Case Study 55
Kenneth Clark, MD
Question 1
• This is a 27-year-old man with a history of pineal
/ dorsal midbrain region teratoma at age 16,
status-post multiple debulking resections,
chemotherapy, and gamma knife radiotherapy in
2001 & 2006. He presents to the emergency
room following a grand mal seizure. He
immediately underwent an MRI scan of the
head.
• How would you describe the neuroradiologic
findings?
Axial T1
Axial T1 + Contrast
Sagittal T1
Axial T2 FLAIR
Coronal T1 + Contrast
Answer
• A large expansile multicystic mass centered
within the pineal region causing mass effect and
distortion of the adjacent brain stem and
extending superiorly to the level of the splenium
of the corpus callosum. The lesion shows
complex heterogeneous enhancement (T1 +
Contrast) and T2 FLAIR activity in contiguous
white matter regions. Overall, the mass showed
mild interval enlargement since the most recent
surveillance scan 9 months prior.
Question 2
• Name at least 5 intracranial lesions that have
cystic changes
Answer
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Juvenile Pilocytic Astrocytoma (JPA)
Ganglioglioma
Hemangioblastoma
Pineal Cyst
Dermoid/Epidermoid Cyst
Rathke Cleft Cyst
Metastatic Lesions
Colloid Cyst
Teratoma
Question 3
• How common are CNS germ cell tumors and
what are the different histologic subtypes?
Answer
• Of all primary CNS neoplasms, CNS germ cell tumors
account for approximately 0.3-0.6% in the United States
and as high as 3% in the east Asia. They account for
approximately 3-5% of all intracranial tumors seen in
patients younger than 20 years of age.
• Types of germ cell tumors
– Pure germinoma ~ 65%
– Non-germinomatous germ cell tumors (NGGCT) ~
35%
• Teratoma (mature or immature) ~ 15%
• Mixed ~ 20%
– Choriocarcinoma, embryonal carcinoma, Yolk
sac tumor
Question 4
• Where do CNS germ cell tumors usually occur?
Answer
• The gross majority of CNS germ cell tumors
occur along the midline, most often in the pineal
and suprasellar regions (>90%), although cases
have been reported in virtually all areas of the
brain.
Question 5
• What is the demographic profile of germ cell
tumors (age and sex distribution)?
Answer
• They typically affect children and young adults
(first and second decades of life) with a the peak
incidence is from 10-19 years of age. The
exception is pure germinoma, with a peak
incidence in the 5th decade of life. There is a
clear male predominance, ranging from 75-90%
depending of the histologic subtype.
Question 6
• In what way are teratomas histopathologically
unique, and what are the three general types of
teratomas?
Answer
• Teratomas differentiate along all three embryonic germ
cell layers – endodermal, mesodermal and ectodermal.
Likewise, they recapitulate a combination of
corresponding tissues/structures from these three layers.
• Types:
– Mature (composed of fully differentiated elements)
– Immature (incompletely differentiated “fetal” elements)
– Teratoma with Malignant Transformation
Question 7
• A portion of the lesion was resected and
submitted for pathological examination. Describe
the findings. Is there anything particularly
unusual or concerning?
• Click here to view the slide
Answer
• The majority of the sample is comprised of
dense fibrous tissue admixed with regions of
necrosis. One focus shows well-differentiated
glandular epithelium with cribriforming marked
architectural tortuosity. The cells show moderate
nuclear pleomorphism with hyperchromasia,
clumped chromatin and contour irregularities.
Many of the atypical cells show cytoplasmic
vacuoles and appear to be producing mucinous
material.
• This kind of atypia is unusual for teratoma with
mature elements and is concerning for
adenocarcinoma.
Question 8
• Which stains would you order to help better
characterize the lesion?
Answer
• Cytokeratins (CK7, CK20, Pankeratin)
• Mucicarmine
• Germ cell markers (AFP, Oct-4, Glypican,
SALL4)
• Ki67 (proliferation marker)
• Click to view CK7, Mucicarmine, Ki67
Question 9
• Based on the results of the stains (see below)
and H&E slides, what is the most compatible
diagnosis?
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CK7 – strong diffuse staining of tumor cells
CK20 – negative
Mucicarmine – highlights mucin in tumor cells and glandular lumens
Ki67 – strong staining of 40-50% tumor cells overall, focally up to
80%
AFP – negative
Glypican3 – negative
Oct4 – negative
SALL4 - negative
Answer
• Mucin-producing adenocarcinoma arising
in a previously irradiated teratoma
(Carcinoma Ex Teratoma)
Question 10
• How often does malignant transformation occur
in teratomas?
Answer
• Malignant transformation in teratomas is
exceedingly rare. These typically are case
reports.
Question 11
• Would evaluation of serum markers (AFP, HCG)
have been useful in detecting this lesion earlier?
Answer
• No. While many germ cell tumors are associated
with elevated tumor marker secretion, teratomas
(and germinomas) are not. This patient had
normal serum tumor markers at the time or
resection.
References
• Louis D, Ohgaki H, Wiestler O, Cavanee W. WHO Classification of
Tumours of the Central Nervous System. IARC: Lyon 2007.
• Echevarria M, Fangusaro J, Goldman S. Pediatric Central Nervous
System Germ Cell Tumors: A Review (2008). The Oncologist.
13:690-699.
• Fujimaki T. Central Nervous System Germ Cell Tumors:
Classification, Clinical Features, and Treatment With a Historical
Overview (2009). Journal of Child Neurology. 24(11):1439-1445.
• Freilich R, Thompson S, Walker R, Rosenblum M.
Adenocarcinomatous Transformation of Intracranial Germ Cell
Tumors (1995). Am J Surg Path. 19:537-544.