Xuewen Liu

Next-Generation Sequencing of Pulmonary Sarcomatoid Carcinoma Reveals High Frequency of Actionable MET Gene Mutations

PURPOSEnTo further understand the molecular pathogenesis of pulmonary sarcomatoid carcinoma (PSC) and develop new therapeutic strategies in this treatment-refractory disease.nnnMATERIALS AND METHODSnWhole-exome sequencing in a discovery set (n = 10) as well as targeted MET mutation screening in an independent validation set (n = 26) of PSC were performed. Reverse transcriptase polymerase chain reaction and Western blotting were performed to validate MET exon 14 skipping. Functional studies for validation of the oncogenic roles of MET exon 14 skipping were conducted in lung adenosquamous cell line H596 (MET exon 14 skipped and PIK3CA mutated) and gastric adenocarcinoma cell line Hs746T (MET exon 14 skipped). Response to MET inhibitor therapy with crizotinib in a patient with advanced PSC and MET exon 14 skipping was evaluated to assess clinical translatability.nnnRESULTSnIn addition to confirming mutations in known cancer-associated genes (TP53, KRAS, PIK3CA, MET, NOTCH, STK11, and RB1), several novel mutations in additional genes, including RASA1, CDH4, CDH7, LAMB4, SCAF1, and LMTK2, were identified and validated. MET mutations leading to exon 14 skipping were identified in eight (22%) of 36 patient cases; one of these tumors also harbored a concurrent PIK3CA mutation. Short interfering RNA silencing of MET and MET inhibition with crizotinib showed marked effects on cell viability and decrease in downstream AKT and mitogen-activated protein kinase activation in Hs746T and H596 cells. Concurrent PIK3CA mutation required addition of a second agent for successful pathway suppression and cell viability effect. Dramatic response to crizotinib was noted in a patient with advanced chemotherapy-refractory PSC carrying a MET exon 14 skipping mutation.nnnCONCLUSIONnMutational events of MET leading to exon 14 skipping are frequent and potentially targetable events in PSC.

Papillary thyroid cancer: Dual-energy spectral CT quantitative parameters for preoperative diagnosis of metastasis to the cervical lymph nodes

PURPOSEnTo evaluate the use of dual-energy spectral computed tomographic (CT) quantitative parameters compared with the use of conventional CT imaging features for preoperative diagnosis of metastasis to the cervical lymph nodes in patients with papillary thyroid cancer.nnnMATERIALS AND METHODSnThis study was approved by the ethics committee and all patients provided written informed consent. Analyses of quantitative gemstone spectral imaging data and qualitative conventional CT imaging features were independently performed by different groups of radiologists. Excised lymph nodes were located and labeled during surgery according to location on preoperative CT images and were evaluated histopathologically. Single and combined parameters were fitted to simple and multiple logistic regression models, respectively, by means of the generalized estimating equations method. Sensitivity and specificity analyses were performed by using receiver operating characteristic curves and were compared with data from the qualitative analysis.nnnRESULTSnThe slope of the spectral Hounsfield unit curve ( λHU slope of the spectral Hounsfield unit curve ), normalized iodine concentration, and normalized effective atomic number measured during both arterial and venous phases were significantly higher in metastatic than in benign lymph nodes. The best single parameter for detection of metastatic lymph nodes was venous phase λHU, with sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of 62.0%, 91.1%, 80.6%, 79.7%, and 81.0%, respectively. The best combination of parameters was venous phase λHU slope of the spectral Hounsfield unit curve and arterial phase normalized iodine concentration, with values of 73.0%, 88.4%, 82.9%, 78.0%, and 85.3%, respectively. Compared with qualitative analysis, the venous phase λHU slope of the spectral Hounsfield unit curve showed higher specificity (91.1% vs 83.0%, P < .001) and similar sensitivity (62.0% vs 61.9%, P > .99), and the combined venous phase λHU slope of the spectral Hounsfield unit curve and arterial phase normalized iodine concentration showed higher sensitivity (73.0% vs 61.9%, P < .001) and specificity (88.4% vs 83.0%, P < .001).nnnCONCLUSIONnQuantitative assessment with gemstone spectral imaging quantitative parameters showed higher accuracy than qualitative assessment of conventional CT imaging features for preoperative diagnosis of metastatic cervical lymph nodes in patients with papillary thyroid cancer.

