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Neoplasm

Myxoma of the cranial baseLiwei Zhang, MDa,⁎, Mingshan Zhang, MSb, Junting Zhang, MSa, Lin Luo, PhDc, Zuolin Xuc,

Guilin Li, PhDc, Yongji Tian, MDa, Yu Wang, MSa,Zhen Wu, MSa, Zhongcheng Wang, MDa

aDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, ChinabThe Brain Sciences Institute of Beijing, Beijing 100038, China

cBeijing Institute of Neurosurgery, Beijing 100050, China

Received 14 September 2007; accepted 15 September 2007

Abstract Background: In 1871, Virchow described a type of tumor, which he named myxoma, which had a

Abbreviations: CTimaging.

⁎ CorrespondingE-mail address: zl

0090-3019/$ – see frodoi:10.1016/j.surneu.2

similar appearance to mucinous tissue of the umbilical cord. Myxoma occurs most frequently in theheart and jawbone, less frequently in the temporal bone mastoideum, and rarely in the cranial base ofthe brain. From an etiologic perspective, intracranial myxoma is divided into either primary orsecondary induction. The majority of primary myxomas are found at the skull base, whereassecondary intracranial myxomas are mainly caused by metastatic tumor emboli from the cardiacmyxomas; the emboli may also transfer to cerebrovascular endothelium to cause fusiform aneurysm.From October 1983 until November 2005, 23 patients with cranial base myxoma, as confirmed bypathology, were treated in the neurosurgery department of Beijing Tiantan Hospital. Few data areavailable from published literature on diagnosis and treatment of cranial base myxoma; therefore, theaim of this study was to describe a large series of patients undergoing treatment for cranial basemyxoma and to analyze and discuss clinical manifestations, diagnosis, and treatment of cranialbase myxoma.Methods: A retrospective analysis was undertaken of 23 cases of cranial base myxoma, as confirmedby pathologic diagnosis. The review included all patients treated between October 1983 andNovember 2005. Among the 23, 8 patients received adjuvant radiotherapy after surgery. Postsurgicaloutcome data were unavailable for 12 patients. The mean duration of follow-up in the remaining11 patients was 64.5 months.Results: Tumors were commonly located at the middle fossa, parasellar, and jugular regions withcharacteristic calcification demonstrated with magnetic resonance imaging. Patients presented withheadache and multiple lesions of the cranial nerves. Surgical approaches were variable and selectedaccording to tumor locations. Partial resections were achieved in 16 cases and total resections in7 cases. Complete relief of clinical symptoms was achieved in 2 cases, unchanged in 11 cases, andaggravated in 9 cases. During the period of follow-up, remission was gained in 6 cases and tumorrecurrence in 4 patients; 1 patient died.Conclusions: Cranial base tumors are difficult to diagnose. By clinical features and neuroradio-logical findings, it is hard to distinguish myxoma from chondroma and chordoma in this region.Treatment results are seldom encouraging; the goal of complete surgical resection is rarely achieved,and the outcome of radiotherapy is not very successful.© 2007 Elsevier Inc. All rights reserved.

Keywords: Cranial base; Myxoma; Surgery; Operation; Pathology

, computed tomography; DSA, digital subtraction arteriography; MRA; magnetic resonance angiography; MRI, magnetic resonance

author. Tel.: +86 13501018097; fax: +86 010 67051377.wtt@yahoo.com.cn (L. Zhang).

nt matter © 2007 Elsevier Inc. All rights reserved.007.09.015

Fig. 1. Computed tomography scan. A: A tumor with calcified mass wasilluminated at the right parasellar area, and erosion of the parasellar bone wasdocumented. B: A tumor lesion with dispersive calcification was revealed atthe upper clivus. The tumor with high-density imaging was pathologicallyconfirmed as broken exoskeletal plates and new bone formation.

