Pineal region tumors: Analysis of treatment results

Inr I Radrorrm Oncology Bwl Phw Vol Pnntcd I” Ihe U.S.A. All n&s mrved

IO. pp 991-997

0 Original Contribution PINEAL

REGION

TUMORS:

ANALYSIS

OF TREATMENT

RESULTS

BEATRIZ E. AMENDOLA, M.D.,* KENNETH MCCLATCHEY, M.D.-f AND MARCO A. AMENDOLA, University

M.D.+

of Michigan Medical School, Box 056. Room X3003, Main Hospital. 405 E. Ann St.. Ann Arbor. MI 48109

This article represents a review of 32 patients with pineal region tumors seen and treated at the University of Michigan Medical Center from January 1950 to December 1980. All patients presented with manifestations of increased intracranial pressure: limitation of the upward gaze (Parinaud’s syndrome), hydrocephalus and a mass in the posterior aspect of the third ventricle. The tumor was demonstrated by pneumoencephalography, ventriculography, angiography or CT scans. Ventricular decompression was performed in all patients. Eighteen of the 32 patients (56%) had a histological diagnosis of germinoma, one patient had a diagnosis of hamartoma; no histological diagnosis was obtained in the remainder of the patients. Twenty-seven patients received post-operative irradiation. Irradiation dosage ranged between 30 and 55 Gy. The overall 10 year survival for evaluable patients was 16/24 (67%). The low incidence of spinal cord metastasis in these patients does not justify routine use of spinal irradiation. Pineal tumors, Radiation

therapy,

Germinoma.

seen and treated at the University

of Michigan Medical Center from January 1950 to December 1980 was conducted (information obtained through tumor registry). Fourteen females and 19 males were included in the study. Ages ranged from 9 months to 48 years with an average age of 19. The male to female ratio was 1.4 to 1. The most common clinical signs and symptoms were headaches in 27 of 32 (84%) patients, and paralysis of the upward gaze, Parinaud’s syndrome, in 24 of 32 patients (75%), (Table 1). The diagnosis was based on clinical and radiographic findings which included skull radiographs, conventional tomography, pneumoencephalograms, ventriculograms, arteriograms and, more recently, computed tomography (CT) of the head. Hydrocephalus and a mass in the posterior aspect of the third ventricle were the most common radiographic findings in 20 of 32 patients (63%) (Table 2). All patients underwent ventricular shunting. The most commonly used shunt was the intracranial type (ventricular cistemostomy or Torkildsen shunt); others had external shunts with valve placement (Holter type). Twenty-three out of 32 patients (72%) underwent craniotomy and subtotal resection. Histological diagnosis was obtained in 19 of 32 patients (60%). Twenty-nine patients received post-operative irradiation. This treatment was delivered mainly by Cobalt 60 megavoltage irradiation, except for eight patients, five of

INTRODUCTION Neoplasms arising in the region of the pineal body, around the area of the third ventricle and in the suprasellar region represent less than 1% of all intracranial tumors.” Regardless of their histologic type, they produce a similar clinical picture characterized by increased intracranial pressure, Parinaud’s syndrome and occasionally precocious or delayed puberty. They encroach upon the posterior aspect ofthe third ventricle and aqueduct of Sylvius producing hydrocephalus. Direct compression of the quadrigeminal plate interrupts fibers coursing from the cortex to the superior colliculi and subsequently the oculomotor nuclei, causing bilateral paralysis of the upward gaze and mild ptosis (Parinaud’s syndrome). Other less common findings related to the compression of the dorsal tectum or its projection include ataxia, pupillary dilatation, nystagmus and hearing loss.’ Surgical approaches to this area, even with improved techniques, have a small but definite morbidity. 2.3 This report is a review of the University of Michigan Medical Center experience in the treatment of 32 patients with pineal region tumors. METHODS

AND MATERIALS

A retrospective analysis of 32 medical records of patients diagnosed as having tumors of the pineal region

Reprint requests to: B. E. Amendola, M.D. Accepted for publication 2 I March 1984.

* Dept. of Radiation Therapy. t Dept. of Pathology. $ Dept. of Radiology. 991

992

Radiation Oncology ??Biology 0 Physics

Table

I.