Computed tomography characterization of neuroendocrine tumors of the thymus can aid identification and treatment

Background Neuroendocrine tumors of the thymus are extremely rare anterior mediastinal tumors. The few studies reporting these tumors have focused on the clinical manifestations and do not provide a summary of characteristic computed tomography (CT) findings. Purpose To investigate the CT appearances of neuroendocrine tumors of the thymus in order to improve the diagnostic and resection efficacy. Material and Methods Nine cases of pathologically identified thymic neuroendocrine tumors were retrospectively analyzed by CT. All the patients underwent non-enhanced and contrast-enhanced CT. Multiple CT features were examined, including tumor location, shape, margins, CT attenuation, involvement of surrounding structures, and distant metastasis. Results A total of nine masses were examined in this study. The maximum tumor diameter ranged from 5 to 14 cm (average, 9 cm). The shapes of six masses were lobulated and three were rounded or oval and the margins of seven masses were unclear while two masses were sharp. All the masses showed hypodensity or isodensity compared to muscles in the anterior thoracic wall on non-enhanced CT images. Two masses showed homogeneous attenuation by non-enhanced CT imaging and moderate homogeneous enhancement after contrast administration, while seven masses showed heterogeneous attenuation with patchy low-attenuation foci and showed moderate to strong heterogeneous enhancement. Involvement of adjacent structures was observed in six cases. Five cases were observed to have lymph node metastases and four cases had distant metastases. Conclusion Neuroendocrine tumors of the thymus are rare tumors of the anterior mediastinum with a number of distinct CT characteristics. Most importantly, the density of the tumors was heterogeneous with necrosis or cystic degeneration and moderately or strongly enhancement after bolus injection of contrast medium, which may allow for more efficient tumor identification. Thus, CT can improve of the diagnosis of neuroendocrine tumors and provide critical information for surgical planning.

Radiation-induced sarcomas of the head and neck in post-radiation nasopharyngeal carcinoma

common, with a crude incidence in adults of less than 0.5 % in various situations [1–5]. With improved patient survival [6–8], RIS is likely to be encountered more frequently. It is now generally believed that complete surgical resection of RIS provides the only chance of a cure [3, 4]. Unfortunately, the reported prognosis is poor owing to advanced RIS at diagnosis [3, 4, 9]. RIS has become a critical problem that can limit long-term survival and hinder quality of life. To detect an RIS at an earlier stage, the radiologist should be aware of the common radiological appearances, which can be scrutinized on follow-up scans. The purpose of this study was to document the clinical findings and the radiological features on computed tomography (CT) and magnetic resonance imaging (MRI) of RIS in the head and neck following RT for NPC.

MRI characterization of inflammatory myofibroblastic tumors in the maxillofacial region

PURPOSEnWe aimed to investigate the magnetic resonance imaging (MRI) appearance of inflammatory myofibroblastic tumors (IMTs) in the maxillofacial region in order to improve diagnostic quality and resection efficacy.nnnMATERIALS AND METHODSnTen cases of pathologically identified IMTs were analyzed by MRI. The MRI features were examined, including tumor location, tumor shape, tumor margins, and involvement of the surrounding tissues.nnnRESULTSnOf ten masses investigated in this study, eight masses were irregular neoplasms with unclear margins and two masses, in the parotid gland, were regular neoplasms with clear margins. Precontrast T1-weighted images of all ten masses exhibited isointense signals compared to the adjacent tissue, while contrast-enhanced T1-weighted images showed strong enhancement. Six masses were hypointense and four masses were slightly hyperintense in T2-weighted images. Involvement of the adjacent structures was observed in eight of ten cases. Meanwhile, two patients experienced intracranial involvement.nnnCONCLUSIONnIMTs are rare tumors in the maxillofacial region, displaying a number of distinct MRI characteristics. Most importantly, they display low T2 signal intensity and strong enhancement, and they frequently invade surrounding structures. Thus, MRI can improve the accuracy of IMT diagnoses and provide critical information for surgical planning.