JC virus granule cell neuronopathy in progressive multifocal leukoencephalopathy

Types of demyelinating lesions in the cerebellar white matter (WM) and focal cell loss of granule cell neurons (GCNs) in the GC layer (GCL) of patients with progressive multifocal leukoencephalopathy. (A, C, E, G) Double immunohistochemistry (IHC) for myelin and oligodendrocytes (CNPase, brown) and JC virus (JCV) VP1 capsid (PAB597, dark blue), displayed in 25,000,000 pixel pictures of 1 cm² representative portions of cerebellum, shows areas of demyelination and JCV-infected cells (dark blue, marked by arrows in all insets). (B, D, F, H) Double IHC for neurons (NeuN, brown) and JCV VP1 capsid (PAB597, dark blue). (A) Type I, an isolated JCV infected cell is present in the GCL (arrow, inset) in the absence of a PML lesion in the cerebellar WM. This cell is not visible in the adjacent section (B), which shows an intact GCL. (C) Type II, a small demyelinating lesion at the GCL/WM junction contains JCV-infected cells at the periphery (arrows, inset). (D) The JCV-infected cells are detected in a preserved GCL in the same area. (E) Type III, numerous confluent demyelinating lesions penetrating the GCL harbor JCV-infected cells (arrows, inset), whereas rare JCV-infected cells (arrows, inset) are present in the GCL, which has no to limited focal GCN loss (F). (G) Type IV, a cavitated PML lesion shows almost complete disappearance of myelin and oligodendrocytes in both the folia and the GCL. Almost all JCV-infected cells disappeared and only rare apoptotic JCV-infected cells or debris of JCV-infected cells (arrows, inset) are still present at the border of the demyelinated areas. These cells and debris are not visible in the inset of the adjacent section (H), which shows some areas of focal GCN loss (arrowheads, inset).