Presenting signs and symptoms in 32 patients with pineal region tumors

Symptoms

Number of patients

Headache Paralysis of upward gaze Visual problems, blurring, diplopia Optic atrophy, papilledema Nausea and vomiting Diabetes insipidus Obesity Lethargy Confusion Growth retardation Personality disorder III cranial nerve palsy Anorexia nervosa

Table 2. Radiological Findines

24

7s

15

47

15 15 14

47 47 44 31 31 25 19 I9

10 10 8 6 6 3

findings

Patients were grouped as I, II or III according to the treatment used. Group I (Table 3) consisted of 12 patients with tumors of the pineal region without histologicallyproven diagnosis. 6 of 12 patients had craniotomy performed for decompression and to explore the region without biopsy being obtained. All of these patients received post-operative irradiation to local fields using lateral opposed ports; field sizes ranged from 6 X 8 cm to 12 X 12 cm. Doses ranged from 3000 to 5000 cGy with an average of 4600 cGy. Two patients died of intercurrent disease 20 to 26 years after diagnosis, the remainder are alive and well at least 10 years after diagnosis. Two of 12 patients ( 17%) had some psychological disorder. One patient with positive cerebral spinal fluid for malignancy (CSF) who only received radiation to a local field committed suicide 22 years after treatment; autopsy failed to show tumor in the pineal region. Group II (Table 4) includes 15 patients treated in the same manner as Group I: however, surgical biopsy of the tumor was included in the procedure. The pathological classification was according to Rubinstein (Table 5)’ ’All 15 patients were diagnosed as germinoma; all tumors exhibited large pleomorphic cells with vesicular nuclei in a loose neurofibrillary stroma (Figure 1). Nine patients received radiation therapy to local fields ranging in size from 6 X 6 to 10 X 12 cm using lateral opposed ports. Cobalt 60 megavoltage equipment was used, except for two patients who received treatment by orthovoltage

in pineal region tumors of oatients

Percent

20

63

20 I2 IO 8

63 38 32 25

whom received orthovoltage and three who were treated with Cesium therapy. Local fields, 7 X 7 cm to 12 X 12 cm, were used except for four patients who received whole

Table 3. Pineal tumors

treated

with radiation

therapy

without

Radiation Age/Sex I. 2. 3. 4. 5.

Year of diagnosis

48 F 30 F l2M 44 F I6 M

1952 1959 1971 1957 1951

6. 26 M 7. II F 8. 34 F

1968 I960 1963

9. 27 M

1952

IO. 34 F II. II M

1959 1950

I2

1961

I7 M

Surgical

procedure

Shunt/Torkildsen Shunt/Torkildsen Shunt/Halter Shunt/Halter Shunt/Suboccipital craniotomy Shunt/Halter Shunt/Frontal craniotomy Post. fossa exploration Shunt/Halter ShuntfTorkildsen ShuntJCraniotomy Frontal craniotomy/shunt exploration post RT Craniotomy (+CSF)

7

RESULTS

9 3

1

Number

Hydrocephalus Posterior III ventricle tumor mass Suprasellar mass Calcification Bony erosion

84

IO. Number

brain irradiation Doses ranged from 3000 to 5600 cGy. with an average of 4400 cGy. All fields were treated daily, five days per week with fractions of 200 cGy.

Percent

27

July 1984. Volume

histological

diagnosis

(Group

I)

therapy

Field

200 KV cs 50 Co 60 cs 50 200 KV

12 x 12 7X-l 9x9 6X8 II x I2

3000 4000 5000 4000 3000

NED.dead/CHF NED NED NED NED

20 23 13 25 30

Co 60 Co 60 Co 60

IO x 10 7x7 8X8

5000 4200 5000

NED NED (retarded) NED

I5 22 I9

3000

NED. behavior disorder NED NED, behavior disorder * NED. Suicidet

30

200 KV Co 60 cs 50 Co 60

* Dead of intercurrent disease. t Autopsy showed atrophy and Hypophysis. NED = No evidence of recurrent disease: CHF = Congestive

7x7

8X8 IO x 10 8X8

heart failure:

Dose/cGy

5000 3ooo Palliative 5140

+CSF

= Positive

Status

Follow-up (years)

Machine

cerebral

spinal fluid.

22 26 I2

YY3

Pmeal region tumors @ B. E. AMENDO~A CI 01

Table 4. Pineal

region tumors with tissue diagnosis* treated with radiation therapy (Group 111) Radiation

Year of diagnosis

Age/sex

Surgical procedure

8.

