Midline Glioblastoma Multiforme With Bilateral = Symmetric Cysts

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Journal=20 List > J=20 Korean Neurosurg Soc > v.4= 3(2);=20 Feb 2008

PubMed articles by:

J Korean Neurosurg = Soc.=20 2008 = February;=20 43(2):=20 105=E2=80=93108.

Published online 2008 = February 20.=20 doi:=20 10.3340/jkns.2008.43.2.105.

PMCID:=20 PMC2588232

Midline Glioblastoma Multiforme With = Bilateral=20 Symmetric Cysts

Hai-Ong Lee, M.D., = Eun-Jeong Koh,=20 M.D.,=20 Young-Min Oh, M.D., and Ha-Young Choi, M.D.

Department of Neurosurgery, Research = Institute for=20 Clinical Medicine, Chonbuk National University Medical = School/Hospital,=20 Jeonju, Korea.

Corresponding=20 author.

Address for reprints: Eun-Jeong Koh, M.D. = Department of Neurosurgery, Research Institute for Clinical = Medicine,=20 Chonbuk National University Medical School/Hospital, 634-18 = Geumam-dong,=20 Deokjin-gu, Jeonju 561-712, Korea. Tel: +82-63-250-1870, Fax:=20 +82-63-277-3273, Email: dmsqufns/at/paran.com

Received October 23, 2007; Accepted = January 16,=20 2008.

Abstract

Cystic = glioblastoma=20 multiforme (GBM) is a rare disease. Its exact prevalence has not = yet been=20 reported. Also, the mechanism of cyst formation remains to be = elucidated.=20 We report a case of GBM with a large peripheral cyst. A = 43-year-old woman=20 visited our clinic with a 3-month history of severe headache, = memory=20 impairment and general weakness. T1-weighted gadolinium-enhanced = magnetic=20 resonance (MR) image revealed a midline enhanced solid mass and = bilateral=20 symmetric banana-shaped peripheral cysts. A centrally enhanced = mass was=20 measured 2=C3=974 cm in size and both mass and cysts as 7=C3=977 = cm. Both the=20 frontal lobe and the frontal horn were severely compressed = inferiorly and=20 posteriorly. We resected a midline solid tumor and cysts via the = bilateral=20 interhemispheric transcortical approach. Histopathologic = examination=20 revealed GBM. The patient was subsequently treated with = fractionated=20 conventional brain radiation therapy, followed by temozolomide=20 chemotherapy. Eighteen months later, there was no tumor recurrence = and no=20 neurological deficits were noted. Our patient showed no tumor = recurrence=20 and a long survival at a long follow-up.

Keywords: Glioblastoma multiforme, Cyst,=20 Prognosis

INTRODUCTION

Glioblastoma multiforme (GBM) usually occurs as a unilateral = solitary=20 tumor in the cerebral hemisphere. The presence of associated cysts = is rare=20 and the prevalence of cystic GBM has not yet been reported. = Maldaun and=20 his colleagues have reported that patients with a GBM that = contains a=20 large cyst survive longer and have a longer time to recurrence = than those=20 who lack such a cyst⁴).=20 Several reports have indicated that cystic GBM is less = infiltrative than=20 noncystic GBM with a better prognosis¹^,³^,⁶).=20 However, the mechanism of cyst formation remains to be elucidated. = The=20 hypotheses of cyst formation include necrotic degeneration of the = tumor=20 tissue, central hemorrhage with subsequent liquefaction, = entrapment of=20 adjacent cerebrospinal fluid (CSF) and plasma fluid leaking from a = local=20 disruption of the blood-brain barrier²^,⁶^,⁷⁾.=20 We report a case of cystic GBM which showed no tumor recurrence at = a long=20 follow-up.

