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This medical case study discusses the MRI findings of a 46-year-old male with mental status change and right-sided hemiparesis. The case covers differential diagnosis, cytologic features, intraoperative diagnosis, microscopic description, and recommended stains.
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Case Study 16 Gabrielle Yeaney, M.D.
Question 1 46-year-old male with mental status change and right-sided hemiparesis. Describe the MRI findings (location, enhancement, mass effect).
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 • Defer • 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? • Make sure you have enough tissue for diagnosis • Ask the surgeon if s/he has sent sterile tissue for culture • Get 5-cc’s of the patient’s blood in a purple top tube for possible future studies • All of the above
Answer The correct answer is: • 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.
