Papillary Tumor Of The Pineal Region Research Articles

A case of rare Papillary Tumor of the Pineal Region (PTPR) with leptomeningeal metastases treated with Bevacizumab and Chemotherapy (P6.135)

A case of rare Papillary Tumor of the Pineal Region (PTPR) with leptomeningeal metastases treated with Bevacizumab and Chemotherapy (P6.135)

Papillary Tumor of the Pineal Region: A Case Report

Pineal region tumors are uncommon lesions in the central nervous system. Papillary tumor of the pineal region is recently recognized as a separate disease. Its incidence, treatment, and outcome are not well-defined. We have reported the case of a 6 yearold- boy with papillary tumor of the pineal region. He presented with headaches, nausea and vomiting and, after a biopsy, was referred for radiotherapy. The patient received 54 Gy irradiation to the pineal region followed by a chemotherapy regimen of cisplatin, vincristine, and lomostine. His tumor decreased slightly. After 4 years, the patient has remained well and attends school. He is under routine follow-up. We suggest radical radiotherapy as the main treatment for papillary tumors of the pineal region.

Unedited microneurosurgery of a large recurrent papillary tumor of the pineal region.

Background:Papillary tumor of the pineal region (PTPR) is a new entity introduced in the 2007 World Health Organization (WHO) nomenclature to describe a rare grade II–III pineal lesion with epithelial-like papillary architecture and particular immunohistochemical features. PTPR is extremely rare in children. Herein, we present an unedited gross total microsurgical resection of a histologically confirmed WHO grade III PTPR. Our aim is to demonstrate the efficiency and safety of our microsurgical technique into deep brain territories under the principle “simple, clean, and preserving the normal anatomy.” For this, a posterior occipital interhemispheric approach and a proper praying sitting position were essential.Case Description:A patient with recurrent PTPR after a subtotal resection abroad underwent sitting praying position and left occipital craniotomy. The opened dura based on the superior sagittal sinus was strongly retracted providing hemostasis of the epidural space. The pericallosal cistern was reached by an interhemispheric approach with cerebrospinal fluid release. Under careful navigation, the tumor was recognized. Following high microscopic magnification, tissue samples were obtained for immediate histological studies and internal debulking of the tumor was performed with ring forceps and long bipolar forceps as well. After a careful dissection and devascularization of the lesion, the tumor was softly but constantly pulled out with long ring microforceps in the right hand, whereas a thumb-regulated suction tube in the left hand acted oppositely, detaching the lesion from surrounding structures. Bipolar coagulation forceps were used to shrink the tumor and to remove it by piecemeal reduction. Water irrigation provided a clean surgical field and helped us to separate deep borders of the lesion by water dissection technique. Finally, careful tumor detachment from the deep venous system and meticulous hemostasis of the surgical site ensured a safe surgery. The postoperative course was uneventful. The patient underwent radiohemotherapy as an adjuvant treatment and is alive and free of recurrence almost 4 years after surgery.Conclusion:This unedited video offers all detailed aspects that are, as the senior author JH considers, essential for a neurosurgeon when performing an efficient and safe surgery into the pineal region for this very rarely documented papillary tumor.Videolink:http://surgicalneurologyint.com/videogallery/pineal-region-tumor

Papillary tumor of the pineal region accompanied by Parinaud's syndrome: magnetic resonance imaging findings.

Papillary tumor of the pineal region accompanied by Parinaud's syndrome: magnetic resonance imaging findings.

One burr-hole craniotomy: Posterior interhemispheric approach in Helsinki Neurosurgery.

Background:In this video abstract, we present a one burr-hole craniotomy for the posterior interhemispheric approach developed in Helsinki Neurosurgery to access posteriorly the medial surface of cerebral hemispheres, falx cerebri, and deep midline cerebrovascular structures. Therefore, preoperative imaging is essential to achieve an optimal operative corridor for a safest and more effcient approach.Case Description:The patient with a papillary tumor of the pineal region is placed in sitting position. A midline single-layer skin incision is made in front of the superior sagittal sinus. Strong retraction maintains a clean space for craniotomy. Aiming to reduce the risk of sinus transgression or cortical veins damaging in the eloquent frontal–parietal area, a burr-hole is made over the superior sagittal sinus at the anterior border of the bone flap and the bone is detached from the dura posteriorly with blunt dissectors. Thus, proximal detachment of the dura under some visual control remains safe. A long blunt flexible dissector is used during this stage in case of elderly patients with an adherent dura. Craniotomy around the superior sagittal sinus is performed to expose 2–3 cm of the dura lateral to the sagittal sinus according to the exact location of the lesion. Moreover, craniotomy extends slightly over the contralateral side to allow some retraction of the sagittal sinus. Two cuts, from both sites of the burr-hole, are joined along the posterior midline. A few drill holes are made for tack-up sutures. Finally, a hemostatic agent covers the sagittal sinus and a sinus-based dura opening is performed under the microscope.Conclusion:The described one burr-hole craniotomy may represent a more efficient manner for performing a posterior interhemispheric approach.Videolink:http://surgicalneurologyint.com/videogallery/posterior-interhemispheric-approach

