|Year : 2011 | Volume
| Issue : 3 | Page : 56-71
Tumors of the posterior third ventricular region in pediatric patients: The Indian perspective and a review of literature
Sanjay Behari1, Sushila Jaiswal2, Prakash Nair1, Pallav Garg1, Awadhesh K Jaiswal1
1 Department of Neurosurgery, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
2 Department of Neuropathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
|Date of Web Publication||10-Oct-2011|
Department of Neurosurgery, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Diverse tumors in the posterior third ventricular region (TPTVR) frequently occur in children. A decade's experience with pediatric TPTVR is presented, focusing on the Indian perspective. Materials and Methods: 25 children (age range: 3-18 years; mean age: 13.32 years; presentation range: 7 days-2.5 years) had clinico-radiological assessment with contrast computed tomography (CT) and magnetic resonance imaging (MRI). The ventricular/lumbar cerebrospinal fluid (CSF) alpha feto protein (AFP)/beta human chorionic gonadotrophin (HCG) estimation was done when radiological suspicion of a germ cell tumor was present. Extent of resection was deemed partial when some tumor mass remained at the end of surgery, near total when <10% was retained over vital neurovascular structures, and total when complete resection was attained. Results: Operations included infratentorial supracerebellar approach (n = 12), occipito-transtentorial approach (n = 2), endoscopic biopsy and third ventriculostomy (n = 1), frontal parasagittal craniotomy, interhemispheric transcallosal subchoroidal approach (n = 2), middle temporal gyrus transcortical transventricular approach (n = 1), fronto-temporo-zygomatic combined transylvian and subtemporal approach (n = 1) and right ventriculoperitoneal shunt and stereotactic biopsy (n = 1). Only CSF diversion was performed for five patients with a small TPTVR. CSF diversion was required in 12 (48%) patients. Tumor pathology included pinealoblastoma (n = 4; one with pineocytic differentiation), nongerminomatous germ cell tumor (NGGCT; n = 3), germinoma (n = 3), pilocytic astrocytoma (n = 2), epidermoid (n = 3) and primitive neuroectodermal tumor (PNET), fibrillary astrocytoma, glioblastoma, teratoma, and meningioma (n = 1, respectively). A patient with neurocysticercosis was diagnosed solely on MRI (four did not undergo biopsy). Fractionated radiotherapy was administered in 13 patients with primary pineal tumors, PNET, NGGCT, fibrillary astrocytoma and glioblastoma. Extent of excision was total in 10 (40%), near total in 5 (20%), partial in 3 (12%) and a biopsy in 2 (8%) patients. Conclusions: Histopathologic characterization of TPTVR is essential prior to their further management. Benign lesions often have a good prognosis following gross total surgical resection. Pure germinomas are highly susceptible to radiotherapy. NGGCTs often have malignant components that require adjuvant therapy following surgery. The advancements in microsurgical techniques have led to gratifying perioperative results in these deep-seated lesions.
Keywords: Histology, infratentorial supracerebellar approach, occipital transtentorial approach, pineal tumors, posterior third ventricle, surgery
|How to cite this article:|
Behari S, Jaiswal S, Nair P, Garg P, Jaiswal AK. Tumors of the posterior third ventricular region in pediatric patients: The Indian perspective and a review of literature. J Pediatr Neurosci 2011;6, Suppl S1:56-71
|How to cite this URL:|
Behari S, Jaiswal S, Nair P, Garg P, Jaiswal AK. Tumors of the posterior third ventricular region in pediatric patients: The Indian perspective and a review of literature. J Pediatr Neurosci [serial online] 2011 [cited 2018 Jan 20];6, Suppl S1:56-71. Available from: http://www.pediatricneurosciences.com/text.asp?2011/6/3/56/85713
| Introduction|| |
Tumors in the posterior third ventricular region (TPTVR) have a common anatomical location, yet present a diverse spectrum of histopathology, radiological characteristics, natural history and prognosis. ,,,,,, A proper categorization of these tumors into their histological subtypes considerably helps in effectively managing these lesions as well as in their prognostication. These tumors are rare, comprising less than 11% of all pediatric tumors. , In children, approximately 60% of pineal region tumors are of germ cell origin.  A multimodality strategy consisting of surgery (total resection being possible in nearly 30% of tumors), radio- and chemotherapy, often encompassing minimally invasive techniques such as stereotactic biopsy, radiosurgery and endoscopic surgery, has considerably improved outcomes in these lesions. , In the present review, a decade's experience with TPTVR in the pediatric population is presented with a focus on the Indian perspective.
| Materials and Methods|| |
Records of pediatric patients with TPTVR operated over the last decade were retrieved from their case files and operation theater register. Histology of the cases where surgical excision/biopsy was performed was confirmed from the histopathology reports. Their preoperative evaluation consisted of clinical and radiological assessment with contrast-enhanced computerized tomography (CECT) and gadolinium-enhanced magnetic resonance imaging (MRI). The ventricular/lumbar cerebrospinal fluid (CSF) was subjected to alpha feto protein (AFP)/human chorionic gonadotrophin (HCG) assessment when radiological suspicion of a germ cell tumor (GCT) was present. Extent of resection was deemed partial resection when some tumor mass remained at the end of surgery, near total when less than 10% was retained over vital neurovascular structures, and total when complete resection was attained.
| Results|| |
In this series of 25 pediatric patients, the age ranged from 3 to 18 years, with a mean age of 13.32 years. [Table 1] The male:female ratio was 19:6. The duration of presentation ranged from 7 days to 2.5 years. The procedures performed for accessing TPTVR included infratentorial supracerebellar approach (n = 12), right occipito-transtentorial approach (n = 2), endoscopic biopsy and third ventriculostomy (n = 1), right frontal parasagittal craniotomy, interhemispheric transcallosal subchoroidal approach (n = 2), right transcortical and transventricular approach through the middle temporal gyrus (n = 1), fronto-temporo-zygomatic craniotomy, combined transylvian and subtemporal approach (n = 1) and right ventriculoperitoneal shunt and stereotactic biopsy (n = 1). No definite procedure for the primary TPTVR was performed for five patients.