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1. Methods

There were 14 male and 9 female patients in this groupaged from 18 to 50 years with a median age of 32.7 years;male to female ratio was 1.6:1. Durations of medicalhistories were from 7 days to as long as 13 years; themean duration was 2.7 years. None of the patients had ahistory of heart myxoma. The tumors were located at theparasellar area in 14 cases, the jugular foramen in 4 cases,and the clivus in 2 cases. Single cases were located in the

Fig. 2. Magnetic resonance imaging. A, B, and C represent T1, T2, and contrast-enhclivus with nonuniform long T1, long T2, and inhomogeneous contrast-enhanced ssuture; mild erosion of the clivus bone was observed. E: A tumor with inhomogeneoof honeycomb briquet. F: A tumor in the region of the jugular foramen was enhan

posterior cranial base, behind the sigmoid sinus, at theplanum sphenoidale, and at the anterior cranial baseintruding into the sphenoidal sinus.

Clinical features associated with myxomas can beextremely variable according to their different locations.Among the more common symptoms are headache andmultiple lesions of the surrounding cranial nerves. In thisstudy, the most common presenting symptom was headache,which was observed in 11 patients at a mean time point of2.7 months before diagnosis. In addition, 4 patients presentedwith optic atrophy and 2 patients presented with a visual fielddefect. Oculomotor paralysis was noted in 8 patients, andabducent paralysis was noted in 7 patients. Facial twitchingwas noted in 1 patient, trigeminal nerve paralysis in 8patients, and preoperative difficulty in shrugging in 2patients. Masticator muscle atrophy occurred in 1 patient.Presenting signs included facial paralysis (n = 5); tinnitus andimpaired hearing (n = 4); bucking (n = 3); hoarse voice(n = 7); hypoglossal nerve paralysis (n = 5); ataxia (n = 2); andmuscle weakness (n = 2).

Radiologic examination plays a key role in the diagnosisof myxoma. Computed tomography scan was undertaken inall patients and some patients had further investigations, suchas MRI (n = 16) and DSA (n = 3). Computed tomographyscan of these tumors produced variable results: isodense;slightly low density or high density; high-density imaging toinclude an irregular large calcified mass (Fig. 1); eggshell-like calcification; bone chips; and/or new bone formation.

anced T1 of axial MRI images, respectively. Tumor was demonstrated at theignals. D: The tumor mass was at the clivus, initially at the sphenooccipitalus enhanced signals was in the parasellar region, presenting a typical imagingced uniformly and intensely.

Fig. 3. Digital subtraction arteriography examination. A: Expansion of aright internal carotid artery in the siphonal area and displacement of themiddle cerebral artery. There was no visible parasellar myxoma (right). B: Atumor located at the jugular foramen, with obvious occlusion of internalcarotid artery seen on MRA.

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The bone window imaging had slight bone erosion withoutmass effect. Magnetic resonance imaging examinationresults depended upon the tissue components of the tumor.Those tumors with extensive mucus displayed homogeneouslong T1 and long T2 signals. When calcification and boneytissue predominated, they demonstrated nonhomogeneouslong T1 and long T2 signals (see Fig. 2A-D). Myxomas inthe parasellar and clivus regions and the posterior cranialbase showed nonhomogeneous contrast enhancement, typi-cally presenting as a “honeycomb briquette” sign (Fig. 2E).Myxomas of the anterior cranial base and jugular foramen,after gadolinium infusion, have enhanced uniformity andintensity of appearance (see Fig. 2F). With regard to DSAexamination, the tumors did not stain and had mass effect(Fig. 3A). One MRA displayed occlusion of the right internalcarotid artery (Fig. 3B).