Papillary tumor of the pineal region

Pineal region tumors make up 0.4-1.0% of intracranial tumors in adults. These tumors may arise from pineal gland itself or structures around pineal gland which are all termed as pineal region tumors. Papillary tumor of the pineal region is a non-parenchymal tumor of the pineal region. It was first documented in 2003. We presented a 21 years old female patient with pineal tumor. Supracerebellar infratentorial approach was performed. The total excision of the lesion was achieved successfully. Histopathological examination revealed papillary tumor of the pineal region. The case is discussed in the light of our preoperative surgical experience, its pre-and post-operative radiological and histopathological evaluation. Supracerebellar infratentorial approach is encountered as the favoured approach generally. As recurrence rates are high, adjuvant treatment is advised after surgery. Further research on this pathology will enlighten the neurosurgeons for effective treatment.

Nuclear CRX and FOXJ1 Expression Differentiates Non-Germ Cell Pineal Region Tumors and Supports the Ependymal Differentiation of Papillary Tumor of the Pineal Region.

Papillary tumor of the pineal region (PTPR) is a neuroepithelial neoplasm first described in 2003. Despite the anatomic association of PTPR with the pineal gland, the features of these tumors resemble those of the ependymal circumventricular subcommissural organ (SCO) of the posterior third ventricle. Given the presumed distinct derivation of PTPR and pineal parenchymal tumors, we hypothesized that expression of lineage-specific transcription factors could distinguish these tumors and provide additional insight into the differentiation of PTPR. A broad series of pineal region samples was reviewed, including 7 benign pineal glands, 4 pineal cysts, 13 pineocytomas, 28 pineal parenchymal tumors of intermediate differentiation, 11 pineoblastomas, and 18 PTPR. All samples were evaluated by immunohistochemistry for expression of CRX, a master transcriptional regulator of photoreceptor differentiation expressed in pineal gland and retina and/or FOXJ1, a master transcriptional regulator of ciliogenesis expressed in normal ependymal cells and ependymal neoplasms. Diffuse nuclear CRX expression is present in 100% of pineal samples. FOXJ1 is negative in all pineal samples. CRX staining is present in 53% of PTPR, though expression is nearly always limited to rare cells. Diffuse nuclear FOXJ1 expression is present in 100% of PTPR. Fetal human SCO diffusely expressed FOXJ1 but was negative for CRX. Immunohistochemistry for FOXJ1 and CRX differentiates non-germ cell pineal region tumors with high sensitivity and specificity, including pineal parenchymal tumors and PTPR. Our findings support the hypothesis that PTPR have ependymal differentiation and are phenotypically more similar to SCO than pineal gland.

Histology-Stratified Tumor Control and Patient Survival After Stereotactic Radiosurgery for Pineal Region Tumors: A Report From the International Gamma Knife Research Foundation.

Pineal region tumors represent a rare and histologically diverse group of lesions. Few studies are available to guide management and the outcomes after stereotactic radiosurgery (SRS). Patients who underwent SRS for a pineal region tumor and for whom at least 6 months of imaging follow-up was available were retrospectively assessed in 5 centers. Data were collected from the medical record and histology level analyses were performed, including actuarial tumor control and survival analyses. A total of 70 patients were treated between 1989 and 2014 with a median follow-up of 47 months. Diagnoses were pineocytoma (37%), pineoblastoma (19%), pineal parenchymal tumor of intermediate differentiation (10%), papillary tumor of the pineal region (9%), germinoma (7%), teratoma (3%), embryonal carcinoma (1%), and unknown (14%). Median prescription dose was 15 Gy at the 50% isodose line. Actuarial local control and survival rates were 81% and 76% at 20 years for pineocytoma, 50% and 56% at 5 years for pineal parenchymal tumor of intermediate differentiation, 27% and 48% at 5 years for pineoblastoma, 33% and 100% at 5 years for papillary tumor of the pineal region, 80% and 80% at 20 years for germinoma, and 61% and 67% at 5 years for tumors of unknown histology. New focal neurological deficit, Parinaud syndrome, and hydrocephalus occurred in 9%, 7%, and 3% of cases, respectively. SRS is a safe modality for the management of pineal region tumors. Its specific role is highly dependent on tumor histology. As such, all efforts should be made to obtain a reliable histologic diagnosis.

