- Email: [email protected]
Tumoral markers in tumors of the pineal region
G Model
ARTICLE IN PRESS
NEUCHI-616; No. of Pages 3
Neurochirurgie xxx (2014) xxx–xxx
Disponible en ligne sur
ScienceDirect www.sciencedirect.com
Report 2013: Tumors of the pineal region
Tumoral markers in tumors of the pineal region Marqueurs tumoraux de la région pinéale C. Faure-Conter Centre Léon-Bérard, 28, rue Laennec, 69008 Lyon, France
a r t i c l e
i n f o
Article history: Received 31 October 2013 Received in revised form 6 December 2013 Accepted 27 December 2013 Available online xxx Keywords: Tumoral markers Pineal tumor Germ cell tumor
a b s t r a c t In cases of pineal tumors, a germ cell tumor should always be suspected. As some of them are secreting tumors, tumoral markers (AFP and/or hGC) are an important part of the diagnostic process. Their positivity either in the serum and/or in the cerebrospinal fluid may lead to an accurate diagnosis, avoiding a potentially dangerous surgical biopsy. Follow-up of tumoral markers is useful during and after treatment in order to monitor response to chemotherapy or a remission status. © 2014 Elsevier Masson SAS. All rights reserved.
r é s u m é Mots clés : Marqueurs tumoraux Tumeur pinéale Tumeur germinale
Une tumeur germinale doit toujours être suspectée devant une tumeur de localisation pinéale. Certaines tumeurs germinales secrètent des marqueurs tumoraux (AFP et/ou hCG). Leur positivité dans le sérum et/ou le liquide cérébrospinal LCS permet d’éviter une documentation histologique potentiellement dangereuse, de s’assurer de la réponse au traitement et d’assurer le suivi post-thérapeutique. © 2014 Elsevier Masson SAS. Tous droits réservés.
1. Introduction
than 12 months and in adults, its seric concentration is less than 10 ng/mL. In premature babies, eutrophic newborn and infants less than 12 months, the level may be higher than this cut-off point, and the interpretation should take in account the reference charts that show progressive decrease with aging (Fig. 1). This is an important point as one may over diagnose a NGGCT. Sometimes, only the follow-up will allow decide whether or not there is an underlying tumor in an infant [3]. Some pathological states may also elevate these levels but usually at modest levels. Hemochromatosis, type 1 tyrosinemia, ataxia-telangiectasia, Fanconi’s anemia, cirrhosis, chronic hepatitis or exposure to phenytoin or methotrexate. Therefore, the laboratory investigations should include liver parameters in all patients to exclude hepatic disease. Other neoplastic conditions associated with elevated serum AFP include hepatoblastoma, hepatocellular carcinoma, pancreaticoblastoma and pancreatic, gastrointestinal, or bronchial adenocarcinomas. At least some cases of familial elevation of AFP have been reported, but as previously mentioned at modest levels, without any underlying disease [4]. HCG is a glycoproteic hormone that is physiologically produced by placental trophoblastic cells during pregnancy. It is composed of
Among tumoral markers (TM), few are specific enough to lead to an accurate diagnosis, and tumor sampling by biopsy or tumoral resection is then required, which is particularly the case for CA-125 and CEA (carcinoembryonic antigen) in breast and colorectal cancer respectively [1,2]. Nevertheless, tumor markers play a key role in the diagnostic process of pineal tumors. 2. Types of tumor markers TM investigated in pineal tumors are those of germ cell tumors (GCT). These TM are alpha fetoprotein (AFP), and human chorionic gonadotropin (HCG). AFP is a transport glycoprotein that is physiologically secreted initially by the yolk sac and then by the fetal liver. Its half-life is 5 to 7 days. Its synthesis is repressed at birth. In normal babies older
E-mail address: [email protected] http://dx.doi.org/10.1016/j.neuchi.2013.12.006 0028-3770/© 2014 Elsevier Masson SAS. All rights reserved.
Please cite this article in press as: Faure-Conter C. Tumoral markers in tumors of the pineal region. Neurochirurgie (2014), http://dx.doi.org/10.1016/j.neuchi.2013.12.006
G Model NEUCHI-616; No. of Pages 3
ARTICLE IN PRESS C. Faure-Conter / Neurochirurgie xxx (2014) xxx–xxx
2
using a spinal tap in cases of pineal region tumor, due to the risk of subsequent cerebral herniation. 4. Tumor markers and histological subtypes
Fig. 1. Average normal serum alpha fetoprotein (AFP) values for infants according to age. Taux sérique médian d’alpha-fœtoprotéine (AFP) chez l’enfant selon son âge.