All of the 23 patients underwent surgical interventionover a period of 13 years. The selection criteria used todetermine the surgical approach for each patient evolvedover this period and included tumor size and pathologiccharacteristics, extension of the tumor, and location of thetumor, as measured on MRI. A subfrontal-transbasalapproach was selected for tumors in the planum sphenoidale;

Fig. 4. Postoperative MRI. A: Remnant cavity of a tumor resection, revealed on axsagittal imaging. C: Residual parts of the tumor were documented by coronal ima

an extended subfrontal approach for tumors in the anteriorcranial base intruding into the sphenoidal sinus; and asuboccipital-paramedian approach for tumors behind thesigmoid sinus at the posterior cranial base. Either afrontotemporal approach or a retrolabyrinthine-presigmoidapproach was chosen for tumors in the area of the clivus.Either a suboccipital-paramedian approach or a cerebello-pontine angle approach was chosen for tumors in the area ofthe jugular foramen. With respect to the parasellar myxoma,3 approaches were chosen: frontotemporal, frontotemporal-transzygomatic, or subtemporal-transtentorial.

Adjuvant radiotherapy was used after surgery in8 patients: 4 with conventional radiotherapy; 2 usingγ-knife treatment; 1 using X-knife; and 1 using P32 injectioninside the tumor. Among the 23 cases, treatment follow-upwas possible in 11 subjects over a wide range of time from 1to 214 months, with an average duration of 64.5 months. Forthe remaining 12 cases, no follow-up data were available.

2. Results

In this group of 23 patient, 16 with cranial base myxomareceived partial tumor resection and 7 tumors were whollyresected (see Fig. 4). During surgeries (see Fig. 5), typicalmyxoma appeared as a parenchymatous, gelatinous, andgrayish-white mass under the dura mater, with soft andfragile consistency and a poor blood supply. In a few cases,characteristics of tumors varied in coloration betweengrayish-yellow and grayish-red; a few were cystic or had ahard and tough consistency.

This type of tumor was found to be aggressive and locallyinvasive with tumor expansion possibly resulting in boneerosion of the cranial base or invasion of spongy bone. Insuch cases, using light microscope, a calcified mass and bonechips surrounded by a translucent gelatinous substance wereobserved. Sometimes, there was even a “coral reef” shapeowing to a mixture of calcified mass and bone chips. Underthe microscope, the tumor cells were diffusely distributed,with an asteroid or fusiform shape containing red cytoplasmand round or oval nuclei; these nuclei were deep stainingwith karyokinesis. The background among the tumor cells

ial imaging of a parasellar myxoma. B: An abnormal clivus was observed onging of the jugular foramen.

Fig. 5. Anatomy of a myxoma during surgery. A: A grayish-whitetranslucent gelatinous tumor with poor blood supply, observed in theparasellar region under dura mater. B: A grayish-red tumor with ossifiedtissue was seen in the region of the clivus.

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was filled with extensive mucoid stromas and acidification.Amid the light blue mucous stroma, calcification, bonechips, and new bone formation were observed.

Postoperative results included improvement of clinicalsymptoms: a facial spasm that resolved quickly, and a second

Fig. 6. Light microscopic findings of various components in so-called myxoma. Aembedded in the background of light blue mucus. Cytoplasm of stellate or fusiformkaryokinesis (hematoxylin and eosin [H&E] staining, original magnification ×20magnification ×100). C: Positive H&E staining of fibroblasts around newly forme

patient with ptosis, which also improved but less dramati-cally. Unresolved symptoms were reported in 11 cases.Worsening of preexisting clinical symptoms occurred in2 patients, each with diplopia and hoarse voice. There were5 patients with newly developed symptoms that includedfacial paralysis, impaired hearing, ptosis, and mix aphasia.Hemorrhage of an internal carotid artery occurred in 1 caseduring surgery; this patient also had hemiplegia andaphemia, which corresponded to a postsurgical cerebralinfarction. One patient with myxoma of the clivus experi-enced an intracranial hematoma and infarction of the brainstem, which led to death 14 days after surgery.

