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Incidence of pineal tumours. A review of the literature
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Report 2013: Tumors of the pineal region
Incidence of pineal tumours. A review of the literature Incidence des tumeurs pinéales. Revue de la littérature C. Mottolese ∗ , A. Szathmari , P.-A. Beuriat Neurological and Neurosurgical Hospital « P. Wertheimer », Pediatric Neurosurgery E, 59, boulevard Pinel, 69677 Bron, France
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Article history: Received 10 April 2013 Received in revised form 13 January 2014 Accepted 24 January 2014 Available online xxx Keywords: Pineal tumours Incidence of pineal tumours Germ cell tumours Pineal gliomas
a b s t r a c t The knowledge of the incidence of pineal tumours is important not only for diagnostic care but also for its therapeutic programme. We reviewed the incidence of pineal tumours reported in literature in an attempt to establish if a difference existed between pineal gland tumours and the pineal region tumours as different authors use both expressions to indicate the same thing. The rate of frequency of these tumours is useful to guide the therapeutic choice for patients as the decisional tree is completely different for either germ cell tumours, pineal gland tumours or pineal gliomas and eventually papillary tumours of the pineal region. According to the French Register of pineal tumours, true pineal tumours represent: 27% pineal parenchymal tumours (PPT), 27% germ cell tumours, 17% gliomas, 8% papillary tumours. True pineal gland tumours are represented by: pineocytomas - (13%), pineal parenchymal tumours with intermediary differentiation PTT-ID - (66%) and pinealoblastomas - (21%). There was no statistical difference found between the French register and the Lyon series concerning histological diagnosis. It seemed to us important to discover its true incidence by comparing the data published in the literature and to stress the utility of the French Register for these uncommon tumours not only for recording new histological cases but also to document clinical symptomatology, therapeutic programmes, length of follow-up and clinical results for each patient treated. A better understanding of their natural history and improved evaluation of different treatments and their complications should contribute to improve clinical results. © 2014 Published by Elsevier Masson SAS.
r é s u m é Mots clés : Tumeurs de la pinéale Incidence des tumeurs de la pinéale Tumeurs germinales Gliomes pinéales
Il est important d’établir l’incidence des tumeurs propres de la glande pinéale et de la région pinéale. Le fait de connaître l’incidence de ces tumeurs peut aider d’un point de vue pratique à une meilleure prise en charge de celles-ci. La stratégie thérapeutique est différente selon qu’il s’agit d’une tumeur du parenchyme, d’une tumeur germinale ou d’une tumeur papillaire. L’étude des cas recensés par le Registre franc¸ais des tumeurs pinéales a mis en évidence que 27 % des cas sont des tumeurs du parenchyme pinéal, 27 % des cas des tumeurs germinales, 17 % des gliomes de la glande pinéale et 8 % des cas des tumeurs papillaires. Les tumeurs de la glande pinéale sont réparties en pinéalocytomes (13 %), tumeurs pinéales à différenciation intermédiaire (66 %) et pinéaloblastomes (21 %). Il n’y a pas de différences statistiques importantes en ce qui concerne la distribution anatomo-pathologique entre les chiffres du Registre franc¸ais et ceux de Lyon. La nécessité et l’importance d’un Registre pour ces tumeurs rares regroupant différents types histologiques et nécessitant différentes stratégies thérapeutiques, semblent donc évidentes pour le recensement des nouveaux cas histologiques, pour l’établissement des données cliniques, des protocoles thérapeutiques et pour la vérification de courbes de suivi et de résultats cliniques. Dans ce contexte, le Registre franc¸ais prend toute son importance, en particulier, parce qu’il permet la confrontation des études de ces tumeurs aux différentes expériences de la littérature. © 2014 Publie´ par Elsevier Masson SAS.
∗ Corresponding author. E-mail address: [email protected] (C. Mottolese). http://dx.doi.org/10.1016/j.neuchi.2014.01.005 0028-3770/© 2014 Published by Elsevier Masson SAS.
