Abstract BACKGROUND AND IMPORTANCE This report illustrates a case of a low-grade glioma that showed significant disease progression during pregnancy, and then subsequent regression spontaneously in the postpartum period without treatment. This is a rare case of spontaneous glioma regression in the postpartum period, and may suggest underlying mechanisms of hormonal influences upon glioma progression. CLINICAL PRESENTATION The patient is a 27-yr-old female who underwent placement of a right-sided ventriculoperitoneal shunt for aqueductal stenosis at 8 wk of age. At the age of 24 yr, she was evaluated for chronic headaches and was found on magnetic resonance imaging (MRI) for the first time to have a small nonenhancing tectal glioma that remained stable on follow-up MRI. At the age of 25 yr, she returned for annual follow-up after giving birth and reported a significant increase in headache frequency and severity during the pregnancy. Repeat imaging now showed a larger, contrast-enhancing lesion. A decision was made to pursue radiosurgery, but during the pretreatment planning phase, the lesion and symptoms regressed spontaneously, and the lesion has remained stable on repeat MRI studies over a 30-mo period since delivery of her child. CONCLUSION A young woman with a tectal glioma developed symptomatic disease progression during pregnancy, and subsequently had regression of the lesion and symptoms in the postpartum period without treatment. This case supports watchful waiting in select cases and suggests a potential role of hormones in glioma progression. Disease Progression, Glioma, Headache, Pregnancy, Regression, Watchful Waiting ABBREVIATIONS ABBREVIATIONS MR Magnetic resonance MRI magnetic resonance imaging During pregnancy, various factors including hormonal changes,1,2 alterations in blood flow, and other physiological mechanisms have been hypothesized to lead to growth and/or hemorrhage in select cases of various intracranial tumors including pituitary adenomas,3,4 gliomas, and meningiomas.5,6 Several studies have pointed to a potential role of estrogen and progesterone receptors in glioma growth.7,8 Pregnancy is characterized by high levels of progesterone along with alterations in the hypothalamus-pituitary axis. Placental growth hormones may induce release of growth factors that upregulate glioma proliferation and migration. Regression of intracranial tumors postpartum has not been previously described in the literature.9 A case is presented of a suspected low-grade glioma that demonstrated evidence of growth and imaging features concerning for malignant transformation to a higher grade during pregnancy with subsequent spontaneous tumor regression in the postpartum period without treatment of the lesion. The case is summarized and possible mechanisms discussed.10 CLINICAL PRESENTATION Informed consent was obtained from the patient. The patient is a 27-yr-old Caucasian female. At 8 wk of age, she had a right parieto-occipital ventriculoperitoneal shunt placement at another institution for hydrocephalus due to apparent aqueductal stenosis (Figure 1). No apparent tumor was identified at that time. She was followed by neurosurgeons periodically over the years and generally was in good health with no significant issues except chronic headaches. At 20 yr of age, she was evaluated at another institution for headache associated with nausea and vomiting. Computed tomography of the head was performed, and a subsequent radio-isotope “shuntogram” did not identify any evidence of shunt malfunction (Figure, Supplemental Digital Content 1). A diagnosis of migraine headaches was made, and she was started on prophylactic medications. She did not require any neurosurgical intervention over the years including no revisions of the shunt. She generally functioned well, completed a college education, and maintained a full-time job. FIGURE 1. View largeDownload slide Timeline outlining patient's clinical course and pertinent medical history. Representative images are included. FIGURE 1. View