17

M

1980

9.t

13

F

1952

Torkildsen/suboccipitaI craniotomy (extensive. involving hypothalamus) Craniotomy/shunt subtotal resection Craniotomy and VP/ shunt (subtotal resection) Torkildsen shunt, then recurrence and occipital craniotomy (subtotal removal Right frontal craniotomy and shunt Craniotomy. subtotal removal, CSF. hypothalamic involvement. Shunt/Halter, frontal craniotomy, subtotal removal Subtotal/shunt, craniotomy to optic tract, craniotomy Craniotomy

IO.

20

F

1980

Craniotomy/shunt

I.

IO

M

1958

3.

I9

M

1966

3.

II

M

I980

4.

15

F

1959

5.t

II

M

1963

6.t

II

M

1961

7.

15

F

1969

Machine

Field

Co 60

7X1

Co 60

therapy

IO x 10

Status

4600

DcD. local failure

Z years

5000

autopsy = necrosis and residual tumor NED

I5 years

NED

3.5 years Alive

3000

Blind, retarded

24 year5 Alive

7x7

4200

10 years

Co 60

8X8

4000

Dwarf, DcD. blind brain metastasis Retarded, recurrent brain mets. DcD

Co 60

6X 6

5000

DcD. autopsy

I .5 years

Whole Brain/ Spine

5000/4000

= recurrent brain mets NED

10.5 x I I

3000

Co 60

Whole Brain

5600 + CTX

Co 60

Whole Brain/ Spine 6X8

4000+1000

Co 60

Whole braIn/ spine

5500/4000

Co 60

7x1

Co 60

Co 60

200 KV

9 mos F

1980

Craniotomy/shunt

(+CSF) 12.t 13.t

14.t

15.

9 II

13 29

F M

F M

1955 1958 1965

Shunt subtotal removal

Co 60 Co 60 Co 60

1966

Frontal craniotomy subtotal resection Recurrent local

1963

R frontal craniotomy

Co 60

1956

subtotal excision Shunt/Torkildsen/ biopsy

Co 60

Co 60

7X7

3x4 10 x 12 8X8 IO x IO

I7 years

3.5 years Alive

DcD. autopsy = brain necrosis and residual germinoma DcD. cord compression DcD. spine/brain

9 months

1200 4000 3700

DcD. autopsy = local failure NED

5 years

4000

6 years

4500

No further follow-up Obese, NED

2400

Died during RT

(+CSF) 11.

Follow-up

Dose/cGY

6 months I year

20 years -

* Histology showed Germinoma in all cases. t Patients from previous series (Simpson et al.). DcD = dead with disease; NED = no evidence of disease; Mets = metastasis; +CSF = positive cerebral spinal fluid.

equipment. In 4 patients the whole brain was treated; the entire neuroaxis was treated in 3 patients. Two patients had malignant cells in the CSF; one of them received intrathecal chemotherapy instead of spinal radiation therapy. Eleven of 15 patients at 3 years (65%) are free of disease. The 5 and 10 year survival for evaluable patients is 6 out of 13 (46%) and 5 out of 13, respectively. However, 2 patients in this group developed recurrence in the brain and died 17 and 10 years after diagnosis. Group III represents 5 patients treated with surgery

alone (Table 6). Radiation therapy was not used in one patient with the diagnosis of hematoma and in the remainder of the patients, 3 died of immediate post-surgical complications. One died 7 months after diagnosis of progressive disease and he was never referred to radiation therapy. There were 8 failures in the Group II; most failures occurred in the brain. Three local failures in the treated area at 1 and 2 years after treatment, and 5 marginal failures occurred in the brain. This may be due to geo-

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Radiation Oncology 0 Biology 0 Physics

July 1984. Volume IO. Number 7

Table 5. Pineal tumors I. Tumors of germ cell origin A. Germinoma: Pinealoma, atypical pineal teratoma. suprasellar germinoma, ectopic pinealoma B. Teratoma C. Choriocarcinoma D. Embryonal carcinoma II. Tumors of pineal parenchyman cell origin A. Pineocytoma B. Pineoblastoma III. Other cell origin A. Glioma B. Ganglioneuroma and ganglioglioma

graphical

miss. In 2 patients

with brain metastasis,

spinal

cord seeding was also observed (one of the patients developed cord compression 6 months after whole brain irradiation of 5600 cGy and intrathecal chemotherapy). Few failures, less than 8% occurred in the spinal cord. The overall 5 year survival for the entire group who received post-operative radiation therapy is 17 out of 24 evaluable patients (75%). DISCUSSION Because of the poor results obtained from surgery of the pineal region tumors through the years, radiation therapy has become the treatment of choice.2.8.‘3 Several

