Choroid plexus tumor

Choroid plexus tumor

Choroid plexus tumors are rare intraventricular papillary neoplasms derived from choroid plexus epithelium.

They account for approximately 2% to 4% of intracranial tumors in children and

Choroid plexus tumors occur more frequently in children, comprising approximately 4% of all pediatric brain tumors. Up to 20% of these tumors occur during the first year of life.

They account for 0.5% of intracranial tumors in adults.

Choroid plexus tumors most commonly arise from the lateral ventricles (50%), followed by the fourth (40%) and the third ventricle (5%). Other locations are rare, including the cerebellopontine angle, supresellar region, brain parenchyma and the spine.

They include three histologies, choroid plexus papilloma (WHO grade I), atypical choroid plexus papilloma (WHO grade II) and choroid plexus carcinoma (WHO grade III). All together, they account for 0.4-0.6% of all brain tumors 1) 2).

Results support the role of aggresome as a novel prognostic molecular marker for pediatric choroid plexus tumors (CPTs) that was comparable to the molecular classification in segregating samples into two distinct subgroups, and to the pathological stratification in the prediction of patients’ outcomes. Moreover, the proteogenomic signature of CPTs displayed altered protein homeostasis, manifested by enrichment in processes related to protein quality control 3).

see Choroid plexus metastases.

On CT, choroid plexus tumors appear heterogeneous and isodense with calcifications and necrosis.

Amer et al. examined the presence of aggresomes in 42 patient-derived tumor tissues by immunohistochemistry and we identified their impact on patients’ outcomes. We then investigated the proteogenomics signature associated with aggresomes using whole-genome DNA methylation and proteomic analysis to define their role in the pathogenesis of pediatric CPTs.

Aggresomes were detected in 64.2% of samples and were distributed among different pathological and molecular subgroups. The presence of aggresomes with different percentages was correlated with patients’ outcomes. The ≥ 25% cutoff had the most significant impact on overall and event-free survival (p-value < 0.001) compared to the pathological and the molecular stratifications.

These results support the role of aggresome as a novel prognostic molecular marker for pediatric CPTs that was comparable to the molecular classification in segregating samples into two distinct subgroups, and to the pathological stratification in the prediction of patients’ outcomes. Moreover, the proteogenomic signature of CPTs displayed altered protein homeostasis, manifested by enrichment in processes related to protein quality control 4).

2015

A total of 349 patients with CPTs were identified (120 CPCs, 26 aCPPs, and 203 CPPs). Patients with CPC presented at a younger age (median 3, mean 14.8 years) relative to CPP (median 25, mean 28.4 years; p < 0.0001). Histology was a significant predictor of OS, with 5-year OS rates of 90, 77, and 58 % for CPP, aCPP, and CPC, respectively. Older age and male sex were prognostic for worse OS and CSS for CPP. Only extent of surgery had a significant impact on survival for CPC. The use of adjuvant RT in patients with CPC undergoing surgery was not associated with a significantly improved OS (p = 0.17). For patients undergoing GTR without RT as part of an initial course of therapy, estimated 5- and 10-year OS were 70 % (±7 %) and 67 % (±8 %), respectively. Prospective data are required to define the optimal combination of surgery with adjuvant therapies, including chemotherapy 5).


Seventeen childhood patients were recorded with CPT. Cases were distributed so that 9 cases were choroid plexus-papilloma (CPP) (52.9%), 2 cases atypical CPP (11.7%) and 6 cases choroid plexus-carcinoma (CPC) (35.2%). Age at diagnosis was less than 2 years in 14 of the 17 patients (82.3%) and the incidence was higher in males (82.3% of the cases). Gross total resection was performed in 16 patients (94.1%). Adjuvant treatment was used in 6 patients (all this cases with CPC) (35.2%). Two of the 17 patients died (11.7%), showing an incidence density of 0.01 deaths/year.

