiation and/or tumor compression, 10 years after the initial manifestations. Sufficient debulking was safely achieved via the transsphenoidal route and histological examination revealed squamous cell carcinoma, indicating malignant transformation of craniopharyngioma. The tumor relapsed after only one month, so transsphenoidal tumor debulking was tried again. However, the postoperative course was unfavorable because of intraoperative bleeding from the right ICA. Malignant transformation of craniopharyngioma may be included in moyamoya syndrome. The treatment strategy should be carefully considered in such a complicated situation 13).


Ishida et al.,report a case of malignant transformation in craniopharyngioma after radiation therapy.

Histopathological and immunohistochemical analyses were carried out for specimens of the suprasellar tumor (from three resections, with the third surgery performed after radiation therapy).

The resected tumors from the first and second surgeries comprised islands of loosely cohesive aggregates of epithelial cells, so-called stellate reticulum. At the periphery of the nests, palisaded columnar epithelium was observed. Wet keratins were scattered, and few mitotic figures were seen. The third surgical specimen was composed of irregular large nests of basaloid cells that had large, round to oval nuclei with prominent nucleoli, and mitotic figures were frequently seen (21/10 high power fields). In the center of the nests, eosinophilic ghost cells, resembling wet keratin, were observed. Accordingly, the diagnosis of malignant transformation in craniopharyngioma was made. Immunohistochemical studies revealed that the p53 protein was over-expressed in the malignant component, whereas its expression was much lower in the benign component.

Similar to the ten previously reported cases of malignant transformation in craniopharyngioma, the present case occurred after radiation therapy. p53 protein overexpression was also observed in the earlier cases of malignant craniopharyngioma as well as in the present case (6/6 cases). They concluded that radiation therapy and p53 mutations could be involved in malignant transformation in craniopharyngioma 14).

2009

A case of malignant craniopharyngioma in a 46-year-old woman presenting clinically with visual disturbance and bifrontal headache is reported. Histopathologic examination of the suprasellar mass showed a lesion characterized by nests of epithelial cells with a basaloid appearance, round-to-oval nuclei, moderate pleomorphism, hyperchromasia, increased nuclear cytoplastic ratio and high mitotic activity. Immunohistochemically, the tumor cells were positive for Ki-67 (44.3%), p53 (98%), and p63 (100%), but negative for estrogen and progesterone receptors 15).

2007

Rodriguez et al., report 3 patients with craniopharyngiomas exhibiting histologic malignancy, 2 of which received radiation therapy before its appearance. Hematoxylin and eosin-stained slides and selected immunohistochemical stains were reviewed in all cases. Microvessel density analysis was performed in case 2. The patients included 2 men and 1 woman, age 14, 31, and 58 years at presentation, respectively. All patients expired 3 months to 9 years after first resection and 3 to 9 months after identification of histologic malignancy. The latter developed after multiple recurrences and radiation therapy in 2 cases, but seemed to arise de novo in 1 case resembling odontogenic ghost cell carcinoma and lacking any definite low-grade craniopharyngioma precursor. The malignant component of the other 2 cases resembled squamous cell carcinoma and low-grade myoepithelial carcinoma, respectively. The MIB-1 labeling index was markedly increased in the malignant component in comparison with the low-grade precursor 16).

2006

Malignant transformation of craniopharyngioma: a case report 17).

2004

A 21-year-old woman, who developed a malignant tumour arising from a craniopharyngioma 14 years after the original diagnosis. The remarkable response of this malignant tumour ex-craniopharyngioma to cis-platin based chemotherapy, together with other midline tumour characteristics of craniopharyngioma, raise the question as to whether craniopharyngioma should any longer be separately considered from suprasellar germ cell tumour 18).

2000

Kristopaitis et al., describe a case of squamous cell carcinoma arising in a previously benign craniopharyngioma in a 42-year-old woman. The patient was diagnosed with craniopharyngioma in 1982; during the subsequent 15 years she experienced 7 tumor recurrences, for which surgical resections and 3 courses of radiotherapy were performed. In 1998, the tumor recurred with involvement of the nasal cavity and sphenoid and ethmoid sinuses. Histologic evaluation revealed foci of typical adamantinomatous craniopharyngioma associated with a moderately differentiated squamous cell carcinoma. The transition of typical craniopharyngioma to squamous cell carcinoma was well demonstrated, suggesting that carcinoma arose from the underlying craniopharyngioma. Radiation may have been a contributing factor to carcinogenesis in this case 19).

