Search

Papillary tumors of the pineal region (PTPR) can be observed among adults with poor prognosis and high recurrence rates. Standards of therapy involve total surgical excision along with radiation therapy, with no promising prospects for primary adjuvant chemotherapy, as long-term treatment options have not been explored. Chromosome 10 loss is characteristic of PTPR, and PTEN gene alterations are frequently encountered in a wide range of human cancers and may be treated with mTORC1 inhibitors such as everolimus. In parallel, there are no reports of treating PTPR with everolimus alone as a monopharmacotherapy. We report the case of a patient diagnosed with PTPR (grade III) characterized by a PTEN R130Q alteration with chromosome 10 loss that was treated with everolimus pharmacotherapy alone, resulting in an asymptomatic course and tumor regression, a rare yet notable phenomenon not described in the literature so far with potential to alter the management approach to patients with PTPR.

Background: Neoplasms from the ventricular system share a common location but have highly variable histogenesis. Many are slowly growing tumors that behave in a benign fashion. They can be classified as primary and secondary tumors. The most common primary tumors are ependymomas, subependymomas, subependymal giant cell astrocytomas, central neurocytomas, choroid plexus tumors, meningiomas, germinomas, pineal parenchymal tumors, papillary tumors of the pineal region, chordoid gliomas, rosette-forming glioneuronal tumors of the fourth ventricle, and craniopharyngiomas. Pilocytic astrocytomas, medulloblastomas, and atypical teratoid/rhabdoid tumors often show secondary involvement of the ventricular system. Summary: Advances in neurosurgery have facilitated access to the ventricular system increasing the number of cases in which such tumors can be biopsied. In this context, cytology has been proven to be an extremely useful diagnostic tool during intraoperative pathologic consultations. Many ventricular tumors are infrequent, and the cytologic information available is limited. In this review, we describe the cytologic features of the uncommon ventricular tumors and report on unusual findings of the more common ones. For the cytologic evaluation of brain tumors, many neuropathologists prefer formalin fixation and hematoxylin and eosin staining. In this review, we highlight the cytologic findings as seen with Diff-Quik, a very popular staining method among cytopathologists. In fact, when pathologists are unfamiliar with cytology, it is common to request the assistance of cytopathologists during the evaluation of intraoperative procedures. Key Message: Ventricular tumors of the central nervous system comprise a group of heterogeneous tumors with very different cytologic features. The cytomorphology of these tumors, including rare entities, is often very characteristic, allowing a precise recognition during intraoperative pathologic consultations. Diff-Quik is a valuable staining method that can be used alone or as a complement to hematoxylin and eosin staining. Diff-Quik allows for clear visualization of the overall architecture, cytoplasmic details, and extracellular material.

Background Clinical outcomes and biological behavior of papillary tumors of the pineal region (PTPR) are still under investigation. The best therapeutic strategy has not been defined. Objective To perform a comprehensive patient-level analysis of all PTPR cases and identify their clinical features, treatment options, and prognostic factors. Methods A search of the medical databases for case series and reports on PTPRs from January 2003 to June 2017 was performed. Data addressing PTPR's clinical presentation, imaging, treatment, and histological features were. Variables associated with the primary outcome of 36-mo survival were identified through Cox regression models. Results The initial search yielded 1164 studies, of which 71 were included (60 case reports and 11 case series), containing 177 patients (mean age 33.0 ± 15.3 yr and 53.2% male). Intracranial hypertension and hydrocephalus prevailed as the clinical picture. Surgery was performed on 82.0% and gross total resection (GTR) was achieved on 71.4%. A total of 56.8% recurred after a median 29 mo (quartiles 10.5-45.5). The 36-mo survival rate was 83.5% (95% confidence interval [CI] 76.2-89.2%). Good functional outcomes (Glasgow Outcome Scale 4/5) were observed in 60.0%. The variables of interest were inconsistently reported and the multivariable analysis final sample was 133 patients. After adjustment for age, tumor size (each additional centimeter, hazard ratio [HR] 1.99, 95% CI 1.12-3.53, P = .019) and surgical treatment (HR 0.16, 95% CI 0.05-0.45, P = .001) were associated with 36-mo survival. Conclusion Tumor size and surgery are associated with improvement in 36-mo survival. We did not observe any significant benefits from GTR or adjuvant treatments.

