i’l Ni7.41,
T
hi OURS
SO
Pineal Tumours: A Clinical Study of 23 Cases s. c. s o Nezucastle General Hospital, Newcastle u p o n Tyne
A srrirs of 23 cases of pineal twnours is prescnted, and their salient clinical featitres are mnlysrd. The rationole of the present trend of treatment is discussed, and the relevant litcrature is reviewed. T II 1- re1,itive inaccessibility of tumours occurring in the region of the pineal gland reiitlers histological diagnosis in life inipracticahle. Rluch reliance is placed on radiology for diagnosis (Greitz, 1972). The unfavourable e\periences associated with direct surgical inter\ ention on these tumours has swung the pentluliuii of treatinent towards a more conieriative ,ittrtutle in recent years. At present, mtliation therap! is the main line of treatment in the niajorit! of neurosurgical clinics of the worltl Tlie following report is a retrospective itutly of L A cases of “pinealoma”, three of d i i c h were ectopic. All were diagnosed in life 1)) iiie:Lns of radiological investigation, but the diagnosis wa5 verified histologically in only seven Thrv were seen in the Department of Neurositrgery. Newcastle General Hospital, (luring the period 1960 to 1974 ; an attempt was matle to euamine the rationale and value of treatment, a n d the literature was reviewed. P A 7 l l ~ h ’Sl 4SD CLTNICA4L FINDINGS
and sc.r tlistribzition.-The age and sex t1istriI)utioti i n the series are expressed in Figure I . Our experience has been in accordance with reports i n the literature that pinealoni;ts are most frequently seen in young inales in the first. sccoiitl and third decades (Davidoff, 1$)7 : l’oppcn and Marino, 1968 ; Araki and Matswimto. 1969). This series consists of 15 inales and eight females. ranging in age from Reprints . Department of Neurosurgery, Newraitle Genci al Hospital, Westgate Road, Newcastle upon Tyne, NEq 6RE, England. !.UST.
N.Z. J.
S U I G , VOL.
46 - NO.
I, FEBRUARY,
1976
three to 50 years. Two of the three patients with ectopic pinealomas are females aged eight and 17 years respectively. Clinical signs and symptowzs.--These are shown in Tables I and 2. Symptoms of headache, nausea and vomiting suggestive of raised intracranial pressure are usually the first mani-
0-10
11-20
21-30
31-40
41-50
FIGUREI : Histogram showing age and sex distribution of patients with pineal tumours. Vertical scale shows number of patients ; horizontal scale shows age in years. Hatched areas indicate males ; clear areas indicate females.
festations of tumours i n the pineal region (Poppen and Marino, 1968). They are due to distortion of the aqueduct of Sylvius and ohstruction to the flow of cerebrospinal fluid early in the development of pineal tumours. Seventeen patients in this series had evidence of raised intracranial pressure when first seen. Paritlaud’s syndrome as evidence of upper
75
so inid-brain involvement was present in nine cases. One of the signs considered to be highly suggestive of a pineal tumour is paralysis of conjugate upward gaze. The underlying inechanism responsible for this disturbance is postulated to lie involvement of the rostra1 portion of the superior colliculi. In juxtaposition to the site where the aqueduct of Sylvius leaves the third ventricle lie the nucleus o f llarkshevich and the interstitial nucleus of Cajal. These nuclei, which are TABLEI Summary oj C k n i ~ a tSvmptoms Symptom Headache . . Visual disturbances' Diplopia ., Blurred vision . . Lethargy, somnolence Nausea, vomiting Polynria, polydipsia Unsteadiness .. Epilepsy . . .. Infantilism ..
Number of cases
: :. ,
.. .. .. ,, ,
. .. ,
.
IS 13 S
n
,
4 2 2 I
directly connected with the oculomotor nuclei via the medial longitudinal fasciculus, coordinate not o n l y the ocular muscles for vertical movcments, Init also the muscles of the upper cyelitl (Szentagothai, 1950; Nittner and Petrovici, 1974). A peculiar type of bilateral ptosis niay be produced if these nuclei are involved, antl this was ohserved in five of the nine p;itients with Parinaud's syndrome. The ptosis, unlike that i n oculomotor palsy, is only partial. Its appearance is 4niilar to that due to muscle weakness.
