Transformation From Adenocarcinoma to Pleomorphic Carcinoma as an Acquired Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors

Abstract

Pulmonary pleomorphic carcinoma is a very rare histological type of primary lung cancer, and usually provides aggressive clinical courses. A 65-year-old Japanese woman was diagnosed by transbronchial biopsy of the primary tumor as c-stage IV (cT4N3M1b) of adenocarcinoma harboring L858R point mutation in the exon 21 of epidermal growth factor receptor (EGFR). She received EGFR tyrosine kinase inhibitors (TKIs) (gefitinib and erlotinib) and subsequently cytotoxic chemotherapies. Gefitinib achieved partial response, but was switched to erlotinib due to elevated serum aspartate transaminase. After resistance to EGFR-TKIs, the second transbronchial re-biopsy revealed pulmonary pleomorphic carcinoma. Both carcinomatous and sarcomatous components retained the L858R mutation, but did not acquire T790M mutation. This case suggested that the histological transformation to pulmonary pleomorphic carcinoma may be one of mechanisms of drug resistance to EGFR-TKIs.

Transformation of adenocarcinoma into small cell lung cancer as one of the mechanisms of acquired resistance to anti-EGFR tyrosine kinase inhibitors

“…Повторна біопсія нових осередків із морфологічним та ІГХ-дослідженням підтвердила наявність трансформації аденокарциноми у дрібноклітинний рак легені з нейроендокринною диференціацією (рис. 4,5,6).…”

“…Трансформація аденокарциноми в ДКРЛ є унікальною біологічною властивістю ракової клітини, що відповідає за механізм набутої резистентності до EGFR-інгібіторів тирозинкінази [4].…”

Histologic transformation in lung cancer: when one door shuts, another opens

“…For example, there have been several reports on transformations to sarcomatoid carcinoma. 23 , 24 Specifically, six sarcomatoid HTs [five cases with EGFR mutations and one with c-ros oncogene 1 ( ROS1 ) mutations] were reported, and the interval from initial diagnosis to HT was 9–88 (median: 31.5) months. 25 Giant cells were the most common form of sarcomatoid transformations, and overall survival (OS) after HTs in patients with lung cancer was reported to be 2.5 months, which was shorter than for HTs to HGNEC.…”