CNS tumor
Choroid plexus tumors
Choroid plexus tumors (papilloma, atypical papilloma, carcinoma)

Editor-in-Chief: Debra L. Zynger, M.D.
Ashirwad Merve, M.B.B.S., Ph.D.

Minor changes: 1 April 2021

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PubMed Search: Choroid plexus[TI] tumors CNS

Ashirwad Merve, M.B.B.S., Ph.D.
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Cite this page: Merve A. Choroid plexus tumors (papilloma, atypical papilloma, carcinoma). PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/cnstumorchoroidplexuspapillomas.html. Accessed May 10th, 2021.
Definition / general
  • Choroid plexus tumors are rare neoplasms derived from the choroid plexus epithelium
  • They occur within the ventricle system of the brain
Essential features
  • Rare intracranial tumor arising in the ventricle, mainly occurring in children
  • 3 histological grades (WHO grade I, II, III): choroid plexus papilloma (CPP), atypical choroid plexus papilloma (aCPP), choroid plexus carcinoma (CPC)
  • Histological classification is based on architecture (preservation of papillary pattern), cellular density, cytology (nuclear pleomorphism), proliferation (mitoses) and necrosis / brain invasion
  • Diagnostically, transthyretin (TTR), KIR7.1, cytokeratin and Ki67 immunohistochemistry are most helpful
  • Based on methylation profiling, these tumors are now categorized in to 3 subtypes
  • In line with other CNS tumors, integrated phenotype genotype diagnosis is preferred, which will guide appropriate management
Terminology
  • Conventionally, as per current WHO classification, these tumors are termed as choroid plexus papilloma (CPP, WHO grade I), atypical choroid plexus papilloma (aCPP, WHO grade II) and choroid plexus carcinoma (CPC, WHO grade III) (Acta Neuropathol 2016;131:803)
  • Based on recent DNA methylation profiling, they are being classified into 3 prognostically relevant epigenetic subgroups: supratentorial pediatric low risk choroid plexus tumors (CPP and aCPP), infratentorial adult low risk choroid plexus tumors (CPP and aCPP) and supratentorial pediatric high risk choroid plexus tumors (CPP and aCPP and CPC) (J Neurooncol 2020;148:39)
ICD coding
  • ICD-O:
    • 9390/0 - choroid plexus papilloma, NOS
    • 9390/1 - atypical choroid plexus papilloma
    • 9390/3 - choroid plexus carcinoma
  • ICD-10:
    • D33.2 - benign neoplasm of brain, unspecified
    • C71.9 - malignant neoplasm of brain, unspecified
Epidemiology
Sites
  • Lateral ventricle (common in children)
  • Fourth ventricle (distributed across all age groups)
  • Rarely in spinal cord or ectopic sites
  • Multifocal in exceptional circumstances
Pathophysiology
Clinical features
  • Hydrocephalus / raised intracranial pressure
  • Headache, vomiting, papilledema
Diagnosis
  • Clinical features, imaging (CT or preferably MRI)
  • Biopsy with histologic examination for definitive diagnosis
Radiology description
  • Intraventricular papillary or lobulated lesions on MRI; hypo or isointense on T1, hyper or isointense on T2 and enhanced in postcontrast imaging (Cancer Imaging 2019;19:17)
Radiology images

Contributed by Kshitij Mankad, M.D.
MRI coronal

MRI coronal

MRI sagittal

MRI sagittal

MRI transverse

Prognostic factors
  • Historically, histological grade alone has been used for prediction of outcome
  • Recent studies suggest 3 prognostic risk groups based on epigenetics, patient age and tumor location (Neuro Oncol 2016;18:790):
    • Supratentorial pediatric low risk choroid plexus tumors
    • Infratentorial adult low risk choroid plexus tumors
    • Supratentorial pediatric high risk choroid plexus tumors
  • Cerebrospinal fluid spread, drop metastasis and tumor recurrence after treatment are known and when present, carry poorer prognosis (BMJ Case Rep 2012;2012:bcr0120125681)
Case reports
Treatment
  • Surgery to achieve gross total resection
  • Adjuvant radiotherapy or chemotherapy, based on the clinical need
Gross description
  • Papillomas are well circumscribed cauliflower-like masses
  • Cysts, hemorrhages and calcifications may be present
  • Carcinomas are invasive, solid and necrotic
Gross images

Images hosted on other servers:

Fourth ventricle tumor

Microscopic (histologic) description
  • Choroid plexus papilloma (CPP, WHO grade I):
    • Papillary (finger-like) architecture, resembling normal choroid plexus
    • Single layer of cuboidal to columnar monomorphic cells
    • Loss of cobblestone surface
    • Mild nuclear pleomorphism, mitotic activity rare (< 2/10 high power fields), lacks necrosis
  • Atypical choroid plexus papilloma (aCPP, WHO grade II):
    • Higher cellularity relative to CPP
    • Moderate nuclear pleomorphism, blurring of papillary pattern
    • Occasional mitoses (> 2/10 high power fields), with or without necrosis
  • Choroid plexus carcinoma (CPC, WHO grade III):
    • Frankly malignant
    • High cellularity, hyperchromatic nuclei and nuclear pleomorphism
    • Blurring of papillary pattern and solid arrangement
    • Frequent mitoses (> 5/10 high power fields), necrosis, with or without brain invasion
Microscopic (histologic) images

Contributed by Ashirwad Merve, M.B.B.S., Ph.D.
Benign tumor Choroid plexus papilloma

