Pineal tumours: Experience of the French National Register and the Lyon School, results and considerations.

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Neurochirurgie xxx (2014) xxx–xxx

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Report 2013: Tumors of the pineal region

Pineal tumours: Experience of the French National Register and the Lyon School, results and considerations Tumeurs pinéales : expérience du Registre français des tumeurs pinéales et de l’École lyonnaise. Résultats et commentaires C. Mottolese ∗ , P.A. Beuriat , A. Szathmari Neurological and Neurosurgical Hospital « P. Wertheimer », 59, boulevard Pinel, 69677 Bron, France

a r t i c l e

i n f o

Article history: Received 6 June 2013 Received in revised form 21 November 2013 Accepted 18 February 2014 Available online xxx Keywords: Pineal tumours Pineocytomas Pineoblastomas Germ cell tumours Papillary tumours French National Register of pineal tumours

a b s t r a c t The experience of the French National Register of pineal tumours and the experience of the Lyon School are reported. Data were collected from 26 French neurosurgical centres from 1989 in Lyons and in other centres from 1997. For radiological and pathological studies, 517 cases were considered while only 452 with sufficient clinical and follow-up data were retained for further analysis. These data highlight the importance of the initial diagnosis for a therapeutic strategy that can be completely different in cases of pineal or germ cell tumours. As regards the latter, chemotherapy and radiotherapy can avoid surgery. Pineocytomas are benign lesions and their complete removal guarantees the cure. Pineal parenchymal tumours with intermediate differentiation (PTT-ID) require complete removal and complementary treatment in cases of histological abnormalities with approximately 66% of patients who remain alive. Pineoblastomas have a poor prognosis and the rate of survival in the French National Register is only 33% of cases. Germinomas can be treated with chemotherapy or radiotherapy alone and generally the indication for surgical removal is limited to residual tumours. The rate of survival is 64% at 10 years. For papillary tumours of the pineal region (PTPR) complete removal is a good prognostic factor. Radiotherapy seems to be effective in cases of residual tumours. The experience and results with radiosurgery treatment have been limited in the French national and Lyon experience. © 2014 Published by Elsevier Masson SAS.

r é s u m é Mots clés : Tumeurs pinéales Pinéalocytomes Pinéaloblastomes Tumeur germinales Gliomes de la glande pinéale Tumeurs papillaires Registre français des tumeurs de la pinéale

L’expérience du Registre français des tumeurs pinéales et de l’École lyonnaise est rapportée. Les données ont été colligées parmi 26 centres de neurochirurgie en France, depuis 1989 à Lyon et depuis 1997 dans les autres centres. Pour l’évaluation anatomopathologique et radiologique, 517 dossiers ont été examinés mais pour l’étude clinico-chirurgicale et pour l’évaluation des résultats, seulement 452 dossiers avec des données suffisantes ont été retenus. L’analyse des données met en évidence l’importance du diagnostic initial dans la stratégie thérapeutique qui est différente pour les tumeurs de la glande pinéale par rapport aux tumeurs germinales. Dans ces dernières, la chimiothérapie et la radiothérapie peuvent éviter la chirurgie. Les pinéalocytomes sont des lésions bénignes et leur exérèse complète garantit la guérison. Les tumeurs du parenchyme pinéal à différentiation intermédiaire nécessitent une exérèse complète et un traitement complémentaire en présence d’anomalies histologiques. Leur taux de survie est de 66 %. Les pinéaloblastomes ont un mauvais pronostic car le taux de survie est très bas et dans la série du Registre Français, seulement 33 % des patients sont vivants. Les tumeurs germinales peuvent être traitées avec de la radiothérapie et chimiothérapie et dans ces cas l’exérèse chirurgicale doit être réservée aux résidus. Leur taux de survie est de 64 % à 10 ans. Pour les tumeurs papillaires de la région pinéale l’exérèse complète représente un facteur pronostique favorable. La radiothérapie semble avoir une efficacité en cas de résidu. Notre expérience du traitement des tumeurs de la pinéale par radio-chirurgie est limitée. © 2014 Publie´ par Elsevier Masson SAS.

∗ Corresponding author. E-mail address: [email protected] (C. Mottolese). http://dx.doi.org/10.1016/j.neuchi.2014.02.006 0028-3770/© 2014 Published by Elsevier Masson SAS.

Please cite this article in press as: Mottolese C, et al. Pineal tumours: Experience of the French National Register and the Lyon School, results and considerations. Neurochirurgie (2014), http://dx.doi.org/10.1016/j.neuchi.2014.02.006

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ARTICLE IN PRESS C. Mottolese et al. / Neurochirurgie xxx (2014) xxx–xxx

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1. Introduction Pineal tumours currently represent a challenging pathology. Due to the various types of pineal gland tumours, different strategies are required that oblige all participants to discuss each case before a final therapeutic decision can be made. A multidisciplinary approach is consequently obligatory to establish what is the best and most reliable procedure for an accurate diagnosis, which tumours necessitate a direct approach and if required what type of complementary treatment is needed for children or adult patients. In this article, we report the data of the French National Register for the treatment of pineal tumours concerning both paediatric and adult populations, emphasising the differences with the Lyon experience. The series of patients included in the French National Register of pineal tumours were treated at 26 neurosurgical centres in France: Angers, Besançon, Bordeaux, Brest, Caen, Amiens, Clermont-Ferrand, Colmar, Dijon, Grenoble, Lille, Lyon, Marseille, Montpelier, Nancy, Nantes, Nice, Orleans, Paris, Poitiers, Reims, Rennes, Réunion, St-Étienne, Toulouse, Tours. The collection of data represents a retrospective study. The French National Register was established in 2008 with the National Commission for Information Technology and Civil Liberties (CNIL) in Lyons and has reported on patients since 1972 and in other centres from 1997. All tumours were reviewed and classified by A. Jouvet who was a founder and always an active member of the National French Register of Pineal Tumours. The first patients included were the object of a scientific thesis by A. Jouvet in 1989 regarding a study of 19 patients with pineal tumours, with a morphological ultrastructural and immunohistochemical assessment [1]. 2. Material and methods From 1972 to 2012, the French National Register of Pineal Tumours enrolled 517 patients: 288 men and 229 women. Of these, 136 patients were of paediatric age (Figs. 1 and 2).

