Pineal Germinoma Research Articles

Primary medulla oblongata germinoma – an unusual posterior fossa tumors in young adults

We encountered 2 patients with germinoma arising from the medulla oblongata in whom preoperative radiological diagnosis was difficult. A 30-year-old woman presented due to aspiration pneumonia caused by bilateral lower cranial nerve palsies, and a 24-year-old man presented with headache caused by obstructive hydrocephalus. In both patients, there was a midline tumor that extended from the lower part of the fourth ventricle to the C1 lamina level. It was well-demarcated and homogeneously enhanced tumor with a slightly high density on plain CT scan. The preoperative diagnosis for both patients was ependymoma. The former patient had persistent lower cranial nerve palsies due to brain stem injury after tumor resection. Both patients achieved complete remission with adjuvant therapy. Fewer than 10 cases of germinoma affecting the medulla oblongata have been reported. Radiological findings resembling those of the pineal region germinoma were observed in the two patients reported here. We would like to stress the importance of remembering germinoma when making a preoperative differential diagnosis of fourth ventricular tumors in young adults.

Chemotherapy and Dose-adapted Radiotherapy (RT) for Central Nervous System (CNS) Germinoma: Long Term Follow-up of the Mayo Clinic Experience

Since 1989, CNS germinoma patients at the Mayo Clinic have been treated with chemotherapy (cisplatin/etoposide) followed by limited field and reduced-dose RT depending on response to chemotherapy. Here we present the long term results of patients treated in this manner. A retrospective chart review identified 28 patients diagnosed with CNS germinoma on the basis of biopsy or imaging with appropriate serum markers and treated with chemotherapy followed by RT between 1989-2007. Five patients were female. Median age was 16 years (range 9-42). Tumor locations were isolated suprasellar (n = 9) isolated pineal (n = 8) multiple intracranial (n = 6) and spinal leptomeningeal or positive CSF cytology (n = 5). Patients who had less than a complete response to chemotherapy (n = 7) underwent surgical resection and were included in analysis if pathologic examination of the specimen demonstrated residual germinoma (n = 2) scar tissue (n = 1) or teratoma without malignant features (n = 4). Serum hCG levels were <50 IU/dL in 23 patients (range 0-4.1) and unknown in 5. CSF hCG levels were <50 IU/dL in 20 patients (range 0-17) and unknown in 8. Serum AFP was <10 IU/L in 24 patients (range 0-6) and unknown in 4. CSF AFP was <2 IU/L in 20 patients (range 0-2.5) and unknown in 8. Median follow-up was 6.6 years (range 0.8-16.4). RT fields consisted of local tumor site only (n = 17), craniospinal axis (n = 10), and whole ventricle (n = 1). Total dose was 30.3-30.6 Gy (n = 23), 54 Gy (n = 3), 56 Gy (n = 1), and unknown in 1. Tumor recurrence occurred in 2 (of 28) patients. Both patients were male, young (11 and 19 y) and achieved a compete response (CR) to chemotherapy. One patient with an obstructing pineal germinoma received 30.6 Gy to local fields. He recurred at 1.1 y with in-field pineal failure and synchronous spinal leptomeningeal drop metastases. The second patient presented with a suprasellar germinoma with invasion into the optic tract and third ventricle. He received 30.6 Gy to local fields. He experienced an out-of-field recurrence in the right lateral ventricle and corpus callosum at 3.4 y. Review of initial diagnostic images revealed an unappreciated pineal cyst that resolved after chemotherapy. Both patients were successfully salvaged and are NED 16.4 y and 4 y after initial diagnosis, respectively. No patient experienced treatment- or tumor-related death. Treatment of CNS germinoma with chemotherapy and dose-reduced local RT resulted in 100% overall survival and 93% recurrence-free survival after a median follow-up of 7 y. Two of 17 patients (12%) treated with limited RT fields experienced local failure but were successfully salvaged. Patients with multiple midline tumors or brain parenchyma invasion may be at higher risk for recurrence.

