Miliary brain metastases from lung adenocarcinoma with EGFR (L858R) and CTNNB1 mutations

Abstract

A 76‐year‐old man was referred to our hospital with a cough. Chest computed tomography (CT) revealed a 45‐mm mass in the lingular segment of the left upper lobe. Transbronchial tumor biopsies showed adenocarcinoma. Contrast‐enhanced CT and bone scintigraphy revealed lung, pleura, and bone metastases. The patient was diagnosed with left upper lobe adenocarcinoma cT2bN3M1c stage IVB. A genetic analysis of the primary tumor using the Oncomine Dx Target Test Multi‐CDx system revealed positivity for epidermal growth factor receptor (EGFR) (L858R) and CTNNB1 mutations. Based on these findings, the patient was treated with osimertinib (80 mg/day) as first‐line therapy. Six months later, the tumor increased in size, indicating progressive disease. Osimertinib was stopped and second‐line therapy with carboplatin (area under the curve 5) and pemetrexed (500 mg/m2) was initiated. After three cycles of chemotherapy, the patient developed dementia and disorientation. Contrast‐enhanced magnetic resonance imaging of the head showed miliary brain metastases. Miliary dissemination is a rare form of brain metastasis. Miliary patterns of lung metastases have been strongly associated with the EGFR exon 19 deletion. The radiological features of miliary brain metastases of non‐small cell lung cancer with the exon 19 deletion have been reported. To the best of our knowledge, this is the first case report of lung cancer with miliary brain metastases and co‐mutations of EGFR (L858R) and CTNNB1. In conclusion, co‐mutations of EGFR (L858R) and CTNNB1 and the discontinuation of EGFR‐tyrosine kinase inhibitor may contribute to the development of miliary brain metastases. Further case studies are warranted.

T1‐weighted Gd‐enhanced magnetic resonance images showed a significant number of small nodules in the brain. This report is the first case report of lung cancer with miliary brain metastases and co‐mutations of EGFR (L858R) and CTNNB1. Co‐mutations of EGFR (L858R) and CTNNB1 and the discontinuation of EGFR‐TKI may contribute to the development of miliary brain metastases.

A 76‐year‐old man was referred to our hospital with a cough. Chest computed tomography (CT) revealed a 45‐mm mass in the left upper lobe. Transbronchial tumor biopsies showed adenocarcinoma. CT and bone scintigraphy revealed lung, pleura, and bone metastases. The patient was diagnosed with left upper lobe adenocarcinoma cT2bN3M1c stage IVB. A genetic analysis of the primary tumor using the Oncomine Dx Target Test Multi‐CDx system revealed positivity for epidermal growth factor receptor (EGFR) (L858R) and CTNNB1 mutations. Based on these findings, the patient was treated with osimertinib (80 mg/day) as first‐line therapy. He achieved clinical improvement and a partial response. Six months later, the tumor increased in size, indicating progressive disease. Osimertinib was stopped, and second‐line therapy with carboplatin (area under the curve 5) and pemetrexed (500 mg/m²) was initiated. After three cycles of chemotherapy, the patient developed dementia and disorientation. Contrast‐enhanced magnetic resonance imaging of the head showed miliary brain metastases (Figure 1). The patient was treated with whole brain irradiation; however, his symptoms rapidly progressed and he was transferred to palliative care. Miliary dissemination is a rare form of brain metastasis which is characterized by perivascularly distributed diffuse miliary nodules not accompanied by intraparenchymal invasion. In 1951, Meadow and Alpers described the first case of cancerous encephalitis, now called “miliary brain metastasis”. ¹ Lung cancer is the most common source of miliary brain metastases, and the histological type in the majority of cases is adenocarcinoma. ² Miliary patterns of lung metastases have been strongly associated with the EGFR exon 19 deletion. To the best of our knowledge, this is the first case report of lung cancer with miliary brain metastases and co‐mutations of EGFR (L858R) and CTNNB1. CTNNB1 mutations are an important contributory factor to EGFR‐tyrosine kinase inhibitor (TKI) resistance. ³ They have also been implicated in the development of a non‐inflamed tumor microenvironment. ⁴ In patients with EGFR‐mutant lung cancer, the discontinuation of EGFR‐TKI is associated with a clinically significant risk of disease flare. ⁵ In conclusion, co‐mutations of EGFR (L858R) and CTNNB1 and the discontinuation of EGFR‐TKI may contribute to the development of miliary brain metastases.

FIGURE 1.

Magnetic resonance imaging (MRI) findings. T1‐weighted gadolinium‐enhanced images showing a significant number of small nodules in the brain.

CONFLICT OF INTEREST STATEMENT

The authors declare no conflict of interest.

Kunishige M, Takeuchi E. Miliary brain metastases from lung adenocarcinoma with EGFR (L858R) and CTNNB1 mutations. Thorac Cancer. 2023;14(34):3419–3420. 10.1111/1759-7714.15144