largeDownload slide Timeline outlining patient's clinical course and pertinent medical history. Representative images are included. At 24 yr of age, the patient presented for neurosurgical evaluation for assessment of an exacerbation of her chronic headaches and to establish adult neurosurgical evaluation. Given her previous history of shunted hydrocephalus, magnetic resonance imaging (MRI) of the brain was completed (Figure 2). The MRI demonstrated small ventricles, and it was concluded that her shunt was functioning well. In addition, a 6-mm nonenhancing lesion was identified in the midbrain tectal region with MRI characteristics consistent with a low-grade glioma. The headaches were managed medically with a plan for interval imaging. After 6 additional months, a follow-up MRI was stable, and plans were made for patient to return in 1 yr with a repeat MRI. FIGURE 2. View largeDownload slide A brain MRI at age 24 revealed a non-enhancing T1 hypointense, T2/FLAIR hyperintense lesion eccentrically located in the dorsal midbrain measuring 7 mm (transverse) × 5.7 mm anterior-posterior consistent with a tectal glioma. This lesion had not been identified on imaging at the time of diagnosis of hydrocephalus and aqueductal stenosis at 8 wk of age, or on subsequent imaging during her childhood. A, Axial T1 contrast-enhanced scan. B, Axial T2-contrast enhanced scan. C, Sagittal T1 scan. FIGURE 2. View largeDownload slide A brain MRI at age 24 revealed a non-enhancing T1 hypointense, T2/FLAIR hyperintense lesion eccentrically located in the dorsal midbrain measuring 7 mm (transverse) × 5.7 mm anterior-posterior consistent with a tectal glioma. This lesion had not been identified on imaging at the time of diagnosis of hydrocephalus and aqueductal stenosis at 8 wk of age, or on subsequent imaging during her childhood. A, Axial T1 contrast-enhanced scan. B, Axial T2-contrast enhanced scan. C, Sagittal T1 scan. In the interim, the patient noted a dramatic increase in headache frequency after becoming pregnant. The pregnancy itself was uncomplicated except for a subjective increase in migraine headaches. Her physicians pursued close monitoring of her headaches and neurological condition without imaging during pregnancy. Subsequent MRI studies during the postpartum period revealed a significant increase in the size of the apparent tectal glioma (Figure, Supplemental Digital Content 2). At this time, the lesion was noted to be exerting mass effect on the cerebral aqueduct. Various specialists including neurosurgeons and radiation oncologists evaluated the patient. Options of observation, stereotactic radiosurgery, and surgery were discussed. The lesion had nearly doubled in size and showed avid central contrast enhancement. A confirmatory scan 1 mo later showed evidence of further progression and growth (Figure 3). Magnetic resonance (MR) spectroscopy showed an increased choline/N-acetylaspartate ratio in the left dorsal midbrain in comparison to normal brain parenchyma (Figure 4A-4B), while MR perfusion scanning revealed increased perfusion in the tumor (Figure 4C-4D). Findings were inconclusive but strongly suggestive of a tectal glioma. Discussions were had as to whether nursing of her child would have any hormonal effects upon the growth of the tumor, and as that could not be determined with any certainty, she chose to discontinue breast-feeding her child. FIGURE 3. View largeDownload slide A follow-up MRI at approximately 3 mo postpartum showed further mild increase in the size of the lesion with central enhancement. A, Axial T1 contrast-enhanced scan. B, Axial T2 contrast-enhanced scan. C, Sagittal T1 contrast-enhanced scan. D, Sagittal T2 contrast-enhanced scan. FIGURE 3. View largeDownload slide A follow-up MRI at approximately 3 mo postpartum showed further mild increase in the size of the lesion with central enhancement. A, Axial T1 contrast-enhanced scan. B, Axial T2 contrast-enhanced scan. C, Sagittal T1 contrast-enhanced scan. D, Sagittal T2 contrast-enhanced scan. FIGURE 4. View