Microsurgical Resection After Failed Gamma Knife Radiosurgery of Papillary Tumor of the Pineal Gland.

Abstract Primary papillary tumors of the pineal region (PTPR) are rare entities with distinct histopathological characteristics. Most common surgical approaches include the supra-cerebellar infratentorial corridor or the occipital interhemispheric approach. Gamma knife radiosurgery (GKRS) is an acceptable treatment modality for parenchymal tumors of the pineal gland, and often used as a primary treatment modality for asymptomatic and indolent lesions, and as an adjunct to surgical resection. In this presentation, we describe the surgical nuances of posterior interhemispheric approach in an elderly male with a previously failed empirical GKRS. Intraoperatively, the tumor was mostly avascular, presumed to be due to prior GKRS; however, a good tumor-brain interface allowed a gross total resection of the mass. Histopathological examination of the mass was consistent with PTPR. Post-operative course was uneventful and long-term follow up showed no signs of tumor recurrence. The video discusses radiological findings, clinic-pathological correlates, and emphasizes on key microsurgical techniques including the significance of patient positioning and incision type for meticulous resection of pineal tumors.

Supraorbital subfrontal trans-laminar endoscope-assisted approach for tumors of the posterior third ventricle

Different surgical approaches have been developed for dealing with third ventricle lesions, all aimed at obtaining a safe removal minimizing brain manipulation. The supraorbital subfrontal trans-lamina terminalis route, commonly employed only for the anterior third ventricle, could represent, in selected cases with endoscopic assistance, an alternative approach to posterior third ventricular lesions. Seven patients underwent a supraorbital subfrontal trans-laminar endoscope-assisted approach to posterior third ventricle tumors (two craniopharyngiomas, one papillary tumor of the pineal region, one pineocytoma, two neurocytomas, one glioblastoma). Moreover, a conventional third ventriculostomy was performed via the same trans-laminar approach in four cases. Complete tumor removal was accomplished in four cases, subtotal removal in two cases, and a simple biopsy in one case. Adjuvant radiotherapy and/or chemotherapy was administered, if required, on the basis of the histologic diagnosis. No major complications occurred after surgery except for an intratumoral hemorrhage in a patient undergoing a biopsy for a glioblastoma, which simply delayed the beginning of adjuvant radiochemotherapy. No ventriculoperitoneal shunt placement was needed in these patients at the most recent clinical and radiologic session (average 39.57months, range 13-85months). Two illustrative cases are presented. The supraorbital subfrontal trans-laminar endoscope-assisted approach may provide, in selected cases, an efficient and safe route for dealing with posterior third ventricular tumors.

Papillary tumor of the pineal region detected at the onset of facial paralysis: a case report

Papillary tumor of the pineal region detected at the onset of facial paralysis: a case report

Papillary tumor of pineal region: Case reports

Background: The papillary tumor of the pineal region (PTPR) was a new distinct entity described in 2003 WHO classification and later included in the subsequent 2007 and 2016 WHO classification of Central Nervous System tumours. They are commonly associated with obstructive hydrocephalus and are difficult to distinguish from other clinical entities, more particularly pineocytoma. Due to the limited number of reported cases, treatment strategies are not well established. Case report: We report two cases of PTPR who presented with headache impaired gaze and diplopia. In first case MRI showed a cystic mass in the third ventricle and pineal region whereas the tumor had displaced the tectal plate in second case. The initial squash suggested a neoplastic lesion of probable glial origin favoring ependymoma. On microscopy, the tumor displayed papillary architecture with perivascular pseudo rosettes displaying multi layering of cuboidal to columnar cell with vesicular nucleus. Based on histological features the differential diagnostic conditions considered were choroid plexus tumor, papillary ependymoma, choroid plexus carcinoma, PTPR, and metastatic carcinoma. PTPR was confirmed on immunohistochemistry workup. Both the patients had recurrence, after one year and six months respectively. Conclusion: PTPR is an important differential diagnosis to be considered in cases where the tumoris arising in the vicinity of pineal region showing papillary architecture. Keywords: pineal region papillary tumor; PTPR; pineal region; subcommissural organ

