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Pineal region tumors are a relatively uncommon, deep-seated heterogeneous group of mass lesions of the brain. Their management is much more complicated in children with cancer, both in terms of survival and sequelae, due to primary location of the tumor and treatment modality. The goal of this retrospective study was to report the presentation, treatment, and outcome of tumors that arose from this region in 24 children treated at our institution between March 1975 and May 2006. In all, 15 (62.5%) of the 24 children were initially treated with partial or complete resection, adjuvant radiotherapy was given to 18 (75%) patients, and chemotherapy was given to 15 (62.5%) of the patients. Overall survival was 44.5%. Although statistically insignificant, the most favorable outcome were obtained in patients with grossly resected tumors (66%) and in children >10 years of age (80%). Long-term sequelae occurred at a high rate in this study due to the primary location of the tumors and treatment modalities, which warrants further investigation., (Copyright Georg Thieme Verlag KG Stuttgart New York.)

Papillary tumor of the pineal region (PTPR) was recently added to the 2007 WHO classification of tumors of the central nervous system as a rare pineal tumor. We present a case of a 17-year-old man who developed a 3-cm pineal tumor that was incompletely excised following two operations. The pathological findings presented were extensive epithelial papillary structures surrounding vessels mimicking "perivascular pseudo-rosettes," leading to a diagnosis of "papillary ependymoma." Subsequently, the residual tumor recurred on three separate occasions. Immunohistochemical studies showed the tumor was positive for cytokeratin 18 (CK 18), microtubule-associated protein (MAP 2), neuron-specific enolase (NSE), neuronal nuclei (NeuN), and transthyretin, consistent with mature neuronal differentiation. Given these findings, the diagnosis of PTPR was made. The patient's survival time of 218 months is the longest reported to date for this tumor.

Intracranial germ cell tumors (GCTs), especially pineal tumors have attracted the special attention of neuropathologists and neurosurgeons because of their unique growth sites, characteristic subtypes with different histology, and high incidence in Japan and other Asian countries. This chapter describes the general clinical features of pineal GCTs and current treatment of intracranial GCTs. Despite excellent long-term results for patients with germinoma treated with radiation therapy, the potential for late effects makes the treatment controversial. Most patients with nongerminomatous tumors treated by conventional treatment with surgery and radiation therapy failed to survive longer than 3 years. After combination chemotherapy with cisplatin was confirmed to be effective in gonadal GCTs, GCTs of the brain became candidates for chemotherapy. For germinoma, a trial with chemotherapy alone failed with a high rate of recurrence, but Japanese and European trials with chemotherapy and reduced dose and volume of radiation therapy demonstrate good event-free survival rates. Ongoing phase II studies with combined chemotherapy and radiation therapy for nongerminomatous tumors will result in a 5-year survival rate of >50%, which is better than that by radiation therapy alone., (Copyright (c) 2009 S. Karger AG, Basel.)

We report a boy who in 1994, at the age of 11, presented with headache and vomiting. The fi nal diagnosis was papillary tumor of the pineal region (PTPR). Magnetic resonance imaging (MRI) revealed a heterogeneous mass. Hydrocephalus was addressed by immediate ventricle drainage; subsequently, we attempted tumor removal. As the intraoperative diagnosis of the hemorrhagic tumor was primitive neuroectodermal tumor (PNET), we did not proceed to total removal. After the delivery of radiotherapy (50.4 Gy) and one course of Nimustine hydrochloride (ACNU) chemotherapy, the residual tumor was completely resected. The diagnosis at that time (1994) was papillary pineocytoma. He was followed on an outpatient basis for 15 years and remained free of recurrence. This type of tumor was later proposed to represent a new distinct tumor subtype, papillary tumor of the pineal region (PTPR). Our data indicate that our patient's tumor should be included in this category.

A 20-year-old man presented with a rare case of germinoma with a large component of epithelioid cell granuloma manifesting as oscillopsia. Magnetic resonance imaging demonstrated a mass in the pineal region with homogeneous enhancement with gadolinium. Craniotomy was performed, ending in biopsy. The initial histological diagnosis was epithelioid cell granuloma, but systemic investigation detected no evidence of granulomatous disorder. A revised diagnosis of germinoma was based on positive immunohistochemical staining for placental alkaline phosphatase (PLAP) and c-kit. Histological diagnosis is sometimes incorrect if granulomatous reaction is dominant. Immunohistochemical staining for PLAP and c-kit should be performed if germinoma is clinically suspected.

Primary germ cell tumors (PGCT) of the central nervous system usually develop in the third ventricle area, and most frequently in the pineal region. The suprasellar region is the second preferential site for development of these tumors which are rarely simultaneously present in these two sites. We report five new cases of PGCT with pineal and suprasellar localizations, which appeared in late puberty in four boys and one girl aged 17-19 years. The clinical picture associated signs of intracranial hypertension, convergence and verticality palsies, diabetes insipidus and pituitary deficiency. Encephalic MRI revealed a double localization. Endocrine tests revealed a particular pattern associating central diabetes insipidus and a hypothalamic-pituitary disconnection syndrome. Following identification of the pathological type of lesions via a neurosurgical approach, treatment was based on a combined method using chemotherapy, radiotherapy and hormone replacement. Based on this treatment, prolonged remissions were obtained with a good quality of life.