Background Papillary tumors of the pineal region (PTPRs) are malignant World Health Organization grade II/III tumors; however, they may perfectly mimic benign tumors (e.g., pineocytomas [World Health Organization grade I]). Case Description We present a case of a 28-year-old man with a 35-mm tumor of the pineal region. Considering the typical radiological and pathologic presentation, the tumor was first diagnosed as pineocytoma. However, despite first total resection, the tumor recurred after 7 years. The recurrent neoplasm was composed mainly of papillary structures with low-grade atypical cells positive for CKAE1/AE3 and CK18. This categorization led to the final diagnosis of PTPR. The patient underwent adjuvant radiotherapy, which vastly improved his neurologic condition and resulted in significant tumor regression. Conclusions This case exemplifies that PTPRs can perfectly mimic pineocytomas and simple staining for cytokeratins may warrant correct diagnosis and better treatment.

Pineal parenchymal tumors are categorized into WHO Grade I pineocytoma, WHO Grade II or III pineal parenchyma tumor of intermediate differentiation (PPTID), and WHO Grade IV pineoblastoma. Aggressive surgery to achieve gross total resection (GTR) may be challenging in the pineal region due to the risk of neurologic injury. There is currently no consensus from phase III prospective data to guide adjuvant therapy in PPTID, but focal radiotherapy should be considered in this setting to improve local control. Papillary tumors of the pineal region (PTPR) is another rare neuroectodermal tumor with limited published literature and no established guidelines with respect to adjuvant therapy after surgical resection; however, focal radiotherapy should also be considered to improve local control. In this chapter, we present general principles of treatment planning for these two disease entities of the pineal region.

Tumors of pineal cell origin are rare intracranial lesions. They are the second most common entity encountered in the pineal gland, after tumors of germ cell origin. They are classified according to their differentiation in pineocytomas (World Health Organization [WHO] grade I tumor), pineal parenchymal tumors of intermediate differentiation, papillary tumors of the pineal region, and pineoblastomas (WHO grade 4 tumor). Differentiation between pineal and germ cell tumors is essential, and for this purpose serum and cerebrospinal fluid (CSF) markers are used, alongside imaging techniques. Often, the only way to differentiate these two types of tumors is through a biopsy, which may be carried out with or without a simultaneous third ventriculocisternostomy. Retrospective series show an association between the extent of resection and improved outcomes, and benign lesions may be cured by performing a gross total resection. However, the approaches to this region are highly complex, because of the plethora of essential neuroanatomical structures in the area. The approaches need to be tailored to the specific anatomy of the patient and should aim at minimizing surgical morbidity. Because of their complexity, these lesions should mainly be performed in centers with sufficient experience in the treatment of pineal region lesions.

Papillary tumor of the pineal region (PTPR) is a recently defined tumor entity. Its clinical course is characterized by frequent local recurrence, and patients may experience the burden of symptoms due to the anatomical location of the growing mass. Guidelines for treatment protocols, and the role of radiotherapy are still being investigated.We report the case of a 27-year old woman who was referred to our department after she was diagnosed with PTPR and had undergone multiple surgical interventions. We delivered adjuvant conformal radiotherapy on the gross residual tumor to a total dose of 59.4 Gy (33 × 1.8 Gy).After a follow-up period of 41 months, we obtained a complete response to the treatment, according to the Response evaluation criteria in solid tumors criteria (RECIST). Radiation treatment was well tolerated, and the patient did not develop acute and late side effects. The neurological symptoms, which were documented at the diagnosis and after the surgical procedure, have not been recorded at last follow-up.Formal consensus for managing patients with a diagnosis of PTPR are nonexistent. Despite surgery, this tumor has a tendency to recur. Radiotherapy could have a role in the adjuvant setting and needs to be investigated in a multicenter setting with a long follow-up.Key words: radiotherapy - neurosurgery - magnetic resonance - pineal region - brain tumor.

Background: Papillary tumors of the pineal region are rare neuroepithelial lesions that were described for the 1st time in the WHO 2007 classification. Management of such lesions remains controversial. Case Description: We describe the case of a 26-year-old female who presented with intracranial hypertension syndrome secondary to a 1.9 cm3 lesion of the pineal region causing hydrocephalus. The patient benefited from an endoscopic third ventriculocisternostomy and a biopsy of her lesion in favor of a papillary tumor of the pineal region. After discussion of the surgical risks, the patient refused the surgical option and a stereotactic radiosurgery (SRS) was performed. She improved both clinically (allowing her to regain autonomy) and radiologically (reduction of 60% of tumor volume) at 1 year follow-up. Conclusion: Because of the rarity of the lesion, literature is yet not able to find consensus concerning management of such lesion, but SRS has proven efficiency for these Grades II or III lesions with high recurrence rates. Therefore, it should be considered as a primary therapeutic option allowing good outcome with low risks for the patient.