CASE REPORT

A 43-year-old woman presented with a 3-month history of severe=20 headache, memory disturbance and general weakness. Neurological = deficits=20 were not noted on neurological examination. Computed tomography = (CT)=20 revealed a homogenously enhanced mass in the midline and lesions = with=20 peripheral low density in the bilateral frontal areas. MR imaging = revealed=20 a moderately enhanced interhemispheric mass and bilateral = symmetric=20 banana-shaped peripheral cysts. The enhanced mass was measured = 2=C3=974 cm in=20 size and the solid portion and bilateral cysts measured as = 7=C3=977 cm (Fig.=20 1). The cystic wall was not enhanced. Both frontal lobe and = frontal=20 horn were severely compressed laterally and posteriorly (Fig.=20 2). Peritumoral edema was observed diffusely at the base of = the=20 frontal bone and pericystic area had an edema measuring several=20 millimeters (Fig.=20 3). Transfemoral carotid angiography (TFCA) did not show any = tumor=20 blushing. We performed gross total surgical resection of the tumor = mass=20 and cystic walls via the bilateral interhemispheric transcortical=20 approach. Cystic fluid was clear and brown. No tumor cells were = found in=20 the cystic fluid and its chemical components were similar to those = of CSF=20 except that it had a high protein level (260 mg/dl). Since the = cystic wall=20 showed no tumor cell infiltrations, it was left undisturbed. The = tumor was=20 gray-purple and friable. Histopathological findings were = suggestive of GBM=20 (mitosis with nuclear atypia, microvascular proliferation and = ischemic=20 necrosis) (Fig.=20 4). After operation, her symptoms improved and these were no=20 neurological deficits. One month after operation, MR imaging = revealed=20 disappearance of preoperative edematous area of the frontal lobe = and the=20 pericystic area showed no abnormal signals. The patient was = subsequently=20 treated with fractionated conventional brain radiation therapy = (LINAC).=20 Twentyfive fractionations of 200 cGy were administered once daily, = and=20 followed by four cycles of temozolomide chemotherapy (200=20 mg/m²). There was no tumor recurrence on the followup = brain MR=20 images which was obtained 18 months after operation (Fig.=20 5). She had no neurological deficits.

Fig.=20 1

Axial = T1-weighted=20 magnetic resonance imaging with gadolinium enhancement = demonstrates=20 a 2=C3=974 cm interhemispheric mass and 7=C3=977 cm = bilateral symmetric=20 banana-shaped peripheral=20 cysts.

Fig.=20 2

Sagittal=20 T1-weighted magnetic resonance imaging with gadolinium = enhancement=20 displays a tumor compressing bilateral frontal lobes and = bilateral=20 frontal horns laterally and=20 posteriorly.

Fig.=20 3

Magnetic = resonance=20 FLAIR imaging shows peritumoral and pericystic=20 edema.

Fig.=20 4

Photomicrography of=20 the tumor discloses aggregations of ischemic necrosis (A) = and=20 microvascular proliferation (B). Immunohistochemical stains = for=20 vimentin (C) and GFAP (D) reveal positive reactions (A-D, = H&E,=20 original magnification =C3=97200).=20 (more ...)

Fig.=20 5

Follow-up = axial=20 T1-weighted magnetic resonance imaging with gadolinium = enhancement=20 reveals no tumor=20 recurrence.

DISCUSSION

Cysts are commonly found in low-grade astrocytomas (>50% of = the=20 cases) and in most pilocytic astrocytomas. In these low-grade = tumors,=20 cysts correlate with a better prognosis. Cysts may develop in = high-grade=20 tumors but the presence of cysts in GBMs is extremely rare. The = cause of=20 cyst formation is unknown. Satoshi et al.⁶⁾=20 have suggested pathophysiologic mechanisms for cyst formation in = glioma=20 are perituomoral vasogenic brain edema, ischemia, tumor necrosis = and fluid=20 resorption. One hypothesis regarding cyst formation is that GBM is = a=20 malignant transformation of a previously undiagnosed cystic = low-grade=20 glioma²^,⁶⁾.=20 GBMs have been reported to arise from low-grade astrocytomas in=20 approximately 20% of the cases. These "secondary" GBMs tend to = occur in=20 younger patients (median age, 45 years) who have a long history of = seizures and have genetic and molecular patterns different from = those of=20 so-called "primary" or de novo GBMs. Secondary GBMs sequentially = show p53=20 mutation, PDGF-A and PDGFR-=CE=B1 overexpression, LOH 19q and RB = alteration,=20 and loss of LOH 10 and DCC expression. In primary GBM, = overexpression and=20 amplification of EGFR and MDM2, PTEN mutation, and p16 deletion = developed=20 simultaneously²⁾.=20 Our patient had no history of chronic seizure and a short duration = of=20 symptoms. She was clinically diagnosed with primary GBM. Since we = did not=20 perform chromosome analysis, we could not determine whether this = tumor was=20 primary or secondary GBM. Other hypotheses have been suggested to = explain=20 the presence of cysts in GBMs. These include necrotic degeneration = of the=20 tumor tissue (extensive necrosis of the central part of the tumor = or=20 necrosis along with the surrounding pseudopalisading structures of = the=20 tumor), central hemorrhage with subsequent liquefaction, = entrapment of the=20 adjacent cerebrospinal space, and a blood-brain barrier = disruption²^,⁶^,⁷⁾.=20 In our case, since MR imaging showed a central tumor and bilateral = peripheral cysts, we postulated that the cysts occurred through = necrosis=20 with the surrounding pseudopalisading structures of the tumor or=20 entrapment of the adjacent cerebrospinal space, not through = central tumor=20 necrosis or central hemorrhage. MR findings in our case showed = that the=20 cystic wall was not enhanced and had a narrow peritumoral edema. = This=20 supports the hypothesis of entrapment of the adjacent = cerebrospinal space.=20 Chemical components of the cystic fluid similar to those of CSF = except for=20 a high protein level support the hypothesis of CSF entrapment. The = propensity of glial tumors that invade the normal brain is one of = their=20 hallmarks. GBMs typically invade the adjacent brain tissue. This = invasion=20 frequently occurs in the white fiber tracts, along the blood = vessels, by=20 subependymal dissemination, or through the subpial space⁷⁾.=20 Tumor infiltration is thought to cause early postoperative = recurrence and=20 disease progression despite aggressive resection¹^,³^,⁵^,⁷⁾.=20 Previous histological studies in which the relationship of the = cyst wall=20 with the brain was analyzed have demonstrated that cystic GBMs = appear to=20 have a relatively narrow pericystic rim of the glioma, with = limited=20 infiltration of the surrounding neutrophils. This result indicates = that=20 cystic GBMs may be less infiltrative than non-cystic ones⁶⁾.=20 Such histological changes may be related to a proposition for = lower=20 recurrence of the tumor and a longer overall survival after = surgery in=20 patients with cystic GBMs. Our patient also showed a narrow = pericystic=20 edema with a sharp margin.

