Pseudo-small cell transformation in EGFR-mutant adenocarcinoma

Objectives: To investigate the phenomenon of pseudo-small cell transformation (SCT) by reviewing SCT cases from the past 2 years.

Materials & methods: A total of 11 cases with reported SCT cases from 7282 lung cancer cases treated in West China Hospital of Sichuan University were identified between January 2017 and March 2018. All initial lung adenocarcinoma pathological slides of SCT patients were reviewed carefully by independent, blinded pathologists. Immunohistochemistry was used to identify the expression of EGFR^L858R, RB1 and TP53.

Results: Surprisingly, 8 of 11 previously SCT samples actually contained variable, but discernible amounts of SCLC components, varying from less than 1%-5%. Dubious small-cell components were found in two other patients. Only one patient's sample had no SCLC component on previous adenocarcinoma sections and was therefore defined as a real SCT case. In the current study, we found that at least 72.7 % (8/11) of SCT cases were actually pseudo-SCT. The immunohistochemistry results showed that the EGFR^L858R protein was only expressed in the adenocarcinoma component, but not in the SCLC component, indicating that they may not originate from identical cell clones. RB1 deletion and mutated TP53 overexpression were observed in either pseudo-SCT or real SCT.

Conclusions: Our findings indicated that most SCT may be pseudo-SCT in real world. Pseudo-SCT may lead to bias conclusion from previous researches about SCT. The real mechanism of SCT deserves further investigation.