Pineal germinoma morphological features in a liquid‐based cerebrospinal fluid sample

Diagnostic CytopathologyVolume 36, Issue 9 p. 645-646 Images in Cytology Pineal germinoma morphological features in a liquid-based cerebrospinal fluid sample Anna Maria Buccoliero M.D., Ph.D., Corresponding Author Anna Maria Buccoliero M.D., Ph.D. [email protected] Department of Biomedicine, Careggi Hospital, Florence, ItalyDepartment of Biomedicine, Careggi Hospital, Viale GB Morgagni 85, 50134 Florence, ItalySearch for more papers by this authorIacopo Sardi M.D., Iacopo Sardi M.D. Division of Neurosurgery, Anna Meyer Children's Hospital, Florence, ItalySearch for more papers by this authorFrancesca Castiglione M.D., Francesca Castiglione M.D. Department of Human Pathology and Oncology, University of Florence, Florence, ItalySearch for more papers by this authorFederico Mussa M.D., Federico Mussa M.D. Division of Neurosurgery, Anna Meyer Children's Hospital, Florence, ItalySearch for more papers by this authorFlavio Giordano M.D., Flavio Giordano M.D. Division of Neurosurgery, Anna Meyer Children's Hospital, Florence, ItalySearch for more papers by this authorLorenzo Genitori M.D., Lorenzo Genitori M.D. Division of Neurosurgery, Anna Meyer Children's Hospital, Florence, ItalySearch for more papers by this authorGian Luigi Taddei M.D., Gian Luigi Taddei M.D. Department of Human Pathology and Oncology, University of Florence, Florence, ItalySearch for more papers by this author Anna Maria Buccoliero M.D., Ph.D., Corresponding Author Anna Maria Buccoliero M.D., Ph.D. [email protected] Department of Biomedicine, Careggi Hospital, Florence, ItalyDepartment of Biomedicine, Careggi Hospital, Viale GB Morgagni 85, 50134 Florence, ItalySearch for more papers by this authorIacopo Sardi M.D., Iacopo Sardi M.D. Division of Neurosurgery, Anna Meyer Children's Hospital, Florence, ItalySearch for more papers by this authorFrancesca Castiglione M.D., Francesca Castiglione M.D. Department of Human Pathology and Oncology, University of Florence, Florence, ItalySearch for more papers by this authorFederico Mussa M.D., Federico Mussa M.D. Division of Neurosurgery, Anna Meyer Children's Hospital, Florence, ItalySearch for more papers by this authorFlavio Giordano M.D., Flavio Giordano M.D. Division of Neurosurgery, Anna Meyer Children's Hospital, Florence, ItalySearch for more papers by this authorLorenzo Genitori M.D., Lorenzo Genitori M.D. Division of Neurosurgery, Anna Meyer Children's Hospital, Florence, ItalySearch for more papers by this authorGian Luigi Taddei M.D., Gian Luigi Taddei M.D. Department of Human Pathology and Oncology, University of Florence, Florence, ItalySearch for more papers by this author First published: 01 August 2008 https://doi.org/10.1002/dc.20870Citations: 7AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article.Citing Literature Volume36, Issue9September 2008Pages 645-646 RelatedInformation

Metachronous mature teratoma in the corpus callosum occurring 12 years after a pineal germinoma

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.

Cavernomas in children with brain tumors: a late complication of radiotherapy

Delayed complications of radiation therapy comprise cerebral atrophy, radionecrosis and induction of tumors. Recent reports indicate the possibility of the "de-novo" formation of intracranial cavernomas in patients submitted to radiation therapy to the brain. To report three children, two with medulloblastomas and one with a pineal germinoma, treated with radiotherapy that developed intracerebral cavernous hemangiomas some years after treatment. With this work, we aim to draw attention to this occurrence in the neurosurgical community. The patients were two girls and one boy with ages comprised between 2.5 and 7 years (mean 5.2 years). The average interval from irradiation to the appearance of cavernoma was of 5.3 years (range 5-6 years). The lesions were found during the routine neuroimaging studies performed for the follow-up of their primary neoplasms. No patient showed signs or symptoms related to the cavernomas. However, the three children will need both clinical and neuroimaging surveillance to monitor the evolution of these incidentally discovered lesions. Intracranial cavernomas can occur years after cerebral radiation therapy. In spite of previous reports that show a high incidence of bleeding lesions, cavernomas may be found incidentally during the neuroimaging surveillance studies that are performed to children with brain tumors previously treated with radiotherapy. In these cases, a conservative attitude seems to be advisable, reserving surgery only for those lesions that grow or bleed.