2 subunits. The ␣ sub unit is shared with other hormones such as LH, FSH, TSH. The  subunit is specific. Under pathological conditions, HCG is a marker for placental tumors, fetal diseases and GCTs, as it is produced by trophoblastic components contained within these tumors. It is necessary to be aware of specificity and sensitivity of immunoassay methods used to determine HCG since it can be found as a dimer (= full molecule) or as fragments of it ( subunits). Terminology used in current oncological literature or in previously reported studies refers to “HCG”. However, the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) has established an unambiguous nomenclature [4,5]: • HCG or intact HCG: only assays the dimer HCG and measurements units are mUI/mL; • free  HCG: only assays the  free chain, which is biologically inactive; measurements units: ng/mL; • total HCG (former called “HCG”): that evaluates both linked intact HCG and free  HCG; its measurement is in units mUI/mL. The clinician should request both free -subunit or “free  HCG” and “total HCG”. At present, there are > 50 commercial kits for HCG around the world. It is crucial that each oncological center treating intra- and extracranial GCTs is aware of the potential and limits of the kits used in their own laboratory and be informed if the kit is able to detect  subunits (free or as a dimer), or only intact HCG or both. Moreover, appropriate preservation instructions and timing of samples must be observed for best detection of free  and dimer because the halflife is short (half-life of total HCG is 24 to 36 hours, and the free chain is 3 to 4 hours). If the test is performed following a prolonged stay after sampling, the levels could be underestimated. Apart from pregnant women, seric levels in children and adults are less than 7 mUI/mL and less than 0.1 ng/mL for total and free chain respectively. It should not be present in the cerebro-spinal fluid (CSF) of normal subjects. Other TM (CEA for example) are not useful in the diagnosis process of pineal tumor. 3. Sampling site Markers should be evaluated both in serum and in CSF. For unknown reasons, their level may be elevated exclusively in blood or in CSF, it is thus obligatory to obtain both results [6,7]. CSF is obtained either by lumbar puncture when there is no contraindication, and/or during endoscopic third ventriculostomy or shunting. One recent study suggest that ventricular CSF values might be inferior to lumbar CSF values [8]. However, one must be cautious when
GCTs are heterogeneous diseases that may contain various subtypes of tumors. Markers are specific for certain tumor types. Not all GCT show positive results. AFP is the marker of yolk sac tumors and HCG is the marker for choriocarcinoma. Pure germinomas (histologically equivalent to the testicular seminoma) may secrete some HCG (usually at modest levels), but no AFP: this type of germinoma has been considered by some groups as an intermediate prognosis [9]. Mixed tumors and embryonal carcinomas may also produce some marker secretion. Mature and immature teratomas contain no marker secretion. Any pineal tumor other than a GCT, such as pineal parenchymal tumor or glioma does not secrete AFP or total HCG. 5. Diagnostic process Tumor markers should be evaluated before any biopsy or surgery in cases of a pineal tumor. Indeed, those TM are specific enough to lead to an accurate diagnosis, if physiological or pathological situations lead to elevated AFP or HCG, and as described previously are ruled out [10]. The diagnostic process is described in Fig. 2. If AFP is increased in the serum or CSF, diagnosis of nongerminomatous germ cell tumor (NGGCT) can be established without histological confirmation. If HCG is increased, the tumor can be a germinoma or a non-NGGCT. By convention in the European protocol, if the total HCG level is above 50 mUI/mL, diagnosis of NGGCT is confirmed. In contrast, if the level is below 50, a biopsy should be performed to confirm the histological nature of the tumor (i.e. NGGCT or germinoma). It is crucial to distinguish a germinoma versus NGGCT, because sensitivity to treatment is very different. Germinomas are very chemo- and radiosensitive tumors but tend to disseminate through the ventricles, which requires adapted fields of radiation, including ventricular areas [11]. NGGCT require more intensive chemotherapy, surgical resection of any residue and more elevated irradiation doses [9,12]. In cases of negative markers, histological analysis is required. 