Pinealgland tumors comprise 0.5%-1% of adult brain tumors. Pineoblastomas constitute less than half of these pineal gland tumors. Due to the key anatomic location, these tumors produce hydrocephalus by pressing on the aqueduct of Sylvius. Headache is a very common symptom. We describe the case of a 20-year-old female who presented with new onset persistent headache. Workup revealed a pineoblastoma. These tumors can be detected by MRI and diagnosed on cytology of cerebrospinal fluid (CSF) showing blue round tumor cells with specific tumormarkers. Combined chemo radiation therapy is the treatment for these tumors. New onset persistent headaches are present in 50%-60% of intracranial tumors. All new onset persistent headaches should be promptly evaluated.

The significance of histological diagnosis was retrospectively investigated in the treatment of 79 consecutive patients with pineal region tumours. Histological diagnoses were consistent with clinical diagnoses in 38 out of 39 patients with germ cell tumours and in all eight patients with non-germ cell tumours. The single exception was pineoblastoma. Forty-one patients were treated under a clinical diagnosis of pineal germ cell tumour using neoadjuvant chemotherapy and radiation therapy without histological verification. Of the 41 patients, 32 achieved an excellent response, whereas nine required the delayed resection of a residual tumour. Of these nine tumours, seven were mature or immature teratomas or scars. These patients had elevated levels of tumour markers. Most cases of pineal germ cell tumour could be identified on the basis of clinical findings only, and could be treated appropriately using neoadjuvant chemotherapy and radiation therapy without histological diagnosis. However, second-look surgery should be considered in cases with residual teratomatous components or unusual responses.

The authors report a metachronous germ cell tumor with different histological type occurring 12 years after resection of a pineal germinoma. Histological examination of the original tumor revealed germinoma without any other component of germ cell tumor, and the patient underwent chemotherapy followed by 24 Gy of localized irradiation. Twelve years later, follow-up MR imaging showed a round mass in the genu of the corpus callosum. Two courses of chemotherapy were administered, but the tumor size remained stable. A second operation was performed and this second tumor was completely removed. The histological diagnosis was mature teratoma. The second tumor was considered as a metachronous mature teratoma rather than a recurrence of the original germinoma. To the authors' knowledge, this combination of metachronous germ cell tumor has not previously been reported in the literature.

The exact incidence of pineal germ-cell tumors is largely unknown. The tumors are rare, and the number of patients with these tumors, as reported in clinical series, has been limited. The goal of this study was to describe pineal germ-cell tumors in a large number of patients, using data from available brain tumor databases. Three different databases were used: Surveillance, Epidemiology, and End Results (SEER) database (1973-2001); Central Brain Tumor Registry of the United States (CBTRUS; 1997-2001); and National Cancer Data Base (NCDB; 1985-2003). Tumors were identified using the International Classification of Diseases for Oncology, third edition (ICD-O-3), site code C75.3, and categorized according to histology codes 9060-9085. Data were analyzed using SAS/STAT release 8.2, SEER*Stat version 5.2, and SPSS version 13.0 software. A total of 1,467 cases of malignant pineal germ-cell tumors were identified: 1,159 from NCDB, 196 from SEER, and 112 from CBTRUS. All three databases showed a male predominance for pineal germ-cell tumors (>90%), and >72% of patients were Caucasian. The peak number of cases occurred in the 10- to 14-year age group in the CBTRUS data and in the 15- to 19-year age group in the SEER and NCDB data, and declined significantly thereafter. The majority of tumors (73%-86%) were germinomas, and patients with germinomas had the highest survival rate (>79% at 5 years). Most patients were treated with surgical resection and radiation therapy or with radiation therapy alone. The number of patients included in this study exceeds that of any study published to date. The proportions of malignant pineal germ-cell tumors and intracranial germ-cell tumors are in range with previous studies. Survival rates for malignant pineal germ-cell tumors are lower than results from recent treatment trials for intracranial germ-cell tumors, and patients that received radiation therapy in the treatment plan either with surgery or alone survived the longest.

Background: High-dose chemotherapy (HDCT) with autologous stem cell rescue (ASCR) has been reported to be effective in treating children with recurrent central nervous system (CNS) malignancies., Methods: To evaluate the efficacy and toxicities of HDCT and ASCR, the medical records of 27 children with recurrent CNS malignancies who received such therapy at St. Jude Children's Research Hospital between 1989 and 2004 were reviewed., Results: The median age at diagnosis was 4.5 years (range, 0.4-16.6 years) and that at ASCR was 6.7 years (range, 1.1-18.5 years). Diagnoses included medulloblastoma (13 patients), primitive neuroectodermal tumor (3 patients), pineoblastoma (2 patients), atypical teratoid rhabdoid tumor (2 patients), ependymoma (3 patients), anaplastic astrocytoma (2 patients), and glioblastoma multiforme (2 patients). The 5-year overall and progression-free survival (PFS) rates were 28.2% and 18.5%, respectively. The 5-year PFS rate for patients aged<3 years at diagnosis (57.1%) was significantly better than older patients (5.0%) (P=.019). Among the 6 long-term survivors (5 with M0 disease and 1 with M3 disease at diagnosis), 5 received both radiotherapy and HDCT as part of their salvage regimen; 4 were aged<3 years at diagnosis and had received chemotherapy only as part of frontline therapy. Two patients died of transplant-related toxicities; 44% experienced grade 3 or 4 transplant-related toxicities (toxicities were graded according to the National Cancer Institute Common Toxicity Criteria)., Conclusions: HDCT with ASCR is not an effective salvage strategy for older children with recurrent CNS malignancies. The significantly better outcome in the younger cohort was most likely related to the use of radiotherapy as part of the salvage strategy., (Copyright (c) 2008 American Cancer Society.)