The CSF diversion procedures were performed in 12 (48%) patients and included a biventriculoperitoneal shunt (n = 1), revision of blocked ventriculoperitoneal shunt (n = 1), revision of blocked third ventriculostomy by placement of a ventriculoperitoneal shunt (n = 1), a primary ventriculoperitoneal shunt (n = 5), third ventricle-supracerebellar cisternal shunt (n = 1) and an endoscopic third ventriculostomy (n = 3).
Gross total excision of the tumor was performed in 10 (40%) patients. A near total excision was performed in 5 (20%), partial excision in 3 (12%) and a biopsy in 2 (8%) patients. No definitive surgery for the primary tumor was performed in 5 (20%) patients with a small TPTVR causing aqueductal obstruction, who received a CSF diversion procedure for hydrocephalus. The latter are on a regular follow-up with a serial assessment of the size of their primary tumor.
|Table 1: Spectrum of pediatric patients with posterior third ventricular lesions|
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The tumor pathology included the following: Pinealoblastoma (n = 4; one with pineocytic differentiation) [Figure 1] and [Figure 2], nongerminomatous GCT (NGGCT; n = 3) [Figure 3], germinoma (n = 3) [Figure 4] and [Figure 5], primitive neuroectodermal tumor (PNET, n = 1) [Figure 6], pilocytic astrocytoma (n = 2) [Figure 7], fibrillary astrocytoma (n = 1), [Figure 8] and [Figure 9], glioblastoma (n = 1) [Figure 10], teratoma (n = 1) [Figure 11], epidermoid (n = 3) [Figure 12] and [Figure 13] and meningioma (n = 1) [Figure 14]. A patient with neurocysticercosis was diagnosed solely on MRI [Figure 15]. Four other patients did not undergo biopsy for their primary tumor. Fractionated radiotherapy was administered in 13 patients with primary pineal tumors, PNET, NGGCT, fibrillary astrocytoma and glioblastoma.
|Figure 1: Patient 1. (a) T1 sagittal and (b) T2 axial MR images showing iso- to hyperintense, intraventricular lesion with moderate hydrocephalus. (c) Endosopic biopsy from the tumor (arrow). (d) H and E stained section (×400) showing sheets of small cells displaying round to oval hyperchromatic nuclei and scant cytoplasm with few fibrillary areas. Mitosis is seen. Occasional formation of rosettes is also noted. Calcification is prominent. The findings are suggestive of a pineoblastoma|
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|Figure 2: H and E stained section (×200) shows a moderately cellular tumor composed of small round to oval cell with mildly hyperchromatic nuclei in the background of fibrillary material. At places, pineocytic rosettes are seen. Mitosis is sparse. The findings are suggestive of a pineocytoma|
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|Figure 3: Patient 6. (a) T1 contrast axial MR image showing a uniformly enhancing tumor. (b) H and E sections showing different components of a mixed germ cell tumor. Foci of germinoma (×400) showing sheets of tumor cells with clear cytoplasm, round to irregular nuclei with prominent nucleoli; (c) microcystic areas of yolk sac (×100) component; (d) undifferentiated mesenchymal elements with (×100) epithelial gland formation; and (e) the higher power (×400) of the same|
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|Figure 4: Patient 8. (a) T1 contrast sagittal and (b) T1 contrast axial MR images showing uniform homogenous enhancement in pineal tumor infiltrating third ventricle until foramen of Monro and brain stem. (c) Postoperative T1 sagittal and (d) axial images showing complete tumor removal. (e) H and E (×400) sections showing round to polygonal tumor cells disposed in groups, displaying conspicuous nucleoli at places and variable amount of pale to amphophilic cytoplasm. The groups of tumor cells are separated by fibrous septa infiltrated by small mature lymphocytes. (f) Tumor cells are positive for CD117 (immunohistochemical stain; ×400). (g) Tumor cells are positive for placenta-like alkaline phosphatase (PLAP) (immunohistochemical stain; ×400). The histopathology and immunohistochemistry confirm the presence of a germinoma|
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|Figure 5: Patient 8. Infratentorial, supracerebellar approach in sitting position. (a) The dura is opened with a "Y" shaped incision and reflected superiorly along the transverse sinus. (b) The anastomotic veins between the superior surface of cerebellar hemispheres and the tentorium are coagulated. (c) The arachnoid covering the tumor in the posterior third ventricular region is seen due to gravity-assisted fall of the cerebellum and (d) the precentral cerebellar vein is coagulated and divided. The arachnoid is removed and tumor decompressed in a piecemeal manner. The opening of the third ventricle following tumor removal drains CSF|
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|Figure 6: Patient 11. (a) T1 contrast axial and (b) sagittal MR showing heterogeneous contrast enhancement in a large lobulated lesion in right thalamus and medial wall of trigonal region of lateral ventricle reaching to posterior third ventricular region. Pineal gland is seen separately from lesion. There is midline shift toward left. (c) H and E stained sections (×400) showing diffuse infiltration by sheets of atypical round cells which are small to medium sized having enlarged hyperchromatic nuclei with nuclear membrane irregularity, coarse chromatin, inconspicuous nucleoli and scant amount of cytoplasm. Increased mitotic figures and apoptotic bodies are also noted. The findings are suggestive of a primitive neuroectodermal tumor|