largeDownload slide A, Localizer for MR spectroscopy imaging at 3 mo postpartum. B Spectroscopy reveals an increased ratio of choline to N-acetylaspartate (NAA ratio), a finding consistent with glioma. C, D, Axial and sagittal slices from MR perfusion scan highlighting increased cerebral blood volume in the tumor. Arrow denotes lesion location. FIGURE 4. View largeDownload slide A, Localizer for MR spectroscopy imaging at 3 mo postpartum. B Spectroscopy reveals an increased ratio of choline to N-acetylaspartate (NAA ratio), a finding consistent with glioma. C, D, Axial and sagittal slices from MR perfusion scan highlighting increased cerebral blood volume in the tumor. Arrow denotes lesion location. After lengthy discussions of the treatment options with multiple specialists, the patient decided to pursue Gamma-KnifeTM (Elekta Inc, Stockholm, Sweden) stereotactic radiosurgery. Shortly after these discussions, during the subsequent weeks of the postpartum period, before radiosurgery was performed the symptoms of headache dramatically regressed. The patient opted for observation with close follow-up, and no treatment was administered. MRI studies at this time (4 mo postpartum) showed a decrease in the lesion size (Figure, Supplemental Digital Content 3); repeat MRI studies after 2 additional months (Figure, Supplemental Digital Content 4) and again after 5 more months demonstrated continued reduction of the size of the lesion, and it was no longer contrast enhancing. The lesion on MRI demonstrated continued stability on the last follow-up assessments at 15 mo and 21 mo since the delivery of her child, and the patient has remained symptom free. She returned for 30-mo follow-up and remains stable (Figure 5). FIGURE 5. View largeDownload slide MRI scan at 30 mo postpartum showed a stable lesion. A, Axial T1 contrast-enhanced scan. B, Axial T2 contrast-enhanced scan. C, Sagittal T1 contrast-enhanced scan. D, Sagittal T2 contrast-enhanced scan. FIGURE 5. View largeDownload slide MRI scan at 30 mo postpartum showed a stable lesion. A, Axial T1 contrast-enhanced scan. B, Axial T2 contrast-enhanced scan. C, Sagittal T1 contrast-enhanced scan. D, Sagittal T2 contrast-enhanced scan. DISCUSSION Intracranial tumors including meningiomas, pituitary adenomas, and gliomas have been demonstrated in select patients to grow and/or hemorrhage during pregnancy.11,12 A number of hormonal changes, alterations of blood flow, and other physiological parameters have been identified as possibly contributing to this phenomenon. To our knowledge, this is the first reported case of spontaneous regression of a glioma in the postpartum period without treatment. It is likely that hormonal changes during pregnancy contributed to the growth of the tumor, and the subsequent normalization of these hormonal changes also played a role in the eventual spontaneous tumor regression. While the lesion was not biopsied for tissue sampling, the proposed diagnosis of tectal glioma is highly likely in light of the MRI characteristics, spectroscopic findings, and general behavior. Additionally, when the lesion first arose cannot be ascertained with certainty. There are case reports of pediatric patients diagnosed with hydrocephalus secondary to aqueductal stenosis that later were identified to develop an obstructive tumor,13 and this scenario may be the case for the patient described in this report. There is a growing body of evidence that shows hormonal changes associated with pregnancy can stimulate glial cell growth14 and may confer an increased risk of tumors of the central nervous system.15-18 Clinically, there is growing evidence that pregnancy increases the growth rate and the risk of malignant transformation of low-grade gliomas.9,19-21 De-novo tumors that arise during pregnancy are also more likely to be high-grade lesions.22 The management of brain tumors during pregnancy remains an active area of investigation.23 In many cases, radiological and surgical treatment is deferred to the immediate postpartum period unless