- Email: [email protected]
Ventriculo-peritoneal shunt associated ascites in a child with multicentric low grade glioma
Accepted Manuscript Ventriculo-peritoneal shunt associated ascites in a child with multicentric low grade glioma Dhwanee Thakkar, Rana Patir, Sunita Ahlawat, Satya Prakash Yadav PII:
S2468-1245(17)30063-3
DOI:
10.1016/j.phoj.2017.09.002
Reference:
PHOJ 50
To appear in:
Pediatric Hematology Oncology Journal
Received Date: 22 May 2017 Revised Date:
7 September 2017
Accepted Date: 8 September 2017
Please cite this article as: Thakkar D, Patir R, Ahlawat S, Yadav SP, Ventriculo-peritoneal shunt associated ascites in a child with multicentric low grade glioma, Pediatric Hematology Oncology Journal (2017), doi: 10.1016/j.phoj.2017.09.002. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Ventriculo-peritoneal shunt associated ascites in a child with Multicentric Low grade Glioma Dhwanee Thakkar1, Rana Patir2, Sunita Ahlawat3, Satya Prakash Yadav1 1.Pediatric Hematology Oncology & Bone Marrow Transplant Unit, Department of
RI PT
Pediatrics, Fortis Memorial Research Institute, Gurgaon, Haryana, India.
2. Department of Neurosurgery, Fortis Memorial Research Institute, Gurgaon.
M AN U
SC
3. Department of Pathology, SRL Laboratories, Fortis Memorial Research Institute, Gurgaon.
Correspondence: Dr Satya P Yadav, Pediatric Hematology Oncology & BMT Unit, Department of Pediatrics, Fortis Memorial Research Institute, Gurgaon, Haryana, India
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122001.
Email: [email protected], Fax: +91 1244962222 Total Pages – 8
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Table – 1
EP
Abstract (word count) – N/A
Figure - 0
Text (word count) –707
Running title – Multicentric Glioma with Ascites Key words- Multicentric Glioma; Ascites; VP shunt
ACCEPTED MANUSCRIPT Ventriculo-peritoneal shunt associated ascites in a child with Multicentric Low grade Glioma To the editor:
RI PT
Low grade gliomas (LGG) are among the most common pediatric brain tumours with an excellent prognosis and long term survival.1,2 However, multicentric LGG/dissemination at diagnosis of LGG are rare (5%) and do not carry a comparably good prognosis. With
SC
improvements in neuroimaging technology, this phenomenon is being identified with increasing frequency.3-11 We report a case of an infant with multicentric LGG who developed
M AN U
ascites post Ventriculo-peritoneal (VP) shunt placement most probably due to increased CSF protein content as has been reported previously in a few cases with optic pathway gliomas due to increased protein exuded by the widely exposed mass.12,13
A 7-month-old male infant was referred to our institute with complaint of gradually
TE D
increasing head size. He was noticed to have this complaint since 4-months of age and a cranial ultrasound was done which was normal. Child was admitted for evaluation. A neurosurgery opinion was sought and the infant underwent a biopsy and ventriculo-peritoneal
EP
shunt insertion. The investigations are summarized in Table I. The infant was discharged and chemotherapy was planned after 2 weeks. He was admitted to the hospital as he developed
AC C
ascites 5 days after shunt placement. The parents did not report any fever, difficulty in breathing, altered sensorium or seizures. A shunt tap and an ascitic tap were done and sent for analysis, the results of which are summarized in Table I. He developed fever after admission; and a sepsis work up was sent which did not reveal any cause. CSF had shown high protein content. He had abdominal distension and mild respiratory distress due to ascites. Infant was irritable and oral intake was decreased. After neurosurgery consultation shunt revision was done and a
ACCEPTED MANUSCRIPT ventriculo-atrial shunt was placed. Within the first post operative day, he developed CSF collection in the medial aspect of right sternocleidomastoid muscle which needed drainage. He also required mechanical ventilation for one day after the procedure and was extubated a day later before transition to the ward. The swelling in neck subsided and the infant was
against chemotherapy and abandoned treatment.
