The role of next-generation sequencing in detecting gene fusions with known and unknown partners: a single-center experience with methodologies' integration.

AIMS: Next-generation sequencing (NGS) is becoming a new gold standard for determining molecular predictive biomarkers. This study aimed to evaluate the reliability of NGS in detecting gene fusions, focusing on comparing gene fusions with known and unknown partners. METHODS: We collected all gene fusions from a consecutive case series using an amplicon-based DNA/RNA NGS platform and subdivided them into two groups: gene fusions with known partners and gene fusions with unknown partners. Gene fusions involving ALK, ROS1 and RET were also examined by immunohistochemistry (IHC) and/or fluorescent in situ hybridization (FISH). RESULTS: Overall, 1174 malignancies underwent NGS analysis. NGS detected gene fusions in 67 cases (5.7%), further subdivided into 43 (64.2%) with known partners and 24 (35.8%) with unknown partners. Gene fusions were predominantly found in non-small cell lung carcinomas (52/67, 77.6%). Gene fusions with known partners frequently involved ALK (20/43, 46.5%) and MET (9/43, 20.9%), while gene fusions with unknown partners mostly involved RET (18/24, 75.0%). FISH/IHC confirmed rearrangement status in most (89.3%) of the gene fusions with known partners, but in only one (4.8%) of the gene fusions with unknown partners, with a significant difference (p < 0.001). In 17 patients undergoing targeted therapy, the log-rank test revealed that the overall survival was higher in the known partner group than in the unknown partner group (p = 0.002). CONCLUSIONS: NGS is a reliable method for detecting gene fusions with known partners, but it is less accurate in identifying gene fusions with unknown partners, for which further analyses (such as FISH) are required.

Pseudocarcinomatous Mesothelioma: A Hitherto Unreported Presentation closely simulating primary lung cancer.

Malignant mesothelioma (MM) has a wide range of clinical, radiologic, and pathologic presentations, mimicking lung cancer or interstitial lung diseases when predominantly involving the lung parenchyma. The case herein refers to a 79-year-old man, active smoker without asbestos exposure, incidentally discovered to have a pulmonary nodule in the right upper lobe (1.5 cm). The lesion was misinterpreted as primary lung adenocarcinoma at the frozen section in light of the predominant lepidic growth pattern. Definitive examination confirmed neoplastic proliferation along alveolar structures. However, the unusual globous shape of tumor cells along the alveoli abruptly merging with normal pneumocytes prompted us to perform some immunostains that surprisingly revealed a mesothelial differentiation (positive staining with calretinin, cytokeratins (CK5/6), D2-40, and negativity with BRCA-associated protein 1 (BAP1), Thyroid Transcription Factor 1 [TTF-1], claudin-4, carcinoembryonic antigen [CEA], and napsin). MM represents the pathologic counterpart of so-called pseudomesotheliomatous carcinoma, since it appears as a localized pulmonary neoplastic nodule displaying a predominant lepidic growth pattern (pseudocarcinomatous mesothelioma). The challenging diagnostic features of this unique case and a review of similar cases in the literature are discussed.

Intrapulmonary solitary fibrous tumour: a rare neoplasm of the lung and a challenging pre-operative diagnosis.

BACKGROUND: Case report of a 78-year-old male who came to our observation for a growing pulmonary mass of the left upper lobe without a pre-operative diagnosis. Post-operative histopathology revealed an intrapulmonary Solitary Fibrous Tumour (SFT) of the lung. CASE REPORT: The pulmonary lesion was an ovoid mass centrally located in the left upper lobe; it had been known and stable in size for two years; the last Chest Computed Tomography (CT) Scan highlighted a marked increase in maximum diameter (35 versus 22 mm) with contrast enhancement. In view of the growth of the lesion, the patient was referred for surgery after multidisciplinary team evaluation, although a pre-operative diagnosis had not been reached. The patient underwent Video-Assisted Thoracic Surgery (VATS) left upper lobectomy by a biportal approach. The pulmonary nodule consisted of a proliferation of bland-looking spindle cells intermingled with fibrotic stroma and alternating sclerotic and cellular areas. At immunohistochemistry, the spindle cells expressed CD34, bcl2 and CD99. A final diagnosis of intrapulmonary SFT was reached. The 36-month follow-up was negative for relapses. CONCLUSIONS: Primary intrapulmonary SFTs are extremely rare neoplasms, generally with benign biological behaviour; surgical resection is safe and essential in order to be curative and can be achieved by a minimally invasive approach. Pre-operative diagnosis is challenging, due to aspecific clinical and radiological features. KEY WORDS: Lung, Solitary Fibrous Tumour, Video-Assisted Thoracic Surgery Lobectomy.