Background: Pineal gland tumors range from the well-differentiated “pineocytoma” [World Health Organization (WHO) grade I], which have a very good prognosis, to the aggressive and poorly differentiated “pineoblastoma” (WHO grade IV) with “pineal parenchymal tumor of intermediate differentiation” (PPTID; WHO grades II and III) occupying intermediary differentiation and prognosis. Papillary tumor of the pineal region (PTPR; WHO grades II and III) is a distinct entity with propensity for recurrence and spinal dissemination. However, the diagnostic criteria to differentiate these entities, especially between WHO grades II and III of both PPTID and PTPR, remain nebulous. Objective: To evaluate the relative frequency of the individual entities and histomorphological (including the proliferation indices) features across the spectrum of pineal parenchymal tumors (PPTs) [including PTPRs] along their course. Design: All cases of PPTs were retrieved, reviewed, and graded based on the histological criteria defined in the literature. Results: PPTID, more commonly seen in young adults, was the most common subtype of PPT. This was followed by pineoblastoma which was more commonly seen in children. Clinical progression was seen in both grades II and III of PPTID; however, it was more commonly seen in cases with a MIB1 labeling index of >10%. PTPRs (both grades II and III) showed an aggressive histological transformation and also intraparenchymal metastasis. Conclusion: PPTIDs are the most common adult primary PPTs and have the potential to progress and disseminate in both grades II and III. Both grades of PTPRs have a metastatic potential. These findings suggest the need for postoperative adjuvant therapy in both grades of PPTID and PTPR.

Pineal region tumors represent a heterogeneous group of different histologic entities, for which the management can be a significant challenge, due to their critical location and frequent aggressive behavior. Traditional management includes surgical resection, fractionated radiation therapy, and chemotherapy. Stereotactic radiosurgery (SRS) is being increasingly used in the treatment of these tumors. It is used as primary therapy for pineocytomas and papillary tumors of the pineal region, as an adjuvant radiation boost in combination with radiation or chemotherapy for pineoblastomas and germ cell tumors, or in the context of tumor recurrence. The reported morbidity is low, consisting in transient oculomotor disturbance in most cases. As a non-invasive alternative to microsurgical resection, SRS should always be considered when discussing these challenging cases.

Papillary tumors of the pineal region (PTPR) are a rare tumor entity first described in 2003, later codified in the 2007 WHO tumor classification system. PTPRs most commonly occur in the third and fourth decades, with exceedingly rare presentations in pediatric populations. Herein, we present an additional case of a 10-year-old female found to have PTPR in conjunction with Trisomy 21 managed successfully with cerebrospinal fluid diversion and gross total resection (GTR). Three years after resection she has returned to baseline without recurrence. We also performed a comprehensive review of the current literature discussing the diagnosis, treatment, and pathophysiologic correlations in children. Diagnosis and management of PTPRs is a topic that is increasingly garnering attention in the literature given the recent characterization of this tumor entity. However, relatively little is known about the presentation of PTPRs in pediatric populations. In adults, PTPRs have been linked with several chromosomal and genetic abnormalities; however this correlation is limited in pediatric literature. Although GTR is the mainstay for treatment, the application of adult treatment protocols may not be advisable due to age and the developmental changes of the CNS in children.

Introduction: Papillary tumors of the pineal region (PTPR) are rare brain tumors characterized by frequent local recurrences. Standardized treatment strategies are not yet defined. Case report: We present the case of a 3-year-old girl diagnosed with PTPR. Due to her young age, adjuvant radiotherapy was omitted after gross total tumor resection. Thirty-six months later, local tumor recurrence occurred. Considering the possible risks of secondary surgery, the recurrent tumor was irradiated with proton radiotherapy. Three months later, the tumor showed near-complete remission. Discussion: Based on this experience and other pediatric case reports from the literature, local radiotherapy might be suggested also after complete tumor resection

This chapter describes the four recognized histologic types of pineal parenchymal tumors (PPTs). Clinical presentation and common signs and symptoms caused by tumors of the pineal region are described. Clinical workup, including relevant imaging studies and laboratory testing, is outlined. The general treatment approach is considered. Roles of surgery, chemotherapy, and radiation in the definitive and adjuvant setting are discussed for each histologic type. Radiation therapy techniques are described in detail. Included are delineation of treatment volumes, commonly used treatment doses, and treatment delivery systems, including stereotactic radiosurgery and intensity-modulated radiotherapy (IMRT). Possible acute and chronic radiation toxicities and suggestions for posttreatment surveillance conclude the chapter.