Pineoblastomas are uncommon pineal tumors, which demonstrate rapid growing and poor prognosis. We report the case of a 43-year-old man with an enhancing pineal region mass, which showed restriction of the diffusion on diffusion-weighted (DW) MR images. The surgical biopsy defined the diagnosis of pineoblastoma and the therapy was initiated with radiation and chemotherapy. Three months later, the follow-up MR imaging showed areas suggestive of necrosis and the DW images demonstrate no significant areas of restricted diffusion. The differential diagnosis of pineal region masses that could show restriction of diffusion is discussed.

Primary pineal gland malignancies are uncommon and seldom have papillary architecture. We report a case of a 22-year-old male patient who presented with progressive headache, horizontal nystagmus and worsening diplopia. MRI of the brain showed a lesion in the pineal region. The patient was taken for resection of the lesion which was classified as papillary tumor of pineal region (PTPR). Histologically, the neoplasm was cellular, characterized by eosinophilic cells with indistinct borders, large pleomorphic nuclei, numerous apoptotic figures without necrosis or microvascular proliferation. Prominent perivascular pseudorosettes were seen. Diffuse immunoreactivity for cytokeratin 8-18 was noted. Synaptophysin antibody showed membranous and cytoplasmic positivity. Weak staining for GFAP, vimentin, S-100 protein, and neuron specific enolase (NSE) were observed only focally. This is a case report of this rare pineal region neoplasm which only recently has been described as a histopathologic entity. Although the clinicopathological characteristics of this tumor are not entirely understood, a brief review of the literature as well as our contribution suggest an indolent neoplasm with a tendency for local recurrence. Histologically, PTPR demonstrates a unique assortment of epithelial, ependymal, and neuroendocrine features. The differential diagnosis of papillary neoplasms of the pineal region is reviewed.

A 48-year-old female presented with an extremely rare primary tumor of the pineal region with papillary features manifesting as morning headaches persisting for 1 month. Magnetic resonance imaging showed a well-defined mass, with some cystic components, in the region of the pineal gland. The tumor was completely removed through an occipital transtentorial approach in the prone position. Histological examination found a distinctive papillary growth pattern in which the vessels were covered by multiple layers of tumor cells. The histological diagnosis was papillary tumor of the pineal region (PTPR), which has recently been described as a distinct clinicopathological entity requiring careful follow up because the prognosis is not well understood. Postoperatively, the patient has continued to do well, with no recurrence at the 8-month follow-up examination. PTPR should be considered in the differential diagnosis of pineal tumors. PTPR may have been frequently misinterpreted in the past as either ependymoma or choroid plexus papilloma due to the similar morphology.

Objective: We report two rare cases of primary choriocarcinoma in the pineal region verified histologically. In both cases, the pre-operative serum level of human chorionic gonadotropin (HCG) was significantly elevated to 128-/+935.7 and 9 -/+088.9 mIU/ml, respectively, and serum alpha-fetoprotein (AFP) was negative. The tumors were microsurgically removed, and postoperative hydrocephalus were treated by endoscopic third ventriculostomy. Both patients underwent chemotherapy and radiotherapy. After adjunctive treatment, the serum HCG decreased within normal range. During the two-year-long follow-up, no radiological (MRI) evidence was found to suggest recurrence in MR imaging, and the serum HCG was normal in one patient, but mildly elevated in the other. HCG measurement can be crucial to the diagnosis and post-treatment monitoring of choriocarcinoma, and radical surgical tumor removal and combined modality therapy including chemotherapy and radiotherapy may ensure good results.

Background: Papillary pineocytoma is an extremely rare tumor usually with a poor outcome., Case Report: We report a case of a 10-year-old-girl with pineal gland tumor and obstructive hydrocephalus diagnosed using MRI. The child was successful treated by insertion of a ventriculoperitoneal shunt and consecutive tumor resection by supracerebellar-infratentorial approach. Histopathological examination showed a papillary structure of the pineocytoma. As such, tumors are considered to be aggressive the child was subjected to radio- and chemotherapy., Conclusion: At six year follow-up after surgery, the patient is symptom-free and the MRI shows no tumor recurrence.

Objective and Importance: We report the extremely rare occurrence of a second germ-cell tumor at a different site and with different histological types long after total resolution of a pineal germinoma., Clinical Presentation: A 21-year-old man who presented with headache and diplopia was admitted to our hospital. Neuroradiological studies revealed a tumor in the pineal region. The tumor was biopsied with endoscope, and third ventriculostomy was performed. Histologically, the tumor proved to be a germinoma. The patient received 3 cycles of combination chemotherapy consisting of carboplatin and etoposide with radiotherapy. The tumor was totally resolute. Twelve months later, he was readmitted with headache and diplopia. Neuroradiological studies showed a tumor in the right temporal lobe., Intervention: The second tumor was totally removed. Histologically, the tumor proved to be a mixed germ-cell tumor, which consisted a yolk-sac tumor and a germinoma. After the second course of chemotherapy, magnetic resonance image studies revealed no evidence of the tumor., Conclusion: The second tumor was considered to be a metachronous neoplasm rather than a recurrence of the original mixed germ-cell tumor, which consisted a yolk-sac tumor and a germinoma.

