Journal of Medical Cases, ISSN 1923-4155 print, 1923-4163 online, Open Access
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Case Report

Volume 12, Number 9, September 2021, pages 359-365


Pembrolizumab-Induced Meningoencephalitis: A Brain Autopsy Case

Figures

Figure 1.
Figure 1. Chest computed tomography imaging of the primary tumor in the left lower lobe (shown by black arrow) before the start of pembrolizumab (a), and brain magnetic resonance imaging (MRI) of metastasis in the cerebellum (shown by white arrow) in T1-weighted image with gadolinium enhancement at the first visit to our hospital in March 2018 (b).
Figure 2.
Figure 2. Chest computed tomography imaging did not show regrowth of the primary tumor in the left lower lobe (shown by black arrow) on admission (a). Brain magnetic resonance imaging (MRI) in plain T2-weighted image on the hospital day 4 did not suggest a diagnosis of encephalitis and meningitis (b).
Figure 3.
Figure 3. Medulla oblongata obtained through autopsy: infiltration of lymphocytes, plasma cells and macrophages in the meninges (Hematoxylin and Eosin stain).
Figure 4.
Figure 4. Immunohistochemistry of medulla oblongata stained by anti-CD3 (a), CD4 (b), CD8 (c) and CD20 (d) antibodies. CD: cluster of differentiation.

Tables

Table 1. Summary of Previous Brain Autopsy Cases of Encephalitis Induced by Immune Checkpoint Inhibitors
 
Authors (year)Age/sexCancerInitial symptomsICIs (course)/(response)TimingaBrain metsPNS antibodyTreatmentSymptom to deathbMain lesionLym type
aInterval from the start of ICI to symptom presentation. bInterval from symptom presentation to death. cBefore nivolumab treatment and after the onset of encephalitis. ACV: acyclovir; Ad: adenocarcinoma; CR: complete remission; F: female; ICI: immune checkpoint inhibitor; Ig: immunoglobulin; Ipi: ipilimumab; Lym: lymphocyte; LC: lung cancer; mets: metastasis; M: male; mPSL: methylprednisolone; Nivo: nivolumab; PC: pleomorphic carcinoma; PE: plasma exchange; Pem: pembrolizumab; PNS: paraneoplastic syndrome; PR: partial response; SQ: squamous cell carcinoma; CD: cluster of differentiation.
Bossart et al, 2017 [5]60/MMelanomaGeneralized tiredness, weakness, appetite lossIpi (4)→Pem (1)/(CR)6 monthsYesNot evaluatedNone> 2 wksPons, medullaCD8-positive T cells
Leitinger et al, 2018 [4]67/FLC, SQDyspnea, confusion, anxietyNivo (1)/(not described)17 daysNoNegativemPSL, Ig, ACV40 daysThalami, left central regionFew CD3-positive T cells
Matsuoka et al, 2018 [3]60/MLC, PCDaytime drowsiness, memory disturbanceNivo (2)/(PR)33 daysNoHucHigh-dose mPSL, PE6 moHippocampus, pons, spinal cords, temporal lobe, thalamus, cerebellumCD8-positive T cells, macrophage
Ours67/FLC, AdFeverPem (13)/(PR)8 monthsYesNot evaluatedmPSL pulse, ACV10 daysBrain stem, temporal lobesCD8-positive T cells

 

Table 2. Summary of Previous Cases of Non-Small Cell Lung Cancer With Encephalitis Induced by Immune Checkpoint Inhibitors
 