Somatic KIT mutations occur predominantly in seminoma germ cell tumors and are not predictive of bilateral disease: Report of 220 tumors and review of literature

Mutations in the KIT gene occur in approximately 8% of all testicular germ cell tumors (TGCT) and KIT is the most frequently mutated known cancer gene. One report has shown that 93% of patients with bilateral disease have a mutation at codon 816 of the KIT gene. Importantly, this suggests that the identification of a mutation in KIT is predictive of the development of a contralateral TGCT. We investigated the frequency and type of mutations in KIT in a series of 220 tumors from 211 patients with TGCTs and extragonadal germ cell tumors. In 170 patients with unilateral TGCT and no additional germ cell tumour, we identified one exon 11 mutation in a patient with unilateral TGCT and eight activating KIT mutations in exon 17 (9/175, 5.1%). In 32 patients with bilateral TGCT, one patient had an activating KIT mutation in exon 17 (3.1%). The incidence of activating KIT mutations in sporadic TGCT vs. familial TGCT was not significantly different. All mutations were identified in seminomas. Three extragonadal primary germ cell tumors were examined and in one tumor an activating KIT mutation was demonstrated in the pineal germinoma. Interestingly, this mutation was also seen in the patient's testicular seminoma. We find no evidence for an increased frequency of KIT mutations in bilateral TGCT.

Neurohypophyseal germinoma with metastasis to the spine

Germ cell tumours constitute 0.1–3.4% of all intracranial tumours and germinomas are malignant intracranial germ cell tumours with a peak incidence in children and adolescents. The pineal gland is the most common site of origin constituting about 50%, followed by the suprasellar region (20–30%). Suprasellar and pineal region germinomas account for approximately 6–10% of intracranial germ cell tumours. There were numerous reports which correlated pathological and imaging findings of suprasellar germinomas and concluded that these tumours involve the hypothalamo-neurohypophyseal axis (hypothalamus, infundibulum and posterior lobe of the pituitary gland). On the basis of these findings, suprasellar germinoma is also called neurohypophyseal germinoma. Germinomas spread readily through the subarachnoid space and involve the spinal meninges and infiltrate directly into the surrounding structures. Intracranial germinomas are highly susceptible to irradiation and chemotherapy and are potentially curable. Therefore we hope to highlight the importance of differentiating germinoma from other midline sellar-suprasellar intracranial tumours and one should be more diligent in looking for possible spinal dissemination at presentation and during follow-up.

Late intrathoracic relapse of pineal germinoma connected to intraspinal canal

Extraneural metastases of intracranial germinoma are rarely reported. The authors describe the first case of metastatic lung germinoma of the thoracic spine. A 27-year-old man presented with right shoulder pain and right upper limb weakness. He had a history of repetitive radiation therapy - nine (whole-abdomen; 15Gy), 12 (whole brain; 30Gy, whole spine 42Gy) and 14 years ago (local; 32Gy) - for abdominal metastasis, temporal and fourth ventricle metastasis and spinal dissemination and metastatic pineal germinoma, respectively. Magnetic resonance imaging revealed a lung mass invading the thoracic spine that was diagnosed as a germinoma by tumor biopsy. He was treated by irradiation with 54Gy and two cycles of chemotherapy with cisplatin and etoposide. He did not have any sign of tumor eight years later.

Mixed or metachronous germ-cell tumor?

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. 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. 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. 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.

Germinoma with synchronous lesions in the pineal and suprasellar regions

Germinomas represent the most frequent tumour type in the pineal region and the synchronous involvement of the suprasellar region, frequently termed bifocal disease, is increasingly recognised. The incidence, pathogenesis, histomorphological, radiological, clinical features, and management strategies are discussed. A 6-year-old girl presented with clinical features of hypothalamic-pituitary axis dysfunction. MRI showed two distinct lesions in the pineal and suprasellar regions. Tumour markers for germ cell tumours from blood and cerebrospinal fluid were within the normal range. The suprasellar lesion was biopsied and the histology revealed a germinoma. She received a radical course of radiotherapy covering the entire craniospinal axis (24 Gy/15#) followed by focal boost to the sites of primary disease (16 Gy/10#). Three months after the completion of treatment, the patient achieved a complete clinical and radiological response, which was maintained during the 13-month follow-up period. The optimum management of primary intracranial pineal and suprasellar (bifocal) germinomas still remains controversial. The definition as either localised or disseminated disease has major implications on required treatment and its associated late morbidity. Prospective studies with large cooperative groups worldwide and consensus meetings may reduce uncertainties regarding available management options.