Among the 23 surgical cases reviewed, follow-up wasunavailable in 12, leaving 11 patients with follow-up dataover a period of 13 years. A return to normal function, after apostsurgical cranial nerve deficit, was achieved in 6 cases. In4 patients, myxoma recurrence was noted during postsurgi-cal years 3, 5, 6, and 9, respectively, and the mean duration ofrecurrence was 5.9 years. At the time of writing this report,3 of the latter underwent reoperation. One patient withmultiple cranial nerve deficits did not undergo furthertreatment. Finally, 1 patient with a parasellar tumor died2 years after surgery but the reason for death was unclear.

3. Discussion

Myxoma of the cranial base is a rare medical conditionwith very few data available from epidemiological literature.These reported 23 cases of cranial base myxoma account forapproximately 0.58% of homochronous intracranial tumorsin our hospital, representing the largest group of such casesin current literature. It has been reported that jawbonemyxoma commonly occurs in the age range of 20 to 30 yearswith a bias toward females [6]. In this group of 23 patientswith cranial base myxoma, patient age ranged from 18 to50 years with a median age of 32.7 years; males slightlyoutnumbered females with a ratio of 1.6:1.

: Myxomatous components, composed of scattered stellate or fusiform cellscells was red and their nuclei were round or oval, deep staining, and without0). B: Positive H&E staining of a calcified mass (H&E staining, originald bone (H&E staining, original magnification ×100).

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Myxoma may occur in any part of the cranial base butmainly occurs at the bone joints, such as the sphenopetrosalsuture and the petrooccipital suture. It has been reported thattumors were located behind the sigmoid sinus of theposterior fossa base [3]; in the hypophysial fossa [4]; inthe cerebellopontine angle area [9]; and in the mastoideum ofthe temporal bone [5-9]. Among the 23 patients in this report,18 tumors were confirmed in the parasellar region andjugular foramen. The clinical manifestation of cranial basemyxoma mainly presented as headache and multiple lesionsof the cranial nerves. Headache was explained in 2 ways.First, the tumor was under the dura mater and, therefore,expansion of the tumor resulted in increased tension on thedura mater. Second, the nerve innervating the dura mater ofthe cranial base was stimulated. The majority of patientswith parasellar myxoma presented with cavernous sinussyndrome, with oculomotor paralysis most commonlyidentified. Tumor located at the jugular foramen oftencaused jugular foramen syndrome, with hoarse voiceattributed to this.

There was a special type of cranial base myxoma withinthis group. A 30-year-old male patient with a right parasellarmyxoma presented with a history at age 10 of enchondromain the left ring finger, the left little finger, and the right littlefinger; later on, these 3 fingers were all amputated. Thispatient was diagnosed with Ollier disease combined withmyxoma of the cranial base, which has not been reported inthe current literature.

3.1. Neuroradiology findings

The most common view on CT scan was a mass of mixeddensity with a hyperdense center, surrounded by a hypo-dense layer without an enhancement effect. The hyperdensecenter presented as diffuse spots, an irregular mass, or aneggshell-like appearance. We confirmed during surgery thatthe isodense or slightly low-density image was mucus andthat the high-density image was calcification, bone chips, ornew bone formation. Bone window imaging revealed mildbone erosion. Computed tomography imaging is also avaluable tool to observe changes in tumors of high-densitymass. In 1 case of parasellar myxoma, an eggshell-like high-density image was seen on CT scan; this was confirmed bypathology during the initial surgery; after 3 years, when thetumor recurred, a large irregular high-density segment wasseen on CT; during surgery, this was revealed as new boneformation. This phenomenon is explained by the makeup ofa myxoma—undifferentiated mesenchymal cells with thepotential to become osteoblasts that form new bone.Microscopic examination revealed new bone surroundedby fibrous tissue.

