Journal of Clinical Neuroscience 19 (2012) 1516–1519

Contents lists available at SciVerse ScienceDirect

Journal of Clinical Neuroscience

journal homepage: www.elsevier .com/ locate/ jocn

Clinical Study

Isolated primary craniopharyngioma in the cerebellopontine angle

Mahmoud Reza Khalatbari a,⇑, Hamid Borghei-Razavi b, Mohammad Samadian c,Yashar Moharamzad a, Uta Schick b

a Department of Neurosurgery, Arad Hospital, Somayeh Street, Between Dr. Shariati and Bahar Avenue, Tehran 1445613131, Iranb Department of Neurosurgery, Clemens Hospital, Munster, Germanyc Department of Neurosurgery, Shahid Beheshti University of Medical Sciences, Tehran, Iran

a r t i c l e i n f o a b s t r a c t

Article history:Received 11 June 2011Accepted 30 September 2011

Keywords:Cerebellopontine angleCraniopharyngiomaEpithelial tumor

0967-5868/$ - see front matter � 2011 Elsevier Ltd. Ahttp://dx.doi.org/10.1016/j.jocn.2011.09.029

⇑ Corresponding author. Tel.: +98 21 66515001–9;E-mail address: mrkhalatbari@hotmail.com (M.R.

Between January 2000 and January 2011, we diagnosed three patients with isolated craniopharyngiomain the cerebellopontine angle (CPA). Brain MRI revealed cystic lesions with various imaging characteris-tics, including hypointensity on T1-weighted (T1W) images and hyperintensity on T2-weighted (T2W)images. The first patient’s lesion showed rim enhancement after gadolinium administration. The secondpatient’s lesion showed mixed signal intensity on both T1W and T2W images. The third patient’s MRIshowed a well-defined cystic lesion in the right CPA that compressed the brainstem. This lesion washyperintense on T1W images and hypointense relative to cerebrospinal fluid on T2W images, and wasperipherally enhanced after gadolinium administration. All three patients underwent surgical interven-tion through a suboccipital retrosigmoid craniotomy/craniectomy and lesions that did not adhere to adja-cent tissues were removed completely. Histopathological examination confirmed the tumors to beadamantinomatous craniopharyngioma. The post-operative course was uneventful for all patientsuneventful and no tumor recurrences were detected at the last follow-up. Primary CPA craniopharyngi-oma can be completely removed surgically, provided it does not densely adhere to vital structures.

� 2011 Elsevier Ltd. All rights reserved.

1. Introduction

Craniopharyngiomas are benign epithelially derived tumorsthat arise from remnants of Rathke’s pouch. They account for1.2% to 4.6% of all intracranial tumors.1,2 The tumor is most com-monly located in the suprasellar region between the sella andthe hypothalamus, either anterior to, or posterior to, the optic chi-asma. A smaller number of craniopharyngiomas are located in theintrasellar region,1,3–6 or extend in multiple directions. Anterior,middle, and posterior cranial fossa extensions have been noted in5%, 2%, and 4% of patients, respectively.4,7 Unusual locations for re-ported craniopharyngiomas include the posterior fossa,4,7 temporalextradural space,3 and infrasellar region.6

Isolated primary craniopharyngioma of the cerebellopontineangle (CPA) is rare, and to our knowledge only six patients havebeen reported in the English literature (Table 1). We report threepatients with isolated primary craniopharyngioma of the CPAand discuss the pathogenesis, clinical, radiological and surgicalfindings of these patients, with a review of the literature.

ll rights reserved.

fax: +98 21 66517118.Khalatbari).

2. Materials and methods

Between January 2000 and January 2011, three patients werediagnosed with isolated craniopharyngioma of the CPA in our ter-tiary referral medical centre. All patients underwent brain CT scansand MRI and the lesions were surgically removed. Histopatholo-gical examination confirmed the tumors were adamantinomatouscraniopharyngiomas. The patients’ post-operative courses wereuneventful and the cranial nerve deficits observed upon originalpresentation improved. The patients were followed after surgeryfor between three months and five years, and no tumor recur-rences were reported.