During the same period, 277 patients were studied in Lyon with 152 (55%) males, 125 (45%) females and 71 patients of paediatric age (26%) (Figs. 3 and 4). All patients in the French National Register were considered for pathological and radiological evaluation, surgical considerations and clinical results which were reported on only true pineal tumours, germ cell tumours, pineal gliomas, papillary tumours and pineal cysts. Consequently, 452 patients from the French National Register with 232 patients from the Lyon series were considered. Clinical and survival analysis were reported in this group of patients assessing: age, sex, length of follow-up, clinical symptomatology, radiological data, type of surgery, biopsy or removal, total or partial, treatment of hydrocephalus, complementary treatment, complications, survival and quality of life. 3. Symptomatology A non-specific intracranial hypertension syndrome has characterized the clinical symptomatology in both groups of patients. The principal clinical signs are summarized in Table 1. 4. Surgical procedures The analysis of the Register data concerning the different approaches used and the amount of surgical removal shows that 136 patients (30%) out of 452 were initially biopsied: 100 had a stereotactic biopsy (74%), 16 (12%) an open surgical approach and 20 patients (15%) an endoscopic approach. In the paediatric patients (n = 136) a stereotactic biopsy was performed in only 21 (15%) patients. Three hundred and twenty eight patients were treated using a direct approach: 164 with a complete removal (50%), 80 with a partial removal (24%) whereas for 84 patients the quality of removal was not mentioned (26%). The infratentorial supracerebellar approach was carried-out in 57% of cases. In the Lyon series, only 36 patients (15%) were biopsied. In 19 patients (53%) the biopsy was performed under endoscopic conditions, in 15 patients (42%) under stereotactic conditions (2 paediatric) and in 2 patients by a direct surgical approach (5%).

Fig. 1. Sex distribution in the French National Register series. Distribution des sexes dans la série française.

Fig. 3. Sex distribution in Lyon series. Distribution des sexes dans la série lyonnaise.

Fig. 2. Rate of paediatric cases in French National Register series.

Fig. 4. Rate of paediatric case in Lyon series.

Distribution des cas pédiatriques dans la série française.

Distribution des cas pédiatriques dans la série lyonnaise.


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C. Mottolese et al. / Neurochirurgie xxx (2014) xxx–xxx Table 1 Symptomatology of pineal tumours. Symptomatologie des tumeurs pinéales. Symptomatology

France

ICH Headache Diplopia Papillary oedema Parinaud’s syndrome Cerebellar syndrome Ataxia Epilepsy Tinnitus Memory disturbances Torticollis Incidental Asthenia Precocious puberty Diabetes insipidus Pituitary insufficiency SAH

213 60 43 37 31 23 9 3 2 2 1 1 5 5 12 4 1

%

Lyon

%

47 13 10 8 7 5 2 0.7 0.4 0.4 0.2 0.2 1.1 1.1 2.7 0.9 0.2

107 45 23 17 9 15 – 2 – 2 1 – 3 2 3 3 –

46 19 10 7 4 6 – 0.9 – 0.9 0.4 – 1.3 0.9 1.3 1.3 –

ICH: intracranial hypertension; SAH: subarachnoid haemorrhage. ICH : hypertension intra-cranienne ; SAH : hémorragie subarachnoïdienne.

Of the 233 cases of pineal tumours treated surgically, 172 patients (74%) were operated on using a direct approach: 118 (69%) with a total removal, 34 patients (20%) a partial removal and for 31 patients the quality of removal was not specified (18%). 5. Histology, surgical and complementary treatment of the French National Register The French National Register of pineal tumours included 517 cases, that have all been reviewed by Professor Jouvet, with 142 (27.5%) cases of true pineal parenchymal tumours (PPT), 141 (27%) cases of germinomas, 87 (17%) gliomas, 38 (7.5%) papillary tumours of the pineal region (PTPR), 37 (7%) cysts, 6 (1%) primitive neuroepithelial tumours (PNET) and 1 atypical teratoid/rabdoid tumour (AT/RT) (Table 2). Forty-five cases were not considered for analysis because they represented tumours of the pineal region rather than tumours of the pineal gland: papilloma 2 patients, metastasis 6 patients, melanoma 4 patients, meningiomas 24 patients, inflammatory processes 4 cases and 5 were angiomas. Twenty-one cases were excluded after re-evaluation because their diagnosis could not be confirmed. In the group of true pineal tumours (142 cases), 19 (13%) cases were pineocytomas (PC), 93 (66%) were PPT-ID and 30 (21%) cases were pineoblastomas (PB) (Figs. 4 and 5). Forty-four patients were biopsied with a stereotactic approach in 30 cases, by endoscopy in 7 and an open surgical approach in other 7 cases. In one case, based on the results of a stereotactic

Fig. 5. Histological distribution of French National Register for pineal tumours. Distribution des tumeurs dans le registre français.

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biopsy, the patient underwent surgery with an incomplete removal of the tumour. In 81 cases, a direct approach was performed with a large or complete tumour removal while for 18 patients it was impossible to obtain information about quality of surgery. Thirteen cases of PCs were treated with a complete surgical removal, in 6 cases a biopsy preceded the surgical removal, in three cases a stereotactic biopsy and in three cases an endoscopic biopsy. Three cases required second-look surgery to accomplish a total removal. In the group of 93 cases with PPT-ID, 32 patients had a biopsy: stereotactic in 23 patients, by open surgery in 5 and endoscopic in 4 cases. Forty-four patients were treated using a direct approach and in 27 cases the surgical removal was complete while in 17 patients it was partial. For 17 patients there was no information available about the surgery. For PTT-ID, complementary treatment was necessary in 64 patients: chemotherapy was performed in 13 patients while 51 patients were irradiated: a conformational radiotherapy in 43 patients, interstitial radiotherapy in one patient and stereotactic irradiation in 7 patients. In the PB group (30 cases), 3 patients were treated by stereotactic biopsy, 2 by open surgical biopsy, eight patients had a complete removal, sixteen a partial removal and for one patient it was impossible to establish the quality of the surgical removal. The complementary treatment administered was chemotherapy for 13 patients (43%), radiotherapy and chemotherapy for 7 patients (23%) and for 18 patients (60%) radiotherapy alone. In thirty-eight patients, a papillary tumour of the pineal region (PTPR) was diagnosed. Nineteen patients had a biopsy which was performed in 18 cases under stereotactic conditions and in one patient via endoscopy. After the biopsy, eleven patients were operated on using a direct approach, seven with a complete removal and four cases with a partial removal. For papillary tumours the surgical removal was total for 21 patients (55%), partial in 10 patients (26%) and 7 patients had only a stereotactic biopsy followed by radiotherapy in 4 cases and in 3 cases no information was available about the complementary treatment. Twenty-six patients received complementary treatment: 5 patients chemotherapy alone, 18 patients radiotherapy and 3 patients chemotherapy and radiotherapy. One hundred forty-one patients belonged to the germ cell tumour (GCT) group: 89 germinomas (63%), 19 immature teratomas (IT) (13%), 11 mature teratomas (MT) (8%) and 22 (16%) non germinomatous germ cell tumours (NG-GCT). The average size of the tumour was 30.8 mm with a median of 30 mm. Seventy-five patients (53%) were treated for hydrocephaly with a ventriculo-peritoneal (VP) shunt in 54 cases (72%) and with an endoscopic third ventriculostomy (ETV) in 21 patients (28%). Fifty-one patients were treated by biopsy: in 31 cases a stereotactic biopsy, in 11 cases an endoscopic procedure and in six cases an open surgical approach. A surgical removal was performed in 56 patients: complete in 46 cases, partial in 10 cases, in 30 cases the quality of surgery could not be determined; and finally in 7 patients no data regarding the quality of surgery, or biopsy or tumour markers were available. Twenty-seven patients were operated on because the tumour markers were negative. Out of 89 patients with germinomas, 66 (74%) were irradiated and chemotherapy was associated in 32 patients. Five patients were treated with chemotherapy alone. For 18 patients it was impossible to exactly establish the complementary protocol received.


