Case Study 57
Kenneth Clark, MD
Question 1
• This is a 37-year-old woman who presented to
the emergency room following minor accidental
head trauma. An MRI of the head was
performed.
• Describe the MRI findings.
Axial T1
Axial T1 + Contrast
Sagittal T1
Axial T2 FLAIR
Coronal T1 + Contrast
Answer
• A large complex (solid and cystic)
heterogeneously enhancing intraventricular
mass centered within the body of the left lateral
ventricle. Solid components appear to enhance
homogeneously. There is a moderate amount of
surrounding parenchymal T2/FLAIR
hyperintensity. The lesion appears fairly wellcircumscribed.
Question 2
• What is the differential diagnosis of an
intraventricular mass lesion?
Answer
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•
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Choroid Plexus Tumor
Ependymoma
Subependymoma
Meningioma
Central Neurocytoma
Oligodendroglioma
Astrocytoma
Medulloblastoma
Question 3
• A small piece of the lesion was submitted for
intra-operative evaluation. What is your
impression (i.e. what would your intra-op
diagnosis be)?
• Click here to see the frozen section slide
Answer
• The smear shows a highly cellular lesion
comprised of relatively monomorphic cells with
generally round nuclei, evenly distributed,
stippled chromatin, slight nuclear contour
irregularities and modest amounts of pale pink
cytoplasm. In some areas the cells appear
dyscohesive while in others they appear to form
papillary structures. No mitotic figures are seen.
• A. Neoplastic
• B. Defer definitive diagnosis to permanent
sections
Question 4
• The lesion was resected and submitted for
pathologic examination. Describe the H&E
sections.
• Click here to see the H&E slide
Answer
• The tissue shows a cellular neoplasm arranged
in nests and sheets with occasional acinar
formation. The neoplastic cells show mild
nuclear pleomorphism with stippled chromatin
and inconspicuous nucleoli, and have
predominantly eosinophilic cytoplasm with focal
clearing. No readily identifiable mitoses are
seen. The background tissue additionally shows
eosinophilic hyaline material and abundant
hemosiderin, cholesterol clefts, and scattered
calcifications.
Question 5
• What is your diagnostic impression?
Answer
• Neuroendocrine tumor
• Choroid plexus tumor (adenoma, carcinoma)
• Metastatic tumor (lung, kidney, thyroid,
melanoma)
• Unusual meningioma
• Unusual lymphoid neoplasm
• Hemangioblastoma
Question 6
• The differential diagnosis is broad. What stains
would you order in order to better characterize
this lesion and limit your differential?
Answer
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•
•
•
•
•
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Keratins (CK7, CK20, Cam5.2, AE1/3)
S100, MelanA, HMB45 (r/o melanoma)
Synaptophysin, Chromogranin (neuroendocrine markers)
EMA, p63, GFAP (meningioma, glial)
CD20, CD3, CD68, Pax-8 (inflammatory, lymph)
CD10, TTF1, Thyroglobulin (renal, lung, thyroid)
Transthyretin (choroid plexus tumors)
Ki67 (proliferation index)
• Click to see Cam5.2, AE1/3, CK7, Transthyretin,
Synaptophysin, Ki67, p53, GFAP, S100, Reticulin
Question 7
• Based on the H&E and immunohistochemical
findings (see below), what is your diagnosis?
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Cam 5.2 – positive in tumor cells
AE1/3 & cytokeratin 7 – focally positive in tumor cells
Transthyretin and Synaptophysin – strong positive in tumor cells
Ki-67 proliferation index - approximately 1-2%
p53 – focal weak nuclear staining of tumor cells
S100, GFAP – negative in tumor cells; highlights background
parenchyma
• CD3, CD20, CD68 – highlights scattered mature T-cells, B-cells and
macrophages
• Negative Stains - Cytokeratin 20, p63, chromogranin, calcitonin,
thyroglobulin, TTF-1, EMA, CD10, PAX-8, HMB45, and Melanin A.
Answer
• Choroid Plexus Papilloma, WHO grade 1
Question 8
• How are choroid plexus tumors graded?
Answer
• Choroid Plexus Papilloma – WHO grade 1
• Atypical Choroid Plexus Papilloma – WHO
grade 2
• Choroid Plexus Carcinoma, WHO grade 3
Question 9
• How are atypical choroid plexus papillomas
(WHO 2) and choroid plexus carcinomas (WHO
3) distinguished from choroid plexus papilloma
histologically?
Answer
• CPP – Fibrovascular connective tissue fronds
covered by single layer of cuboidal to columnar
epithelium with basally situated monomorphic
nuclei. Scant to no mitotic activity.
• ACPP – Identical histology as CPP except for
increased mitotic activity (2 or more per 10 HPF)
• CPC – Frank signs of malignancy (need at least
4 of the following features):
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–
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>5 mitoses / 10 HPF
nuclear pleomorphism
increased cell density
tumor sheeting
necrosis
Question 10
• This tumor shows regions of increased cellularity
and blurring of the papillary architecture. Are
these features concerning?
Answer
• No. Grade 1 choroid plexus papillomas
can show focal regions of increased
cellularity, pleomorphism, architectural
blurring, necrosis and even brain invasion.
However, without increased mitotic activity
and/or at least 4 of these features
together, the lesion should still be
considered low grade.
Question 11
• How does the Ki67 proliferation index help
in making a diagnosis?
Answer
• Ki67 proliferation indices have been reported to
range from 0.2-6% (mean 1.9%) in choroid
plexus papillomas.
• Reported Ki67 proliferation indices in choroid
plexus carcinomas range from 7.3-60% (mean
13.8%).
• Despite focal areas of atypical features seen in
this lesion, the Ki67 index of 1-2% gives us more
confidence in calling it a WHO grade 1 CPP.
References
• Louis D, Ohgaki H, Wiestler O, Cavanee W. WHO Classification of
Tumours of the Central Nervous System. IARC: Lyon 2007.
• Gyure K, Morrison A. Cytokeratin 7 and 20 expression in choroid
plexus tumors: utility in differentiating these neoplasms from
metastatic carcinomas (2000). Mod Pathology. 13(6):638-643.