Proton Therapy in Neurosurgery: A Historical Review and Future Perspective Based on Currently Available New Generation Systems

Purpose: To evaluate of Proton therapy (PT) for neurosurgery patients and is also to explain the need for this system in Iran.Methods: A literature review was conducted (1984–2016). The strategy included a combination of keywords including proton therapy, neck, neurosurgery, brain, head, tumor, spine, arteriovenous malformation (AVMs), cervical and spine in database of PubMed. New generation PT systems were assessed. Findings are summarized, with a focus on the application of PT in neurosurgery. Finally, the future of PT is discussed.Results: A total of 1329 citations were screened. In all, 60 articles were included. The synthesis of the data showed two applications of PT in neurosurgery, including: (a) the use in head disease such as AVMs, acromegaly, medulloblastoma, primitive neuroectodermal tumors, papillary tumors of the pineal region, low-grade astrocytoma, head and neck adenoid cystic carcinoma, meningioma, mesenchymal tumors, pediatric cranial tumors, squamous cell carcinoma of the head, craniospinal, and skull base chordomas and chondrosarcomas; (b) the apply in the spinal disease as chordoma or chondrosarcoma of the cervical, sacrum, thoracic and lumbar spine, ependymomas, tumor locations included cervical, thoracic, lumbar, S1-S2, and S3 or below. In addition, the combination of a gantry and cyclotron with new proton therapy systems, results in a lower cost.Conclusion: PT may be associated with better outcomes for selected patients with malignant diseases of the head and spine. The findings suggest that there exists a need for at least one center to treat the patient demand in Iran.

Papillary Tumor of the Pineal Region: Clinical Presentations, Prognostic Factors, Treatments, and Outcomes

: The pineal region is a rare site for primary tumors of the central nervous system. Papillary tumor of the pineal region (PTPR) is a relatively new phenomenon in this region. Considering the rarity of this tumor, the clinical course, treatment, and outcomes are not well studied. In the present study, we searched PubMed for relevant articles. A total of 72 articles were retrieved from PubMed. The exclusion criteria were autopsy and archive series, animal studies, and reports without clinical data. We had no access to the full - text of some articles; accordingly, 19 articles were excluded from the analysis. Data from 53 reports, including 50 case reports and three case series (a total of 73 patients), were collected and analyzed. The patients’ mean age was 33.5 (± 15.4) years. Forty - two cases were male and 31 were female. The most common symptom was headache in patients (80%). Other common symptoms included visual complaints (40%), nausea (31%), memory loss (7%), Parinaud’s syndrome (4%), and impaired gait (2%). Among 73 patients, 32 had undergone complete tumor resection. Twenty - nine patients had received conventional external beam radiotherapy, stereotactic radiosurgery (n, 10), brachytherapy (n, 5), and proton therapy (n, 1). Eight patients received no adjuvant therapy, and data presented in other reports were incomplete. Among the patients (n, 73), 11 received chemotherapy. Fifty patients had no evidence of recurrence at the time of report, while three patients had died. Local recurrence was the most common pattern of relapse (28%); nonetheless, parenchymal and meningeal involvement was also observed. The median disease - free survival (DFS) was 24 months, while five- and ten - year DFS rates were 50.1% and 25.0%, respectively. The median overall survival was 24 months. Generally, PTPR has an indolent course with a tendency towards local recurrence; nonetheless, an aggressive clinical course, associated with parenchymal and meningeal metastases, is well established.

NHERF1/EBP50 and NF2 as diagnostic markers for choroid plexus tumors.

The adaptor protein NHERF1 (Na/H exchanger-3 regulatory factor-1) and its associated ezrin-radixin-moesin-merlin/neurofibromin-2 (ERM-NF2) family proteins are required for epithelial morphogenesis and have been implicated in cancer progression. NHERF1 is expressed in ependymal cells and constitutes a highly sensitive diagnostic marker for ependymoma, where it labels membrane polarity structures. Since NHERF1 and ERM-NF2 proteins show polarized expression in choroid plexus (CP) cells, we tested their diagnostic utility in CP neoplasms. NHERF1 immunohistochemistry in 43 adult and pediatric tumors with papillary morphology revealed strong apical plasma membrane staining in CP papilloma (WHO grade I) and cytoplasmic expression in CP carcinoma (WHO grade III). Ezrin and moesin showed similar but less distinctive staining. NHERF1 also labeled papillary tumors of the pineal region in a microlumen and focal apical membrane pattern, suggestive of a transitional morphology between CP papilloma and ependymoma. CP tumors of all grades could be differentiated from metastatic carcinomas with papillary architecture by NF2, which showed polarized membranous staining in CP tumors. NHERF1 and NF2 immunohistochemistry showed enhanced sensitivity and specificity for CP tumors compared to commonly used markers, including cytokeratins and Kir7.1, emerging as reliable diagnostic tools for the differential diagnosis of papillary tumors of the central nervous system.Electronic supplementary materialThe online version of this article (doi:10.1186/s40478-016-0329-0) contains supplementary material, which is available to authorized users.