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1. Introduction The knowledge of the true incidence of pineal tumours and pineal region tumours is of great importance because different histological entities are represented and consequently for a particular tumour an adapted therapeutic programme has to be established. In other words, the histological diagnosis can condition the choice of surgical or complementary treatment except for the treatment of hydrocephaly. Generally, in the literature, when pineal or pineal region tumours are reported there is some mention of the incidence of different histological specimens that can develop in the pineal region. In order to define the true incidence of pineal tumours from that of the pineal region we were prompted to review various papers in the literature that reported the incidence of pineal and pineal region tumours. In the pineal tumours group, we have included true pineal tumours, germ cell tumours, pineal gliomas and papillary tumours of the pineal region that are considered the most frequent pineal tumours. 2. Anatomy of the pineal gland and pineal region The pineal gland develops in a deep-seated region, the pineal region, which is located in the posterior part of the incisural space [1]. The pineal gland belongs to the posterior part of the third ventricle and it is located between the posterior commissure at the top and the tectal plate below. The gland that is a small reddish brown structure has a size which varies between 10 and 14 mm. The pineal gland develops as a diverticulum in the diencephalic roof of the third ventricle and is attached to the posterior board with a stalk. The pineal region is surrounded by different structures that at the same time defines its boundaries: the roof, anterior wall, lateral wall and the floor of the posterior incisura. The roof of the pineal region is formed by the lower surface of the splenium of the corpus callosum, the hippocampal commissure and the crus of the fornix. The pineal body, the tectal plate and the posterior third ventricle make up the anterior wall of this region. In the lateral wall, we find the pulvinar, the crus of the fornix and the medial surface of the cerebral hemisphere. The floor of the pineal region is formed by the superior surface of the cerebellar vermis. The particular anatomical relationship of the pineal gland and the pineal region render the surgical approach difficult. 3. Data from the literature of the incidence for pineal tumours The incidence of pineal tumours is 0.4 to 1% of all intracranial adult tumours [2,3]. Jouvet reported an incidence of 1% [4] (Table 1). For Zhu, they represent less than 1% of all intracranial neoplasms [5]. For Chibbaro, they account for 0.6–0.9% of all brain tumours [6]. For Dahll, they represent 0.4% of all central nervous system tumours in adults [7]. Al-Hussaini reported 0.8% for all ages from the SEER data base [8]. In children, the incidence is higher, i.e. between 2.7 to 11% [2,3,8–12]. Raimondi and Tomita [13] reported an incidence of 9.4% corresponding to one of the most elevated incidences in the literature. For Villano and Shibui, the incidence varied between 3 to 5% among children [14,15]. For Bruce, pineal tumours represented 3 to 8% of all brain tumours in the paediatric age [16] whereas Wilson reported an incidence of 11% of all paediatric tumours considering lesions of the posterior part of the third ventricle [17]. The incidence reported by Wong from the Brain Tumour Registry of Japan was of 3.2% in children and adults [18].
For Dahll, the incidence was 2.8% in children up to 19 years of age [7]. There is no theoretical explanation for the more significant frequency of pineal tumours in children; it seems to be more an epidemiological factor. Russel and Rubinstein reported that pineal tumours represented 0.1 to 1% of intracranial growths and affirmed that they were much more frequent in children [19]. As regards pineal germ cell tumours that occur more frequently in adolescence one could evoke possible hormonal factors but with no scientific proof [20]. The peak incidence observed during adolescence and early adulthood suggests that endocrinological changes which occur during puberty may be involved in the awakening of dormant cells. Melatonin, the hormone of the pineal gland involved in the sleep pattern, interfering with follicle-stimulating luteinizing hormone release, may play a role in the activation of germ cell tumours within the pineal region [20].
4. Data from the literature regarding the incidence of pineal region tumours Pineal region tumours accounted for 0.6–0.9% in North America and Europe whereas they represented 3%–3.2% in Japan and in Southeast Asia and 3% in China [21] (Table 2). According to the centralized brain tumour registries the incidence of pineal tumours varies from 0.4 to 1% among adult patients [22]. These deep-seated tumours consisted in only 0.5% to 1% intracranial neoplasms in adults in different European and American series, with an unexplained higher incidence of 3.2 to 4% in the Japanese literature [23,24]. For Herrada–Pineda the incidence of pineal region tumours was between 3 and 8% [25]. The frequency in Japan is 5 times higher than in the Western countries [26] (CBTRJ, 2008). For Tseng pineal tumours represented 0.4–0.5 of intracranial lesions [27]. Shin reported a frequency of less than 1% for adults and between 3 and 8% in children [28]. Pineal region tumours accounted for 0.4 to 1% of all central nervous system tumours in adults [29] and the same the incidence of 0.4% in adults was reported by the CBTRUS [30]. Senapati reported an incidence of less than 1% in adults and from 3 to 8% in children [31]. Cuccia also reported an incidence of 0.4 to 1% in adults and 3 to 8% in children [32]. For Smith, pineal region tumours represented 3% to 8% of intracranial neoplasms in children [22] and Mandera reported an incidence of between 3 and 11% in children [29]. The same incidence of 2.8% in children up to 19 years of age was reported in the statistical report on brain tumours in the United States (CBTRUS 2000–2004, reported in 2008). These tumours are rare, consisting in less than 11% of all paediatric tumours, and approximately 60% of pineal region tumours were of germ cell origin [33]. Oi reported that the epidemiological characteristics of Japanese patients were completely different from those of Caucasian or even other Asian populations such as the Chinese [11,34] and confirmed that the patient population in Japan and Korea were almost identical [11,35]. Also, Konovalov reported a higher unexplained incidence of 3.2% in the Japanese literature [36].