the "Peter Pan" type of infantilism. Although precocious puberty is a well-documented manifestation of pinealomas (Kitay, 1954), no such cases were found in this series. The duration of symptoms ranged from a month to three years, with a mean of 8.3 months. There was no correlation between the duration of symptoms and the severity of neurological deficits, or with the size of the tumour as assessed radiologically. Radiographic Findings.-These are listed in Table 3. Radiological evidence of raised intracranial pressure was present in the majority of cases (except in the three patients with ectopic pinealoma) . Obstructive hydrocephalus was invariably present. This has an important bearing on the subsequent management of the patient. Four patients (three males, one female) showed abnormal calcification in the pineal region indicative of a tumour. The results obtained with 99Tc scanning of the brain were disappointing (four abnormal scans TABLE 3
Summary of RadiograPhic Findings Evidence
Number of cases
Tumour mass in posterior third ventricle , . Obstructive hydrocephalus . . .. ,, Erosion of posterior clinoids ,. .. Suture diastasis .' Abnormal pineal caldi'fication ' ' **Tcscan (done only in seven casesj
:
.. .. ,. ' '
::
zn
In
9 6 4 4 Abnormal
Of the three patients with ectopic pinealoma, two were Qhownto have a mass in the suprasellar region, and one a mass in the anterior floor of the third ventricle.
The incidence of hypothalamic-hypophyseal tlisturhance in this series is higher than is generally reported in the literature (Poppen antl Marino. 1968; Bradfield and Perez, 1973 ; l>e Girolatni and Schmidek, 1973). Somnolence and diabetes insipidus were the predominant manifestations in this group. One patient, a young man aged 19 years, presented with
out of seven). The number, however, is too small for any conclusion to be drawn. Ventriculography with either air or Myodil was carried out in all cases and proved to be the most valuable investigation. This was also the experience of Greitz (1972). Vertebral angiography was carried out in order to delineate the posterior limits of the tumour in those cases in which a stereotaxic lQsAu implant was contemplated. Carotid angiography was of no value, apart from demonstrating the presence of hydrocephalus. Ectopic pinealomas usually occur in the suprasellar region, resulting in hypothalamic and chiasmal compression. Their radiological appearance in a pneunioencephalogram is no different from that of any other space-occupying suprasellar mass. Their true nature was revealed after operative interference.
76
AUST N.Z. J.
TABLE 2 Summary of Physacal Fandangr Sign Papillodema , . .. .. Parinaud's syndrome . . .. Nystagmus .. .. .. Ataxia . , Paralysis of sixid cra& ner;k Pyramidal tract signs . . Paralysis of third cranial nerik Hypopituitarism .. ..
Number of cases 17
I
S U R C , VOL46-No.
I, FEBRUARY, 1976
PI N E:A 1. '1' IT M OURS
so
TREATMENT A N D RESULTS The treatment given is summarized in Table 4. T n general. a non-aggresive attitude was adopted except in the three patients with ectopic pinealomas, where chiasmal compression was present. Some form of cerebrospinal fluid shunting procedure in the presence of ohstructive hydrocephalus is mandatory. Yentriculo-atrial shunt with a Spitz-Holter valve was the procedure most frequently TABLE 4 Summary of Treatment Treat men t
Number of cases
Ventriculo-atrial shunt+external irradiation .. Ventriculo-atrial shunt fstereotaxic lUsAuimplant Torktldsen's operation +stereotaxic 'enAu implant Torkildsen's operation+external irradiation ., Third ventririiloStomy+ezterrial irradiation ,. External irradiation alone . , ,. ., ..
14 2 I I I
I
The three patirnts with ectopic pinealoma underwent direct surgery, two of them receiving postoperative external Irradiation.