Background Tumors of the pineal region are rare in adulthood, accounting for approximately 1% of intracranial neoplasms in this age range. Because of their rarity, it has proven to be difficult to establish the optimal therapy. Furthermore, microsurgical total resection in this eloquent location is associated with not low rates of morbidity. Case Description We describe 2 patients diagnosed with papillary tumors of the pineal region by stereotactic biopsy and referred for Gamma Knife radiosurgery after shunting for hydrocephalus. We report a long-term follow-up of 15 and 20 years, respectively, showing a good response to the treatment. Conclusions After a diagnosis of papillary tumors of the pineal region, radiosurgery is an alternative treatment, with high local control and low morbidity.

Pineal tumors are rare and include a large variety of entities. Germ cell tumors are relatively frequent and often secreting lesions. Pineal parenchymal tumors include pineocytomas, pineal parenchymal tumor of intermediate differentiation, pineoblastomas and papillary tumors of the pineal region. Other lesions including astrocytomas and meningiomas as well as congenital malformations i.e. benign cysts, lipomas, epidermoid and dermoid cysts, which can also arise from the pineal region. Imagery is often non-specific but detailed analysis of the images compared with the hormone profile can narrow the spectrum of possible diagnosis.

Papillary tumors of the pineal region (PTPR) are recognized as a distinct entity in the World Health Organization classification of CNS tumors. Papillary tumors of the pineal region frequently show loss of chromosome 10, but no studies have investigated possible target genes on this chromosome. Chromosome 10 harbors the PTEN (phosphatase and tensin homolog) gene, the inactivation of which, by mutation or epigenetic silencing, has been observed in different brain tumors, including high-grade gliomas. In this study, we investigated copy number changes by molecular inversion probe (MIP) analysis and the mutational status of PTEN in 13 PTPR by direct sequencing. MIP analysis of 5 PTPR showed chromosome 10 loss in all cases. In addition, there were losses of chromosomes 3, 14, 22, and X, and gains of whole chromosomes 8, 9, and 12 in more than 1 case. One case had a homozygous PTEN deletion; and 2 point mutations in exon 7 of PTEN (G251D and Q261stop) were found. Immunohistochemistry revealed decrease or loss of the PTEN protein and increased expression of p-Akt and p-S6. These results indicated that PTEN mutations and activation of the PI3K/Akt/mTOR signaling pathway may play a role in the biology of PTPR. This evidence may lead to the possible use of PI3K/Akt/mTOR inhibitors in therapy for patients with PTPR.

Primary papillary tumors of the central nervous system and particularly the pineal region are rare. Papillary tumor of the pineal region (PTPR) is a recently described neoplasm that has been formally recognized in the 2007 World Health Organization Classification of Tumors of the Nervous System. Because of their rarity, further pheno- and genotypical observations as well as therapeutic experience are necessary to differentiate PTPR from other primary or secondary papillary tumors of this region. We herein present three cases of PTPR characterized by local recurrence in two of them. Primary and recurrent tumors were analyzed by immunohistochemistry and comparative genomic hybridization (CGH). From our results clonal chromosomal aberrations can be postulated which seem to be a feasible tool to differentiate PTPRs from other primary or secondary papillary tumors of this region.

Pineal region tumors are heterogeneous lesions and include mainly pineal parenchymal tumors (PPTs), papillary tumors of the pineal region (PTPRs) and germ cell tumors (GCTs). This article describes the cystic pineal gland compared with normal tissue and histopathological features of the most frequent pineal region tumors. PPTs are subdivided into pineocytoma (grade I), pineoblastoma (grade IV) and tumors with intermediate differentiation (PPTIDs; grades II–III). A grading system based on the number of mitoses and neurofilament protein expression distinguishes low- from high-grade PPTID. PTPR is a new tumoral entity thought to originate from the subcommissural organ. GCTs include germinoma, embryonal carcinoma, teratoma, yolk sac tumor and choriocarcinoma and are often of mixed histologic composition. New histogenetic data for GCTs are presented.

A 13-year-old boy presented with a history of intracranial hypertension. Radiologic studies revealed triventricular hydrocephalus secondary to a space-occupying lesion in the pineal region. Endoscopic third ventriculostomy was performed to treat hydrocephalus, and the lesion was biopsied. Complete resection of the tumor was subsequently performed. After a period of uncertainty, the diagnosis of papillary tumor of the pineal region was established. Tumor bed radiotherapy at a dose of 50 Gy was associated. With a follow-up of 15 months, the postoperative course was satisfactory with return to school and no residual tumor on magnetic resonance imaging. Papillary tumors of the pineal region constitute a rare entity, with a difficult diagnosis, an uncertain prognosis, and a high risk of local recurrence; they must be treated by a combination of surgery and radiotherapy. The only identified prognostic factor is the complete or incomplete nature of surgical resection.

