Management of Pineal Body Tumors
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1 Management of Pineal Body Tumors THESIS Submitted for Partial Fulfillment of M.D. in Neurosurgery By Ahmed Ali Mohamed Mohamed M. SC. (Cairo 2009). Supervisors Prof. Dr. Abd El Alim Ragab Professor of Neurosurgery Faculty of Medicine Cairo University Prof. Dr. Essam Mohammed Rashad Professor of Neurosurgery Faculty of Medicine Cairo University Prof. Dr. Mohammed El Beltagy Assist Prof. of Neurosurgery Faculty of Medicine Cairo University Dr. Wael Mohamed Nazem Lecturer on neurosurgery Faculty medicine Bani Suef University Faculty of Medicine Cairo University 2012
2 Acknowledgement Above all my deep thanks are to "God" the Great, for everything and for giving me health and strength to finish this work. I am greatly honored to express my deepest gratitude and respect to Prof. Dr. Abd El Alim Ragab Professor of Neurosurgery, Faculty of Medicine, Cairo University, for his stimulating supervision and continuous advice were the motives for this work. I am greatly honored to express my deepest gratitude and respect to Prof. Dr. Essam Rashad, Professor of Neurosurgery, for his valuable supervision, everlasting support, guidance and encouragement. No words can describe my deep gratitude to Assistant Professor of Neurosurgery Prof. Dr. Mohammed Elbeltagy faculty of Medicine, Cairo University. He supervised closely its progress with great interest. Without his continuous guidance and unlimited help, this work wouldn t come to light. Special appreciation is indebted to Dr. Wael Mohamed Nazem lecturer of Neurosurgery, Bani Suef University to his guidance and encouragement, to my parents, my professors Dr Ahmed salah, Dr Ahmed el said and colleagues in the Neurosurgery Department, Cairo University. Ahmed Ali (2012)
3 List of Content Pages List Abbreviation List of Tables List of Figures Introduction. 1 Review of Literature Chapter (1) 4 Anatomy.. Chapter (2) 28 Pathology... Chapter (3) 45 Clinical Picture Chapter (4) 58 Investigations... Chapter (5) 76 Management Patients and methods Results 131 Case presentation Discussion. 155 Conclusions Summary 169 References. 171 Arabic Summary.
4 List of Abbreviations PCA MPCHA LPCHA Posterior cerebral artery. Medial posterior choroidal artery. Lateral posterior choroidal artery. B- HCG Beta- human chronic gonadotropins. NGGCT GCTS AFP ETV MRS CSF SCA PPT Ng ml NNA EVD CUSA Nongerminomatous germ cell tumors. Germ cell tumors. Alpha-fetoprotein. Endoscopic 3 rd ventriculostomy. Magnetic resonance spectroscopy. Cerebro spinal fluid. Superior cerebellar artery. Pineal parenchymal tumor. Nanogram. Milliliter. n- acetyl aspartate. External ventricular drain. Cavitronic ultrasonic aspirator. I
5 GY ICP MRI CT PNET HIOMT LH Gray. Intracranial pressure. Magnetic resonance imaging. Computed tomography. Primitive neuroectodermal tumor. Hydroxy indale o- methyl transferase. Luteinizing hormone. List of Tables Tables Pages 1 Karnofsky performance scale Master table Pathology of pineal body tumors Management of pineal body tumors Adjuvant therapy for pineal body tumors 138 II
6 List of Figures: Figures Pages 1 The site of pineal body. 7 2 The site of pineal body. 7 3 Coronal section in the brain Saggital section in the pineal region Veins of the pineal region Classification of pineal tumors Clinical picture of pineal tumors Imaging of pineal germinoma Pineal region teratoma MRI Pineal region Astrocytoma imaging Pineoblastoma MRI Management strategy of pineal region tumor Methods of treatment of pineal region Approaches of the pineal tumors Position of the patient during the operation Incision of the supracerebellar infratentorial approach Opening of the dura in supracerebellar infratentorial Skin incision of occipital transtentorial approach Percentage of surgery of pineal region Percentage of pathology of pineal region Percentage of adjuvant therapy Protocol of management of NGGCT Protocol of infantile patient with pineoblastoma Protocol of management of adult patient with pineoblastoma 141 III
7 25 Protocol of ependymoma Protocol of management of ependymoma Preoperative & postoperative MRI Preoperative & postoperative MRI Preoperative & postoperative MRI Preoperative & postoperative MRI Preoperative & postoperative MRI 154 IV
8 Abstract Objective: The aim of this work is to review the literature regarding the different strategies for management of the pineal region tumors and study the data obtained from the cases operated upon by supracerebellar infratentorial approach and occipital transtentorial approach to analyze and compare it with different series. Methods: 25 cases with pineal region tumors operated upon by supracerebellar infratentorial approach and occipital transtentorial approach. 17 males, 8 females, most of them were under age of 20 years old. Results: The leading symptoms and signs were those of increased intracranial tension, the pathology was (20%) glial, (8%) PNET (44%) germ cell tumors and (24%) pineal parenchymal tumors. Conclusion: The MRI is the investigation of choice specially the mid sagittal image, the choice of the approach depend on the site of the deep venous system in relation to the tumor, the extension of the tumor, the experience of the surgeon with this approach. Finally the total excision of the tumor depend on the choice of the proper approach as well as knowing that if the deep venous system engulfed or displaced, the tumor growth is expansion or infiltration and also the hand skills. Key words: (pineal tumors, principles of treatment, supracerebellar infratentorial approach, deep venous system). V
