D-40225 Dsseldorf
(10) Rao, 5., Constantini, S., Gomori, J. M., Siegal, T, Epstein, F. Spontaneousinvolution of an intraaxial brain stem lesion: A case report. Pediatr. Neurosurg. 23,279-282 (1995).
At 6. 10 years, he hComplete Remission of a Diffuse Pontine Gliomaad learned to ride a bike, to swim, and had to be rescued from the topof a cherry tree by the fire brigade.
He was seen by a child neurologist at the age of 20 months who described a broad-basedataxic gait, uncoordinated grasping, and intention tremor. Reflexes and cranial nervefunctions were reported as normal.
(9) Langmoen, I. A., Lundar, T., Storm-Matheisen, I., Lie, S. 0., Hovind, K. H. Managementof pediatric pontine gliomas. Childs nerv. Syst 7, 13-15 (1 99 1).
Wschr. 139, 660-665 (1997).
Case report
Amongst paediatric patients with gliomas of the brain stem those with diffuse intrinsicgliomas of the pons have the worst prognosis. Though prolonged duration of brain stemsymptoms and signs prior to diagnosis - more than 1 year in our patient - is consideredprognostically vourable, pontine location, great tumour volume, and brain stemenlargement - as in our patient - correlate with a particularly adverse outcome (7).3-year survival times in the literature vary between 3 and 21 % (for summary see Freemanand Farmer 1998 [61). The usual Kaplan- Meyer tables do not provide information concerningthe further clinical and radiological course in the surviving patients. There is, however,no reason to assume that any one of those survived free of symptoms or even without aremaining tumour.
(5) Freeman, C. R., Bourgouin, P. M., Sanford, R. A., Cohen, M. E., Friedman, H. S., Kurz,L. E. Long term survivors of childhood brain stem gliomas treated with hyperfractionatedradiotherapy. Cancer 77, 555-562 (1996).
(3) Constantini, S., Epstein, F Surgical indication and technical considerations in themanagement of benign brain stem gliomas. J Neuro-Oncol. 28, l93-205 (1996).
Complete Remission of a Diffuse Pontine Glioma
We report on a 2-years-old boy with a large diffuse fibrillary astrocytoma of the pons inwhom the clinical symptoms abated without any conventional therapy other than shunting on occlusive hydrocephalus. The tumour progressively decreased in size on repeated MRIscans, and was no longer visible after 5 years. Only one similar case has been published,though without histological documentation, by Rao et al (10).
At the age of 23 months, the boy was seen in our department. He could walk only when heldon both hands. He showed muscular hypotonia, ataxia, and intention tremor. There were analternating convergent strabism, bilateral weakness of the N. abducens, vertical gazepalsy, up-beat nystagmus, and pale optic discs without prominence. Reflexes were increasedon the legs, pyramidal signs inconstantly positive. The boy appeared alert and attentive,but did not speak
On the last MRI examination at the age of 6.6 years, the tumour was no longer visible.With the exception of two small CSF- isointense lesions within the pons which wereassigned to the stereotactic biopsy, signal intensity in the pons and the midbrain wasclearly normal.
Introduction
(1) Allen, J. C., Siffert, J. Contemporary chemotherapy issues for children with brainstemgliomas. Pediatr. Neurosurg. 24, 98-102 (1996).
The first follow-up study by MRI, performed at the age of 3.5 years, revealed a clearshrinkage of the tumour. Hydrocephalus had regressed due to the ventriculo-peritonealshunt. An additional MRI examination 11 months later showed an ongoing decrease of thetumour size with an incomplete tumour remission.
The cause of the complete remission in our patient remains unknown. The effect which is tobe attributed to the unconventional therapies applied is rated differently by the authorsof this report according to their medical and philosophical background.
(7) Kaplan, A. M., Albright, A. L., Zimmerman, R. A., Rorke, L. B., Li, H., Boyett, J. M.,et al. Brainstem gliomas in children. Pediatr. Neurosurg. 24,185-192 (1996).
Rao et al (10) reported on spontaneous involution of an intrinsic brain stem lesion in a4-year-old child. Though a histological diagnosis was not available, clinical and MRIfindings were very similar to those in our patient and the authors assumption that thesecharacteristics "strongly suggest a tumour etiology" appears completelyjustified. We therefore refrain from presenting our patient as the first one with acomplete remission of a diffuse pontine glioma,
tumor
though he may be the first one in whom thediagnosis is morphologically documented.The patient, the third of four children from a healthy mily, was born withoutcomplications after an uneventful pregnancy. He developed normally until the age of 11months when he was able to stand and to walk a few steps without support. He then stoppedunaided walking, moved around only in a sitting position or by crawling without the use ofhis left leg.
(6) Freeman, C. R., Farmer 1. P. Pediatric brain stem gliomas: a review. Int. J. RadiationOncology Biol. Ph5,s. 40, 265-271 (1998).
At 2.5 years, the boy was able to speak a few words and to walk some steps unaided.Neurological examination still showed generalized hypotonia, a broad-based ataxic gait,uncoordinated grasping, and a convergent strabism.
A patient is described in whom a large diffuse glioma of the pons extending into themidbrain was diagnosed at the age of 2 years. Biopsy showed a fibrillary astrocytoma.After shunting of a hydrocephalus, the clinical symptoms abated without convencionaltherapy. Repeated MRI studies showed a continuous decrease of the tumour which was nolonger visible when the patient was 6.6 years old.