RI PT
discharged home after a few days. He was advised chemotherapy; however parents opted
Although metastatic/multicentric LGG is a rare entity, it has been reported with increased
SC
frequency due to increased index of suspicion and the use of advanced imaging technique.1, 3
M AN U
We report a case of an infant with multicentric LGG who went on to develop VP shunt associated ascites in view of the rarity of its occurrence. Ascites is an uncommon complication following VP shunt placement. It can be attributable to either infection or tumour seeding in the peritoneal cavity. However there was no evidence of either of these in our patient. Very few cases have been reported of post VP shunt ascites without an
TE D
attributable infection/tumour seeding. In optic pathway glioma, a large surface area of the tumour is exposed to the CSF space likely leading to the exudation of protein in to the
EP
subarachnoid space. An elevation in the CSF protein concentration can be a possible explanation for ascites after VP shunt placement in such patients. Three similar cases have
AC C
been reported by West G.A. et al and just as in our patient, ascites resolved after revision of shunt to a ventriculo-atrial shunt.12 Gil Z. et al has also reported a higher incidence of ascites post VP shunt in patients with optic pathway gliomas which was not associated with infection, tumour metastasis, tumour size or multiple shunt revisions.13 Multicentric LGG in children are relatively lesser known and under-diagnosed tumours, though the reported incidence is now increasing1, 2. These tumours carry a poor prognosis as compared to unicentric LGG. As per largest published study from St Judes 40% of the patients died at 6 yr from daignosis.14 Reasons for the poorer outcome are not clear.
ACCEPTED MANUSCRIPT Symptoms are similar. Surgical resection from multiple sites difficult and cranio-spinal radiotherapy is best avoided for young children. Chemotherapy is believed to be the best modality of treatment for such cases. 14 VP shunt associated ascites is a rare complication and has been conventionally thought to be due to infection or tumour seeding in most of the
RI PT
cases. However for tumours that are widely exposed to the CSF space, VP shunt associated ascites can occur due to elevated proteins exuded from the tumour into CSF. When this is suspected, a ventriculo-atrial shunt is the procedure of choice if CSF diversion is required
SC
which was performed in our case as well References:
M AN U
1. Pollack IF, Hurtt M, Pang D, Albright AL. Dissemination of low grade intracranial astrocytomas in children. Cancer 1994; 73: 2869-78.
2. Rorke LB, Schut L. Introductory survey of pediatric brain tumours. In: McLaurin RL, Schut L, Venes JL, Epstein F. Pediatric Neurosurgery. 2nd ed. Philadelphia: WB
TE D
Saunders, 1989:335-7.
3. Prados M, Mamelak AN. Metastasizing low grade gliomas in children. Redefining an old disease. Cancer. 1994 Jun 1; 73(11):2671-3.
EP
4. Civitello LA, Packer RJ, Rorke LB, Siegal K, Sutton LN, Schut L. Leptomeningeal
AC C
dissemination of low-grade gliomas in childhood. Neurology 1988; 38:562-6. 5. Kocks W, Kalff R, Reinhardt V, Grote W, Hilke J. Spinal metastasis of pilocytic astrocytoma of the chiasma opticum. Childs Nerv Syst 1989; 5:118-20.
6. McLaughlin JE. Juvenile astrocytomas with subarachnoid spread. JPathol 1976; 118:lOl-7. 7. Obana WG, Cogen PH, Davis RL, Edwards MSB. Metastatic juvenile pilocytic astrocytoma. ] Neurosurg 1991; 75:972-5.
ACCEPTED MANUSCRIPT 8. Rutka JT, George RE, Davidson G, Hoffman HJ. Low-grade astrocytoma of the tectal region as an unusual cause of knee pain: case report. Neurosurgery 1991; 29:608-12. 9. Shapiro K, Shulman K. Spinal cord seeding from cerebellar astrocytomas. Child’s Brain 1976; 2:177-86.