The extent of surgical resection is also a significant = prognostic=20 factor for GBM. The larger the peritumoral edema region is, the = poorer the=20 prognosis is. Since peritumoral edema extends in three dimensions, = surgical removal is difficult and involves a high risk of creating = new=20 neurologic deficits. Although resection of the peritumoral = edematous=20 region improves treatment outcomes of GBM, complete resection of = the=20 edematous region is extremely difficult to perform¹^,³^-⁵⁾.=20 In our patient, she had a narrow pericystic edema and a cystic = wall which=20 provided the boundary for tumor resection, thus resulting in = complete=20 resection and good surgical outcomes. Maldaun et al. estimated = that the=20 median survival time after surgery was 18.2 months in patients = with cystic=20 GBM, whereas it was 14.3 months in patients with noncystic = GBM⁴⁾.=20 They also showed that no recurrence was observed in 45% of the = patients at=20 1 year after surgery and 38% of patients at 2 years after surgery, = whereas=20 the corresponding numbers for patients with non-cystic GBM was 14% = and 9%,=20 respectively⁴⁾.=20 At follow-up, our patient showed no recurrence 18 months after=20 surgery.

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CONCLUSION

We report a patient with a central GBM mass containing a large=20 peritumoral cyst with narrow pericystic edema. The definite cystic = wall=20 and scanty pericystic edema provided the boundary of tumor = resection and=20 allowed complete resection of the tumor. Postoperatively, = recurrence-free=20 survival time was longer in our case than that of non-cystic=20 GBMs.

References

Hulshof, MC; Koot, RW; Schimmel, EC; Dekker, = F; Bosch,=20 DA; Gonzalez, D. Prognostic factors in glioblastoma multiforme: 10 = years=20 experience of a single institution. Strahlenther Onkol. 2001;177:283=E2=80=93290. [PubMed]

Kleihues, P; Ohgaki, H. Primary and secondary = glioblastomas: From concept to clinical diagnosis. Neuro-oncol. 1999;1:44=E2=80=9351. [PubMed]

Lacroix, M; Abi-Said, D; Fourney, DR; = Gokaslan, ZL;=20 Shi, W; DeMonte, F, et al. A multivariate analysis of 416 patients = with=20 glioblastoma multiforme: prognosis, extent of resection, and = survival.=20 J Neurosurg. 2001;95:190=E2=80=93198. [PubMed]

Maldaun, MV; Suki, D; Lang, FF; Prabhu, S; = Shi, W;=20 Fuller, GN, et al. Cystic glioblastoma multiforme: survival = outcomes in=20 22cases. J Neurosurg. = 2004;100:61=E2=80=9367. [PubMed]

Park, JW; Hwang, JH. The long-term survival = in patients=20 with anaplastic astrocytoma or glioblastoma. J Korean Neurosurg Soc. 2003;34:514=E2=80=93520.

