A Case Report of a Metastatic Adenocarcinoma of Lung with Dual Positivity for EGFR Mutation and ALK Fusion

Abstract

Non-small cell lung cancer ranks among the most lethal cancers worldwide. The rate of epidermal growth factor receptor (EGFR) mutations and echinoderm microtubuleassociated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) gene fusion is the most common in younger age, non-smoking Asian adenocarcinoma lung cancer patients. EGFR mutations and ALK gene rearrangements are known to be mutually exclusive and as mutual causes of resistance to EGFR-tyrosine kinase inhibitors (TKIs) or ALK-TKIs. However, rarely such co-alterations do co-exist in some clinical cases. Here we report a 62 year old male, heavy smoker with cough, hemoptysis and fatigue. Histopathological examination of bronchoscopic guided biopsy showed adenocarcinoma histology. Staging evaluation, he was found to have stage IV disease on positron emission tomography-computed tomography scan. The biopsy blocks tested positive for both EGFR mutation and ALK fusion. Patient was initiated on tablet Gefitinib 250 mg once daily. To the best of our knowledge, there has been no report of dual EGFR mutation and ALK fusion positivity from India.

Concomitant expression of exon 19 mutation epidermal growth factor receptor and anaplastic lymphoma kinase gene rearrangement in metastatic adenocarcinoma lung responsive to crizotinib

“…With around 100 such concomitant cases reported in the world,[ 14 ] Kamath et al . [ 4 ] have reported the only case in India, while we report the second case in an upfront metastatic patient. Kamath et al .…”

“…[ 1 2 ] ALK rearrangements correlate with specific clinical and pathological features and may cause potential resistance to anti-EGFR tyrosine-kinase inhibitors (TKIs). [ 3 ] Use of EGFR-TKIs gefitinib[ 4 ] or erlotinib[ 3 5 6 7 8 ] and ALK-TKI crizotinib[ 9 10 ] in a concomitant lung adenocarcinoma has shown mixed results with few progressing[ 4 6 7 8 9 ] and few responding. [ 5 6 10 ] Patients housing both mutations have shown an objective response and increased sensitivity to ALK-TKI alone[ 11 12 ] but can also be sensitive to both targeted therapies, thus suggesting a variable dependence on EGFR and ALK oncogenes.…”

“…[ 14 ] EGFR mutations have been known to predominate in well-differentiated while ALK in poorly differentiated adenocarcinomas[ 15 16 ] in young Asian nonsmokers. [ 4 ] However, around 100 cases of concomitant presence have been reported in the world[ 14 ] and only one case in India. [ 4 ] Regarding such coexistence, few have described it to be about 1%,[ 2 ]1.3%,[ 17 ]1.6%,[ 1 ] and even 0.3%.…”

“…[ 4 ] However, around 100 cases of concomitant presence have been reported in the world[ 14 ] and only one case in India. [ 4 ] Regarding such coexistence, few have described it to be about 1%,[ 2 ]1.3%,[ 17 ]1.6%,[ 1 ] and even 0.3%. [ 11 ]…”

“…Kamath et al . [ 4 ] used gefitinib 250 mg/day, however, the disease progressed after 3 months. The patient was upfront metastatic which prompted the use of crizotinib 250 mg twice/day.…”