A 44-year-old Chinese man with a 7 pack-year smoking history was referred to Shanghai Pulmonary Hospital in February 2013 for a left upper lobe lung mass with multiple bilateral intrapulmonary metastases, left pleural effusion, and 2R/4R/10L/11L lymphadenopathy.
Pleural fluid cytology revealed adenocarcinoma and Scorpion Amplification Refractory Mutation system (AmoyDx Co., Xiamen, China).
showed no detectable epidermal growth factor receptor mutation.
He commenced chemotherapy with gemcitabine and cisplatin.
However, after a single cycle, his symptoms worsened and imaging confirmed progressive disease.
A second opinion was requested from the University of Colorado and a computed tomography–guided biopsy of the left upper lobe lesion was performed to permit additional molecular testing.
In the interim, the patient commenced pemetrexed and nedaplatin.
Unfortunately, after two cycles his shortness of breath worsened, with evidence of further progression on his scans (Fig.1A).
Molecular testing on his repeat biopsy specimen revealed no mutations by SNaPshot multiplex PCR testing (Life Technologies, Carlsbad, CA).
However, although technically negative, the ALK break-apart FISH test showed an atypical negative pattern.
Specifically, 68% of cells demonstrated single copies of the 5′ ALK signal and numerous cells with doublets of the 5′ ALK signal combined with one 3′ ALK signal (Fig.2A).
Subsequently, confirmatory diagnostic assays demonstrated ALK protein expression by IHC using the D5F3 antibody (Cell Signaling Technology Inc., Danvers, MA; H score = 150; Fig.2B) and the presence of an echinoderm microtubule-associated protein-like 4 (EML4)-ALK transcript (E13; A20) by RT-PCR (Fig.2C).
The patient then received crizotinib (250 mg twice daily) as third-line therapy in May 2013 with an impressive symptomatic improvement and CT response after 1 month of therapy (Fig.1B).
He remains on treatment with crizotinib with no evidence of progression as of September 2013.