Ganglioneuroblastoma During Pregnancy – Case Report

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Rare case of ganglioneuroblastoma during pregnancy – case report

Abstract

Ganglioneuroblastoma is a very rare tumor, especially in pregnancy. So far the association between this tumor and pregnancy has not been reported. We present a case of ganglioneuroblastoma relapse at a 3rd trimester pregnant woman.

Neurological symptoms developed late, increased by the effects of pregnancy on the brain tumor.

Therapeutic management in this case represents a medical dilemma regarding mode setting and timing of delivery, taking into account the maternal-fetal risk-benefit. In this case caesarean section under general anesthesia was settled, with the need of postpartum brain tumor excision.

Keywords: ganglioneuroblastoma, pregnancy, treatment, caesarean section

Introduction

Ganglioneuroblastoma is a neuroblastic tumor containing malignant elements characteristic to neuroblastoma and benign elements found in ganglioneurinoma (1).

Intracranial tumors are extremely rare in pregnancy (2). By their rarity and their diagnosis in the last trimester of pregnancy, intracranial tumors have an increased risk of maternal and fetal morbidity and mortality. Cranial tumors tend to increase and become symptomatic in the last trimester of pregnancy, the causes not being entirely known.

Therefore any woman with an existing neurological condition should consult her obstetrician and her neurologist before she becomes pregnant (3).

Management of these cases should evaluate whether the mother’s and the fetus’s lives are threatened. A multidisciplinary team recommends the optimal timing for the termination of pregnancy, as determined by the fetus maturity and mother’s neurological condition (4).

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The present study reports one case of pregnant women in the third trimester with ganglioneuroblastoma. The patient underwent caesarean section under general anesthesia at 36 weeks gestation with favorable postoperative evolution. So far, there are no well-established protocols regarding the management of intracranial tumors (especially ganglioneuroblastoma) in pregnant women.

Case report

I.A., 20-year-old woman, G1P1L0, was admitted to our hospital due to weak, irregular uterine contractions in her 36th week of gestation. Patient’s history: in 2005 the patient was diagnosed with right parietal lobe ganglioneuroblastoma. She had undergone surgery followed by radiochemotherapy and anticonvulsive therapy with phenytoin for about one year with favorable outcome. Six years following resection, the patient had no radiologic recurrence.

The pregnant woman was taken out by a gynecologist in the first trimester of pregnancy, with the usual analyzes of pregnancy, ultrasound and regular prenatal checkups without objective neurological signs until the 3rd trimester of pregnancy.

Therapeutic attitude assumed identification of neurological symptoms in order to determine the optimal treatment, maintaining a low fetal risk and continuing uncomplicated pregnancy until birth.

Methods

Investigation protocol included routine tests and imaging tests. Neurological examination revealed vestibular syndrome and nystagmus which recommended contrast MRI.

MRI conclusions:

In the right parietal lobe, postcentral, viewed a well-shaped image of 32mm in diameter, nongadolinium-enhanced, sequel looking. An area of oedema with irregular outline in white matter was surrounding it. In the right temporal lobe, adjacent to the sylvian seizure, in hyposignal T2 image showed a nodular-shaped tumor of about 7mm in diameter with discrete central heterogenity (gadolinium-enhanced). No perilesional oedema. Ventricular system located on the midline.

MRI based neurosurgical consultation has determined that the tumor was operable and stated the need of postpartum surgery (excision of the brain tumor).

All fetal biometric parameters studied were below the 10th percentile for gestational age, showing a linear decrease with gestation until the end of pregnancy. The difference between menstrual age and gestational age determined by ultrasound was 3 weeks and 3 days. Estimated fetal weight was 2420 g, which placed the infant in the 6th percentile. The amniotic fluid index was 7.5 cm, confirming the diagnosis of IUGR.

The patient had received dexamethasone treatment with double purpose: fetal lung maturation and reduced perilesional cerebral oedema in order to decrease focal neurological symptoms.

The association between IUGR, repeated variable cardiotocography decelerations and brain tumor recurrence with emphasized neurological symptoms imposed urgent caesarean section.