1999

Virik et al., report a further case of malignant transformation in recurrent craniopharyngioma following radiotherapy 20).

1989

Two cases of a craniopharyngioma with malignant transformation are reported. Case 1 involved a 3-year-old male who had received a partial resection and radiotherapy for a suprasellar tumor. Histologically, a biopsy specimen showed craniopharyngioma. Eight years later, the child died of an intracerebral and nasopharyngeal invasion of the recurrent tumor. Case 2 involved a 9-year-old male who initially had been diagnosed as having a craniopharyngioma in the suprasellar region. Five years after the first operation, he died from growth of the tumor in spite of radiotherapy and a partial resection. The pathological examinations of these two cases showed an apparent transition of the craniopharyngioma into a squamous cell carcinoma 21).

1988

A 49-year-old woman presented with recurrence of a suprasellar craniopharyngioma diagnosed 35 years previously. The patient had been treated surgically for recurrence on five occasions. Radiation therapy had been administered 7 years before the final presentation. Tissue obtained from the fifth operation revealed malignant degeneration in a typical craniopharyngioma 22).

1987

Akachi et al., report a rare case of a 10-year-old girl with craniopharyngioma which showed malignant change after the first operation and irradiation. In June 1981, the patient complained of headache, nausea and vomiting. CT revealed obstructive hydrocephalus due to the calcified mass lesion which extended to the third ventricle. In order to alleviate the high intracranial pressure, the right ventriculo-peritoneal shunt was first settled and after that, partial removal of the tumor was performed. The pathological diagnosis of the specimen was typical adamantinomatous type of craniopharyngioma without any findings of malignancy. After this operation irradiation was performed. The tumor almost disappeared and the patient was discharged from the hospital and went to school, showing some signs of panhypopituitarism. In May 1984, she complained of decreased left visual acuity, right temporal anopsia, headache, nausea and vomiting. CT revealed recurrence of the tumor which obstract the foramen of Monro bilaterally. As an emergency measure, the left ventriculo-peritoneal shunt was added and the state of the patient became recovered. In order to improve decreased visual acuity, the tumor located around the optic nerves and over the frontal base was removed in June 1984, resulting in partial improvement of visual acuity bilaterally. The pathological examination of the second specimen showed, in addition to the part of adamantinomatous type of craniopharyngioma which was the same as before, the existence of thick layer of stratified large atypical cells which partially covered the cyst wall and partially invaded into the surrounding tissues. The pathological diagnosis was poorly differentiated squamous cell carcinoma with craniopharyngioma of ‘adamantinoma’ type 23).