Tumors of the pineal region represent a diverse collection of tumors with a variety of natural histories. This diversity necessitates accurate histologic diagnosis to allow rational therapeutic planning. Evaluation of a pineal lesion should begin with craniospinal MRI and analysis of the cerebrospinal fluid (CSF). Whereas certainty of the histologic diagnosis is now a requirement for treatment in Western nations, some Asian centers continue to recommend a test dose of radiation therapy based on the high incidence of germinoma in those countries. If there is high clinical suspicion of a germinoma or tectal glioma, stereotactic or endoscopic biopsy may be pursued. All other lesions should be referred for open biopsy with microsurgical techniques. This approach provides adequate tissue for diagnosis, may be curative in low-grade tumors, and may substantially improve survival in patients with malignant tumors. If open surgery is not desired by the patient or practitioner, stereotactic or endoscopic biopsy may be followed by radiosurgery for localized, well-demarcated tumors. Radiation therapy is the first-line therapy for germinomas. Although the optimal radiation dosage and volume have not been decided, the current Children's Oncology Group trial may offer definitive evidence to address this dilemma in germ cell tumors. Evidence of CSF seeding requires craniospinal radiation and adjuvant chemotherapy regardless of tumor type. Diagnosis of any of the malignant tumors (non-germ cell tumors, pineoblastomas, and parenchymal tumors of intermediate determination) also requires craniospinal radiation (with local tumor doses of at least 50 Gy) and adjuvant chemotherapy (generally platinum based). Patients with tectal gliomas may undergo excision with or without postoperative radiation; however, they also may be observed with vigilant follow-up alone.

Objective: Evaluation of results of the neurofiberscopic biopsy of tumors of the pineal region and posterior third ventricle., Methods: From 2001 to 2004, 23 patients (mean age, 30.6 yr) with tumors located in the pineal region or posterior third ventricle underwent neurofiberscopic biopsy with simultaneous third ventriculostomy. The procedure was indicated for verification of the histological diagnosis of the neoplasm, which was planned to be treated by radiotherapy and/or chemotherapy without open surgery (eight patients), establishment of the pathological diagnosis for further choice of the most appropriate treatment strategy (11 patients), differentiation of the recurrent neoplasm and radiation necrosis (two patients), and decompression of the large tumor-associated cyst (two patients). In six previously shunted patients, substitution of the ventriculoperitoneal shunt on the third ventricle stoma was performed., Results: There was no postoperative mortality or permanent morbidity. In all cases, the obtained tissue sample was sufficient for pathological diagnosis. Transient postoperative complications included fever (15 patients), nausea and vomiting (three patients), and diplopia (one patient). On the long-term follow-up, delayed third ventricular stoma failure caused by tumor regrowth and scar formation was found in one patient, and dissemination of the malignant glioma through the subarachnoid space was found in another patient., Conclusion: Neurofiberscopic biopsy represents a useful method for sampling of tumors of the pineal region and posterior third ventricle, which can be effectively used in both previously shunted and shunt-free patients.

This two part series of articles presents poignant narratives based on interviews done with two mothers who suffered the worst pain imaginable--the pain of losing a child. Each woman describes an insensitive health care system with providers unaware of parental views and needs when confronted with difficult decisions during their children's illnesses and subsequent deaths. Each woman also hoped that telling her story might help nurses and other health care providers better understand how to help. Part 1 of the series is the story of a professional, highly educated mother who experienced periods of extreme distress while she tried to give her premature daughter an identity and meaningful life in the neonatal intensive care unit and the difficulties faced when she was transferred to another unit as she became more ill Part 2 of the series is the story of a highly devoted working mother who tried to understand the information that was rarely offered to her as she lived through the extreme surgical and uncertain medical interventions given her toddler daughter with a fast-growing brain tumor. Both women faced hard decisions along their daughters' illness trajectories. Both hoped for support from their health care providers in being active in decision-making. These narratives are in their own voices, from their own points of view.

Pineal parenchymal tumors (PPT), including pineoblastomas, are very uncommon, especially in adults. Because of the small number of reported cases, the histological and biological features of these tumors are still being defined, as is their optimal management. Also, the pathological variability of these tumors makes it difficult to draw general conclusions about their behavior. We report the case of a PPT of intermediate differentiation (PPTID) with an excellent outcome. A 3.2 cm tumor in the pineal and tectal region with obstructive hydrocephalus was found in a 28-year-old female complaining of headaches and hypoesthesia of the right side of the face. Stereotactic biopsy revealed a highly cellular tumor composed of small cells that contained little cytoplasm that were arranged in a diffuse pattern. Mitotic activity was low and there was no evidence of necrosis. Immunohistochemical examination demonstrated positive staining for neuron-specific enolase and synaptophysin. There was no expression of neurofilaments or GFAP. Ki-67 proliferation index was 12%. The diagnosis was a PPTID. Treatment consisted of combined neoadjuvant chemotherapy and craniospinal radiotherapy. Six years after treatment, the patient is alive and free of any clinical or radiological signs of relapse. This paper discusses the pathological and biological features of these tumors and the treatment options available.

We report a patient with an immature teratoma of the pineal region with high levels of alpha-fetoprotein (AFP) in serum and cerebrospinal fluid. This is very rare and to the best our knowledge, the second case reported in the literature.