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|Figure 7: Patient 12. (a) T1 sagittal, (b) T2 axial and (c) T2 coronal MR showing T1 hypointense, T2 hyperintense, multiseptate lesion in third ventricle, extending from pineal region to foramen of Monro arising from midbrain and pons. (d and e) T1 axial postoperative images showing tumor excision. (f) H and E stained sections (×200) showing the tumor composed of oval to elongated nuclei with fine chromatin, inconspicuous nucleoli and moderate amount of thin piloid cytoplasm with bipolar processes lying in a fibrillary matrix. Occasional hyaline globules and Rosenthal's fibers are also seen. The findings are suggestive of a pilocytic astrocytoma|
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|Figure 8: Patient 14. (a) T1 axial, (b) Flair, (c) T1 sagittal, (d) T2 sagittal and (e) T1 contrast sagittal images showing T1 isointense, T2 hyperintense lesion with superior cystic component and patchy inhomogenous enhancement with perifocal edema. (f) H and E stained sections (×200) showing moderately cellular neoplasm comprising atypical astrocytes in fibrillary background. Tumor cells are round to oval with central vesicular nuclei with moderate amount of cytoplasm. The findings are suggestive of fibrillary astrocytoma grade|
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|Figure 9: Patient 14: Right frontal parasagittal craniotomy, interhemispheric transcallosal subchoroidal approach. (a) Right frontal lobe retraction for interhemispheric exposure; (b) bilateral distal anterior cerebral arteries exposed; (c) exposure of corpus callosum; (d) corpus callosal incision and CSF drainage; (e) exposure of lateral ventricular choroid plexus; (f) subchoroidal approach to third ventricle; (g) exposure of the tumor; (h) tumor decompression; (i) the lax right frontal lobe after surgery|
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|Figure 10: Patient 15. (a and b) Contrast-enhanced CT scan showing a hyperdense lesion with central necrosis and peripheral enhancement in right thalamic region, extending to posterior third ventricular region, medial wall of trigone and splenium of corpus callosum with midline shift and hydrocephalus. (c) H and E stained sections (×200) showing sheets of moderately pleomorphic cells on a fibrillary background along with necrosis. (d) Foci of interspersed endothelial proliferation and mitotic figuresare also noted. The findings are suggestive of a glioblastoma multiforme (WHO grade IV)|
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|Figure 11: Patient 20. (a and b) T1 axial, (c) T2 sagittal and (d) T1 contrast sagittal MR image showing a T1 iso- to hyperintense, T2 heterogenously hypo- to hyperintense nonenhancing lesion with gross hydrocephalus. (e) H and E stained sections (×200) showing keratinized stratified squamous epithelium with keratin flakes. Subepidermal zone shows numerous sebaceous glands, fibrofatty tissue along with areas of hemorrhage. The findings are suggestive of a teratoma|
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|Figure 12: Patient 22. (a) T1 contrast axial and (b) T1 contrast sagittal MR images showing T1, T2 hypointense, nonenhancing lesion in posterior third ventricular region, ambient and quadrigeminal cisterns with mild hydrocephalus. (d) Diffusion weighted images showing restriction of diffusion. (e) Postoperative axial and (f) sagittal images showing total excision. (f) H and E (×400) section showing a cyst lined by thinned out stratified squamous epithelium filled with keratin material suggestive of an epidermoid|
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|Figure 13: Patient 22. Right occipital craniotomy, posterior interhemispheric, transtentorial approach adopted in prone position with the Table tilted about 20°-30° toward the side of approach. (a) The dural exposure that extends until the rim of the torcula and transverse sinus inferiorly and the posterior part of the superior sagittal sinus medially. (b) Gentle lateral retraction of the right parieto-occipital lobe exposes the falx cerebri and its junction with the tentorium that encloses the straight sinus within its leaves at the junctional area. The tentorium is traced until its incisura parallel to the straight sinus. (c) The tentorial surface is coagulated and divided parallel and slightly away from the straight sinus and the arachnoidal covering of the epidermoid removed exposing the tumor. (d) The vein of Galen and basal vein of Rosenthal and (e) the posterior thalamus, collicular plate and the quadrigeminal cistern are visible following tumor removal. (f) The lax brain after the procedure|
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|Figure 14: Patient 24. (a) T1 contrast MR sagittal MR image showing a uniformly enhancing tumor in quadrigeminal region and supracerebellar cistern. (b) H and E stained sections (×200) showing tumor arranged in whorls and nests displaying round to oval nuclei, dispersed chromatin, indistinct nucleoli and moderate amount of cytoplasm suggestive of a meningothelial meningioma|
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|Figure 15: Patient 25. H and E stained section (40) shows a protoplasmic cyst comprising an outer eosinophilic cuticular layer, subcuticular cellular layer with dark staining nuclei and an inner fibrillary reticular layer consistent with neurocysticercosis|
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Following surgery, there was increase in ataxia, postoperative mutism, CSF leak through operative wound and pseudomeningocele formation in one patient each, respectively. One patient did not improve from the preoperative status of spontaneous eye opening, spontaneous limb movement and not following commands. There was no mortality in the series.
| Discussion|| |
Histopathologic characteristics that govern management
TPTVR may be divided into four diverse groups: Pineal parenchymal tumors, GCTs, glial tumors and miscellaneous tumors. , In our pediatric series, we had a heterogeneous mix of the characteristic histopathologic spectrum of TPTVR.