years, even decades, are needed to accumulate an adequate number of cases, because of the low incidence of this tumor. During this period surgical techniques in the pineal region have definitely changed and improved. The three groups of patients studied demonstrate that for patients with clinical and radiographic evidence of disease, a ventricular shunt followed by radiation therapy appears to be the treatment of choice. In Group I, 12 out of 12 patients did well when treated to a local field with a dose in the range of 3000 to 5000 cGy, and survived up to 25 years. Two of these patients who were thought to be inoperable underwent partial excision and did well up to 26 and 12 years, the former dying of intercurrent disease and the latter of suicide (no tumor found on autopsy). The tumors in Group II appear to be more extensive and locally aggressive, deserving a ,more strenuous surgical approach. Subtotal removal was done in all patients; 15 of 15 were germinoma. There were 8 failures in Group II. This occurred in spite of more aggressive radiation therapy in 4 of these patients, including whole Table 6. Pineal region tumors

Procedure

Age/sex 8 I3 24 17 20

F F M M M

Craniotomy/subtotal Craniotomy/subtotal Shunt Craniotomy Shunt

resection resection

multiple

shunts

w. . h

.

r.=.

*-

.i

Fig. I. High power view of germinoma with pleomorphic vesicular nuclei in an edematous neurofibrillary stroma (X280).

brain irradiation (3 patients) and whole brain and spine ( 1 patient). Two of them died of local/regional and spinal cord metastasis; the other 2 patients are doing well at this time. In Group III. 4 out of 5 patients died within one to seven months of diagnosis. There is only one patient diagnosed of hamartoma still alive. but at this time is unable to function by herself. Most patients recurred in the brain at the margin of the field of radiation therapy. which might be a result of geographical misses. This could have been avoided by using “generous” fields for the tumor including the ventricular system. DeGirolami and Schmidek found that in more than 60% of patients with pineal region tumors, the tumors spread extensively and diffusely beyond the primary site.’ Six out of I7 (35%) patients diagnosed as germinoma failed in the local field and in the surrounding brain. Four of these patients

were treated

with very small

fields (7

X 7 cm), 2 received whole brain irradiation in adequate doses. (Example: 4000 cGy for a 9 month-old baby and 5600 cGy for a 20 year-old female.) Only two patients who failed in the brain also failed in the spine. One is a 20 year-old white female who presented 6 months after whole brain irradiation and intrathecal chemotherapy with a diagnosis of spinal cord compression. The other is a 9 month-old baby that recurred in the brain and spine after irradiation (I year). There was only an 8% incidence of spinal cord metastasis in the entire group studied. treated

with surgery alone Histological diagnosis

Status

Follow-up

Hamartoma Germinoma No tissue Germinoma No tissue

Retarded DcD DcD DcD DcD

Alive at I5 years 2 months 7 months I month I month

Pineal region tumors 0 B. E. AMENDOLA

ef (I/

995

Fig. 2A. Post contrast CT scan in a 1I year-old white male with pineal germinoma. Note markedly enhanced pineal tumor and associated hydrocephalus. 2B. Non-contrast CT scan in the same patient one week later following subtotal surgical resection and ventricular shunt decompression. Note the hyperdense lesion indicating residual tumor. 2C. Follow-up CT scan 2% years later; status post craniospinal irradiation. The patient shows no evidence of disease, clinically or radiographically.

The low incidence of spinal seeding in our case material does not indicate the need for routine spinal irradiation. Salazar et al. I3 demonstrated similar findings, but Sung et al. reported a high incidence of spinal cord seeding

(37% of the suprasellar germinomas and 10%of the midline pineal tumors).” Sung et al. recommend irradiation of the entire neural axis for locally extensive tumors, simultaneous pineal and hypothalamic lesions and all biopsy-proven germinomas.” Eight out of 14 histologically proven germinomas (57%) metastasized in the neuroaxis. In addition, Bradfield and Perez found 25% of the patients with pineal tumors had spinal metastases.’ We have found late recurrences up to 10 and 17 years after diagnosis. The capacity for a long chronic course is another feature of the pineal region neoplasm.” Controversy remains regarding the field size and dose to be used in the treatment of pineal tumors. Salazar et al. demonstrated the patterns of spread of the neoplasm of the pineal region in a recent series.13 They reported a high incidence (50%) of contigual seeding and spread along the third ventricle and into the entire ventricular system. I3 Doses in the rang e of 5000-5500 cGy are recommended by Sung et al. ” They found 6 out of 6 patients failed locally when doses of 4000 cGy or lower were used (between 4-7 years).”

