Primary Gamma Knife Radiosurgery for pineal region tumors: A systematic review and pooled analysis of available literature with histological stratification.

Pineal region tumors (PTs) represent extremely rare pathologies, characterized by highly heterogeneous histological patterns. Most of the available evidence for Gamma Knife radiosurgical (GKSR) treatment of PTs arises from multimodal regimens, including GKSR as an adjuvant modality or as a salvage treatment at recurrence. We aimed to gather existing evidence on the topic and analyze single-patient-level data to address the efficacy and safety of primary GKSR. This is a systematic review of the literature (PubMed, Embase, Cochrane, Science Direct) and pooled analysis of single-patient-level data. A total of 1054 original works were retrieved. After excluding duplicates and irrelevant works, we included 13 papers (n = 64 patients). An additional 12 patients were included from the authors' original series. A total of 76 patients reached the final analysis; 56.5% (n = 43) received a histological diagnosis. Confirmed lesions included pineocytoma WHO grade I (60.5%), pineocytoma WHO grade II (14%), pineoblastoma WHO IV (7%), pineal tumor with intermediate differentiation WHO II/III (4.7%), papillary tumor of pineal region WHO II/III (4.7%), germ cell tumor (2.3%), neurocytoma WHO I (2.3%), astrocytoma WHO II (2.3%) and WHO III (2.3%). Presumptive diagnoses were achieved in the remaining 43.5% (n = 33) of cases and comprised of pineocytoma (9%), germ cell tumor (6%), low-grade glioma (6%), high-grade glioma (3%), meningioma (3%) and undefined in 73%. The mean age at the time of GKSR was 38.7 years and the mean lesional volume was 4.2 ± 4 cc. All patients received GKSR with a mean marginal dose of 14.7 ± 2.1 Gy (50% isodose). At a median 36-month follow-up, local control was achieved in 80.3% of cases. Thirteen patients showed progression after a median time of 14 months. Overall mortality was 13.2%. The median OS was not reached for all included lesions, except high-grade gliomas (8mo). The 3-year OS was 100% for LGG and pineal tumors with intermediate differentiation, 91% for low-grade pineal lesions, 66% for high-grade pineal lesions, 60% for germ cell tumors (GCTs), 50% for HGG, and 82% for undetermined tumors. The 3-year progression-free survival (PFS) was 100% for LGG and pineal intermediate tumors, 86% for low-grade pineal, 66% for high-grade pineal, 33.3% for GCTs, and 0% for HGG. Median PFS was 5 months for HGG and 34 months for GCTs. The radionecrosis rate was 6%, and cystic degeneration was observed in 2%. Ataxia as a presenting symptom strongly predicted mortality (odds ratio [OR] 104, p = .02), while GCTs and HGG histology well predicted PD (OR: 13, p = .04). These results support the efficacy and safety of primary GKSR treatment of PTs. Further studies are needed to validate these results, which highlight the importance of the initial presumptive diagnosis for choosing the best therapeutic strategy.

Endoscopic supracerebellar infratentorial retropineal approach for tumor resection.

BACKGROUND: Lesions located in the pineal region represent a surgical challenge. Multiple approaches to this region have been described, each with its advantages and disadvantages. We report the first application of the endoscopic supracerebellar infratentorial approach for complete resection of a pineal tumor. Unlike transventricular endoscopy, this technique poses no risk to the fornices and can be applied independent of ventricular size. CASE DESCRIPTION: A 21-year-old man sought treatment for diplopia. Magnetic resonance images of brain revealed a heterogeneous, contrast-enhancing mass that originated from the pineal gland. This tumor exerted the mass effect on the tectum and invaded to the bilateral dorso-medial thalamus and hypothalamus but caused no obstructive hydrocephalus. The results of a cytological study of the cerebrospinal fluid, alpha-fetoprotein, and beta-human chorionic gonadotropin were negative. The patient was referred for the surgical work-up. TECHNIQUE: The patient was positioned in the semi-sitting position. The supracerebellar infratentoria corridor was accessed through two paramedian burr holes, which provided natural by-gravity cerebellar traction. The excellent illumination and magnification without sacrificing the inferior occipital sinus could be achieved with the aid of the endoscope. The pineal tumor was resected completely via the full-endoscopic approach. Postoperatively, the patient's diplopia resolved completely, and his hospital course was uneventful. CONCLUSIONS: Taking the advantages of the endoscope and peculiar supracerebellar infratentoria corridor, we could successfully remove the gross-total tumor without violating the critical neurovascular structures. Moreover, this approach can be performed regardless of the size of the ventricle. Consequently, it is an excellent minimally invasive surgical option for resection of symptomatic pineal tumor.