Diagnostic value of markers M2A, OCT3/4, AP‐2γ, PLAP and c‐KIT in the detection of extragonadal seminomas

To compare the suitability of new seminoma markers including transcription factors AP-2gamma, OCT3/4 and M2A for detection of metastatic and extragonadal seminomas with the two well-known markers c-KIT and PLAP. The immunohistochemical distribution of PLAP, c-KIT, M2A, AP-2gamma and OCT3/4 was examined in two pineal germinomas, 28 metastatic seminomas and 10 of their testicular primaries. Evaluation of specificity was achieved by additional tissue array studies on 75 malignancies other than germ cell tumours (GCT). Clinical data including serum PLAP were available in 18 patients. Compared with other markers, significantly better staining results were observed with antibodies to M2A and AP-2gamma in all seminomatous GCT. In contrast, the staining pattern with antibodies to c-KIT, PLAP and OCT3/4 was variable or absent. The lowest specificity was obtained with c-KIT, which was expressed in a variety of non-GCT. The only M2A+ mesothelioma expressed no other seminoma markers. No correlation between serum PLAP level and tissue PLAP expression was found. M2A and AP-2gamma are the most sensitive markers for seminoma metastases or primary extragonadal seminomas. Combination of these markers provides highly specific and clear results for detection of a seminomatous GCT.

Pure pineal germinomas: analysis of gender incidence

Pure pineal germinomas have been rarely reported in girls. Gender incidence and differences of pure pineal germinomas are not well known. The authors report a series of pure pineal germinoma and its gender characteristic is reviewed. Of a total of 50 germ cell tumors operated on between 1988 and 2004 we found 26 cases (median age at diagnosis, 12 years) of pineal germ cell tumors. Of these, 14 cases (male/female ratio: 13/1) were pure pineal germinomas, and 12 cases (male/female ratio: 12/0) were non-germinoma germ cell tumors. In pure pineal germinomas, the main clinical presentations were intracranial hypertension and cranial nerve dysfunction. Imaging studies disclosed a homogeneous type of tumor (n = 10) and associated hydrocephalus (n = 6). Cases were managed with biopsy and subsequent radiation therapy and chemotherapy. After a follow up of 10 years, pure germinoma cases have no neurological deficits and tumor recurrence. The literature on gender incidence of pure pineal germinomas is analyzed and possible causes are discussed. Although rare, pure pineal germinoma can be found in female subjects. On the basis of the literature review, the male/female ratio in cases of pure pineal germinoma is between 5:1 and 22:1 (mean 14:1). In our series, the male/female ratio was 13:1.

Akute Nierenkolik aufgrund einer ventrikuloperitonealen Shunt-Metastase eines intrakraniellen Germinoms

Extracranial metastases of pineal germinomas are rare. The case of a metastasis of a primary intracranial germ cell tumor via a temporary-ventriculo-peritoneal shunt as a cause of acute abdominal pain is reported. The germ cell tumor markers were useful in establishing the diagnosis. With an appropriate clinical history, intra-abdominal metastases via a temporary ventriculo-peritoneal shunt should be considered in the differential diagnosis of acute abdominal pain.

D2-40 antibody immunoreactivity in developing human brain, brain tumors and cultured neural cells

D2-40 antibody is raised against an oncofetal antigen, the M2A antigen. It has been used as a marker for lymphatic endothelium as well as mesothelioma and cerebellar hemangioblastoma. We demonstrate here that positive D2-40 immunoreactivity was found in the developing cerebrum, particularly in the germinal matrix layer, immature ependyma, choroid plexus and meninges. In the developing cerebellum, positive D2-40 immunoreactivity was found in the external granular layer particularly of the outer portion and the Purkinje cell layer as well as meninges. Some brain tumors such as anaplastic ependymoma, some medulloblastomas, glioblastoma, pineal germinoma, craniopharyngioma, choroid plexus papilloma, choroid plexus carcinoma, and meningioma showed positive immunoreactivity with D2-40. Therefore, D2-40 antibody is considered a useful marker for research on developing brain and diagnosis of brain tumors, differentiation between choroid plexus carcinoma and metastatic carcinoma. In addition, on cultured human neural cells, D2-40 immunoreactivity was found in nestin-positive neural stem/progenitor cells and neuronal lineage cells. As D2-40 antibody recognizes cell surface antigen M2A, it might be a candidate cell surface marker for isolation of human neural stem cells/neuronal lineage cells in the fluorescence-activated cell sorting technique.