Tumours of neuroepithelial tissue Pineal parenchymal tumours Pineocytomas PPT-ID Pineoblastoma

9361/1 9362/3 9362/3

N

142 19 93 30

M

60 12 39 9

F

Age (years)

82 7 54 21

Size (mm)

Reported surgery

Biopsy

Complementary treatment

m

Med

m

Med

T

St

Ob

St

38.5 50.4 40.5 23.4

36 53 37 17

31.5 26 32 38.4

30 23 30 40

48 13 27 8

32 + 1a

7

17 15 + 1a

5 2

29 3 23 3

7 3 4

7

1

a

a

Endo

Surgery NS

ND or other

18 17 1

38

19

19

32.5

29

29

28

14 + 7

10 + 4

Astrocytic tumours Pilocytic astrocytomas Fibrillary astrocytomas Anaplastic astrocytomas Glioblastomas

9421/1 9420/3 9401/3 9440/3

64 35 11 8 10

28 14 6 3 5

36 21 5 5 5

30.7 14 17.5 25 43

22.5 13.5 13 24.5 46

29 29.1 nd 38.5 33.8

20 20 nd 38.5 21.5

17 + 4a 16 + 4a

10 + 6a 2 + 3a 2a 2 + 1a 6

Oligodendroglial tumours Oligodendrogliomas

9450/3

6

3

3

nd

nd

nd

nd

1

5

Oligoastrocytic tumours Ologoastrocytomas

9382/3

2

1

1

nd

nd

nd

nd

1

1

Gangliogliomas Ganglioglioma Anaplastic ganglioglioma

9505/1 9505/3

1 1

1 1

nd nd

nd nd

nd nd

nd nd

1a

Ependymomas Ependymoma, anaplastic

9391/3 9392/3

5 3

2 1

3 2

44 34

41 19

23 23

20 15

1a

1a

1

2 3

Germ cell tumours Germinomas Yolk sac tumour Choriocarcinoma Mature teratoma Immature teratoma Mixed germ cell tumour

9064/3 9071/3 9100/3 9080/0 9080/3 9085/3

141 89 6 2 11 19 14

124 83 5 2 10 15 9

18 6 1

16.1 17.7 16 20.5 13 12.7 15.2

30.8 30 46.5 31 27.5 23.7 29.7

30 30 48 31 27.5 16 28

40 + 3a + 3 20 1 1a 11 4 + 1a 5 + 2a + 1

10 7

6 6

31 30

2 4 5

18.6 20.3 15.3 20.5 14.4 11.3 15

1 1

1

PNET

9473/3

6

2

4

15.3

11

35.3

38

1

1

3

37

19

18

25

22

16

15

23

8

Pineal gland cysts

1

2 2

4 4

12 3 3 5 1

9 1 6 2

CT + RT

ND

27 1 13 13

71 2 51 18

8 1

3

7

3

5

18

3

4

16

1 3

6 10

1 1 1

11 10

30 9 5

1

13 3

1

1 5c

7 7

46 27 + 1b 6 2

83 64 + 2b 4 2

32 23 4 2

18 18

4 6

5 6

3 9

13

1

3

1

3

1

N: number; M: male, F: female; m: average; Med: median; T: total; St: subtotal; Ob: open biopsy; St: stereotactic; Endo: endoscopic; NS: not specified; ND: no data; nd: not determined, CT: chemotherapy; RT: radiotherapy. N : nombre ; M : homme; F : femme ; m : moyenne ; Med : médiane ; T : total ; St : sous-total ; Ob : biopsie ouverte ; St : stéréotaxique ; Endo : endoscopique ; NS : non signalé ; ND : absence de données ; nd : non déterminé ; CT : chimiothérapie ; RT : radiothérapie. a Surgery after biopsy or chemotherapy. b RT or CT only. c Cystostomy. a Chirurgie après biopsie ou chimiothérapie. b RT or CT seule. c Cystostomie.

ARTICLE IN PRESS

9395/3

RT

C. Mottolese et al. / Neurochirurgie xxx (2014) xxx–xxx

Papillary tumour of the pineal region

CT

G Model

ICD-O


4


Table 2 Histological distribution of patients of the French National Register. Répartition histologique des patients du Registre français des tumeurs pinéales.



In the group with immature teratomas (IT- 19 patients) one patient had an endoscopic biopsy, 5 patients (26%) a complete removal, one patient had a partial removal, and for 13 patients no specific data were available about the quality of removal. Five patients (26%) were treated by radiotherapy, 4 (21%) with chemotherapy. Eleven patients with mature teratomas (MT) were operated on with a complete removal. For NG-GCT (mixed germ cell 14, choriocarcinomas 2, yolk sac tumours 6) that concerned 22 patients in 3 cases (14%) a stereotactic biopsy was done, in 10 cases (45%) a direct approach with a complete removal, while in 2 patients only a partial removal was possible (9%). For 8 patients there were no data available concerning the quality of surgical removal. To summarize, among patients with a germ cell tumour (141 patients), 46 patients (33%) had a complete surgical removal and only 10 patients (7%) had partial removal. Fifty-one patients had a biopsy (36%): 31 patients a stereotactic biopsy, 11 an endoscopic biopsy and 6 using a direct approach. For 30 patients, the quality of removal could not be determined and for 7 patients it was impossible to establish which type of surgical procedure was performed. Eighty-three patients received complementary treatment (59%) with radiotherapy either after a surgical removal or after biopsy. Forty-six patients (33%) received neo-adjuvant or adjuvant chemotherapy associated to radiotherapy in 25% of cases. Only one patient had been treated for an AT/RT. Seventy-nine patients (17%) were treated for a pineal glioma. Of these patients, 27 (34%) were children. Treatment for hydrocephaly was necessary for 25 patients (32%) with a VP shunt in 14 cases (56%) and an ETV in 11 cases (44%). Sixteen patients (20%) had a stereotactic biopsy, followed by a complete removal in 4 cases and a partial removal in 6 cases. Fifty-two patients (66%) underwent surgery. In 24 patients (30%) a complete surgical removal was performed and in 16 patients (20%) only a partial removal was possible. In 12 cases the type of the surgery was not specified. In 16 cases we have no data regarding treatment. A histological review showed 35 cases of astrocytomas of WHO grade I (44%), 19 cases of astrocytomas of grade II–III (24%) and in 10 cases a grade IV (17%). For 4 patients, the histological grade was not specified whereas in one case, a type I neurofibromatosis, the biopsy was not performed. Six patients were treated for an oligodendroglioma, one patient had a complete removal while for the other 5 patients no data were available concerning the type of surgery or the complementary treatment. Two patients presented with an oligoastrocytoma. One had a complete surgical removal while for the other we have no data about surgery. In one patient with a ganglioglioma no data about the surgical removal were available and another patient, with an anaplastic ganglioglioma, was treated via a complete surgical removal after a biopsy. Finally, this last patient received radiotherapy as complementary treatment. Eight cases of ependymomas were diagnosed: 5 grade II ependymomas and 3 anaplastic. Seven cases were biopsied using the stereotactic technique and one case with an open surgical biopsy. One patient was operated on with a complete tumour removal after biopsy, in one patient only a partial removal was possible, and in one patient presenting with an acute intracranial hypertension the diagnosis was made after an autopsy. One patient was irradiated whereas for the other patients we do not know the complementary treatment that was given.