ATPS-88TEMOZOLOMIDE AND EVEROLIMUS IN THE TREATMENT OF PAPILLARY TUMOR OF THE PINEAL REGION

Papillary tumor of the pineal region (PTPR) is a rare neuroepithelial tumor thought to arise from the ependymal cells of the subcommissural organ which was first described in 2003 and subsequently classified as a Grade II-III tumor in the WHO registry in 2007. They tend to be well-circumscribed, occasionally cystic tumors that, histologically, consist of sheets of epithelioid cells and perivascular pseudorosettes with papillary structures consisting of cuboidal cells. These tumors have a high rate of local recurrence but infrequent CSF dissemination. Because fewer than 100 cases have been reported, a consensus on treatment has not been reached, though maximal surgical resection correlates with a better prognosis and radiotherapy may confer a benefit, as well. The role of chemotherapy remains unclear and regimens including procarbazine, lomustine, and vincristine as well at temozolomide have been reported. Recently, chromosome 10 deletions and mutations in the PTEN (phosphatase and tensin homolog) gene located on chromosome 10 are common in PTPR. Because PTEN is involved in the PI3K/Akt/mTOR signaling pathway, mTOR inhibitors, such as everolimus may be effective against this tumor type. We present a patient with PTPR who underwent complete resection followed by local radiotherapy. He later developed leptomeningeal disease and underwent whole brain radiation therapy. He was also treated with metronomic temozolomide and subsequently by everolimus after he developed a temozolomide-resistant durally-based metastatic lesion.

GENO-20NOVEL CANDIDATE ONCOGENIC DRIVERS IN PINEOBLASTOMA

INTRODUCTION: Pineoblastoma (PB) is one of the rarest and most aggressive brain tumors of childhood. PB is considered a primitive neuroectodermal (PNET) based on histology, and commonly treated using treatment protocols developed for medulloblastoma. A subset of PBs may occur in the setting of germline mutations involving DICER1, but no next-generation sequencing studies have been published on PB to date, and the genetic drivers of sporadic PB remain unknown. METHODS: 21 tumor samples with a histological diagnosis of PB (including recurrent/metastatic samples) from 15 patients were included in this study. Matching germline DNA was available from 2 patients. We performed genome-wide methylation array profiling (Illumina Infinium 450k) on all samples, as well as whole-genome (for samples with matching germline DNA) or whole-exome sequence analysis. Fluorescence in situ hybridization (FISH) and digital droplet PCR (ddPCR) was performed to confirm select focal somatic gains. RESULTS: 14/18 samples from 9/13 patients analyzed by 450k profiling had a methylation signature similar to previously profiled PBs from a reference cohort. Samples from 4 patients were found to be more consistent with a diagnosis of embryonal tumor with multilayered rosettes (ETMR) - like tumor (non 19q amplified), papillary tumor of the pineal region, or pineal parenchymal tumor of intermediate differentiation, respectively. No mutations in DICER1 or RB1 were found. Homozygous deletions in DROSHA were found in tumors from 3 PB patients. We identified novel and recurrent somatic gains involving chromosomal region 1q21 that were confirmed by FISH and ddPCR in 4/5 PB patients. CONCLUSION: Our studies revealed multiple candidate drivers of oncogenesis in PB. We identified novel homozygous deletions in DROSHA, a nuclease involved in microRNA processing. We also identified novel, highly recurrent somatic focal gains involving chromosomal region 1q21, which has been linked to brain growth, autism and schizophrenia, but not previously associated with cancer.

Papillary tumor of the pineal region: A case report and review of the literature.

