PMC9676932_01
(A) PET scan at baseline showing the presence of lesions at the lung and the and mediastinal lymph nodes; (B) Magnetic brain resonance at baseline showing the presence of multiple brain metastases.
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A 45-year-old non-smoking female patient received a diagnosis of stage IV lung adenocarcinoma on March 2021 with pleural, bilateral lung lesions and the involvement of mediastinal lymph nodes, the sternum and the right pubic symphysis ( Figure 1A ). T6-T7 up to T9-T10, and dural enhancement anteriorly to the spinal cord of T8. The brain MR showed at least 12 lesions at sub and supratentorial sites ( Figure 1B ). To obtain a diagnosis, the patient underwent video-assisted thoracoscopic surgery with the identification of multiple alterations in the parietal, diaphragmatic, mediastinal, and visceral pleura.
(A) Hematoxylin and eosin staining of acinar and solid adenocarcinoma grade 2 of the lung; (B, C) Interphase dual color break apart FISH using a NTRK3 probe (B) and a EML4 probe (C) displayed one normal orange/green fusion signal and one single orange signal and one single green signal in the majority of the neoplastic nuclei, indicating a rearrangement of both NTRK3 and EML4; (D) Immunohistochemistry staining with panTRK antibody (Roche).
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Histologic diagnosis described multiple localizations of acinar and solid adenocarcinoma (grade 2) of the lung ( Figure 2A ). The EML4::NTRK3 gene fusion was identified (EML4 exon2-NTRK3 exon14), and confirmed by both fluorescence in situ hybridization (FISH) analysis, using ZytoLight SPEC NTRK3 Dual Color Break Apart and ZytoLight SPEC EML4 Dual Color Break Apart ( Figures 2B, C , and immunohistochemistry staining with panTRK antibody (Roche) ( Figure 2D ).
PET scan showing a partial response following 2 months of therapy.
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The PET scan ( Figure 3 ) and the brain MR performed two months following the beginning of treatment showed a partial response.
Timeline showing the clinical history of the patient.
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In  Figure 4 , a summary of the patient's clinical history.