3. Results

3.1. Patient 1

A 40-year-old man was admitted for evaluation of two-yearprogressive hearing loss in the left ear, which had been accompa-nied by tinnitus and diplopia for the past three months. He hadalso experienced intermittent severe headaches for the pastmonth. His hearing was diminished on the left side and he wasataxic. There were no sensory or motor deficits. Neurologicalexamination confirmed a slight lower motor neuron paresis of

Table 1Reported patients with isolated primary cerebellopontine angle adamantinomatous craniopharyngioma

Yearref Age,gender

Presenting symptoms CT scan MRI Extentofremoval

Outcome

199012 17/F Headache, vomiting, loss ofhearing, ataxia

Left CPA cystic mass,hydrocephalus

NP Total Excellent

20022 29/M Headache, tinnitus, deficitof cranial nerves V, VI, VII,VIII, IX, and X, with FAP

Rt CPA hyperdense masswith few calcifications

Mixed signal, solid and partiallycystic mass, mixed enhancement

Subtotal Well, transient dysphagia,persistent hearing loss

20061 31/M Headache, vomiting ataxia,blurred vision, with FAP

Rt CPA well-defined cysticlesion, enhancing muralnodule, hydrocephalus

Heterogeneous, partially cystic,patchy peripheral enhancement

Neartotal

Excellent

200710 12/F Headache, vomiting NR Left CPA mass, T1W MRI = isointense,T2W MRI = hyperintense,FLAIR = hyperintense, DWI = dark

Neartotal

Well, palsy of cranialnerves VI and VII,V1 andV2 nerve sensory deficit

200911 54/F Headache, tinnitus, ataxia,left hemiparesis, deficit ofright cranial nerves V–X

Heterogeneous enhancingmass with nodularcalcification

T1W MRI = mixed signal, T2WMRI = mixed signal, GDimage = significant enhancement

Subtotal Poor, dysphagia,hemiparesis, pneumonia

20115 34/M Hemiparesis, tinnitus, lefthearing loss with FAP

Left CPA mass, hyperdense,calcified non-homogenousenhancement

T1W MRI = hyperintense, T2WMRI = heterogeneous, hypointense,non-homogeneous enhancement

Total Excellent

2012 – presentstudy

40/M Tinnitus, left hearing loss,diplopia, headache, palsy ofcranial nerves VI and VII

NP Left CPA mass, T1WMRI = hypointense, T2WMRI = hyperintense, rimenhancement

Total Excellent

2012 – presentstudy

22/M Headache, vomiting,diplopia, tinnitus, ataxia,left hearing loss, palsy ofcranial nerves VII and VI

NP Left CPA mass, mixed signal on T1Wand T2W MRI, heterogeneousenhancement

Total Excellent

2012 – presentstudy

28/M Headache, vomiting,diplopia

NP Rt CPA mass, T1WMRI = hyperintenseT2W = hypointense, rimenhancement

Total Excellent

CPA = cerebellopontine angle, DWI = diffusion-weighted image, F = female, FAP = familial adenonomatous polyposis, FLAIR = fluid-attenuated inversion recovery, GD = gad-olinium-enhanced, M = male, NR = not reported, NP = not performed, Rt = right, T1W = T1-weighted, T2W = T2-weighted.

M.R. Khalatbari et al. / Journal of Clinical Neuroscience 19 (2012) 1516–1519 1517

the left facial nerve and a partial left sixth nerve palsy. The othercranial nerves were intact. Brain MRI revealed a large, cystic,well-defined lesion in the left CPA that compressed the leftcerebellum and brainstem. The lesion was hypointense on T1-weighted (T1W) images, hyperintense on T2-weighted (T2W)images and showed rim enhancement after gadolinium adminis-tration (Fig. 1a,b). There was no evidence of a sellar or suprasellarlesion.

The patient underwent a left suboccipital retrosigmoid craniec-tomy. A large cystic lesion with xanthochromic fluid was found andcompletely removed under microscopic magnification. Histopa-thological examination revealed an adamantinomatous craniopha-ryngioma (Fig. 1c). The post-operative course was uneventful anddeficits in the cranial nerves improved three months after surgery.At the four-year follow-up there was no tumor recurrence (Fig. 1d).