We present here an unusual case of papillary neuroepithelial tumor of the pineal region. The patient was a 29-year-old female who presented with headaches. A computed tomography scan revealed a tumorous lesion at the pineal region and hydrocephalus. The resected tumor was composed of columnar and cuboidal cells showing characteristics of papillary growth. The tumor cells exhibited diffuse and intense immunoreactivity to cytokeratins and neural cell adhesion molecule. The tumor expressed abundant levels of transthyretin (prealbumin) and appeared ependymal in nature, with numerous microlumens delineated by punctate and ring-like patterns in epithelial membrane antigen staining. Reactivity to synaptophysin and glial fibrillary acidic protein was observed only in the infiltrated non-neoplastic pineal parenchyma. These histological characteristics matched the description of the recently reported papillary tumor of the pineal region thought to originate from the specialized ependyma of the subcommissural organ (SCO). Transthyretin expression of the present case further supports the likelihood of SCO origin, as transthyretin is one of the proteins presumed to be secreted by human SCO.

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.

Papillary tumors of the pineal region are rare glial tumors located in the vicinity of the third ventricle, the clinical behavior of which is often aggressive. Little is known about the prognostic markers that might aid to identify patients at increased risk for recurrence. Therefore, the prognostic value of histopathologic and clinical features was examined in a series of 21 patients. Median age of the 12 male and 9 female patients was 35 years (range, 10 to 56 y). On histopathologic examination, all tumors were characterized by loose papillary structures and tumor cells forming broad perivascular pseudorosettes showing cytokeratin expression. In addition, tumors showed increased cellularity (n=4; 19%), nuclear pleomorphism (n=4; 19%), solid growth (n=11; 52%), necrosis (n=8; 38%), increased mitotic activity (≥3 mitoses per 10 high-power fields [n=10; 48%]), and increased proliferation (Ki67/MIB1 index ≥10% [n=8/20; 40%]). Gross total resection could be achieved in 13/21 patients (62%). Postoperatively, 13 patients received radiotherapy and 4 patients chemotherapy. Median recurrence-free survival was 66 months in 19 patients, for whom detailed follow-up information was available. Twelve patients (63%) experienced tumor progression. Three patients (16%) died of disease. Among the clinical and histopathologic features examined, only increased mitotic activity (52 [8 to 96] vs. 68 [66 to 70] mo [median [95% confidence interval]]) and proliferative activity (29 [0 to 64] vs. 67 [44 to 90] mo) were significantly associated with recurrence (P

Objective The pineal region is a rare intracranial site for metastasis. We report three patients initially considered to have metastatic papillary adenocarcinoma to the pineal region. On review, these papillary, keratin-positive neoplasms meet the criteria for papillary tumor of the pineal region (PTPR). Clinical presentation These neoplasms occurred in three women (age range, 37-55 yr). Imaging studies demonstrated well-circumscribed lesions in the pineal region. All patients presented with obstructive hydrocephalus and symptoms attributable to hydrocephalus and tectal compression. Intervention All three patients underwent near total microsurgical resection of the pineal region neoplasm, followed by adjuvant radiotherapy. The two patients with long-term follow-up (56-60 mo) have remained clinically stable without evidence of local or distant recurrence. The first two patients were initially diagnosed as having papillary metastatic carcinoma of unknown origin. The third patient was treated after the recent description of PTPR and met the histopathological diagnostic criteria. Retrospective pathological review of the previous two patients resulted in designation as PTPR. Conclusion The morphological features of the tumors in our series, along with the clinical presentations, are similar to those in the original description of the PTPR. Our findings agree with the original hypothesis that the cells composing the PTPR are similar to ependymal cells of the subcommissural organ, thus furthering the hypothesis that the PTPR derives from a specialized ependymocyte associated with the subcommissural organ. The two patients with long-term follow-up (56-60 mo) have remained clinically stable without evidence of local or distant recurrence.

