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Case Reports
. 2023 May 29;12(6):772.
doi: 10.3390/pathogens12060772.

Detection of SARS-CoV-2 RNA by In Situ Hybridization in Lung-Cancer Cells Metastatic to Brain and in Adjacent Brain Parenchyma

Tibor Valyi-Nagy  1 , Brian Fredericks  1 , Jessica Wilson  2 , Sajal Deea Shukla  1   3 , Suman Setty  1 , Konstantin V Slavin  4   5 , Klara Valyi-Nagy  1
Affiliations
Case Reports

Detection of SARS-CoV-2 RNA by In Situ Hybridization in Lung-Cancer Cells Metastatic to Brain and in Adjacent Brain Parenchyma

Tibor Valyi-Nagy et al. Pathogens. .

Abstract

The mechanisms by which severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may spread to the human brain are poorly understood, and the infection of cancer cells in the brain by SARS-CoV-2 in Coronavirus disease 2019 (COVID-19) patients has been the subject of only one previous case report. Here, we report the detection of SARS-CoV-2 RNA by in situ hybridization in lung-cancer cells metastatic to the brain and adjacent brain parenchyma in a 63-year-old male patient with COVID-19. These findings suggest that metastatic tumors may transport the virus from other parts of the body to the brain or may break down the blood-brain barrier to allow for the virus to spread to the brain. These findings confirm and extend previous observations that cancer cells in the brain can become infected by SARS-CoV-2 in patients with COVID-19 and raise the possibility that SARS-CoV-2 can have a direct effect on cancer growth and outcome.

Keywords: SARS-CoV-2; brain; cancer; clinical case/report; in situ hybridization; metastatic carcinoma.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Brain axial T1 MRI with contrast, demonstrating two ring-enhancing lesions within the left-centrum semiovale with extensive adjacent edema.
Figure 2
Figure 2
(A): hematoxylin- and eosin-stained section of resected metastatic carcinoma demonstrating large and cohesive tumor cells with prominent inflammation involving both tumor and adjacent brain tissue. (B): brown staining represents immunohistochemical detection of cytokeratin 7 in metastatic carcinoma cells. Brown staining represents immunohistochemical detection of TTF-1 (C), napsin A (D), cytokeratin 5/6 (E), and p63 (F) in metastatic carcinoma cells. Magnification is 400×.
Figure 3
Figure 3
Detection of SARS-CoV-2 RNA by in situ hybridization (ISH) with the RNA Scope® detection system and probe for genomic RNA coding for the spike protein in metastatic carcinoma. (A–D) patient tissue: brown staining represents SARS-CoV-2 RNA detected by in situ hybridization in scattered metastatic cancer cells (blue arrows) and in occasional cells with morphologic features of glial cells in adjacent brain tissue (red arrows). Positive and negative control tissues represent human-lung tissues with (E) and without (F) history of SARS-CoV-2 infection. Brown staining in (E) represents SARS-CoV-2 RNA detected by in situ hybridization in cells (blue arrows). Magnification is 400×.
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