9 Introduction Introduction Pineal tumors account for about 1% of all intracranial tumors. Where germ cell tumors are common, pineal-cell tumors constitute 4% to 7% of all intracranial tumors. Germ cell tumors (GCTS) account for approximately one-third of all pineal tumors and are histologically identical to gonadal GCTs. They predominate in men and usually occur in children and adolescents.pineal tumors occur equally in boys and girls. GCTs fall into 2 major categories: germinomas and non-germinomatous germ cell tumors (NGGCT) (Balmaceda and Finlay, 2008). Primary pineal-cell tumors are classified as low-grade pineocytoma, intermediate-grade or the highly malignant pineoblastoma. The higher grade tumors tend to occur in children and young adults, where as pineocytomas usually occur in adults. Pineal tumors of all histological grades may seed the leptomeninges (Plowman et al., 2004). Pineal region tumors may become symptomatic from one of three mechanisms: increased intracranial pressure from hydrocephalus, direct compression of brainstem and cerebellum, or endocrine dysfunction. Headache associated with hydrocephalus is the most common symptom at onset. More advanced hydrocephalus may result in papilledema, gait disorder, nausea, vomiting, and lethargy and memory disturbance. Direct midbrain compression may cause disorders of ocular movements. Fourth nerve palsy with diplopia and head tilt may be seen. Ataxia and dysmetria may result from direct cerebellar compression. Endocrine dysfunction is rare, usually arising from secondary effects of hydrocephalus or tumor spread to the hypothalamic region (Kochi et al., 2007)
10 Introduction MRI with gadolinium is mandatory for all pineal tumors to determine the presence of hydrocephalus, and to evaluate tumor size, vascularity and homogeneity. In particular, sagittal MRI reveals the relationship of the tumor to surrounding structures, and also evaluates possible ventricular seeding. Angiography is not performed unless a vascular anomaly is suspected. Measurement of AFP and β-hcg in serum and CSF is required. If β-hcg or AFP levels are elevated, malignant germ-cell elements are present even if histologic examination fails to reveal NGGCT elements. Despite improved imaging and CSF markers, a definite histologic diagnosis requires pathologic examination of tumor tissue and all patients should undergo surgery (Smith et al., 2006). Owing to the wide variety of pineal region tumor subtypes, a histologic diagnosis is mandatory for optimal patient management. The pineal region may be reached surgically from one of several approaches; a complete excision is the goal for any pineal tumor. Nearly one-third of pineal tumors are benign and curable with complete resection alone. With malignant tumors, aggressive tumor resection provides the best opportunity for accurate histologic diagnosis and may increase the effectiveness of adjuvant radiotherapy or chemotherapy. For patients with obviously disseminated tumor or those with medical problems that pose excessive surgical risks, stereotactic biopsy is a reasonable alternative for obtaining diagnostic tissue (Spunt et al., 2009)
11 Introduction Aim of the Work Stating management based on the clinical presentation, MRI characteristics; understanding the surgical anatomy with pathology to assess the most appropriate group of patients in whom different forms of surgery; radiotherapy; chemotherapy would be beneficial
12 Chapter (1) Anatomy Anatomy The pineal gland is located nearly in the center of the brain, in any mammal is a small white structure; shaped somewhat like a pinecone. In man this organ is roughly a quarter of an inch long and weighs about a tenth of a gram. The function of the pineal body has never been clearly understood. The pineal has become perhaps the last great mystery in the physiology of mammalian organs. This mystery may be nearing a solution. Studies conducted within the past few years indicate that the pineal is an intricate and sensitive "biological clock, "converting cyclic nervous activity generated by light in the environment into endocrine that has a hormonal-information. It is not yet certain what physiological processes depend on the pineal clock for cues, but the evidence at hand suggests that the pineal participates in some