Pineal Germinoma Research Articles

Pineal Germinoma with Extracranial Metastases: Case Report

Pineal germinoma is the commonest pineal region tumor of childhood and adoles- cence. Metastatic germinoma most commonly occurs via the cerebrospinal fluid (CSF), and it is usually limited to the cerebrospinal axis. Extacranial hematogenous metastasis is known to be very rare. We report here on a case of pineal germinoma with gradual extracranial metastases that occurred both through the CSF pathway and by hematogenous spread. The pa- tient had multifocal CSF seeding after his surgery for pineal germinoma, and the left il- iac metastasis and lung metastasis then occurred.

Metástasis ovárica de germinoma encefálico

Cerebrospinal fluid drainage to the abdominal cavity through a ventricular-peritoneal shunt is a frequent procedure in the treatment of hydrocephaly secondary to brain tumors. However, there are reports that identify these shunts as the means of tumoral cell dissemination.Clinical report: A 19-year-old woman with pineal germinoma was treated with radiotherapy and underwent ventricular-peritoneal shunting. Fifteen months later, she was readmitted due to possible ovarian pseudotorsion caused by a 7cm-length formation located in the right ovary. The definitive diagnosis was metastases from an embryonic tumor of the pineal gland.

Chronic myelogenous leukemia following therapy for pineal germinoma

Chronic myelogenous leukemia following therapy for pineal germinoma

Successful treatment of extracranially metastasized pineal gland germinoma with high-dose methotrexate

Germinoma of the pineal gland is a rare disease usually confined to the brain which responds well to radiotherapy. Spinal seeding occurs in ∼4% of cases and distant metastases are extremely rare. We report on a 27-year-old female with an intracranially metastasized pineal gland germinoma, meningeal carcinomatosis and distant bone metastases. Treatment was initiated with intrathecal methotrexate (MTX) and continued with high-dose intravenous MTX. The therapy was very well tolerated apart from reversible hepatic toxicity requiring a dose reduction. The patient was in complete remission after three courses followed by two consolidation cycles; the patient has now been in continuous complete remission for more than 22 months. This is the first report to show that MTX is a potent drug in treating pineal gland germinoma. Long-term side effects of radiotherapy such as reduced mental function or hypopituitarism can probably be avoided. Single-agent high-dose MTX may provide high efficacy with limited adverse effects, especially at a more advanced tumor stage with spinal seeding and extracranial disease.

Metastasis of pineal gland germinoma through a ventriculoperitoneal shunt and subsequent presentation with abdominal pain and GI bleeding

Metastasis of pineal gland germinoma through a ventriculoperitoneal shunt and subsequent presentation with abdominal pain and GI bleeding

Precocious puberty in children with tumours of the suprasellar and pineal areas: Organic central precocious puberty

During the past 11 y, 115 children younger than 8/9 y of age (female/male) with tumours of the suprasellar or pineal areas were followed in our clinic to study the incidence of precocious puberty. In addition, type of central lesion, clinical characteristics and gonadotropic secretion were studied in order to elucidate the different mechanisms of gonadal activation. A control group of 21 patients with idiopathic precocious puberty and a control group of 10 age-matched patients with suprasellar tumours without precocious puberty were also studied. Precocious puberty associated with organic central lesions was found at diagnosis in 30 patients (26%), in 9 out of 48 patients with glial cell tumours (18.7%), 6 out of 9 patients with germ cell tumours (66.6%), 11 out of 11 patients with hypothalamic hamartomas (100%) and in 4 out of 4 patients with subarachnoid cysts or arachnoidocele (100%). Precocious puberty was not found in any of 36 patients with craniopharyngioma. With the exception of one patient with pineal germinoma, all lesions were localized to the suprasellar area. In all patients with hypothalamic hamartoma, precocious puberty was diagnosed before 4 y of age, while in most patients with the other lesions, it was diagnosed after this age. Height SDS, weight increase and advancement of bone age were similar in both idiopathic and organic central precocious puberty. Maximal LH responses to GnRH in idiopathic and organic central precocious puberty were similar except for germ cell tumours. Patients with suprasellar tumours without precocious puberty had lower maximal LH (but not FSH) responses to GnRH, with the exception of germ cell tumours. In the latter, elevation of serum beta-hCG indicates that this gonadotropin was responsible for gonadal stimulation. In hypothalamic hamartomas, the prepubertal hiatus in the activity of the GnRH pulse generator was absent. The mechanism of this failure in the inactivation of GnRH is unknown. Data suggest that in glial cell tumours and in subarachnoid cysts, an unknown factor, probably secreted by the tumours, advances the tempo of GnRH maturation. Therefore, the aetiology of organic central precocious puberty is multiple and is directly related to location and type of lesion. This clinical information suggests that the onset of puberty is not the result of the disruption of a putative pulse generator inhibitory influence but the consequence of secretion of stimulatory substances by the lesions.