The case series is consistent with previous published in scientific literature regarding epidemiology, tumor grade, clinical presentation, radiological features and therapeutic approach. Gross total resection is considered the therapeutic gold standard for choroid plexus tumors. Chemotherapy and radiotherapy should be used as adjuvant treatment in CPC and recurrent or remaining atypical CPP 6).


1)

Fuller CE, Narendra S, Tolocica I. Choroid plexus neoplasm. Adesina AM, Tihan T, Fuller C, Young Poussaint T, editors. , Atlas of pediatric brain tumors. New York: Springer Publication; 2010. pp 269-279
2)

Gopal P, Parker JR, Debski R, Parker JC., Jr. Choroid plexus carcinoma. Arch Pathol Lab Med 2008;132:1350-4
3) , 4)

Amer N, Taha H, Hesham D, Al-Shehaby N, Mosaab A, Soudy M, Osama A, Mahmoud N, Elayadi M, Youssef A, Elbeltagy M, Zaghloul MS, Magdeldin S, Sayed AA, El-Naggar S. Aggresomes predict poor outcomes and implicate proteostasis in the pathogenesis of pediatric choroid plexus tumors. J Neurooncol. 2021 Jan 26. doi: 10.1007/s11060-020-03694-3. Epub ahead of print. PMID: 33501605.
5)

Cannon DM, Mohindra P, Gondi V, Kruser TJ, Kozak KR. Choroid plexus tumor epidemiology and outcomes: implications for surgical and radiotherapeutic management. J Neurooncol. 2015 Jan;121(1):151-7. doi: 10.1007/s11060-014-1616-x. Epub 2014 Oct 1. PubMed PMID: 25270349.
6)

Cuervo-Arango I, Reimunde P, Gutiérrez JC, Aransay A, Rivero B, Pérez C, Budke M, Villarejo F. [Choroid plexus tumour treatment at Hospital Infantil Niño Jesús in Madrid: Our experience over the last three decades.]. Neurocirugia (Astur). 2015 Feb 24. pii: S1130-1473(15)00005-6. doi: 10.1016/j.neucir.2015.01.001. [Epub ahead of print] Spanish. PubMed PMID: 25724620.

Cerebellopontine Angle Synchronous Tumor

Cerebellopontine Angle Synchronous Tumor

Synchronous cerebellopontine angle (CPA) tumors are a rare entity, heterogeneous lesions with a marked predisposition toward poor facial nerve outcomes, potentially attributable to a paracrine mechanism that simultaneously drives multiple tumor growth and increases invasiveness or adhesiveness at the facial nerve-tumor interface. Preceding nomenclature has been confounding and inconsistent; Graffeo et al. recommended classifying all multiple CPA tumors as “synchronous tumors,” with “schwannoma with meningothelial hyperplasia” or “tumor-to-tumor metastases” reserved for rare, specific circumstances 1).

Several publications refer to surgery for such tumors and their classification. Yet, there are no publications on upfront radiosurgery for synchronous CPA tumors.

Simultaneous and stepwise radiosurgery for synchronous CPA tumors seems to be safe and effective. There were no side effects or complications. To the best of our knowledge this is the first report on upfront radiosurgery for synchronous CPA tumors 2).

Mindermann and Heckl presented two patients with sporadic synchronous benign CPA tumors who underwent upfront radiosurgery. One patient had two separate schwannomas of the CPA and the other had a cerebellopontine angle schwannoma and a cerebellopontine angle meningioma. One patient underwent stepwise radiosurgery treating one tumor after another and the other patient underwent simultaneous radiosurgery for both tumors at the same time.

Simultaneous and stepwise radiosurgery for synchronous CPA tumors seems to be safe and effective. There were no side effects or complications. To the best of our knowledge this is the first report on upfront radiosurgery for synchronous CPA tumors 3).