Aim: In patients with space-occupying lesions of the pineal region, increased intracranial pressure is due to direct compression of the sylvian aqueduct. Based on results of the recent literature, neuroendoscopic management of obstructive hydrocephalus, secondary to tumors of the pineal gland, has gained a preeminent role respect to shunting procedures., Methods: In 14 select cases, hydrocephalus was secondary to midline and pineal lesions. The patient's age ranged from 1 to 56 years (mean 47.3+/-12.5), with a follow-up ranged from 3 months to 5 years after discharge. In 9 cases the endoscopic procedure represented the only surgical treatment. In 5 cases, microsurgical removal of the lesions and/or ventriculo-peritoneal shunts placement were performed, as additional treatment, while adjuvant radiotherapy was utilized in 4 cases; high dose chemotherapy followed by bone marrow transplantation was performed in 3 cases., Results: In our series, obstructive hydrocephalus secondary to midline and pineal lesions, was successful treated by neuroendoscopic approach alone in 9 cases, with an unremarkable course and good outcome, except in 1 case., Conclusions: Neuroendoscopic approach affords a minimally invasive way to obtain 4 objectives by one-step surgical approach, such as resolution of obstructive hydrocephalus by endoscopic third ventriculostomy (ETV), cerebrospinal fluid sample to detect tumor markers and to perform cytological analysis, biopsy specimens and tissue diagnosis, associated to absence of shunt-related complications. Therefore, in experienced hands, ETV should be the treatment of first choice, in cases of hydrocephalus secondary to lesions of the pineal gland.

Purpose: To review the literature on the occurrence of osseous metastases in recurrent pineoblastoma, and to report upon the feasibility and efficacy of treatment using intensive conventional chemotherapy to achieve a remission, followed by consolidation with marrow ablative chemotherapy and autologous hemopoietic stem cell rescue., Patient and Methods: An adult with isolated extraneural, osseous and bone marrow metastases from a pineoblastoma, received conventional cyclical chemotherapy, followed by consolidation with marrow ablative chemotherapy (thiotepa, carboplatin and temozolomide) and autologous hemopoietic stem cell rescue., Results: A complete radiographic and histopathologic response was achieved after almost one year of conventional chemotherapy that was tolerated without significant sequelae. Following successful harvesting of peripheral blood stem cells, the patient underwent myeloablative chemotherapy with autologous stem cell rescue, without difficulty in hemopoietic reconstitution and without serious or permanent side effects., Conclusions: Osseous metastases from pineoblastoma are an extremely rare occurrence. We conclude that conventional chemotherapy can achieve a complete response, and subsequent consolidation with marrow ablative chemotherapy and autologous hemopoietic stem cell rescue is feasible and well tolerated.

A 20-year-old man presented with diplopia. Neurological examination revealed mild skew deviation and upbeat nystagmus. Computed tomography showed a clover-shaped isodense mass in the pineal region with homogeneous enhancement. The lesion was isointense on both T(1)- and T(2)-weighted magnetic resonance (MR) imaging with homogeneous enhancement by gadolinium-diethylenetriaminepenta-acetic acid. Cerebral angiography showed no tumor staining. Serum and cerebrospinal fluid were negative for beta-human chorionic gonadotropin, alpha-fetoprotein, and placental alkaline phosphatase. Open biopsy was performed using a right occipital transtentorial approach. Histological examination revealed a tumor consisting of clusters of germinoma cells, but with prominent infiltration of lymphocytes, plasma cells, and macrophages, and proliferation of small vessels. The histological diagnosis was germinoma with granulomatous reaction. MR imaging showed complete disappearance of the tumor after chemoradiotherapy. Neurosurgeons should be aware of this rare tumor to avoid misdiagnosis as granulomatous inflammation.

A 21-year-old man with a 5-month history of diplopia caused by isolated vertical ocular misalignment had normal laboratory studies, including brain magnetic resonance imaging (MRI). Eight months after the onset of diplopia, he reported dry mouth, polydipsia, polyuria, and absent sweating. Examination now disclosed light-near dissociation of the pupillary responses, convergence-retraction nystagmus, and upgaze palsy. MRI revealed enhancing suprasellar and pretectal masses presumed to be germinomas. Two years after brain irradiation and systemic chemotherapy, no lesions are apparent on MRI and hypothalamic dysfunction has partially resolved. In a young patient with isolated vertical diplopia and normal brain imaging, one should consider an early pretectal syndrome and inquire after manifestations of hypothalamic dysfunction.

Pineoblastoma is a rare tumor in adults, and factors influencing survival are poorly understood. Data from the Brain Tumor Registry of Japan (BTRJ) was analyzed to examine patient, tumor, and treatment characteristics associated with increased survival in adults with pineoblastomas. All pineoblastoma cases in adults aged 16 years or older were identified in the BTRJ. Data were extracted on demographics, presentation, tumor characteristics, treatments, and outcomes. Kaplan-Meier plots, the log rank method, and p value <0.15 was used to screen variables for inclusion in a multivariate Cox regression estimating survival. In the final Cox multivariate model, all variables with p values <0.05 were considered significant predictors of survival, and all variables with p values 0.05-0.099 were considered trends. The BTRJ contained 34 adults with pineoblastomas diagnosed from 1969-1998. The patients were predominantly male (22 patients), with a median age of 35 years (range 16-66 years). Median survival from diagnosis was 25.7 months, with a median follow up of 20.5 months. Median surgical resection was 75-94%, and five of the 34 patients had gross total resection. Twenty-nine of the 34 patients received cranial irradiation therapy with a median dose of 50 Gy (range 30-70 Gy). In the final multivariate model, cranial irradiation > or =40 Gy (p=0.014) and gross total resection (p=0.034) were associated with improved survival. There was a trend towards improved survival for women (p=0.099). Adult pineoblastoma patients have poor survival prognosis. Cranial irradiation therapy using at least 40 Gy and complete surgical resection are associated with improved survival.