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Fig. 6. Distribution of the true parenchymal tumours in French National Register. Distribution des sous-types des tumeurs du parenchyme pinéale dans le registre français.

Thirty-seven patients (8%) presented with a pineal cyst: 19 men and 18 women, median age was 22. The average diameter of the lesion was 16 mm and the median 15. Surgical removal was total for 23 cases and incomplete for 8 patients. Five patients were treated using a marsupialization under endoscopic conditions associated at the same time with an ETV. In 1 patient, the quality of the removal was not specified. 6. Histology, surgical and complementary treatment of the Lyon series The Lyon experience concerns 277 patients and the anatomopathological revision permitted the diagnosis of: 54 PPT (19.5%), 77 GCT (28%), 58 gliomas (21%), 3 ependymomas (1%), 10 PTPR (3,6%), 1 AT/RT and 30 cysts (11%) (Table 3). In one group of 44 patients there were 2 papillomas (0.7%), 2 melanomas (0.7%), 5 metastases (1.8%), 2 inflammatory processes (0.7%), 21 meningiomas (7.7%) and 5 angiomas (1.8%)but these tumours were not studied because they were considered pineal region tumours. Seven cases (2.5%) were excluded after reinterpretation by pathologists (Figs. 6 and 7). In the group of true pineal tumours 11 cases were PPT grade I (20%), 28 PPT-ID (52%) and 15 were PB (28%) (Fig. 8). In the group of 11 PTT grade I, 5 patients were females and 6 males. The average diameter of tumour at moment of surgery was of 24 mm with a median of 20 mm. Three patients were biopsied: with endoscopy in 2 cases and a stereotactic approach in one patient. Finally, all 3 patients underwent surgery with a complete removal in 2 cases and a partial removal in one.

Fig. 7. Histological distribution in Lyon Register of pineal tumours. Distribution des tumeurs dans le registre français.


N

M

F

Age (years)

Size (mm)

Reported surgery

m

Med

m

Med

T

St

Biopsy Ob

Complementary treatment St

Endo

Surgery NS

Tumours of neuroepithelial tissue Pineal tumours Pineocytomas PPT-ID Pineoblastomas

9361/1 9362/3 9362/3

54 11 28 15

22 6 11 5

32 5 17 10

36.7 54.4 42.1 10.3

38.5 54 42 4

33 24 33.7 39.8

30 20 30 40

27 + 3a 8 + 2a 12 + 1a 7

7 + 8a 1a 7a 7

Papillary tumour of the pineal region

9395/3

10

7

3

42.1

40.5

25.1

23

7 + 1a

1 + 1a

Glial tumours Pilocytic astrocytomas Fibrillary astrocytomas Anaplastic astrocytomas Glioblastomas

46 25 11 5 5

20 10 6 1 3

26 15 5 4 2

23.9 14.3 17.5 20.5 57.5

18 16.5 13 20 57

23.4 22 nd nd nd

18 19 nd nd nd

18 18

5

8

9421/1 9420/3 9401/3 9440/3

2 2 1

1 3 4

Oligodendroglial tumours Oligodendrogliomas

9450/3

5

3

2

nd

nd

nd

nd

1

Oligoastrocytic tumours Ologoastrocytomas

9382/3

2

1

1

nd

nd

nd

nd

1

Gangliogliomas Gangliogliomas Anaplastic gangliogliomas

9505/1 9505/3

1 1

1 1

nd nd

nd nd

nd nd

nd nd

1a

1 1

nd nd

nd nd

nd nd

nd nd

1

16.3 18.1 nd 15.1 8 12.7

15.2 16.2 nd 13 8 15

29.1 28.4 nd 27.5 27 31.9

30 30 nd 27.5 27 31

31 + 4a 11 + 4a

22

14

16

15

23

2 1

1

Germ cell tumours Germinomas Yolk sac tumours Mature teratomas Immature teratomas Mixed germ cell tumours

9064/3 9071/3 9080/0 9080/3 9085/3

77 39 1 11 16 10

65 36 9 13 7

12 3 1 2 3 3

31

17

14

Pineal gland cysts

13 2 4 7

1

1

RT

CT + RT

22 2 13 7

4

ND 3

4 3

5 15 7 8

2

2

2

1 1

1 1

1 1

4

1

1 1 1 1 4 + 1a 3 + 1a 1

11 2 7 + 1◦

1 1

1 1

1 10 4 (9–5)

11 9

1 2 3

14 1

22 15 1

34 25

15 12

11

13

2 4

3 6

1 2

11

5b

N: number; M: male; F: female; m: average; Med: median; T: total; St: subtotal; Ob: open biopsy; St: stereotactic; Endo: endoscopic; NS: not specified, ND: no data, nd: not determined; CT: chemotherapy; RT: radiotherapy. N : nombre; M : homme ; F : femme ; m : moyenne ; Med : médiane ; T : total ; St : sous-total ; Ob : biopsie ouverte ; St : stéréotaxique ; Endo : endoscopique ; NS : non signalé ; ND : absence de données ; nd : non déterminé ; CT : chimiothérapie ; RT : radiothérapie. a Surgery after biopsy or chemotherapy. b Cystostomy. a Chirurgie après biopsie ou chimiothérapie. b Cystostomie.

ARTICLE IN PRESS

9391/3 9392/3

CT


Ependymomas Ependymomas, anaplastic

ND or other

G Model

ICD-O


6


Table 3 Histological repartition of patients of Lyonnais Register series. Répartition histologique des patients de la série lyonnaise du Registre des tumeurs pinéales.



Fig. 8. Distribution of the parenchymal tumours in Lyon Register. Distribution des sous-types des tumeurs du parenchyme pinéal dans le registre lyonnais.