Papillary tumor of the pineal region (PTPR) is a recently recognized entity. We present the pathologic findings of two cases of PTPR as examples, and discuss the presence of cellular pleomorphism in these tumors. Patient 1 is a 48-year-old man with a pineal region mass. The tumor had unique biphasic patterns, papillary/pseudopapillary areas, and increased mitotic activity. Juxtaposed areas had marked pleomorphism, including nuclear enlargement, smudgy chromatin, nuclear pseudoinclusions, and cytoplasmic vacuolation. Mitoses were absent in these areas. Immunohistochemical staining revealed strong S100 expression. CAM 5.2 and CK18 were strongly positive in a patchy fashion. MIB1 labeling indices were high in classic PTPR regions but very low in pleomorphic areas. Patient 2 was a 35-year-old male with a pineal region tumor characterized by papillary architecture and overall cellular monotony, rare mitoses, and pleomorphism as a more isolated finding, with associated nuclear enlargement and crowding. S100 and CAM 5.2 labeling were present, and MIB1 labeling index was very low throughout the tumor. We discuss the pathologic and phenotypic features of PTPR. Variable pleomorphism may be present, reflected in size variation and nuclear hyperchromasia, but was not accompanied by increased proliferative activity in these cases, suggesting a degenerative phenomenon.

Neuroepithelial papillary tumor of the pineal region (PTPR) has been defined as a distinct entity that is increasingly being recognized, with 96 cases now reported. This tumor shares morphologic features with both ependymomas and choroid plexus tumors. PTPR is characterized by an epithelial-like growth pattern in which the vessels are covered by layers of tumor cells forming perivascular pseudorosettes. These tumors exhibit various combinations of papillary and solid architecture, making the differential diagnosis of PTPR difficult to establish. We report the detailed description of the histopathologic features of a large series of PTPRs from 20 different centers and distinguish 2 subgroups of tumors with either a striking papillary growth pattern or a papillary and solid growth pattern. We highlight the findings that PTPRs have unusual vessels with multiple lumina and frequently show detachment of the border of the tumoral cells from the vascular wall. The 2 PTPR subgroups present similar clinical characteristics and immunophenotypes. We confirmed and extended the results of previous ultrastructural studies on the presence of intercellular junctions at the apical part of tumoral cells. The expression of the tight junction proteins claudin-1, claudin-2, and claudin-3 was investigated by immunohistochemistry. Claudin-1 and claudin-3, but not claudin-2, were expressed in PTPRs and in the fetal subcommissural organ, potentially the origin of this tumor. In contrast, all 3 claudins were expressed in choroid plexus papillomas. Claudin expression may help in the diagnosis of PTPRs and can be used in combination with other markers, such as CK18, NCAM, E-cadherin, MAP-2, and Kir 7.1.

We evaluated the efficacy of interstitial brachytherapy (IBT) using (125)Iodine ((125)I) seeds for treatment of papillary tumors of the pineal region. Between September 2003 and September 2010, four patients (M/F = 2/2; median age, 57.3 years; range 29.2-69.1 years) with papillary tumors of the pineal region underwent IBT using (125)I seeds. Before brachytherapy two patients underwent endoscopic ventriculo-cisternotomy, because of occlusive hydrocephalus, and subsequent microsurgical resection was performed on one; three patients were primarily treated with IBT. Median tumor volume was 3.3 ml (range 1.6-4 ml), the tumor surface dose ranged between 50 and 65 Gy. For three patients the seeds were implanted permanently whereas one patient received temporary implants (28 days). The median follow-up time was 53.6 months (range 13-103.4 months). After brachytherapy, follow-up MR images revealed complete remission in one patient, partial remission in two, and stable disease in the remaining patient. Neurological status improved in all patients (reduced headache and nausea/vomiting for four patients; improvement of oculomotor dysfunction for two of three patients partially and for one of three patients completely). Neither treatment-related morbidity nor mortality was observed. Our results are indicative of good local control of papillary tumors of the pineal region after IBT, without treatment-related morbidity.

Papillary tumors of the pineal region (PTPR) are very rare. We describe the first report of a PTPR empirically managed with gamma knife radiosurgery. The patient was initially shunted and referred for empirical gamma knife radiosurgery. After initially showing some improvement, he had recurrence of tumor after 7 years. For recurrence he underwent a gross total resection and the biopsy established the diagnosis of PTPR. Further research needs to be done as to the efficacy of gamma knife surgery for PTPR. In addition, the role of stereotactic biopsy for eligible patients should be considered as the initial step to direct the treatment of choice.