6. Prognostic values of TM Levels of AFP and HCG are correlated with prognostic in intracranial [13] as in extracranial locations, and both in adults [14] and children [15]. Results of the GCT96 European protocol for intracranial GCT (not yet totally published) report that AFP level > 1000 ng/dL constitute an adverse prognosis factor. This group of patients is treated in the current protocol (SIOP/CNS GCT II), with more intensive chemotherapy. 7. Follow-up of GCT evolution with tumor markers While treating the patient, standard imaging usually shows progressive disease regression. Similarly, secreting tumors should be monitored by regular assessment of seric (and CSF) TM. Decline rate (i.e. time to markers normalization) might also be a prognostic factor. This has been reported in extracranial adult GCT [16,17] and more recently in intracranial GCT [18]. Most often, decline of markers parallels volume diminution. It may happen that TM decrease while tumor volume increases: this situation is usually secondary to a growing teratoma; all sensitive components have
Please cite this article in press as: Faure-Conter C. Tumoral markers in tumors of the pineal region. Neurochirurgie (2014), http://dx.doi.org/10.1016/j.neuchi.2013.12.006
G Model NEUCHI-616; No. of Pages 3
ARTICLE IN PRESS C. Faure-Conter / Neurochirurgie xxx (2014) xxx–xxx
3
Pineal Tumor
Evaluaon of TM hCG> 50 mUI/ml or raised AFP
hCG< 50 mUI/ml and normal AFP
Biopsy
No biopsy
Non germinoma
Pure Germinoma
Non GCT
Disseminaon ? and specific treament Fig. 2. Decision tree for pineal tumor. Arbre décisionnel de prise en charge pour les tumeurs pinéales.
disappeared, leaving an insensitive compartment, i.e. a teratoma that grows independently [19]. When treatment has ended, a regular follow-up of TM and imaging is necessary in order to detect possible early progression. Ideally, TM determination should always be performed at the same institution to allow relevant comparisons. 8. Conclusions Always suspect a GCT if a pineal tumor is detected, and always request TM since they are a major component of the decision tree (Fig. 2). Both seric and CSF levels should be requested. Follow-up of TM during and after treatment allows early detection of any recurrence. References [1] Basuyau JP, Blanc-Vincent MP, Bidart JM, SOR Working Group, et al. [Standards, Options and Recommendations (SOR) for tumor markers in breast cancer]. Bull Cancer 2000;87:723–37. [2] Eche N, Pichon MF, Quillien V, et al. [Standards, options and recommendations for tumor markers in colorectal cancer]. Bull Cancer 2001;88:1177–206. [3] Wu JT, Book L, Sudar K. Serum alpha fetoprotein (AFP) levels in normal infants. Pediatr Res 1981;15:50–2. [4] Schneider DT, Calaminus G, Gobel U. Diagnostic value of alpha 1-fetoprotein and beta-human chorionic gonadotropin in infancy and childhood. Pediatr Hematol Oncol 2001;18:11–26. [5] Bristow A, Berger P, Bidart JM, et al. Establishment, value assignment, and characterization of new WHO reference reagents for six molecular forms of human chorionic gonadotropin. Clin Chem 2005;51:177–82. [6] Allen J, Chacko J, Donahue B, et al. Diagnostic sensitivity of serum and lumbar CSF bHCG in newly diagnosed CNS germinoma. Pediatr Blood Cancer 2012;59:1180–2. [7] Qaddoumi I, Sane M, Li S, et al. Diagnostic utility and correlation of tumor markers in the serum and cerebrospinal fluid of children with intracranial germ cell tumors. Childs Nerv Syst 2012;28:1017–24.