Precocious puberty in children with tumours of the suprasellar and pineal areas: Organic central precocious puberty

During the past 11 y, 115 children younger than 8/9 y of age (female/male) with tumours of the suprasellar or pineal areas were followed in our clinic to study the incidence of precocious puberty. In addition, type of central lesion, clinical characteristics and gonadotropic secretion were studied in order to elucidate the different mechanisms of gonadal activation. A control group of 21 patients with idiopathic precocious puberty and a control group of 10 age-matched patients with suprasellar tumours without precocious puberty were also studied. Precocious puberty associated with organic central lesions was found at diagnosis in 30 patients (26%), in 9 out of 48 patients with glial cell tumours (18.7%), 6 out of 9 patients with gem cell tumours (66.6%), 11 out of 11 patients with hypothalamic hamartomas (100%) and in 4 out of 4 patients with subarachnoid cysts or arachnoidocele (100%). Precocious puberty was not found in any of 36 patients with craniopharyngioma. With the exception of one patient with pineal germinoma, all lesions were localized to the suprasellar area. In all patients with hypothalamic hamartoma, precocious puberty was diagnosed before 4 y of age, while in most patients with the other lesions, it was diagnosed after this age. Height SDS, weight increase and advancement of bone age were similar in both idiopathic and organic central precocious puberty. Maximal LH responses to GnRH in idiopathic and organic central precocious puberty were similar except for germ cell tumours. Patients with suprasellar tumours without precocious puberty had lower maximal LH (but not FSH) responses to GnRH, with the exception of germ cell tumours. In the latter, elevation of serum β-hCG indicates that this gonadotropin was responsible for gonadal stimulation. In hypothalamic hamartomas, the prepubertal hiatus in the activity of the GnRH pulse generator was absent. The mechanism of this failure in the inactivation of GnRH is unknown. Data suggest that in glial cell tumours and in subarachnoid cysts, an unknown factor, probably secreted by the tumours, advances the tempo of GnRH maturation. Therefore, the aetiology of organic central precocious puberty is multiple and is directly related to location and type of lesion. Conclusion: This clinical information suggests that the onset of puberty is not the result of the disruption of a putative pulse generator inhibitory influence but the consequence of secretion of stimulatory substances by the lesions.

Pathology of pineal region tumors.

Various histological types of tumors arise in the pineal region. The most common tumors are pineal parenchymal tumors and germ cell tumors. Pineal parenchymal tumors are divided into pineocytoma, pineal parenchymal tumor with intermediate differentiation and pineoblastoma. Pineocytomas are well-differentiated tumors and retain the morphological and immunohistochemical features of pineal parenchymal cells. Lobular architectures and pineocytomatous rosettes are also typical features. In contrast, pineoblastomas are embryonal tumors resembling primitive neuroectodermal tumors (PNET). However, pineoblastomas are distinct from PNET in other sites due to their exhibiting photosensory differentiation including Flexner-Wintersteiner rosettes and fleurettes. Although pineal cysts are tumor-like lesions, and not true neoplasms, they are occasionally difficult to distinguish from pineocytoma and astrocytoma. From the therapeutic aspect, a precise differential diagnosis is critical. The pineal region is the most common site of the brain in which germ cell tumors occur. Germinoma, teratoma, embryonal carcinoma, yolk sac tumor and choriocarcinoma are encountered, and the latter three types of tumors usually constitute elements of mixed germ cell tumors. The morphological and immunohistochemical features of intracranial germ cell tumors are very similar to those of gonadal germ cell tumors, although there are some differences in germinoma. Pineal germinoma may exhibit carcinomatous differentiation. Other types of tumors are occasionally observed, including fibrillary and pilocytic astrocytoma, glioblastoma, ependymoma, melanoma, meningioma and so on. Metastatic pineal tumors are also rare. The most common site of origin for pineal metastasis is the lung.

The need for the moving junction in craniospinal irradiation.

