Cystic brain metastases in ALK-rearranged non-small cell lung cancer

The central nervous system (CNS) is a common site of disease progression in patients with non-small-cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK)-rearrangement treated with crizotinib. Cystic brain metastases (CBM) have been recently identified as one possible variant of this disease. An illustrative case report is presented along with a literature review performed in order to track relevant papers about CBM in ALK-rearranged NSCLC, including possible pathophysiology, differential diagnosis and treatment options for this condition. Three case reports have been published describing six ALK-rearranged NSCLC patients presenting with CBM, all of which were under treatment with crizotinib by the time of CBM diagnosis. Treatment with CNS-penetrating tyrosine kinase inhibitors (TKIs) resulted in CNS disease control in three of the six cases reported either as single therapy or in combination with radiation therapy (RT). Investigation of differential diagnoses of CBM might be necessary, which include inflammatory and demyelinating disorders, primary brain tumours and infectious diseases, especially neurocysticercosis that might mimic CBM images. Treatment options include RT, CNS-penetrating TKIs and invasive procedures, such as stereotactic drainage. Thus, CBM are associated with ALK-rearranged NSCLC, particularly in patients who use crizotinib and should prompt investigation of differential diagnosis. CNS-penetrating TKIs are effective in the control of solid brain metastases and also seem to be active in CBM as single therapy or in combination with RT.