Transcript Case Study 19 - University of Pittsburgh

Case Study 19
Craig Horbinski, M.D., Ph.D.
Question 1
The patient is a 50-year-old white female who
was diagnosed with breast cancer in
2002. Treatment included chemotherapy,
radiation, and tamoxifen. The patient presented
to an outside hospital with mental status
changes, confusion, repeated falls, and
headaches. An MRI of the brain is shown. In
addition, multiple liver lesions were identified
that were biopsy-proven metastatic breast
carcinoma (not shown).
What do you see? What type of disease
process do you think is going on?
T1
T2
FLAIR
DWI
T1 with contrast
Answer
Bilateral cortical and subcortical T2
prolongation. These areas of T2 prolongation
contain spots of reduced T2 signal, suggestive of
hemorrhage. There is minimal signal on T1, with
no significant enhancement. DWI is not all that
bright, and the areas that are a little brighter
correspond to the reduced T2 signal, again
consistent with hemorrhagic foci. Taken together,
these findings suggest a diffuse process such as a
vasculitis or arteriopathy. Since discrete
enhancing lesions are not seen, metastatic
disease in the brain is unlikely.
Question 2
A stereotactic biopsy of the right frontal lobe is
performed. The neurosurgeon calls you down to the OR
to assess the biopsy. He wants to know the diagnosis.
What is your diagnosis? Did the neurosurgeon hit the
lesion?
Click here to view slide.
Answer
The smear shows mostly white matter—note the long axons in the
smear plus the relative lack of neurons. Compared to normal white
matter, this smear looks a little hypercellular and has some reactiveappearing astrocytes (cells with fairly abundant pink cytoplasm and
multiple processes). The blood vessels look a little reactive as
well. There are no obviously malignant-appearing cells, though, and
no obvious inflammation. Thus, it is best to defer on the neoplasm
versus non-neoplasm decision, and to simply describe it as “abnormal
white matter.” This is the sort of smear often seen in relatively
nonenhancing processes with T2 prolongation, so the neurosurgeon
probably has hit the lesion and obtained diagnostic tissue—the
precise diagnosis will just have to wait for permanent paraffinembedded sections.
Question 3
The permanent sections have arrived. What do you
see? What is your diagnosis?
Click here to view slide.
Answer
Sections show mostly white matter with multiple foci of
fibrinoid thrombi within the small blood vessels. Some of
these thrombi are composed mostly of platelets. The
white matter surrounding these thrombi is necrotic and
edematous with axonal spheroids. This is an excellent
example of thrombotic microangiopathy.
Question 4
Checking up on the patient’s lab values showed the
following:
Platelet count
Day 1: 363,000
Day 2: 355,000
Day 3: 227,000
Day 4: 187,000
Day 5: 175,000
Haptoglobin as low as <5.8 mg/dl (NL 36-195), LDH as
high as 2455 IU/L (NL 313-618).
What do these results mean?
Answer
These lab values (steadily decreasing platelet count,
increased lactate dehydrogenase, and decreased
haptoglobin), in conjunction with the neurologic
symptoms, support the diagnosis of microangiopathic
hemolytic anemia and thrombocytopenia.
Question 5
Is this pathology related to her known metastatic breast
cancer?
Answer
Yes. Malignancy-associated microangiopathic hemolytic anemia is
well-known, and is sometimes called TTP.1 However, note that
classic idiopathic TTP responds well to plasma exchange, whereas
malignancy-associated microangiopathic hemolytic anemia does
not.2
References:
1.von Bubnoff N, Sandherr M, Schneller F, Peschel C. Thrombotic
thrombocytopenic purpura in metastatic carcinoma of the breast. Am
J Clin Oncol. 2000 Feb; 23(1):74-7.
2.Francis KK, Kalyanam N, Terrell DR, Vesely SK, George JN.
Disseminated malignancy misdiagnosed as thrombotic
thrombocytopenic purpura: A report of 10 patients and a systematic
review of published cases. Oncologist. 2007 Jan; 12(1):11-9.