employed i n this series. In all patients with ohstructive hydrocephalus, 4ymptoms of raised intracranial pressure were effectively relieved after cerehrospinal fluid diversion. A course of eutertial irradiation, the dose ranging from 4000 to 5000 radq, was given to those patients thought unsuitable for a stereotaxic lgsAu implant. The spinal axis was not included in the field of irradiation without histological confirniatioti of the diagnosis. Stereotaxic '98Au implnutation was deemed appropriate on]) if the diameter of the tumour as shown 11j ventriculography and vertebral angiography wa5 less than four centimetres and there was 110 e\ itlencc. of tumour infiltration into adjacent structures (Hankinson, 1965, 1975). The aim of interstitial irr:idiation is to cause tumour desttuction with a view to opening up cerelmxpitial fluid pathways. The total dose deliveretl to the tuniour with 1 9 8 A ~according ~, to the size of the turnour, ranges from 7,000 to 1 0 , o o o rads The advantage of interstitial irt adiation as compared with external irradiation has been well cited by Hankinson (1965). Three patients in the present series received a stereotaxic l g 8 h implant. Pathology-In only seven of these 23 patients were the tutnours verified histologically as such Histological examination in life was available for the three patients with ectopic pinealoma : two were diagnosed as teratonias and one as a germinoma. HistoAUST. N.Z. T. SUKG., VOL.46-No. F
I,
FEBRUARY, 1976
logical features in the other four cases were derived from post-mortem findings. There were two teratomas, one germinoma and one pineocytoma. The germinoma also showed subarachnoid metastases in the posterior fossa as well as along the whole of the ipinal axis. Results.-These are summarized in Table 5. There was one postoperative death. The patient was an eight-year-old girl with an ectopic pinealoma, who died of uncontrollable diabetes insipidus one week after exploratory craniotomy. Of the 17 patients receiving external irradiation following a shunt procedure, eight are living and well, with no disabling neurological deficits. The shortest follow-up period is six months and the longest 15 years, with a mean of 4'2 years. The nine patients who died presented with tumour recurrence or subarachnoid metastases or both, six months to three and a half years after initial treatment. The average period of survival was 2.2 years. One feature of note in this group is that despite rapid recurrence the patients were free of any disabling neurological deficit until the terminal stage. The quality of survival prior to the terminal illness was considered good. Of the three patients who received a stereotaxic lgsAu implant, the first is still alive and well 1 1 3 years after treatment and has given birth t o two normal babies during this period. The second died after three years of tumour recurrence, and the third died suddenly a TABLE 5 Summary of Results
---_ Result
..
Dead Operative Tumour recurkence Living . . ..
Number of cases
..
.. ,. ..
I3 I
1 2 (From 6 months to 10 (Follow-up period 6
3h years) months to 15 years)
month after surgery. Post-mortem examination revealed massive hxmorrhage in the tumour cavity. Tw o of the three patients with ectopic pinealoma are living, at one and ten years respectively, without undue complications. The symptom of diabetes insipidus continued unabated following external irradiation, and all four patients in this category required Pitressin. Three of these four patients also required anterior pituitary hormone replacement. Six of the nine patients with Parinaud's
77
so
s ~ n d r o m e liad resolution of their eye signs following treatment. Whether this was related to the relief of increased intracranial presswe or to tiimour destructioii or to both is speculative. Tuniours arising in the pineal region are of rare occurrence, averaging one case a year ( D e Girolanii and Schmidek, 1973). Sufficient experience in their treatment is difficult to obtain, and an authoritative opinion is seldom eupre\setl. Initial experience mainly concerns direct surgical intervention. Dandy ( 1921) reportctl a mortality of 20%. I n 1949,Horrax stated that not more than seven patients who survived total extirpation of the tumour had been reported in the literature. Cummins c t olii (1960) had three operative deaths in five cases. Rant1 antl Lemmen’s (1953) figure of 70% mortality is even more disheartening. Ue (;irolami and Schmidek ( 1973), reviewing the case records from Massachusetts General Hospital, Boston, stated that the mortality rate of total and subtotal removal was 6070, and that that of open biopsy was 337%. Even in such experienced hands, formidable mortality was unavoidable Accordingly, a more conservative attitude has beeii adopted. Horrax (1949, 1950) was one of the first to report favourable results ohtainetl from radiation therapy combined with a decompressive procedure. Kahn (rgC,r) had 12 patients out of 18 surviving for four to rz years following this combination of trEatment. Siiice then, reports in the literature of the use of external irradiation combined with some form of decompreisive procedure in the treatnient of these tuniours in general indicate stirviva1 rates superior to those following tlirect surgical intervention (Matsuoko and Uozumi, 1966 : 1)avidoff. 