Pineal parenchymal tumors [Figure 1] and [Figure 2] include the entire range from the benign and well-differentiated pineocytoma to the malignant and aggressive pinealoblastoma and the intermediate-grade mixed pineal tumors (including the pinealoblastoma with pineocytic differentiation) interspersed in between. Pineocytomas are well-differentiated, moderately cellular neoplasms composed of relatively small, uniform, mature appearing pineocytes often forming large pineocytomatous rosettes. They show strong immunoreactivity for synaptophysin, neuron specific enolase (NSE) and neurofilament protein (NFP). They behave more aggressively in children than in adults. Gross total resection or radiosurgical treatment often results in long-term tumor-free survival without additional adjuvant therapy. , In our pediatric patients, a pure pineocytoma was not seen although one patient had an intermediate-type pinealoblastoma with pineocytic differentiation.
Pinealoblastomas are highly malignant embryonal tumors (WHO grade IV) composed of dense patternless sheets of small cells with round to somewhat irregular nuclei and scant cytoplasm. Pineocytomatous rosettes are lacking, but Homer Wright and Flexner-Wintersteiner rosettes may be seen. The immunophenotype of pinealoblastomas is similar to that of pineocytomas and includes reactivity for neuronal, glial and photoreceptor markers. Positivity for synaptophysin, NSE, NFP, class III β-tubulin and chromogranin A may be seen as can retinal S-antigen staining. Average molecular immunology borstel (MIB)-1 indices are high. Within the pediatric population, they are increasingly aggressive with decreasing age of presentation. They are indistinguishable on histological grounds from medulloblastomas and other PNETs and routinely require adjuvant radio-chemotherapy after resection. Surgical decompression to less than 1 cm 3 may be associated in a survival benefit as occurs in the patients with medulloblastomas. Their malignant nature and potential to spread through CSF, however, is responsible for a much poorer prognosis as compared to pineocytomas. A pineal parenchymal neoplasm of intermediate-grade malignancy affects all ages and is composed of diffuse sheets or large lobules of uniform cells with mild to moderate nuclear atypia and low to moderate level mitotic activity. The intermediate-grade mixed pineal tumors have an unpredictable course and should be treated as malignant lesions. ,,
GCTs include two categories: (a) germinomas and (b) NGGCT such as endodermal sinus tumors, choriocarcinomas, embryonal carcinomas and mature and immature teratomas [Figure 3]. , They represent the malignant correlate of a normal embryonic stage of development: The primordial germ cell (germinoma), the embryonic differentiated derivative (teratoma) of the pluripotential stem cell of the embryo proper (embryonal carcinoma), as well as the extraembryonic differentiated derivatives which form the yolk sac endoderm (endodermal sinus tumor) and trophoblast (choriocarcinoma). , Central nervous system variants, like the other extragonadal GCT sites, preferentially affect the midline. Eighty percent or more arise in structures approximating the third ventricle, with the region of the pineal gland being their most common site of origin.
Germinomas [Figure 4] and [Figure 5] are the commonest TPTVR in adolescent boys and young men. The cells appear undifferentiated resembling primordial germinal elements. The most consistent immunohistochemical findings are strong cell membrane labeling for c-kit and nuclear reactivity for stem cell marker octamer binding trascription protein (OCT)- 4. Placenta like alkaline phosphatase (PLAP) positivity is less common. They may also show positivity for β-HCG as well as human placental lactogen (HPL). They are extremely radiosensitive and may be treated with radiotherapy after a confirmatory open or stereotactic biopsy.  The latter is necessary as they do not have any special distinguishing feature on MRI except for having an uniform and intense enhancement.  As long-term sequel of radiation therapy in pediatric patients may be particularly disabling, chemotherapeutic trials have also been instituted in children too young to undergo radiotherapy. Germinomas with giant syncytiotrophoblastic cells may have positivity for marker HCG in serum/CSF and have a poorer prognosis when compared to pure germinomas. 
NGGCTs usually have mixed histological patterns and a pure individual histology is rarely encountered [Figure 3]. A yolk cell tumor (endodermal sinus tumor) is composed of primitive appearing epithelial cells representing yolk sac endoderm. These are set in a loose, variably cellular and often conspicuously myxoid matrix resembling extra-embryonic mesoblast. They show Schiller-Duval Bodies More Details and may contain polyvescicular vitelline or reticular pattern. A diagnostic, although inconsistent, feature is the presence of periodic acid Schiff positive and diastase-resistant hyaline globules that may appear in the cytoplasm of the epithelial cells or may be seen free in the adjoining stroma. They show positivity with AFP and are characteristically non-reactive for c-kit and OCT4. Hyaline globules of this tumor are also AFP positive. An embryonal carcinoma is composed of solid sheets of undifferentiated cells or show sign of early differentiation toward embryonic structures, trophoblasts, or extraembryonic endoderm or mesoderm in the form of papillary or granular formation. They show positivity for CD30 and cytokeratin. The choriocarcinoma is characterized by extra-embryonic differentiation along trophoblastic lines. The diagnosis requires the identification of cytotrophoblastic elements and syntrophoblastic giant cells. Syntrophoblastic giant cells' immunoreactivity for β-HCG and HPL is characteristic.