Medical committee composed of obstetrician, anesthesiologist, neurosurgeon and neonatologist decided caesarean section under general anesthesia, which was performed 5 days after the admission of the patient.

Results

A 20 year-old patient, I.A., known with operated and radiochemotreated ganglioneuroblastoma eight years earliar, with ongoing pregnancy (36 weeks) was admitted to our clinic for weak uterine contractions and associated neurological symptoms (vestibular syndrome, nystagmus, slightly right motor deficit). She followed a protocol of blood tests, imaging and interdisciplinary consultations establishing the diagnosis of brain tumor, possible relapse of old pathology. Fetal biometry measurements and fetal biological parameters objectified the existence of fetal distress risk of premature birth or miscarriage. Those set the need for preoperative corticosteroid therapy (Dexamethasone) for lung maturation and perilesional brain oedema control and emergency caesarean under general anesthesia.

Caesarean section was performed 5 days after admission, without early nor late intraoperative and postoperative complications.

It resulted an unique live female newborn, weighing 2670g, 9 Apgar, with physiological vital functions, not requiring special follow-up.

Recovery of the mother was complication-free with persistent, constant postoperative neurological symptoms.

When discharged, the patient was recommended ambulatory neurosurgical exam to establish the opportunity of surgery targeting the brain tumor.

Discussions

Ganglioneuroblastoma is a tumor of the sympathetic nervous system that arises from primitive sympathogonia and is composed of both mature gangliocytes and immature neuroblasts and has intermediate malignant potential (5). These tumors are rare. They occur in fewer than five out of one million children each year (6). Ganglioneuroblastomas are extremely rare in adults, with only about 50 cases documented in people over the age of 20, and only five cases observed in the adult brain (7). There are no reports of ganglioneuroblastoma presenting during pregnancy in medical literature (8).

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Objectification of brain tumor by contrast MRI was necessary to establish the subsequent therapeutic management, although in literature there are “not enough studies to determine the safe use of contrast in pregnancy (9). MRI is probably the imaging diagnostic procedure of choice and should be performed when a brain tumor is suspected (10).

Before pregnancy the patient was declared cured, as no clinical nor radiological tumor relapse existed for six years. It is likely that pregnancy-induced changes have a tumorigenic effect, due to several factors such as fluid retention, increased blood volume and hormonal changes (11). Pregnancy is an aggravating factor for brain tumours on which it acts by three mechanisms: acceleration of tumor growth, increase of peritumoral oedema and the immunotolerance to foreign tissue antigens that is proper to pregnancy (12). Normal physiological changes during the pregnancy, such as increased levels of gonadotropins and augmented fluid volume status may accelerate the growth of some types of brain tumors (13).

The combination of oligohydramnios and IUGR portends a less favorable outcome, and early delivery should be considered (14). Treatment of brain tumor in pregnancy requires an integrated multidisciplinary approach, which includes neurosurgery, ophthalmology, radiology, obstetrics, neonatal pediatrics (15).

Indication for type of delivery is controversial. The best moment to recommend the craniotomy and the neurosurgical removal of the tumor will depend of the mother’s neurological condition, the histological tumor type as well as the gestational age. In a study published in 2011, performed on 10 patients with brain tumors diagnosed during pregnancy, prior to craniotomy, five patients had caesarean sections, two others had vaginal deliveries, in three patients the delivery took place after the brain tumor treatment(16).

The caesarean section was made under general anesthesia. Studies have shown that general anesthesia remains safe and dependable for operative delivery in parturients with intracranial tumor. Tracheal intubation allows maternal hyperventilation thereby controlling raised intracranial pressure. Hemodynamic stability is readily achieved to maintain cerebral perfusion (17).

Conclusions

Ganglioneuroblastoma is a rare brain tumor in childhood, and appears exceptionally in pregnant women.

Pregnancy and brain tumor have mutual negative effect on the patient.

Brain tumors that develop in pregnant women have to be diagnosed and assessed through MRI, although the effect of gadolinium contrast on the pregnancy is yet unknown and needs further medical studies.

The order of obstetrical an neurosurgical treatment of pregnant women with brain tumors requires an integrated multidisciplinary approach, including neurosurgery, radiology, obstetrics, neonatal pediatrics which have to assess all maternal-fetal risks and benefits.