5. Discussion The data reported in the literature are sometimes confusing concerning the incidence of pineal or pineal region tumours as well as in relation to other factors such as age, sex and racial origin. Concerning racial differences, recent studies have not been able to demonstrate this higher incidence as reported by Cheng and Oi
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Table 1 Review of the literature of pineal tumour incidence (* incidence of N/S = north and south, **=SEER report). L’incidence des tumeurs de la pinéale dans la littérature (*N/S = nord et sud; **=résultats SEER). Authors
Year
Rate of incidence (%)
Al-Hussaini Al-Hussaini Al-Hussaini** Bruce CBTRJ CBTRJ Chibbaro Cushing Dahll Dahll Hoffman Hoffman Jennings Jennings Jouvet Raimondi Russel Shibui Villano Villano Zhu L Wilson Wong
2009 2009 2009 1990 2003 2003 2012 1932 2010 2010 1994 1994 1985 1985 2000 1982 1971 2009 2008 2008 2011 2012 2011
0.5 2.7 0.8 3–8 0,4 2.8 0.6–0.9 2.7 0.4 2.8 3–8 0.4–1 0.4–1 3–8 1 9.4 0.1–1 3–5 3–5 0.4–1 <1 11 3.2
Adults
Children
N/S* America
+ + +
+ + + +
+ +
Europe
Asia
+ +
+ + +
+ + + + + + + +
+ + +
([34], [11]). In fact, on the contrary they show a similar incidence between Asian countries and United States ([37], [38]). This different incidence of pineal tumours in different ethnic populations does not have an explanation and recently a more equal rate between Western or Far Eastern countries was reported. This could be related to the more uniform way with which patients are managed with a more confirmed histological diagnosis [39]. Al-Hussaini reported a different incidence depending on age which represented 0.5% of all central nervous system tumours in adults, 1% in young adults (aged 20–34 years), 2.7% in children (aged 1–12 years) [8]. These authors reported the experience of the Surveillance Epidemiology and End Results (SEER) that provides population-based incidence and survival data for primary malignant tumours collected from 17 registries in the United States. In this study, 77,264 tumours were registered from 1975 to 2005 and of those 633 (0.8%) were pineal tumours: 75% males and 25% females. The median age for the cohort was 17 years (range 0–83 years) and 56% of cases were younger than 18 years at time of diagnosis.
+ + + + + + +
+ + + + + + + + + + + + + + + + + + +
According to this study, germ cell tumours (GCT) (335) and pineal parenchymal tumours (PPT) (185) were the most common subtypes and accounted for 89% of all pineal tumours. The cohort for 5-year overall survival was 65.1 + –2.1 years and the median survival time was 19.3 years. Factors influencing overall survival, i.e. female gender, age older than 18 years, non-GCT histological subtype and diagnosis before 1993 and no treatment with radiotherapy were all associated with a worse survival while the extent of surgical removal did not seem to affect worse survival. For patients not undergoing surgical tumour removal the 5-year overall survival was 70.7% and for patients treated surgically it was 67%. Concerning the histological subtypes for GCT (373 patients) the patients treated with radiotherapy had the best overall survival. For PPT, (187 tumours) these patients showed a worse survival than patients with other pineal tumour histology and the overall survival was only 47.2% with a median survival of 4.5 years. For these patients the analysis of different factors such as gender,
Table 2 Review of the literature of pineal region tumour incidence (*N/S = north and south). L’incidence des tumeurs de la région pinéale dans la littérature (*N/S = nord et sud). Author
Years
Rate of incidence %
Bruce CBTRUS CBTRUS Cuccia Cuccia Herrada-Pineda Jia Jia Konovalov Mandera Mandera Sano Senapati Senapati Shin Shin Smith B Smith B Tseng
1990 2008 2008 2006 2006 2013 2011 2011 2003 2011 2011 1998 2012 2012 1998 1998 2010 2010 2012
3–8 0.4 2.8 0.4–1 3–8 3–8 0.6–0.9 3–3.2 3.2 0.4–1 3–11 3.2–4 <1 3–8 <1 3–8 0.4–1 3–8 0.4–0.5
Adults
Children
N/S* America
+
+ + + + + + +
+ + + + + + + + + +
+ + + + +
Europe
Asia
+ + + +
+ +
+ + + + +
+ + + + + +
+ + +
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age, surgery and radiation therapy did not show any significant difference as regards survival. The SEER study produced evident arguments to establish that for pineal tumours the histological analysis permits to establish a good correlation for survival. The fact that surgical removal does not play an important role for survival can be explained by the fact that the most frequent tumours are GCT and they can be cured, in a large number of cases, by radiotherapy or chemotherapy associated with radiotherapy [40]. Sometimes a stereotactic or an endoscopic biopsy can be considered [11,18,41]. 6. Incidence of pineal tumours in France In France, a French Register for pineal tumours was created and has recorded all the pineal tumours treated in the country over the past twenty years. This register was also subsequently established in Lyon with French Government support in 2008 and now currently includes 540 additional cases of pineal tumours that were collected over a longer period of time. In Lyon, we continue to implement the Local Register for pineal tumours and since 1972 this Register has enrolled patients, which now includes 277 and can be considered as the offspring of the French Register. It is difficult to establish the exact incidence of pineal tumours in France but if we consider the French Brain Tumour Data Base that collected, between 2004 and 2008, new histological diagnosed primary central nervous system tumours, 25,756 cases, true pineal tumours represented 0.6% of