Small cell lung cancer (SCLC) components were identified in the majority of cases previously labeled as small cell transformation (SCT), according to data from a small retrospective study published in Lung Cancer.1
Although SCT is a known mechanism of treatment-resistant EGFR-mutant adenocarcinoma non-small cell lung cancer (NSCLC), there is a hypothesis that these cases harbor both SCLC and NSCLC components, with EGFR inhibitor therapy thought to eliminate the NSCLC portion of the tumor.
Li et al’s investigation into SCT and its pseudo presentation was prompted by an incidental finding of a pseudo-SCT case. “We recently treated an interesting SCT case and found that small cell components actually existed in the initial diagnosis of adenocarcinoma specimen. Therefore, we reviewed all SCT cases in the past 2 years and investigated the phenomenon of pseudo-SCT,” the study authors wrote.
The study identified 1083 lung cancers classified as SCLC or combined SCLC in a pathology database at a hospital in China between January 2017 and March 2018. Of the 215 cases with initial biopsy results, 13 had an original diagnosis of adenocarcinoma only and 11 of these patients had received prior EGFR inhibitor therapy. The original pathology slides of these 11 patients were reviewed for SCLC components.
SCLC components comprising 1% to 5% of the slides were identified in 8 of the 11 patients, suggesting that these patients had pseudo-SCT. The original pathology slides of 25 patients with EGFR inhibitor resistance (but not classified as SCT) were also evaluated and were found to have no SCLC components.
“This demonstrated that pseudo-SCT was not due to bias from missed detection of small cell components on the initial slides, and that misdiagnosis of SCLC components may be an important factor in SCT,” the investigators said.
Sufficient tissue was available for immunohistochemistry of pRB and p53 among 4 patients, including 1 patient with real SCT and 3 patients with SCLC components. Overexpression of mutated p53 was present before and after SCT diagnosis, regardless of whether the case was real or pseudo-SCT. The same was true of RB1 loss.
The authors concluded that “Our findings indicated that most SCT may be pseudo-SCT in [the] real world,” the study authors concluded. They added that “further studies about the real mechanism of SCT need to be conducted in additional centers.”
Li R, Jiang L, Zhou X, Lu Y, Zhang Y. Pseudo-small cell transformation in EGFR-mutant adenocarcinoma. Lung Cancer. Published online January 10, 2021. doi:10.1016/j.lungcan.2020.12.036