Your 54-year-old male patient who is a lifelong nonsmoker comes back to your office for followup of a RUL nodule after a recent biopsy you performed revealed stage IV non-small cell lung cancer. His oncologist said that a “signet ring” sign was seen on his biopsy and that he has a gene abnormality seen on the FISH sample. The patient wants to know your opinion of how well people with his condition respond to traditional chemotherapy and if there are any new drugs on the horizon which could help.
What genetic defect is most likely given the patient’s description and what is its response to treatment?
A. EGFR mutation; longer survival with tyrosine kinase inhibitors
B. EGFR mutation: longer survival with crizotinib
C. EML4-ALK gene rearrangement; longer survival with tyrosine kinase inhibitors
D.EML4-ALK gene rearrangement; longer survival with crizotinib
E. KRAS mutation; less than optimal response to traditional chemotherapy
See the following:
John Kioka and I are at CC and we believe that because of the signet ring sign and the non-smoking status, we think the answer is D.
Sterling heights Represent!
The answer is D. EML4-ALK mutation and treatment with crizotinib.
This fusion gene produces subset of adenocarcinoma that produces mucus thus the signet ring appearance. This is common in nonsmoker or light smokers.
Treatment is with ALK inhibitor which is crizotinib which improves their progression free survival but no overall mortality. Crizotinib has a high resistance attributed to mutation of the ALK domain and thus the development of another ALK inhibitor called Ciritinib.
In conclusion, we have shown that inhaled budesonide for 1 year significantly reduces the size of non-solid and partially solid nodules, compared with placebo, and that this reduction remained evident 4 years after treatment cessation. Since some of these nodules may be adenocarcinoma precursors, the potential effect of budesonide on the development of lung adenocarcinomas deserves continuing investigation.