Feasibility of neuroendoscopic biopsy of pediatric brain tumors.

PURPOSE: The purpose of this study was to investigate the potential value of neuroendoscopic biopsies in pediatric patients with peri- or intraventricular tumors. METHODS: From 2001 to 2008, 49 pediatric patients (mean age, 12.16 years) with tumors located in the intraventricular or paraventricular areas underwent neuroendoscopic biopsy, with or without simultaneous endoscopic third ventriculostomy. Neuroendoscopic biopsies were performed to verify the histological diagnosis of neoplasms and to establish pathological diagnoses necessary for planning appropriate treatment strategies. RESULTS: In 45 of 49 patients (91.8%) neuroendoscopic biopsy specimens were appropriate for diagnosis and revealed 27 germinomas, 11 astrocytomas, and one ependymoma, etc. The tumor location included the pineal gland (n = 28), thalamus (n = 7), intraventricle (n = 3), hypothalamus (n = 3), suprasellar area (n = 2), and diffuse multifocal area (n = 3). In two patients (4.1%) biopsy specimens were informative but not diagnostic. Tumor tissue specimens were undiagnostic in two patients (4.1%). There were eight transient morbidities, including four EOM limitations, two central DI, one EVD infection, and one CSF leakage. One patient experienced postoperative tumor bleeding requiring emergent operation. There was no case of operative mortality. CONCLUSION: Neuroendoscopic biopsy can be considered as the first choice for tissue sampling of periventricular and intraventricular tumors with acceptable risks.

Papillary tumor of the pineal region: a case report.

We report a case of papillary tumor of the pineal region (PTPR) and describe the morphological, immunohistochemical, and neuroimaging findings. A 43-year-old man presented with signs of increased intracranial pressure and upward gaze palsy. Magnetic resonance (MR) imaging demonstrated a heterogeneously enhanced mass in the pineal region and obstructive hydrocephalus. Proton MR spectroscopy revealed increased choline and decreased N-acetyl aspartate peaks with a slightly increased lactate peak. Minimum apparent diffusion coefficient value was 0.60 x 10(-3) mm2/s. Positron emission tomography showed significantly increased [18F]fluorodeoxyglucose uptake at the site of the lesion. He underwent total resection of the pineal region mass, resulting in resolution of the symptoms. The tumor consisted of columnar and cuboidal cells, with papillary growth pattern. Immunohistochemical staining showed positive reaction for neuron-specific enolase, S-100 protein, and vimentin. Ki-67 labeling index (LI) was 13.1%. These features were consistent with PTPR. Postoperatively, the patient received radiochemotherapy, and maintenance chemotherapy at our outpatient clinic, and was doing well without tumor recurrence 1 year after the surgery. Although the morphological features agree with those in the original description of the PTPR, the Ki-67 LI and radiologic findings suggest the malignant nature and the necessity for adjuvant therapy.

Peri-operative quality of life assessment in endoscopically treated patients with pineal region tumours.

