Intracranial tumors in neonates: A report of seventeen cases

Surg Neurol 1984;21:165-70

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Intracranial Tumors in Neonates: A Report of Seventeen Cases Rashid Jooma,

F . R . C . S . , B r i a n E. K e n d a l l , F . R . C . R . ,

and Richard D. Hayward,

F.R.C.S.

Departments of Neurosurgery and Neuroradiology, The Hospital for Sick Children, Great Ormond Street, London, United Kingdom

J o o m a R, Kendall BE, Hayward RD. Intracranial tumors in neonates: a report of seventeen cases. Surg N e u r o l 1984;2 l : 165-70.

Seventeen patients with intracranial neoplasms that were symptomatic within the first 2 months of life were studied. Macrocrania was the commonest clinical feature, and radiologic studies including computed tomographic examination in five of the patients, showed that the tumors tended to be large, rapidly growing, and located along the neural axis. The outlook was poor, with a high operative and case mortality. The risks of irradiating young infants are discussed, and a conservative surgical approach with careful case selection is advocated.

KEY WORDS: Brain neoplasm; Newborn infant; Macrocrania; Computed tomography; Radiotherapy; Treatment

The incidence of intracranial neoplasms in the neonatal period has been estimated at 0.34 per million live births [7], and their rarity is reflected in the small n u m b e r of cases reported, which n u m b e r e d 103 when Takaku [13] surveyed the world literature in 1978. H o w e v e r , most such reports have described p o s t m o r t e m findings; the n u m b e r of babies subjected to any form of treatment has been very limited. With the widespread use of prenatal ultrasound scanning and c o m p u t e d tomography (CT) in the investigation o f infants with macrocrania, the n u m b e r of brain tumors detected in neonates is certain to increase [12]. T h e available literature documents the poor results o f the surgical treatment of these refractory lesions, but does not provide adequate information on their management, scarcely mentioning, for example, the use of irradiation or chemotherapy. In an attempt to fill this hiatus, we undertook a retrospective study of patients presenting with intracranial tumors symptomatic within the first 2 months of life.

Address reprint requests to: Rashid Jooma, D e p a r t m e n t of N e u r o surgery, Frenchay Hospital, Bristol, BS16 1LE, United K i n g d o m ©

1984 by Elsevier Science Publishing Co., Inc.

Clinical Material and Results During the period 1953-1981, 7625 children were admitted to the Neurosurgical unit of the Hospital for Sick Children, London, England, and in 1296 (16.9%) a clinical or histologic diagnosis of intracranial neoplasm was made. Seventeen of these latter patients were symptomatic within 2 months of birth, the average age at onset of the first symptom recognized by the attendants being 2.4 weeks (range: birth to 8 weeks). T h e r e was a lag of 6 weeks average duration before the diagnosis was made, at which time the average age of the group was 8.5 weeks (range: 2 days to 3 months). The most c o m m o n abnormality noted was an alteration of behavior, with anorexia, irritability, or unusual quietness (Table 1). Vomiting was another frequent symptom, and was sufficiently prominent in several patients as to suggest pyloric stenosis. In the case of one infant the parents noticed an abnormally warm area on the patient's scalp, which overlay a vascular intracranial tumor. Four neonates were symptomatic at birth, two with large heads, one with intractable vomiting, and the fourth with respiratory distress. Macrocrania with an occipito-frontal circumference exceeding the 98th percentile was present in 10 cases (60%), and was in each instance associated with a bulging fontanelle, an abnormal percussion note, and the other features of infantile hydrocephalus. Two infants with suprasellar tumors exhibited rotary nystagmus; one of these also exhibited the emaciation, euphoria, and elfinlike look characteristic of the "diencephalic syndrome" of Russell [11], while the other, who had a glioma of an optic nerve and the chiasm, presented with unilateral proptosis. In two instances a bruit caused by a highly vascular neoplasm was heard over the skull, and in one of these there was a soft bulge of the skull localized over the tumor. A review of radiographs of the skull revealed an abnormality in 14 cases (82%); there was also evidence of an increased intracranial pressure (65%) or features more specific to a particular type of tumor. These included enlarged optic foramina in the two cases of optic gliomas, together with erosion of the presellar sphenoid in one 0090-3019/84/S~,00

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Table 1. Presenting Features Macrocephaly Seizures Vomiting Abnormal eye movements Failure to thrive Irritability Respiratory distress

