High-grade intraductal carcinoma of the parotid gland harboring CTNNA1::ALK rearrangement: Changes in genetic status using genetic testing during treatment with an ALK inhibitor.

Background: Salivary gland carcinomas harboring anaplastic lymphoma kinase (ALK) rearrangements are rare. Here, we present the pathological characteristics, clinical course, and changes in the genetic status of a salivary gland carcinoma harboring a catenin alpha 1 (CTNNA1)::ALK rearrangement during treatment with an ALK tyrosine kinase inhibitor (TKI).

Methods: A 59-year-old man with a parotid tumor and cervical lymph node metastases underwent total parotidectomy and radical neck dissection. One month after completion of postoperative radiotherapy, the patient experienced multiple recurrences.

Results: Subsequent treatment with the ALK-TKI alectinib was initially effective against the intraductal carcinoma harboring CTNNA1::ALK rearrangement and TP53 mutation. However, 10 months later the patients' condition deteriorated, and an additional phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutation was detected. The patient ultimately succumbed to multiple organ failure.

Conclusion: The clinical course suggested the concurrent emergence of TP53 and PIK3CA mutations and ALK-TKI drug-selective growth of non-ALK rearrangement gene tumor cells.