1967 : Poppen and hl;iriiio. 1968; Rradfieltl antl Perez, 1972, T’:l-Mahtli r t dii, 1972 ; De Girolanii and Schmitlelc. 197.3) However, improved results in total tnnionr extirpation cannot be left ,~nachnowletlgetl (Kunicke, 1960 ; Suzuki and 1wal)uchi, I965 ; Jamieson, 1971). I n the present series, ten patients out of 23 survivrtl for six months to 15 years, an additional piece of evidence in favour of conservat ive treatment. Detailed morbidity assessment in tcrnis of permanent disabling neurological
tleficit and duration of convalescence following direct surgical intervention is unfortunately not available in most of the series reported. A considerable number of Kunicke’s (1960) and Suzuki and Iwabuchi’s (1965) patients liad a long period of hospital stay, and almost half of their patients had either transient or permanent neurological deficits following surgery. The experience of radiation therapy in the present series shows that morbidity is minimal. Ventriculo-atrial shunt is a relatively simple and minor procedure, with little mortality or morbidity. I t is very effective in relieving symptoms in cases of obstructive hydrocephalus. Poppen and Marino in 1968 concluded that “the conservative treatment of ventriculoatrial shunt followed by irradiation has giveii the longest survival time with the fewest residual neurological deficits”. The low morbidity, allowing useful survival following conservative treatment i n the present series, again speaks in favour of a non-aggressive attitude. I t may be argued that the type of tumour should always be verified histologically before irradiation is carried out. The high mortality figures resulting from surgical intervention make this procedure unjustified. Furthermore, De Girolanii and Schmidek (1973) showed that more than 70% of the tumours in the posterior third ventricle are highly radiosensitive. Even with blind application of radiation therapy, the majority of these should respond. Surgical exploration should only be seriously considered in those cases resistant to radiation therapy. Hankinson in 1961 reported his first experience of interstitial irradiation by means of stereotaxic implantation of l Q 8 A ~inside i the tumour in 3 case of pinealoma. Further experience in this method of treatment, using either radio-isotope or cryogenic lesions, has since been reported (Mundinger and Riechert, 1962 ; Hankinson, 1965 ; Conway, 1973 ; Mundinger and Hoefer, 1974). I n general, the results obtained have been favourable. The number of cases involved, however, is too small to allow any conclusion to be drawn. The three stereotaxic lg8Ait implants in the present series were performed by Hankinson following his initial experience. One of these three patients is still living 11: years after treatment with no signs of tumour recurrence. The danger
;S
AUST.N.Z. J. SURG., VOL.46-No.
DISCUSSION
I,
FEBRUARY, 1976
PINEALTIJMOURS
so
of operative hremorrhage resulting from introduction of the probe into the tumour cavity is real, although no such experience was encountered in these three cases. Delayed spontaneous hzniorrhage resulting from tumour necrosis following interstitial irradiation is a potential risk. This was probably the cause of death of one of the patients in this series. Certainly, radio-isotope implantation or cryogenic lesions created hy stereotaxis have a place in the treatment of pineal tumours.
CONCLUSION The following points need to be emphasized. I. Radiation therapy combined with some form of shunting procedure in the presence of ohstructive hydrocephalus should be the first choice in the treatment of pineal tumours. The use of ventriculo-atrial shunt is recommended. 2 . Tnterstitial irradiation should be considered if the tumour diameter as assessed by radiology is less than four centimetres and if there is no evidence of tumour infiltration into adjacent structures. 3. Direct surgical extirpation of the tumour should he reserved for cases resistant to irradiation. 4. The mor1)idity following conservative treattnent is low, and survival is useful. A C K NOWLEDCEMENT
The author would like to express his thanks to Professor J. Hankinson and Mr L. P. Lassman for permission to review their patients and for their criticism in the preparation of this paper.
AUST.N.Z. J. SURG.,VOL.46 - No.