cases but pineal gliomas were not considered for inclusion [42]. The pineal tumours from the French register, after histological revision, shows the following distribution: 27% PPT, 27% GCT, 17% gliomas, 8% papillary tumours, 7% pineal cysts and 1% primitive neuroectodermal tumours. Nineteen cases were excluded after rereading because the diagnosis was not confirmed. The true pineal tumours are represented by pinealocytomas (PC) (13%), pineal parenchyma tumours of intermediary differentiation (PTT-ID) (66%) and pinealoblastomas (21%). As regards the Lyon pineal tumour register, histological analysis shows the occurrence of 22% true pineal tumours, 28% GCT, 22% gliomas or exophytic gliomas, 3.6% papillary tumours of the pineal region and 11% of pineal cysts. PC represent 20% of true pineal tumours, 28% were pinealoblastomas (PB) and 55% were PPT-ID. Other lesions are represented by meningioma, metastasis, vascular or inflammatory lesions that represent more lesions of the pineal region than the pineal gland. There was no significant difference about the rate of incidence between the French Register and the Lyon Register The difference is further accentuated by other reported studies in literature: for Wong GCT represented 50–80% of cases, PC 1.2–5.6% of cases, PB 4.2–16.2% of cases and astrocytic gliomas 2.4–8.1% of cases [18]. For Chibbaro, GCT represented 20–37% of cases, true pineal tumours 22–27% of cases and gliomas 12–32% of cases and other lesions 12–32% of cases [6]. 7. Survival and Histology The therapeutic decisional tree depends on the anatomopathological classification and consequently it is important to know the true incidence of pineal tumours to guide the choice towards the best treatment and to improve the rate of cured patients. The survival rate is entirely related to the histology of lesions including the experience of the French Register. PCs are benign lesions, with no mitosis or positive immunostaining for neuron-specific enolase, rare in children, which can be cured with excellent results
by surgery alone. Radiotherapy for these lesions must be reserved only for particular cases [17] and should be considered with caution as reported by Fauchon [43]. In contrast, PBs generally have a bad prognosis in children and an age below three years is a very poor prognostic factor. They correspond to grade 4 of Jouvet’s classification and contain a high mitotic index and no or weak immunostaining [4]. For PBs, craniospinal irradiation is a prerequisite to achieve long-term survival. For PPT-ID, the histological determination of more aggressive subtypes suggests to strengthen the treatment and therefore improves the survival rate ([4]; [44]). Grade 2 corresponds to lobulated, diffuse or transitional PPT types with less than 10 mitoses per 10 fields. Grade 3 includes cases with less than 6 mitoses and negative or weak immunostaining, and cases with positive immunostaining and 6 or more mitoses [4]. For grade 2 or 3 PPT the series of Fauchon reported a significant difference in evolution: in grade 2 a risk of local recurrence and in grade 3 a significant risk of metastatic spread [44]. Germinomas can be cured with chemo or radiotherapy alone without the necessity of a direct complete tumour removal [14,37,45]. Concerning the factors influencing survival it seems to us that the statement suggesting that the extension of surgery does not affect survival has to be conditioned by a precise knowledge of the histological diagnosis. The new anatomopathological classification of Jouvet based on the architecture, the evaluation of mitotic figures and the immunostaining with filaments, has permitted the direction of treatment leaving surgery for benign lesions and selecting patients for radiotherapy or chemotherapy for more aggressive lesions. [4]. In other words the possibility to identify histological and biological markers of aggressiveness permits to reinforce the treatment especially for grade 2 PPT with a total or a partial surgical removal. Grade 3 PPT also requires craniospinal irradiation after a complete tumour removal [43,44,46]. The role of surgery could be better defined leading to complete removal in each case, when required, which is a necessary condition in order to achieve a low morbidity and mortality. It is clear that, except for true germinomas, that can be cured only with radiotherapy this strategy can also be programmed for gliomas or papillary tumours of the pineal gland, particularly in children where almost fifty per cent of pineal tumours are benign and consequently surgery alone can guarantee the cure of these patients.
8. Conclusion In conclusion, it seems useful to identify the incidence of pineal gland and pineal region tumours. The role of a register for these tumours is of paramount importance from all points of view but mainly for the improvement of patient care: the complete knowledge of a disease facilitates the reduction of the rate of morbidity and mortality, also favouring the improvement of the quality of survival. The French Register will permit to obtain an overview of statistics, treatment patterns and survival of pineal tumours. It will also permit the comparison with other database centres from other countries and represents an important instrument for the modern and multidisciplinary approach for this rare disease. Furthermore, it also improves the clinical and therapeutic evaluation of different protocols used. The better knowledge of this rare pathology will permit to ensure the optimal treatment improving quality of survival, incidence of sequelae and adapted strategy avoiding iatrogenic complications.