an acute intervention is needed. This phenomenon of tumor regression postpartum is one that clinicians should bear in mind when managing patients with brain tumors during pregnancy and the postpartum timeframe. Furthermore, a clearer understanding of the hormonal and physiological factors that might lead to such tumor progression and regression during and after pregnancy might give some insight into possible mechanisms of glioma growth, and possible strategies to target for therapeutic intervention. CONCLUSION A case of a young woman with symptomatic growth of an apparent low-grade tectal glioma during pregnancy with subsequent spontaneous regression of the tumor and symptoms during the postpartum period is presented. While several small case series and retrospective cohort analyses of both low- and high-grade gliomas have shown increased growth and malignant transformation during pregnancy, spontaneous tumor regression in the postpartum period has not been previously described. This case supports watchful waiting in select cases and suggests a potential role for hormones in glioma progression. Disclosures Dr Chicoine received funding from IMRIS Inc for an unrestricted educational grant that has helped support an intraoperative magnetic resonance imaging and brain tumor database and outcomes studies. Additional funding for advanced brain tumor imaging was provided to Dr Benzinger from the Barnes-Jewish Hospital Foundation. The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article. REFERENCES 1. Benson VS, Kirichek O, Beral V, Green J. Menopausal hormone therapy and central nervous system tumor risk: large UK prospective study and meta-analysis. Int J Cancer . 2015; 136( 10): 2369- 2377. Google Scholar CrossRef Search ADS PubMed 2. Schoenberg BS, Christine BW, Whisnant JP. Nervous system neoplasms and primary malignancies of other sites: the unique association between meningiomas and breast cancer. Neurology . 1975; 25( 8): 705- 712. Google Scholar CrossRef Search ADS PubMed 3. Bronstein MD, Paraiba DB, Jallad RS. Management of pituitary tumors in pregnancy. Nat Rev Endocrinol 2011; 7( 5): 301- 310. Google Scholar CrossRef Search ADS PubMed 4. Bronstein MD. Prolactinomas and pregnancy. Pituitary . 2005; 8( 1): 31- 38. Google Scholar CrossRef Search ADS PubMed 5. Lusis EA, Scheithauer BW, Yachnis AT et al. Meningiomas in pregnancy: a clinicopathologic study of 17 cases. Neurosurgery . 2012; 71( 5): 951- 961. Google Scholar CrossRef Search ADS PubMed 6. Isla A, Alvarez F, Gonzalez A, Garcia-Grande A, Perez-Alvarez M, Garcia-Blazquez M. Brain tumor and pregnancy. Obstet Gynecol . 1997; 89( 1): 19- 23. Google Scholar CrossRef Search ADS PubMed 7. Khalid MH, Shibata S, Furukawa K, Nadel A, Ammerman MD, Caputy AJ. Role of estrogen receptor-related antigen in initiating the growth of human glioma cells. J Neurosurg . 2004; 100( 5): 923- 930. Google Scholar CrossRef Search ADS PubMed 8. Tavares CB, Gomes-Braga F, Costa-Silva DR et al. 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Roland JL, Price RL, Kamath AA et al. Hydrocephalus presenting as idiopathic aqueductal stenosis with subsequent development of obstructive tumor: report of 2 cases demonstrating the importance of serial imaging. J Neurosurg Pediatr . 2017; 20( 4): 329- 333. Google Scholar CrossRef Search ADS PubMed 14. Gutierrez-Rodriguez A, Hansberg-Pastor V, Camacho-Arroyo I. Proliferative and invasive effects of progesterone-induced blocking factor in human glioblastoma cells. BioMed Res Int . 2017; 2017: 1- 10. Google Scholar CrossRef Search ADS 15. Benson VS, Pirie K, Green J et al. Hormone replacement therapy and incidence of central nervous system tumours in the million women study. Int. J Cancer . 2010; 127( 7): 1692- 1698. Google Scholar CrossRef Search ADS PubMed 16. Kabat GC, Etgen AM, Rohan TE. Do steroid hormones play a role in the etiology of glioma? Cancer EpidemiolBiomarkers Prev . 2010; 19( 10): 2421- 2427. 