PMC8012892_01
A series of imaging studies shown here are CT scans of the chest in either soft tissue or lung windows, a magnetic resonance imaging (MRI) of the spine, and a bone scan obtained spanning 10 years period. The patient had an EGFR Del-19-mutant ADC (2009/07/09). The ADC showed excellent tumor regression after five cycles of induction chemotherapy and three months of gefitinib (2010/02/09 and 2010/06/01). During effective gefitinib treatment, the patient developed an uneventful transitory pneumonitis documented on 2011/04/26. She received the same treatment until 2013/04/05, when she developed extensive-stage SCCT, causing impending spinal cord compression. There was a relapse of small cell carcinoma in the lung parenchyma (2014/03/26) after combined chemoradiotherapy with etoposide-cisplatin and prophylactic cranial irradiation. However, after lung tumor resection and second-line weekly topotecan treatment, the SCCT went into complete remission. Follow-up scans (2018/04/25 through 2019/07/27) demonstrate a quiescent bone scan and fibrotic changes at the previous ADC site.
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Chest computed tomography (CT) revealed a huge lobulated lung mass measuring up to 6.87 cm in the right lower lobe, with a daughter nodule in the same lung lobe ( Figure 1 , upper panel, leftmost). However, the patient developed bilateral leg weakness resulting from spinal cord compression in April 2013 ( Figure 1 , upper series, rightmost panel). On March 26, 2014, a subcentimeter nodule was noted in the right upper lung lobe ( Figure 1 , lower panel, second left).
Histomorphology and mutation analysis of the EGFR gene. (A) The original lung biopsy showing ADC arranged in an acinar architecture. (B) Deletion at codon 746-750 in exon 19 of the EGFR gene in the original lung biopsy. The DNA, extracted from paraffin sections, was subjected to PCR amplification for exons 18, 19, 20, and 21 of the EGFR gene. These amplicons were then sequenced. The result shows codon 756-750 deletion in exon 19, resulting in deletion amino acids ELREA. (C) Repeat lung biopsy revealing the transformation of small cell carcinoma, which is demonstrated by sheets of crushed, small sized tumor cells, with high nuclear to cytoplasmic ratio, smudged chromatin and minimal cytoplasm. (D) MALDI-TOF MS of repeat lung biopsy indicating that the deletion in codon 746-750 in exon 19 of the EGFR gene was retained. The quality and quantity of extracted DNAs (concentration: 4.85 ng/ul) are measured by NanoDrop (ND-1000), and the mutation detection is measured by the MassARRAY genotyping (SEQUENOM) incorporating a MALDI-TOF mass spectrometer. Result confirmed the presence of Type 1 Exon 19 deletion: c.2235_2249del p (Glu746_Ala750del). (D) shows the spectrogram, mass (X-axis) versus intensity (Y-axis), and the diagnostic mass peaks from 5,354 to 5,400.
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The original lung biopsy showed atypical glands with lepidic and acinar architecture and enlarged and hyperchromatic nuclei ( Figure 2A ). EGFR analysis performed using targeted exon sequencing identified the deletion of codon 746-750 in exon 19, resulting in the deletion of the amino acids ELREA ( Figure 2B ). Two additional pathologists independently confirmed the final pathological diagnosis of SCCT ( Figure 2C ). EGFR mutation analysis using matrix-assisted-laser-desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS) for SCLC identified the same deletion in exon 19 ( Figure 2D ).
Post-SCCT induction treatment monitoring and long-term follow-up with CT scans over the years. The schema diagram illustrates a series of computerized tomography coronal sections through the right lower lobe primary adenocarcinoma, which has turned into post-treatment fibrosis and recently asymptomatic bronchiectatic change. Through these non-progressive CT scans, one can be confident post-hoc that a complete response was attained in 2014 after complete treatment for SCCT. There is no evidence of SCCT recurrence over time.
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As compared with the initial scan images, there was no new lesion during follow-up.  Figure 3  illustrates a series of CT scans at regular follow-ups after the induction treatment for SCCT over the years.