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Case Study 19

This case study explores the diagnostic process and treatment of a 50-year-old female with metastatic breast cancer, presenting with mental status changes and neurological symptoms. The study includes imaging findings, biopsy results, and laboratory values.

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Case Study 19

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  1. Case Study 19 Craig Horbinski, M.D., Ph.D.

  2. 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?

  3. T1

  4. T2

  5. FLAIR

  6. DWI

  7. T1 with contrast

  8. 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.

  9. 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.

  10. 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 reactive-appearing 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 paraffin-embedded sections.

  11. Question 3 The permanent sections have arrived.  What do you see?  What is your diagnosis? Click here to view slide.

  12. 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.

  13. Question 4 Checking up on the patient’s lab values showed the following:Platelet countDay 1: 363,000Day 2: 355,000Day 3: 227,000Day 4: 187,000Day 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?

  14. 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.

  15. Question 5 Is this pathology related to her known metastatic breast cancer?

  16. 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: • 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. • 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.

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