Choroid Plexus Papilloma Associated with Developmental Delay Abhishek Agarwal, Sandeep Chopra and A.D. Sehgal
Unit of Pediatric Neurosurgery, Sir Ganga Ram Hospital, Old Rajinder Nagar, New Delhi, India.
Abstract. Choroid plexus papillomas are rare, benign tumors of neuroectodermal origin usually observed in the lateral ventricles of children. The usual presenting signs of choroid plexus papillomas are related to hydrocephalus and increased intracranial pressure. A child presented to us with clinical features of delayed milestones, which was later diagnosed as a case of choroid plexus papilloma with hydrocephalus. He underwent complete excision of the tumour with gradual recovery of milestones. [Indian J Pediatr 2004; 71 (8) : 763-766] E-mail :
[email protected] Key words : Choroid plexus papilloma; Delayed milestones. C h o r o i d p l e x u s p a p i l l o m a s are b e n i g n i n t r a c r a n i a l neoplasms of the choroid plexus, a structure made from tufts of villi within the ventricular system that produces cerebrospinal fluid. While the vast majority of these n e o p l a s m s are b e n i g n , a small p e r c e n t a g e can be malignant, termed as choroid plexus carcinomas. In the pediatric age group, papillomas occur most commonly in the lateral ventricle (67%), followed by the fourth ventricle (19%), with a lesser number presenting primarily in the third ventricle (14%). 1 The usual presenting signs are related to h y d r o c e p h a l u s and increased intracranial pressure. Behavioral changes and irritability may be the only clinical s i g n s . 2 Elevation of CSF protein values is characteristic in choroid plexus papillomas and is found in over two-thirds of patients. 3 When m e a s u r e d , the lumbar CSF pressure has nearly always been elevated. Diagnosis is b y CT or MRI, which reveal a 'frond-like' a p p e a r a n c e with intense e n h a n c e m e n t after contrast administration related to the vascular nature of the lesion. When these lesions are symptomatic, the treatment is surgical with total resection as the aim. 1,~'5
features suggestive of psychosis or autism were evident. No ophthalmic signs including that of papilloedema were elicited. Child was assessed using Bayley Scalefor Infant Development (BSID). The p s y c h o m o t o r developmental index (PDI) was 32, while the mental d e v e l o p m e n t a l index (MDI) was 68. All base line blood investigations including complete and differential blood count, ESR, coagulation profile, serum electrolytes, liver and renal functions were within normal limits. CT scan of the head s h o w e d a h o m o g e n o u s lobulated mass in left lateral ventricle. MRI revealed tuInour within the trigone of left lateral ventricle and there was intense h o m o g e n o u s enhancement on contrast administration suggestive of a choroid plexus papilloma (Fig. 1), which was till n o w totally unsuspected clinically.
CASE REPORT A 9-month-old male child, full term normally delivered, born of non-consanguineous marriage, presented to us with complaints of inability to hold the head upright and inability to sit without support. There was no significant past history, including history of seizures. The family history was also non-contributory. Clinical examination revealed a conscious child with a head circumference of 48 cm (95~ percentile), flat anterior frontanelle a n d absence of any localizing signs. No
Correspondenceand Reprintrequests : Dr. Abhishek Agarwal, C/o Dr. C.S.Agarwal, 2/22, First floor,-ShantiNiketan, New Delhi-. 110021. Indian Journal of Pediatrics, Volume 71--August, 2004
Fig. 1. Pre operative scan. Contrast enhanced TIW axial image through the region of interest displays a well marginated, lobulated, intensely enhancing mass in the left peri-trigonal region. 763
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The authors used the inferior temporal sutcus approach and performed left temporoparietal craniotomy with transventricular excision of tumour along with coagulation of the pedicle of the papilloma. The gross appearance of the tumour was that of a large, reddish-pink highly vascular mass with a smooth Iobulated surface. Histologically the papillae were lined by tall columnar epithelial cells supported by a stroma of vascularised connective tissue (WHO grade 1) (Fig. 2).