Authors (year)Age/sexHistologyFever symptomICIs (courses)/(response)TimingBrain metsTreatmentPNS-AbCSF proteinCSF cellsOutcome
ACV: acyclovir; Ad: adenocarcinoma; anti-TB: anti-tuberculous drugs; Atezo: atezolizumab; CR: complete remission; CSF: cerebrospinal fluid; Dex: dexamethasone; F: female; GAD65: glutamic acid decarboxylase 65-isoform antibody; Ig: immunoglobulin; Ipi: ipilimumab; Large: large cell carcinoma; Lym: lymphocyte; LymMono: lymphomonocytic cells; M: male; Mono: monocyte; mPSL: methylprednisolone; ND: not described; Neu: neutrophil; Nivo: Nivolumab; NSCLC: non-small cell lung carcinoma; PC: pleomorphic carcinoma; PD: progressive disease; PE: plasma exchange; Pem: pembrolizumab; PNS-Ab: paraneoplastic syndrome antibody; PR: partial response; SQ: squamous cell carcinoma.
Kawamura et al, 2016 [6]54/FAdNoNivo (1)/(ND)> 4 weeksNDDex, mPSL pulseNegative56 mg/dL10/µLDead
Richard et al, 2017 [7]74/MNSCLCNoNivo (1)/(ND)1 weekYesDexNDNDNDRecovered
Raskin et al, 2017 [8]58/MSQNoNivo (17)/(PR)8 - 9 monthsNoDexHu74 mg/dL63/µL (96.8% mononuclear)Recovered
Schneider et al, 2017 [9]78/FSQNoNivo (14)/(PR)28 weeksNomPSLNegative1,027 mg/LLym 16/µLRecovered
Leitinger et al, 2018 [4]67/FSQNoNivo (1)/(ND)17 daysNomPSL, Ig, ACVNegative56 mg/dLLymMono 30/μLDead
Shah et al, 2018 [10]66/FAdNoNivo (ND)/(ND)4 monthsNomPSL pulse, PENovel and unclassified56 mg/dLNormalClinically declined
44/FAdNoNivo (5)/(ND)2.5 monthsNomPSL pulse, PE, rituximabGAD65Normal19 nucleated cells/ (97% Lym)Clinically declined
Matsuoka et al, 2018 [3]60/MPCNoNivo (2)/(PR)33 daysNoHigh-dose mPSL, PEHu162 mg/dL16/µLDead
Niki et al, 2019 [11]51/MSQYesPem (ND)/(ND)8 monthsNoHigh-dose mPSLNegative446 mg/dL58/µL (Lym predominant)Recovered
Honjo et al, 2019 [12]59/MLargeYes (mild)Nivo (22)/(CR)16 monthsNomPSL pulseNegative144 mg/dL61/µL (Mono 85%)Recovered
Yonenobu et al, 2019 [13]61/MSQYesPem (2)/(ND)26 daysNomPSL pulse, anti-TB, ACVNegative209.2 mg/dL79/µL (Mono 100%)Recovered
Fujiwara et al, 2019 [14]70/MAdYes (slight)Nivo (ND)/(PR)5 monthsNoHigh-dose mPSL, anti-TB, ACVNegative166 mg/dL50/µLRecovered
Arakawa et al, 2019 [15]78/MAdYesAtezo (1)/(ND)13 daysYesmPSL pulse, ACVNegative106 mg/dL6/µLRecovered
Yamaguchi et al, 2020 [16]56/MAdYesAtezo (1)/(ND)17 daysNomPSL pulseNegative166 mg/dl20/µLRecovered
Robert et al, 2020 [17]48/FAdYesAtezo (1)/(ND)13 daysNomPSL pulseNDND62 nucleated cells/µL (Neu predominant)Recovered
57/MAdNoPem (3)/(ND)4 monthsNomPSL pulseND1.41 g/L40 nucleated cells/µL (Lym 98%)Recovered
Singh et al, 2021 [18]72/FAdYesIpi + Nivo (4)/(PD)13 weeksYesHigh-dose mPSLNegative> 180 mg/dLND (Lym predominant)Recovered
Ours67/FAdYesPem (13)/(PR)8 monthsYesmPSL pulse, ACVND317.6 mg/L197 cells/µL (Mono 93%)Dead