Atypical Lung Carcinoid With EML4/ALK Fusion Detected With Circulating Tumor DNA

Atypical carcinoids are a rare subset of neuroendocrine tumors that originate from cells within the bronchopulmonary tree. Compared to typical carcinoids, atypical carcinoids are associated with a worse prognosis. EML4-ALK fusions are reported in 5% of non-small cell lung carcinoma, but are rare in atypical carcinoids with only five previously reported cases. We report a case of a 70-year-old female with atypical carcinoid with metastasis to the liver and axial skeleton. She did not respond to standard of care chemotherapy with carboplatin and etoposide and was elected to enroll in hospice because of worsening clinical status. However, a circulating tumor DNA (ctDNA) sample was obtained the same day which revealed an EML4-ALK fusion gene. She immediately began therapy with the second-generation ALK inhibitor alectinib, with a remarkable symptomatic and radiographic response. Seven months later, the disease progression was demonstrated in the liver and the patient was switched to the third-generation ALK inhibitor lorlatinib. At the time of writing, the patient has continued to demonstrate sustained clinical, radiographic, and biochemical responses while on lorlatnib for two years. The dramatic treatment results highlighted in this case make the argument to consider ctDNA after the diagnosis of locally advanced or metastatic atypical carcinoid.