Case Study 26
Craig Horbinski, M.D., Ph.D.
Question 1
The patient is a 79-year-old female with expressive
aphasia for the past three to four days. Past medical
history included hypertension, glaucoma, status post
CABG and status post cholecystectomy. MRI was
done.
Describe the scans.
Answer
MRI: Enhancing mass in the left frontal lobe with central
necrosis, midline shift, and extensive surrounding edema.
Question 2
What is your differential at this time?
Answer
1. High grade glioma
2. Metastatic disease
3. Lymphoma
4. Bacterial abscess
Question 3
During surgery, the neurosurgeon asks you to look at
some tissue he’s taken from the site. You do a couple of
touch preparations on some grossly abnormal
tissue. What do you tell him?
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Answer
 This is neoplastic. There is hypercellularity with
clumpy chromatin, some vacuoles in the relatively
abundant cytoplasm, and necrosis (the granular,
grimy stuff). The tumor cells are broad, epithelioid,
and seem to mostly stick together, although some
are isolated. A few lymphocytes and foamy
macrophages are scattered around.
 An adenocarcinoma is a possibility since the cells
have an epithelioid appearance and show some
vacuoles.
Question 4
The permanent section arrives the next day. Describe
what you see.
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Answer
Sections show an epithelioid tumor consisting of
large round cells with well-demarcated cell
borders. Some cells have prominent nucleoli, and
most have clumpy chromatin. A minor
fasciculating spindle cell population is also
present. There is patchy necrosis, scattered
mitoses, thrombosed vessels, and endothelial
proliferation. The tumor has a pushing border with
adjacent brain which is gliotic and has a modest
inflammatory reaction.
Question 5
What is your differential now? Any immunostains you’d
like to order to prove your suspicion (Hint: the answer is
YES).
Answer
This is definitely a high-grade neoplasm that looks epithelioid and is highly
necrotic. The differential here is glioma versus metastatic carcinoma
(unknown primary) versus metastatic melanoma (primary site is often missed
clinically).
Immunostains to resolve this include:
1.GFAP—positive in gliomas, negative in carcinoma and melanoma
2.Cytokeratins 7/20 or CAM5.2*—positive in carcinomas, negative in gliomas
and melanomas
3.S100—positive in gliomas and melanoma, negative in carcinoma
4.HMB45—positive in melanoma, negative in glioma and carcinoma
5.Vimentin—positive in all three, just a control to make sure the tissue is of
decent quality for immunostaining
*Of note, pankeratin is a bad choice for a carcinoma marker, because the
antibody mixture cross-reacts with glial filament proteins and makes gliomas
seem positive. Cytokeratin AE1/3 used to be a good antibody to avoid this
problem, but recently for some reason it too has false-positive staining in
gliomas.
Question 6
Some immunostains arrive. S100 is shown. HMB45 and
cytokeratins are negative (not shown). GFAP stain failed;
the immunohistochemistry lab will send another stain
tomorrow. How do you interpret these findings? What is
your diagnosis? Are you ready to sign out the case?
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Answer
If you’re thinking melanoma, reasoning that HMB45 can
sometimes be negative in melanomas, think again. S100
is positive in glial cells, too. Best to wait for the GFAP
stain to come out.
Question 7
The GFAP stain finally arrives. What is your diagnosis
NOW?
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Answer
Glioblastoma. This is a classic case of a glioblastoma
mimicking an epithelioid neoplasm, either a carcinoma or
melanoma. Cases like this are why the original name for
this glial tumor was “glioblastoma multiforme,” and why
it’s best to wait for all the immunostains to arrive before
signing the case out. If you were thinking it was some sort
of metastatic carcinoma during the intraoperative phase of
the case, don’t feel too bad—the neuropath attending on
the case made that same diagnostic mistake. Just goes to
show you’re never too good to be fooled…