[8] Legault G, Allen JC. Potential role of ventricular tumor markers in CNS germ cell tumors. Pediatr Blood Cancer 2013;60:1647–50. [9] Bouffet E, Baranzelli MC, Patte C, Société franc¸aise d’oncologie pédiatrique, et al. Combined treatment modality for intracranial germinomas: results of a multicentre SFOP experience. Br J Cancer 1999;79:1199– 204. [10] Allen JC, Nisselbaum J, Epstein F, et al. Alphafetoprotein and human chorionic gonadotropin determination in cerebrospinal fluid. An aid to the diagnosis and management of intracranial germ-cell tumors. J Neurosurg 1979;51: 368–74. [11] Alapetite C, Brisse H, Patte C, et al. Pattern of relapse and outcome of nonmetastatic germinoma patients treated with chemotherapy and limited field radiation: the SFOP experience. Neurooncol 2010;12:1318–25. [12] Matsutani M, Sano K, Takakura K, et al. Combined treatment with chemotherapy and radiation therapy for intracranial germ cell tumors. Childs Nerv Syst 1998;14:59–62. [13] Kim A, Ji L, Balmaceda C, et al. The prognostic value of tumor markers in newly diagnosed patients with primary central nervous system germ cell tumors. Pediatr Blood Cancer 2008;51:768–73. [14] International Germ Cell Cancer Collaborative Group. International Germ Cell Consensus Classification: a prognostic factor-based staging system for metastatic germ cell cancers. J Clin Oncol 1997;15:594–603. [15] Baranzelli MC, Kramar A, Bouffet E, et al. Prognostic factors in children with localized malignant nonseminomatous germ cell tumors. J Clin Oncol 1999;17:1212–8. [16] Fizazi K, Culine S, Kramar A, et al. Early predicted time to normalization of tumor markers predicts outcome in poor-prognosis nonseminomatous germ cell tumors. J Clin Oncol 2004;22:3868–76. [17] Mazumdar M, Bajorin DF, Bacik J, et al. Predicting outcome to chemotherapy in patients with germ cell tumors: the value of the rate of decline of human chorionic gonadotrophin and alpha-fetoprotein during therapy. J Clin Oncol 2001;19:2534–41. [18] Kawaguchi T, Kumabe T, Kanamori M, et al. Logarithmic decrease of serum alpha-fetoprotein or human chorionic gonadotropin in response to chemotherapy can distinguish a subgroup with better prognosis among highly malignant intracranial non-germinomatous germ cell tumors. J Neurooncol 2011;104:779–87. [19] O’Callaghan AM, Katapodis O, Ellison DW, et al. The growing teratoma syndrome in a nongerminomatous germ cell tumor of the pineal gland: a case report and review. Cancer 1997;80:942–7.
Please cite this article in press as: Faure-Conter C. Tumoral markers in tumors of the pineal region. Neurochirurgie (2014), http://dx.doi.org/10.1016/j.neuchi.2013.12.006
ARTICLE IN PRESS
NEUCHI-616; No. of Pages 3
Neurochirurgie xxx (2014) xxx–xxx
Disponible en ligne sur
ScienceDirect www.sciencedirect.com
Report 2013: Tumors of the pineal region
Tumoral markers in tumors of the pineal region Marqueurs tumoraux de la région pinéale C. Faure-Conter Centre Léon-Bérard, 28, rue Laennec, 69008 Lyon, France
a r t i c l e
i n f o
Article history: Received 31 October 2013 Received in revised form 6 December 2013 Accepted 27 December 2013 Available online xxx Keywords: Tumoral markers Pineal tumor Germ cell tumor
a b s t r a c t In cases of pineal tumors, a germ cell tumor should always be suspected. As some of them are secreting tumors, tumoral markers (AFP and/or hGC) are an important part of the diagnostic process. Their positivity either in the serum and/or in the cerebrospinal fluid may lead to an accurate diagnosis, avoiding a potentially dangerous surgical biopsy. Follow-up of tumoral markers is useful during and after treatment in order to monitor response to chemotherapy or a remission status. © 2014 Elsevier Masson SAS. All rights reserved.
r é s u m é Mots clés : Marqueurs tumoraux Tumeur pinéale Tumeur germinale
Une tumeur germinale doit toujours être suspectée devant une tumeur de localisation pinéale. Certaines tumeurs germinales secrètent des marqueurs tumoraux (AFP et/ou hCG). Leur positivité dans le sérum et/ou le liquide cérébrospinal LCS permet d’éviter une documentation histologique potentiellement dangereuse, de s’assurer de la réponse au traitement et d’assurer le suivi post-thérapeutique. © 2014 Elsevier Masson SAS. Tous droits réservés.