I,
FEBRUARY, 1976
REFERENCES ARAXI,C. and MATSUMOTO, S. (1969), J . Neurosurg., 30: 146. BRADFIELD, J. S. and PEREZ, C. A. (1g72), Radiology, 103: 399. L. W. (1973), J. Neurosurg., 38: 453. CONWAY, J. M. and SCHLESINGEK, CUMMINS,F. M., TAVERAS, E. B. (1960), Neurology (Minneab.), 10: 1031. DANDY,W. E. (1921), Surg. Gynec. Obstet., 33: 113. DAVIDOFF, L. M. (1967), Bull. N.Y. A r n d . Med., 43: 537. DE GIROLAMI,U. and SCHMIDEK, H. (1973), J . Neurosurg., 39 : 455. EL-MAHDI,A. M., PHILIPS,E. and LOTT,S. (1g72), Radiology, 103: 407. GREITZ,T. (I972), Acta Radiol. (Stockh.), 12: 513. HANKINSON,J. ( I&I), Second International Congress of Neurological ., Surgeons. &cerbta Med. (Amst.), E7. HANKINSON, J. (1965), Int. J . Neurol., I : 94. HANKINSON, J. ( 1975), personal communication. HORRAX, G. (1949), Radiology, 52: 186. HORRAX, G. (1950), Arch. Neurol. Psychiat. (Chic.), 64: 227. JAMIESON, K. G. (I971), J . Neurosurg., 35: 550. KAHN, E. A. (I$I), Clin. Neurosurg., 7 : 79. KITAY,J. I. (1g54), J . clin. Endocr., 14: 622. KUNICKE,K. (I@o), I. Neurosurg., 17: 815. MATSUOKO,K. and UOZUMI, T. (1966), Neurol. Mediochir. ( T o k y o ) , 8 : 73. F. and HOEFER,T. (1974), A c t a neuroMUNDINGER, chir. (Wien), Suppl. 21 : 93. MUNDINGER, F. and RIECHERT, T. (1962), First International Symposium on Stereoencephalotomy, 1g61, Confin. Neurol. (Basel), 22: 190. NITTNER,K. and PETROVICI, I. N. (1974), Acta Nezwochir. (Wien), Suppl. 21: 57. POPPEN, J. L. and MARINO,R., JR (1968), J. Neurosurg., 28: 357. RAND,R. W. and LEMMEN,L. J. (1953), J . Neuro"
Y
surg.,
1
10: I.
SUZUKI, J. and IWABUCHI, T. (1965), J . Neurosurg., 23: 565. SZENTAGOTHAI, J. (rgso), Sem. H6p. Paris, 26 : 2989.
79
T
hi OURS
SO
Pineal Tumours: A Clinical Study of 23 Cases s. c. s o Nezucastle General Hospital, Newcastle u p o n Tyne
A srrirs of 23 cases of pineal twnours is prescnted, and their salient clinical featitres are mnlysrd. The rationole of the present trend of treatment is discussed, and the relevant litcrature is reviewed. T II 1- re1,itive inaccessibility of tumours occurring in the region of the pineal gland reiitlers histological diagnosis in life inipracticahle. Rluch reliance is placed on radiology for diagnosis (Greitz, 1972). The unfavourable e\periences associated with direct surgical inter\ ention on these tumours has swung the pentluliuii of treatinent towards a more conieriative ,ittrtutle in recent years. At present, mtliation therap! is the main line of treatment in the niajorit! of neurosurgical clinics of the worltl Tlie following report is a retrospective itutly of L A cases of “pinealoma”, three of d i i c h were ectopic. All were diagnosed in life 1)) iiie:Lns of radiological investigation, but the diagnosis wa5 verified histologically in only seven Thrv were seen in the Department of Neurositrgery. Newcastle General Hospital, (luring the period 1960 to 1974 ; an attempt was matle to euamine the rationale and value of treatment, a n d the literature was reviewed. P A 7 l l ~ h ’Sl 4SD CLTNICA4L FINDINGS
and sc.r tlistribzition.-The age and sex t1istriI)utioti i n the series are expressed in Figure I . Our experience has been in accordance with reports i n the literature that pinealoni;ts are most frequently seen in young inales in the first. sccoiitl and third decades (Davidoff, 1$)7 : l’oppcn and Marino, 1968 ; Araki and Matswimto. 1969). This series consists of 15 inales and eight females. ranging in age from Reprints . Department of Neurosurgery, Newraitle Genci al Hospital, Westgate Road, Newcastle upon Tyne, NEq 6RE, England. !.UST.
N.Z. J.
S U I G , VOL.
46 - NO.
I, FEBRUARY,
1976
three to 50 years. Two of the three patients with ectopic pinealomas are females aged eight and 17 years respectively. Clinical signs and symptowzs.--These are shown in Tables I and 2. Symptoms of headache, nausea and vomiting suggestive of raised intracranial pressure are usually the first mani-
0-10
11-20
21-30
31-40
41-50
FIGUREI : Histogram showing age and sex distribution of patients with pineal tumours. Vertical scale shows number of patients ; horizontal scale shows age in years. Hatched areas indicate males ; clear areas indicate females.
festations of tumours i n the pineal region (Poppen and Marino, 1968). They are due to distortion of the aqueduct of Sylvius and ohstruction to the flow of cerebrospinal fluid early in the development of pineal tumours. Seventeen patients in this series had evidence of raised intracranial pressure when first seen. Paritlaud’s syndrome as evidence of upper
75
so inid-brain involvement was present in nine cases. One of the signs considered to be highly suggestive of a pineal tumour is paralysis of conjugate upward gaze. The underlying inechanism responsible for this disturbance is postulated to lie involvement of the rostra1 portion of the superior colliculi. In juxtaposition to the site where the aqueduct of Sylvius leaves the third ventricle lie the nucleus o f llarkshevich and the interstitial nucleus of Cajal. These nuclei, which are TABLEI Summary oj C k n i ~ a tSvmptoms Symptom Headache . . Visual disturbances' Diplopia ., Blurred vision . . Lethargy, somnolence Nausea, vomiting Polynria, polydipsia Unsteadiness .. Epilepsy . . .. Infantilism ..
