Case Study 25
Craig Horbinski, M.D., Ph.D.
Question 1
The patient is a 56 year-old male presenting with
altered mental status. It seems the patient was well
until 2 months ago when he developed a facial droop
and left sided weakness. He did not see a physician at
that time, and was only brought in at his family’s
insistence. He reports he does feel confused but
cannot elaborate any more. He denies headache, neck
pain, or photophobia.
The patient’s past medical history is significant for HIV
(diagnosed in 1998), no CD4 count or viral load since
2005, not on antiviral therapy.
Radiologic scans of his brain are done. Describe the
scans.
Answer
 CT: Large abnormality centered in the left basal ganglia
region, which is causing midline shift to the right, mass
effect on the left lateral ventricle, and contiguous edema
in the left midbrain.
 MRI: Irregular enhancing lesion in the left basal ganglia
with a central necrotic area, midline shift, and extensive
surrounding edema.
Question 2
What is your differential at this time? What would your
differential be if the patient was not
immunocompromised?
Answer
This is a patient with untreated HIV (likely AIDS) who has AMS
(altered mental status) and a ring-enhancing intracerebral
mass. The differential in this case favors an infectious etiology,
but beware—primary EBV-driven CNS lymphomas are quite
common in AIDS patients and also show ring enhancement
with mass effect and edema.
1.Toxoplasmosis
2.Lymphoma
3.Aspergilloma
4.Candidiasis
5.Tuberculosis (especially MAC)
6.Bacterial abscess
7.Cryptococcus (though usually presents as a meningitis, not a
brain mass)
8.JC/PML (typically white matter and multifocal, but good to
keep in mind)
9.High grade glioma
Question 3
While the patient is being stabilized for surgery, his CD4
and viral load count arrive.
Take a guess at what his labs will show. How might this
influence your differential?
Answer
His CD4 count is 4 cells/mm3 and his viral load is 21,000
copies/ml. Using the CDC definition, a CD4 count below
200 in a patient with known HIV positivity has AIDS. This
means that his brain lesion is probably one of the AIDSdefining illnesses.
Question 4
To confirm the brain mass etiology, a stereotactic biopsy
was performed. The neurosurgeon asks you if he’s hit the
lesion, and what the diagnosis is. Describe the
intraoperative smear. What is your diagnosis? (Look
VERY carefully—the full diagnosis is there, even on a
digital slide!)
Click here to view slide.
Answer
The smear is definitely abnormal hypercellular brain tissue. It’s
grey matter since there are a few neurons with big nuclei and
prominent nucleoli, but there are also many large, reactive
astrocytes with big nucleoli, too. (You can tell them apart from
the neurons because the reactive astrocytes have denser pink
cytoplasm with a bunch of thick processes, while the neuronal
nuclei often have the illusion of being “naked,” i.e. no clearlydefined dense cytoplasm surrounding them.) A mononuclearpredominant inflammation is present, especially around blood
vessels.
The key here is to recognize the scattered small dark purple
specks floating around the smear as tachyzoites, plus the
occasional larger cysts (8-10 µm) containing basophilic
bradyzoites. Thus, the patient has toxoplasmosis. The
permanent sections in this case are a mere formality.
Question 5
The next day you receive a permanent section of the
biopsy. Describe what you see. Does it correlate with the
intraoperative smear?
Click here to view slide.
Answer
The brain tissue is gliotic with an intense infiltrate of
lymphocytes and plasma cells, especially
perivascular. Intracellular parasitophagous vacuoles
containing cysts with bradyzoites are present, as are
extracellular tachyzoites. The latter are sometime hard to
distinguish from cellular debris. These findings correlate
perfectly with the intraoperative smear.
Incidentally, even if you weren’t told the location of the
biopsy, you can tell that the brain tissue is from the
striatum from the short streaks of denser pink white
matter scattered in between the larger areas of looser
neuropil.
Question 6
What additional test can you order on this tissue that will
absolutely confirm the diagnosis, even though we all know
what the result will be?
Answer
A Toxoplasma gondii immunostain
Question 7
The Toxoplasma gondii immunostain arrives. Is it
positive? Where is the positivity?
Click here to view slide.
Answer
It’s as positive a Toxo stain as you’ll ever see, highlighting
the intracellular bradyzoite-containing cysts as well as the
free-ranging tachyzoites. Some tachyzoites appear to be
intracellular—in keeping with their status as obligate
intracellular parasites, they cannot reproduce outside a
nucleated cell.
The following slides are questions you need to be able to
answer for your board exams (regardless of your specialty).
Question 8
What is the reservoir of T. gondii? How is it usually
acquired, and in what tissue(s) does it normally reside?
Answer
Cats are the definitive host. The protozoan is
usually contracted by ingesting oocytes in cat
feces, through contaminated drinking water, or
most commonly through eating poorly cooked
pork or beef containing tissue cysts. Once
ingested, the parasite crosses the gut wall and
enters the circulation, usually settling down in
skeletal muscle, eye, brain, and/or heart. An
effective immune response eventually kills most
or all of the parasites.
Question 9
What is the seroprevalence of T. gondii in the Unites
States?
Answer
The seroprevalence of T. gondii antibodies in the U.S. is
between 25-40%, meaning that roughly a third of all
people have been exposed to the protozoan. Most cases
are asymptomatic and never recur.
Question 10
Can a latent/resolved Toxoplasmosis infection in a
previously seropositive mother result in congenital
toxoplasmosis in her baby?
Answer
Probably not. Most believe that only a primary Toxo
infection in a previously non-seropositive pregnant woman
can cause congenital toxoplasmosis, and even then the
risk to the fetus depends on which trimester the maternal
infection takes place (see next question).
Question 11
In utero, what is/are the most likely trimester(s) for
contracting congenital toxoplasmosis? In what
trimester(s) is/are the sequelae most severe?
Answer
In utero, the highest risk of infection is late in the
third trimester, but in this trimester the sequelae
are also less severe, sometimes only with mild
chorioretinitis and a few brain
calcifications. Sometimes such cases are so mild
they never produce any problems and are never
detected. The first trimester has the lowest risk of
infection but also the most severe sequelae,
including catastrophic encephalomalacia,
hydrocephalus, prominent intraparenchymal
calcifications, and destructive retinitis (remember
the TORCH set of diseases).