Lack of brain tumor reccurence 6 years after currative neurosurgical treatment was not enough to establish that the patient was cured. The patient suffered a brain tumor relapse 8 years after brain surgery probably due to metabolic and hormonal changes induced by pregnancy.

References

1.Robertson H.E. Das Ganglioneuroblastom ein besonederer Typus im System der Neurome. Virchows Arch [Pathol Anat]. 1915;63: 147-168

2. Pavlidis NA. Coexistence of pregnancy and malignancy. The Oncologist 2002;7: 279-87.

3. Carmel Armon, Stephen A Berman. Neurologic Disease and Pregnancy. Medscape reference; 8 nov 2012

4. Ducray F, Colin P, Cartalat-Carel S, et al. Management of malignant gliomas diagnosed during pregnancy. Rev Neurol (Paris) 2006;162: 322–9.

5. Lonergan GJ, Schwab CM, Suarez ES, Carlson CL. Neuroblastoma, ganglioneuroblastoma, and ganglioneuroma: radiologic-pathologic correlation. Radiographics 2002; 22: 911-34.

6. Linda J., Vorvick, MD and Yi-Bin Chen, MD. Also reviewed by David Zieve, MD. A.D.A.M. Medical Encyclopedia. Ganglioneuroblastoma; Last reviewed: February 7, 2012.

7. Schipper MH, van Duinen SG, Taphoorn MJ, Kloet A, Walchenbach R, Wiggenraad RG, Vecht CJ. Department of Neurology, Medical Center Haaglanden, The Hague, The Netherlands. Cerebral ganglioneuroblastoma of adult onset: two patients and a review of the literature. Clin Neurol Neurosurg. 2012 Jul;114(6):529-34.

8. Manjusha Sanjay Rathi. Ganglioneuroblastoma: First presentation during pregnancy; Program: Abstracts – Orals, Featured Poster Presentations, and Posters Monday, June 17, 2013; King’s Mill Hospital, Sutton in Ashfield, United Kingdom

9. Black P, Morokoff A, Zauberman J, Claus E, Carroll R. Meningiomas: science and surgery. Clin Neurosurg. 2007;54:91-9.

10. Awada A, Watson T, Obeid T. Cavernous angioma presenting as pregnancy-related seizures. Epilepsia, 38 (7): 844-6, 1997.

11. Wlody D: Neurosurgery in the pregnant patient. Newfield P, Cottrell J, editors. Philadelphia: WW Lippincott; 1999.

12. Depret-Mosser S, Jomin M, Monnier JC, Vinatier D, Bouthors-Ducloy AS, Christiaens JL, Krivosic-Horber R. Cerebral tumors and pregnancy. Apropos of 8 cases. J Gynecol Obstet Biol Reprod (Paris). 1993; 22(1):71-80.

13. Poisson M, Pertuiset BF, Hauw JJ, Philippon J, Buge A, Moguilewsky M, et al. Steroid hormone receptors in human meningiomas, gliomas and brain metastases. J Neurooncol 1983;1:179-89.

14. Golan A, Lin G, Evron S, Arieli S, Niv D, David MP. Oligohydramnios: maternal complications and fetal outcome in 145 cases. Gynecol Obstet Invest. 1994;37:91–5.

15. Khalil E Rajab, FRCOG, FFFP Nouf Behzad N, MD, Arab Board. Brain Tumor in Pregnancy. Bahrain Medical Bulletin, Vol 35, No 1, March 2013.

16. Lynch JC, Gouvêa F, Emmerich JC, Kokinovrachos G, Pereira C, Welling L, Kislanov S. Management strategy for brain tumour diagnosed during pregnancy. Br J Neurosurg. 2011 Apr;25(2):225-30. doi: 10.3109/02688697.2010.508846. Epub 2010 Sep 8.