Number of cases
: :. ,
.. .. .. ,, ,
. .. ,
.
IS 13 S
n
,
4 2 2 I
directly connected with the oculomotor nuclei via the medial longitudinal fasciculus, coordinate not o n l y the ocular muscles for vertical movcments, Init also the muscles of the upper cyelitl (Szentagothai, 1950; Nittner and Petrovici, 1974). A peculiar type of bilateral ptosis niay be produced if these nuclei are involved, antl this was ohserved in five of the nine p;itients with Parinaud's syndrome. The ptosis, unlike that i n oculomotor palsy, is only partial. Its appearance is 4niilar to that due to muscle weakness.
the "Peter Pan" type of infantilism. Although precocious puberty is a well-documented manifestation of pinealomas (Kitay, 1954), no such cases were found in this series. The duration of symptoms ranged from a month to three years, with a mean of 8.3 months. There was no correlation between the duration of symptoms and the severity of neurological deficits, or with the size of the tumour as assessed radiologically. Radiographic Findings.-These are listed in Table 3. Radiological evidence of raised intracranial pressure was present in the majority of cases (except in the three patients with ectopic pinealoma) . Obstructive hydrocephalus was invariably present. This has an important bearing on the subsequent management of the patient. Four patients (three males, one female) showed abnormal calcification in the pineal region indicative of a tumour. The results obtained with 99Tc scanning of the brain were disappointing (four abnormal scans TABLE 3
Summary of RadiograPhic Findings Evidence
Number of cases
Tumour mass in posterior third ventricle , . Obstructive hydrocephalus . . .. ,, Erosion of posterior clinoids ,. .. Suture diastasis .' Abnormal pineal caldi'fication ' ' **Tcscan (done only in seven casesj
:
.. .. ,. ' '
::
zn
In
9 6 4 4 Abnormal
Of the three patients with ectopic pinealoma, two were Qhownto have a mass in the suprasellar region, and one a mass in the anterior floor of the third ventricle.
The incidence of hypothalamic-hypophyseal tlisturhance in this series is higher than is generally reported in the literature (Poppen antl Marino. 1968; Bradfield and Perez, 1973 ; l>e Girolatni and Schmidek, 1973). Somnolence and diabetes insipidus were the predominant manifestations in this group. One patient, a young man aged 19 years, presented with
out of seven). The number, however, is too small for any conclusion to be drawn. Ventriculography with either air or Myodil was carried out in all cases and proved to be the most valuable investigation. This was also the experience of Greitz (1972). Vertebral angiography was carried out in order to delineate the posterior limits of the tumour in those cases in which a stereotaxic lQsAu implant was contemplated. Carotid angiography was of no value, apart from demonstrating the presence of hydrocephalus. Ectopic pinealomas usually occur in the suprasellar region, resulting in hypothalamic and chiasmal compression. Their radiological appearance in a pneunioencephalogram is no different from that of any other space-occupying suprasellar mass. Their true nature was revealed after operative interference.
76
AUST N.Z. J.
TABLE 2 Summary of Physacal Fandangr Sign Papillodema , . .. .. Parinaud's syndrome . . .. Nystagmus .. .. .. Ataxia . , Paralysis of sixid cra& ner;k Pyramidal tract signs . . Paralysis of third cranial nerik Hypopituitarism .. ..
Number of cases 17
I
S U R C , VOL46-No.
I, FEBRUARY, 1976
PI N E:A 1. '1' IT M OURS
so
TREATMENT A N D RESULTS The treatment given is summarized in Table 4. T n general. a non-aggresive attitude was adopted except in the three patients with ectopic pinealomas, where chiasmal compression was present. Some form of cerebrospinal fluid shunting procedure in the presence of ohstructive hydrocephalus is mandatory. Yentriculo-atrial shunt with a Spitz-Holter valve was the procedure most frequently TABLE 4 Summary of Treatment Treat men t
Number of cases
Ventriculo-atrial shunt+external irradiation .. Ventriculo-atrial shunt fstereotaxic lUsAuimplant Torktldsen's operation +stereotaxic 'enAu implant Torkildsen's operation+external irradiation ., Third ventririiloStomy+ezterrial irradiation ,. External irradiation alone . , ,. ., ..