1) Akachi K, Takahashi H, Ishijima B, Nakamura Y, Oda M, Takizawa T, Iwamoto M, Kuriyama G, Shizuki K. [Malignant changes in a craniopharyngioma]. No Shinkei Geka. 1987 Aug;15(8):843-8. Japanese. PubMed PMID: 3431651.
2) , 6) Sofela AA, Hettige S, Curran O, Bassi S. Malignant transformation in craniopharyngiomas. Neurosurgery. 2014 Sep;75(3):306-14; discussion 314. doi: 10.1227/NEU.0000000000000380. Review. PubMed PMID: 24978859.
3) Virik K, Turner J, Garrick R, Sheehy JP. Malignant transformation of craniopharyngioma. J Clin Neurosci. 1999 Nov;6(6):527-30. PubMed PMID: 18639199.
4) , 14) Ishida M, Hotta M, Tsukamura A, Taga T, Kato H, Ohta S, Takeuchi Y, Nakasu S, Okabe H. Malignant transformation in craniopharyngioma after radiation therapy: a case report and review of the literature. Clin Neuropathol. 2010 Jan-Feb;29(1):2-8. Review. PubMed PMID: 20040326.
5) , 16) Rodriguez FJ, Scheithauer BW, Tsunoda S, Kovacs K, Vidal S, Piepgras DG. The spectrum of malignancy in craniopharyngioma. Am J Surg Pathol. 2007 Jul;31(7):1020-8. PubMed PMID: 17592268.
7) Jeong TS, Yee GT, Kim NR. Malignant Transformation of Craniopharyngioma without Radiation Therapy: Case Report and Review of the Literature. J Korean Neurosurg Soc. 2017 Jan 1;60(1):108-113. doi: 10.3340/jkns.2015.0707.022. PubMed PMID: 28061501.
8) Wang W, Chen XD, Bai HM, Liao QL, Dai XJ, Peng DY, Cao HX. Malignant transformation of craniopharyngioma with detailed follow-up. Neuropathology. 2015 Feb;35(1):50-5. doi: 10.1111/neup.12142. PubMed PMID: 25112406.
9) Lu Y, Qi S, Peng J, Pan J, Zhang X. Malignant transformation of craniopharyngioma in an infradiaphragmatic case. Chin Med J (Engl). 2014;127(17):3187-8. PubMed PMID: 25189968.
10) Lauriola L, Doglietto F, Novello M, Signorelli F, Montano N, Pallini R, Maira G. De novo malignant craniopharyngioma: case report and literature review. J Neurooncol. 2011 Jun;103(2):381-6. doi: 10.1007/s11060-010-0382-7. Review. PubMed PMID: 20814809.
11) Gao S, Shi X, Wang Y, Qian H, Liu C. Malignant transformation of craniopharyngioma: case report and review of the literature. J Neurooncol. 2011 Jul;103(3):719-25. doi: 10.1007/s11060-010-0407-2. Review. PubMed PMID: 20872276.
12) Aquilina K, Merchant TE, Rodriguez-Galindo C, Ellison DW, Sanford RA, Boop FA. Malignant transformation of irradiated craniopharyngioma in children: report of 2 cases. J Neurosurg Pediatr. 2010 Feb;5(2):155-61. doi: 10.3171/2009.9.PEDS09257. PubMed PMID: 20121363.
13) Ujifuku K, Matsuo T, Takeshita T, Hayashi Y, Hayashi K, Kitagawa N, Hayashi T, Suyama K, Nagata I. Malignant transformation of craniopharyngioma associated with moyamoya syndrome. Neurol Med Chir (Tokyo). 2010;50(7):599-603. PubMed PMID: 20671391.
15) Boongird A, Laothamatas J, Larbcharoensub N, Phudhichareonrat S. Malignant craniopharyngioma; case report and review of the literature. Neuropathology. 2009 Oct;29(5):591-6. doi: 10.1111/j.1440-1789.2008.00986.x. Review. PubMed PMID: 19077042.
17) Yue Y, Da JP. [Malignant transformation of craniopharyngioma: a case report]. Zhonghua Bing Li Xue Za Zhi. 2006 Jul;35(7):439. Chinese. PubMed PMID: 17069689.
18) Plowman PN, Besser GM, Shipley J, Summersgill B, Geddes J, Afshar F. Dramatic response of malignant craniopharyngioma to cis-platin-based chemotherapy. Should craniopharyngioma be considered as a suprasellar ‘germ cell’ tumour? Br J Neurosurg. 2004 Oct;18(5):500-5. PubMed PMID: 15799153.
19) Kristopaitis T, Thomas C, Petruzzelli GJ, Lee JM. Malignant craniopharyngioma. Arch Pathol Lab Med. 2000 Sep;124(9):1356-60. PubMed PMID: 10975938.
20) Virik K, Turner J, Garrick R, Sheehy JP. Malignant transformation of craniopharyngioma. J Clin Neurosci. 1999 Nov;6(6):527-30. PubMed PMID: 18639199.
21) Suzuki F, Konuma I, Matsumoto M, Aoki M, Hayakawa I. [Craniopharyngioma with malignant transformation–a report of two cases]. Gan No Rinsho. 1989 May;35(6):723-8. Review. Japanese. PubMed PMID: 2657129.
22) Nelson GA, Bastian FO, Schlitt M, White RL. Malignant transformation in craniopharyngioma. Neurosurgery. 1988 Feb;22(2):427-9. PubMed PMID: 3352897.
23) Akachi K, Takahashi H, Ishijima B, Nakamura Y, Oda M, Takizawa T, Iwamoto M, Kuriyama G, Shizuki K. [Malignant changes in a craniopharyngioma]. No Shinkei Geka. 1987 Aug;15(8):843-8. Japanese. PubMed PMID: 3431651.

Update: Vernet’s syndrome


In contrast to the majority of classic brainstem syndromes, the interpretation of Schmidt’s syndrome (ipsilateral palsy of the IX, X, XI, and XII cranial nerves with contralateral hemiparesis) and Vernet’s syndrome (ipsilateral palsy of the IX, X, and XI nerves with contralateral hemiparesis) is controversial. They are sometimes addressed as crossed brainstem syndromes but also as syndromes due to multiple cranial nerve lesions without contralateral hemiparesis. In this study, the historic descriptions and recent publications about Schmidt’s and Vernet’s syndromes were reviewed and critically analysed. We conclude that historic descriptions and later publications describe exclusively patients with extracerebral lesions of multiple cranial nerves. “Central” syndromes of Schmidt and Vernet caused by brainstem lesion appear not to exist. An extremely extensive lesion explaining these hypothetical unilateral brainstem syndromes is theoretically possible but, however, was apparently never observed in any of the known unilateral brainstem diseases 1).