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Report 2013: Tumors of the pineal region
Incidence of pineal tumours. A review of the literature Incidence des tumeurs pinéales. Revue de la littérature C. Mottolese ∗ , A. Szathmari , P.-A. Beuriat Neurological and Neurosurgical Hospital « P. Wertheimer », Pediatric Neurosurgery E, 59, boulevard Pinel, 69677 Bron, France
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Article history: Received 10 April 2013 Received in revised form 13 January 2014 Accepted 24 January 2014 Available online xxx Keywords: Pineal tumours Incidence of pineal tumours Germ cell tumours Pineal gliomas
a b s t r a c t The knowledge of the incidence of pineal tumours is important not only for diagnostic care but also for its therapeutic programme. We reviewed the incidence of pineal tumours reported in literature in an attempt to establish if a difference existed between pineal gland tumours and the pineal region tumours as different authors use both expressions to indicate the same thing. The rate of frequency of these tumours is useful to guide the therapeutic choice for patients as the decisional tree is completely different for either germ cell tumours, pineal gland tumours or pineal gliomas and eventually papillary tumours of the pineal region. According to the French Register of pineal tumours, true pineal tumours represent: 27% pineal parenchymal tumours (PPT), 27% germ cell tumours, 17% gliomas, 8% papillary tumours. True pineal gland tumours are represented by: pineocytomas - (13%), pineal parenchymal tumours with intermediary differentiation PTT-ID - (66%) and pinealoblastomas - (21%). There was no statistical difference found between the French register and the Lyon series concerning histological diagnosis. It seemed to us important to discover its true incidence by comparing the data published in the literature and to stress the utility of the French Register for these uncommon tumours not only for recording new histological cases but also to document clinical symptomatology, therapeutic programmes, length of follow-up and clinical results for each patient treated. A better understanding of their natural history and improved evaluation of different treatments and their complications should contribute to improve clinical results. © 2014 Published by Elsevier Masson SAS.
r é s u m é Mots clés : Tumeurs de la pinéale Incidence des tumeurs de la pinéale Tumeurs germinales Gliomes pinéales
Il est important d’établir l’incidence des tumeurs propres de la glande pinéale et de la région pinéale. Le fait de connaître l’incidence de ces tumeurs peut aider d’un point de vue pratique à une meilleure prise en charge de celles-ci. La stratégie thérapeutique est différente selon qu’il s’agit d’une tumeur du parenchyme, d’une tumeur germinale ou d’une tumeur papillaire. L’étude des cas recensés par le Registre franc¸ais des tumeurs pinéales a mis en évidence que 27 % des cas sont des tumeurs du parenchyme pinéal, 27 % des cas des tumeurs germinales, 17 % des gliomes de la glande pinéale et 8 % des cas des tumeurs papillaires. Les tumeurs de la glande pinéale sont réparties en pinéalocytomes (13 %), tumeurs pinéales à différenciation intermédiaire (66 %) et pinéaloblastomes (21 %). Il n’y a pas de différences statistiques importantes en ce qui concerne la distribution anatomo-pathologique entre les chiffres du Registre franc¸ais et ceux de Lyon. La nécessité et l’importance d’un Registre pour ces tumeurs rares regroupant différents types histologiques et nécessitant différentes stratégies thérapeutiques, semblent donc évidentes pour le recensement des nouveaux cas histologiques, pour l’établissement des données cliniques, des protocoles thérapeutiques et pour la vérification de courbes de suivi et de résultats cliniques. Dans ce contexte, le Registre franc¸ais prend toute son importance, en particulier, parce qu’il permet la confrontation des études de ces tumeurs aux différentes expériences de la littérature. © 2014 Publie´ par Elsevier Masson SAS.
∗ Corresponding author. E-mail address: [email protected] (C. Mottolese). http://dx.doi.org/10.1016/j.neuchi.2014.01.005 0028-3770/© 2014 Published by Elsevier Masson SAS.