1. Introduction
than 12 months and in adults, its seric concentration is less than 10 ng/mL. In premature babies, eutrophic newborn and infants less than 12 months, the level may be higher than this cut-off point, and the interpretation should take in account the reference charts that show progressive decrease with aging (Fig. 1). This is an important point as one may over diagnose a NGGCT. Sometimes, only the follow-up will allow decide whether or not there is an underlying tumor in an infant [3]. Some pathological states may also elevate these levels but usually at modest levels. Hemochromatosis, type 1 tyrosinemia, ataxia-telangiectasia, Fanconi’s anemia, cirrhosis, chronic hepatitis or exposure to phenytoin or methotrexate. Therefore, the laboratory investigations should include liver parameters in all patients to exclude hepatic disease. Other neoplastic conditions associated with elevated serum AFP include hepatoblastoma, hepatocellular carcinoma, pancreaticoblastoma and pancreatic, gastrointestinal, or bronchial adenocarcinomas. At least some cases of familial elevation of AFP have been reported, but as previously mentioned at modest levels, without any underlying disease [4]. HCG is a glycoproteic hormone that is physiologically produced by placental trophoblastic cells during pregnancy. It is composed of
Among tumoral markers (TM), few are specific enough to lead to an accurate diagnosis, and tumor sampling by biopsy or tumoral resection is then required, which is particularly the case for CA-125 and CEA (carcinoembryonic antigen) in breast and colorectal cancer respectively [1,2]. Nevertheless, tumor markers play a key role in the diagnostic process of pineal tumors. 2. Types of tumor markers TM investigated in pineal tumors are those of germ cell tumors (GCT). These TM are alpha fetoprotein (AFP), and human chorionic gonadotropin (HCG). AFP is a transport glycoprotein that is physiologically secreted initially by the yolk sac and then by the fetal liver. Its half-life is 5 to 7 days. Its synthesis is repressed at birth. In normal babies older
E-mail address: [email protected] http://dx.doi.org/10.1016/j.neuchi.2013.12.006 0028-3770/© 2014 Elsevier Masson SAS. All rights reserved.
Please cite this article in press as: Faure-Conter C. Tumoral markers in tumors of the pineal region. Neurochirurgie (2014), http://dx.doi.org/10.1016/j.neuchi.2013.12.006
G Model NEUCHI-616; No. of Pages 3
ARTICLE IN PRESS C. Faure-Conter / Neurochirurgie xxx (2014) xxx–xxx
2
using a spinal tap in cases of pineal region tumor, due to the risk of subsequent cerebral herniation. 4. Tumor markers and histological subtypes
Fig. 1. Average normal serum alpha fetoprotein (AFP) values for infants according to age. Taux sérique médian d’alpha-fœtoprotéine (AFP) chez l’enfant selon son âge.
2 subunits. The ␣ sub unit is shared with other hormones such as LH, FSH, TSH. The  subunit is specific. Under pathological conditions, HCG is a marker for placental tumors, fetal diseases and GCTs, as it is produced by trophoblastic components contained within these tumors. It is necessary to be aware of specificity and sensitivity of immunoassay methods used to determine HCG since it can be found as a dimer (= full molecule) or as fragments of it ( subunits). Terminology used in current oncological literature or in previously reported studies refers to “HCG”. However, the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) has established an unambiguous nomenclature [4,5]: • HCG or intact HCG: only assays the dimer HCG and measurements units are mUI/mL; • free  HCG: only assays the  free chain, which is biologically inactive; measurements units: ng/mL; • total HCG (former called “HCG”): that evaluates both linked intact HCG and free  HCG; its measurement is in units mUI/mL. The clinician should request both free -subunit or “free  HCG” and “total HCG”. At present, there are > 50 commercial kits for HCG around the world. It is crucial that each oncological center treating intra- and extracranial GCTs is aware of the potential and limits of the kits used in their own laboratory and be informed if the kit is able to detect  subunits (free or as a dimer), or only intact HCG or both. Moreover, appropriate preservation instructions and timing of samples must be observed for best detection of free  and dimer because the halflife is short (half-life of total HCG is 24 to 36 hours, and the free chain is 3 to 4 hours). If the test is performed following a prolonged stay after sampling, the levels could be underestimated. Apart from pregnant women, seric levels in children and adults are less than 7 mUI/mL and less than 0.1 ng/mL for total and free chain respectively. It should not be present in the cerebro-spinal fluid (CSF) of normal subjects. Other TM (CEA for example) are not useful in the diagnosis process of pineal tumor. 