A 13-year-old male was diagnosed as having pineal germinoma in July 1998. Since then, he had been treated with tumor excision, radiation and chemotherapy. In June 2002, he was diagnosed as having the chronic phase of chronic myelogenous leukemia (CML), and following treatment with interferon-alpha, he achieved hematological complete remission. Although CML is rare in secondary leukemia, the present case seemed therapy-related CML because of its clinical course, as the CML occurred after the period with radiation and chemotherapy. This is the first case of secondary CML following therapy for intracranial tumors.

In patients with pineal tumors, clinical symptoms are due to direct compression of adjacent structures. The most common signs include increased intracranial pressure (80%) caused by obstruction of the sylvian aqueduct, and Parinaud syndrome (50%) caused by direct compression of the superior colliculi. Hearing loss is rare in patients with tumors in this location. The authors report on the case of a 12-year-old boy in whom a malignant pineal germ cell tumor was found together with the unusual occurrence of severe hearing loss due to direct bilateral compression of the inferior colliculi. This condition resolved completely after tumor regression.

Pineal region lesions consist of a wide variety of rare tumor types, including deep midline cysts, intrinsic pineal tumors, germ cell tumors and vascular lesions. Advances in microsurgical, endoscopic and stereotactic techniques have helped to lower morbidity and mortality in the care of patients harboring these lesions. Surgery can be the definitive treatment in cysts and benign lesions. This report summarizes the retrospective experience of the authors with 64 pineal region and associated lesions encountered in multiple institutions over the last 20 years. Histology was obtained in 53 out of 64 radiographically apparent lesions. Direct surgical biopsy of solid and vascular tumors in the pineal region enables precise histological assessment of mixed tumors. By avoiding sampling error, precise treatment can be planned. This series, along with previously published data, shows a much higher incidence of intrinsic pineal tumors, glial tumors and nongerminomatous germ cell tumors in series from North America and Europe than in those from Japan and Korea, where germinoma is much more common. We experienced an incidence of 20.4% germinoma out of 49 solid and vascular pineal tumors, while other authors have described incidences of 51.2 and 53.5%, respectively. The fact that histology is more diverse in Western populations leads to a need to have more representative sampling. Early surgical resection combined with diversion of cerebrospinal fluid is effective in the treatment of pineal lesions and seems to be superior to the alternative of treatment based on the diagnostic response to radiation and/or on tumor markers alone., (Copyright 2003 S. Karger AG, Basel)

The November 2002 COM. A 72-year-old immunocompetent woman presented with recent confusion, memory loss, visual and a gait disturbance. MRI scans demonstrated a T2 hypointense, gadolinium enhancing mass in her pineal region. A whole body CT scan identified a large retroperitoneal mass and significant lymphadenopathy. She underwent a biopsy of the pineal lesion. The intraoperative smear contained discohesive, basophilic malignant cells of moderate size that had only scant cytoplasm, an increased nuclear-to-cytoplasmic ratio and irregular, hyperchromatic nuclei containing prominent nucleoli. Mitotic figures, apoptotic and lymphoglandular bodies were frequent. Histologic examination showed malignant cells infiltrating and almost completely replacing the residual pineal gland. The tumor cells immunoreacted with LCA and CD-20. Scattered CD3 and UCHL-1 positive cells were also present. The diagnosis was stage IV, high grade, large B-cell lymphoma involving the pineal gland and retroperitoneum. Four cycles of systemic chemotherapy significantly reduced the patient's retroperitoneal mass. However, a repeat head MRI scan continued to show gadolinium-enhancement in the pineal region, now with extension into contiguous brain parenchyma and the subependymal region. The patient died 4 months after presentation. At autopsy, the lymphoma encased the pineal region and disseminated along the ventricular walls and into the subarachnoid spread. Pineal-region tumors are rare in the elderly population, and although unusual, lymphomas should be considered in this context. The behavior of this circumventricular organ lymphoma was comparable to both peripheral and primary central nervous system lymphomas.

We report a case of a 14-year-old Chinese boy with immature teratoma of the pineal gland who manifested with parkinsonism. Diagnostic evaluation revealed hydrocephalus and an immature teratoma of the pineal gland extending to the thalamus. An urgent ventriculoperitoneal shunt was inserted, and chemotherapy was given to reduce the tumor size. The tumor was completely excised 2 months after diagnosis with improvement of clinical signs and symptoms. His symptoms recurred 3 months later with sudden onset of obtundation, tremors, cogwheel rigidity, and marked bradykinesia. Magnetic resonance imaging (MRI) revealed a small enhancing lesion in the pineal region and progressive hydrocephalus on serial studies. He was treated with carbidopa/levodopa and amantadine, but marked improvement was only observed after reprogramming his VP shunt. Features consistent with the growing teratoma syndrome were noted during this period. These were progressive pineal gland tumor enlargement documented on MRI without increase in previously elevated alpha-fetoprotein levels. The tumor continued to enlarge despite gamma knife radiosurgery. Secondary parkinsonism is a rare presentation of pineal gland tumors and has not been reported in association with the growing teratoma syndrome.

Recurrence along an endoscope tract has been described after endoscopic biopsy and resection of malignant tumors arising in multiple organ systems. We describe a case of tract recurrence following the ventriculoscopic biopsy of a central nervous system tumor. A retrospective review of the patient's clinical course, radiology and pathology was undertaken to formulate a case report. A 14-year-old boy was treated with endoscopic third ventriculostomy and endoscopic biopsy of a pineal germinoma associated with hydrocephalus. Persistent hydrocephalus required repeat third ventriculostomy. The patient subsequently received focal external beam radiotherapy. Seventeen months after the first third ventriculostomy, a routine MRI revealed a 2-cm enhancing mass in the ventriculoscope tract. This was removed via a right frontal craniotomy. Again the pathology was germinoma. Serum and CSF markers were negative at initial presentation and at the time of recurrence. The potential for tract recurrence and CSF dissemination should be considered following the endoscopic biopsy of pineal germ cell tumors as this could affect the extent of radiotherapy and/or chemotherapy., (Copyright 2001 S. Karger AG, Basel)

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.