way in the regulation of the gonads or sex glands (Bowen, 2011). Until quite recently most investigators thought that the mammalian pineal was simply a vestige of a primitive light-sensing organ: the "third eye" found in certain cold-blooded vertebrates such as the frog. Other workers, noting the precocious sexual development of some young boys with pineal tumors, had proposed that in mammals the pineal was a gland. When the standard endocrine tests were applied to determine the possible glandular function of the pineal, however, the results varied so much from experiment to experiment that few positive conclusions seemed justified (Bowen, 2011). The pineal gland is a small endocrine gland located in the middle area of the brain between the two hemispheres of the brain. The pineal gland contains specialized cells called pineocytes, which produce the - 4 -
13 Chapter (1) Anatomy hormone melatonin. The pineal gland and the melatonin it produces play a large role in the regulation of sleep cycles and circadian rhythm among other actions. Conditions that can afflict the pineal gland include light exposure, jet lag, nightshift work, radiation exposure, pineal gland tumors, calcification of the pineal gland, and trauma (Deshmukh et al, 2004). The pineal body (epiphysis) is a small reddish-gray body, about 8 mm. in length which lies in the depression between the superior colliculi. It is attached to the roof of the third ventricle near its junction with the mid-brain. It develops as an outgrowth from the third ventricle of the brain (Deshmukh et al, 2004). In early life it has a glandular structure which reaches its greatest development at about the seventh year. Later, especially after puberty, the glandular tissue gradually disappears and is replaced by connective tissue (Ashley et al., 1996). The pineal gland or epiphysis synthesizes and secretes melatonin, a structurally simple hormone that communicates information about environmental lighting to various parts of the body. Melatonin has the ability to entrain biological rhythms and has important effects on reproductive function of many animals. The light-transducing ability of the pineal gland has led some to call the pineal the "third eye"(bowen, 2011). The pineal gland is located in the posterior roof of the third ventricle at the rostral portion of the midbrain adjacent to the posterior and habenular commissures. The splenium of the corpus callosum is located directly above the pineal, rostral to the vein of Galen. The velum - 5 -
14 Chapter (1) Anatomy interpositum is rostral and dorsal to the gland and contains the internal cerebral veins as they combine to form the vein of Galen. These veins can often be seen radiographically over the dorsal surface of the tumor. The pineal gland is innervated by the sympathetic nervous system through a pathway beginning in the retina and coursing through the suprachiasmatic nucleus of the hypothalamus and the superior cervical ganglion. This pathway is responsible for the circadian rhythm of melatonin secretion by pineocytes as modulated by light and dark cycle (Bruce, 2004). The pineal region anatomy includes Gross anatomy, Microscopic anatomy; and Histology of the pineal gland: 1) Gross anatomy: The pineal body: The pineal body is rounded or oval in shape, it measures 7.4 mm in the longitudinal length, 6.9 mm in the transverse width, and 2.5 mm in the thickness. It lies above the midbrain within the quadrigeminal cistern and in the midline (Gray's anatomy, 2011). The pineal region: It is the region limited dorsally by the splenium of the corpus callosum and tela choroidea, ventrally by quadrigeminal plate, rostrally by the posterior part of the third ventricle and caudally the vermis of the cerebellum (Gray's anatomy, 2011)
15 Chapter (1) Anatomy Fig. (1): The site of the pineal body (Radovanovic, 2009). Fig. (2): The site of the pineal body (Radovanovic, 2009)
16 Chapter (1) Anatomy 2) Microsurgical anatomy of the pineal region: The pineal region has a roof, floor, anterior, and lateral walls, and it extends backwards to the level of the tentorial apex (Yamamoto and Kageyama, 1980). The anterior wall: The quadrigeminal plate is located at the center of the anterior wall. The anterior wall is divided by the colliculi into rosteral part and caudal part, the rosteral part is formed by the pineal body, the habenular trigones and commissure. The caudal part is formed in the midline by the lingula of the vermis and laterally by the superior cerebellar peduncles as they ascend beside the lingula (Yamamoto and Kageyama, 1980). The roof: The roof of the posterior incisural space corresponds to the pineal region is formed by the lower surface of the splenium, the terminal part of the crura of the fornices, and the hippocampal comissure (Rhoton et al., 2002). The floor: The floor of the pineal region is formed by the anterior superior part of the cerebellum and consists of the culmen of the vermis in the midline and quadrangular lobules of the hemispheres laterally (Rhoton, 2002). The lateral wall: The lateral wall is formed by the pulvinar, crus of the fornix, and the medial surface of the cerebral hemisphere. The anterior part of the lateral wall is formed by the part of the pulvinar located just lateral to the pineal body (Rhoton et al., 2002)
