Aria Fallah MD, MSc, FRCSC

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1 Aria Fallah MD, MSc, FRCSC Department of Neurosurgery David Geffen School of Medicine at UCLA Pineal Region Tumors Brain Tumor Symposium August 22, 2015

2 Disclosures None

3 Pineal Gland Arises from an invagination of neuroepithelial tissue of roof of third ventricle during 2 nd month Adult size by 4 years 200 mg 10 mm x 5 mm x 5 mm

4 The pineal region anatomical Anatomy Bordered by CSF spaces (not bathed in CSF), Surrounded by pia Rostral: Posterior third ventricle Caudal: Quadrigeminal cistern Neural structures Ventral: Quadrigeminal plate of midbrain Posterior: Cerebellar vermis Dorsal: Splenium of Corpus Callosum Laterally: Posterior thalami Anteroinferiorly: Tegmentum of midbrain Blood supply Arterial: medial post choroidals a. Venous: to internal cerebral v. considerations

5 The major arteries in the region: Posterior cerebral a. Superior cerebellar a. Medial posterior choroidal a. Calcarine a. Parieto-occipital a.

6 1: Inferior sagittal sinus 2: Straight sinus 3: Internal cerebral vein 4: Vein of Galen 5: Basal vein of Rosenthal 6: Thalamostriate vein 7: Transverse sinus 8: Superior sagittal sinus Deep Venous System - Vein of Cerebellomesencephalic fissure/precentral cerebellar v. - Superior vermian vein

7 Venous drainage system

8 Pathology and Pathobiology Heterogeneous and rare (1% of CNS) Tumors Pineal Origin Germ cell Tumors Pineal Parenchymal Cell Tumors Extra pineal origin (from surrounding neural or mesenchymal structures) Astrocytomas Meningiomas Ependymomas Choroid Plexus Papillomas Etc.

9 Differential Diagnosis Germ Cell Tumors (60%) M>F Germinomas (60%) Non-Germinomatous Germ Cell tumors Teratoma (mature/immature) Embryonal Carcinoma Yolk Sac Tumor Choriocarcinoma Mixed Pineal Parenchymal Tumors (15%) Pineocytoma Pineal parenchymal tumor of intermediate diff Pineoblastoma Papillary Tumor of the pineal region Mixed Primary neuroectodermal tumors (15%) Glioma (pineal, tectal,,thalamic) Ependymoma Oligodendroglioma Non-neuroectodermal tumors (5%) Choroid plexus papilloma Meningioma Metastasis Others (5%) Pineal cysts, arachnoid cysts Vein of Galen malformations, AVM, Cavernoma

10 Pineal Tumors Germ Cell Tumors Germinomatous 60% NonGerminomatous Embryonal Carcinoma (most primitive) 3% Extraembryonal differentiation Yolk sac (endoderm) 2% Choriocarcinoma (syncytiotrophoblast, rare) 1% Embryonic Immature teratoma 25% Mature teratoma 10%

11 Pineal Parenchymal Tumors Pineoblastoma 1 st - 3 rd decades HW and FW rosettes Prognosis better that spnet 60% 5 year Pineocytoma Young adults Pineocytomatous rosette Good prognosis with surgery >70% 5 year S-antigen

12 Pineal Cysts Common autopsy finding 2% incidence on MRI Rarely symptomatic?focal degeneration of pineal All symptomatic are greater than 2 cm F>M 3:1 Case courtesy of Dr Frank Gaillard, Radiopaedia.org, rid: 25891

13 Signs and Symptoms Increased ICP due to obstructive hydrocephalus Diplopia secondary to ICP or Tectal compression Parinaud s Phenomenon (50-70%) Cerebellar signs Precocious Puberty (choriocarcinoma β-hcg) DI, visual, endocrine, hypothalamic (Synchronous lesions) Sudden onset Perinaud s think Pineal tumor apoplexy

14 Investigations Imaging Ophthalmology Endocrine Serum Markers CSF Markers

15 Immunohistochemistry Lab markers important for: Diagnosis Monitoring response to treatment and relapses

16 Germ Cell Tumors Germinoma marker negative, β-hcg mild increase Embryonal carcinoma AFP, HCG Yolk sac carcinoma (Endodermal Sinus Tumor) AFP Choriocarcinoma HCG (syncytiotrophoblast) Mixed HCG + AFP

17 Generalities If hydrocephalus- requires CSF diversion Shunt vs. ETV Serum/CSF markers If Serum/CSF markers are positive- NGCT Treat with Chemo + Rad Possible second look surgery If Serum/ CSF markers are negative- tissue required Biopsy vs. open Further Treatment decided on histological diagnosis

18 Stereotactic biopsy Indication: Widely disseminated disease, clearly invasive malignant tumor and patients with multiple medical problems Risks: Most reports indicate the risks are minimal. *Hemorrhage in this location is a serious potential concern Specially Pineoblastomas, Choriocarcinomas Risk of non-diagnostic tissue (2-12%) Not able to resect if resectable tumor Poor sampling of tumor (NB mixed pathologies)

19 Neuroendoscopic Biopsy Advantages: Obtaining tissue for diagnosis and CSF for marker (Reported yield up to 94%) Performing an endoscopic third ventriculostomy Unexpected tumor seeding may be recognized that s not apparent on MRI Disadvantages: Sampling error (may miss mixed portions of GCT) Inability to control bleeding/temporary EVD may be necessary Challenges: Accessing the posterior third ventricle. Consider: 30 degree angle rigid scope Flexible scope A more anteriorly placed burrhole (at the hairline)