RI PT
10. Polmeteer FE, Kernohan JW. Meningeal gliomatosis: a study of 42 cases. Arch Neurol Psychiatry 1947; 57:593-616.
11. Cairns H, Russell DS. Intracranial and spinal metastases in gliomas of the brain. Brain
SC
1931; 54:377-420.
12. West G.A., Berger M.S., Geyer J.R. Childhood Optic Pathway Tumors Associated
M AN U
with Ascites following Ventriculoperitoneal Shunt Placement. Pediatr Neurosurg 1994; 21:254–259.
13. Gil Z, Beni-Adani L, Siomin V, Nagar H, Dvir R, Constantini S. Ascites following ventriculoperitoneal shunting in children with chiasmatic hypothalamic glioma.
TE D
Childs Nerv Syst. 2001 Jun; 17(7):3958.
14. Chamdine, O., Broniscer, A., Wu, S., Gajjar, A. and Qaddoumi, I. (2016), Metastatic Low-Grade Gliomas in Children: 20 Years' Experience at St. Jude Children's
AC C
EP
Research Hospital. Pediatr Blood Cancer, 63: 62–70.
ACCEPTED MANUSCRIPT Table I. Details of Imaging , Histopathology , CSF and Ascites fluid analysis Investigation
Results
MRI Brain
A large mass measuring 5.4 x 4.2 x 4.1 cm with multiple areas of cyst formation in the suprasellar/anterior 3rd ventricle region extending to the left medial temporal lobe. Lesion - isointense on diffusion weighted
RI PT
images with variable ADC, causing mass effect on the ventricular system with obstructive hydrocephalus and showing heterogenous enhancement on post contrast study. The chiasma not seen separate to
SC
the mass. Nodular enhancement also seen along the surface of midbrain, pons, cervical spinal cord and left tonsil indicating meningeal spread. A large arachnoid cyst noted in relation to the anterior pole of the left
M AN U
temporal lobe.
6.4 ng/ml (0-8.1)
Serum βhCG
<1.2 mIU/ml (0-2)
Serum Cortisol
20 µg/dL (3.7-19.4)
CSF AFP
0.52 ng/ml (0-99999.99)
CSF βhCG
<1.2 mIU/ml (0-2)
TE D
Serum AFP
CSF R/E
Clear, colourless, cob web absent, Glucose-48mg/dl (45-80), protein <2 mg/dl (15-45), TLC 11cells/mm3 (0-5), mononuclear cells 45.5% (16-
EP
94), neutrophils 54.5% (0-8)
No growth
Biopsy Morphology with IHC
Section from the ventricular cyst wall shows ependymal lining with
AC C
CSF Gram stain and C/S
underlying glial tissue with spindle cells and gemistocytic cells. Specimen from tumor tissue shows glial tumor composed of spindle cells and round to polygonal cells, thin vasculature, no necrosis or mitosis. The spindle cells express GFAP & Vimentin, do not express EMA or Synaptophysin or Neu N, CD34 also does not high light dysplastic neurons, Ki67 labelling index is low 1-2%, thus features of low grade glioma possibly Pilocytic Astrocytoma.
CSF R/E (shunt tap)
Clear, pale yellow, cobweb absent, glucose 39mg/dl (45-80), protein 740
ACCEPTED MANUSCRIPT mg/dl (15-45),TLC 29 cells/mm3, mononuclear cells 96.6% (16-94), neutrophils 3.4% (0-8%), RBCs 1000cells/mm3 Ascitic tap fluid
Hazy, pale yellow, clot absent, protein <2 g/dl, glucose 75 mg/dl, TLC 84 cells/mm3,mononuclear cells+ macrophages+ mesothelial cells 97.6% , neutrophils 2.4%, RBCs 2000 cells/mm3, no malignant cells,
Procalcitonin
<0.05 ng/ml
Blood C/S
No growth
Ascitic tap fluid C/S
No growth
SC
<5 mg/dl (0-10)
AC C
EP
TE D
M AN U
CRP
RI PT
degenerated mesothelial cells with few inflammatory cells.