Fig. 2. Pathology slide. Papillary tumour having "frond like" appearance, whichhave thin fibrovascularcorescoveredby a singlerow of columnarcells. No postoperative deficit was observed. Immediate post-operative MRI of the brain showed no residual tumor (Fig. 3). Anti-epileptic drug (Phenytoin sodium) was started after the diagnosis of CPP was made and continued post-operatively. Patient was followed up regularly at intervals of I month, being monitored by his head circumference (52 cm/95 ~ percentile). He also underwent early intervention and stimulation program
Fig. 3. Postoperativescan. TIW axial image showsno evidenceof any residual lesion.The ventricleis alsonormalin size. 764
by developmental team on a regular basis. Assessment at 2 years of age using BSID showed child had PDI of 72 and MDI of 76 and he is still following the early intervention program. DISCUSSION
Guerard gave the first description of lateral ventricle choroid plexus papillomas in 18334. Choroid plexus papillomas (CPPs) are rare, comprising 0.4 -0.1% of primary brain tumors, most often occurring in children and constituting 1.5-4% of childhood intracranial neoplasms with a predilection for younger age groups. They comprise 4-6% of the intracranial neoplasms in children younger than 2 years and 12-13% of intracranial neoplasms in children younger than 1 year. 1,6,7The theories for the etiology of CPPs are varied and associations with the Li-Fraumeni cancer syndrome (an autosomal dominant syndrome characterized by a mutation in the TP53 gene),a.9 Aicardi syndrome, 1~Von Hippel-Lindau syndrome z~have been proposed. Another postulate in the pathogenesis is the role of Simian SV 40related viral DNA in the development of papillomas as documented in experimental animal models.12,13,~4 The choroid plexus is a neuroepithelial-lined papillary projection of the ventricular ependyma. The papillae consist of cores of fibrovascular tissue lined by lowcuboidal neuroepithelial cells. Symptoms generally result from secretion of CSF by the tumor cells, leading to an increased a m o u n t of fluid and eventually, to hydrocephalus. Not infrequently, the tumor itself can cause mass effect, with symptoms depending on tumor location. Cases of hydrocephalus sometimes do not resolve with surgery, possibly because of derangement of reabsorption mechanisms or blockage at other sites in the ventricular system.6 Patients usually present with signs and symptoms of increased intracranial pressure such as headache, nausea and vomiting, drowsiness, ocular and gaze palsies (cranial nerves [CN] III and VI), papilledema, visual disturbances, and, eventually, blindness. Unusual presentations include trochlear palsies (CN W), psychosis, or, occasionally, seizures. In patients with lateral ventricle tumors, irritability, lethargy, hemiparesis and corticospinal tract involvement may be present. However, delayed milestones and regression are under recognized and under reported, as pointed out by Lena et al. is It is however a rather consistent clinical feature of lateral ventricle choroid plexus papilloma in children. 15In the series by Nagib et al, 6 out of 7 children presented with this particular clinical sign.4 CPPs are non-malignant; however, malignant evolution may occur, with an incidence of 10%. Plexus papillomas outnumber carcinomas by a ratio of 5 : 1.~6The lateral ventricles are the most common sites for malignant degeneration. Russel and Rubinstein defined Choroid plexus carcinomas (CPCs) as WHO grade 3 tumors which are Indian Journal of Pediatrics, Volume 71--August, 2004
Choroid Plexus Papilloma Associated with Developmental Delay characterized by presence of invasion of adjacent neural tissue and an ill d e f i n e d p a t t e r n of g r o w t h (loss of papillary architecture, mitosis, varying nuclear size and chromatin content and cellular pleomorphism). However, the distinction between CPPs and CPCs can be difficult and their histological features may have no co-relation with their respective biological behavior. These tumors frequently express CEA and CD44 as markers, s,17 Grossly, the presence of irregular margins should raise concerns about malignancy. However, CPPs may also have limited parenchymal invasion, which makes the d i s t i n c t i o n of the b e n i g n t u m o r f r o m its m a l i g n a n t counterpart difficult. The presence of mitotic figures, although rare in CPPs, may be predictive of the likelihood of both recurrence and malignant evolution. CT scan u s u a l l y d e m o n s t r a t e s a h o m o g e n e o u s l y hypodense to slightly hyperdense enhancing mass with cystic areas. This mass m a y be sizeable and m a y be associated w i t h h y d r o c e p h a l u s . 18,19I n t r a v e n t r i c u l a r extension, an ancillary diagnostic sign of CPP, is readily identified in coronal sections. For these reasons MRI is considered as the investigation of choice for the diagnosis of c h o r o i d p l e x u s t u m o r s , in w h i c h p a p i l l o m a s are characteristically multi-lobulated, variable sized with enhancement centered around the trigone. MRI is also useful in distinguishing b e t w e e n b e n i g n from m o r e a g g r e s s i v e c h o r o i d p l e x u s t u m o r s . 