996

Radiation Oncology 0 Biology ??Physics

We agreed with others’3.‘8,‘Ythat doses of 4000 to 4500 cGy are sufficient to control these tumors if the field size is large enough to encompass the areas at risk (ventricular system). Depending on the appearance (clinical and radiographic) and aggressiveness of the tumor, the radiotherapist must vary the technique, dose, and treatment field. One of the most important developments regarding the diagnosis and treatment of pineal tumors is the advent of computed tomography (CT). This diagnostic tool has high accuracy for detection and characterization of the tumor as well as value in the histological prediction.*’ CT is also effective for evaluation of response to therapy. Germinomas typically appear as a well defined mass of slightly higher density than the surrounding normal brain on plain CT scans. On follow-up intravenous contrast injection, there is marked uniform enhancement of the lesion (Figure 2A, B, C).5.20 Partial brain irradiation (Figure 3) encompassing the entire ventricular system appears sufficient for small size tumors without proven seeding of the CNS. For more extensive tumors and evidence of CNS seeding by examination of the CSF (centrifuged), an extended whole brain and entire spinal axis appears indicated (Figure 4). Mincer et al. reported 88% survival (7/8 patients) in patients treated with small local fields.* It is clear that the patients who underwent only minimal surgical procedures did significantly better. The possibility of increased incidence of meningeal seeding after surgical manipu-

Fig. 3. Generous local tield. encompassmg system. lateral opposed ports.

the entire ventricular

July 1984. Volume IO. Numk

7

PINEAL TUMORS CSF+ I spare

C3 I

Fig. 4. Whole brain and spinal axis ports. “Moving nique about the level of cervical spine C-3.

gap” tech-

lation should be considered and has been expressed by others.” Rao et al., in their review of 18 patients with pineal tumors, did not demonstrate spinal metastasis.” The majority of their patients had received irradiation to large fields which most likely prevented spinal seeding. Another reason for this result may be that only 2 out of 18 patients had surgical manipulation. The question of detrimental effect from biopsy of this tumor has been raised by others. Wara et al.. in a review of 1 18 patients, demonstrated that 14 patients with biopsy-proven germinoma had spinal metastases versus 1.7% in the non-biopsy group.” This is also consistent with the findings of Jenkin et 01. and Rao et ~1.~~‘~ In general, spinal irradiation is not recommended ,4~8~9~“.‘3.‘8~‘ in 9view of the low rate of meningeal seeding. Elective spinal irradiation should depend on CSF findings. Experience with microsurgical techniques has improved the results of surgery of the pineal region.16 The surgical dissection of tumors of the pineal region has considerable risk because of the deep location of these tumors and the need to preserve important neural and vascular structures around the tumor. Stein reported that with his technique. only 1 of 21 patients died from complications; this represents a significant improvement.16 Sano and Matsutani have demonstrated a 10 year survival of 69.3% for patients with pineal germinomas treated with resection by infratentorial, supracerebellar approach and post-operative irradiation.‘4 They have also found a better survival rate for childhood pineal germinoma, which along with the work of Jenkin ef ul. showed findings of 5 year survival of 81% in patients younger than 25, and 37% in older patients.6 They have also found a low incidence of spinal seeding, 5%. demonstrating that sur-

Plneal region tumors@

did not increase spinal metastasis.‘4 The large number of patients 20/33 (63%) under 18 years of age in our series is not unusual. Salazar. in a review of the literature,” revealed that over 40?& of all pineal region neoplasms occur in children under the age of 12. This was found to be a prognostic factor and consistent with our review. In the future. with the advances in surgical techniques, it is likely that more biopsies of these lesions will be obtained; however. the ultimate treatment decision should be made on the basis of the clinical and CT findings and in most cases histological proof may not be needed.20

B. E. AMENWLA

997

PI a/

CONCLUSION

gery

We recommend that patients with tumors of the pineal and ectopic location be treated by ventricular decompression in the presence of hydrocephalus followed by wide partial brain fields to a total of 4500 cGy in four and a half weeks. If the tumor is extensive and CSF is positive for malignant cells, the entire CNS should be treated with 4000 cGy to the whole brain and a boost of 1000 cGy to the tumor bed and 3000 cGy to the spine over 3-4 weeks, using the moving gap technique.