This 8-year-old girl presented with a papillary ependymoma in the thoracic spinal cord. Resection was followed by recurrence at the primary site and later in the lumbosacral thecal sac, followed by cerebrospinal fluid dissemination to the brain approximately 5 years after her initial presentation. The tumor showed cytological and immunohistochemical features overlapping those of classic ependymomas and choroid plexus tumors similar to those seen in uncommon supratentorial papillary ependymomas, also known as papillary tumors of the pineal region. The histopathological and clinical courses of this rare spinal papillary ependymoma exhibiting mixed ependymal and choroid plexus–like differentiation are discussed.

Papillary tumor of the pineal region (PTPR) is an uncommon tumor recently added to the WHO classification of CNS tumors. We report a case of PTPR in a young boy that was noteworthy for early CSF dissemination and relentless progression. In spite of intensive chemotherapy and comprehensive radiotherapy, the boy died. The neuroimaging appearance is unique with possible multicentric origin of the tumor and intense uptake of (111)In-DTPA-pentetreotide.

SUMMARY: We report the imaging features of 4 cases of patients with papillary tumor of the pineal region, a tumor newly recognized in the 2007 World Health Organization “Classification of Tumors of the Nervous System.” In each case, the tumor was intrinsically hyperintense on T1-weighted images with a characteristic location in the posterior commissure or pineal region. The pathologic hallmarks of the tumor are discussed, including a possible explanation for the MR imaging characteristics in our cases.

Pineal region tumors account for 2.8-9% of all CNS malignancies in children. The differential diagnosis of a pediatric pineal region tumor is broad and diagnostic strategies can vary. Literature combining medical and radiographic data prior to considering surgical biopsy is sparse. At times a biopsy and/or resection may not be necessary and carries associated morbidity. By using specific criteria to direct diagnosis these risks can be minimized. The criteria utilized show how tumor markers and presence of bifocal disease are utilized to diagnose different germ cell tumors without a biopsy. A pineal region tumor with elevation of AFP or B-hCG greater than 100mIU/ml is consistent with a nongerminomatous germ cell tumor. A pineal region tumor with normal AFP and B-hCG elevated but less than

Papillary tumor of the pineal region (PTPR) is a recently described tumor entity thought to arise from the specialized ependyma of the subcommissural organ. Whereas histologic features of PTPR are well defined, data on the prognostic value of PTPR remain scarce. We therefore investigated clinicopathologic features, including data on progression-free survival and overall survival, in a retrospective series of 31 PTPR. The age of the 14 males and 17 females ranged from 5 to 66 years (median age, 29 years). Histologically, all tumors were characterized by an epithelial-like growth pattern in which the vessels were covered by layers of columnar or cuboidal tumor cells forming perivascular pseudorosettes. Most of the tumor cells showed strong expression of neuron-specific enolase, cytokeratins (particularly CK18), S-100 protein, and vimentin. Most PTPRs examined also expressed microtubule-associated protein-2. Expression of synaptophysin, epithelial membrane antigen, transthyretin, neural cell adhesion molecule, and nestin was encountered in some tumors. Gross total resection could be achieved in 21 of 31 cases; 15 patients received radiotherapy on resection of the primary tumor. Nevertheless, the majority of patients experienced recurrences; 5-year estimates for overall survival and progression-free survival were 73% and 27%, respectively. To conclude, the clinical course of PTPR is characterized by frequent local recurrence, and the value of radiotherapy on disease progression will need to be investigated in future prospective trials.

Primary papillary tumors of the central nervous system are rare. We have encountered a series of six papillary tumors of the pineal region with distinctive features that appear to represent a clinicopathologic entity. The tumors occurred in four women and two men, ranging in age from 19 to 53 years. Imaging studies showed a large well-circumscribed mass in the pineal region. The tumors were characterized by an epithelial-like growth pattern, in which the vessels were covered by a layer of tumoral cells. In papillary areas, the neoplastic cells were large, columnar or cuboidal, with a clear cytoplasm. Nuclei, round or infolded, were found generally at the basal pole of tumoral cells. Immunohistochemically, the tumor cells showed strong staining for cytokeratin, S-100 protein, neuron-specific enolase, and vimentin but only weak or no staining for epithelial membrane antigen and glial fibrillary acid protein. Ultrastructural examination of two cases revealed abundant rough endoplasmic reticulum with distended cisternae filled with secretory product, microvilli, and perinuclear intermediate filaments. The morphofunctional features of these papillary tumors of the pineal region, remarkably uniform within this series, are similar to those described for ependymal cells of the subcommissural organ, and the papillary tumors of the pineal region may be derived from these specialized ependymocytes.

