PMC9978328_01
The timeline and brain imaging over course of treatment. Enhanced computed tomography (CT) image (A) showed a right temporal lesion (orange arrow) before the first cranial surgery. The lesion was resected as shown in figure (B) (orange arrow). Magnetic resonance imaging (MRI) (T1-weighted with gadolinium enhancement) (C) demonstrated a recurrent right temporal lesion (red arrow) in situ and a right frontal tumor (yellow arrow). MR T1 contrast (D) demonstrated the resected space of the right temporal tumor (red arrow) after the second cranial surgery. CT scanning (E) indicated an extradural hematoma (red circle) one week after the second cranial surgery. Figure (F-J) represent the MR T1 contrast images 1 day, 8 days, 29 days, 56 days and 1252 days after pembrolizumab administration.
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Head computed tomography (CT) demonstrated a right temporal mass ( Figure 1A ). In October 2018, the patient underwent his first cranial surgery ( Figure 1B ). Head MRI ( Figure 1C ) demonstrated a recurrent right temporal tumor (red arrow) in situ and a newly diagnosed right frontal tumor (yellow arrow) with apoplexy. The right temporal tumor was resected, and the right frontal tumor was too risky to resect under the same bone window then left for chemo- and targeted therapy ( Figure 1D ). CT showed an extradural hematoma in the surgical field ( Figure 1E , red circle). Day1-14) were still tried to treat the right frontal tumor ( Figure 1F ) based on the advice from a neuro-oncologist. Four weeks after the first cycle of administration, the MRI ( Figure 1H ) showed that the tumor shrank nearly 80% compared to 3 weeks earlier ( Figure 1G ). Eight weeks after the treatment began, the tumor site achieved a complete response (CR) ( Figure 1I ) according to the Response Evaluation Criteria in Solid Tumors (Recist, version 1.1). D ). During the last follow-up (May 2022), the MRI indicated no abnormal signal in the surgical field and right frontal lobe ( Figure 1J ). The overall clinical course is shown in  Figure 1 .
PET-CT before first cranial surgery and after immunotherapy. PET-CT showed a right temporal lesion (orange arrow) before the first cranial surgery (A). Coronal PET-CT image (B) of the chest showed a right mediastinal metastasis (green arrow). Figure (C) showed the original tumor sites (red arrow and yellow arrow) remained stable without diseases recurrence. Coronal PET-CT image (D) of the chest indicated the tumor site (green arrow) remained stable without recurrence 16 months after mediastinal surgery.
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Positron-emission tomography-computed tomography (PET-CT) of the brain ( Figure 2A ) and chest ( Figure 2B ) showed evidence of multiple metastases.
Histologic findings of the first and second cranial surgery. Hematoxylin and eosin (HE) staining (A) and positive cytokeratin 8 (CK8) immunohistochemistry staining (B) of the tumor tissue indicated a poorly differentiated adenocarcinoma (magnification, bar=50mum). HE staining (C) of the tumor tissue demonstrated a recurrent adenocarcinoma (magnification, bar=50mum). Immunohistochemistry of PD-L1 (D) was completely negative in both immune cells and tumor cells (magnification, bar=50mum). Multiplex immunohistochemistry/immunofluorescence (mIHC/IF) assay of the second brain metastasis specimens combining CD4, CD8, CD20 and CD68 markers (E) displayed a dense tumor-infiltrating CD8+ T lymphocytes surrounding the tumor cells (magnification, bar=50mum).
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Post-operative pathological test confirmed a metastatic adenoma ( Figures 3A, B ). Hematoxylin and eosin (HE)-stained ( Figure 3C ) specimens of the brain lesion revealed a poorly differentiated adenocarcinoma. Immunohistochemical (IHC) staining ( Figure 3D ) revealed the BrM was completely negative for B7H1 (PD-L1) in both immune cells and tumor cells, as the combined positive score (CPS) and tumor cell proportion score (TPS) of PD-L1 in this patient was rated below 1 and 1% respectively.