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Journal of Neuro-Oncology 32: 175–178, 1997. 1997 Kluwer Academic Publishers. Printed in the Netherlands.

Clinical Study

Gliomatosis cerebri mimicking a metastatic breast cancer: Fatal outcome

Angel Iglesias1, Mercedes Garcıa2, Juan San Millan3, Carmen Villanueva2, Guadalupe Fraile1 andManuel Serrano1

Departments of 1Internal Medicine, 2Pathology and 3Radiology, Ramon y Cajal Hospital, Madrid, Spain

Key words: brain neoplasms, breast neoplasms, estrogens, glioma, gliomatosis

Summary

Gliomatosis cerebri (GC) is defined by the World Health Organization as a neoplasm of the glial cells. It isextremely rare, and there exists only 160 documented cases since 1897. There is no known treatment and themedian survival rate is one year. The association of extracranial and CNS tumors is unusual, only three casesof breast cancer have been associated with gliomas and meningiomas but none with GC. Below we describe acase of breast cancer associated with GC and review the anatomoclinical and radiological manifestations ofGliomatosis Cerebri.

Introduction

The World Health Organization defines Gliomato-sis Cerebri (GC) as a neoplasm of the glial cells inthe central nervous system [1]. GC is very rare, only160 cases have been identified since 1897 [2].Scheinker and Evans [3] have described the criteriafor GC which have been accepted by various au-thors [2, 4]. These are: a) the cerebral structures stayintact but are enlarged, b) there is no clear limit be-tween healthy and affected tissue, c) the glial cellsproliferate and invade interstitial connective tissue,d) there is no damage to the axon nor to the neuronbut there exists myelinolysis, and e) there is no sec-ondary degeneration.

No cases of GC associated with breast cancerhave been reported, yet there are 3 cases of thecombination of glioma and meningioma associatedwith breast cancer [5–7]. Some of these authorshave pointed to estrogens as a possible cause [5, 8].The best actual method for diagnosis is the MRI [9]and neither radiotherapy [10] nor chemotherapy[11] are effective in the treatment of GC. Below, wewill describe a case of GC associated with breast

cancer, and we will review the anatomoclinical andradiological characteristics of GC.

Case report

In August of 1990 a 70 year woman was diagnosedwith ductal invasive left breast cancer. According tothe TNM staging system, the stage of the tumor wasIIA (T2N0M0). The receptor analysis of estrogensand progesterone was negative. The treatment thatthe patient received was radical modified mastecto-my without adjuvant Chemo-, hormono- or radio-therapy. The patient was asymptomatic until Febru-ary of 1992 when she presented with dizziness,memory loss and ataxia. The head CT scan with in-travenous contrast revealed a non enhancing hypo-dense lesion involving the left frontal, parietal andtemporal lobes with midline shift (Figure 1). No fur-ther tests were done and the patient was diagnosedwith cerebral metastasis from a breast cancer andreceived initial treatment with dexamethasone,4 mg every 6 hours for a few days. Because she didnot improve, the CT scan of the head was repeated,

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Figure 1. Contrast enhanced axial CT scan: left fronto-temporo-parietal hypointense lesion without enhancement. Ventricularcompression and midline shift.

Figure 2. A) Coronal section of the brain with expansion ofthe white matter of the left frontal and temporal lobes. Mid-line structures are shifted to the right. There are left subfal-cine and uncal herniation. B) Diffused infiltration by neo-plastic astrocytic cells (H.E., × 200).

A

B

which showed uncal herniation in addition to whatwas shown previously. Radiation was not consid-ered at that point because it could have increasedthe preexisting edema and precipitated a coma. At11 days, she went into a coma and died. The autopsydid not reveal a metastasis from breast cancer. Themacroscopic study of the brain revealed left uncalherniation and diffuse augmentation of the leftfrontal, temporal and parietal lobes which demon-strated soft and gray discoloration. The corticalmargin was not well defined. The ventricular sys-tem was compressed and there was a midline shift tothe right (Figure 2A). The microscopic analysis re-vealed that the white matter of the frontal, parietaland temporal left lobes, the corpus callosum, basalganglia, thalamus and internal capsule of bothhemispheres were infiltrated with well differentiat-ed astrocytes with nuclear pleomorphism (Figure2B). There was a positive staining of glial fibrillaryacidic protein (GFAP) in the astrocytic cells.