A 64-year-old woman and a 42-year-old man presented with symptoms referable to the CPA. Magnetic resonance imaging in both patients revealed 2 separate contiguous tumors. Retrosigmoid craniotomy and tumor removal in each case confirmed VS and meningioma. Systematic literature review identified 42 previous English-language publications describing 46 patients with multiple CPA tumors. Based on Frassanito criteria, there were 4 concomitant tumors (8%), 16 contiguous tumors (33%), 3 collision tumors (6%), 13 mixed tumors (27%), and 11 tumor-to-tumor metastases (23%). Extent of resection was gross total in 16 cases and subtotal in 16 cases (50% each). Unfavorable House-Brackmann grade III-VI function was documented in 27% overall and in 33% of patients with VS and meningioma, a marked increase from the observed range in isolated VS 4).


A 57-year-old female patient presented with headache, speech disturbance, left facial numbness and deafness in the left ear. Magnetic resonance imaging demonstrated two different tumors in the left CPA. These tumors were not in continuity. The tumors were totally removed through the left suboccipital approach. Histopathological examination revealed that the large tumor was a vestibular schwannoma and the smaller was a meningioma. Neurofibromatosis was not diagnosed in the patient. No recurrence was observed at the end of 9 years after the operation. The simultaneous occurrence of vestibular schwannoma and meningioma in the CPA appears coincidental. This association must be kept in mind if two different tumors are detected radiologically in the same CPA 5).


1) , 4)

Graffeo CS, Perry A, Copeland WR 3rd, Giannini C, Neff BA, Driscoll CL, Link MJ. Synchronous Tumors of the Cerebellopontine Angle. World Neurosurg. 2017 Feb;98:632-643. doi: 10.1016/j.wneu.2016.11.002. Epub 2016 Nov 12. PMID: 27836701.
2) , 3)

Mindermann T, Heckl S. Radiosurgery for Sporadic Benign Synchronous Tumors of the Cerebellopontine Angle. J Neurol Surg A Cent Eur Neurosurg. 2020 Oct 21. doi: 10.1055/s-0040-1714424. Epub ahead of print. PMID: 33086420.
5)

Izci Y, Secer HI, Gönül E, Ongürü O. Simultaneously occurring vestibular schwannoma and meningioma in the cerebellopontine angle: case report and literature review. Clin Neuropathol. 2007 Sep-Oct;26(5):219-23. doi: 10.5414/npp26219. PMID: 17907598.

Atypical teratoid/rhabdoid tumor

Atypical teratoid/rhabdoid tumor

A malignant WHO grade IV embryonal tumor of the CNS comprised of poorly differentiated elements and rhabdoid cells and, by definition, includes inactivation of SMARCB1 (INI1) or (extremely rarely) SMARCA4 (BRG1). Histologically similar tumors lacking these molecular genetics should be classified as CNS embryonal tumors with rhabdoid features.

Many of these tumors were probably previously misdiagnosed as MDBs. Occurs primarily in infants and children (> 90% are < 5 years of age, with most age < 2 years). A minority are associated with primary renal rhabdoid tumor. The ratio of supratentorial to infratentorial AT/RTs is 4:3. Posterior fossa AT/RTs may occur in the cerebellar hemispheres, cerebellopontine angle (CPA) and brainstem. 33% have CSF spread at presentation. Althogh the prognosis is poor, not all AT/RTs have the same behavior, and at least 2 different molecular classes have been identified.


Atypical teratoid rhabdoid tumor (AT/RT) is a rare, highly malignant, true rhabdoid tumor in the central nervous system predominantly presenting in young children.

It was originally described a histological variant of Wilm’s tumor in 1978.


Atypical teratoid rhabdoid tumors (ATRTs) comprise at least two transcriptional subtypes with different clinical outcomes; however, the mechanisms underlying therapeutic heterogeneity remained unclear. In a study, Torchia et al., analyzed 191 primary ATRTs and 10 ATRT cell lines to define the genomic and epigenomic landscape of ATRTs and identify subgroup-specific therapeutic targets.

They found ATRTs segregated into three epigenetic subgroups with distinct genomic profiles, SMARCB1 genotypes, and chromatin landscape that correlated with differential cellular responses to a panel of signaling and epigenetic inhibitors. Significantly, they discovered that differential methylation of a PDGFRB-associated enhancer confers specific sensitivity of group 2 ATRT cells to dasatinib and nilotinib, and suggest that these are promising therapies for this highly lethal ATRT subtype 1).

