Pontocerebellar Progressive Multifocal Leukoencephalopathy. Radiological, Clinical, Histological and Immunohistochemical Findings in a Hematological Patient

Abstract

Objective: To describe the radiological, histological and immunohistochemical findings in a case of Progressive Multifocal Leukoencephalopathy (PML) affecting the cerebellar peduncles in a patient with chronic lymphocytic leukemia. Patient and Methods: Magnetic Resonance Imaging (MRI), histological picture (H.E., Kluver-Barrera) and immunohistochemical picture (GFAP, neurofilaments, CD68, JC virus) were obtained. Results: 1) Magnetic resonance imaging: Asymmetric and progressive lesions on middle cerebellar peduncles, that were hyperintense in T2/FLAIR, extended towards the pons, had no mass effect and were unmodified after intravenous contrast. 2) Histology: Marked reactive gliosis with cytopathic changes suggesting viral infection, plus demyelination areas with axonal preservation. 3) Immunohistochemistry: Marked positivity for viral (polyoma and JC virus) markers in glial cells showing cytopathic changes. Conclusions: The importance of histological and immunohistochemical diagnosis in everyday assistance; of the collaboration between clinicians, radiologists and pathologists; and the validity of postmortem studies as a key element for research and clinical quality assessment must be stressed.

John Cunningham Virus and Progressive Multifocal Leukoencephalopathy: A Falsely Played Diagnosis

“…In fact, PML-IRIS lesion neuroimaging demonstrates contrast enhancement, mass effect, and interstitial edema [32]. But even in cases of hematological malignancies, these findings may differ across possible other prior medical conditions and the drugs that may be used to treat them [38][39][40].…”

“…Thus, although PML was thought to be a non-inflammatory illness that specifically targeted astrocytes and oligodendrocytes in the white matter of people in immunosuppressive states, it can manifest during an immune reconstitution immune system infection (IRIS) that affects a range of phenotypes, from those with mild-to-moderate immunosuppression to those who are completely immunocompromised or on immunomodulation medication. Glial cells thought to be JCPyV-infected are often found at the gray matter-white matter junction or directly into the gray matter, where they cause demyelination in cortical and subcortical regions [38,42]. Additionally, it has been said that may the virus infect neurons, thus resulting into both JCPyV granule cell neuronopathy or/and JCPyV encephalopathy [42].…”

“…Concerning CSF, apart from the viral DNA, in HIV-infected PML patients, pleocytosis was not common but increased protein levels could be possible in almost half of the patients, yet abnormal decreases in glycose level may not be observed [88]. For the IRIS-PML cases, a study reported that the total leukocyte count median was 1 cell/mm 3 (0-2), while the median glucose and protein levels were 61 mg/dL (50-69) and 36 mg/dL (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41), respectively [89]. A study on CSF analysis in 108 patients with PML demonstrated that compared to the routine CSF parameters, 22% had an elevated cell count and 35% showed an increased Qalbumin indicating a disturbed blood-CSF-barrier; the mean lactate content was 1.64 mmol/L, whereby 6% presented with elevated lactate levels; PML patients showed an increased cell count-mainly driven by HIV-PML cases, among whom a significantly higher proportion had a disturbed blood-CSF-barrier function [99].…”