Please cite this article in press as: Mottolese C, et al. Incidence of pineal tumours. A review of the literature. Neurochirurgie (2014), http://dx.doi.org/10.1016/j.neuchi.2014.01.005
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1. Introduction The knowledge of the true incidence of pineal tumours and pineal region tumours is of great importance because different histological entities are represented and consequently for a particular tumour an adapted therapeutic programme has to be established. In other words, the histological diagnosis can condition the choice of surgical or complementary treatment except for the treatment of hydrocephaly. Generally, in the literature, when pineal or pineal region tumours are reported there is some mention of the incidence of different histological specimens that can develop in the pineal region. In order to define the true incidence of pineal tumours from that of the pineal region we were prompted to review various papers in the literature that reported the incidence of pineal and pineal region tumours. In the pineal tumours group, we have included true pineal tumours, germ cell tumours, pineal gliomas and papillary tumours of the pineal region that are considered the most frequent pineal tumours. 2. Anatomy of the pineal gland and pineal region The pineal gland develops in a deep-seated region, the pineal region, which is located in the posterior part of the incisural space [1]. The pineal gland belongs to the posterior part of the third ventricle and it is located between the posterior commissure at the top and the tectal plate below. The gland that is a small reddish brown structure has a size which varies between 10 and 14 mm. The pineal gland develops as a diverticulum in the diencephalic roof of the third ventricle and is attached to the posterior board with a stalk. The pineal region is surrounded by different structures that at the same time defines its boundaries: the roof, anterior wall, lateral wall and the floor of the posterior incisura. The roof of the pineal region is formed by the lower surface of the splenium of the corpus callosum, the hippocampal commissure and the crus of the fornix. The pineal body, the tectal plate and the posterior third ventricle make up the anterior wall of this region. In the lateral wall, we find the pulvinar, the crus of the fornix and the medial surface of the cerebral hemisphere. The floor of the pineal region is formed by the superior surface of the cerebellar vermis. The particular anatomical relationship of the pineal gland and the pineal region render the surgical approach difficult. 3. Data from the literature of the incidence for pineal tumours The incidence of pineal tumours is 0.4 to 1% of all intracranial adult tumours [2,3]. Jouvet reported an incidence of 1% [4] (Table 1). For Zhu, they represent less than 1% of all intracranial neoplasms [5]. For Chibbaro, they account for 0.6–0.9% of all brain tumours [6]. For Dahll, they represent 0.4% of all central nervous system tumours in adults [7]. Al-Hussaini reported 0.8% for all ages from the SEER data base [8]. In children, the incidence is higher, i.e. between 2.7 to 11% [2,3,8–12]. Raimondi and Tomita [13] reported an incidence of 9.4% corresponding to one of the most elevated incidences in the literature. For Villano and Shibui, the incidence varied between 3 to 5% among children [14,15]. For Bruce, pineal tumours represented 3 to 8% of all brain tumours in the paediatric age [16] whereas Wilson reported an incidence of 11% of all paediatric tumours considering lesions of the posterior part of the third ventricle [17]. The incidence reported by Wong from the Brain Tumour Registry of Japan was of 3.2% in children and adults [18].
For Dahll, the incidence was 2.8% in children up to 19 years of age [7]. There is no theoretical explanation for the more significant frequency of pineal tumours in children; it seems to be more an epidemiological factor. Russel and Rubinstein reported that pineal tumours represented 0.1 to 1% of intracranial growths and affirmed that they were much more frequent in children [19]. As regards pineal germ cell tumours that occur more frequently in adolescence one could evoke possible hormonal factors but with no scientific proof [20]. The peak incidence observed during adolescence and early adulthood suggests that endocrinological changes which occur during puberty may be involved in the awakening of dormant cells. Melatonin, the hormone of the pineal gland involved in the sleep pattern, interfering with follicle-stimulating luteinizing hormone release, may play a role in the activation of germ cell tumours within the pineal region [20].
4. Data from the literature regarding the incidence of pineal region tumours Pineal region tumours accounted for 0.6–0.9% in North America and Europe whereas they represented 3%–3.2% in Japan and in Southeast Asia and 3% in China [21] (Table 2). According to the centralized brain tumour registries the incidence of pineal tumours varies from 0.4 to 1% among adult patients [22]. These deep-seated tumours consisted in only 0.5% to 1% intracranial neoplasms in adults in different European and American series, with an unexplained higher incidence of 3.2 to 4% in the Japanese literature [23,24]. For Herrada–Pineda the incidence of pineal region tumours was between 3 and 8% [25]. The frequency in Japan is 5 times higher than in the Western countries [26] (CBTRJ, 2008). For Tseng pineal tumours represented 0.4–0.5 of intracranial lesions [27]. Shin reported a frequency of less than 1% for adults and between 3 and 8% in children [28]. Pineal region tumours accounted for 0.4 to 1% of all central nervous system tumours in adults [29] and the same the incidence of 0.4% in adults was reported by the CBTRUS [30]. Senapati reported an incidence of less than 1% in adults and from 3 to 8% in children [31]. Cuccia also reported an incidence of 0.4 to 1% in adults and 3 to 8% in children [32]. For Smith, pineal region tumours represented 3% to 8% of intracranial neoplasms in children [22] and Mandera reported an incidence of between 3 and 11% in children [29]. The same incidence of 2.8% in children up to 19 years of age was reported in the statistical report on brain tumours in the United States (CBTRUS 2000–2004, reported in 2008). These tumours are rare, consisting in less than 11% of all paediatric tumours, and approximately 60% of pineal region tumours were of germ cell origin [33]. Oi reported that the epidemiological characteristics of Japanese patients were completely different from those of Caucasian or even other Asian populations such as the Chinese [11,34] and confirmed that the patient population in Japan and Korea were almost identical [11,35]. Also, Konovalov reported a higher unexplained incidence of 3.2% in the Japanese literature [36].