Discussion

The first reported case of GC was in 1897, accordingto a review conducted by Jennings et al. [2]. In 1938,Nevin [12] proposed the term gliomatosis cerebri forthe first time and Scheinker and Evans [3] describedthe anatomopathological criteria which were ac-cepted by other authors [2, 4]. In January of 1995Jennings et al. [2] described 3 new cases of GC andhas to date, reported the most complete literaturereview. Jennings reported 160 cases including the se-ries of 10 patients by Artigas et al. [10], another se-ries of 4 patients by Couch and Weiss [13], and 10patients by Ros et al. [14]. All authors had the samefindings of the anatomoclinical manifestations ofGC, which are in order of frequency: corticospinal

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tract deficits, dementia, headaches, seizures, cranio-neuropathy (CN III–XII), papilledema, increasedintracranial pressure, spinocerebellar deficit, men-tal status alterations (lethargy, obtundation), behav-ioral changes, psychosis, sensory deficits, paresthe-sias, visual alterations (blindness, hemianopsia, ob-scurations), pain (back or radicular), and myelo-pathy. The most common symptom in the series ofCouch and Weiss [13] was personality alterations.The median age of GC is between 40 and 50 yearswith a range from the neonatal period to 83 years ofage. The ratio between male/female is 1.07:1 and thesurvival rate from the onset of the first symptom is 12months in 48% of the cases, 24 months in 37% ofcases and 36 months in 26% of cases [2]. In our case,the patient experienced a rapid neurologic deterio-ration in spite of treatment and she died in 11 days.The most common cerebral areas affected are: cen-trum semiovale, cerebrum, mesencephalon, pons,thalamus, basal ganglia and cerebellum. In our anat-omopathological study, we found tumor enlarge-ment with mass effect, ventricular collapse and un-cal herniation. Uncal herniation was found in 8 outof 32 cases reviewed by Couch and Weiss [13]. Thestaining for fibrillary acidic protein (GFAP) and forS-100 protein was positive in the cases in which it wasutilized [2]. Our microscopic exam revealed diffuseinfiltration of cells, and the staining for GFAP waspositive. The best actual method for diagnosis is theMRI which has a higher sensitivity and specificityrate than the CT scan, according to a comparativestudy of 8 patients [9]. The MRI showed enhance-ment of focal points of enhanced T-1weighted imag-es. It also found isodense or hypodense lesions of T-1images and diffuse lesions of high intensity in bothcerebral hemispheres of the T-2 weighted images.Yet the CT scan found less specific results includingpoorly defined isodense and hypodense lesions [9].Artigas et al. [10] found in 5 out of 10 patients thatthe CT scan showed great hypodense areas withmass effect in some cases and normality in others. Inour patient, the CT scan showed a hypodense area,compressed ventriculi and midline shift. But theMRI allows a differential diagnosis of the GC withother demyelinating process and the MRI furtherallows for a better delineation of the tumor whichthe CT scan does not permit [9].

The prognosis of GC continues being poor be-cause there is no established treatment, in part dueto the absence of prospective or retrospective stud-ies. We should be alerted to cases like the one pre-sented here, especially when the clinical course andfindings on the CT scan do not fit the characteristicof cerebral metastasis.

Acknowledgements

We thank Marıa C. Gonzalez-Iglesias for her help inthe translation.

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Address for offprints: A. Iglesias, Building 10, 12N226, MedicineBranch, National Cancer Institute, NIH, Bethesda, Maryland20892, USA