Two patients were treated with radiotherapy and 2 others with chemotherapy because of doubts regarding histological results at that time. Ten patients had a complete removal. Among the 28 patients with a PPT-ID, 17 patients were females and 11 males. The size of the lesion varied from 15 mm to 60 mm (average 33.7) with a median of 30 mm. Eighteen patients were treated for hydrocephalus. The surgical removal was complete in 12 cases and partial in 7 cases and one patient with a partial removal underwent secondlook surgery with a complete removal. Seventeen patients received complementary treatment with radiotherapy in 13 patients, radiotherapy combined with chemotherapy in 4 and chemotherapy alone in 4 patients. Pineoblastomas were diagnosed in 15 patients, 10 females, 5 men and 9 cases were children. The average and median size of the lesion was approximately 40 mm. Fourteen patients presented with hydrocephalus treated in 12 cases with a shunt and in 2 cases with an ETV. Seven patients underwent a complete surgical removal, 7 patients a partial removal and only one patient had a stereotactic biopsy followed by radio-chemotherapy. Seven patients were cured with radiotherapy alone, 7 were treated with chemotherapy while for 3 patients it was impossible to know the complementary program carried-out. Ten patients were treated for a PTPR as follows: 3 females, 7 males and one child. The average size of the lesion was 25.1 mm and the median of 23 mm. Five patients presented with an hydrocephalus treated in 2 cases with a VP shunt and in the other 2 cases with an ETV. In eight cases a complete removal was possible while it was partial in the other 2 cases. Two patients underwent a stereotactic biopsy before an open approach with a complete removal for one and incomplete for the other patient. Five patients were irradiated. Seventy-seven patients presented a germ cell tumour with true germinomas in 39 patients (51%), mature teratoma in 11 (14%), immature teratomas in 16 (21%) and a non germinomatous germ cell tumour in 11 patients (14%). The middle size of the lesion was 29.1 mm with a median 30. Forty patients (52%) were treated for hydrocephalus, 25 (62%) with a VP shunt and 15 (38%) with an ETV. Twelve patients (16%) were biopsied, 10 under endoscopic conditions, one stereotactic and one by open surgery. Forty patients (52%) were treated using a direct approach: 35 patients with complete removal and 5 with a partial removal. For 11 patients (14%) the quality of removal was not mentioned. For 14 patients (18%) no data about the treatment were available. Fifteen patients were treated with an ETV associated with a biopsy. Of these, 5 patients were reconsidered for surgery with complete tumour removal in 4 and partial removal in one patient.

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Thirty-four patients (44%) were irradiated, 22 patients (29%) were treated with chemotherapy and 15 patients with chemotherapy and radiotherapy. As regards germinomas (39 patients), 25 patients (64%) were irradiated, 15 (38%) were treated by chemotherapy and 12 (31%) with chemo- and radiotherapy. In the group of immature teratomas (IT 16 patients), one patient was biopsied under endoscopic conditions, 2 (13%) had a complete removal and for 13 patients (81%) data were not available regarding surgical treatment. Three patients (19%) received radiotherapy, 2 chemotherapy (13%), and for the others no data was available. For mature teratomas (MT 11 patients) all of them were treated surgically with a complete tumour removal. In the group of NG-GCT (11 patients: 10 mixed germ cell tumour and 1 yolk sac tumour), 8 patients (72%) had a complete removal, one a partial removal and in 2 the removal was not mentioned. Six patients (55%) who were irradiated and 5 (45%) received chemotherapy. One patient was diagnosed with an AT/RT had a complete surgical removal. Fifty-five patients were diagnosed with gliomas of the pineal gland. Twenty-five patients presented with a pilocytic astrocytoma (WHO grade I), 16 a grade II or III glioma and 5 a grade IV glioma. In one patient with confirmed neurofibromatosis the biopsy was not performed and was considered a low-grade astrocytoma. Five patients with an oligodendroglioma were operated on with a complete tumour removal in one case and an incomplete removal in 4 cases. Gangliogliomas concerned 2 patients: for one patient, a benign ganglioglioma, although we have no data regarding treatment and the other was treated for an anaplastic ganglioglioma with complete removal followed by radiotherapy. In 3 patients, the diagnosis of an ependymoma was performed. Of these, one patient was treated via a direct surgical approach and a complete removal, another had a partial removal after biopsy and in one patient the diagnosis was obtained after the autopsy. Thirty-one patients were treated for a pineal gland cyst: 14 female and 17 males with an average age of 22 years and median of 14 years. For 23 patients (74%) the complete removal was possible after a direct surgical approach. For 3 patients the removal was incomplete because a piece of the capsule was left at level of the vein of Galen and 5 patients were treated with a marsupialization under endoscopic conditions associated in the same time with an ETV. In two patients a VP shunt was necessary after the surgical removal of the tumour.

7. Results and follow-up The clinical results are reported in relation to the histological diagnosis. Different modalities of irradiation and different cycles of chemotherapy have been consequently used. Therefore, we have only reported results if patients were, in fact, treated and which treatment was used without analysing the different protocols that have been used over the past 20 years according the SFOP or the ANOCEF guidelines, and in recent years following the indications of the local oncological advisory commission. The follow-up of the patients that we assessed varies between twenty years and at least one year with a median follow-up for all patients of 8 years and six months. As previously reported patients with no information about their clinical evolution have been eliminated by analysis and clinical considerations.




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Fig. 9. Rate of survival for each type of tumour in the French National Register at 10 years. Pourcentage de la survie pour chaque groupe tumoral dans le registre français à 10 ans.

8. Results of the French National Register The survival data for pineal lesions of the French National Register is reported in Figs. 9 and 10. The median survival of all pineal lesions is 49% and it is correlated with their histological pathology. The average follow-up for all patients is 5.8 years (median 4.47) varying from 1 to 23 years but generally after ten years patients were considered cured and the follow-up ended. Among the survivors (n = 315), the Karnofsky index was available for 279 patients with an average score of 90 (median 100). The overall mortality was 137 patients (30%). In paediatric patients among survivors the quality of life was considered normal in about 85% of the population with minor sequelae in only 15% of cases. Children of school age were able to attend a normal school programme in 87% of cases. Concerning true pineal gland tumours out of 19 patients treated for a pineocytomas (PC) 16 are still alive and three patients are dead but this was not related to the disease except one case treated with radiotherapy 4 years after the stereotactic biopsy. The average of follow-up was 6.7 years (median 4 years) with a good quality of life for all patients except one who had persistent mild Parinaud’s syndrome. In the PPT group with intermediary differentiation (PPT-ID) 61 patients (66%) are still alive while 28 patients died and 4 patients were lost to follow-up. The average follow-up was 5.35 years (median 4.9 years) For PBs that represent 30 cases, 10 patients (33%) are still alive, 14 patients (47%) died and 6 patients (20%) were lost to follow-up. The average follow-up was 3.5 years (median 4.2years)

If we consider germ cell tumours, for germinoma (n = 89) 57 patients (64%) are still alive, 15 patients (17%) died and 17 patients (19%) were lost to follow-up. As regards immature teratomas (IT) 6 patients (32%) are still alive, 2 patients had died and 11 patients (58%) were lost to followup. For mature teratomas (MT = 11 patients), all were treated by complete surgical removal and two patients (18%) are still alive, 2 patients died and 7 patients (63%) were lost to follow-up. The group of patients with NG-GCT concerns 22 patients and only 15% of patients are still alive and in this group a high mortality rate (85%) was reported. Finally, among 141 patients with germ cell tumours 81 patients (57%) are still alive, 26 patients (18%) died, and 36 patients (25%) were lost to follow-up. The only patients operated on for an AT/RT of the pineal gland died: a child operated in emergency in a post-haemorrhagic severe deep coma with mild bilateral pupillary reflex and a long comatose evolution after surgery. In the group of gliomas 35 patients presented a grade I astrocytoma (40%): 20 patients (57%) are still alive, 2 patients died and 13 were lost to follow-up. Nineteen patients had a grade II–III astrocytoma (22%): 5 patients (26%) are still alive, 6 patients (32%) died and 7 (42%) patients were lost to follow-up. In the group of patients with a grade IV glioma (10 patients, 18%) only three patients are still alive while 7 patients died. In 4 patients with a glioma, the grade was not specified and in another case with a type I neurofibromatosis the biopsy was not done (total 5 patients not mentioned in Table 2 or Table 3). Out of 8 patients with an ependymoma 5 patients are still alive and three patients died. Among patients with oligodendrogliomas 4 are alive and 2 patients were lost to follow-up. Of the 2 patients with an oligoastrocytoma one is still alive and one patient was lost to follow-up. One patient with a ganglioglioma and another with an anaplastic ganglioglioma are still alive. In the group with PTPR, 24 patients (63%) are still alive, 10 patients (26%) died and 4 patients (11%) were lost to the follow-up. All patients with pineal cyst are still alive. 9. Results of the Lyons series The Lyon patients have been included in the French National Register. However, it could be interesting and important to report

Fig. 10. Rate of survival for each type of tumour in the Lyon series at 10 years. Pourcentage de la survie pour chaque groupe tumoral dans la série lyonnaise à 10 ans.