17. Lily Chang, Lian Looi-Lyons, Lydia Bartosik, Simon Tindal; Anesthesia for cesarean section in two patients with brain tumours. Canadian Journal of Anesthesia. January 1999, Volume 46, Issue 1, pp 61-65

1

Rare case of ganglioneuroblastoma during pregnancy – case report

Abstract

Ganglioneuroblastoma is a very rare tumor, especially in pregnancy. So far the association between this tumor and pregnancy has not been reported. We present a case of ganglioneuroblastoma relapse at a 3rd trimester pregnant woman.

Neurological symptoms developed late, increased by the effects of pregnancy on the brain tumor.

Therapeutic management in this case represents a medical dilemma regarding mode setting and timing of delivery, taking into account the maternal-fetal risk-benefit. In this case caesarean section under general anesthesia was settled, with the need of postpartum brain tumor excision.

Keywords: ganglioneuroblastoma, pregnancy, treatment, caesarean section

Introduction

Ganglioneuroblastoma is a neuroblastic tumor containing malignant elements characteristic to neuroblastoma and benign elements found in ganglioneurinoma (1).

Intracranial tumors are extremely rare in pregnancy (2). By their rarity and their diagnosis in the last trimester of pregnancy, intracranial tumors have an increased risk of maternal and fetal morbidity and mortality. Cranial tumors tend to increase and become symptomatic in the last trimester of pregnancy, the causes not being entirely known.

Therefore any woman with an existing neurological condition should consult her obstetrician and her neurologist before she becomes pregnant (3).

Management of these cases should evaluate whether the mother’s and the fetus’s lives are threatened. A multidisciplinary team recommends the optimal timing for the termination of pregnancy, as determined by the fetus maturity and mother’s neurological condition (4).

The present study reports one case of pregnant women in the third trimester with ganglioneuroblastoma. The patient underwent caesarean section under general anesthesia at 36 weeks gestation with favorable postoperative evolution. So far, there are no well-established protocols regarding the management of intracranial tumors (especially ganglioneuroblastoma) in pregnant women.

Case report

I.A., 20-year-old woman, G1P1L0, was admitted to our hospital due to weak, irregular uterine contractions in her 36th week of gestation. Patient’s history: in 2005 the patient was diagnosed with right parietal lobe ganglioneuroblastoma. She had undergone surgery followed by radiochemotherapy and anticonvulsive therapy with phenytoin for about one year with favorable outcome. Six years following resection, the patient had no radiologic recurrence.

The pregnant woman was taken out by a gynecologist in the first trimester of pregnancy, with the usual analyzes of pregnancy, ultrasound and regular prenatal checkups without objective neurological signs until the 3rd trimester of pregnancy.

Therapeutic attitude assumed identification of neurological symptoms in order to determine the optimal treatment, maintaining a low fetal risk and continuing uncomplicated pregnancy until birth.

Methods

Investigation protocol included routine tests and imaging tests. Neurological examination revealed vestibular syndrome and nystagmus which recommended contrast MRI.

MRI conclusions:

In the right parietal lobe, postcentral, viewed a well-shaped image of 32mm in diameter, nongadolinium-enhanced, sequel looking. An area of oedema with irregular outline in white matter was surrounding it. In the right temporal lobe, adjacent to the sylvian seizure, in hyposignal T2 image showed a nodular-shaped tumor of about 7mm in diameter with discrete central heterogenity (gadolinium-enhanced). No perilesional oedema. Ventricular system located on the midline.

MRI based neurosurgical consultation has determined that the tumor was operable and stated the need of postpartum surgery (excision of the brain tumor).

All fetal biometric parameters studied were below the 10th percentile for gestational age, showing a linear decrease with gestation until the end of pregnancy. The difference between menstrual age and gestational age determined by ultrasound was 3 weeks and 3 days. Estimated fetal weight was 2420 g, which placed the infant in the 6th percentile. The amniotic fluid index was 7.5 cm, confirming the diagnosis of IUGR.

The patient had received dexamethasone treatment with double purpose: fetal lung maturation and reduced perilesional cerebral oedema in order to decrease focal neurological symptoms.

The association between IUGR, repeated variable cardiotocography decelerations and brain tumor recurrence with emphasized neurological symptoms imposed urgent caesarean section.