The moving junction is used in craniospinal irradiation (CSI) to smooth out any dose inhomogeneity across the head/spine junction. The aim of this study was to demonstrate the extent of the head/spine junction inhomogeneity in treatment plans of actual patients and to compare stationary and moving junction data. The radiotherapy plans, prescriptions and case notes of 18 patients (12 medulloblastomas, 3 supratentorial primitive neuroectodermal tumours, 2 pineoblastomas and 1 pineal germinoma) treated with CSI (35 Gy in 21 fractions over 29 days) were examined. At 16 months median follow-up (range 1.5-35.5 months), no junctional recurrences or myelopathy were observed. Using the moving junction technique the mean maximum anterior cord dose, from 5 cm caudal to 3 cm cephalad of the Day 1 junction, was 36.3 Gy, and the mean minimum anterior cord dose was 32.9 Gy, with a mean within-patient variation of 3.4 Gy (9.7% of 35 Gy). In four patients, comparison of dose variation across the field junction was made between the original plans and a re-plan using a stationary junction. The effect of a matched junction, a 2 mm overlap and a 2 mm gap were studied both for moving junction and stationary junction techniques. Dose variations were similar in all cases for exactly-matched fields, but for a 2 mm overlap or gap the dose variation was smaller in all but one case for the moving junction technique. These data suggest that the moving junction is important to minimize the risk of overdose or underdose across the spine/head junction in CSI.

Proton magnetic resonance spectroscopic imaging in children with recurrent primary brain tumors.

Proton magnetic resonance spectroscopic imaging ((1)H-MRSI) is a noninvasive technique for spatial characterization of biochemical markers in tissues. We measured the relative tumor concentrations of these biochemical markers in children with recurrent brain tumors and evaluated their potential prognostic significance. (1)H-MRSI was performed on 27 children with recurrent primary brain tumors referred to our institution for investigational drug trials. Diagnoses included high-grade glioma (n = 10), brainstem glioma (n = 7), medulloblastoma/peripheral neuroectodermal tumor (n = 6), ependymoma (n = 3), and pineal germinoma (n = 1). (1)H-MRSI was performed on 1. 5-T magnetic resonance imagers before treatment. The concentrations of choline (Cho) and N-acetyl-aspartate (NAA) in the tumor and normal brain were quantified using a multislice multivoxel method, and the maximum Cho:NAA ratio was determined for each patient's tumor. The maximum Cho:NAA ratio ranged from 1.1 to 13.2 (median, 4.5); the Cho:NAA ratio in areas of normal-appearing brain tissue was less than 1.0. The maximum Cho:NAA ratio for each histologic subtype varied considerably; approximately equal numbers of patients within each tumor type had maximum Cho:NAA ratios above and below the median. Patients with a maximum Cho:NAA ratio greater than 4.5 had a median survival of 22 weeks, and all 13 patients died by 63 weeks. Patients with a Cho:NAA ratio less than or equal to 4.5 had a projected survival of more than 50% at 63 weeks. The difference was statistically significant (P =.0067, log-rank test). The maximum tumor Cho:NAA ratio seems to be predictive of outcome in children with recurrent primary brain tumors and should be evaluated as a prognostic indicator in newly diagnosed childhood brain tumors.

The role of chemotherapy in intracranial germinoma: A case report

The case of a 29-year-old man with histologically proven simultaneous germinoma (seminoma) of the pineal gland and a stage I embryonal carcinoma of the testis is reported. An intradural metastatic lesion from the pineal germinoma was diagnosed at the level of the first thoracic vertebra. Treatment, after inguinal orchiectomy, was chemotherapy only, rather than conventional radiotherapy for the pineal germinoma. Therapy consisted of bleomycin (B), etoposide (E) and cisplatin (P). MRI was used to assess the effectiveness of BEP chemotherapy. A complete remission of the pineal gland germinoma and the epidural metastasis was documented after two cycles of BEP chemotherapy and after 15 months of follow-up the patient remains free of relapse. The pathogenesis of simultaneously occurring germinoma of the pineal gland and embryonal cell carcinoma of the testis is discussed. The choice of therapy in these circumstances is a matter of debate and the good result of chemotherapy alone in this patient suggest that primary chemotherapy may be the therapy of choice in patients with pineal germinomas.

Relapse and subarachnoid dissemination of a pineal germinoma 14 years after radiation therapy

Intracranial germinomas are rare tumours which are highly curable with radiotherapy. In recent years treatment with chemotherapy has gained importance. Recurrence and dissemination is seen in about 10–20% of cases within the first 2 years after diagnosis; late recurrence and dissemination is very rare. We describe a patient with a recurrent germinoma 14 years after radiotherapy of a pineal tumour. We further report the management with chemotherapy, the late side effects of radiotherapy and the course of the disease with its fatal dissemination. We conclude that the use of radiotherapy, despite being highly effective, is clearly limited by its late side-effects. New regimens with chemotherapy seem promising but proved to be less effective in our case with tumour seeding throughout the subarachnoid space.