4,1s,2~P r o t o n MR spectroscopy of choroid plexus papilloma is characterized b y high levels of choline-containing c o m p o u n d s and c o m p l e t e absence of creatine and n e u r o n a l / a x o n a l marker- N acetyl aspartate. 21 Surgery appears to be the best therapeutic approach in choroid plexus papillomas. Complete removal of the tumor is generally curative and leads to resolution of the presenting symptoms in nearly all patients. In the series by Wolff et al, 17 the patients with complete resection had a 10-year survival rate of 85%. This compared to 56% with less than gross total resection and to a 1-year survival rate of only 50% in patients after biopsy. In infants, choroid p l e x u s p a p i l l o m a s are the b r a i n t u m o r s w i t h best prognosis25,17 The use of neuroendoscopic surgery and radiosurgery has been tested with some success, but these remain alternate methodologies till date. z2 Subdural effusions have been a particularly vexing problem post-operatively, which results from persistence of v e n t r i c u l o - s u b d u r a l fistulae after a trans-callosal approach or due to tearing of cortical vessels after collapse of the thin cortex. It can be prevented by the use of an intersulcal approach, filling the ventricles with saline and by the use of pre or postoperative ventricular drainage. 4~ The prognosis for both CPPs and CPCs is determined by the completeness of removal of the lesion at surgery. While gross total resection of intra-ventricular CPPs effects a cure, it should be the primary objective of CPCs. The prognosis for CPCs is dismal, with a 5-year survival rate of 26%. Sub-totally resected papillomas or localized carcinomas often do well with adjuvant therapy in the Indian Journal of Pediatrics, Volume 71--August, 2004
form of chemotherapy a n d / o r cranio-spinal irradiation. While pre-operative chemotherapy has been advocated to reduce vascularity and facilitate total surgical excision, radiotherapy has been associated with significantly better survival rates in CPCs. Relapse after primary treatment is a poor prognostic factor in CPCs but not in CPPs. 5,6,17 M o r b i d i t y in c h o r o i d plexus p a p i l l o m a relates to delayed milestones in 39% of pediatric patients, severe behavioral problems in 17%, and epilepsy in 48%. 1 The use of m o d e m diagnostic techniques, microneurosurgery, safer n e u r o - a n a e s t h e s i a and pediatric intensive care support should allow for an operative and preoperative mortality of less than 1% and a cure should be the aim for all children with choroid plexus papillomas.
CONCLUSION Delayed milestones was the clinical manifestation of choroid plexus papilloma in our patient, with the other signs or symptoms invariably reported in other cases of choroid plexus papillomas, such as raised intracranial pressure or cranial nerve palsies, being conspicuously absent. Hence, awareness of this presentation is important to avoid delay in the diagnosis and treatment of this curable condition.
Acknowledgement The authors express their gratitude to Dr K Chugh, Dr A Sachdev (Pedriatric Intensivist), and Dr Praveen Mehta (Developmental Pediatrician) for their support in publishing this report.
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Abhishek Agarwal et al cancer. Arch Pathol Lab Med 2002; 126 : 70-72. 10. Taggard DA, Menezes AH. Three choroid plexus papillomas in a patient with Aicardi syndrome. A case report (review). Pediatr Neurosurg 2000; 33 : 219-223. 11. Blamires TL, Friedmann I, l~loffat DA. Von Hippel-Lindau disease associated with an invasive choroid plexus tumor presenting as a middle ear mass. J LaryngolOto11992;106 : 429435. 12. Bergsagel DJ, Finegold MJ, Butel JS, Kupsky WJ, Garcea RL. D N A sequences similar to those of simian virus 40 in ependymomas and choroid plexus tumors of childhood. N Engl J Med 1992; 326 : 988-993. 13. Huang H, Reis R, Yonekawa Y, Lopes JM, Kleihues P, Ohgaki H. Identification in human brain tumors of DNA sequences specific for SV40 large T antigen. Brain Pathol 1999; 9 : 33-42. 14. Lednicky JA, Garcea RL, Bergsagel DJ, Butel JS. Natural simian virus 40 strains are present in human choroid plexus and ependymoma tumors. Virology 1995; 212 : 710-717. 15. Lena G, Genitori L, Molina J, Legatte JRS, Choux M. Choroid plexus tumors in children. Review of 24 cases. Acta Neurochir
(Wien) 1990; 106: 68-72. 16. Rickert CH, Paulus W. Tumors of the choroid plexus (review). Microscopy Researchand Technique. 2001; 52" 104-111. 17. Wolff JE, Sajedi M, Brant R, Coppes MJ, Egeler RM. Choroid plexus tumors. Br J Cancer. 2002; 87: 1086-1091. 18. Coates TL, Hinshaw DB, Peckman N. Peadiatric choroid plexus neoplasms. MR, CT and pathological correlation. Radiology 1989; 173: 81-88. 19. Kendell B, Grosswasser I, Valentine A. Diagnosis of masses presenting within the ventricles on computed tomography. Neuroradiology 1983; 25: 11-22. 20. Taylor MB, Jackson RW, Hughes DG, Wright NB. Magnetic Resonance Imaging in the diagnosis and management of choroid plexus carcinoma in children. PediatrRadio12001; 31: 624-630. 21. Horska A, Ulug AM, Melhem ER, Filippi CG et al. Proton magnetic resonance spectroscopy of choroid plexus tumors in children. J Magn Reson Imag 2001; 14 : 78-82. 22. Gaab MR, Schroeder HW. Neuroendoscopic approach to intraventricular lesions. J Neurosurg 1998; 88 : 496-505.
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