Medical committee composed of obstetrician, anesthesiologist, neurosurgeon and neonatologist decided caesarean section under general anesthesia, which was performed 5 days after the admission of the patient.

Results

A 20 year-old patient, I.A., known with operated and radiochemotreated ganglioneuroblastoma eight years earliar, with ongoing pregnancy (36 weeks) was admitted to our clinic for weak uterine contractions and associated neurological symptoms (vestibular syndrome, nystagmus, slightly right motor deficit). She followed a protocol of blood tests, imaging and interdisciplinary consultations establishing the diagnosis of brain tumor, possible relapse of old pathology. Fetal biometry measurements and fetal biological parameters objectified the existence of fetal distress risk of premature birth or miscarriage. Those set the need for preoperative corticosteroid therapy (Dexamethasone) for lung maturation and perilesional brain oedema control and emergency caesarean under general anesthesia.

Caesarean section was performed 5 days after admission, without early nor late intraoperative and postoperative complications.

It resulted an unique live female newborn, weighing 2670g, 9 Apgar, with physiological vital functions, not requiring special follow-up.

Recovery of the mother was complication-free with persistent, constant postoperative neurological symptoms.

When discharged, the patient was recommended ambulatory neurosurgical exam to establish the opportunity of surgery targeting the brain tumor.

Discussions

Ganglioneuroblastoma is a tumor of the sympathetic nervous system that arises from primitive sympathogonia and is composed of both mature gangliocytes and immature neuroblasts and has intermediate malignant potential (5). These tumors are rare. They occur in fewer than five out of one million children each year (6). Ganglioneuroblastomas are extremely rare in adults, with only about 50 cases documented in people over the age of 20, and only five cases observed in the adult brain (7). There are no reports of ganglioneuroblastoma presenting during pregnancy in medical literature (8).

Objectification of brain tumor by contrast MRI was necessary to establish the subsequent therapeutic management, although in literature there are “not enough studies to determine the safe use of contrast in pregnancy (9). MRI is probably the imaging diagnostic procedure of choice and should be performed when a brain tumor is suspected (10).

Before pregnancy the patient was declared cured, as no clinical nor radiological tumor relapse existed for six years. It is likely that pregnancy-induced changes have a tumorigenic effect, due to several factors such as fluid retention, increased blood volume and hormonal changes (11). Pregnancy is an aggravating factor for brain tumours on which it acts by three mechanisms: acceleration of tumor growth, increase of peritumoral oedema and the immunotolerance to foreign tissue antigens that is proper to pregnancy (12). Normal physiological changes during the pregnancy, such as increased levels of gonadotropins and augmented fluid volume status may accelerate the growth of some types of brain tumors (13).

The combination of oligohydramnios and IUGR portends a less favorable outcome, and early delivery should be considered (14). Treatment of brain tumor in pregnancy requires an integrated multidisciplinary approach, which includes neurosurgery, ophthalmology, radiology, obstetrics, neonatal pediatrics (15).

Indication for type of delivery is controversial. The best moment to recommend the craniotomy and the neurosurgical removal of the tumor will depend of the mother’s neurological condition, the histological tumor type as well as the gestational age. In a study published in 2011, performed on 10 patients with brain tumors diagnosed during pregnancy, prior to craniotomy, five patients had caesarean sections, two others had vaginal deliveries, in three patients the delivery took place after the brain tumor treatment(16).

The caesarean section was made under general anesthesia. Studies have shown that general anesthesia remains safe and dependable for operative delivery in parturients with intracranial tumor. Tracheal intubation allows maternal hyperventilation thereby controlling raised intracranial pressure. Hemodynamic stability is readily achieved to maintain cerebral perfusion (17).

Conclusions

Ganglioneuroblastoma is a rare brain tumor in childhood, and appears exceptionally in pregnant women.

Pregnancy and brain tumor have mutual negative effect on the patient.

Brain tumors that develop in pregnant women have to be diagnosed and assessed through MRI, although the effect of gadolinium contrast on the pregnancy is yet unknown and needs further medical studies.

The order of obstetrical an neurosurgical treatment of pregnant women with brain tumors requires an integrated multidisciplinary approach, including neurosurgery, radiology, obstetrics, neonatal pediatrics which have to assess all maternal-fetal risks and benefits.