Classification

AT/RT can occur anywhere in the central nervous system (CNS) including the spinal cord. About 60% will be in the posterior cranial fossa (particularly the cerebellum). One review estimated 52% posterior fossa, 39% sPNET (supratentorial primitive neuroectodermal tumors), 5% pineal, 2% spinal, and 2% multi-focal.

In the United States, three children per 1,000,000 or around 30 new AT/RT cases are diagnosed each year. AT/RT represents around 3% of pediatric cancers of the CNS.

Around 17% of all pediatric cancers involve the CNS; it is the most common childhood solid tumor.

see Adult sellar atypical teratoid rhabdoid tumor.

see Cerebellopontine angle atypical teratoid rhabdoid tumor.

Atypical Teratoid Rhabdoid Tumor of the Cauda Equina.

Atypical Teratoid Rhabdoid Tumor of the Conus Medullaris.

Pathology

Typically shows rhabdoid cells which can also be seen in other tumors, but it is differentiated from other tumors by the specific genetic alteration involving the SMARCB1 gene. Only a few cases of AT/RT arising in low-grade glioma have been reported. A 13-year-old girl presented with headache, dizziness, nausea and vomiting.A 4.7 cm cerebellar mass was found on MRI.The mass was totally removed. Histologically, the tumor revealed two distinct morphologic appearances: central areas of AT/RT containing rhabdoid cells and sarcomatous component in the background of pleomorphic xanthoastrocytoma(PXA). Immunohistochemically, PXA areas retained nuclear expression of INI-1 and low Ki-67 proliferation index, whereas AT/RT component showed loss of INI-1 nuclear expression and markedly elevated Ki-67 proliferation index. Epithelial membrane antigen (EMA), smooth muscle actin (SMA), and p53 protein were positive only in AT/RT. BRAF V600E mutation was identified in PXA by real-time polymerase chain reaction.We report a rare case of AT/RT arising in PXA which is supposed to progress by inactivation of INI-1 in a pre-existing PXA 2).

Treatment

Atypical teratoid rhabdoid tumor treatment.

Outcome

Patient age at the time of diagnosis, supratentorial location of the mass and fewer complications with adjuvant treatments seem to be factors yielding good prognosis for AT/RT tumors. In agreement with the latest international protocols, multidisciplinary treatment is the ideal treatment, consisting of radiotherapy and chemotherapy after complete tumor resection 3).

Case series

Twenty-eight pediatric patients with CNS AT/RT who were treated with radiation therapy (RT) as part of multimodality treatment regimens at a single institution (1996-2015) were reviewed. Survival outcomes were analyzed in relation to possible prognostic factors.

The 28 patients analyzed were followed up for a median 48-month period. Median progression-free survival (PFS) was 11 months, and overall survival (OS) was 57 months. Patients < 3 years old had RT delayed for a longer period after surgery (p = 0.04), and the mean RT dose to tumor bed was lower (p < 0.01) than in patients ≥ 3 years old. In multivariate analysis, a higher primary tumor bed RT dose was identified as a favorable prognostic factor for both PFS (hazard ratio [HR] = 0.85 per gray, p < 0.01) and OS (HR = 0.92 per gray, p = 0.02). In addition, an interval between surgery and RT initiation > 2 months, with disease progression observed before RT, as compared with an interval ≤ 2 months without disease progression prior to RT, was associated with worse PFS (HR = 8.50, p < 0.01) and OS (HR = 5.27, p < 0.01).

Early and aggressive RT after surgery is critical for successful disease control in AT/RT patients. Conversely, a delay in RT until disease progression is observed that leads to unfavorable outcomes 4).