The NGGCTs may have elevated serum/CSF markers. A choriocarcinoma has HCG positivity in serum/CSF while an endodermal sinus tumor has AFP positivity. An immature teratoma may have AFP positivity and an embryonal cell carcinoma may have both HCG and AFP positivity. Their ability to be distinguished based upon their serological/CSF markers may permit their treatment without a tissue diagnosis. Tumor markers are also useful for monitoring response to adjuvant therapy and for detecting early recurrence. Open cytoreductive surgery with histological confirmation is the procedure of choice. ,,,,,
Teratomas in the central nervous system are histologically subcategorized as GCTs [Figure 11]. CNS teratomas contain diverse cell lineages that may retain an embryonal character and display phenotypical differentiation that may be attributed to the three classic germ layers.  Mature and immature components should be differentiated on histological examination as mature teratomas are potentially curable by gross total resection. Mature teratomas are composed of fully differentiated, "adult-type" tissue elements. Immature teratomas contain incompletely differentiated components resembling fetal tissues. Occasionally, a focal malignancy of somatic type in an otherwise mature teratoma may develop, which is known as teratoma with malignant transformation. Surgical excision alone entails a recurrence rate that is much higher for immature or malignant teratomas than that for mature teratomas. Teratomas that have high serum HCG/AFP may show poorer treatment responses than those with the same histological feature and normal levels of these markers. Teratomas, therefore, appear extremely heterogeneous in their responses to therapy, which may lead to fatal treatment failures. ,,, A recent approach that has dramatically improved the survival in these tumors is to give radiation or chemotherapy initially followed by surgery in case a persistent tumor is seen on radiology following the initial treatment. This approach ensures removal of the remaining teratomatous or scar tissue. 
Glial tumors may include pure pineal astrocytomas and astrocytomas infiltrating into the posterior third ventricular region from the surrounding structures such as the brain stem, the thalamus and the subependymal region [Figure 7], [Figure 8], [Figure 9], and [Figure 10]. These are usually low-grade lesions (WHO grade 1 pilocytic astrocytomas and low-grade fibrillary astrocytomas), but the more malignant grade III astrocytomas and glioblastomas may also be encountered usually infiltrating from surrounding regions. Glial tumors may also include ependymomas arising from the third ventricular ependymal wall lining. The circumscribed and cystic lesions in this location are easily resectable, but the diffuse infiltrating lesions are managed by decompression and radiotherapy. ,
The miscellaneous lesions in this location include meningiomas [Figure 14],  pineal cysts (cystic structures surrounded by normal pineal parenchymal tissue),  epidermoids [Figure 12] and [Figure 13] and dermoids, ,,, parasitic cysts [Figure 15], hemangiopericytomas, lymphomas, choroid plexus papillomas, adenocarcinomas, metastasis [Figure 16], atypical teratoid-rhabdoid tumor and chemotectomas.  Some rare tumors have been reported in the Indian literature. Ghosal et al., have described a sporadic case of pinealoblastoma with prominent retinoblastic differentiation in whom the tumor showed a PNET with numerous Flexner-Wintersteiner rosettes and the tumor cells were strongly positive for synaptophysin and negative for glial fibrillary acidic protein (GFAP), S-100 protein and epithelial membrane antigen.  Husain et al., have described a rare pineal papillary glioneuronal tumor.  Srinivas and colleagues have reported a rare pleomorphic xanthoastrocytoma in this region.  Sharma et al.,  and Vaghela et al.,  have described papillary tumors of the pineal region, consisting of both solid and papillary areas with immunohistochemistry showing strong and diffuse positivity for synaptophysin, NSE, chromogranin A, S-100 protein, microtubule associated protein (MAP)-2 and cytokeratin. In all these miscellaneous lesions, the choice of surgical decompression/adjuvant radio-chemotherapy is dictated by the histology of the lesion.
