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Updated: Jul 24, 2025
Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
Published on: February 8, 2018
Pathology for severe inflammatory PML with PD1/PD-L1 expression of favorable prognosis: What's a prognostic factor
Yukiko Shishido-Hara1,2, Jiro Akimoto3, Shinjiro Fukami3
1Department of Anatomic Pathology, Tokyo Medical University, Tokyo, Japan.
Abstract:
A 72-year-old woman with dermatomyositis (DM) developed neurological manifestation, and magnetic resonance imaging (MRI) revealed multiple T2/fluid-attenuated inversion recovery (FLAIR)-hyperintense lesions predominantly in the deep white matter of the cerebral hemisphere. Punctate or linear contrast enhancement was observed surrounding the T1-hypointense area. Multiple T2/FLAIR-hyperintense lesions were aligned along with the corona radiata. Malignant lymphoma was first suspected, and a brain biopsy was performed. Pathological investigation suggested the provisional diagnosis of "suspicious of malignant lymphoma." Owing to emergent clinical conditions, high-dose methotrexate (MTX) therapy was conducted, and then T2/FLAIR-hyperintense lesions were dramatically reduced. However, the diagnosis of malignant lymphoma was concerning since multiplex PCR demonstrated clonal restriction of the Ig H gene for B cells and TCR beta genes for T cells. Histopathology revealed the infiltration of both CD4+ and CD8+ T cells, and the CD4+ /CD8+ ratio was 4.0. Moreover, prominent plasma cells were observed, in addition to CD20+ B cells. Atypical cells with enlarged nuclei were present, and they were not hematopoietic but found as glial cells. JC virus (JCV) infection was verified with both immunohistochemistry and in situ hybridization; the final diagnosis was progressive multifocal leukoencephalopathy (PML). The patient was treated with mefloquine and discharged. This case is informative in understanding the host anti-viral response. Variable inflammatory cells were observed, including CD4+ and CD8+ T cells, plasma cells, and a small amount of perivascular CD20+ B cells. PD-1 and PD-L1 expression was observed in lymphoid cells and macrophages, respectively. PML with inflammatory reactions was thought fatal, and autopsy cases of PML with immune reconstitution inflammatory syndrome (IRIS) demonstrated excessive infiltration of only CD8+ T cells. However, this case revealed infiltration of variable inflammatory cells, and a favorable prognosis would be expected under PD-1/PD-L1 immune-checkpoint regulation.
Insights
This case study details a rare instance of progressive multifocal leukoencephalopathy (PML) in a dermatomyositis patient, initially misdiagnosed as lymphoma. The study highlights the importance of accurate diagnosis and understanding the host
Area of Science:
- Neurology and Infectious Diseases: Focuses on neurological complications of autoimmune diseases and viral infections of the central nervous system.
Background:
- Dermatomyositis (DM) can present with neurological manifestations, posing diagnostic challenges.
- Distinguishing between demyelinating lesions, infections, and primary CNS malignancies is critical.
Observation:
- A 72-year-old woman with DM developed white matter lesions on MRI, initially suspected as malignant lymphoma.
- High-dose methotrexate (MTX) therapy led to lesion reduction, but further investigation revealed JC virus (JCV) infection.
- Histopathology showed a mixed inflammatory infiltrate, including CD4+ and CD8+ T cells, plasma cells, and B cells.
Findings:
- The final diagnosis was progressive multifocal leukoencephalopathy (PML), a rare JC virus complication.
- Multiplex PCR initially suggested lymphoma due to clonal gene restriction, complicating the diagnosis.
- The case exhibited a unique inflammatory response with variable immune cell infiltration and PD-1/PD-L1 expression.
Implications:
- This case underscores the need for comprehensive diagnostic workup in immunocompromised patients with neurological symptoms.
- Understanding the host's anti-viral immune response, including inflammatory cell profiles and immune checkpoint regulation (PD-1/PD-L1), is crucial for prognosis.
- The observed inflammatory pattern suggests a potentially favorable prognosis in PML under immune-checkpoint modulation.