Symptoms

Symptoms of this syndrome are consequences of this paresis. As such, in an affected patient, you may find:

dysphonia/hoarseness

soft palate dropping

deviation of the uvula towards the normal side

dysphagia

loss of sensory function from the posterior 1/3 of the tongue

decrease in the parotid gland secretion

loss of gag reflex

sternocleidomastoid and trapezius muscles paresis.

Etiology

A variety of neoplasms, vascular insults, infections, and trauma have been reported to cause JFS 2).


The causes of Vernet syndrome are primary tumors such as Glomus jugulare tumors (most frequently), meningioma, vestibular schwannoma, cerebellopontine angle metastases, inflammation such as meningitis and malignant otitis externa, and sarcoidosis, Guillain-Barre syndrome 3).

Trauma 4) 5).

Cholesteatoma (very rare) 6).

Obstruction of the jugular foramen due to bone diseases 7).

Varicella-zoster virus 8).

Giant cell arteritis 9) 10).

Internal jugular vein thrombosis 11).

After carotid endarterectomy 12).

Large mycotic aneurysm of the extracranial internal carotid artery after acute otitis media 13).

Systemic erythematous lupus 14).


1) Krasnianski M, Neudecker S, Zierz S. [The Schmidt and Vernet classical syndrome. Alternating brain stem syndromes that do not exist?]. Nervenarzt. 2003 Dec;74(12):1150-4. Review. German. PubMed PMID: 14647918.
2) Robbins KT, Fenton RS. Jugular foramen syndrome. J Otolaryngol. 1980 Dec;9(6):505-16. PubMed PMID: 7206037.
3) Ha SW, Kim JK, Kang SJ, Kim MJ, Yoo BG, Kim KS, et al. A case of Vernet’s syndrome caused by non-specific focal inflammation of the neck. J Korean Soc Clin Neurophysiol. 2007;9:81–84.
4) , 5) Kim HS, Ko K. Penetrating trauma of the posterior fossa resulting in Vernet’s syndrome and internuclear ophthalmoplegia. J Trauma. 1996 Apr;40(4):647-9. PubMed PMID: 8614050.
6) Erol FS, Kaplan M, Kavakli A, Ozveren MF. Jugular foramen syndrome caused by choleastatoma. Clin Neurol Neurosurg. 2005 Jun;107(4):342-6. PubMed PMID: 15885397.
7) Erol FS, Kaplan M, Kavakli A, Ozveren MF.Jugular foramen syndrome caused by choleastatoma. Clin Neurol Neurosurg. 2005 Jun;107(4):342-6.
8) Jo YR, Chung CW, Lee JS, Park HJ. Vernet syndrome by varicella-zoster virus. Ann Rehabil Med. 2013 Jun;37(3):449-52. doi: 10.5535/arm.2013.37.3.449. PubMed PMID: 23869347; PubMed Central PMCID: PMC3713306.
9) Jeret JS. Giant cell arteritis and Vernet’s syndrome. Neurology. 1999 Feb;52(3):677. PubMed PMID: 10025824.
10) Cherin P, De Gennes C, Bletry O, Lamas A, Launay M, Dubs A, Godeau P. Ischemic Vernet’s syndrome in giant cell arteritis: first two cases. Am J Med. 1992 Sep;93(3):349-52. PubMed PMID: 1524092.
11) Shima K, Iwasa K, Yoshita M, Yamada M. Vernet’s syndrome induced by internal jugular vein thrombosis. J Neurol Neurosurg Psychiatry. 2016 Nov;87(11):1252-1253. doi: 10.1136/jnnp-2015-311665. PubMed PMID: 26354943.
12) Tamaki T, Node Y, Saitoum N, Saigusa H, Yamazaki M, Morita A. Vernet’s syndrome after carotid endarterectomy. Perspect Vasc Surg Endovasc Ther. 2013 Dec;25(3-4):65-8. doi: 10.1177/1531003514525476. PubMed PMID: 24625858.
13) Amano M, Ishikawa E, Kujiraoka Y, Watanabe S, Ashizawa K, Oguni E, Saito A, Nakai Y, Ikeda H, Abe T, Uekusa Y, Matsumura A. Vernet’s syndrome caused by large mycotic aneurysm of the extracranial internal carotid artery after acute otitis media–case report. Neurol Med Chir (Tokyo). 2010 Jan;50(1):45-8. PubMed PMID: 20098025.
14) Leache Pueyo JJ, Campos del Alamo MA, Gil Paraíso P, Ortiz García A. [Vernet’s syndrome as an early manifestation of systemic erythematous lupus]. An Otorrinolaringol Ibero Am. 1997;24(2):135-41. Spanish. PubMed PMID: 9199109.