Fig. 1. (a) Axial T2-weighted brain MRI showing a large hyperintense mass in the leftCoronal post-contrast brain MRI showing a rim-enhancing tumor at the left CPA. (c) Hstratified squamous epithelium with peripheral palisading and containing keratin, whichoperative contrast-enhanced brain MRI showing no tumor recurrence. Stain = HematoxScience Direct at http://www.sciencedirect.com/.)

3.2. Patient 2

A 22-year-old man presented with a three-month history ofintermittent headaches, nausea and vomiting. In addition, he re-ported diplopia, tinnitus and truncal ataxia for the past two weeks.Neurological examination showed he was ataxic and had hearingloss in his left ear, a mild left-side facial paresis and partial palsyof the left sixth cranial nerve. Other examinations were normal.A brain MRI showed a partially cystic lesion in the left CPA thatcompressed the adjacent brainstem and cerebellum. The lesionshowed mixed signal intensity on both T1W and T2W images. Het-erogeneous enhancement of the lesion was observed followinggadolinium administration. Neither a sellar nor suprasellar lesionwas identified, nor tumor extension around the clivus or foramenmagnum (Fig. 2a–c).

cerebellopontine angle (CPA) that compressed the cerebellum and brainstem. (b)istopathological examination of the surgical specimen showing cords and nests ofare features compatible with adamantinomatous craniopharyngioma. (d) Axial post-ylin & Eosin and magnification = � 100. (This figure can be viewed in colour on

Fig. 2. (a) Axial T1-weighted brain MRI showing a mixed signal intensity mass in the left cerebellopontine angle (CPA). (b) Axial T2-weighted (T2W) brain MRI showing amixed signal intensity mass in the left CPA. (c) Coronal gadolinium-enhanced brain MRI showing a non-homogeneously enhancing mass in the left CPA. (d) Axial T2W brainMRI showing post-operative changes in the left CPA with no mass lesion.

Fig. 3. (a) Axial T1-weighted (T1W) brain MRI showing a hyperintense well-defined lesion in the right cerebellopontine angle (CPA) that compressed the brainstem. (b)Sagittal T2-weighted brain MRI showing a slightly hypointense mass in the right CPA, posterior to the clivus. (c) Histopathological examination of the lesion was consistentwith adamatinomatous craniopharyngioma. (d) Sagittal T1W brain MRI five years post-operation, showing no tumor recurrence. Stain = Hematoxylin & Eosin andmagnification = � 100. (This figure can be viewed in colour on Science Direct at http://www.sciencedirect.com/.)

1518 M.R. Khalatbari et al. / Journal of Clinical Neuroscience 19 (2012) 1516–1519

A left suboccipital retrosigmoid craniotomy was performed andthe cyst, which contained bloody fluid, was totally removed. Thecyst had no dense adhesion to the cranial nerves or the brainstem.Histopathological examination of the lesion confirmed the tumorwas an adamantinomatous cranipharyngioma. The patient recov-ered well and a brain MRI three months after surgery showed nomass lesion (Fig. 2d).

3.3. Patient 3

A 28-year-old man presented with a six-month history of se-vere headaches radiating to his neck, with nausea and vomiting.He also had a two-month history of diplopia, progressive parapare-sis, and gait disturbance. Neurological examination showed he hada partial palsy of the right sixth nerve, decreased right corneal re-flex, hypoesthesia in the V1 and V2 distributions of the trigeminalnerve, hearing loss in the right ear, hyper-reflexia in the lowerextremities, bilateral Babinski’s sign, and spasticity in both legs.A brain MRI showed a well-defined cystic lesion in the right CPAthat compressed the brainstem. The lesion showed extensions tothe foramen magnum on mid-sagittal MRI and around the clivus,but no evidence of a sellar or suprasellar lesion was detected.The cystic lesion was hyperintense on T1W images, hypointenserelative to cerebrospinal fluid (CSF) on T2W images and wasperipherally enhanced after gadolinium administration (Fig. 3a,b).