These tumors had a clear boundary and smooth surface onMRI, as dura mater was outside the mucoid mass. Furtherexpansion of the tumor destroyed the surrounding duramater. With the loss of shaping by intact dura mater, thetumor surface became irregular and nodular. Imaging of evenlong T1 and long T2 signals appeared as mucous stromas,

which could be mistaken as cystic degeneration. All cranialbase myxomas were parenchymatous tumors; cystic degen-eration has yet to be documented. In spite of a poor bloodsupply, these tumors were found to have affluent capillaryvessels in the interstitial tissue, creating nonhomogeneousenhancement on MRI. Digital subtraction arteriography isextremely valuable in the diagnosis of this disease. In ourgroup of 23 patients, 1 patient with jugular foramen myxomawas reported to experience vertigo before surgery. Occlusionof an internal carotid artery, seen on MRA, was considered tobe the cause of this symptom. The symptom resolvedcompletely after surgery. The question of whether the tumorwas the reason for arterial occlusion needs to be confirmedby long-term observation.

3.2. Pathology and differential diagnosis

Currently, pathologic diagnosis applies the Stout standard[8]: (1) fusiform and stellate cells embedded in a pulpymucoid stroma; (2) chondroblast, lipoblast, striated muscle,and other differentiated cells not seen within the tumor;(3) few tumor vessels and capillaries, with capillaries notfasciculated; and (4) monocentric orientation. Under themicroscope, the tumor cells in these patients were diffuselydistributed; they were asteroidal or fusiform in shape withred cytoplasm and round or oval nuclei, which were deepstaining with minimal karyokinesis. The background sur-rounding these tumor cells was filled with extensive mucoidstromas, which were extensively acidic (see Fig. 6A). Amidthe light blue mucous stroma, calcification (see Fig. 6B),bone chips, and new bone formation (see Fig. 6C) wereobserved, and there were no chondroblast, lipoblast, striatedmuscle cells, or other differentiated cells observed.

The presurgical diagnoses of myxoma are extremelydifficult [2], as the parasellar myxoma is generallymisdiagnosed as a schwannoma, a cavernous hemangioma,meningioma, chondrogenic tumor, or chordoma. When inthe clivus, myxoma is generally misdiagnosed as achordoma, making the radiologic evaluation and multi-analyses essential for presurgical diagnosis. In certain cases,such investigations could help in the process of differentialdiagnosis. The phenomenon of center calcification, as seenin myxoma, is barely found in a schwannoma or cavernoushemangioma. An enhanced tumor, as seen on angiography,is also a key point in distinguishing meningioma frommyxoma. But it is difficult to differentiate myxomas fromchondrogenic tumors or chordomas in the cranial base,especially chondroma.

There are 4 types of tumors that originate from embryonicmesoblast cells and may also contain similar components.Myxomas may derive from differentiated chondrogeniccells. Chondromas also might demonstrate mucus degenera-tion. Chordomas may derive from embryonic notochordresidue and may demonstrate both mucus degeneration andchondrogenic components. Chordomas may originate fromthe clivus bone, with aggressive growth and bone erosionquite obvious; the resulting lesion might involve the whole

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clivus. Myxomas and chondrogenic tumors have their originin the joints of the occipital bone and sphenoid. The tumormass is located in the upper clivus and tumor growthoccurs mainly toward the brain stem, barely into the clivusbone; in addition, bone erosion is mild. Pathologic evalua-tion is critical in establishing the essential criteria fordiagnosis of such tumors. It needs to be noted that a largevolume of tumor tissue needs to be collected for successfulpathologic assessment.

3.3. Treatment and prognosis

Myxoma is considered a benign tumor and offers thepotential for cure after total resection of tumor mass. In areport by Gosh et al [1], 10 cases of jawbone myxoma wereresected to the edges of normal tissue. Recurrence associatedwith residual tumor occurred in only 1 patient [1]. Actually,it was difficult to achieve a total resection of cranial basemyxoma. Cranial base myxoma primarily originates fromthe sutures, which is closely correlated with cranial basestructure. Also, these tumors frequently contain areas ofcalcification or necrotic bone chips, which may adhere toadjoining cranial nerves and/or intracranial arteries.