5. Discussion The data reported in the literature are sometimes confusing concerning the incidence of pineal or pineal region tumours as well as in relation to other factors such as age, sex and racial origin. Concerning racial differences, recent studies have not been able to demonstrate this higher incidence as reported by Cheng and Oi
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Table 1 Review of the literature of pineal tumour incidence (* incidence of N/S = north and south, **=SEER report). L’incidence des tumeurs de la pinéale dans la littérature (*N/S = nord et sud; **=résultats SEER). Authors
Year
Rate of incidence (%)
Al-Hussaini Al-Hussaini Al-Hussaini** Bruce CBTRJ CBTRJ Chibbaro Cushing Dahll Dahll Hoffman Hoffman Jennings Jennings Jouvet Raimondi Russel Shibui Villano Villano Zhu L Wilson Wong
2009 2009 2009 1990 2003 2003 2012 1932 2010 2010 1994 1994 1985 1985 2000 1982 1971 2009 2008 2008 2011 2012 2011
0.5 2.7 0.8 3–8 0,4 2.8 0.6–0.9 2.7 0.4 2.8 3–8 0.4–1 0.4–1 3–8 1 9.4 0.1–1 3–5 3–5 0.4–1 <1 11 3.2
Adults
Children
N/S* America
+ + +
+ + + +
+ +
Europe
Asia
+ +
+ + +
+ + + + + + + +
+ + +
([34], [11]). In fact, on the contrary they show a similar incidence between Asian countries and United States ([37], [38]). This different incidence of pineal tumours in different ethnic populations does not have an explanation and recently a more equal rate between Western or Far Eastern countries was reported. This could be related to the more uniform way with which patients are managed with a more confirmed histological diagnosis [39]. Al-Hussaini reported a different incidence depending on age which represented 0.5% of all central nervous system tumours in adults, 1% in young adults (aged 20–34 years), 2.7% in children (aged 1–12 years) [8]. These authors reported the experience of the Surveillance Epidemiology and End Results (SEER) that provides population-based incidence and survival data for primary malignant tumours collected from 17 registries in the United States. In this study, 77,264 tumours were registered from 1975 to 2005 and of those 633 (0.8%) were pineal tumours: 75% males and 25% females. The median age for the cohort was 17 years (range 0–83 years) and 56% of cases were younger than 18 years at time of diagnosis.
+ + + + + + +
+ + + + + + + + + + + + + + + + + + +
According to this study, germ cell tumours (GCT) (335) and pineal parenchymal tumours (PPT) (185) were the most common subtypes and accounted for 89% of all pineal tumours. The cohort for 5-year overall survival was 65.1 + –2.1 years and the median survival time was 19.3 years. Factors influencing overall survival, i.e. female gender, age older than 18 years, non-GCT histological subtype and diagnosis before 1993 and no treatment with radiotherapy were all associated with a worse survival while the extent of surgical removal did not seem to affect worse survival. For patients not undergoing surgical tumour removal the 5-year overall survival was 70.7% and for patients treated surgically it was 67%. Concerning the histological subtypes for GCT (373 patients) the patients treated with radiotherapy had the best overall survival. For PPT, (187 tumours) these patients showed a worse survival than patients with other pineal tumour histology and the overall survival was only 47.2% with a median survival of 4.5 years. For these patients the analysis of different factors such as gender,
Table 2 Review of the literature of pineal region tumour incidence (*N/S = north and south). L’incidence des tumeurs de la région pinéale dans la littérature (*N/S = nord et sud). Author
Years
Rate of incidence %
Bruce CBTRUS CBTRUS Cuccia Cuccia Herrada-Pineda Jia Jia Konovalov Mandera Mandera Sano Senapati Senapati Shin Shin Smith B Smith B Tseng
1990 2008 2008 2006 2006 2013 2011 2011 2003 2011 2011 1998 2012 2012 1998 1998 2010 2010 2012
3–8 0.4 2.8 0.4–1 3–8 3–8 0.6–0.9 3–3.2 3.2 0.4–1 3–11 3.2–4 <1 3–8 <1 3–8 0.4–1 3–8 0.4–0.5
Adults
Children
N/S* America
+
+ + + + + + +
+ + + + + + + + + +
+ + + + +
Europe
Asia
+ + + +
+ +
+ + + + +
+ + + + + +
+ + +
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age, surgery and radiation therapy did not show any significant difference as regards survival. The SEER study produced evident arguments to establish that for pineal tumours the histological analysis permits to establish a good correlation for survival. The fact that surgical removal does not play an important role for survival can be explained by the fact that the most frequent tumours are GCT and they can be cured, in a large number of cases, by radiotherapy or chemotherapy associated with radiotherapy [40]. Sometimes a stereotactic or an endoscopic biopsy can be considered [11,18,41]. 6. Incidence of pineal tumours in France In France, a French Register for pineal tumours was created and has recorded all the pineal tumours treated in the country over the past twenty years. This register was also subsequently established in Lyon with French Government support in 2008 and now currently includes 540 additional cases of pineal tumours that were collected over a longer period of time. In Lyon, we continue to implement the Local Register for pineal tumours and since 1972 this Register has enrolled patients, which now includes 277 and can be considered as the offspring of the French Register. It is difficult to establish the exact incidence of pineal tumours in France but if we consider the French Brain Tumour Data Base that collected, between 2004 and 2008, new histological diagnosed primary central nervous system tumours, 25,756 cases, true pineal tumours represented 0.6% of cases but pineal gliomas were not considered for inclusion [42]. The pineal tumours from the French register, after