5 4 2 2 2 1 1

o f these (Figure 1), and t u m o r calcification in both of the cases o f teratomas (Figure 2). Five tumors were studied angiographically; all were vascular (Figures 3 and 4), and their large size was evident from prominent displacement of the vessels. C o m p u t e d tomograms were made in five cases, the findings in which are listed in Table 2; all involved large tumors with well-defined edges, suggesting growth by expansion rather than infiltration. I n v o l v e m e n t of the optic nerve, chiasm, and tract characterized the optic gliomas (Figure 5), and in the case of teratoma an absolute diagnosis was made possible through the presence of both calcification and fat (Figure 6). T h e rapidity of growth was well illustrated in this case, in which CT scans and angiograms 3 weeks apart showed an increase in tumor size. Cerebral infarction due to arterial narrowing was caused by one primitive glial t u m o r (Figure 7); an intratumoral hemorrhage was shown in this case and in one other tumor which was also o f the primitive glial type. Twelve of the 17 tumors (71%) were supratentorial, and these were equally divided between hemispheric

and axial locations. All of the five infratentorial tumors (29%) were related to the fourth ventricle. A histologic diagnosis was available in 13 cases, through operation in 10 and autopsy in 3; the 4 unverified tumors were all located in the region o f the third ventricle, and were characterized by neuroradiologic studies. O f the 13 verified tumors, 6 9 % were neuroectoderreal in origin, consisting of three medulloblastomas, two astrocytomas (one cerebellar), two primitive neuroectodermal tumors, one e p e n d y m o m a of the fourth ventricle, and one choroid-plexus papilloma of a lateral ventricle. The nonglial tumors comprised two teratomas, one cavernous angioma and one metastatic lesion from

Figure 2. Teratoma. X-ray study of the skull. (A) Anteroposterior and (B) lateral view. There is irregular nodular calcification in the region of the anterior horn and adjacent parts of the bodies of the lateral ventricles, more extensive on the right side.

A

Figure 1. Grade 111 suprasellar astrocytoma. X-ray examination of the skull," lateral view. There is erosion of the presellar sphenoid.

....

B

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A

B

F i g u r e 3. Teratoma. Right carotid angiogram. Lateral projection. (A) Early and (B) late arterial phase. There are irregular tumor vessels, with segmental enlargement of a cortical branch of the middle cerebral artery supplying the tumor, and early venous drainage from it.

19 months, giving a total case mortality of 80%. O f the two survivors, one had an intraventricular cavernous angioma removed 1 week after birth 14 years ago while the other had a medulloblastoma excised 2 years ago. This latter child had initially presented 2 days after birth with gross hydrocephalus, which responded to ventriculoperitoneal shunting. Development was normal to the age of 10 months, when cerebellar ataxia supervened, necessitating a craniectomy done through the posterior fossa, followed by radiotherapy and chemotherapy. O f the four infants in the series with unverified suprasellar tumors, two received radiotherapy and two were not treated; only one of these four patients is alive, 4 years after undergoing irradiation for a chiasmal glioma. Two of the patients in whom tumors were verified at autopsy died 3 months and 1 year, respectively, after the insertion of a shunt, while the third child, who had a parietal metastasis, died during a laparotomy for the primary tumor. Thus, of the total series of 17 patients, only 3 are alive, the rest dying within 2.5 years of presentation (average 45 weeks). The five patients treated with radiotherapy received a reduced dosage, ranging from 3000 rads within a 4week period for a suprasellar tumor to 5000 rads over a 6-week period for a medulloblastoma. In none of these infants was the therapy interrupted because of intolerance; however, two of the three infants who survived for at least 1 year were severely retarded, while the third, now aged 3 years, has a functional age of 2.

a hepatoblastoma. The management and outcome in the foregoing cases are summarized in Table 3. Ten patients had their tumors treated by operation, preceded in two instances by a cerebrospinal fluid shunt and followed in two cases by irradiation. In this group there were four deaths within 10 days, giving an operative mortality of 40%, while a further four of the patients died within F i g u r e 4. Primitive glial tumor. Right carotid angiogram. Lateral projection." arterial phase. The large frontal mass with capillary circulation displaces and narrows the terminal carotid and anterior cerebral arteries.

Discussion

,~. . . .