The patient underwent a right suboccipital retrosigmoid crani-otomy. Under microscopic magnification, a well-defined cystic le-sion was identified in front of the complex of the VII–VIII cranialnerves, which compressed the complex posteriorly. The tumordid not adhere to the posterior fossa nerves, or the great vesselsand brainstem. The bloody fluid of the cyst was aspirated and

the cyst was completely removed. Histopathological examinationconfirmed the tumor was an adamantinomatous craniopharyngi-oma (Fig. 3c). Post-operatively, the right sixth nerve palsy wors-ened; however, after six months, the patient had no neurologicaldeficits. A five-year follow-up MRI showed there was no tumorrecurrence (Fig. 3d).

4. Discussion

Craniopharyngiomas arise from squamous rests located at anypoint along the invagination of the primitive stomodeum, Rathke’spouch, from the nasopharynx to the hypothalamus.6 These tumorshave a bimodal age distribution. More than 50% of patients arechildren or adolescents and the peak incidence occurs between fiveand 14 years of age; there is also a second, smaller peak in the sixthdecade of life.8–10 Despite this, tumors may become symptomaticat any age.9 Craniopharyngiomas are generally sporadic and theirmolecular pathogenesis is poorly defined. However, tumors occur-ring in association with Gardner’s syndrome have beenreported.1,2,5

Two clinicopathological variants of craniopharyngiomas havebeen identified.8–11 The adult type (papillary squamous type),which largely occurs in adults and mainly consists of mature strat-ified squamous cells, may be of metaplastic origin and has a betterprognosis. The childhood type (classical adamantinomatous vari-ant), which occurs in patients of all ages and contains palisadingcolumnar cells that resemble the ameloblast of fetal tooth buds,may be of embryonic origin.8–10 The three reported patients hadthe latter type of craniopharyngioma.

Craniopharyngiomas of the posterior fossa are rare. More than30 patients have been described,1,4 and three distinct types of

M.R. Khalatbari et al. / Journal of Clinical Neuroscience 19 (2012) 1516–1519 1519

lesions have been recognized: (i) extension of a large suprasellarlesion to the posterior fossa (most patients); (ii) recurrence of a tu-mor after surgery for a sellar or suprasellar craniopharyngioma;and (iii) isolated primary craniopharyngioma of the posteriorfossa.1,2,4,5,11

Embryologically, craniopharyngioma arises from squamous epi-thelial remnants along the involuted craniopharyngeal duct. Dur-ing the fourth week of gestation, an invagination of theembryonic stomodeum (oral cavity roof) lined by epithelial cellsforms Rathke’s pouch, which migrates cranially to meet the down-wardly projecting infundibular bud, which is the precursor of thefuture neurohypophysis. The migration path of Rathke’s pouchforms the craniopharyngeal duct.3,4,8,9 In the embryonic period,the adenohypophysis arises from the proliferation and rotation ofthe cells of Rathke’s pouch; the remnant of the craniopharyngealduct spreads through the intra- and suprasellar regions. Becausecells multiply at different rates during the rotation of the adenohy-pophysis, the cells of the craniopharyngeal duct dominantly spreadthrough the suprasellar/sellar region. However, a few cells may mi-grate into, or become trapped in, the CPA. These ectopic cells maydevelop into an ectopic primary craniopharyngioma of the CPA.8,10

Assuming this theory is correct, the pathological type of all primaryCPA craniopharyngiomas should be adamantinomatous. The histo-pathology of previously reported CPA craniopharygiomas showedthat all tumors were adamantinomatous, which is compatible withthis theory and our report. An alternative hypothesis for the devel-opment of craniopharyngioma suggests these tumors derive fromresidual metaplastic squamous epithelium found in the adenohy-pophysis and anterior infundibulum.3,7–9

The clinical manifestations of craniopharyngiomas are relatedto the tumor’s location and mass effect with compression of thesurrounding structures. In general, symptoms can be categorizedas endocrine, visual, cognitive, and those derived from increasedintracranial pressure.8–10 Patients with suprasellar craniopharyn-giomas usually present with visual disturbances; in contrast, pa-tients with CPA craniopharyngiomas usually present withheadaches, hearing loss, tinnitus, ataxia, and lower cranial nervedeficits.1,2,5,10–12