S2468-1245(17)30063-3
DOI:
10.1016/j.phoj.2017.09.002
Reference:
PHOJ 50
To appear in:
Pediatric Hematology Oncology Journal
Received Date: 22 May 2017 Revised Date:
7 September 2017
Accepted Date: 8 September 2017
Please cite this article as: Thakkar D, Patir R, Ahlawat S, Yadav SP, Ventriculo-peritoneal shunt associated ascites in a child with multicentric low grade glioma, Pediatric Hematology Oncology Journal (2017), doi: 10.1016/j.phoj.2017.09.002. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Ventriculo-peritoneal shunt associated ascites in a child with Multicentric Low grade Glioma Dhwanee Thakkar1, Rana Patir2, Sunita Ahlawat3, Satya Prakash Yadav1 1.Pediatric Hematology Oncology & Bone Marrow Transplant Unit, Department of
RI PT
Pediatrics, Fortis Memorial Research Institute, Gurgaon, Haryana, India.
2. Department of Neurosurgery, Fortis Memorial Research Institute, Gurgaon.
M AN U
SC
3. Department of Pathology, SRL Laboratories, Fortis Memorial Research Institute, Gurgaon.
Correspondence: Dr Satya P Yadav, Pediatric Hematology Oncology & BMT Unit, Department of Pediatrics, Fortis Memorial Research Institute, Gurgaon, Haryana, India
TE D
122001.
Email: [email protected], Fax: +91 1244962222 Total Pages – 8
AC C
Table – 1
EP
Abstract (word count) – N/A
Figure - 0
Text (word count) –707
Running title – Multicentric Glioma with Ascites Key words- Multicentric Glioma; Ascites; VP shunt
ACCEPTED MANUSCRIPT Ventriculo-peritoneal shunt associated ascites in a child with Multicentric Low grade Glioma To the editor:
RI PT
Low grade gliomas (LGG) are among the most common pediatric brain tumours with an excellent prognosis and long term survival.1,2 However, multicentric LGG/dissemination at diagnosis of LGG are rare (5%) and do not carry a comparably good prognosis. With
SC
improvements in neuroimaging technology, this phenomenon is being identified with increasing frequency.3-11 We report a case of an infant with multicentric LGG who developed
M AN U
ascites post Ventriculo-peritoneal (VP) shunt placement most probably due to increased CSF protein content as has been reported previously in a few cases with optic pathway gliomas due to increased protein exuded by the widely exposed mass.12,13
A 7-month-old male infant was referred to our institute with complaint of gradually
TE D
increasing head size. He was noticed to have this complaint since 4-months of age and a cranial ultrasound was done which was normal. Child was admitted for evaluation. A neurosurgery opinion was sought and the infant underwent a biopsy and ventriculo-peritoneal
EP
shunt insertion. The investigations are summarized in Table I. The infant was discharged and chemotherapy was planned after 2 weeks. He was admitted to the hospital as he developed
AC C
ascites 5 days after shunt placement. The parents did not report any fever, difficulty in breathing, altered sensorium or seizures. A shunt tap and an ascitic tap were done and sent for analysis, the results of which are summarized in Table I. He developed fever after admission; and a sepsis work up was sent which did not reveal any cause. CSF had shown high protein content. He had abdominal distension and mild respiratory distress due to ascites. Infant was irritable and oral intake was decreased. After neurosurgery consultation shunt revision was done and a
ACCEPTED MANUSCRIPT ventriculo-atrial shunt was placed. Within the first post operative day, he developed CSF collection in the medial aspect of right sternocleidomastoid muscle which needed drainage. He also required mechanical ventilation for one day after the procedure and was extubated a day later before transition to the ward. The swelling in neck subsided and the infant was
against chemotherapy and abandoned treatment.
