Ensartinib in a primary pulmonary ALK-rearranged mesenchymal neoplasm harboring a novel HMBOX1::ALK fusion: a case report and literature review

Anaplastic lymphoma kinase (<i>ALK</i>) gene rearrangements have been increasingly detected in mesenchymal neoplasms. <i>ALK</i>-rearranged mesenchymal neoplasms occur mainly in superficial tissues but rarely in internal organs. Herein, we firstly report a primary lung lesion presenting as a rare <i>ALK</i>-rearranged mesenchymal neoplasm. The patient diagnosed with primary pulmonary <i>ALK</i>-rearranged mesenchymal neoplasm (PPAMN) received ensartinib as postoperative adjuvant therapy, achieving a disease-free survival of 10 months. Continuation of ensartinib as first-line treatment enabled him to benefit from a partial response, with a progression-free survival of 11 months. Second next-generation sequencing (NGS) revealed elevated <i>HMBOX1::ALK</i> abundance along with secondary <i>NF2</i> mutation. After local radiotherapy combined with ensartinib continuation, his disease was temporarily stable for 7 months. Unfortunately, this disease became uncontrolled with an overall survival (OS) of 34 months. This is the first case of <i>ALK</i>-rearranged mesenchymal neoplasm manifested as a primary lung lesion and a novel <i>HMBOX1::ALK</i> fusion was identified by NGS. The family of <i>ALK</i>-rearranged mesenchymal neoplasms is expanding and ensartinib could be a potential treatment option for patients with <i>HMBOX1::ALK</i>. Repeated biopsy and NGS detection are critical to guide treatment selection at disease progression.