|Figure 16: H and E stained section (×100) showing cellular tumor with large areas of necrosis with tumor cells viable around the blood vessels. The tumor cells display round to oval hyperchromatic nuclei, dispersed chromatin, inconspicuous nucleoli and scant cytoplasm. Brisk mitotic activity is also seen. The findings are suggestive of metastatic carcinoma|
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The majority of patients in our series presented with symptoms and signs of raised intracranial pressure along with secondary optic atrophy and/or VI nerve palsy leading to visual deterioration. This was due to hydrocephalus consequent to compression or obstruction at the aqueductal/third ventricular region. Midbrain compression may result in (a) Perinaud's syndrome due to superior collicular compression resulting in upgaze palsy, near-light reflex dissociation, pupillary asymmetry and nystagmus retractorius; (b) Sylvian aqueduct syndrome comprising horizontal gaze or down gaze palsy; and (c) lid retraction, ptosis or IV nerve palsy with diplopia and compensatory head tilt. Cerebellar ataxia due to superior peduncular or vermian compression, hemiparesis due to compression on the posterior limb of the internal capsule or due to cerebral peduncle involvement, and bilateral hearing impairment due to inferior collicular compression may also be seen. Endocrinal dysfunction may be in the form of hypothalamic manifestations or hypopituitarism with or without diabetes insipidus due to infiltration of the third ventricular floor and suprasellar region by GCTs, and precocious puberty seen with pineal tumors such as a choriocarcinoma or a germinoma containing syncytiotrophoblastic cells that secrete HCG. Occasionally, pineal apoplexy may manifest with sudden severe headache, neck stiffness and rapid neurological deterioration. , Germinomas may have a synchronous presence in the posterior third ventricular and the suprasellar region, with combined manifestations of both these locations. ,
MRI with contrast enhancement helps in identifying the type of tumor (the uniform enhancement of a germinoma;  the nonenhancing, irregular lesion infiltrating into multiple cisterns without mass effect signifying the presence of an epidermoid; ,, the rounded, nonenhancing cystic neurocysticercus cyst;  the diffusely infiltrative, irregularly and minimally enhancing astrocytoma; the evidence of hemorrhage and calcification in pineocytomas/pinealoblastomas, etc.). However, for a majority of primary pineal and GCTs, the MR picture is not diagnostic, and therefore a tissue biopsy becomes mandatory unless the serum markers are pathognomonic. , MRI also helps in deciding whether the surgical approach to be used is supra or infratentorial based upon the superior or inferior displacement of the deep venous system by the tumor. The degree of infiltration into the brain stem, the ventricular ependyma or the hypothalamus often helps in predicting the degree of resectability of the lesion.
Anatomical considerations and choice of surgical approaches
The pineal gland, situated extra-axially in the posterior third ventricular region, is surrounded ventrally by the posterior commissure and third ventricle, dorsally by the velum interpositum enclosing the internal cerebral veins that join the basal vein of Rosenthal forming the vein of Galen before draining into the straight sinus, and posteriorly by the habenular commissure and the quadrigeminal cistern separating it from the superior cerebellar vermis. TPTVR usually originate in the infratentorial compartment and expand into third ventricle and the quadrigeminal cistern. Infiltrative lesions may also invade the brain stem and thalamus. ,,, Horsley was the first to attempt surgery for these lesions. The credit for the first successful excision of tumors of this region goes to Krause  in 1913, who utilized the infratentorial supracerebellar approach, an approach revived by Stein in 1971.  The alternative approaches to this region are Jamieson's  and Poppen's occipital transtentorial approach,  Van Wagenen's posterior transventricular approach  and Dandy's posterior transcallosal approach. 
Infratentorial supracerebellar approach
This is the commonly used approach for lesions of the pineal gland, dorsal midbrain and superior vermis [Figure 5], [Video 1]. ,,, -
The midline trajectory of the approach to the tumor avoids injury to the deep venous channels that usually are located superior to the lesion. The approach is toward the center of the tumor from where it may be extended eccentrically. There is a good exposure with minimal neural damage. The sitting position offers a good exposure with gravity-assisted drainage of blood and CSF.
Lesions with a significant component extending laterally until the trigone of the lateral ventricle or lesions involving the corpus callosum are difficult to remove completely by this trajectory and require supratentorial approaches. The sitting position in which this surgery is usually performed increases the risk of air embolism, tension pneumocephalus and cervical hyperflexion injury leading to quadriplegia.
The sitting position is the preferred position for this approach although a three-fourth prone or lateral decubitus position has also been used. The latter positions are used in the pediatric age group, particularly under 2 years of age. The head in the sitting position must be adequately flexed to align the tentorium in the horizontal position for an adequate exposure of the supra-vermian infratentorial space.
A midline vertical incision extending from the C3 spinous process to 2-3 cm above the external occipital protuberance is utilized. The muscles of the suboccipital and posterior cervical region are retracted after dividing the avascular ligamentum nuchae in the midline. The pericranium covering the occipital bone is dissected off the bone. The suboccipital craniectomy or craniotomy exposes the rim of the torcula and the transverse sinus superiorly and reaches inferiorly until the foramen magnum.
The dura is opened in a "V" or "Y" manner with the base toward the transverse sinus. In case the surgical field of view is not adequate, the bridging veins from the dorsal cerebellar surface to the tentorium may be sacrificed to permit gravity-dependent descent of the cerebellum. Gentle retraction with self-retaining retractors aids in depressing the cerebellum for establishment of the operative corridor between its superior vermian surface and the inferior surface of tentorium.
The arachnoid of the quadrigeminal cistern is thickened and opaque. The midline pre-central cerebellar vein traversing vertically downward in the midline just anterior to the thickened arachnoid may either be retracted or coagulated. This permits a trajectory toward the quadrigeminal cistern, velum interpositum, collicular plates and the third ventricle. Once the tumor is encountered, internal decompression is done followed by careful dissection from the surrounding structures including the deep venous system superiorly and the brain stem, collicular plates and the thalamus anteriorly. Following tumor decompression, the third ventricular cavity and the lining ependyma is well visualized right until the foramen of Monro. In the case of dense adhesions of the tumor capsule to the surrounding vital structures, it is preferable to leave parts of the capsule than risk retraction injury by persisting with its complete removal.
In patients with significant hydrocephalus, a preoperative CSF diversion procedure may be employed prior to the definitive surgery.