RI PT
discharged home after a few days. He was advised chemotherapy; however parents opted
Although metastatic/multicentric LGG is a rare entity, it has been reported with increased
SC
frequency due to increased index of suspicion and the use of advanced imaging technique.1, 3
M AN U
We report a case of an infant with multicentric LGG who went on to develop VP shunt associated ascites in view of the rarity of its occurrence. Ascites is an uncommon complication following VP shunt placement. It can be attributable to either infection or tumour seeding in the peritoneal cavity. However there was no evidence of either of these in our patient. Very few cases have been reported of post VP shunt ascites without an
TE D
attributable infection/tumour seeding. In optic pathway glioma, a large surface area of the tumour is exposed to the CSF space likely leading to the exudation of protein in to the
EP
subarachnoid space. An elevation in the CSF protein concentration can be a possible explanation for ascites after VP shunt placement in such patients. Three similar cases have
AC C
been reported by West G.A. et al and just as in our patient, ascites resolved after revision of shunt to a ventriculo-atrial shunt.12 Gil Z. et al has also reported a higher incidence of ascites post VP shunt in patients with optic pathway gliomas which was not associated with infection, tumour metastasis, tumour size or multiple shunt revisions.13 Multicentric LGG in children are relatively lesser known and under-diagnosed tumours, though the reported incidence is now increasing1, 2. These tumours carry a poor prognosis as compared to unicentric LGG. As per largest published study from St Judes 40% of the patients died at 6 yr from daignosis.14 Reasons for the poorer outcome are not clear.
ACCEPTED MANUSCRIPT Symptoms are similar. Surgical resection from multiple sites difficult and cranio-spinal radiotherapy is best avoided for young children. Chemotherapy is believed to be the best modality of treatment for such cases. 14 VP shunt associated ascites is a rare complication and has been conventionally thought to be due to infection or tumour seeding in most of the
RI PT
cases. However for tumours that are widely exposed to the CSF space, VP shunt associated ascites can occur due to elevated proteins exuded from the tumour into CSF. When this is suspected, a ventriculo-atrial shunt is the procedure of choice if CSF diversion is required
SC
which was performed in our case as well References:
M AN U
1. Pollack IF, Hurtt M, Pang D, Albright AL. Dissemination of low grade intracranial astrocytomas in children. Cancer 1994; 73: 2869-78.
2. Rorke LB, Schut L. Introductory survey of pediatric brain tumours. In: McLaurin RL, Schut L, Venes JL, Epstein F. Pediatric Neurosurgery. 2nd ed. Philadelphia: WB
TE D
Saunders, 1989:335-7.
3. Prados M, Mamelak AN. Metastasizing low grade gliomas in children. Redefining an old disease. Cancer. 1994 Jun 1; 73(11):2671-3.
EP
4. Civitello LA, Packer RJ, Rorke LB, Siegal K, Sutton LN, Schut L. Leptomeningeal
AC C
dissemination of low-grade gliomas in childhood. Neurology 1988; 38:562-6. 5. Kocks W, Kalff R, Reinhardt V, Grote W, Hilke J. Spinal metastasis of pilocytic astrocytoma of the chiasma opticum. Childs Nerv Syst 1989; 5:118-20.
6. McLaughlin JE. Juvenile astrocytomas with subarachnoid spread. JPathol 1976; 118:lOl-7. 7. Obana WG, Cogen PH, Davis RL, Edwards MSB. Metastatic juvenile pilocytic astrocytoma. ] Neurosurg 1991; 75:972-5.
ACCEPTED MANUSCRIPT 8. Rutka JT, George RE, Davidson G, Hoffman HJ. Low-grade astrocytoma of the tectal region as an unusual cause of knee pain: case report. Neurosurgery 1991; 29:608-12. 9. Shapiro K, Shulman K. Spinal cord seeding from cerebellar astrocytomas. Child’s Brain 1976; 2:177-86.
