DCTN1-ALK fusion

Here we report a case of a 71 year-old man with metastatic pulmonary IMT harboring a DCTN1::ALK fusion that progressed during alectinib TKI treatment...To our knowledge, this is the first report of acquired p. V1180L mutation in IMTs treated with TKIs. In cases of ALK-positive IMTs that progress on TKI therapy, targeted sequencing for acquired ALK mutations may inform clinical decisions to adopt second-line therapeutic strategies.

ALK inhibition was initiated with alectinib, resulting in rapid improvement of cutaneous lesions and eventual complete resolution of abnormal imaging findings, which was sustained at 24 months of follow-up. This case adds to the spectrum of ALK-positive histiocytoses and further demonstrates the positive response with targeted therapy.

The tumor showed an indolent behavior with local recurrence 3 years after excision. This study broadens the molecular spectrum of spindle cell/sclerosing RMS and this molecular aberration may represent a potential therapeutic target for unresectable or disseminated disease.

The echinoderm microtubule associated protein-like 4 gene (EML4) encodes the predominant anaplastic lymphoma kinase (ALK) fusion partner in non-small-cell lung cancer (NSCLC); however, the dynactin subunit 1 (DCTN1)-ALK rearrangement is extremely rare. This literature review shows that EGFR inhibition was an indispensable aspect of the treatment of patients with EGFR/ALK co-alterations in the pre-alectinib era and that ALK inhibition with crizotinib did not show more eye-catching therapeutic results. Considering the effectiveness achieved by alectinib, this case study provides a new perspective for the treatment of lung cancer brain metastasis patients with concurrent EGFR/ALK mutations.

Histological transformation into small cell carcinoma occurred in one patient. This real-world life study highlights the relevance of re-biopsy at the time of disease progression, contributing to understand resistance mechanisms and to guide treatment strategies.

The discordance of IHC/RT-PCR was mainly due to limited coverage of non-EML4-ALK fusions in the RT-PCR assay. NGS based DNA/RNA sequencing appears to be a promising rescue technique for non-clear-cut IHC/RT-PCR cases and also offers a unique opportunity to identify novel ALK fusions.

IMT is a rare but important diagnostic consideration when evaluating an intracranial mass in a pediatric patient as it has a better prognosis than most other CNS tumors. Gene sequencing is crucial for confirming the correct diagnosis and guiding treatment with targeted immunotherapy. The patient’s tolerance and response to entrectinib after developing a hypersensitivity to alectinib supports alternative ALK inhibitor use as a substitute to desensitization therapy, which can be time intensive and carry risk.

EFH is not always purely epithelioid and its spindled cell variant, spindle cell histiocytoma (SCH), should be included in the differential diagnosis of superficial dermal spindled cell neoplasms. ALK immunostain is a useful diagnostic marker for this entity and further studies may be useful to investigate whether DCTN1-ALK fusion mutations are specific to EFH with spindled cell features.