When Arnstein reported a neonatal brain tumor in 1950, his survey of the literature yielded only 13 previous cases, and although 103 cases had been documented by 1978 [13], only recently has the antemortem diagnosis

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Table 2. Computed-Tomographic Findings in Neonatal Tumors Histology

Site

Primitive glial tumor

Bifrontal

Primitive glial tumor (Figure 7)

Bifrontal

Grade III astrocytoma (Figure 5)

Right optic nerve optic chiasm. Right optic tract Right lateral ventricle

Teratoma (Figure 6)

Medulloblastoma

Density relative to brain High, with central low density containing hematoma Mixed, with hemorrhage into tumor and left ventricle

Cerebellar vermis

Enhancement

Edema

Additional features

Edge

Marked

-

Defined

--

Irregular

+

Defined

Slightly higher

Marked

-

Defined

Mixed, mainly equal with calcification and fat Low

Irregular

-

Defined

Communicating hydrocephalus. Rapid tumor growth

Irregular

+

Ill defined

Obstructing fourth ventricle. Hydrocephalus with periventricular lucency

Right middle cerebral infarction. Communicating hydrocephalus followed bleeding

o f these lesions begun to be achieved at an earlier stage, making their surgical treatment a m o r e practical venture [13,14]. T h e dissemination of c o m p u t e d t o m o g r a p h y (CT) and nuclear magnetic resonance ( N M R ) imaging will continue to increase the n u m b e r of neonates presenting for treatment, and it is therefore important to accumulate information on the results to be expected from the surgical treatment and the use of adjuvant therapy of neonatal intracranial tumors. It has been stated that tumors presenting in the first 2 months of life could be considered congenital, and the "embryonal rest" theory has been invoked to explain their origin. O f particular interest in this respect is the report by Whittle and Simpson [14] of an intracranial teratoma associated with palatolabial malfusion, sug-

gesting that the tumor was present at 7 to 9 weeks gestation. O n e patient in the present series (case 10) was the second of monozygotic twins; the first twin is completely normal, and we therefore assume that the oncogenetic factors in this instance were not inherited. Case 8 in our series exemplifies the rapid growth that is a characteristic feature of most neonatal tumors. Bloom et al [2] found that Collins' law, which was formulated for Wilms' tumor, held true for medulloblastomas. O u r series shows, however, that the "period of risk" is not applicable to brain tumors in neonates, with the majority of such tumors reported having been teratomas, which are particularly malignant at this age. In our series there is a scatter of histologic types, with neurectodermal tumors comprising 6 9 % of these. T h e r e were two highly

Figure 5. Grade III astrocytoma. (A) Plain C T scan, and (B) similar level after contrast-medium enhancement. There is a contrast-medium-enhancing mass of mainly slightly increased density in the right optic nerve, chiasm, and right optic tract. It erodes the presphenoid and widens the adjacent cisterns.

Figure 6. Teratoma. (A) Computed tomographic scan done on September 7, 1978. There is a large mass containing both calcification and fat within the dilated right lateral ventricle and extending across the midline. (B) Computed-tomographic section a similar level, done on September 29.1978. showing a considerable increase in the size of the tumor mass.

A

A

B

B

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cellular, large, and rapidly growing

A

B

C

D

Figure 7. Primitive glial tumor (A and B); plain C T scan, August 8. •979. There is a large bifrontal mass of mixed density with a little surrounding edema. Part of the density is due to haematoma, and there is blood in the left lateral ventricle. (C) Plain C T section done on August 29, 1979 at similar level to that in (B). (D) Computed-tomographic scan done with contrast-medium enhancement at the same level. The mass is smaller and of lower density, with irregular enhancement. There is a contrast-mediumenhanced infarct in the right middle cerebral distribution, and moderate hydrocephalus has developed.

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primitive glial tu-

mors, which are known to have a poor prognosis [9]. The most favorable experience was with the case of cavernous angioma, which has previously been associated with an excellent outcome [8]. Optic gliomas are slow-growing pilocytic astrocytomas compatible with p r o l o n g e d s u r v i v a l [ 3 ] , a l t h o u g h t h e a f f e c t e d c h i l d will be visually handicapped. The recent progress in noninvasive neuroradiologic m e t h o d s is p a r t i c u l a r l y v a l u a b l e w i t h r e g a r d t o y o u n g infants, in whom the risk of complications stemming f r o m t h e u s e o f c o n t r a s t m e d i u m is s i g n i f i c a n t l y i n c r e a s e d o u t s i d e s p e c i a l i z e d c e n t e r s . I t is n o w p o s s i b l e to use CT to assess the extent of the tumor and potential f o r its o p e r a t i v e t r e a t m e n t , a n d t o r e s e r v e a n g i o g r a p h y

T a b l e 3. Patient Characteristics, Treatment. a n d Outcome Case No.