Moorenstr. 5
(11) Walter, A. W, Gajjar, A., Ochs, J. S., Langston, J. W, Sanford, R. A., Kurz, L. E.,et al. Carboplatin and etoposide with hyperfractionated radiotherapy in children withnewly diagnosed diffuse pontine gliomas: A phase I/II study Med. Pediatr. Oncol. 30, 28-33(1998).
Discussion
Department of Paediatrics
The parents, unable to accept the dismal prognosis, asked for therapeutic attempts, evenif there would b e no scientific foundatioxi for the hope of a positive effect. Treatmentwas started with a mistletoe preparation (Iscador P 3%0) combined with homeopathicdilutions. After 3 months, Iscador was replaced by Helleborus 1 %, and these drugs werecontinued allernatiiigly in 3- months intervals. Already after six weeks of treatment, theboy started playing with other children and began to communicate verbally; there svere sWIfew eye movements and barely any rriimic reactions. Improvement continued during thefollowing months.
(4) Fischbein, N. J., Prados, M. D., Wara, W., Russo, C., Edwards, M. S. B., Barkovich, A.1. Radiologic classification of brain stem tumors: Correlation of magnetic resonanceimaging appearance with clinical outcome. Pediatr. Neurosurg. 24, 9-23 (1996).
Histopathological investigation of the stereotactic biopsy specimens showed a diffuselyinfiltrating astrocytoma of low cellularity. Morphological signs of anaplasia, i.e.,mitoses, necroses or microvascular proliferations, were absent. No Rosenthal fibres oreosinophilic granular bodies were seen. There were no inflammatory infiltrates.Immunohistochemically, the tumour cells strongly expressed glial fibrillary acidicprotein. Individual tumour cells (< 1%) stained positive for theproliferation-associated nuclear antigen Ki-67 (MIB1). Nuclear immunoreactivity for thetumour suppressor protein p53 was noted in a considerable fraction of tumour cells whileimmunoreactivity for epidermal growth ctor receptor was weak. Staining for leukocytecommon antigen and CD68 revealed neither lynphocytic infiltrates nor evidence formicroglial activation. The final neuropathological diagnosis was fibrillary astrocytoma ofWorld Health Organisation (WHO) grade 11.
According to sufficiently well documented case reports, spontaneous remission in oncologicdisorders is considered to occur with a frequency of 1 in 60,000 to 100,000 cases (2)Reports concerns, besides the well known cases of neuroblastoma in inncy, metastasizingbronchial carcinomas, malignant melanomas, kidney carcinomas, and malignant lymphomasincluding certain forms of leukaemia. Brain-stem tumours, especially pontine gliomas, arenot mentioned in extensive reviews (8).
(2) Cole W. H. Efforts to explain spontaneous regression of cancer., J. Surg. Oncol. 17,201-209 (198 1).
(8) Kappauf, H. Spontasion bei Krebserkrankungen. Mnch. Med.
Germany
Except for some behavioural problems at school there were no complaints, and theneurological examination was normal.
In reviews on spontaneous remissions of oncologic disorders we were unable to find acase of a biologically benign brain stem tumour. There is one isolated report on a similarcase, though without histologic documentation.
Abstract
Gliomas of the brain stem can be classified according to their location and growth patternas focal, dorsal exophytic, cervico-medullary, and diffuse intrinsic (6). Although a moreactive surgical approach has become feasible (3) the overall prognosis is stillunvourable with a 5-year survival rate in the range of 30 %. The prognosis is especiallypoor for the subgroup of diffuse intrinsic pontine gliomas resulting in "pontinehypertrophy". These tumours are not aglioma prognosismenable to surgery. Treatment by radiotherapy(5, 7), by chemotherapy (1), or by a combination of both (11) mav induce short-termremissions but has up to now not improved a 2-4 year survival rate of less than 20% (4).
Hans-Gerd Lenard, M. D.
At 3.7 years, the motor functions had further improved. The boy could walk, stand on oneleg, and had a normal neurological status except for a strabism.
Langmoen et al (9) described a 2-year old boy with hypodense expansion of the pons whosurvived for 12 years without treatment. No information on neuroradiological follow-up isavailable to the authors (Langmoen, personal communication).
Laboratory values from blood, urine and CSF were normal. On cranial CT a hypodense tumourwithout contrast enhancement was seen in the pons, compressing the 4th ventricle andcausing a triventricular hydrocephalus. On MRI the tumour was hypointense on T1 andhyperintense on T2-weighed images, without enhancement after i.v. application of Gd-DTPA.The tumour was located in the pons extending into the midbrain. Both cerebral peduncleswere involved, the right one slightly more than the left. Tumour margins were smoothwithin the pons with some small irregular tumour extensions into the adjacent brain at thelevel of the midbrain. A severe triventricular hydrocephalus with transependymal oedemawas seen due to the tumour compression of the aquaeduct of the mesencephalon. A ventriculoperitoneal shunt was inserted and a stereotactic biopsy performed.
Surgical intervention, irradiation or chemotherapy appeared not feasible due to thelocation and extent of the tumour, the age of the patient, and the result of the biopsy.The boy therefore was discharged and the parents were informed about a dismal prognosis.Further care and treatment was taken up by another paediatric hospital where one of theauthors (Ch. T.) is the responsible oncologist.