Satoshi, U; Hidehiro, O; Sachio, S; Satoru, = S;=20 Yoshinori, T; Koji, K, et al. Pathological and clinical features = of cystic=20 and noncystic glioblastomas. Brain = Tumor=20 Pathol. 2006;23:29=E2=80=9334. [PubMed]

Thorsen, F; Tysnes, BB. Brain tumor cell = invasion,=20 anatomical and biological considerations. Anticancer Res. 1997;17:4121=E2=80=934126. [PubMed]

<= /DIV>

Articles=20 from Journal of Korean=20 Neurosurgical Society are provided here courtesy of =
The=20 Korean Neurosurgical Society

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'this' to reuse same window, else ""=0A= // windowname: Reference name for window=0A= // additional: Attributes for window.open, from:=0A= // width, height, resizable, scrollbars, toolbar, location, = directories,=0A= // status, menubar, copyhistory.=0A= // Notes: Book version always provides menubar, toolbar, etc.=0A= //=0A= function startTargetBook(link,windowname,width,height,additional)=0A= {=0A= startTarget(link,windowname,width,height,additional)=0A= }=0A= =0A= =0A= //=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=0A= function startTarget(link,windowname,width,height, additional)=0A= {=0A= if(! window.focus)=0A= return;=0A= =0A= var sizestring =3D ",width=3D" + width + ",height=3D" + height;=0A= var opt =3D = "menubar=3Dno,toolbar=3Dno,status=3Dno,scrollbars=3Dyes,resizable=3Dyes,d= ependent=3Dyes,location=3Dno";=0A= var allOptions =3D opt + sizestring;=0A= if (additional) { allOptions =3D allOptions + ',' + additional; }=0A= =0A= windowname =3D String(windowname).replace(/-/g, "_")=0A= var moveToXDefault =3D 75=0A= var moveToYDefault =3D 50=0A= =0A= var moveToX =3D moveToXDefault=0A= var moveToY =3D moveToYDefault=0A= =0A= try {=0A= if (window.screen.width && width > 0)=0A= moveToX =3D Math.ceil((window.screen.width - width)) - 15=0A= moveToX =3D (moveToX > 0 ? moveToX : moveToXDefault)=0A= =0A= if (window.screen.height && height > 0)=0A= moveToY =3D Math.ceil((window.screen.height - height)) - 50=0A= moveToY =3D (moveToY > 0 ? moveToY : moveToYDefault)=0A= }=0A= catch (e) {}=0A= =0A= var wLeftTopCornerOptions =3D ',left=3D' + moveToX + ',top=3D' + = moveToY + ',screenX=3D' + moveToX + ',screenY=3D' + moveToY=0A= =0A= allOptions =3D allOptions + wLeftTopCornerOptions=0A= =0A= w =3D window.open ("", windowname, allOptions)=0A= w.focus()=0A= =0A= link.target=3Dwindowname=0A= }=0A= =0A= =0A= //=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=0A= function focuswin(windowname)=0A= {=0A= windowname =3D String(windowname).replace(/-/g, "_")=0A= w =3D = window.open("",windowname,"menubar=3Dyes,scrollbars=3Dyes,toolbar=3Dyes,l= ocation=3Dyes,status=3Dyes,directories=3Dyes,resizable=3Dyes");=0A= w.focus();=0A= =0A= return true;=0A= }=0A= =0A= =0A= //=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=0A= function reverseString (inStr)=0A= {=0A= var outStr =3D ''=0A= =0A= for (i =3D0; i <=3D inStr.length; i++)=0A= {=0A= outStr =3D inStr.charAt(i) + outStr=0A= }=0A= =0A= return outStr=0A= }=0A= =0A= =0A= //=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=0A= function reverseAndReplaceString (inStr, findStr, newStr)=0A= {=0A= return reverseString(inStr).replace(findStr, newStr)=0A= }=0A= =0A= //=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=0A= function initUnObscureEmail (className, innerHTML)=0A= {=0A= =0A= try{=0A= if (window.addEventListener)=0A= window.addEventListener('load', function() {unObscureEmail = (className, innerHTML)}, false)=0A= else if (window.attachEvent)=0A= window.attachEvent('onload', function() {unObscureEmail = (className, innerHTML)})=0A= }catch(e){=0A= }=0A= }=0A= =0A= //=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=0A= function unObscureEmail (className, innerHTML)=0A= {=0A= try {=0A= if (typeof(unObscuredEmails) =3D=3D 'undefined')=0A= unObscuredEmails =3D new Array()=0A= =0A= if (! 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