Transcript Case Study 16 - University of Pittsburgh

Case Study 16
Gabrielle Yeaney, M.D.
Question 1
46-year-old male with mental status change and rightsided hemiparesis.
Describe the MRI findings (location, enhancement,
mass effect).
Axial T1 pre and post contrast
Axial T2/ FLAIR/ T1 post-contrast
Answer
There are patchy areas of T2 prolongation and
enhancement in the left frontoparietal subcortical white
matter. No mass-effect is identified. No midline shift is
seen.
Question 2
Give a differential diagnosis based on MRI/ age.
Answer
 Lymphoma
 PML
 Atypical infection
 Glioma
 Imaging features are not consistent with
toxoplasmosis or pyogenic abscess (ring-enhancing
lesion).
Question 3
Describe the cytologic features of the smear.
Click here to view slide.
Answer
The smear shows hypercellular glial tissue with a
polymorphic population of cells. Some have
small round nuclei (lymphocytes) and others have
elongated atypical nuclei and scant cytoplasm
(microglia/ astrocytes?). Another population of
cells shows large round nuclei and prominent
nucleoli abundant eosinophilic cytoplasm with
processes (reactive astrocytes). Cells with
eccentric nuclei and foamy cytoplasm are present
(macrophages).
Question 4
What additional history might be ascertained from the
surgeon?
Answer
You should inquire about clinical signs of infection. Is this
patient immunosuppressed, febrile, HIV-positive? Was
CSF culture/ PCR done?
Question 5
The surgeon tells you that this patient has a known
diagnosis of HIV with a CD4 count of 64. Stereotactic
biopsies of the left cerebral white matter are given to you
on saline moistened Telfa. You perform a smear the tissue
on a glass slide. What is your intraoperative diagnosis? (A.
Neoplastic / Defer / Non-neoplastic, B. ______)
Click here to view slide.
Answer
A. Defer
B. Lesional tissue or Gliotic tissue with chronic
inflammation—Most importantly the surgeon
needs to know if the tissue is consistent with
the radiologic findings. You might favor a
reactive/ infectious/ demyelinating process but
lymphoma or even glioma (with reactive
background) are still possibilities. Infarct is
less likely given the location/ imaging findings.
Question 6
The surgeon thanks you for your assessment and
indicates that s/he is about to close. At this point,
before leaving the OR/ frozen room, what should
you do?
A.Make sure you have enough tissue for
diagnosis
B.Ask the surgeon if s/he has sent sterile tissue
for culture
C.Get 5-cc’s of the patient’s blood in a purple top
tube for possible future studies
D.All of the above
Answer
The correct answer is:
D. All of the above.
When you make your smear, do a quick gross evaluation of the tissue
(color, size, texture) and then select a small portion from each end of
the core biopsy or from areas with different gross appearance. After
evaluating the cytology of the smear, go back to the gross
specimen: Is the diagnostic area on the smear represented on the
remaining tissue? Do you have more than 1 core with diagnostic
material? If your answer is no to either question, ASK for more
tissue! The surgeon should obtain fresh tissue for microbiology in the
OR under sterile conditions. Once you open the container in the
frozen section/ gross room, consider it contaminated. In this case,
glioma may be in your differential, so it wouldn’t hurt to get a 5-cc
purple top just in case you need it for LOH studies—but it’s less
important than A and B.
Question 7
Review the H&E paraffin section and give a microscopic
description.
Click here to view slide.
Answer
The biopsies show hypercellular white matter with
large reactive astrocytes in an inflammatory
background. Some nuclei show smudged
chromatin suggestive of viral effect. A diffuse
chronic inflammatory infiltrate is present
consisting of lymphocytes, plasma cells and
macrophages/ activated microglia. There are
occasional Creutzfeldt cells. A few mitotic figures
are seen. Vessels show reactive endothelium.
Question 8
What stains do you want to order?
Answer
The most important study would be in situ hybridization
for JC virus. Since this is an immunosuppressed patient,
stains to look for other opportunistic infections, like
toxoplasma, should be done even though the MRI in
inconsistent and no tachy/bradyzoites are seen on
H&E. Other reasonable studies include: IHC for HSV/
CMV, gram stain, Grocott and AFB although acute
inflammation and granulomatous inflammation are
absent. Luxol fast blue would show lytic effect on
myelin. Lymphoma is less likely given the lack of large
atypical lymphs and abundant plasma cells but CD20
could help you there.
Question 9
You receive the following immunohistochemical
study. What is you interpretation?
Click here to view slide.
Answer
In-situ hybridization studies for JC virus show several
cells with nuclear reactivity. FYI: Immunohistochemical
studies for Toxoplasma were negative.
Question 10
What is your final diagnosis?
Answer
Progressive multifocal leukoencephalopathy (PML)—a
demyelinating opportunistic infection of the CNS caused
by the JC papova virus.
Question 11
What cell of the central nervous system is infected in this
disease?
Answer
The oligodendrocyte shows the cytopathic effect in PML.
Question 12
You aren’t sure if the lesion is neoplastic or
inflammatory/infectious so you get an immunostain for
p53. The p53 stain is positive. Does this result help you
to “rule in” astrocytoma in this case?
Answer
No—Infected oligodendrocytes and reactive astrocytes
are often strongly positive for p53 (and MIB-1) in PML.