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Fig. 11. Number of patients alive, dead or loss to follow-up in the French National Register. Nombre des patients survivants, décédés ou perdus de vue du registre français.

the results of a single centre where, for a long time, this pathology has been of particular interest and to emphasise possible differences (Figs. 11 and 12). The median survival rate of the Lyon series was 47%. For adult patients an evaluation of the quality of life based on the Karnofsky scale was possible in 174 patients (75%). This group presented an average score of 92 (median 100). In the paediatric population the quality of life was normal in 93% of patients with 89% of patients able to follow a normal school programme. The overall mortality was 74 patients (26%). Considering true pineal tumours pineocytomas were found in 11 patients and 10 patients are alive while one patient died from a disease not related to the initial pathology. In the group of PPT-ID, 17 patients out of 28 are still alive. Eleven patients died but only seven due to the disease. Out of 15 patients with pineoblastomas two patients are alive and two were lost to follow-up (one patient is in complete remission and one has a stabilized disease). All patients of paediatric age (n = 9) died. Out of ten patients treated for a PTPR, 4 patients (40%) are still alive and 5 patients (50%) died while one patient was lost to followup. If we consider the group of germ cell tumours that concerned 77 patients, 38 patients (49%) are still alive, 13 (14%) died and 28 (37%) patients were lost to follow-up. In the true germinomas group, 24 patients are still alive, five are dead and 10 patients were lost to follow-up.

Immature teratomas were found in 16 patients with three patients still alive; two died and 11 were lost to follow-up. Mature teratomas concerned 11 patients: two patients are alive, two patients died and 7 were lost to follow-up. Non germinomatous germ cell tumours: 9 patients are still alive while 2 patients died. If the group of gliomas that concerned 61 patients, 24 patients are still alive, 11 patients died and 22 were lost to follow-up. Considering the different subtypes of gliomas in 26 patients of the grade I group (pilocytic astrocytomas) 16 patients are alive and 10 patients were lost to follow-up. In group of grade II and III, which included 16 patients, 4 are alive, 5 died and 7 lost to follow-up. In 5 patients with grade IV gliomas, only one patient remained alive. Pineal ependymoma represent three patients and only one patient remained alive. As regards gangliogliomas: two tumours, one grade I and another anaplastic were found with both patients still alive. Oligodendrogliomas were found in 5 patients who are all are alive at one year follow-up and were later lost to follow-up. Pineal cyst occurred in 30 patients and all patients are still alive. 10. Complications of surgical treatment Overall, postoperative mortality in the French National Register was 1.8%. Postoperative complications were as follows: 1.6% of patients presented a subdural and 0.7% a extradural haematoma

Fig. 12. Number of patients alive, dead or loss to the follow-up in the Lyon series. Nombre des patients survivants, décédés ou perdus de vue (série Lyonnaise).


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that were removed by a surgical procedure. Infectious complications were reported in 5 patients with an operative field abscess in 3, meningitis in 1 and sepsis in 1 patient. Motor and sensitivity deficits after surgery were less than 2% while the rate of residual epilepsy was about 5%. Visual acuity deficit related to conjugate gaze palsy was 3.7% in the French national series. Four patients (0.9%) of patients presented a reduction in visual acuity and 3 patients (0.7%) a hemianopsia. In the Lyon series, the overall postoperative mortality was 1.5%. The rate of postoperative haemorrhage was 1.9% with 3 patients presenting with a subdural haematoma and one patient an extradural haematoma, all required a surgical procedure. One intratumoral haemorrhage was complicated by a stereotactic biopsy. Two patients were treated for an abscess of the operative field and 3 patients presented with a skin infection that required the suppression of the bone flap, and a secondary surgical procedure for cranial reshaping. The rate of Parinaud’s syndrome was 7.3% in the immediate postoperative period but recovered during the followup with a rate of only 1.3%. Four patients (1.5%) presented with diminished visual acuity. A post-surgical epilepsy was observed in 19 patients (7.5%) but all cases were controlled using antiepileptic drugs One particular pinealectomy syndrome after surgery was observed in the Lyon series. This syndrome concerned 10% of adult and paediatric patients. However, its incidence could not be established for other French centres. 11. Analysis and considerations The rate of treatment complications for pineal tumours in the French National Register group and in Lyon series decreased over time either in terms of mortality or morbidity. In the past twenty years postoperative mortality has decreased to 1.8% in the French National Register and to 1.5% in the Lyon series. The analysis of the French National Register of pineal tumours and the Lyons series permits to report some important data regarding the evolution and the results of the treatment of pineal tumours (Fig. 13). As regards the biopsy procedure it was only performed in 30% of patients and the stereotactic biopsy was preferentially adopted for adults. In paediatric population only 25 patients of the National French Register were biopsied under stereotactic condition and only two belong to the Lyon series. In recent years, for patients with hydrocephalus, the endoscopic technique has been preferred. In paediatric patients the stereotactic biopsy has generally been

avoided due to the potential haemorrhagic risks related to the presence of the venous arch. This arch generally recovers the superior pole of the lesion with an anterior-frontal position placing both posterior-parietal trajectories at risk. The diverse varieties of tumour subtypes need particular consideration and therefore, before examining their approach, some recommendations must be considered. In the group of true pineal parenchymal tumours, pineocytomas are benign tumours and their complete removal guarantees a cure as shown not only by patients of the French Register but also by the Lyon experience. In cases of incomplete removal, a secondlook surgery has to be considered increasing the rate of cured patients. With a subtotal removal, the use of adjuvant radiotherapy does not seem to increase the five year overall survival rate as previously reported in literature [2] and consequently a new second-look surgery to complete the removal is obligatory instead of complementary treatment alone. Pineocytomas are well-limited lesions and their complete removal is generally possible. In cases of partial tumour removal the risk of development of malignant foci inside the tumour has been reported in literature [3], and this condition requires complementary treatment. Aggressive surgery alone provides a benefit over subtotal removal associated to radiotherapy and yields an optimal survival [4]. For PPT-IDs the complete surgical removal represents a good prognostic factor and surgery alone should be the preferred treatment for patients with a grade II that are considered as benign lesions [5]. For grade III PPT-IDs complementary radiotherapy and/or chemotherapy are necessary to avoid progression and to decrease the rate of mortality [6,7]. For the Lyon school grade II-III of the PPT-IDs have an aggressive behaviour needing complementary treatment although this opinion has not yet been corroborated by other reports published in the literature. In our opinion, for these particular tumours, the criteria used for the anatomopathological classification of Jouvet make sense [5]. Out 63 patients of the French National Register who are still alive, 44 patients (69%) received radiotherapy while 17 patients (27%) received chemotherapy and radiotherapy. Out of 17 patients still alive, of the Lyon series, 13 patients (76%) received radiotherapy and four (24%) radiotherapy and chemotherapy. The prognosis of pineoblastomas is particularly dismal in the National Register series as well as in the Lyon series. In the latter series, no paediatric patients had survived after treatment with