17 Chapter (1) Anatomy The microsurgical anatomy of the pineal region includes ventricular, arterial, venous, cisternal and neural relationships: A) Ventricular relationships: The posterior portion of the third ventricle and cerebral aqueduct lie anterior to the pineal gland, the atria and the occipital horn of the lateral ventricle are lateral to the pineal region. The supra pineal recess of the third ventricle extend posteriorly between the pineal body and the inferior wall of the velum interpositum towards the posterior incisural space or pineal region. The aqueduct passes ventral to the anterior wall of the posterior incisural space. The atrium is separated from the posterior incisural space by crus of the fornix as it pass posterior to the pulvinar and cortical gyri located in the lateral wall. The choroid plexus, which form a large tuft in this area, is attached along the choroid fissure, between the crus of the fornix and pulvinar (Rhoton et al., 2002). B) Arterial relationship: Most of the arteries in this region arise from the posterior cerebral artery, superior cerebellar artery, and the basilar artery. Generally, the posterior cerebral arteries supply the structures above the level of the lower margin of the superior colliculi, while the superior cerebellar arteries supply the structures below the upper margin of inferior colliculi. There are numerous anastomosis between the two arteries over the surface of the colliculi and between both sides (Gray's anatomy, 2011)
18 Chapter (1) Anatomy Fig. (3): Showing a diagrammatic representation of a coronal section in the brain (Fredric, 1999). a) Posterior cerebral artery (PCA): It originates as a paired terminal branch of the basilar artery. The PCA could be divided into four segments from P-1 to P-4: P-1 segment: arises from its origin to the posterior communicating artery
19 Chapter (1) Anatomy P-2 segment: begins at the posterior communicating artery and terminates at the origin of the inferior temporal arteries and is subdivided into anterior and posterior halves (P-2A and P-2P groups). P-3 segment: extends from the origin of the inferior temporal branches to the origin of the temporal branches. P4 Segment: the P4 segment includes the branches distributed to the cortical surface. Posteriorly, it begins at the anterior end of the calcarine sulcus (Rhoton et al., 2002). The posterior cerebral artery gives the following branches: 1) The circumflex Arteries: These branches arise from the PCA and supply the area of the midbrain and diencephalon. The circumflex arteries are divided into short and long circumflex groups (Margolis et al., 1974). A) The short circumflex arteries: Most of the short circumflex arteries arise from the P-1 segment but may also arise from P-3 segment but may also arise from the P2-A segment. They run medial to PCA around midbrain into thalamogeniculate sulcus and supply small perforating branches to the cerebral peduncle and substantia nigra. Some branches of these arteries supply the mesencephalon near the geniculate bodies (Margolis et al., 1974)
20 Chapter (1) Anatomy B) The long circumflex arteries: They arise from the P-1 segment in most cases but may arise from the P-2A segment as well. They encircle the midbrain between the PCA and the short circumflex arteries, and send small branches to the cerebral peduncle, geniculate bodies and the tegmentum of the midbrain (Rhoton, 2002). 2) The thalamogeniculate artery: Usually it arises from P-2 segment in the ambient cistern near the medial and the lateral geniculate bodies. The average number of these arteries is three per hemisphere. The thalamogeniculate arteries penetrate the thalamus and supply the medial geniculate, the medial half of the lateral geniculate; the posterior part of the lateral posterior nucleus of the thalamus, the ventral lateral pulvinar, the ventral lateral and the ventral posterior nuclei of the thalamus, the nucleus centrum medianum and the intralaminar nuclei of the thalamus (Stephens and Stilwell, 1980). 3) The medial posterior choroidal artery (MPCHA): It arises from the P-2A segment in 57.5 %. The number of the medial post choroidal arteries per hemisphere is ranging from one to three. It runs usually medial to PCA and course in the quadrigeminal cistern then lateral to the pineal body and course in the roof of the third ventricle parallel and medial to the internal cerebral vein in the midline and finally supplies the choroid plexus of the third ventricle till the foramen of Monoro. It sends branches to the tegmentum, the geniculate
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