14 2 I I I
I
The three patirnts with ectopic pinealoma underwent direct surgery, two of them receiving postoperative external Irradiation.
employed i n this series. In all patients with ohstructive hydrocephalus, 4ymptoms of raised intracranial pressure were effectively relieved after cerehrospinal fluid diversion. A course of eutertial irradiation, the dose ranging from 4000 to 5000 radq, was given to those patients thought unsuitable for a stereotaxic lgsAu implant. The spinal axis was not included in the field of irradiation without histological confirniatioti of the diagnosis. Stereotaxic '98Au implnutation was deemed appropriate on]) if the diameter of the tumour as shown 11j ventriculography and vertebral angiography wa5 less than four centimetres and there was 110 e\ itlencc. of tumour infiltration into adjacent structures (Hankinson, 1965, 1975). The aim of interstitial irr:idiation is to cause tumour desttuction with a view to opening up cerelmxpitial fluid pathways. The total dose deliveretl to the tuniour with 1 9 8 A ~according ~, to the size of the turnour, ranges from 7,000 to 1 0 , o o o rads The advantage of interstitial irt adiation as compared with external irradiation has been well cited by Hankinson (1965). Three patients in the present series received a stereotaxic l g 8 h implant. Pathology-In only seven of these 23 patients were the tutnours verified histologically as such Histological examination in life was available for the three patients with ectopic pinealoma : two were diagnosed as teratonias and one as a germinoma. HistoAUST. N.Z. T. SUKG., VOL.46-No. F
I,
FEBRUARY, 1976
logical features in the other four cases were derived from post-mortem findings. There were two teratomas, one germinoma and one pineocytoma. The germinoma also showed subarachnoid metastases in the posterior fossa as well as along the whole of the ipinal axis. Results.-These are summarized in Table 5. There was one postoperative death. The patient was an eight-year-old girl with an ectopic pinealoma, who died of uncontrollable diabetes insipidus one week after exploratory craniotomy. Of the 17 patients receiving external irradiation following a shunt procedure, eight are living and well, with no disabling neurological deficits. The shortest follow-up period is six months and the longest 15 years, with a mean of 4'2 years. The nine patients who died presented with tumour recurrence or subarachnoid metastases or both, six months to three and a half years after initial treatment. The average period of survival was 2.2 years. One feature of note in this group is that despite rapid recurrence the patients were free of any disabling neurological deficit until the terminal stage. The quality of survival prior to the terminal illness was considered good. Of the three patients who received a stereotaxic lgsAu implant, the first is still alive and well 1 1 3 years after treatment and has given birth t o two normal babies during this period. The second died after three years of tumour recurrence, and the third died suddenly a TABLE 5 Summary of Results
---_ Result
..
Dead Operative Tumour recurkence Living . . ..
Number of cases
..
.. ,. ..