BACKGROUND: Therapeutic modalities for pineal region tumours are still matter of debate. Endoscopic treatment is a minimally invasive approach. The aim of this study was to assess the quality of life of patients with pineal region tumours who underwent endoscopic procedures. MATERIALS AND METHODS: Eight patients (male:3, female 5) were included in this study. Post-operative evaluation of surgical outcome in terms of quality of life (QoL) was performed using the Quality of Life Questionnaire (QLQ-C30). The patient's outcome scores were compared with normative outcome values of the German population. Pre-operative and post-operative global QoL and symptoms such as headache, visual disturbance, gait disturbance, cognitive function and unconsciousness were documented. Descriptive and explorative statistics were performed. RESULTS: There were no significant differences between the normal German population and the endoscopically treated patients in different health domains and measures of QLQ-C30 (physical functioning 87.5%, emotional functioning 50%, cognitive functioning 50%, social functioning 62.5%; percentage represents regular functioning). Improved quality of life could be demonstrated in short-term (3-12 months, n = 3) and long-term (21-29 months, n = 5) follow-up. Global QoL improved significantly (p < 0.001; t-test) post-operatively. The following changes between pre-operative and post-operative clinical symptoms were found (headache 87.5%/62.5%, visual disturbance 50%/25%, gait disturbance 87.5%/25%, cognitive functioning 75%/37.5%, unconsciousness 25%/-). CONCLUSION: Endoscopic treatment of patients with pineal region tumours produces improved post-operative quality of life in all health domains. Therefore, the endoscopic approach should be considered as an alternative treatment in patients with newly diagnosed pineal tumours and/or related hydrocephalus.

Pineal germinoma presenting as anorexia nervosa: Case report and review of the literature.

OBJECTIVE: Tumors of the hypothalamic-pineal region may present with a wide variety of symptoms, including disturbed eating. We present a case where such a tumor was misdiagnosed as anorexia nervosa. METHOD: We describe a case of pineal germinoma invading the hypothalamus, which was initially diagnosed as anorexia nervosa. RESULTS: Clinical features included weight loss, vomiting, pyrexia, hypernatraemia, and visual disturbance and the typical psychopathology of anorexia nervosa was absent. CONCLUSION: Organic disorder should always be considered before making a diagnosis of anorexia nervosa, particularly if the presentation is atypical.

Basal ganglia and thalamic tumours: an imaging approximation.

INTRODUCTION: Among brain tumours, those arising from the deep brain are rare. In many cases they are low-grade astrocytomas. But primitive neuroectodermal tumours, ganglion cell tumours, oligodendrogliomas, lymphomas, and germinal neoplasms can also grow up from the basal ganglia and thalamic region. In other occasions peripheral neoplasms developing in neighbouring structures like the cerebral lobes, the ventricular walls, choroidal plexus, pineal gland and the hypothalamic-chiasmatic-suprasellar region can spread to the deep brain. IMAGING: Imaging cannot reliably indicate that a histological picture for a tumour of this kind should be suspected. Although the macro- and microscopical characteristics of brain tumours are often the basis of the imaging findings, these data usually overlap and are only useful as an approximation tool. CONCLUSIONS: Nonetheless, whilst radiologists and clinicians must always be cautious when evaluating the macroscopic peculiarities of a brain tumour, the value of imaging cannot be overestimated when any sort of pathology is encountered. Moreover, besides the classic CT and MRI findings, new MRI-related techniques, such as magnetic resonance spectroscopy (MRS), are able to extract a different kind of information from cerebral neoplasms, and they could be important widespread diagnostic alternatives in the very near future.

[Expanding mature pineal teratoma syndrome. Case report]. / Tératome mature évolutif pinéal. A propos d'un cas.

We present a case of growing teratoma syndrome of the pineal region. To our knowledge, this is the fourth case reported in the literature. A 13-year-old boy was referred for intracranial hypertension and bilateral papillary edema. CT scan showed a pineal region tumor with obstructive hydrocephalus. After CSF (cerebrospinal fluid) shunting, MRI showed that the tumor had a heterogenous signal enhancement. The tumor marker HCG (human chorionic gonadotrophin) was elevated in CSF and serum. After three cycles of chemotherapy, MRI showed an important increase in tumor size with morphologic modifications. However, HCG in CSF and serum returned to normal. Surgical resection was performed and histological examination of the whole specimen showed mature teratoma. On postoperative MRI, there was a small area of signal enhancement of the left thalamus. Radiotherapy was given. The child was in complete remission 15 months after the diagnosis. Growing teratoma syndrome is a mixed germ cell tumor with a secreting portion that responds to chemotherapy and a non secreting portion of mature teratoma that continues to grow under chemotherapy. The treatment should include chemotherapy for the malignant secreting portion and surgery for the mature teratoma.

Multiple primary germinomas (ectopic pinealoma) of the brain.