20 Pre-surgical considerations CT & MRI with DWI & FLAIR +/- Gad CTV or MRV for venous anatomy Consider Preoperative Lumbar Drain Concomitant treatment of hydrocephalus CSF for marker, cytology Frameless stereotaxy, Microscope, CUSA, Frozen section for pathology Case courtesy of Dr Frank Gaillard, Radiopaedia.org, rid: 5687

21 Surgery Management depends on whether hydrocephalus is present and on the status of markers Hydrocephalus EVD (to temporize a sick patient) Shunt (almost never upfront) ETV (obtain CSF, treat hydro, biopsy tumor) Or Resect the tumor to open Aqueduct of Sylvius Tumor Will need a direct approach to tumor if markers negative and if no hydro. Stereotactic biopsy not considered safe by most. Open Biopsy (if cannot do endoscopic) Resection (2 widely used approaches) Supracerebellar (tumor smaller, below tent) Occipital transtentorial (larger, projects above tent, oblique view)

22 Surgical options 1- Stereotactic biopsy 2- Endoscopic biopsy and third ventriculostomy 3- Posterior interhemispheric transcallosal approach: 4- Parietal interhemispheric approach 5- Occipital transtentorial approach 6- Infratentorial supracerebellar approach 7- Combined supratentorial and infratentorial approach

23 Selection of surgical approach based on Anatomical considerations based on neuroimaging Surgeon s familiarity/confidence with approach Tumor location and extent Deep venous system Other factors Patient s age Presence or absence of hydrocephalus Goals of surgery (biopsy vs. total resection)

24 Surgical Approaches to the Pineal Region 1- Supracerebellar-infratentorial 2- Occipital-transtentorial 3- Parietal-interhemispheric

25 Infratentorial supracerebellar approach Advantages: -Provides midline trajectory and approach to center of the tumor -For midline lesion, growing into the posterior fossa -Avoids the inconvenience of working around the deep venous vessels - No normal tissue is violated on route to the tumor Disadvantages: Not suitable for tumors with lateral extension to trigone, or superior extension to corpus callosum or tumor with down ward displacement of venous system

26 Infratentorial supracerebellar Several position: sitting, three/quarter prone, lateral decubitus and concorde position.

27

28 Supratentorial approach The supratentorial approach is best applied to patients with tumors extending supratentorially or laterally into the trigone of the lateral ventricle. Advantages: Wide exposure Disadvantages: 1) Difficult to approach lesion below the convergence of the deep venous system 2) Excessive retraction on the parietal lobe or occipital lobe visual impairments

29 Posterior Interhemispheric transcallosal approach Lesion extend superiorly and involve the posterior part of corpus callosum. Push the deep venous system in the dorsolateral direction. Tumor extending laterally to the region of the trigone

30 Interhemispheric transcallosal approach/retrocallosal approach

31

32 The occipital-transtentorial approach Advantages: Provide excellent approach above and below the tentorium Disadvantages: Required retraction of the occipital lobe and division of the tentorium for adequate exposure. Difficulty to approach lesions below the convergence of the deep venous system and lesion extending to the opposite side Risk: visual defects, disconnection syndrome.

33 Positioning for occipital-transtentorial approach / posterior interhemispheric approach Occipital Transtentorial Approach

34 Complications Complications following pineal region surgery: Air embolism (sitting position) Extraocular muscle dysfunction Impaired hearing (damage to inferior colliculi) Altered mental status Ataxia intra-tumoral hemorrhage (esp. w/ pineal parenchymal tumors) Venous occlusion Supratentorial approaches can result in: seizures hemianopsia hemiparesis

35 Treatments based on Histology Germ Cell tumors Germinomas(90% 5yr) Surgery- no role except for tissue diagnosis Radiation- mainstay of treatment Usually 50Gy to brain (ventricular) Now Gy to whole ventricle with 50 Gy tumor boost with Craniospinal rads if evidence of spread Chemo- trials of chemo alone (although less survival) Trials to combine with lower dose radiation (platinum based)

36 Treatments based on Histology Germ cell Tumors (con t) NGCT (25% 5 yr) Typically diagnosed on serum markers (20-75%) Surgery- reserved for tissue diagnosis and second look - if residual to see if malignant cells (further chemo) or benign lesion (better control with resection) Chemoradiation is current mainstay Craniospinal rads Recurrent disease High dose chemo with stem cell rescue

37 Treatments based on Histology Pineal Parenchymal tumors Pineocytoma (85%- 100% 5-yr) Surgery- total resection can be curative Radiation- for recurrence or possible residual Chemotherapy- uncertain Pineoblastoma (55% 5yr) Surgery- current thoughts are similar to medulloblastoma (maximal resections do better when possible) Radiation- craniospinal Chemotherapy- important PPTID (30-75% 5-yr) Usually surgery plus radiation

38 Treatments based on Histology Gliomas Tectal gliomas CSF diversion and follow Thalamic gliomas Biopsy and Rads/chemo Ependymoma Attempted complete resection with radiation therapy

39 Treatments based on Histology Benign pineal region tumors meningiomas, epidermoids, teratomas, pineal cysts, pilocytic astrocytomas Surgical removal

40 Summary Pineal Region Tumors A histologically varied group of lesion Significantly different treatment regimens dependent on histological diagnosis Many surgical considerations to approach these tumors safely; the extent/need of surgery is often determined by histological diagnosis

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