REFERENCES I.

Bradfield. J.S.. Perez. C.A.: Pineal tumors and ectopic pinealomas: Analysis of treatment and failures. Radiolog?

103: 399-406. 1972. 2. Cummins. F.M.. Taveras. J.M., Schlesinger. E.B.: Treatment

of ghomas of the third ventricle and pinealomas with special reference to the value of radiotherapy. Neurology 10: 103 I 1036. 1960. 3. De Girolami, V.. Schmidek. H.: Clinicopathological study of 53 tumors of the pineal region. J. Neurosurg. 39: 455462. 1973. 4. El-Mahdi. A.M., Philips. E.. Lott, S.: The role of radiation therapy in pinealoma. Radmlug~~ 103: 407-412. 1972. 5 Futrell, N.A., Osbom. A.G., Cheson, B.D.: Pineal region tumors: computed tomographic-pathologic spectrum. Am. J. Radial. 137: 951-956.

1981.

6. Jenkin. R.D.T.. Simpsom. J.K.W., Keen, W.C.: Pineal and suprasellar germinomas:

Results of radiation treatment. J. 1978. 7. Milhorat. T.H.: Pediatric neurosurgery. Contemporary Neurology Series. Philadelphia. F. A. Davis Co. 1978, pp. 21 l-283. 8. Mincer, F.. Meltzer. J., Botstein. C.: Pinealoma: A report of twelve irradiated cases. Caruer 37: 27 13-27 18. 1976. 9. Onoyama, Y., Ono. K.. Nakajima, T., Hiraoka. M., Abe. M.: Radiation therapy of pineal tumors. Radiology 1130: Neurosurg. 48: 99-107,

757-760.

1979.

10. Rao. Y.T,R.. Medini. E., Haselow. R., Jones, R.T., Levitt, S.H.: Pineal and ectopic pineal tumors: The role of radiation therapy. Cancer 48: 708-7 13, I98 I 1I. Rubinstein, L.J.: Tumors of the central nervous system. AI/as qf Tumor Pathology, Series 2. FASC 6. Washington, D.C.. AFIP. 1972.

12. Salazar. O.M.: Moments of Deckon in Primary Brain Tumors. Rubin. P. and Preston, W. (Eds.) American College of Radiology. 1977. pp. I7 I - 184. 13. Salazar. O.M.. Castro-Vita, H.. Bakos. R.S., Feldstein, M.L.. Keller, B., Rubin, P.: Radiation therapy for tumors of the pineal region. Int. J. Radial. Oncol. Biol Phys. 5: 49 l-499. 1979. 14. Sano, K.. Matsutani, M.: Pinealoma (germinoma), treated by direct surgery and postoperative irradiation: A long term follow up. Child’s Brain 8: 8 I-97, I98 I 15. Simpson, L.R.. Lampe, I.. Abell, M.R.: Suprasellar germinomas. Cancer 22: 533-544. 1968. 16. Stein, M.B.: Supracerebellar-infratentorial approach to pineal tumors. Surg. Neural. 2: 331-337. 1979. 17. Sung, D.. Harisiadis, L., Chang, C.H.: Midline pineal tumors and suprasellar germinomas: Highly curable by irradiation. Radiology 128: 745-7 15, 1978. 18. Wara, W.M., Fellows, C.F.. Sheline, G.E., Wilson, C.B., Townsend, J.J.: Radiation therapy for pineal tumors and suprasellar germinomas. Radiolog?, 124: 22 I-223, 1977. 19. Wara, WM., Jenkin, R.D.T., Evans. A., Ertel, 1.. Hittle. R., Ortega, J., Wilson, C., Hammond, D.: Tumors of the pineal and suprasellar region: Children’s Cancer Study Group treatment results l960- 1975. Cancer 43: 698-70 I. 1979. 20. Zimmerman, R.A., Bilaniuk. L.. Wood, J.H.. Bruce, D.A., Schut. L.: Computed tomography of pineal, parapineal. and histologically related tumors. Radiology 137: 669-677, 1980.

21. Zulch, K.J.: Brain Tumors: Their Biology and Pathology. New York, Springer Verlag. 1957, pp. 189-192.