I3 I
1 2 (From 6 months to 10 (Follow-up period 6
3h years) months to 15 years)
month after surgery. Post-mortem examination revealed massive hxmorrhage in the tumour cavity. Tw o of the three patients with ectopic pinealoma are living, at one and ten years respectively, without undue complications. The symptom of diabetes insipidus continued unabated following external irradiation, and all four patients in this category required Pitressin. Three of these four patients also required anterior pituitary hormone replacement. Six of the nine patients with Parinaud's
77
so
s ~ n d r o m e liad resolution of their eye signs following treatment. Whether this was related to the relief of increased intracranial presswe or to tiimour destructioii or to both is speculative. Tuniours arising in the pineal region are of rare occurrence, averaging one case a year ( D e Girolanii and Schmidek, 1973). Sufficient experience in their treatment is difficult to obtain, and an authoritative opinion is seldom eupre\setl. Initial experience mainly concerns direct surgical intervention. Dandy ( 1921) reportctl a mortality of 20%. I n 1949,Horrax stated that not more than seven patients who survived total extirpation of the tumour had been reported in the literature. Cummins c t olii (1960) had three operative deaths in five cases. Rant1 antl Lemmen’s (1953) figure of 70% mortality is even more disheartening. Ue (;irolami and Schmidek ( 1973), reviewing the case records from Massachusetts General Hospital, Boston, stated that the mortality rate of total and subtotal removal was 6070, and that that of open biopsy was 337%. Even in such experienced hands, formidable mortality was unavoidable Accordingly, a more conservative attitude has beeii adopted. Horrax (1949, 1950) was one of the first to report favourable results ohtainetl from radiation therapy combined with a decompressive procedure. Kahn (rgC,r) had 12 patients out of 18 surviving for four to rz years following this combination of trEatment. Siiice then, reports in the literature of the use of external irradiation combined with some form of decompreisive procedure in the treatnient of these tuniours in general indicate stirviva1 rates superior to those following tlirect surgical intervention (Matsuoko and Uozumi, 1966 : 1)avidoff. 1967 : Poppen and hl;iriiio. 1968; Rradfieltl antl Perez, 1972, T’:l-Mahtli r t dii, 1972 ; De Girolanii and Schmitlelc. 197.3) However, improved results in total tnnionr extirpation cannot be left ,~nachnowletlgetl (Kunicke, 1960 ; Suzuki and 1wal)uchi, I965 ; Jamieson, 1971). I n the present series, ten patients out of 23 survivrtl for six months to 15 years, an additional piece of evidence in favour of conservat ive treatment. Detailed morbidity assessment in tcrnis of permanent disabling neurological
tleficit and duration of convalescence following direct surgical intervention is unfortunately not available in most of the series reported. A considerable number of Kunicke’s (1960) and Suzuki and Iwabuchi’s (1965) patients liad a long period of hospital stay, and almost half of their patients had either transient or permanent neurological deficits following surgery. The experience of radiation therapy in the present series shows that morbidity is minimal. Ventriculo-atrial shunt is a relatively simple and minor procedure, with little mortality or morbidity. I t is very effective in relieving symptoms in cases of obstructive hydrocephalus. Poppen and Marino in 1968 concluded that “the conservative treatment of ventriculoatrial shunt followed by irradiation has giveii the longest survival time with the fewest residual neurological deficits”. The low morbidity, allowing useful survival following conservative treatment i n the present series, again speaks in favour of a non-aggressive attitude. I t may be argued that the type of tumour should always be verified histologically before irradiation is carried out. The high mortality figures resulting from surgical intervention make this procedure unjustified. Furthermore, De Girolanii and Schmidek (1973) showed that more than 70% of the tumours in the posterior third ventricle are highly radiosensitive. Even with blind application of radiation therapy, the majority of these should respond. Surgical exploration should only be seriously considered in those cases resistant to radiation therapy. Hankinson in 1961 reported his first experience of interstitial irradiation by means of stereotaxic implantation of l Q 8 A ~inside i the tumour in 3 case of pinealoma. Further experience in this method of treatment, using either radio-isotope or cryogenic lesions, has since been reported (Mundinger and Riechert, 1962 ; Hankinson, 1965 ; Conway, 1973 ; Mundinger and Hoefer, 1974). I n general, the results obtained have been favourable. The number of cases involved, however, is too small to allow any conclusion to be drawn. The three stereotaxic lg8Ait implants in the present series were performed by Hankinson following his initial experience. One of these three patients is still living 11: years after treatment with no signs of tumour recurrence. The danger
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of operative hremorrhage resulting from introduction of the probe into the tumour cavity is real, although no such experience was encountered in these three cases. Delayed spontaneous hzniorrhage resulting from tumour necrosis following interstitial irradiation is a potential risk. This was probably the cause of death of one of the patients in this series. Certainly, radio-isotope implantation or cryogenic lesions created hy stereotaxis have a place in the treatment of pineal tumours.
CONCLUSION The following points need to be emphasized. I. Radiation therapy combined with some form of shunting procedure in the presence of ohstructive hydrocephalus should be the first choice in the treatment of pineal tumours. The use of ventriculo-atrial shunt is recommended. 2 . Tnterstitial irradiation should be considered if the tumour diameter as assessed by radiology is less than four centimetres and if there is no evidence of tumour infiltration into adjacent structures. 3. Direct surgical extirpation of the tumour should he reserved for cases resistant to irradiation. 4. The mor1)idity following conservative treattnent is low, and survival is useful. A C K NOWLEDCEMENT
The author would like to express his thanks to Professor J. Hankinson and Mr L. P. Lassman for permission to review their patients and for their criticism in the preparation of this paper.
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