Child's Nerv Syst (1999) 15:219-221 © Springer-Verlag 1999 BRILF

Önal Gliomatosis cerebri with neurofibromatosis: Çiçek an autopsy-proven case

Gliomatosis cerebri Received: 15 July 1998 Abstract is a stereotactic ante-mortem diagnosis glial neoplastic process that is dif- and the other after autopsy. in this fusely distributed through neural paper. the autopsy-proven case Ç. Önal (BI) 1 • Ç. structures, whose anatomical config- of this rare disease with coexistent Department of Neurosurgery, uration remains Among the neurofibromatosis - the sixth lstanbul School of Medicine, more than 19,000 cases hospitalized case reported in the literature - Universitv of Istanbul, Çapa. Turkey in Istanbul University Istanbul is presented. School of Medicine Department of address: 1 Cad. Özenç Sok .. 4/9. Neurosurgery throughout the past Key words Gliomatosis cerebri · TR-81080 Erenköy-lstanbul. Turkey 45 years, only 2 cases were diag- Neurofibromatosis · Autopsy · Fax: +90-422-34 !O 726 nosed as gliomatosis cerebri. 1 by GFAP

tened gyri showing diffuse oedema and no enhancement lntroduction (Fig. 1 Antibiotic and therapy was begun when the initial diagnosis of meningitis was made. No change was noted on Gliomatosis cerebri is a rare tumour of neuroepithelial or- follow-up CT performed 5 days later. MRI studie~ showed diffuse igin with vague presentation [l. 3. 5-8). Even hypo-isointense lesions in T1 and extensive lesions in with the aid T2-weighted and proton density tPDJ images (Figs. 2. 3). The me- of the most sophisticated techniques, ante-mortem diagno- dulla spinalis was in spite of an therapy. her condi- sis is difficult [2, 8). Among the more than 130 cases re- tion progressively. She became and died corded so far, only 5 cases with neurofibromatosis have 5 after the initial been presented [ 1, 7, 9. 10]. The present case is a new one with coexistent neurofibromatosis.

Macroscopic pathology

Case report The general autopsy showed bilateral purulent bronchop- neumonia, chronic bronchitis and pleuritis. bilateral bron- A 13-year-old Caucasian girl with the chief complaints of headache chiectasia and and diplopia followed by nausea and vomiting was admitted to the fibrosis. No pathologic change to the cal- hospital just after an attack of general weakness and unsteadiness. varial sinuses or dura was remarked. The brain appeared On physical examination she was found have multiple pigmented to be moderately swollen and leptomeninges were hypae- cutaneous lesions evaluated as cafe-au-lait spots and hyperpigmen- remic. Coronal sections ofthe brain revealed bilateral dif- tation in axillary and areas. Neurologically she was fuse yellow-greyish discoloration of the white rnatter and alert. and There was no speech disorder. She had positive meningeal signs. papilledema. Vlth nerve palsy on a relatively soft consistency. especially in the right fron- the Jeft. conjugated gaze paralysis. and tlask tetraparesis. toparietal region with extension to the basa! ganglia and Her gait was slightly ataxic and tendon reflexes were normal. No occipital pole. Similar changes were noted to the brain stem pathologic reflex was remarked. Routine showed and cerebellum near the nucleus dentatus. N omacroscopic normal findings. Cerebrospinal fluid (CSF) examination revealed 40 mg/dl protein. 77 mg/dl glucose. J9/mm 3 lymphocytes and no changes were seen in the cerebellar leptomeninges. Serial polymorphonuclear leucocytes. EEG showed diffuse slow wave ac- sections of the medulla spinalis revealed no gross abnor- occasional focal slowing or spikes. CT scan showed flat- malities. Fig. CT scan of the patient showing diffuse oedema and flattened gyri

Fig. 2 MRI view revealing diffuse hyperintense invoh·ement throughout the neural parenchyma on PO sequences

Fig. 3 Tl-weighted image of lesions on MRI. disclosing the dif- fuse hypointense involvement