We review the current classification of the central nervous system neoplasms focusing on grading and new clinicopathological entities. Moreover a brief synopsis on up to date treatments in different groups of neoplasms is given.

The results of a non-resective treatment approach for pineoblastoma comprising stereotactic biopsy, cerebrospinal fluid diversion, and fractionated radiotherapy in six patients over a period of six years are presented. There were three male and three female patients, with a median age at diagnosis of 20 years. Magnetic resonance imaging of the spine, ventricular cerebrospinal fluid cytology, and tumour markers in cerebrospinal fluid were negative. Tumour response to initial radiotherapy was complete in three patients and partial in three patients. Recurrences were treated with interstitial irradiation with iodine-125 seeds in four instances, repeat radiotherapy when time elapsed was more than five years in one instance, with surgical resection in two instances, and chemotherapy in two instances. The diagnostic and therapeutic effectiveness of this management strategy is assessed. There were no complications related to surgical procedures. The median follow-up time was 48 months (range 14-70 months). Five patients were alive at 14, 45, 51, 57, and 70 months of follow-up. One patient died of disease at 28 months following diagnosis. The overall survival rate was 80 % +/- 17.89 % at 28 months. The results of this study suggest that this non-resective treatment approach is acceptable as an initial treatment alternative to radical surgical resection of pineoblastomas.

Until recently, surgery for pineal region tumours has met with poor results. Although experience remains limited, developments in imaging, surgical approaches, and microsurgery have improved outcomes. Over 26 years we treated 36 patients including: 24 with germinoma; four, teratoma; three, pineal cyst; and one each, embryonal carcinoma, choriocarcinoma, pineocytoma, pineoblastoma and metastasis. All 24 germinomas responded to radiotherapy, as did one case each for teratoma, pineoblastoma, and choriocarcinoma. Eight patients underwent resection, and one patient with germinoma had biopsy via endoscopy. Occipital transtentorial and parieto-occipital transcallosal approaches were used in three each, and infratentorial supracerebellar and a combined infratentorial supracerebellar and occipital transtentorial approach in one each. Total removal was achieved in four patients (50%), and subtotal removal in two. Postoperative complications resolved within 2 weeks. Two patients had recurrence and one had dissemination. All tumours except germinomas should be explored and diagnosed histologically. Current operative techniques allow safe, effective removal of pineal region tumours., (Copyright 2000 Harcourt Publishers Ltd.)

Purpose: The aim of this study was to identify factors that could lead to optimization of the management of pineal parenchymal tumors (PPT) which remains equivocal and controversial., Methods and Materials: In order to determine factors that influence PPT prognosis, a series of 76 consecutive patients from 12 European centers with histologically proven tumors was retrospectively reviewed. The clinical records and material for histologic review were available in all cases. Follow-up was achieved in 90% of cases., Results: According to WHO classification, there were 19 pineocytomas, 28 intermediate and mixed PPT, and 29 pineoblastomas. According to a four-grade institutional classification, there were 11 Grade 1, 27 Grade 2, 20 Grade 3, and 18 Grade 4. Surgical resection was attempted in 44 patients, whereas 30 had biopsy only. In one case, diagnosis was made at autopsy and in another on spinal deposits. Forty-four patients were irradiated following surgery, 15 patients received chemotherapy. Forty-one patients were alive (median follow-up: 85 months); 9 patients died perioperatively; 26 patients relapsed. Univariate analysis showed a good outcome correlated with age above 20 years, tumor diameter less than 25 mm, and low-grade histology. Multivariate analysis confirmed histology and tumor volume to be significant independent prognostic factors. The extent of surgery and radiotherapy had no clear influence on survival., Conclusions: This review highlights the prognostic features of PPT and may help to determine treatment strategies based on radiologic and pathologic characteristics.

The anatomy, pathophysiology nad treatment of the pineal region tumors are presented. The authors stress the role of stereotactic biopsy in the diagnosis and correct management. Based on the literature and their experiences the risk of complications and incorrect diagnosis is discussed.

A pineal tumour in a 27-year-old male is presented with the characteristic histological features of a pineal malignant rhabdoid tumor (MRT) with chondroid formation. Occasionally, tumor cells contained a single well-demarcated hyaline globular inclusion within the cytoplasm adjacent to the nucleus. The stroma of these tumors tends to be densely hyalinized and become chondroid. Immunohistochemical staining was positive for vimentin, epithelial membrane antigen, chromogranin A, synaptophysin, neuron-specific enolase, S-100 protein, and muscle actin. Despite surgery and radiochemotherapy, the tumor recurred in the pineal region and metastasized to the lower lobe of right lung. The patient died 2 years after the initial diagnosis. This is the second published case of central nervous system-MRT appearing in an adult. The clinical and pathological features of pineal MRT in this patient are presented.