Fig. 13. Global survival analysis for each tumour subtype in the French National Register series. Analyse globale de la survie en fonction de l’histologie dans la série française.




surgery and complementary treatment confirming that low age represents a poor survival factor [8]. According the French National Register the only patients still alive are adult patients treated with a complete removal and a complementary treatment with cranio-spinal irradiation but the survival rate remains poor as also reported by Fauchon [9] and Mena [10]. Favourable prognostic factors are the extension of the surgical removal, age of the patient at presentation, a localized disease and treatment with cranio-spinal irradiation [11]. In the group of germ cells tumours true germinomas can be cured only with radiotherapy or with the association of chemotherapy and radiotherapy. A survival rate at five years or at 10 years of 90% has been reported with radiotherapy alone in the Japanese or Asiatic experience [12] and a survival in 90% of cases is reported [13,14]. The results of a Japanese series have shown that the ten years survival with radiotherapy ranges between 60% to 100% of cases [15]. For true germinomas, chemotherapy has permitted, in cases of a localized disease, to reduce the field of irradiation at only the ventricular system. In cases of residual tumour, a boost has to been given to the lesion while in a disseminated disease a cranio-spinal irradiation has to be programmed [16]. In the past, an aggressive surgical strategy for removal of germinomas was adopted also in Lyon but in fact it is admitted that surgery has to be reserved for biopsy or for treatment of hydrocephalus. The study of the tumour markers in the blood and in the CSF is very important. In cases of increased intracranial hypertension without hydrocephalus, the study of CSF markers can be impossible because a spinal tap can be dangerous. In this case the biopsy becomes imperative to programme the best strategy for treatment. In cases of germ cell tumours diabetes insipidus was present in only 13 patients with bifocal tumours as in 3 patients of the Lyon series with the same location. This clinical sign is considered specific to pineal tumours but it is rather characteristic in bifocal localization while it is rare in the exclusive pineal location. Non-germinomatous germ cells tumours represent a heterogeneous group of tumours with a more severe prognosis than germinomas [16]. For embryonal carcinomas, yolk stalk tumours and choriocarcinomas the treatment with the most immediate effective result is chemotherapy that not only reduces the tumour volume but also the results at one year are poor with a rate of mortality of 85% of patients [17]. For these tumours, the treatment starts with chemotherapy and depending on the result obtained volume surgery is then performed followed by radiotherapy. In the literature surgery after radiotherapy has been proposed but the high rate of reported fibrosis seems to increase the surgical difficulties for complete removal and the rate of morbidity [18]. For teratomas, mature teratomas, surgical removal is the only treatment and the rate of survival is of 80% to 100% as reported in the literature. For immature teratomas the survival rate is less significant and chemotherapy is used to destroy the immature contingent of the lesion. After chemotherapy the residual nodule is treated with surgery with the aim of a complete removal. Radiotherapy completes the therapeutic programme. For immature teratomas the five year survival was about 35 to 40% [18]. PTPRs need a complete surgical removal to improve the survival rate and the prognosis. In the series of the French National Register 24 patients (63%) out of thirty are still alive and all had complete tumour removal

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while the other ten patients (26%) with a partial removal or biopsy alone died. This experience stresses that complete surgical removal represents an important prognostic risk factor as reported also by Févre-Montange et al. [19]. Radiotherapy and chemotherapy are necessary to cure patients also if the rate of survival reported at 5 and 10 years is only 34.5 and 8.6% respectively [20]. The surgical results of pineal cysts were satisfactory and surgery represents their treatment in cases of a volume increase rendering them symptomatic, in cases of intracystic haemorrhage or when a pineocytoma is suspected. Endoscopic treatment with their regression has been reported in literature [21]. In the experience of the Register this type of evolution has not been observed: five cases have been treated with endoscopic marsupialization associated to an endoscopic third ventriculostomy (ETV). In all these cases the follow-up with cerebral MRI confirmed the decreased in volume of the cysts without their disappearance. In fact, endoscopic treatment for pineal lesions is widely used particularly in cases associated with hydrocephalus or for biopsy. The complete removal through the ventricular system is rare and difficult especially in cases of haemorrhage because its control is challenging even for experienced surgeons [22]. At the light of the experience of the Register, open surgery has been frequently performed for the removal of a pineal tumours. Only 31% of patients treated with a direct approach have been previously biopsied. From a surgical point of view, different approaches have been proposed but two main have been particularly used: the infratentorial supracerebellar and the sub-occipital transtentorial approach. In the French National register the infratentorial supracerebellar approach was used in 58% of cases while in Lyon it was performed in only 18% of cases. The infratentorial supracerebellar approach is the most frequently used, as reported in the literature. Also, many other routes have been described for these deep-seated tumours [23,24] The sub-occipital transtentorial approach was used in patients of the French National Register in 35% of cases while it was performed in 77% of cases in Lyon. Other approaches have been proposed as the inter-hemispheric transcallosal anterior or posterior trans-splenial, the transventricular inter-thalamo-trigonal, the lateral trans-ventricular etc. All these approaches can have advantages and limitations depending on the extension of the lesion, the axis of growth, their relationship with the third and lateral ventricle. The rate of their use represented 7% for patients of the French National Register and 5% of the Lyon experience. The aim of this paper was not to discuss and criticise the different approaches used but only to report what has previously been done for the surgical treatment of pineal tumours in France. We can only say that in Lyon the major preference for the sub-occipital transtentorial approach was particularly related to the strong message of Lapras’s teaching that modified the occipital approach proposed initially by Poppen. [18] The arguments for this choice were a wide view of the pineal region, the better control of the lateral extension of the tumours inside the lateral ventricles and the better control of the extension inside the third ventricle. We are aware that both these approaches have to be mastered by surgeons to offer the best chances for treatment for their patients but we are also conscious that each surgeon chooses the approach and the surgical position with which they are more familiar. Regarding the discussion between the supporters of large or mini invasive approaches, microsurgery or endoscopic strategies, the most important thing is to know is when we can and how we can do it. Also the capacity to master complications because in reduced spaces the management of complications can be more difficult.