Treatment of an intracranial germinoma spinal metastasis

A 20-year-old male with a solitary intradural extramedullary spinal metastasis from a pineal germinoma presented with progressive spinal cord compression. This was initially treated with radiotherapy and the patient showed rapid clinical improvement with complete resolution of his neurological symptoms and signs. Subsequent systemic chemotherapy resulted in complete radiological resolution of the lesion. This case is presented to demonstrate radiotherapy and chemotherapy as a treatment option for germinoma ‘drop’ metastasis causing spinal cord compression, along with a review of the literature.

Preirradiation evaluation and technical assessment of involved-field radiotherapy using computed tomographic (CT) simulation and neoadjuvant chemotherapy for intracranial germinoma

Purpose: To investigate the importance of preirradiation mental and endocrinological evaluation, and the effectiveness of involved-field radiotherapy following neoadjuvant chemotherapy.Methods and Materials: Following etoposide and cisplatin with or without ifosfamide, 13 patients with nondisseminated disease received involved-field irradiation of 24 Gy in 12 fractions within 3 weeks and 2 patients with disseminated germinoma received 24 Gy craniospinal irradiation (CSI). CT simulation was used to cover the tumor bed.Results: Full-scale intelligence quotient (IQ) tests given at the time of the initial radiotherapy showed less than 90 in 7 of 11 patients who had tumors involving the neurohypophyseal region, but the 4 patients who had solitary pineal tumors showed higher scores. Panhypopituitarism was observed in 9 patients with tumors involving the neurohypophyseal region. All patients are alive without disease, with a median follow-up period of 40 months. No in-field relapse was noted after the involved-field radiotherapy. One patient experienced a recurrence outside of the planning target volume.Conclusion: Decline of neurocognitive and endocrine functions were often seen in patients with tumors involving the hypophyseal region, but not in patients with solitary pineal germinoma before radiotherapy. Involved-field radiotherapy using 24 Gy is effective with the help of CT simulation and neoadjuvant chemotherapy.

Twenty-four hour rhythm of melatonin in patients with a history of pineal and/or hypothalamo-neurohypophyseal germinoma.

Melatonin deficiency after a pinealectomy has been investigated in animals; however, in humans, this status can be assessed solely by investigating patients with a tumor originating in the pineal gland. This study analyzes secretion of melatonin and pituitary hormones in 14 patients with germinoma originating in the pineal or the hypothalamic-neurohypophyseal region. Thirteen patients had been successfully treated prior to this study. One patient was included in this study before the initiation of treatments. Plasma sampling was performed every 2 hr for 24 hr and melatonin concentrations were measured by radioimmunoassay. Melatonin secretion was nearly absent in the patients with pineal germinoma regardless of treatment option, even in the patient who had been untreated. In contrast, melatonin secretion and its circadian rhythms were not affected in patients with a hypothalamo-neurohypophyseal germinoma. The circadian rhythms of growth hormone and adrenocorticotropic hormone were not dysregulated in patients with the melatonin deficiency. We conclude that germinoma cells originating the pineal gland impair the production of melatonin by pineocytes and consequently induce a permanent melatonin deficiency in those patients. Since melatonin exerts multiple physiological functions, once a clinical concept of "melatonin deficiency syndrome" is established, melatonin replacement therapy could be investigated in patients who have a pineal germinoma or who have undergone a neurosurgical pinealectomy.

Long-term follow-up of germinoma after stereotactic biopsy and brain radiotherapy: a cell kinetics study.

The primary aim of this study is to report the long-term outcome of pineal and suprasellar germinoma after stereotactic biopsy and whole brain radiotherapy. The second purpose is to report an investigation of the biological features and cell kinetics of this peculiar and enigmatic brain tumour. Of 34 supratentorial germ cell tumours diagnosed and treated between 1980 and 1993, 20 patients were found to be affected by true germinoma localized in the pineal and/or suprasellar regions. The diagnosis was achieved by stereotactic biopsy in all cases. In 14 patients, the potential proliferative activity of the tumour was investigated by (3H)thymidine in vitro binding and labelling index determination. Chorionic gonadotropin, alpha-fetoprotein and embryonal carcinoma antigen were negative in the cerebrospinal fluid of these patients. All but 1 patient underwent whole brain radiotherapy. Clinical and neuroradiological follow-up ranged between 3 and 13 years (mean 8). Complete clinical and neuroradiological recovery was achieved in all patients after treatment. Fatal recurrences owing to neuraxis dissemination occurred in three cases. The labelling index in the whole series ranged between 0.1 and 5% (median 2.5). Only syncytiotrophoblastic cells had proliferative activity, while none of the lymphoid-like cells showed thymidine labelling.

