ALK rearrangement

We report the case of a 3-year-old boy with progressively worsening biphasic stridor, found to have an isolated ALK+ histiocytic lesion in the subglottis. This case represents the first reported instance of an isolated ALK+ histiocytic lesion of the airway managed with endoscopic debulking.

P2, N=118, Active, not recruiting, Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest | Trial completion date: Jan 2026 --> Apr 2026 | Trial primary completion date: Jan 2026 --> Apr 2026

P2, N=60, Not yet recruiting, University Health Network, Toronto | Trial completion date: Apr 2026 --> Apr 2028 | Trial primary completion date: Apr 2026 --> Apr 2028

The overall concordance of genotyping results between cfRNA-protected SS and paired CNB specimens was 100%, correctly identifying all ALK fusions, ROS1 rearrangements, and MET-14 skipping alterations. These findings highlight that preserving cfRNA in CNB-SS from NSCLC can improve the performance of genomic testing, particularly for RNA-based assays, without compromising the accuracy of DNA-based assays.

P1/2, N=80, Completed, Institut Bergonie | Active, not recruiting --> Completed

P2, N=10, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Dec 2026

Brigatinib was initiated, and a complete radiologic response was documented within 3 months and has been sustained for over 12 months, including durable intracranial disease control. Sustained CR in I1171N-mediated alectinib resistance is rare and highlights the critical role of repeat molecular testing to guide ALK TKI sequencing.

The patient with TRIM24::ALK fusion, following durable responses to alectinib and lorlatinib, relapsed with detection of on-target ALK kinase domain mutations (F1174V, I1171N) and MYC amplification on progression. Comprehensive molecular workup, including RNA-based NGS, is essential for detecting rare but actionable ALK rearrangements and optimizing therapeutic strategy. NGS of CSF was a valuable tool for the detection of clinically suspected leptomeningeal disease and disease monitoring.

We found progressive arthropathy, mostly painless, in one or more joints or intervertebral spaces of patients receiving crizotinib for NSCLC.

Here, we report a lung IMT in a 45-year-old female demonstrating a unique meningothelial-like pattern, equivocal ALK expression (negative for clone 5A4 and positive for clone ALK1), negative ALK rearrangement by FISH, and the presence of the TPM3::ALK fusion. To our knowledge, this is the first reported case of lung IMT displaying meningothelial-like whorls, with a particular focus on differential diagnosis.

This case highlights the value of next-generation sequencing-based profiling in detecting rare actionable alterations missed by standard tests. We also include a discussion on why the EML4-AKL fusion was not detected in the usual test.

P1/2, N=88, Not yet recruiting, Oncomatryx Biopharma S.L.