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Regarding the debate on endoscopic or microsurgical removal, from the experience of the Register, microsurgery was the preferential treatment but what seems evident is that a complete removal is frequently associated with better survival and clinical results. The microsurgical removal of pineal lesions assisted by endoscopy is preferred in Lyon, increasing the rate of complete removal and survival. Endoscopy is used more frequently to perform an ETV for treatment of hydrocephalus because it also permits a biopsy. However, shunts can still be used if necessary. A shunt was performed in 72% of cases while an ETV in 28% of cases in the Register; in Lyon the rate of ETV was 38% while a shunt was used in 38% of cases. Concerning the position used for surgery, the debate between anaesthesiologists and surgeons will continue because of the major advantages that the sitting position offers to surgeons even if there is a potential risk of air embolism, especially in patients with a permanent oval foramen. The potential risks of embolic complications can generate medico-legal problems that force anaesthesiologists to decline the sitting position. A recent a comment on the sitting position about the Helsinki experience showed that, although air embolism can be frequent, severe consequences on blood pressure, heart rate and on other anesthesiological factors are almost insignificant and consequently potential risks can be managed by an experienced team [25]. After recent unpublished multicentre investigation, the ventral position was adopted in 60% of the French centres. In Lyon, the sitting position is preferred because of its advantages that are represented by a wide view of the region, the better acknowledgement of the anatomical structures and better control of haemorrhage with the possibility to work in a clean operative field because blood that flows out of the operative field due to gravity. The acquired experience of the anesthesiological department in the management of possible complications that can occur is also an important factor for this choice. Particular attention is needed regarding a pinealectomy syndrome that can be observed in operated patients. This syndrome was described by Chazot et al. [26] in Lyon and concerned 10% of patients. It has a particular clinical picture characterized by headaches, fatigability, behavioural troubles and a particular perturbation of the circadian rhythm cycle with sleep disturbance. In the same case it is possible to observe anxiety, hypersomnia, auditory hallucinations, memory disorder and hemi cranial headache. In children, this syndrome is also observed and is especially characterized by irritability and tiredness. For this particular syndrome, the administration of melatonin seems to be effective.

12. Conclusions and take home message Multidisciplinary approach is imperative to establish the better strategy for pineal tumours. It is important to consider the age of patients because some tumours of the pineal region are age specific. In infants or in young children we have to think about PNET including pineoblastomas or ATRT or teratoma. In adolescent or young adults it is possible to find germ cell tumours, a pineocytoma, a pineoblastoma or a glioma. In adults gliomas can be more frequent. At the beginning of the decisional tree, it is imperative to be sure of the histological nature of the tumour and to establish the diagnostic strategy. When a pineal tumour is discovered the following decisional tree could be: Investigation of tumour markers in the blood and in the CSF. If the markers are elevated they reveal the presence of a germ cell tumour and treatment will be chemotherapy and radiotherapy; if they are not elevated, depending on age and radiological features, in absence of ventricular dilatation, direct approach or biopsy in stereotactic condition could be performed.

In cases of ventricular dilatation and without elevated markers ETV and biopsy of the tumour remains debatable. In cases of pineocytoma, PPT-IDs, pineoblastoma or benign glioma, the surgical approach should be encouraged for removal. In cases of papillary tumour a complete surgical removal has to be encouraged followed by complementary treatment. In cases of gliomas, exophytic gliomas, the surgical procedure has to be performed and in function depending on the grade, complementary treatment with radiotherapy or chemotherapy or both according the age of patients can be necessary. In case of recurrence the decision tree should take in account the clinical symptomatology, the histology and the grade, the treatment previously delivered. In case of benign lesions or other pineal lesions that can be removed the surgical approach seems to be adapted before the decision of chemo or radiotherapy. Concerning the treatment of pineal lesion with radiosurgery, the experience of the French National Register and of the Lyon experience is limited as well as that of the literature. [27,28]. We think that its indication, especially in the paediatric population, has to be avoided because pineal tumours can be approached surgically with a rate of morbidity and mortality that is currently a very low exception. For malignant tumours cranio-spinal irradiation is rather indicated. It is possible that in the future wider experience and the possibility of reduced post-irradiation risks can increase indications for radiosurgery. We are aware that treatment of pineal tumours is still a difficult challenge for neurosurgeons in relation to specific technical difficulties and different subtypes of tumours. In the future, the progress of genetics and molecular biology could permit to cure more patients based on a tailored treatment, which in fact is the case in oncological pathologies especially in children, i.e. medulloblastomas or brain stem tumours. We are confident that in the future, scientific progress will contribute to improve the clinical results of pineal tumour treatment. In the light of this report, a well-structured and centralized database is required to progress in pineal tumour management. This structure could assure the study of the pineal pathology in all modern aspects: from the clinical picture to the genetics of tumours. Consequently, we would like to not only stimulate all French surgeons but also all surgeons of the French Language Society of Neurosurgery to send data to the new French National Register to contribute to a better knowledge of this particular group of tumours, improve results and decrease morbidity and mortality related to their treatment. The new Register is now available in Lyon and we hope that from now on all pineal tumours can be send and checked in order to have the possibility of studying all their aspects with a more modern vision. Disclosure of interest The authors declare that they have no conflicts of interest concerning this article. Acknowledgement We would like to thank Dr. Anne Jouvet for her extraordinary work and contribution in revising all pineal tumours of the French National Register and for their important work in Lyon. References [1] Jouvet A. Étude morphologique ultrastructurale et immunocytochimique d’un glande pineale humaine kystique et 19 tumeurs pynealocytaire (Pinealome « vraie » dans une serie de 154 processus expoansif de la region epyphysaire. In: Thesis; 1989.




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Results from the French National Esophageal Atresia register: one-year outcome.

Increasing rates of brain tumours in the Swedish national inpatient register and the causes of death register.

Pineal parenchymal tumours and pineal cysts.

Results from the Swedish national anterior cruciate ligament register.

Clinical and morphological studies of pineal tumours.

Neurosurgical experience with tumours of the pineal region at Clinica Puerta de Hierro.

Marker for pineal tumours?

[Tumours of the pineal region: Part II: results of treatment in 23 patients (author's transl)].

Management of pineal region tumours.

Validation of the danish national diabetes register.

Minority ethnicity patient satisfaction and experience: results of the National Cancer Patient Experience Survey in England.

Psychosocial work factors and first depressive episode: retrospective results from the French national SIP survey.

Psychosocial factors at work and sickness absence: results from the French national SUMER survey.

Effectiveness of TNF inhibitor switch in RA: results from the national Swedish register.

Results of first year (1989) of a national register of Down's syndrome in England and Wales.

Video-assisted anal fistula treatment: technical considerations and preliminary results of the first Brazilian experience.

Treatment of tumours of the pineal region and posterior part of the third ventricle.

Tumours in Iceland. 13. Malignant tumours of the testis. A histological classification, epidemiological considerations and survival.

Interest and limits of endoscopic approaches for pineal region tumours.

Melatonin as a marker for pineal tumours.

School Start Time and Adolescent Sleep Patterns: Results From the U.S. National Comorbidity Survey--Adolescent Supplement.

Neuroendoscopy and pineal tumors: A review of the literature and our considerations regarding its utility.

The causes of bullying: results from the National Survey of School Health (PeNSE).

Long-term results of combined liver-kidney transplantation for primary hyperoxaluria type 1: the French experience.