17. Michaud DS, Gallo V, Schlehofer B et al. Reproductive factors and exogenous hormone use in relation to risk of glioma and meningioma in a large European cohort study. Cancer Epidemiol Biomarkers Prev . 2010; 19( 10): 2562- 2569. Google Scholar CrossRef Search ADS PubMed 18. Qi ZY, Shao C, Zhang X, Hui GZ, Wang Z. Exogenous and endogenous hormones in relation to glioma in women: a meta-analysis of 11 case-control studies. PLoS One . 2013; 8( 7): e68695. Google Scholar CrossRef Search ADS PubMed 19. Daras M, Cone C, Peters KB. Tumor progression and transformation of low-grade glial tumors associated with pregnancy. J Neurooncol . 2014; 116( 1): 113- 117. Google Scholar CrossRef Search ADS PubMed 20. Yust-Katz S, de Groot JF, Liu D et al. Pregnancy and glial brain tumors. NeuroOncol . 2014; 16( 9): 1289- 1294. 21. Pallud J, Mandonnet E, Deroulers C et al. Pregnancy increases the growth rates of World Health Organization grade II gliomas. Ann Neurol . 2010; 67( 3): 398- 404. Google Scholar PubMed 22. Zwinkels H, Dorr J, Kloet F, Taphoorn MJ, Vecht CJ. Pregnancy in women with gliomas: a case-series and review of the literature. J Neurooncol . 2013; 115( 2): 293- 301. Google Scholar CrossRef Search ADS PubMed 23. Cohen-Gadol AA, Friedman JA, Friedman JD, Tubbs RS, Munis JR, Meyer FB. Neurosurgical management of intracranial lesions in the pregnant patient: a 36-year institutional experience and review of the literature. J Neurosurg . 2009; 111( 6): 1150- 1157. Google Scholar CrossRef Search ADS PubMed Supplemental digital contentis available for this article at www.neurosurgery-online.com. Supplemental Digital Content 1. Figure. Contrasted head CT scan obtained at age 20 for evaluation of headache with no evidence of a mass lesion. Representative axial slice from contrast-enhanced scan. A radioisotope shuntogram performed at that time showed a normally functioning shunt. Supplemental Digital Content 2. Figure. Follow-up MRI at the age of 25 yr, 1 yr after the MRI study in Figure 3, and approximately 2 mo postpartum showed interval enlargement of the lesion to 1.5 cm by 1.4 cm, with avid central contrast enhancement, and increased cerebral blood volume. The findings on this MRI were interpreted by the neuroradiologists as consistent with pilocytic astrocytoma or high-grade transformation of existing low-grade glioma. A, Axial T1 contrast-enhanced scan. B, Axial T2 contrast-enhanced scan. C, Sagittal T1 contrast-enhanced scan. D, Sagittal T2 contrast-enhanced scan. Supplemental Digital Content 3. Figure. Repeat MRI 4 mo postpartum showed interval decrease in the size of the lesion to 1.2 cm by 1.2 cm with decreased central enhancement (0.8 cm by 0.8 cm). A, Axial T1 contrast-enhanced scan. B, Axial T2 contrast-enhanced scan. C, Sagittal T1 contrast-enhanced scan. D, Sagittal T2 contrast-enhanced scan. Supplemental Digital Content 4. Figure. MRI at 6 mo postpartum demonstrated that the lesion had decreased to 0.9 cm by 0.9 cm, and no longer exhibited central enhancement. A, Axial T1 contrast-enhanced scan. B, Axial T2 contrast-enhanced scan. C, Sagittal T1 contrast-enhanced scan. D, Sagittal T2 contrast-enhanced scan. Acknowledgement The authors would like to thank Tyler Bauman for his assistance with preparing figures for publication. COMMENT The authors describe a case of a patient with a low-grade glioma that progressed during pregnancy and then demonstrated regression postpartum without treatment. The case is interesting although one could make the argument that this is simply a change in the blood brain barrier permeability during pregnancy and not actual tumor growth. Nevertheless, the imaging is interesting. The lesion is quite small so it would be easy to be skeptical of the MR spectroscopy. Without more follow-up or a tissue diagnosis it is unclear what is really going on in this case report. Randy L. Jensen Salt Lake City, Utah Copyright © 2018 by the Congress of Neurological Surgeons This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)
Neurosurgery – Oxford University Press
Published: May 21, 2018
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