Postoperative complications include CSF leak and acute or delayed hemorrhage. This may be due to bleeding within the residual tumor. Alternatively, a point of bleeding may be missed during hemostasis due to gravity-dependent collapse of the bridging veins in sitting position. The rent may open up in the postoperative period when the patient is made supine and his/her blood pressure increases on reversal from anesthesia. Hemorrhagic venous infarction may also occur due to coagulation of a bridging vein.
Occipital transtentorial approach
This approach [Figure 13], [Video 2] -
provides adequate exposure of both the superior and inferior surfaces of the tentorial notch, and hence is excellent for tumors straddling the tentorial notch. This approach is also useful for tumors situated above the confluence of the deep venous system and for tumors extending laterally into the trigone of the lateral ventricle. ,,,,
The patient is placed in prone position or lounging position. In prone position, the table is slightly tilted to the ipsilateral side to facilitate gravity-dependent retraction of the occipital lobe from the falx cerebri.
A square or triangular scalp flap with the longitudinal limb being in the midline and extending from just below the external occipital protuberance to 6-8 cm superior to this point and curving laterally and downward is used. Preferably, the approach is carried out from the non-dominant side.
The craniotomy is fashioned to expose the rim of the transverse sinus inferiorly, the superior sagittal sinus medially and it extends laterally for 5-6 cm. The dural opening may be as two triangular flaps with the base toward the transverse and sagittal sinuses, respectively, or as a square flap medially toward the superior sagittal sinus. In case hydrocephalus is coexistent, the occipital horn/trigone of the lateral ventricle may be tapped to facilitate CSF drainage and brain retraction.
The occipital lobe is gently retracted laterally. This maneuver is facilitated by the fact that bridging veins between the parieto-occipital cerebral surface and the superior sagittal sinus are few and small and may usually be divided with very little risk of venous infarction of the occipital lobe. The falx cerebri, the tentorium, and the dural covering of the straight sinus at the junctional region of these dural folds are visualized from the region of the torcula to the tentorial incisura. The tentorium is coagulated parallel and lateral to the straight sinus (avoiding any venous lakes in close proximity to the straight sinus) and divided until the incisural edge, thereby bringing the superior cerebellar surface in view. The divided leaflets of the tentorium are reflected using stay sutures. The opaque and tough arachnoid over the deep veins is left intact if the tumor is below their level. Working in the arachnoidal plane below the major veins, lesion of the posterior third ventricular regions is exposed. The tumor removal is then carried out in a piecemeal manner. Following tumor removal, the brain stem, the collicular plate and the posterior thalamic regions are well visualized.
Adequate exposure both above and below the tentorial notch is available. Lesions reaching until the trigone and corpus callosum are accessible. This approach is specially preferred in cases where the deep venous system is dorsally displaced as occurs in tentorial meningiomas.
In tumors extending eccentrically to the contralateral side, complete removal is difficult. Care must be taken to avoid damage to the occipital lobe (that may precipitate homonymous hemianopia) and the splenium of corpus callosum (that may result in posterior disconnection syndrome).
Regardless of the approach, Perinaud's syndrome with upward gaze palsy, pupillary and accommodation abnormalities with partial or complete oculomotor nerve palsy, trochlear nerve injury with diplopia or even alteration of sensorium due to brain stem injury may result.
Alternative approaches may be utilized to access pineal region lesions. ,, The posterior interhemispheric transcallosal approach utilizes a parietal, interhemispheric approach to gain access to the lesions situated above the major venous structures and involving the posterior corpus callosum.  The anterior transcallosal, transventricular approach [Figure 9] is useful when the tumor occupies the lateral ventricles or the anterior third ventricle also along with the pineal region. It utilizes the conventional anterior interhemispheric approach to gain access into the lateral ventricle by creating a small opening in the corpus callosum. The access from the lateral to the third ventricle is gained by a subchoroidal approach or an approach medial to the choroid plexus, by dividing the thin velum interpositum that is encountered, and by following a trajectory that is directed posteriorly toward the pineal region infero-lateral to the internal cerebral veins traversing the roof of the third ventricle. Alternatively, after the corpus callosum is divided, the transcallosal interforniceal approach permits direct entry into the third ventricle by separating the fornices in the midline. The lateral paramedian infratentorial approach in park-bench position traverses between the superior surface of cerebellar hemisphere and the lateral tentorium. The trajectory is directed superomedially toward the tentorial incisura. The bridging veins traversing this corridor may be divided to gain additional space. Stereotactic or endoscopic biopsy may also be utilized to identify lesions that have an excellent response to radio- and chemotherapy, thus avoiding the need for a major surgery.
In two patients in this series, two surgical trajectories that have not been categorized as being part of the conventional approaches for TPTVR were utilized. In the first case, a cystic brain stem pilocytic astrocytoma extended to the posterior third ventricular region. This was easily accessible though the frontotemporal zygomatic craniotomy and transylvian and subtemporal, transtentorial approach to the lateral brain stem. The IV nerve entering the tentorial edge was meticulously preserved and the cystic tumor decompressed via the lateral surface of the brain stem. In another patient, the PNET was infiltrating the posterior thalamus, internal capsular region and medial wall of the lateral ventricular trigone and extended until the posterior third ventricular region. This was a soft suckable lesion situated predominantly lateral to the third ventricle and causing a midline shift. It could be accessed by the transcortical, transventricular approach with the initial corticectomy through the middle temporal gyrus.
Management of hydrocephalus: Whether or not to treat the primary lesion?