Microscopic neuropathology

Microscopically there was a diffuse infiltration of cells through the white matter. especially where the yellow- greyish discolouration was seen. The cells were neoplas- tic astrocytes varying in their degree of differentiation (Fig. 4). They took various forms. having oval or fusiform Fig. 4 Infiltration of tumour cells through the white matter nuclei of moderate pleomorphism with bipolar or multipo- moderate pleomorphism (HE x500) lar proccsses in which neuroglial fibrils were observed in some fields. The cells had notched nuclei, and the cyto- plasm was mostly indistinguishable. The chromatin net- work was very dense in some nuclei and thin in others: no Discussion nucleoli were noted. Neovascularity with hyperplastic en- dothelial cells was observed among these anaplastic glial it was Nevin who coined the term 'gliomatosis cerebri' to cells. Occasional nodules of tumour cells were character- describe a pathologic entity characterized by diffuse pro- ized by marked pleomorphism and a higher rate of cellu- liferation of pleomorphic glial cells throughout the central lar growth. The cortex was infiltrated to varying degrees nervous system [7]. It is usually a diffuse. infiltrating astro- but was spared relative to the white matter and basa! gan- cytoma that invades almost ali of the neural structures. pre- glia. Clusters of cells with similar characters were present serving the preexisting cytoarchitecture, with areas of ana- in the leptomeninges and cerebellum and ali over the pa- plasia and glioblastomatous differentiation [1, 4. 5, 7. 8). rieto-occipital area. The neoplastic process infiltrated the The macroscopic pathological findings in gliomatosis first layer of the cerebellar cortex in some regions. Komi- cerebri include the diffuse enlargement of affected areas. croscopic infiltrative growth was seen in the nucleus den- and ehe cut surface of the brain generally shows loca! or tatus area, where macroscopic changes were observed. The diffuse discolouration. Flattened gyri. unca! and tonsillar structure was normal on medullary sections. Myelin dam- hemi ati ons are frequent pathologic findings [ 1. 2. 5-7. 1O]. age was clearly established using myelin stain-luxol fast The microscopic pathology reveals wide of blue in the zones where widespread infiltration occurred. neural tissue, dominant in the white matter, with pleomor- A small portion of the cells were positive for glial fibril- phic astroglial cells. The tumour cells may take various lary acidic protein (GFAP) after the immunohistochemical with oval or fusiform nuclei and bipolar or multi- reaction. polar processes in which fibres can be observed [ I. 5. 7). 221

Cases of gliomatosis cerebri with neurofibromatosis central neurofibromatosis. Diagnostic criteria for neu- haw already been reported [l. 7, 9, 10]. The main aim of rofibromatosis type 1 include six or more cafe-au-lait present report is to record a new case of gliomatosis cere- spots. two or more neurofibromas of any type or one plex- bri with neurofibromatosis - the sixth case in the litera- iform neurofibroma, freckling in the axillary or intertrigi- ture. Among the more than 19.000 cases referred to Istan- nous areas, optic glioma. two or more Lisch nodules. which bul l;niversity Istanbul School ofMedicine Department of are defined as pigmented iris hamartomas appearing as Neurosurgery throughout the past 45 years. only 2 cases translucent yellow-brown elevations. distinctive osseous hada final diagnosis of gliomatosis cerebri, only 1 of these abnormality. and a first-degree relative with neurofibro- concomitant neurofibromatosis. Besides the extreme rare- matosis type l. The existence of at least two of these cri- ness ofthe disease, this very low incidence may be strongly teria. cafe-au-lait spots. which appear in more than 999c of connected with the inconclusive symptoms, noninforma- neurofibromatosis type l cases. and hyperpigmentation in tive laboratory and radiological data. and unaccustomed the axillary and intertriginious areas in the present case. and nonpathognomonic hiscopathological features of glio- pro\·ide enough evidence to confirm the disease [3]. The matosis cerebri. Our other case. which was published in present patient had a great many pigmented cutaneous le- 1996. was one of diffuse cerebrospinal gliomatosis with sions. most of them greater than 1.5 cm in length. but no antemortem stereotactic diagnosis [8]. visceral or cutaneous nodules in autopsy. Since the patient ~eurofibromatosis is the commonest of the neurocut- was 13 years old and tumorous nodules are frequently ob- aneous disorders. There are four distinct types, two of serYed in later periods of life. generally !ate in the second which. types 1 and 2. are common. Type 1 is also called as decade, coexistence of neurofibromatosis and gliomatosis von Recklinghausen ·s or peripheral neurofibromatosis, cerebri was the final diagnosis. and type 2 is also referred to as bilateral acoustic or

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