Lack of brain tumor reccurence 6 years after currative neurosurgical treatment was not enough to establish that the patient was cured. The patient suffered a brain tumor relapse 8 years after brain surgery probably due to metabolic and hormonal changes induced by pregnancy.

References

1.Robertson H.E. Das Ganglioneuroblastom ein besonederer Typus im System der Neurome. Virchows Arch [Pathol Anat]. 1915;63: 147-168

2. Pavlidis NA. Coexistence of pregnancy and malignancy. The Oncologist 2002;7: 279-87.

3. Carmel Armon, Stephen A Berman. Neurologic Disease and Pregnancy. Medscape reference; 8 nov 2012

4. Ducray F, Colin P, Cartalat-Carel S, et al. Management of malignant gliomas diagnosed during pregnancy. Rev Neurol (Paris) 2006;162: 322–9.

5. Lonergan GJ, Schwab CM, Suarez ES, Carlson CL. Neuroblastoma, ganglioneuroblastoma, and ganglioneuroma: radiologic-pathologic correlation. Radiographics 2002; 22: 911-34.

6. Linda J., Vorvick, MD and Yi-Bin Chen, MD. Also reviewed by David Zieve, MD. A.D.A.M. Medical Encyclopedia. Ganglioneuroblastoma; Last reviewed: February 7, 2012.

7. Schipper MH, van Duinen SG, Taphoorn MJ, Kloet A, Walchenbach R, Wiggenraad RG, Vecht CJ. Department of Neurology, Medical Center Haaglanden, The Hague, The Netherlands. Cerebral ganglioneuroblastoma of adult onset: two patients and a review of the literature. Clin Neurol Neurosurg. 2012 Jul;114(6):529-34.

8. Manjusha Sanjay Rathi. Ganglioneuroblastoma: First presentation during pregnancy; Program: Abstracts – Orals, Featured Poster Presentations, and Posters Monday, June 17, 2013; King’s Mill Hospital, Sutton in Ashfield, United Kingdom

9. Black P, Morokoff A, Zauberman J, Claus E, Carroll R. Meningiomas: science and surgery. Clin Neurosurg. 2007;54:91-9.

10. Awada A, Watson T, Obeid T. Cavernous angioma presenting as pregnancy-related seizures. Epilepsia, 38 (7): 844-6, 1997.

11. Wlody D: Neurosurgery in the pregnant patient. Newfield P, Cottrell J, editors. Philadelphia: WW Lippincott; 1999.

12. Depret-Mosser S, Jomin M, Monnier JC, Vinatier D, Bouthors-Ducloy AS, Christiaens JL, Krivosic-Horber R. Cerebral tumors and pregnancy. Apropos of 8 cases. J Gynecol Obstet Biol Reprod (Paris). 1993; 22(1):71-80.

13. Poisson M, Pertuiset BF, Hauw JJ, Philippon J, Buge A, Moguilewsky M, et al. Steroid hormone receptors in human meningiomas, gliomas and brain metastases. J Neurooncol 1983;1:179-89.

14. Golan A, Lin G, Evron S, Arieli S, Niv D, David MP. Oligohydramnios: maternal complications and fetal outcome in 145 cases. Gynecol Obstet Invest. 1994;37:91–5.

15. Khalil E Rajab, FRCOG, FFFP Nouf Behzad N, MD, Arab Board. Brain Tumor in Pregnancy. Bahrain Medical Bulletin, Vol 35, No 1, March 2013.

16. Lynch JC, Gouvêa F, Emmerich JC, Kokinovrachos G, Pereira C, Welling L, Kislanov S. Management strategy for brain tumour diagnosed during pregnancy. Br J Neurosurg. 2011 Apr;25(2):225-30. doi: 10.3109/02688697.2010.508846. Epub 2010 Sep 8.

17. Lily Chang, Lian Looi-Lyons, Lydia Bartosik, Simon Tindal; Anesthesia for cesarean section in two patients with brain tumours. Canadian Journal of Anesthesia. January 1999, Volume 46, Issue 1, pp 61-65

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