Genome-wide analysis of differentially expressed lncRNAs and mRNAs in primary gonadotrophin adenomas by RNA-seq

Long noncoding RNAs (lncRNAs) have received increased research interest owing to their participation via distinct mechanisms in the biological processes of clinically nonfunctioning pituitary adenomas. However, changes in the expression of lncRNAs in gonadotropin secreting pituitary adenoma, which is the most common nonfunctional pituitary adenomas, have not yet been reported.

Li et al., performed a genome-wide analysis of lncRNAs and mRNAs obtained from gonadotrophin adenoma patients’ samples and normal pituitary tissues using RNA-seq. The differentially expressed lncRNAs and mRNAs were identified using fold-change filtering.

They identified 839 lncRNAs and 1015 mRNAs as differentially expressed. Gene Ontology analysis indicated that the biological functions of differentially expressed mRNAs were related to transcription regulator activity and basic metabolic processes. Ingenuity Pathway Analysis was performed to identify 64 canonical pathways that were significantly enriched in the tumor samples. Furthermore, to investigate the potential regulatory roles of the differentially expressed lncRNAs on the mRNAs, they constructed general co-expression networks for 100 coding and 577 non-coding genes that showed significantly correlated expression patterns in tumor cohort. In particular, they built a special sub-network of co-expression involving 186 lncRNAs interacting with 15 key coding genes of the mTOR pathway, which might promote the pathogenesis of gonadotrophin tumor. This is the first study to explore the patterns of genome-wide lncRNAs expression and co-expression with mRNAs, which might contribute to the molecular pathogenesis of gonadotrophin adenoma 1).

Diagnosis

Gonadotroph adenomas are difficult to diagnose because they are usually non-secreting, or they secrete biologically inactive peptides with no clinical effects, and they classically grow silently until neurological symptoms develop.

Clinical signs or symptoms of gonadotropin hypersecretion are very rarely reported, involving a few premenopausal women with ovarian hyperstimulation syndrome and men with macro- orchids.

A large proportion of the adult patients undergoing surgery for clinically nonfunctioning pituitary adenoma had a silent gonadotroph adenoma: the definitive diagnosis can only be established from a positive FSH/LH immunoreactivity.

Most are endocrinologically silent, and neurological symptoms due to their large volume are the first clinical signs; they are rarely reported to be secreting gonadotropins, this usually occurring in cases with clinical endocrine findings.

Among gonadotropinomas, female gender (77%), macroadenoma (84%), young age at diagnosis (28 ± 12 years), delay from first symptoms to diagnosis (up to 15 years), and ovarian cysts/menstrual disorders in females or macro-orchidism in males were the foremost clinical and neuroimaging features.

Male gonadotropin-secreting pituitary adenomas may have a variable clinical expression secondary to testosterone excess. Somatostatin analogs, dopamine agonists or temozolomide may have a role that needs to be assessed case by case.

Treatment

Gonadotrophinomas are often treated surgically because they are unresponsive to conventional medical therapies. Temozolomide was recently recommended for non-responder aggressive pituitary adenoma management 2).


1) Li J, Li C, Wang J, Song G, Zhao Z, Wang H, Wang W, Li H, Li Z, Miao Y, Li G, Zhang Y. Genome-wide analysis of differentially expressed lncRNAs and mRNAs in primary gonadotrophin adenomas by RNA-seq. Oncotarget. 2016 Dec 15. doi: 10.18632/oncotarget.13948. [Epub ahead of print] PubMed PMID: 27992366.
2) Ceccato F, Occhi G, Regazzo D, Randi ML, Cecchin D, Gardiman MP, Manara R, Lombardi G, Denaro L, Mantero F, Scaroni C. Gonadotropin secreting pituitary adenoma associated with erythrocytosis: case report and literature review. Hormones (Athens). 2014 Jan-Mar;13(1):131-9. PubMed PMID: 24722134.