Useful tools currently used for neuroradiological characteriza-tion of craniopharyngiomas include CT scans and MRI. CT scanscan show bony anatomy and calcification, which is difficult tosee on MRI,8,9,11 and typically demonstrate a cystic suprasellarmass with some solid components. Nodular or rim calcificationcan be seen in most instances. Attenuation of the cyst is variableand is often slightly higher than CSF. Nodular or rim enhancementis also seen in most instances after contrast media injection.9,11

CPA craniopharyngiomas show similar CT findings. MRI is the pre-ferred diagnostic tool for craniopharyngiomas and can demon-strate the relationship of the tumor to the surrounding structuresin the axial, coronal and sagittal planes. A craniopharyngioma ap-pears as a heterogeneous mass with highly variable signal inten-sity, especially on T1W images. Most commonly, cysts have lowsignal intensity on T1W and high signal intensity on T2W images,

and enhancement is observed in the cyst wall or the mural tissueafter gadolinium administration.1,11 Tumors may also be hyperin-tense on T1W images due to high protein content or the presenceof blood degradation products, or both, as was the case for our sec-ond and third patients.9

Treatment of CPA craniopharyngioma usually involves excisionthrough a suboccipital retrosigmoid craniectomy or craniotomy.Complete removal of the tumor is preferred.2,5 When vital struc-tures are involved and excision is compromised by significant risksof morbidity and mortality, subtotal resection of the tumor, fol-lowed by radiotherapy, is the preferred treatment.5,10,11 In our pa-tients, total removal was achieved through a suboccipitalretrosigmoid approach.

5. Conclusion

Isolated primary CPA craniopharyngioma is an ectopic cranio-pharyngioma that originates from migrated or trapped ectopicsquamous cells of the craniopharyngeal duct during the rotationof the adenohypophysis in the embryonic period in the CPA.Growth of these ectopic cells can form a CPA craniopharyngioma.We report three patients with isolated primary CPA craniopharyn-gioma who underwent complete tumor removal through a suboc-cipital retrosigmoid approach. In our opinion, primary CPAcraniopharyngioma can be completely removed, provided thatthe tumor does not have dense adhesion to vital structures of theCPA or the posterior fossa.

References

1. Aquilina K, O0Brien DF, Farrell MA, et al. Primary cerebellopontine anglecraniopharyngioma in a patient with Gardner syndrome. Case report andreview of the literature. J Neurosurg 2006;105:330–3.

2. Link ML, Driscoll CL, Giannini C. Isolated, giant cerebellopontine anglecraniopharyngioma in a patient with Gardner syndrome: case report.Neurosurgery 2002;51:221–6.

3. Banczerowski P, Balint K, Sipos L. Temporal extradural ectopiccraniopharyngioma. Case report. J Neurosurg 2007;107:178–80.

4. Bashir EM, Lewis PD, Edwards MR. Posterior fossa craniopharyngioma. Br JNeurosurg 1996;10:613–5.

5. Bozbuga M, Turan Suslu H, Hicdonmez T, et al. Primary cerebellopontine anglecraniopharyngioma in a patient with Gardner syndrome. J Clin Neurosci2011;18:300–1.

6. Fujimoto Y, Matsushita H, Velasco O, et al. Craniopharyngioma involving theinfrasellar region: a case report and review of the literature. Pediatr Neurosurg2002;37:210–6.

7. Shah GB, Bhaduri AS, Misra BK. Ectopic craniopharyngioma of the fourthventricle: case report. Surg Neurol 2007;68:96–8.

8. Garre ML, Cama A. Craniopharyngioma: modern concepts in pathogenesis andtreatment. Curr Opin Pediatr 2007;19:471–9.

9. Karavitaki N, Cudlip S, Adams CB, et al. Craniopharyngiomas. Endocr Rev2006;27:371–97.

10. Powers CJ, New KC, Mclendon RE, et al. Cerebellopontine anglecraniopharyngioma: case report and literature review. Pediatr Neurosurg2007;43:158–63.

11. Yan Y, Tang WY, Yang G, et al. Isolated cerebellopontine anglecraniopharyngioma. J Clin Neurosci 2009;16:1655–7.

12. Gokalp HZ, Mertol T. Cerebellopontine angle craniopharyngioma.Neurochirurgia 1990;33:20–1.