Lung adenocarcinoma with sarcomatoid transformation after tyrosine kinase inhibitor treatment and chemotherapy

Objectives Lung cancers have various acquired resistance mechanisms that lead to treatment failure and disease progression, including secondary epidermal growth factor receptor (EGFR) exon 20 T790 M mutations, EGFR downstream or bypass pathway activation, and histologic transformation from adenocarcinoma to small cell carcinoma, squamous cell carcinoma, or sarcomatoid carcinoma. Materials and Methods This study compared the pathological and immunohistochemical characteristics before and after sarcomatoid transformation. Six advanced cases of lung adenocarcinoma that developed sarcomatoid transformation after treatment were collected. Results Five cases had classic EGFR mutations and one had a ROS1 rearrangement. The interval from initial diagnosis to sarcomatoid transformation ranged from 9 to 88 mo (median of 31.5 mo). The median survival after sarcomatoid transformation was 2.5 mo (1–16 mo). Before sarcomatoid transformation, all cases demonstrated typical adenocarcinoma features, including acinar, micropapillary, or solid/cribriform patterns, negative or weak focal vimentin staining, and strong E-cadherin expression. Histologic features of sarcomatoid transformation included giant cell features (6/6), loose cellular cohesion (6/6), strong staining for vimentin (6/6), decreased or lost E-cadherin expression (5/6), and high PD-L1 expression (5/6; one case demonstrated high PD-L1 staining at initial diagnosis). High MET expression and MET copy number gain (two samples with high polysomy and three with true amplification) were observed in five cases with EGFR mutation treated with tyrosine kinase inhibitors (TKI). One case exhibited MET amplification prior to the start of TKI treatment. Conclusion Sarcomatoid transformation is a type of lung cancer histologic evolution with a poor prognosis and a high proportion of cases with aberrant MET activation and PD-L1 expression.