Case 1 - A seventy-year-old woman diagnosed with Common Variable Immunodeficiency since 2013 has developed global progressive cerebellar syndrome. After a broad investigation, she showed a positive PCR for JCV on cerebrospinal fluid (CSF). A brain MRI revealed diffuse cerebellar atrophy. Case 2 - A forty two-year-old male diagnosed with HIV, presenting undetectable viral load and CD4 = 532 cells/mm³ developed a rapidly progressive global cerebellar syndrome. Brain MRI showed diffuse cerebellar atrophy with "hot-cross bun" sign at the level of the pons. By immunohistochemistry from cerebellar biopsy, it revealed classic cytopathic alterations by JCV. Case 3 - A forty one-year-old female, undergoing radiotherapy treatment associated to chemotherapy with temozolamide due to Glioblastoma Multiforme (GBM) presented with seizures, ataxia and behavioral changes, showing multiple cortical and subcortical lesions on MRI and positive PCR for JCV in CSF sample. Immunohistochemistry from biopsied lesions confirmed JCV-related cytopathic changes.

Two cases of JC Virus Granule Cell Neuronopathy were described, a patient with Common Variable Immunodeficiency and another one with HIV but undetectable viral load and proper CD4, as well as a GBM patient under chemoradiotherapy with progressive and atypical PML pattern secondary to JCV infection. In order to reduce misdiagnosis, a high index of suspicion should be maintained concerning the spectrum of JCV infection’s syndromes, mainly in immunocompromised patients. Therefore, due to the possible false-negative JCV-PCR results, biopsy may benefit atypical clinical courses in this context.