Histologic transformation of an adenocarcinoma to a squamous cell carcinoma after vinorelbine treatment

Background:

These days activating mutations in the epidermal growth factor receptor (EGFR) genes of non-small cell lung cancer (NSCLC) make efficient therapies with tyrosine kinase inhibitors (TKIs) possible. However after treatment with TKIs in most cases resistance emerges. Such resistance pathways include secondary resistance mutations as T790 M, mutations in the PIK3CA pathway as well as a histologic transformation.

Objective:

In this report we describe the rare histologic transformation of an adenocarcinoma to a squamous cell carcinoma (SCC) with a loss of the T790 M resistance mutation after vinorelbine treatment.

Methods:

Liquid biopsies were performed on the cobas apparatus using the EGFR mutation Kit v2 from Roche. The tumor DNA for the next generation sequencing was isolated out of thin tissue sections on the Maxwell 16, using the LEV Blood Kit. The sequencing of possible mutations in the EGFR genes was performed with the TST15 Kit von Illumina on the MiSeq.

Results:

A bronchogenic adenocarcinoma with bilateral pulmonary metastasis, was diagnosed in a 77-year old female patient. An activating EGFR mutation (deletion Exon 19) was diagnosed making treatment with the first generation EGFR tyrosine kinase inhibitors (TKI) gefitinib and erlotinib possible. This led to the resistance mutation T790 M in exon 20 of the EGFR genes and therefore to disease progression. However after vinorelbine treatment a rebiopsy revealed a histologic transformation of the adenocarcinoma to a SCC. Interestingly the Exon 19 deletion persisted, although it is not predictive for SCC, whereas the resistance mutation T790 M disappeared and an additional mutation in the PIK3CA genes was detected.

Conclusion:

Our case demonstrates the importance of a re-biopsy in the setting of inconclusive results of a liquid biopsy and is essential for the detection of a histologic transformation.