PMC6743439_01
Three significant time points of brain disease. (A-C) Left cerebellar metastasis prior to brain surgery (January 2015). (D-F) Leptomeningeal metastasic disease, predominantly left cerebral hemisphere (September 2015). (G-I) Complete brain response with no evidence of leptomeningeal involvement after 3 months of nivolumab treatment (December 2015).
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F1
CT control scan showed at least seven pulmonary nodules affecting the upper and lower right lobes (see Figure 1); in the multidisciplinary committee, surgery was rejected because of multilobar contralateral disease.
Follow-up of right lung disease before and after immunotherapy. (a) Pulmonary right nodule, suggesting contralateral lung disease. (b) Complete lung response during nivolumab treatment.
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F2
Afterwards, brain MRI confirmed our suspicions, detailing leptomeningeal enhancement adjacent to the left cerebellar hemisphere in the surgical area, as well as to the front area of the right cerebellar hemisphere, and also supratentorial involvement adjacent to left tentorium, with associated perilesional moderated edema (see Figure 2).
Tissue specimen of primary tumor sample and brain metastases. (a) Immunohistochemistry stained with PD-L1 primary antibody (28-8 pharmaDx; Dako) in a pretreated formalinfixed paraffin-embedded tissue of primary lung tumor before treatment, exhibiting strong membrane staining in 100% of tumor cells (20x magnification). (b) Cerebellar tissue specimen after complete resection.
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F3
Surprisingly, high expression PD-L1 level was found in both lung and brain sample: tumor cells stained with PD-L1 primary antibody (28-8 pharmaDx; Dako) showed strong membrane staining in 100% of tumor cells (see Figure 3).
Timeline of events since the diagnosis and summary of administered treatments.
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F4
At the time of submission of this manuscript, the patient maintains excellent performance status with no neurological or pulmonary symptoms, either secondary adverse events related to nivolumab, and continues showing complete response in image tests including brain MRIs and CT body scans (see Figure 4).