In a study, Torchia et al. analyzed 191 primary Atypical teratoid rhabdoid tumor ATRTs and 10 ATRT cell lines to define the genomics and epigenomic landscape of ATRTs and identify subgroup-specific therapeutic targets. They found ATRTs segregated into three epigenetic subgroups with distinct genomic profiles, SMARCB1 genotypes, and chromatin landscape that correlated with differential cellular responses to a panel of signaling and epigenetic inhibitors. Significantly, they discovered that differential methylation of a PDGFRB-associated enhancer confers specific sensitivity of group 2 ATRT cells to dasatinib and nilotinib, and suggest that these are promising therapies for this highly lethal ATRT subtype 5).

References

1) , 5)

Torchia J, Golbourn B, Feng S, Ho KC, Sin-Chan P, Vasiljevic A, Norman JD, Guilhamon P, Garzia L, Agamez NR, Lu M, Chan TS, Picard D, de Antonellis P, Khuong-Quang DA, Planello AC, Zeller C, Barsyte-Lovejoy D, Lafay-Cousin L, Letourneau L, Bourgey M, Yu M, Gendoo DM, Dzamba M, Barszczyk M, Medina T, Riemenschneider AN, Morrissy AS, Ra YS, Ramaswamy V, Remke M, Dunham CP, Yip S, Ng HK, Lu JQ, Mehta V, Albrecht S, Pimentel J, Chan JA, Somers GR, Faria CC, Roque L, Fouladi M, Hoffman LM, Moore AS, Wang Y, Choi SA, Hansford JR, Catchpoole D, Birks DK, Foreman NK, Strother D, Klekner A, Bognár L, Garami M, Hauser P, Hortobágyi T, Wilson B, Hukin J, Carret AS, Van Meter TE, Hwang EI, Gajjar A, Chiou SH, Nakamura H, Toledano H, Fried I, Fults D, Wataya T, Fryer C, Eisenstat DD, Scheinemann K, Fleming AJ, Johnston DL, Michaud J, Zelcer S, Hammond R, Afzal S, Ramsay DA, Sirachainan N, Hongeng S, Larbcharoensub N, Grundy RG, Lulla RR, Fangusaro JR, Druker H, Bartels U, Grant R, Malkin D, McGlade CJ, Nicolaides T, Tihan T, Phillips J, Majewski J, Montpetit A, Bourque G, Bader GD, Reddy AT, Gillespie GY, Warmuth-Metz M, Rutkowski S, Tabori U, Lupien M, Brudno M, Schüller U, Pietsch T, Judkins AR, Hawkins CE, Bouffet E, Kim SK, Dirks PB, Taylor MD, Erdreich-Epstein A, Arrowsmith CH, De Carvalho DD, Rutka JT, Jabado N, Huang A. Integrated (epi)-Genomic Analyses Identify Subgroup-Specific Therapeutic Targets in CNS Rhabdoid Tumors. Cancer Cell. 2016 Dec 12;30(6):891-908. doi: 10.1016/j.ccell.2016.11.003. PubMed PMID: 27960086.
2)

Jeong JY, Suh YL, Hong SW. Atypical teratoid/rhabdoid tumor arising in pleomorphic xanthoastrocytoma: a case report. Neuropathology. 2014 Aug;34(4):398-405. PubMed PMID: 25268025.
3)

Valencia-Moya A, González-García L, Ros-López B, Acha-García T, Weil-Lara B, Obando-Pacheco P, Arráez-Sánchez MÁ. Prognosis of atypical teratoid rhabdoid tumors (AT/RT) treated with multimodal therapy protocols. Report of our series. Neurocirugia (Astur). 2015 Apr 17. pii: S1130-1473(15)00020-2. doi: 10.1016/j.neucir.2015.01.003. [Epub ahead of print] PubMed PMID: 25900785.
4)

Yang WC, Yen HJ, Liang ML, Chen HH, Lee YY, Wong TT, Hu YW, Chen YW. Role of early and aggressive post-operative radiation therapy in improving outcome for pediatric central nervous system atypical teratoid/rhabdoid tumor. Childs Nerv Syst. 2019 Apr 13. doi: 10.1007/s00381-019-04126-y. [Epub ahead of print] PubMed PMID: 30982172.
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