Choroid plexus papilloma

Ki67 in choroid plexus papilloma

Ki67 in choroid plexus papilloma

Intermediate grade tumor Atypical choroid plexus papilloma

Atypical choroid plexus papilloma

Ki67 in atypical choroid plexus papilloma

Ki67 in atypical choroid plexus papilloma


Choroid plexus carcinoma Choroid plexus carcinoma

Choroid plexus carcinoma

Ki67 in choroid plexus carcinoma

Ki67 in choroid plexus carcinoma

Transthyretin

Transthyretin

Cytokeratin

Cytokeratin

SMARCB1 (INI1)

SMARCB1 (INI1)

Cytology description
  • Intraoperative crush smear: papillary strands with fibrovascular cores
  • Lesional cells exhibit relative cellular crowding and cytological atypia (in relation to normal choroid plexus epithelium)
Cytology images

Contributed by Ashirwad Merve, M.B.B.S., Ph.D.
Intraoperative smear

Intraoperative smear

Positive stains
Negative stains
Molecular / cytogenetics description
  • The following 3 methylation classes of choroid plexus tumors are recognized based on the German Cancer Research Center (DKFZ) Heidelberg classification:
    • Plexus tumor, subclass adult
    • Plexus tumor, subclass pediatric A
    • Plexus tumor, subclass pediatric B (closely related to methylation cluster 3 described in Neuro Oncol 2016;18:790)
  • TP53 sequencing and testing for germ line TP53 mutation is advisable in children with choroid plexus carcinoma
Molecular / cytogenetics images

Contributed by Ashirwad Merve, M.B.B.S., Ph.D.
Methylation array CNV plot

Methylation array copy number variation plot

Sample pathology report
  • Lateral ventricle, tumor, excision:
    • Atypical choroid plexus papilloma (WHO grade II)
    • Methylation class: Plexus tumor, subclass pediatric B, family class PLEX_T
    • Molecular tests (sequencing): No TP53 mutation
    • Comment: The tumor shows moderate atypia, histologically equivalent to WHO grade II. The methylation array has classified as subclass B, which is closely related to methylation cluster 3 described in Neuro Oncol 2016;18:790.
Differential diagnosis
Additional references
Board review style question #1

A 3 month old boy presented with restless crying and vomiting. His head size was larger than expected for his age. Imaging showed an 8 cm, lobulated, enhancing lesion in the right lateral ventricle. Histology is as above. Which of the following is true?

  1. Choroid plexus tumors are common in adults
  2. Recent studies suggest 3 distinct molecular entities based on methylation profiling, patient age and tumor location
  3. This is a choroid plexus carcinoma (WHO grade III)
  4. TP53 mutation is strongly associated with choroid plexus papilloma
Board review style answer #1
B. Recent studies suggest 3 distinct molecular entities based on methylation profiling, patient age and tumor location. An atypical choroid plexus tumor is shown in the image.

Choroid plexus tumors are rare intracranial tumors arising in the choroid plexus epithelium of the ventricles. They are more common in children. Histologically, they are classified into 3 categories: choroid plexus papilloma (CPP, WHO grade I), atypical choroid plexus papilloma (aCPP, WHO grade II) and choroid plexus carcinoma (CPC, WHO grade III). Although any of these tumors can have CSF spread and recur following treatment, the latter is associated with poor outcome and higher recurrence rate. Recent studies have shown that CPP and aCPP are genetically similar but CPP and aCPP are genetically distinct from CPC. The CPCs are mostly driven by loss of function or mutations of tumor suppressor gene TP53 and may be associated germ line mutations (Li-Fraumeni syndrome). Furthermore, based on methylation profiling, tumor location and age, 3 distinct subgroups with prognostic significance have been described. The advances in understanding of genetics may help deliver appropriate personalized treatment.

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Reference: Choroid plexus tumors (papilloma, atypical papilloma, carcinoma)
Board review style question #2
Which of the following is true regarding the histological differential diagnosis for choroid plexus carcinoma?

  1. Diffuse synaptophysin expression and Homer-Wright rosettes are features of choroid plexus carcinoma
  2. IDH1 is positive in choroid plexus carcinoma
  3. LIN28a is positive in choroid plexus carcinoma
  4. Nuclear INI1 (SMARB1) expression is retained in choroid plexus carcinoma but lost in atypical teratoid / rhabdoid tumor
Board review style answer #2
D. Nuclear INI1 (SMARB1) expression is retained in choroid plexus carcinoma but lost in atypical teratoid / rhabdoid tumor

Choroid plexus carcinomas can mimic other malignant tumors of the childhood, such as CNS embryonal tumors, and it is important to exclude them to guide appropriate treatment. INI1 (SMARCB1) and SMARCA4 immunohistochemistry expression is retained in CPC, which helps to differentiate from aggressive tumor atypical teratoid / rhabdoid tumor (AT / RT). A negative LIN28a differentiates from embryonal tumor with multilayered rosettes (ETMR, bearing C19MC alterations). Diffuse synaptophysin expression with patchy GFAP and presence of Homer-Wright rosettes should raise the possibility of medulloblastoma. Diffuse GFAP expression with possible IDH1 expression (in younger adults) with microvascular endothelial proliferation and necrosis would indicate a high grade glioma / glioblastoma. DNA methylation array and classification of CNS tumors will help in definitive classification. Nevertheless, it is important to have a solid histological diagnosis in case the array fails to confidently classify the tumor.

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Reference: Choroid plexus tumors (papilloma, atypical papilloma, carcinoma)
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