Case report: Navigating treatment pathways for cardiac intimal sarcoma with PDGFRß N666K mutation.

In the realm of rare cardiac tumors, intimal sarcoma presents a formidable challenge, often requiring innovative treatment approaches. This case report presents a unique instance of primary intimal sarcoma in the left atrium, underscoring the critical role of genomic profiling in guiding treatment. Initial genomic testing unveiled a somatic, active mutation in PDGFRß (PDGFRß N666K), accompanied by MDM2 and CDK4 amplifications. This discovery directed the treatment course toward pazopanib, a PDGFRß inhibitor, following irradiation. The patient's response was remarkable, with the therapeutic efficacy of pazopanib lasting for 16.3 months. However, the patient experienced a recurrence in the left atrium, where subsequent genomic analysis revealed the absence of the PDGFRß N666K mutation and a significant reduction in PDGFRß expression. This case report illustrates the complexities and evolving nature of cardiac intimal sarcoma treatment, emphasizing the potential of PDGFRß signaling as a strategic target and highlighting the importance of adapting treatment pathways in response to genetic shifts.

Comprehensive genomic analysis reveals clonal origin and subtype-specific evolution in a case of sporadic multiple meningiomas.

Meningioma is the most common primary intracranial tumor in adults, with up to 10% manifesting as multiple tumors. Data on the genomic and molecular changes in sporadic multiple meningiomas are scarce, leading to ongoing debates regarding their evolutionary processes. A comprehensive genetic analysis of a large number of lesions, including precursor lesions, is necessary to explore these two possible origins: clonal and independent. In the present study, we performed whole-exome sequencing and analyzed somatic single-nucleotide variants (SNVs), insertions/deletions (INDELs), and copy number alterations (CNAs) in a patient with sporadic multiple meningiomas. These meningiomas included two mass-forming lesions of different histological subtypes (transitional and chordoid) and two small meningothelial nests. Genetic analysis revealed CNAs on chromosomes 22q and Y as common abnormalities in the two largest tumors. Furthermore, we identified SNV/INDELs unique to each focus, with NF2 mutation prevalent in the transitional meningioma and CREBBP mutation in the chordoid meningioma. Loss of chromosome 22 was detected in two small meningothelial nests. Overall, we elucidated the clonal origin and subtype-specific evolution of multiple meningiomas in this case. CNAs may serve as the initial driving event in meningioma development.

Challenges in the treatment of BRAF K601E-mutated lung carcinoma: a case report of rapid response and resistance to dabrafenib and trametinib.

We report a case of limited effectiveness of dabrafenib and trametinib in a 59-year-old man with poorly differentiated lung carcinoma and a rare BRAF K601E mutation. The patient, unresponsive to chemotherapy and immunotherapy, received these targeted agents as second-line treatment. Despite a notable initial response, tumor regression lasted only 52 days. A subsequent liquid biopsy revealed additional alterations (BRAF amplification, KIT amplification, TP53 S241F), indicating a complex resistance mechanism. This case underscores the challenges in treating BRAF K601E-mutant lung carcinoma, emphasizing the need for advanced molecular diagnostics, personalized approaches, and further research into more effective therapies for unique genetic profiles.