Internal carotid artery hemorrhage occurred in 1 caseduring surgery, and, hemiplegia and aphemia, correspondingto cerebral infarction, occurred postoperatively. One patientwith clivus myxoma developed intracranial hematoma andbrain stem. This patient died 14 days after surgery.

Within our series of 23 patients, partial resections ofthe cranial base myxomas occurred in 16 cases with resectionof all observable tumor mass occurring in the remaining7 cases. Forced resection of calcified mass and brokenexoskeletal plates might injure nearby cranial nerves ormajor blood vessels, causing serious consequences. In1 case, separating calcified tissue from an internal carotidartery caused leakage at the bifurcation of the internal carotidartery. Suture repair was undertaken immediately butpostsurgical hemiplegia and aphemia occurred, correspond-ing to cerebral infarction. In contrast, partial resection wasundertaken in 1 patient with a heavily calcified tumor.Without resection of the calcified mass, which was close tothe internal carotid artery and the optic nerve, there were noserious complications. The patient's vision was improvedafter surgery and the tumor was stable over the course of a17-year follow-up.

Obviously, a main part of myxomas is mucoid tissue;therefore, it is more important to remove this tissue thancalcified mass and bone chips, to minimize seriouscomplications. But this approach cannot be applied in allcases. In the study published by Windfuhr and Schwerdtfe-ger [2], myxoma of the temporal bone mastoideum had avery high rate of recurrence, and the majority of patients hadrecurrence within 2 years of surgery [8].

In our series, 11 patients were followed for an average of64.5 months. Among them, full recovery was observed in6 cases and imaging examinations showed no apparentchange. Tumor recurrence occurred in 4 cases over an

average of 5.8 years after surgery. Of these 4 patients,3 experienced tumor-related clinical symptoms. Imagingevaluation confirmed the reappearance of tumor; however,outcomes improved after reoperation. Multiple cranial nervedeficits were seen in 1 patient during a 3-year period aftersurgery. The patient's family refused further surgical inter-vention. Tumor recurrence seemed to occur more quickly inyounger than in older patients. Although the calcified andosseous tissues of these tumors were long-standing, thereappeared to be no obvious related clinical symptoms; in ourpatients, clinical symptoms were more obviously associatedwith mucus presence. Therefore, we recommend that clinicalsymptoms be evaluated in the context of imaging evaluationsto better understand tumor recurrence. We would alsorecommend paying special attention to changes in mucus inthe imaging, which might explain the more rapid speedof tumor growth. Among our 23 patients, 1 died of brain steminfarction at 14 days after surgery. A second patient diedwithin 2 years of surgery and the reason for death was unclear.

With respect to radiotherapy, some authors have advo-cated against its use in the jawbone and the myxoma oftemporal bone mastoideum, as those types of tumors appearto be insensitive to radiotherapy; in addition, excessive dosesof radiotherapy may induce cancer [6]. In our series, therewere 8 cases in which radiotherapy was used; 4 cases werecontinued through the follow-up period. In 1 case, the tumorrecurred within 3 years and required a second surgery. After1 case was treated by X-knife, the tumor recurred within6 years, and a second surgery was undertaken. After 1 case ofP32 radiotherapy, the tumor recurred within 2 years. Anotherpatient was subjected to γ-knife treatment; MRI demon-strated that the tumor was reduced after 7 months, but thelong-term effect is unknown. For the full appraisal ofradiotherapy in treating cranial base myxomas, furtherstudy is required.

This retrospective report highlights 2 key considerations.First, cranial base myxomas appear to grow more quickly inyounger than in older patients. Second, disease remainsstable after surgery with or without the presence of calcifiedand osseous components of the tumor, and newly developedclinical symptoms present most commonly when the mucoidtissue reappears. Therefore, with respect to tumor recurrence,either the appearance of mucus on radiologic imaging ornewly developed clinical symptoms should be considered asvery important indictors of tumor recurrence. Clearly,radiologic findings are most valuable in understanding thenature of rapid tumor growth.

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