Since it has become evident that histopathological grading of ependymoma according to the WHO classification of CNS tumors is not capable of accurately classifying patients into meaningful strata, a broadly accepted molecular classification scheme with prognostic significance is desperately needed. In recent years, ependymomas were classified into molecular subgroups based on transcriptomic alterations. In tumors localized within the posterior fossa, two distinct biological entities of ependymoma were delineated by several studies (designated posterior fossa A and posterior fossa B), which show striking differences in genetic characteristics and clinical outcome. A similar consensus for supratentorial and spinal ependymoma is lacking. We studied genome-wide DNA methylation (Illumina HumanMethylation450 (450k) array) in 180 primary ependymal tumors (80 with corresponding gene expression profiling data generated by Affymetrix 133plus2.0 arrays), including ependymomas (posterior fossa, supratentorial, spinal), subependymomas (SE), myxopapillary ependymoma (MPE), pineal parenchymal tumors of intermediate differentiation (PPTID), and papillary tumors of the pineal region (PTPR). We performed hierarchical clustering to identify robust molecular subgroups. Independent gene expression profiling datasets from previously published ependymoma studies (Johnson et al.; Wani et al.; Witt et al.) were used as validation cohorts. DNA methylation data showed that ependymal brain tumors can be classified into eight molecular subgroups. Notably, MPE, SE, PPTID and PTPR tumors formed robust distinct clusters, as did posterior fossa Group A and Group B ependymomas. Supratentorial ependymomas can be classified into two principle molecular subgroups, one of which displays a dismal prognosis, and comprises predominantly children and infants, and is associated with highly recurrent gene fusion. Notably, a significant number of ependymomas previously classified by histology as WHO Grade II/III look like SE by methylation, and also have extremely good survival. In summary, using genome-wide DNA methylation and transcriptome analysis we could decipher robust molecular subgroups of ependymal brain tumors including supratentorial ependymoma. Diagnoses of tumors with challenging histopathological features can now be supported by this technology. Hence, this approach offers the possibility to replace the unambiguous histological grading system that is currently in use with a robust molecular classification that readily distinguishes biologically, genetically, and clinically meaningful subgroups of ependymal brain tumors. Citation Format: Hendrik Witt, Martin Sill, Khalida Wani, Steve Mack, David Capper, Stephanie Heim, Pascal Johann, Sally Lambert, Marina Rhyzova, Volker Hovestadt, Theophilos Tzaridis, Kristian Pajtler, Sebastian Bender, Till Milde, Paul A. Northcott, Andreas E. Kulozik, Olaf Witt, Peter Lichter, V Peter Collins, Andreas von Deimling, Marcel Kool, Michael D. Taylor, Martin Hasselblatt, David TW Jones, Andrey Korshunov, Ken Aldape, Stefan Pfister. Epigenetic classification of ependymal brain tumors across age groups. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3094. doi:10.1158/1538-7445.AM2014-3094

Papillary tumors of the pineal region (PTPRs) are rare and are recognized as a distinct entity in the recent 2007 World Health Organization (WHO) classification of tumors of nervous system. Till date, only 55 cases have been reported. We report another three patients of PTPRs with characteristic radiological features. Histologically, all the three patients exhibited remarkable uniform histology of epithelioid morphology with variable presence of single to multilayered papillary architecture. Consistent absence of fibrillary matrix was noted in all the three cases. None of the cases showed aggressive histology. A large multicenter study is essential for upfront characterizing the biological behavior, as frequency of these tumors is very low.

Papillary tumors of the pineal region are recently described as rare mass lesions with limited literature available on their natural history and imaging features. Magnetic resonance imaging (MRI) including perfusion, diffusion, and spectroscopic features were described in an 18-year-old girl with papillary tumor of pineal region. A well-defined, T1 hyperintense and contrast-enhancing mass lesion was noted in pineal region with few cystic spaces within. Solid portion of lesion showed minimal diffusion restriction with average apparent diffusion coefficient of 0.812 Χ 10 -3 mm 2 /s; on MR spectroscopy elevated myo-inositol peak with reduced N-acetylaspartate and elevated choline in the tumor. On perfusion study there was significantly high relative cerebral blood volume (rCBV) (6-9 times) and relative cerebral blood flow (rCBF). Our findings agree with previous descriptions of cystic areas with T1 hyperintense appearance of this tumor but very high level of tumor perfusion, diffusion restriction, and presence of myo-inositol peak are important imaging findings and may correlate with the recent reports of high tumor recurrence in these cases.

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 material The online version of this article (doi:10.1186/s40478-016-0329-0) contains supplementary material, which is available to authorized users.