RI PT
10. Polmeteer FE, Kernohan JW. Meningeal gliomatosis: a study of 42 cases. Arch Neurol Psychiatry 1947; 57:593-616.
11. Cairns H, Russell DS. Intracranial and spinal metastases in gliomas of the brain. Brain
SC
1931; 54:377-420.
12. West G.A., Berger M.S., Geyer J.R. Childhood Optic Pathway Tumors Associated
M AN U
with Ascites following Ventriculoperitoneal Shunt Placement. Pediatr Neurosurg 1994; 21:254–259.
13. Gil Z, Beni-Adani L, Siomin V, Nagar H, Dvir R, Constantini S. Ascites following ventriculoperitoneal shunting in children with chiasmatic hypothalamic glioma.
TE D
Childs Nerv Syst. 2001 Jun; 17(7):3958.
14. Chamdine, O., Broniscer, A., Wu, S., Gajjar, A. and Qaddoumi, I. (2016), Metastatic Low-Grade Gliomas in Children: 20 Years' Experience at St. Jude Children's
AC C
EP
Research Hospital. Pediatr Blood Cancer, 63: 62–70.
ACCEPTED MANUSCRIPT Table I. Details of Imaging , Histopathology , CSF and Ascites fluid analysis Investigation
Results
MRI Brain
A large mass measuring 5.4 x 4.2 x 4.1 cm with multiple areas of cyst formation in the suprasellar/anterior 3rd ventricle region extending to the left medial temporal lobe. Lesion - isointense on diffusion weighted
RI PT
images with variable ADC, causing mass effect on the ventricular system with obstructive hydrocephalus and showing heterogenous enhancement on post contrast study. The chiasma not seen separate to
SC
the mass. Nodular enhancement also seen along the surface of midbrain, pons, cervical spinal cord and left tonsil indicating meningeal spread. A large arachnoid cyst noted in relation to the anterior pole of the left
M AN U
temporal lobe.
6.4 ng/ml (0-8.1)
Serum βhCG
<1.2 mIU/ml (0-2)
Serum Cortisol
20 µg/dL (3.7-19.4)
CSF AFP
0.52 ng/ml (0-99999.99)
CSF βhCG
<1.2 mIU/ml (0-2)
TE D
Serum AFP
CSF R/E
Clear, colourless, cob web absent, Glucose-48mg/dl (45-80), protein <2 mg/dl (15-45), TLC 11cells/mm3 (0-5), mononuclear cells 45.5% (16-
EP
94), neutrophils 54.5% (0-8)
No growth
Biopsy Morphology with IHC
Section from the ventricular cyst wall shows ependymal lining with
AC C
CSF Gram stain and C/S
underlying glial tissue with spindle cells and gemistocytic cells. Specimen from tumor tissue shows glial tumor composed of spindle cells and round to polygonal cells, thin vasculature, no necrosis or mitosis. The spindle cells express GFAP & Vimentin, do not express EMA or Synaptophysin or Neu N, CD34 also does not high light dysplastic neurons, Ki67 labelling index is low 1-2%, thus features of low grade glioma possibly Pilocytic Astrocytoma.
CSF R/E (shunt tap)
Clear, pale yellow, cobweb absent, glucose 39mg/dl (45-80), protein 740
ACCEPTED MANUSCRIPT mg/dl (15-45),TLC 29 cells/mm3, mononuclear cells 96.6% (16-94), neutrophils 3.4% (0-8%), RBCs 1000cells/mm3 Ascitic tap fluid
Hazy, pale yellow, clot absent, protein <2 g/dl, glucose 75 mg/dl, TLC 84 cells/mm3,mononuclear cells+ macrophages+ mesothelial cells 97.6% , neutrophils 2.4%, RBCs 2000 cells/mm3, no malignant cells,
Procalcitonin
<0.05 ng/ml
Blood C/S
No growth
Ascitic tap fluid C/S
No growth
SC
<5 mg/dl (0-10)
AC C
EP
TE D
M AN U
CRP
RI PT
degenerated mesothelial cells with few inflammatory cells.