Age at first symptom

Age at admission

Tumor histology

!

4 wk

8 wk

Malignant ependymoma Primitive glial tumor --

2

Birth

8 wk

3

4 wk

12 wk

4

2 wk

10 wk

5

4 wk

16 wk

6

2 days

6 days

7

2 wk

3 wk

8 9

8 wk 1 wk

l 1 wk 4 wk

Teratoma Medulloblastoma

10

8 wk

20 wk

Astrocytoma grade I

11

2 wk

7 wk

--

12

2 wk

10 wk

13

5 wk

6 wk

14

6 wk

8 wk

Secondary hepatoblastoma Primitive glial tumor Medulloblastoma

15

Birth

1 wk

16 17

Birth Birth

18 wk 2 days

Choroid plexus papilloma -Cavernous angioma --

Astrocytoma grade IIl Teratoma Medulloblastoma

Tumor location

Treatment

Outcome

Fourth ventricle Bifrontal

Partial excision

Postoperative death

Partial excision

Postoperative death

Anterior third ventricle Lateral ventricle Anterior third ventricle Lateral ventricle Anterior third ventricle Frontal Fourth ventricle

RT 4000 rads in 23 fractions Excision

Alive; blind, retarded, epileptic Postoperative death

Anterior third ventricle

-Excision

Died aged 2 yr Alive and well at 14 yr

-VA shunt Excision RT 3000 rads to post-fossa, 1800 to spine Partial excision RT 3600 rads

Died aged 3 yr Died aged 3 mo Well for 5 mo and then died due to recurrence

Anterior third ventricle Parietal

RT 3500 rads

Died at 5 yr due to recurrence; was blind and retarded Died at 3 mo

Laparotomy

Intraoperative death

Bifrontal

Shunt

Died aged 1 yr

Fourth ventricle Cerebellum

Excision No RT 1. Cyst aspiration 2. Excision (at 18 mo)

Died of recurrence at 5 mo

Subfrontal Fourth ventricle

Partial excision 1. VP shunt (at 10 days) 2. Excision (at 10 mo) RT 5000 rads to post~fossa; 2600 rads to spine Chemotherapy

Normal development to age of 18 mo; symptomatic; postoperative death Postoperative death Normal development at first; at 10 mo symptomatic with delayed milestones

Abbreviations: wk = weeks; mo = months; yr = years; RT = radiation therapy; VP = ventriculoperitoneal; VA = ventriculoatrial

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for those cases in which it is useful for planning the surgical approach. Neonatal brain tumors tend to be large, rapidly growing, and located deeply within a hemisphere or in the region of the third ventricle. Such features make their operative treatment hazardous, and success is generally rewarded by a child with major deficits. The documented results of surgical treatment are dismal; very few patients have survived for even 1 year, and certainly none have been normal. Our results are similar, with the exception of the patient in case 6, who is intellectually and physically normal 14 years after having undergone the removal of an intraventricular cavernous angioma. This lesion, however, is more correctly considered a hamartoma; our longest survivor with a true tumor is a child with an optic glioma, who is blind and retarded at 4 years of age. The brain o f the newborn rat is excessively sensitive to irradiation [4], and on this basis clinicians have been hesitant to subject neonates to a potentially harmful treatment. Studies at our hospital have demonstrated the intellectual impairments occurring in leukemic children receiving prophylactic central nervous system irradiation [6], which were even more frequent and more marked when children receiving therapy for brain tumors were tested (L. Jannoun: unpublished data). Other workers have presented similar findings [5,10]. The experience with the five cases in our series suggests that a young infant will tolerate a radiation dosage o f up to 4000 rads reasonably well, but that mental retardation is a significant risk.

Conclusion A review of neonatal brain tumors suggests that those of only a few histologic types will respond significantly to treatment; these include cavernous angiomas, choroid-plexus papillomas, and small teratomatous cysts. Computed tomography and angiography would be ex-

Jooma et al

pected to be helpful in the preoperative diagnosis of neonatal brain tumors and to facilitate the selection of those tumors suitable for surgical excision. An aggressive approach to most neonatal brain tumors is not currently warranted on the basis o f the results achieved with surgical treatment and the radiation dose used in infants with these lesions must be limited because of the increased sensitivity of the immature brain.

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