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

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. We describe a case of pineal germinoma invading the hypothalamus, which was initially diagnosed as anorexia nervosa. Clinical features included weight loss, vomiting, pyrexia, hypernatraemia, and visual disturbance and the typical psychopathology of anorexia nervosa was absent. Organic disorder should always be considered before making a diagnosis of anorexia nervosa, particularly if the presentation is atypical.

Stereotactic Radiosurgery Followed by Whole Ventricular Irradiation for Primary Intracranial Germinoma of the Pineal Region

Intracranial germinomas can be cured by radiotherapy and/or chemotherapy. Three patients with pineal germinoma were treated with stereotactic radiosurgery using the gamma knife (10 - 12 Gy) to the tumors followed by whole ventricular irradiation (24 Gy). All patients had solitary pineal tumor measuring less than 3 cm, clinically compatible with germinoma, normal cerebrospinal fluid (CSF) and serum levels of alpha-fetoprotein and beta-human chorionic gonadotropin, no disseminated disease on spinal magnetic resonance (MR) imaging, and no abnormal CSF cytology. All patients showed complete response to the combined radiotherapy, and MR imaging has shown no recurrence of the tumor. Combined radiotherapy using gamma knife radiosurgery is effective for pineal germinoma, and reduced the cost of treatment with less need for hospitalization.

Two cases of pineal germinoma with granulomatous inflammation

We report two cases of pineal germinoma with remarkable chronic granulomatous inflammation. In the first case, the pineal mass was totally removed via an occipital transtentorial approach as symptoms were due to direct mass effect. In the second case, endoscopic third ventriculostomy and tissue biopsy was performed to alleviate worsening hydrocephalus. Pathological examination of specimens of both cases showed chronic granulomatous inflammation associated with a few germ cell tumor nests, which demonstrated positive staining for placental alkaline phosphatase. Both patients received post-operative craniospinal irradiation with no subsequent neurological deficits. Follow-up magnetic resonance imaging (MRI) of the second case showed an asymptomatic, shrunken residual tumor mass. MRI of the first case showed no residual or recurrent disease. Thus, a pineal mass with unusual features on MRI and chronic granulomatous inflammation on histopathology, should raise the suspicion of germinoma. In cases with symptomatic mass effect, open resection can be considered. In cases with lesser mass effect, conventional therapeutic modalities without resection can achieve a good outcome, as for other germinomas.

内視鏡下第三脳室開窓術後3年目に再手術を要した松果体部germinomaの1例

内視鏡下第三脳室開窓術後3年目に再手術を要した松果体部germinomaの1例

Extraneural metastasis of the pineal germinoma via ventriculoperitoneal shunt

Extraneural metastasis of pineal germinoma is an infrequent event. We report a case of a 19‐year‐old boy who had pineal germinoma and was successfully treated with irradiation. He was diagnosed with abdominal metastasis of pineal germinoma via ventricuolperitoneal shunt 6 years afterwards. The disease was controlled with surgery and systemic chemotherapy.

Refining the staging evaluation of pineal region germinoma using neuroendoscopy and the presence of preoperative diabetes insipidus.

Treatment strategies for CNS germinoma are currently evolving. Current approaches include reducing the volume and dose of radiation by adding pre-irradiation chemotherapy. Very accurate staging is necessary with such an approach to prevent failures. Eight consecutive patients with pineal germinoma at one institution underwent endoscopic surgery for tumor biopsy, direct visualization of the third ventricular region, and third ventriculostomy for those with hydrocephalus. All patients were treated with 4 cycles of chemotherapy. Conformal field radiation therapy followed, with the dose to the tumor bed dependent on the response to chemotherapy. Patients who had MRI, endoscopic, or cerebrospinal fluid evidence of multicentric or disseminated disease also received craniospinal radiation. Six patients had diabetes insipidus (DI) at presentation. All 6 had tumor studding the floor of the third ventricle on endoscopic visualization, while only 4 of those patients had MRI evidence of disease in that region. All patients have completed therapy and are alive, with no evidence of disease at median follow-up of 31.5 months from diagnosis. Direct endoscopic visualization of the third ventricular region may be more sensitive than MRI for evaluating the presence of suprasellar disease and appears to add important information. This parameter should be added to the staging evaluation when feasible. In this series, the presence of DI was 100% predictive of suprasellar disease, even when the MRI was negative for involvement of that region. Patients should be evaluated for DI as part of the initial staging, and if it is present, the patients should be treated for suprasellar disease regardless of MRI findings.