3. Sampling site Markers should be evaluated both in serum and in CSF. For unknown reasons, their level may be elevated exclusively in blood or in CSF, it is thus obligatory to obtain both results [6,7]. CSF is obtained either by lumbar puncture when there is no contraindication, and/or during endoscopic third ventriculostomy or shunting. One recent study suggest that ventricular CSF values might be inferior to lumbar CSF values [8]. However, one must be cautious when
GCTs are heterogeneous diseases that may contain various subtypes of tumors. Markers are specific for certain tumor types. Not all GCT show positive results. AFP is the marker of yolk sac tumors and HCG is the marker for choriocarcinoma. Pure germinomas (histologically equivalent to the testicular seminoma) may secrete some HCG (usually at modest levels), but no AFP: this type of germinoma has been considered by some groups as an intermediate prognosis [9]. Mixed tumors and embryonal carcinomas may also produce some marker secretion. Mature and immature teratomas contain no marker secretion. Any pineal tumor other than a GCT, such as pineal parenchymal tumor or glioma does not secrete AFP or total HCG. 5. Diagnostic process Tumor markers should be evaluated before any biopsy or surgery in cases of a pineal tumor. Indeed, those TM are specific enough to lead to an accurate diagnosis, if physiological or pathological situations lead to elevated AFP or HCG, and as described previously are ruled out [10]. The diagnostic process is described in Fig. 2. If AFP is increased in the serum or CSF, diagnosis of nongerminomatous germ cell tumor (NGGCT) can be established without histological confirmation. If HCG is increased, the tumor can be a germinoma or a non-NGGCT. By convention in the European protocol, if the total HCG level is above 50 mUI/mL, diagnosis of NGGCT is confirmed. In contrast, if the level is below 50, a biopsy should be performed to confirm the histological nature of the tumor (i.e. NGGCT or germinoma). It is crucial to distinguish a germinoma versus NGGCT, because sensitivity to treatment is very different. Germinomas are very chemo- and radiosensitive tumors but tend to disseminate through the ventricles, which requires adapted fields of radiation, including ventricular areas [11]. NGGCT require more intensive chemotherapy, surgical resection of any residue and more elevated irradiation doses [9,12]. In cases of negative markers, histological analysis is required. 6. Prognostic values of TM Levels of AFP and HCG are correlated with prognostic in intracranial [13] as in extracranial locations, and both in adults [14] and children [15]. Results of the GCT96 European protocol for intracranial GCT (not yet totally published) report that AFP level > 1000 ng/dL constitute an adverse prognosis factor. This group of patients is treated in the current protocol (SIOP/CNS GCT II), with more intensive chemotherapy. 7. Follow-up of GCT evolution with tumor markers While treating the patient, standard imaging usually shows progressive disease regression. Similarly, secreting tumors should be monitored by regular assessment of seric (and CSF) TM. Decline rate (i.e. time to markers normalization) might also be a prognostic factor. This has been reported in extracranial adult GCT [16,17] and more recently in intracranial GCT [18]. Most often, decline of markers parallels volume diminution. It may happen that TM decrease while tumor volume increases: this situation is usually secondary to a growing teratoma; all sensitive components have
Please cite this article in press as: Faure-Conter C. Tumoral markers in tumors of the pineal region. Neurochirurgie (2014), http://dx.doi.org/10.1016/j.neuchi.2013.12.006
G Model NEUCHI-616; No. of Pages 3
ARTICLE IN PRESS C. Faure-Conter / Neurochirurgie xxx (2014) xxx–xxx
3
Pineal Tumor
Evaluaon of TM hCG> 50 mUI/ml or raised AFP
hCG< 50 mUI/ml and normal AFP
Biopsy
No biopsy
Non germinoma
Pure Germinoma
Non GCT
Disseminaon ? and specific treament Fig. 2. Decision tree for pineal tumor. Arbre décisionnel de prise en charge pour les tumeurs pinéales.