We analyzed clinically 30 germinomas (22 pure germinomas and 8 germinomas with syncytiotrophoblastic giant cell (STGC) and also investigated the proliferative potential of 18 germinomas immunohistochemically using MIB-1 monoclonal antibody in formalin-fixed paraffin-embedded sections. The majority of patients responded favorably and completely to the treatment. Seven patients (four had germinomas with STGC and the other three had pure germinomas) suffered recurrence after a complete response to radiotherapy and/or chemotherapy. The patients with germinomas with STGC experienced recurrence significantly more often than those with pure germinomas (P < 0.01). Three of the patients died. The MIB-1 indexes of the germinomas ranged from 18% to 80%. The average MIB-1 index of pure germinomas is 58.5 +/- 17.3%, that of germinomas with STGC is 45.3 +/- 17.1%. There was no significant difference between the two groups. The MIB-1 indexes of 3 recurrent cases were 64.3%, 51.9%, and 20.8%, respectively. There were no significant differences in the MIB-1 indexes between nonrecurrent cases and recurrent ones.

There has been a relative absence of studies that have longitudinally examined the neuropsychological profiles of patients suffering from pineal tumors. A case is reported of an adolescent girl with a pineoblastoma and spinal metastases who received extensive chemotherapy and cranio-spinal irradiation. Neuropsychological assessments conducted approximately 5 months and 2.5 years posttumor diagnosis revealed a diversity of impairments indicative of mild to moderate neuropsychological dysfunction. By the 2nd evaluation (2 years postbaseline) there was evidence of increased neurocognitive impairment suggestive of greater dysfunction of the patient's right, versus left, cerebral hemisphere. Overall, the patient's neuropsychological profile coincided with the Syndrome of Nonverbal Learning Disabilities as proposed by Rourke and his colleagues (Rourke, 1987, 1988, 1995; Rourke & Tsatsanis, 1996). These findings are discussed in light of the Syndrome of Nonverbal Learning Disabilities (and the related white matter model) and the possible negative impact of the patient's pineal tumor and subsequent chemotherapy and cranio-spinal irradiation on her neuropsychological functioning.

A 14-year-old boy presented with an extraneural metastasis of germinoma with syncytiotrophoblastic giant cells (STGC). The tumor was located in the pineal area, suprasellar cistern, and frontal base, and associated with the slight elevation of the beta-human chorionic gonadotropin (HCG) serum level. Following radiation therapy, the tumor completely disappeared, and the beta-HCG level decreased to normal. Two years after the initial treatment, metastasis of the tumor to the left femur was observed without recurrence of the primary lesion. The biopsy specimen revealed germinoma, the diagnosis was germinoma with STGC because of the associated elevation of HCG level. The metastatic tumor was treated by chemotherapy with cisplatin and etoposide, and the tumor completely disappeared. With adjuvant chemotherapy, he has been recurrence-free for 3 years. Extraneural metastasis occurs more frequently from germinoma with STGC than germinoma. Aggressive chemotherapy combined with radiation therapy in the initial treatment might have to be tried to avoid metastasis from germinoma with STGC.

Trilateral retinoblastoma (TRb) is a syndrome involving midline intracranial malignancies in children with the heritable form of retinoblastoma. All cases of TRb reported from 1971 to 1997 were reviewed. The histopathologic findings, clinical features, treatment modalities, and survival rates from 80 cases were evaluated. Histopathologic findings from intracranial malignancies demonstrated primitive neuroectodermal tumors in 61.5% of cases. Various degrees of neuronal or photoreceptor differentiation were seen in the other 38.5% of cases. Autopsy, histopathologic, and radiologic examinations did not show a more definitive site of origin of these intracranial tumors, although "pinealoblastoma" was often the diagnosis reported. These findings, together with analysis of the histopathologic similarities among human primitive neuroectodermal tumors, pinealoblastoma, retinoblastoma, and ependymoblastoma, suggest that TRb more likely arises from a germinal layer of predisposed primitive subependymal neuroblasts that are not necessarily destined for pineal or photoreceptor differentiation. Trilateral tumors have also been found in transgenic mice expressing the simian virus 40 T-antigen. Transgenic murine intracranial tumors are primitive neuroectodermal tumors arising from the subependymal layer. Transgenic mice with the murine interphotoreceptor cell binding protein promoter and simian virus 40 T-antigen also develop pineal tumors. Trilateral retinoblastoma is usually fatal, with an average survival time of 11.2 months. Therapies include radiation, systemic chemotherapy, intrathecal chemotherapy, and surgical resection/craniotomy in combination with radiation and/or chemotherapy. Survival may be prolonged with combination chemotherapy (24.6 months) and if neuroradiologic screening identifies TRb before symptoms are present (23.5 months). Recent success with platinum-based chemoreduction of intraocular retinoblastoma may indicate a similar role for platinum-based chemotherapy in the treatment of TRb. Routine central nervous system imaging should be considered in the management of TRb.

Primary intracranial germ cell tumors are rare neurological diseases. Secreting germ cell tumors that predominantly appear in the pineal region are characterized by elevated levels of beta-HCG and AFP in CSF. Adequate diagnostic and therapeutic regimens of these tumors are still under debate. We present the case of a patient suffering from spinal metastasis of a secreting germ cell tumor with raised levels of beta-HCG in CSF. Six years before, a pineocytoma of intermediate differentiation had been diagnosed by stereotaxic biopsy. This demonstrates the importance of an early detection of a germ cell neoplasm in case of midline-sized brain-tumors by evaluation of beta-HCG and AFP in CSF and serum. Today, different therapeutic strategies depending on the histological diagnosis are available and justify a high priority of a surgical tumor biopsy. However, the value of stereotaxic procedures remains controversial. Recently published data gave evidence of a definite improved prognosis of secreting CNS germ cell tumors following combined treatment with high-dose polychemotherapy, surgical resection and radiation of the tumor area. beta-HCG and AFP may serve as useful markers to enable follow-up of the disease.