{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T08:46:54Z","timestamp":1785833214770,"version":"3.56.0"},"reference-count":42,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T00:00:00Z","timestamp":1731283200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23K06447"],"award-info":[{"award-number":["23K06447"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pathology International"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by JC virus (JCV) infection. Although recognized as an AIDS complication in the 1980s, PML has emerged as a serious adverse event of immunosuppressive therapies since 2005, particularly disease\u2010modifying drugs (DMDs) for multiple sclerosis (MS). PML can also occur in patients with collagenous diseases receiving steroid therapy or with age\u2010related immunosuppression. In some cases, the etiology of immunosuppression remains unclear. These cases often present with early manifestations of PML, which, while common, are less well recognized, as PML was identified at more advanced stages in AIDS\u2010related cases. Early diagnosis poses difficulty due to unfamiliar magnetic resonance (MR) images and low viral loads in cerebrospinal fluid (CSF), and brain biopsy may be conducted. This review summarizes the PML pathology identified through biopsy. Early cytopathological changes of JCV\u2010infected cells, with the importance of dot\u2010shaped inclusions associated with promyelocytic leukemia nuclear bodies (PML\u2010NBs), are described. The variability of host immune responses, including PML immune reconstitution inflammatory syndrome (PML\u2010IRIS), is addressed. The potential role of immune checkpoint inhibitors (ICIs), such as pembrolizumab, is also explored. Understanding the pathology of early PML helps to optimize diagnostic strategies and therapeutic interventions, ultimately improving prognosis.<\/jats:p>","DOI":"10.1111\/pin.13492","type":"journal-article","created":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T12:39:27Z","timestamp":1731328767000},"page":"673-681","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Brain biopsy and pathological diagnosis for drug\u2010associated progressive multifocal leukoencephalopathy (PML) with inflammatory reactions"],"prefix":"10.1111","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4138-1669","authenticated-orcid":false,"given":"Yukiko","family":"Shishido\u2010Hara","sequence":"first","affiliation":[{"name":"Department of Pathology and Applied Neurobiology Kyoto Prefectural University of Medicine Kyoto 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