A significant number of patients in our series presented with CSF pathway obstruction and hydrocephalus, making a ventriculoperitoneal shunt mandatory. Endoscopic third ventriculostomy, as performed for two of our patients, is presently recommended as the procedure of choice for CSF diversion. , It avoids the complications of shunt malfunction and infection; it also avoids peritoneal seeding of the malignant TPTVR; CSF may be obtained for tumor marker study; and usually both CSF diversion as well as tumor biopsy may be undertaken at the same sitting. The disadvantages of an endoscopic biopsy are the risk of bleeding from a vascular tumor or ventricular ependyma while obtaining a biopsy and the failure to obtain a representative sample of tumor tissue due to the extreme variability of the its character in different parts of the tumor substance. The small biopsy sample obtained also makes an accurate grading of TPTVR difficult. ,
In case there is no hydrocephalus, and especially, if spinal seeding is also detected on preoperative MRI, then lumbar CSF may be obtained for tumor marker study as well as for malignant tissue cytology. Tumor types such as pinealoblastomas, ependymomas and germinomas that may spread along CSF pathways may especially require a lumbar CSF examination to confirm a "drop metastasis."
Stereotactic biopsy of TPTVR may also be used to obtain a specimen for histopathologic examination.  An appreciation of the complex neurovascular structures in the posterior third ventricular region is a mandatory requirement. An anterolateral burr hole just anterior to the coronal suture in the midpupillary line or a posterolateral burr hole at the parieto-occipital junction (for tumors with lateral extension) may be utilized. There is, however, an increased risk of hemorrhage in this region. The proximity of major vascular structures in close vicinity, the risk of penetration of pial surfaces en route to the stereotactic target, the frequent presence of a vascular tumor, and the failure of even minor hemorrhage to tamponade within the ventricular CSF may be responsible. A transient exacerbation of the clinical symptoms and the difficulty in interpreting the sample obtained are additional potential complications. ,
Obtaining a tissue diagnosis is mandatory for management of TPTVR. ,, In four of our patients, however, who had a very small posterior third ventricular lesion and were symptomatic due to hydrocephalus consequent to aqueductal stenosis, only a CSF diversion was performed. These patients have been placed on a regular follow-up rather than subjecting them to the risk of an invasive procedure to obtain a histopathologic specimen. Any growth of the primary lesion at follow-up will immediately warrant a definitive interventional procedure in them.
Choice of adjuvant therapy
Bruce and Ogden have succinctly summarized the role of adjuvant therapy for TPTVR. Fractionated radiotherapy of 5500 cGy may be administered to malignant pineal, germ cell and glial tumors. Spinal radiotherapy of 3500 cGy may be given to patients with pinealoblastomas or in patients with spinal seeding. Germinomas, except those tumors with elevated HCG levels, are extremely radiosensitive. 
Malignant NGGCTs, recurrent or disseminated pineal cell tumors, and very young children (3 years and less who may develop cognitive disturbances, hypothalamic and endocrinal dysfunction, cerebral necrosis and delayed de novo tumor formation with radiation) , may receive chemotherapy that may be include cisplatin, vinblastine, bleomycin, ifosfamide or their combinations. , Results on the role of adjuvant therapy for mixed pineal parenchymal tumors are equivocal and essentially depend upon the degree of malignant tissue component within the lesion. In histological benign pineocytomas or ependymomas that have been completely excised, surgical resection provides a long-term cure and adjuvant therapy may not be warranted. Stereotactic radiosurgery may be effective in treating benign lesions like pineocytomas, but often gives poor results for malignant lesions where fractionated radiotherapy is more effective than a single high-dose stereotactic radiosurgery. Stereotactic radiosurgery also does not address the metastatic potential of these lesions, lesions larger than 3 cm and lesions within the ventricular system. It may, however, be used to administer local boost to tumor bed and for treatment of tumors that recur locally. For NGGCT, this modality, therefore, has an undefined role that is perhaps determined by the degree of benign tissue within the lesion. ,,,
Reviewing larger series of patients having TPTVR, the gross total resection has ranged from 37.5 to 65%. In our series, gross total resection was possible in 44% patients. There has been a significant decrease in perioperative mortality and morbidity since 1990, with the combined mortality/morbidity reduced to 2.8% and the mortality rate to 1.8%. Benign tumors after complete surgical removal show an excellent long-term cure. Germinomas are extremely responsive to radiation therapy. In malignant tumors, the evidence suggests that greater resection improves response to adjuvant therapy as well as prognosis. ,
| Conclusions|| |
TPTVR are frequently encountered in children. Their histopathologic characterization is essential due to their diverse spectrum and the failure of imaging techniques to unequivocally differentiate between them. Benign lesions are often amenable to a long-term tumor-free interval following gross total surgical resection. Pure germinomas are highly susceptible to radiotherapy. NGGCTs often have malignant components that require adjuvant therapy following surgery. The advancements in microsurgical techniques have led to extremely gratifying perioperative results in these deep-seated lesions.
| Acknowledgments|| |
We gratefully acknowledge the permission given by the publishers and editors of Journal of Pediatric Neurosciences for permitting us to use parts of our previous publication (Behari S, Garg P, Jaiswal S, Nair A, Naval R, Jaiswal AK. Major surgical approaches to the posterior third ventricular region: A pictorial review. J Pediatr Neurosci 2010;5:97-101) in this article.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10], [Figure 11], [Figure 12], [Figure 13], [Figure 14], [Figure 15], [Figure 16]