histological revision, shows the following distribution: 27% PPT, 27% GCT, 17% gliomas, 8% papillary tumours, 7% pineal cysts and 1% primitive neuroectodermal tumours. Nineteen cases were excluded after rereading because the diagnosis was not confirmed. The true pineal tumours are represented by pinealocytomas (PC) (13%), pineal parenchyma tumours of intermediary differentiation (PTT-ID) (66%) and pinealoblastomas (21%). As regards the Lyon pineal tumour register, histological analysis shows the occurrence of 22% true pineal tumours, 28% GCT, 22% gliomas or exophytic gliomas, 3.6% papillary tumours of the pineal region and 11% of pineal cysts. PC represent 20% of true pineal tumours, 28% were pinealoblastomas (PB) and 55% were PPT-ID. Other lesions are represented by meningioma, metastasis, vascular or inflammatory lesions that represent more lesions of the pineal region than the pineal gland. There was no significant difference about the rate of incidence between the French Register and the Lyon Register The difference is further accentuated by other reported studies in literature: for Wong GCT represented 50–80% of cases, PC 1.2–5.6% of cases, PB 4.2–16.2% of cases and astrocytic gliomas 2.4–8.1% of cases [18]. For Chibbaro, GCT represented 20–37% of cases, true pineal tumours 22–27% of cases and gliomas 12–32% of cases and other lesions 12–32% of cases [6]. 7. Survival and Histology The therapeutic decisional tree depends on the anatomopathological classification and consequently it is important to know the true incidence of pineal tumours to guide the choice towards the best treatment and to improve the rate of cured patients. The survival rate is entirely related to the histology of lesions including the experience of the French Register. PCs are benign lesions, with no mitosis or positive immunostaining for neuron-specific enolase, rare in children, which can be cured with excellent results
by surgery alone. Radiotherapy for these lesions must be reserved only for particular cases [17] and should be considered with caution as reported by Fauchon [43]. In contrast, PBs generally have a bad prognosis in children and an age below three years is a very poor prognostic factor. They correspond to grade 4 of Jouvet’s classification and contain a high mitotic index and no or weak immunostaining [4]. For PBs, craniospinal irradiation is a prerequisite to achieve long-term survival. For PPT-ID, the histological determination of more aggressive subtypes suggests to strengthen the treatment and therefore improves the survival rate ([4]; [44]). Grade 2 corresponds to lobulated, diffuse or transitional PPT types with less than 10 mitoses per 10 fields. Grade 3 includes cases with less than 6 mitoses and negative or weak immunostaining, and cases with positive immunostaining and 6 or more mitoses [4]. For grade 2 or 3 PPT the series of Fauchon reported a significant difference in evolution: in grade 2 a risk of local recurrence and in grade 3 a significant risk of metastatic spread [44]. Germinomas can be cured with chemo or radiotherapy alone without the necessity of a direct complete tumour removal [14,37,45]. Concerning the factors influencing survival it seems to us that the statement suggesting that the extension of surgery does not affect survival has to be conditioned by a precise knowledge of the histological diagnosis. The new anatomopathological classification of Jouvet based on the architecture, the evaluation of mitotic figures and the immunostaining with filaments, has permitted the direction of treatment leaving surgery for benign lesions and selecting patients for radiotherapy or chemotherapy for more aggressive lesions. [4]. In other words the possibility to identify histological and biological markers of aggressiveness permits to reinforce the treatment especially for grade 2 PPT with a total or a partial surgical removal. Grade 3 PPT also requires craniospinal irradiation after a complete tumour removal [43,44,46]. The role of surgery could be better defined leading to complete removal in each case, when required, which is a necessary condition in order to achieve a low morbidity and mortality. It is clear that, except for true germinomas, that can be cured only with radiotherapy this strategy can also be programmed for gliomas or papillary tumours of the pineal gland, particularly in children where almost fifty per cent of pineal tumours are benign and consequently surgery alone can guarantee the cure of these patients.
8. Conclusion In conclusion, it seems useful to identify the incidence of pineal gland and pineal region tumours. The role of a register for these tumours is of paramount importance from all points of view but mainly for the improvement of patient care: the complete knowledge of a disease facilitates the reduction of the rate of morbidity and mortality, also favouring the improvement of the quality of survival. The French Register will permit to obtain an overview of statistics, treatment patterns and survival of pineal tumours. It will also permit the comparison with other database centres from other countries and represents an important instrument for the modern and multidisciplinary approach for this rare disease. Furthermore, it also improves the clinical and therapeutic evaluation of different protocols used. The better knowledge of this rare pathology will permit to ensure the optimal treatment improving quality of survival, incidence of sequelae and adapted strategy avoiding iatrogenic complications.
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Please cite this article in press as: Mottolese C, et al. Incidence of pineal tumours. A review of the literature. Neurochirurgie (2014), http://dx.doi.org/10.1016/j.neuchi.2014.01.005