A case of primary multiple germinomas occurring in the corpus callosum and thalamus with excellent outcome following biopsy and irradiation is reported. The pathogenesis of intracranial germinoma is briefly discussed.

Brain tumor with ipsilateral cerebral hemiatrophy in children.

A series of six cases of cerebral tumor with ipsilateral cerebral hemiatrophy, including four cases admitted at our institute, were studied. Various common clinical features were noted in these six cases. The mechanism whereby ipsilateral hemiatrophy of the cerebrum arises from brain tumor has been discussed on the basis of symptomatologic and clinicopathologic findings noted in these 6 cases. 1) The onset of the disease was between 8 and 14 years of age with a mean of 11 years and 8 months; thus all the 6 patients being juvenile. 2) Presenting symptoms developed from 1 year and 2 months to 4 years before admission, with an average of 2 years and 1 month. The clinical course was therefore relatively chronic in every case. 3) Presenting symptoms were: decline of school work, hemiparesis and loss of consciousness. These symptoms were all progressive throughout the course. The principal symptoms were hemiparesis, hemihypoesthesia, character and emotional changes, deterioration of mental faculties and behavioral abnormalities. No sign or symptom of significant increase of intracranial pressure were observed in any case. 4) Ipsilateral cerebral hemiatrophy on the tumor side was evidenced by carotid angiography and by pneumoencephalography. 5) The common site of tumor in this series was the thalamus and its surrounding areas. 6) The tumor was invariably a pinealoma which seemed to be ectopic in every case. 7) The obtained histopathological findings suggest that the ipsilateral cerebral hemiatrophy was due to thinning of the cerebral cortex with degeneration and disappearance of ganglion cells, demyelination in the subcortex and destruction of axons. Our speculated mechanism of ipsilateral cerebral hemiatrophy due to thalamic tumor is that thalamic tumor causes the degeneration and disappearance of thalamic ganglion cells and nerve fibers, consequently occurring secondary Waller's degeneration of afferent and projecting fibers from the thalamus as well as retrograde degeneration of efferent fibers, thus resulting in an extensive atrophy of the cerebral cortex and subcortical tissue.

Ipsilateral cerebral atrophy with thalamic tumor of childhood. Case report.

A case of cerebral tumor with ipsilateral cerebral hemiatrophy is presented and five previously reported cases are reviewed. The etiology of this entity is discussed on the basis of the symptomatological and clinicopathological findings noted in these six cases. It is suggested that ipsilateral cerebral hemiatrophy is due to thinning of the cerebral cortex with degeneration and disappearance of ganglion cells, demyelination in the subcortex, and destruction of axons. The mechanism proposed for ipsilateral cerebral hemiatrophy due to thalamic tumor is that thalamic tumor causes degeneration and disappearance of thalamic ganglion cells and nerve fibers, with consequent secondary Wallerian degeneration of afferent and projecting fibers from the thalamus as well as retrograde degeneration of efferent fibers, thus resulting in extensive atrophy of the cerebral cortex and subcortical tissue.

Computed tomography: evaluation of the posterior third ventricle.

The normal computed tomography (CT) appearances of the posterior third ventricle and related structures are presented. Seventy-six patients with lesions directly involving this ventricle were studied by CT, and results of other neuroradiological procedures evaluated. Primary tumors, metastases, hematomas, infarcts, and cysts may be reliably distinguished by CT, particularly if contrast enhancement is utilized. Size and density resolution limit the direct visualization of the aqueduct of Sylvius; stenosis however may be inferred. Small infarcts may be difficult to demonstrate by the use of CT scans without contrast enhancement, yet be shown by isotope scans.

Ectopic pinealoma: an unusual clinical presentation and a histochemical comparison with a seminoma of the testis.

A patient with ectopic pinealoma first presented with apparent anorexia nervosa and hypernatraemic coma. A history of diabetes insipidus two months previously was not known on admission to hospital. The diabetes insipidus was unmasked by the administration of steroids. Neuroendocrinal and neuropathological aspects of the case are discussed with reference to the march of symptoms due to the growth of the tumour. Histochemical evidence is presented supporting the similarity between ectopic pinealoma and seminoma which suggests that they may more properly be referred to as atypical teratomas.