Papillary tumor of the pineal region (PTPR) was first described as a distinct tumor entity in 2003 and was introduced into the World Health Organization classification of central nervous system tumors in 2007. This tumor is rare and, to the best of our knowledge, only 7 cases have been reported in children <16 years of age, while the youngest documented patient was a 15-month-old boy. The present study reported a case of PTPR in a 10-year-old girl who underwent magnetic resonance imaging and surgical resection of tumors. Histological and immunohistochemical staining results were presented. Patients with PTPR require long-term follow-up, and the patient of the present study has continued to do well, with no recurrence of the tumor at the 15-month follow-up examination. In addition, a review of the literature on this unusual neoplasm was performed, along with discussion of their differential diagnosis.

Abstract LB-172: Novel candidate oncogenic drivers in pineoblastoma

Abstract INTRODUCTION: Pineoblastoma (PB) is one of the rarest and most aggressive brain tumors of childhood. PB is considered a “primitive neuroectodermal tumor” (PNET) based on histology, and commonly treated using treatment protocols developed for medulloblastoma; however the survival remains poor. A subset of PBs may occur in the setting of germline mutations involving DICER1 or RB1, but no next-generation sequencing studies have been published on PB to date, and the genetic drivers of sporadic PB remain unknown. METHODS: 21 tumor samples with a histological diagnosis of PB (including recurrent/metastatic samples) from 15 patients were included in this study. Matching germline DNA was available from 2 patients. We performed genome-wide methylation array profiling (Illumina Infinium 450k) on all samples, as well as whole-genome (for samples with matching germline DNA) or whole-exome sequence analysis. Fluorescence in situ hybridization (FISH) and digital droplet PCR (ddPCR) was performed to confirm select focal somatic gains. RESULTS: 14/18 samples from 9/13 patients analyzed by 450k profiling had a methylation signature similar to previously profiled PBs from a reference cohort. Samples from 4 patients were found to be more consistent with a diagnosis of embryonal tumor with multilayered rosettes (ETMR) - like tumor (non 19q amplified), papillary tumor of the pineal region, or pineal parenchymal tumor of intermediate differentiation, respectively. No mutations in DICER1 or RB1 were found. Homozygous deletions in DROSHA were found in tumors from 3 PB patients. In addition, we identified novel recurrent somatic gains involving chromosomal region 1q21 that were confirmed by FISH and ddPCR in 4/5 PB patients. CONCLUSION: Our studies revealed multiple candidate drivers of oncogenesis in PB. We identified novel homozygous deletions in DROSHA, a nuclease involved in microRNA processing. We also identified novel, highly recurrent somatic focal gains involving chromosomal region 1q21, which has been linked to brain growth, autism and schizophrenia, but not previously associated with cancer. Citation Format: Matija Snuderl, Kasthuri Kannan, Olga Aminova, Igor Dolgalev, Adriana Heguy, Arline Faustin, David Zagzag, Sharon L. Gardner, Jeffrey C. Allen, Jeffrey H. Wisoff, David Capper, Volker Hovestadt, Sama Ahsan, Charles Eberhart, Stefan M. Pfister, David T. w. Jones, Matthias A. Karajannis. Novel candidate oncogenic drivers in pineoblastoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-172. doi:10.1158/1538-7445.AM2015-LB-172

Papillary Tumor of the Pineal Region: A Distinct Molecular Entity.

Papillary tumor of the pineal region (PTPR) is a neuroepithelial brain tumor, which might pose diagnostic difficulties and recurs often. Little is known about underlying molecular alterations. We therefore investigated chromosomal copy number alterations, DNA methylation patterns and mRNA expression profiles in a series of 24 PTPRs. Losses of chromosome 10 were identified in all 13 PTPRs examined. Losses of chromosomes 3 and 22q (54%) as well as gains of chromosomes 8p (62%) and 12 (46%) were also common. DNA methylation profiling using Illumina 450k arrays reliably distinguished PTPR from ependymomas and pineal parenchymal tumors of intermediate differentiation. PTPR could be divided into two subgroups based on methylation pattern, PTPR group 2 showing higher global methylation and a tendency toward shorter progression-free survival (P = 0.06). Genes overexpressed in PTPR as compared with ependymal tumors included SPDEF, known to be expressed in the rodent subcommissural organ. Notable SPDEF protein expression was encountered in 15/19 PTPRs as compared with only 2/36 ependymal tumors, 2/19 choroid plexus tumors and 0/23 samples of other central nervous system (CNS) tumor entities. In conclusion, PTPRs show typical chromosomal alterations as well as distinct DNA methylation and expression profiles, which might serve as useful diagnostic tools.