PMC9646987_01
Histopathology of tumor with major pathological response (MPR) to neoadjuvant savolitinib. (A) High-power magnification (x200) shows tumor cell nests without inflammatory cell infiltration and initially diagnosed as a poorly differentiated carcinoma. (B) Low-power magnification (x20) shows that only 5% of this tumor was viable with 95% showing fibrosis and chronic inflammation without necrosis tissue in the pathology of postoperative samples by H&E staining. (C, D) Enlargement of the blue and red boxes in (B). (C) H&E staining image shows numerous foam cells, multinucleated giant cells, and cholesterol crystals. No viable tumor was seen. (D) Higher power magnification shows the amount of inflammatory cell infiltration and the formation of lymphoid follicular, with the acinar type of tumor cells growing with adherence. Immunohistochemical (IHC) reveals that tumor cells were positive for TTF-1 (E), Napsin A (F), and CK7 (G) and negative for CK5 (H). The scale length is 1 cm.
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A percutaneous pulmonary biopsy established the diagnosis of a poorly differentiated carcinoma ( Figure 1A ), with immunohistochemical (IHC) manifestation as CK (+), Ki-67 (~10%), TTF-1 (-), P63 (-), CgA (-), and Syn (-). The primary tumor was identified as a highly-moderately differentiated invasive adenocarcinoma ( Figure 1B ), confirmed by IHC [positive for TTF-1 ( Figure 1E ), Napsin A ( Figure 1F ), and CK7 ( Figure 1G ) and negative for CK5/6 ( Figure 1H )], with 5% of the residual viable tumor and 95% of fibrosis and inflammation ( Figures 1B-D ).
Enhanced chest CT scans during therapy: (A) baseline imaging. (B) After 40 days with savolitinib. (C) After 2 months with savolitinib. The red arrow indicates a primary tumor. The yellow arrow indicates metastatic lymph nodes.
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MRI scan of the brain, and bone scintigraphy identified a soft tissue (5.8 x 4.9 cm) in the posterior segment of the right upper lobe, closely adjacent to the right superior lobe vein, compressing the bronchus, with right hilar and mediastinal lymph node enlargement (with a short diameter of 1.7 cm) ( Figure 2A ). Moreover, no distant metastasis was detected. Six weeks later, a CT rescan identified dramatic regressions of the primary tumor (shrinkage of 69%,  Figure 2B ) and lymph nodes. Another CT scan after an additional 1 month indicated an even smaller tumor (shrinkage of 82%,  Figure 2C ).
Timeline of the diagnosis and chest CT scans during the treatment and follow-up of this case. (A) Baseline imaging. (B) Treatment with savolitinib for 6 weeks. (C) Treatment with savolitinib for 10 weeks. (D) After 2 weeks of surgical operation, the patient had dyspnea, chest CT confirmed pneumothorax in the right lung, and closed thoracic drainage was performed on the patient. (E) Enhanced chest CT scans confirmed that the pneumothorax was improved 1 week later. The patient was alive and felt well at the last telephone follow-up on 9 August 2022.
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The patient was discharged and followed up for 8 months.  Figure 3  demonstrates the timeline of the diagnosis, treatment, and follow-up of the patient.