Pineal germinomas with granulomatous inflammation Report of two cases and review of the literature

The authors report on two cases of pineal germinomas with granulomatous inflammation (granulomatous germinomas). Macroscopically, both tumors were relatively hard and grayish in color. Histological examination revealed a germinoma with multinucleated giant cells and Schaumann bodies in one case, and a germinoma with the background of acellular fibrillated matrix in the other. On immunohistochemical analysis, the granulomatous germinomas were shown to contain many macrophages, T- and B-lymphocytes, and glial fibrillary acid protein-positive cells infiltrating the specimens, compared to nongranulomatous germinomas. Analysis of Masson's trichrome staining tests showed that large areas of the granulomatous germinomas were occupied by a collagenous component; this was not the case in cases of nongranulomatous germinomas. Analysis of monoclonal anti-human Ki-67 results showed that the granulomatous germinomas had a lower score than nongranulomatous germinomas (p < 0.05, unpaired t-test), indicating that germinomas with granulomatous inflammation may have a better prognosis.

Primary Intracranial Germ Cell Tumors without an Isochromosome 12p

Primary intracranial germ cell tumors are the result of the transformation of primordial cells that are unable to migrate to their normal place. These tumors are rare, accounting for less than 5% of all intracranial tumors and less than 3% of childhood neoplasias. In this paper, we have studied cytogenetically two primary intracranial germ cell tumors, a pineal region germinoma, and a mature teratoma in the right lateral ventricle. Neither tumor presented polyploidy or isochromosome 12p, considered to be characteristic of gonadal germ cell tumors. In the five reports in the literature, only one intracranial germ cell tumor presented i(12p). Perhaps i(12p) negative cases characterize a subtype of germ cell tumors.

MR Imaging Findings of Pineal Germinoma: Focus on Differential Diagnosis from Other Germ Cell Tumors

MR Imaging Findings of Pineal Germinoma: Focus on Differential Diagnosis from Other Germ Cell Tumors

A phase II trial of preirradiation carboplatin in newly diagnosed germinoma of the central nervous system

Central nervous system (CNS) germinomas respond readily to both radiotherapy and chemotherapy. This study was designed to selectively reduce the dose of radiotherapy in those patients expressing a complete response (CR) to neoadjuvant carboplatin. A Phase II trial with carboplatin was conducted in 11 newly diagnosed patients with histologically confirmed, radiologically evaluable CNS germinomas before they received radiotherapy. All patients had normal cerebrospinal fluid and serum tumor markers (i.e., human chorionic gonadotropin [HCG] and alpha fetoprotein [AFP]). Seven patients had localized tumors (three pineal, three suprasellar, and one thalamus), and four had multifocal disease. Their median age at diagnosis was 13 years (range, 7-31). One course of carboplatin consisted of 150 mg/m2 weekly for 4 consecutive weeks followed by a 2-week break. Response was evaluated after two courses. If a patient had a CR to chemotherapy, the radiotherapy doses to the involved field and the craniospinal axis were lowered from 50 Gy to 30 Gy and from 36 Gy to 21 Gy, respectively. If less than a CR was observed, two additional courses of chemotherapy were administered, after which the patient's response was reevaluated. Less than a CR required full radiotherapy doses. The radiotherapy volume was determined by the extent of disease at diagnosis (i.e., localized disease was treated with an involved field and craniospinal therapy was used for disseminated disease). Seven patients had a CR to carboplatin (five patients after two courses and two patients after four courses). Three patients had a partial response (one after four courses and two after two courses). The investigators of the latter two patients chose not to give additional chemotherapy. Another patient opted for radiotherapy after receiving only one course of chemotherapy and was not evaluable for response. Ten of 11 patients remain in continuous remission for a median of 25 months. One patient had a recurrence. He presented with a localized pineal germinoma and had a CR after two courses of carboplatin. He received 30 Gy of involved field radiotherapy and suffered a relapse 5 months later in multiple CNS sites. He died 23 months after diagnosis with diffuse CNS and peritoneal metastases. His serum AFP and HCG levels were elevated, consistent with a nongerminoma germ cell tumor. Carboplatin was highly active in treating newly diagnosed CNS germinomas. Further chemotherapy studies eventually may permit additional dose reductions and/or elimination of radiotherapy for patients with CNS germinomas.