disappeared, leaving an insensitive compartment, i.e. a teratoma that grows independently [19]. When treatment has ended, a regular follow-up of TM and imaging is necessary in order to detect possible early progression. Ideally, TM determination should always be performed at the same institution to allow relevant comparisons. 8. Conclusions Always suspect a GCT if a pineal tumor is detected, and always request TM since they are a major component of the decision tree (Fig. 2). Both seric and CSF levels should be requested. Follow-up of TM during and after treatment allows early detection of any recurrence. References [1] Basuyau JP, Blanc-Vincent MP, Bidart JM, SOR Working Group, et al. [Standards, Options and Recommendations (SOR) for tumor markers in breast cancer]. Bull Cancer 2000;87:723–37. [2] Eche N, Pichon MF, Quillien V, et al. [Standards, options and recommendations for tumor markers in colorectal cancer]. Bull Cancer 2001;88:1177–206. [3] Wu JT, Book L, Sudar K. Serum alpha fetoprotein (AFP) levels in normal infants. Pediatr Res 1981;15:50–2. [4] Schneider DT, Calaminus G, Gobel U. Diagnostic value of alpha 1-fetoprotein and beta-human chorionic gonadotropin in infancy and childhood. Pediatr Hematol Oncol 2001;18:11–26. [5] Bristow A, Berger P, Bidart JM, et al. Establishment, value assignment, and characterization of new WHO reference reagents for six molecular forms of human chorionic gonadotropin. Clin Chem 2005;51:177–82. [6] Allen J, Chacko J, Donahue B, et al. Diagnostic sensitivity of serum and lumbar CSF bHCG in newly diagnosed CNS germinoma. Pediatr Blood Cancer 2012;59:1180–2. [7] Qaddoumi I, Sane M, Li S, et al. Diagnostic utility and correlation of tumor markers in the serum and cerebrospinal fluid of children with intracranial germ cell tumors. Childs Nerv Syst 2012;28:1017–24.
[8] Legault G, Allen JC. Potential role of ventricular tumor markers in CNS germ cell tumors. Pediatr Blood Cancer 2013;60:1647–50. [9] Bouffet E, Baranzelli MC, Patte C, Société franc¸aise d’oncologie pédiatrique, et al. Combined treatment modality for intracranial germinomas: results of a multicentre SFOP experience. Br J Cancer 1999;79:1199– 204. [10] Allen JC, Nisselbaum J, Epstein F, et al. Alphafetoprotein and human chorionic gonadotropin determination in cerebrospinal fluid. An aid to the diagnosis and management of intracranial germ-cell tumors. J Neurosurg 1979;51: 368–74. [11] Alapetite C, Brisse H, Patte C, et al. Pattern of relapse and outcome of nonmetastatic germinoma patients treated with chemotherapy and limited field radiation: the SFOP experience. Neurooncol 2010;12:1318–25. [12] Matsutani M, Sano K, Takakura K, et al. Combined treatment with chemotherapy and radiation therapy for intracranial germ cell tumors. Childs Nerv Syst 1998;14:59–62. [13] Kim A, Ji L, Balmaceda C, et al. The prognostic value of tumor markers in newly diagnosed patients with primary central nervous system germ cell tumors. Pediatr Blood Cancer 2008;51:768–73. [14] International Germ Cell Cancer Collaborative Group. International Germ Cell Consensus Classification: a prognostic factor-based staging system for metastatic germ cell cancers. J Clin Oncol 1997;15:594–603. [15] Baranzelli MC, Kramar A, Bouffet E, et al. Prognostic factors in children with localized malignant nonseminomatous germ cell tumors. J Clin Oncol 1999;17:1212–8. [16] Fizazi K, Culine S, Kramar A, et al. Early predicted time to normalization of tumor markers predicts outcome in poor-prognosis nonseminomatous germ cell tumors. J Clin Oncol 2004;22:3868–76. [17] Mazumdar M, Bajorin DF, Bacik J, et al. Predicting outcome to chemotherapy in patients with germ cell tumors: the value of the rate of decline of human chorionic gonadotrophin and alpha-fetoprotein during therapy. J Clin Oncol 2001;19:2534–41. [18] Kawaguchi T, Kumabe T, Kanamori M, et al. Logarithmic decrease of serum alpha-fetoprotein or human chorionic gonadotropin in response to chemotherapy can distinguish a subgroup with better prognosis among highly malignant intracranial non-germinomatous germ cell tumors. J Neurooncol 2011;104:779–87. [19] O’Callaghan AM, Katapodis O, Ellison DW, et al. The growing teratoma syndrome in a nongerminomatous germ cell tumor of the pineal gland: a case report and review. Cancer 1997;80:942–7.
Please cite this article in press as: Faure-Conter C. Tumoral markers in tumors of the pineal region. Neurochirurgie (2014), http://dx.doi.org/10.1016/j.neuchi.2013.12.006