A Retrospective Multicenter Italian Analysis of Epidemiological, Clinical and Histopathological Features in a Sample of Patients with Acinic Cell Carcinoma of the Parotid Gland.

BACKGROUND: The acinic cell carcinoma (AciCC) of the parotid gland is a rare tumor with an indolent behavior; however, a subgroup of this tumor presents an aggressive behavior with a tendency to recur. The aim of this multicenter study was to identify and stratify those patients with AciCC at high risk of tumor recurrence. METHODS: A retrospective study was carried out involving 77 patients treated with surgery between January 2000 and September 2022, in different Italian referral centers. Data about tumor characteristics and its recurrence were collected. The histological specimens and slides were independently reviewed by a senior pathologist coordinator (L.C.) and the institution's local head and neck pathologist. RESULTS: The patients' age average was 53.6 years, with a female prevalence in the group. The mean follow-up was 67.4 months (1-258, SD 59.39). The five-year overall survival (OS) was 83.2%. The 5-year disease-free survival (DFS) was 60% (95% CI 58.2-61.7). A high incidence of necrosis, extraglandular spread, lymphovascular invasion (LVI), atypical mitosis, and cellular pleomorphism was observed in the high-risk tumors compared to the low-risk ones. CONCLUSION: AciCC generally had an indolent behavior, optimal OS, DFS with few cervical node metastases, and rare distant relapses. This multicenter retrospective case series provides evidence of the need for clinical-epidemiological-histological stratification for patients at risk of poor outcomes. Our results suggest that the correct definition of high-risk AciCC should include tumor size, the presence of necrosis, extraglandular spread, LVI, atypical mitosis, and cellular pleomorphism.

Contrast-Enhanced Ultrasound in Distinguishing between Malignant and Benign Peripheral Pulmonary Consolidations: The Debated Utility of the Contrast Enhancement Arrival Time.

Background. Limited studies and observations conducted on a too small number of patients prevent determining the actual clinical utility of pulmonary contrast-enhanced ultrasound (CEUS). The aim of the present study was to examine the efficacy of contrast enhancement (CE) arrival time (AT) and other dynamic CEUS findings for differentiating between malignant and benign peripheral lung lesions. Methods. 317 inpatients and outpatients (215 men, 102 women; mean age: 52 years) with peripheral pulmonary lesions were included in the study and underwent pulmonary CEUS. Patients were examined in a sitting position after receiving an intravenous injection of 4.8 mL of sulfur hexafluoride microbubbles stabilized by a phospholipid shell as ultrasound contrast agent (SonoVue-Bracco; Milan, Italy). Each lesion was observed for at least 5 min in real-time and the following temporal characteristics of enhancement were detected: the arrival time (AT) of microbubbles in the target lesion; the enhancement pattern; the wash-out time (WOT) of microbubbles. Results were then compared in light of the definitive diagnosis of community acquired pneumonia (CAP) or malignancies, which was not known at the time of CEUS examination. All malignant cases were diagnosed by histological results, while pneumonia was diagnosed on the basis of clinical and radiological follow-up, laboratory findings and, in some cases, histology. Results. CE AT has not been shown to differ between benign and malignant peripheral pulmonary lesions. The overall diagnostic accuracy and sensibility of a CE AT cut-off value < 10 s in discriminating benign lesions were low (diagnostic accuracy: 47.6%; sensibility: 5.3%). Poor results were also obtained in the sub-analysis of small (mean diameter < 3 cm) and large (mean diameter > 3 cm) lesions. No differences were recorded in the type of CE pattern showed between benign and malignant peripheral pulmonary lesions. In benign lesions we observed a higher frequency of delayed CE wash-out time (WOT) > 300 s. Anyhow, a CE WOT cut-off value > 300 s showed low diagnostic accuracy (53.6%) and sensibility (16.5%) in discriminating between pneumonias and malignancies. Similar results were also obtained in the sub-analysis by lesion size. Squamous cell carcinomas showed a more delayed CE AT compared to other histopathology subtypes. However, such a difference was statistically significant with undifferentiated lung carcinomas. Conclusions. Due to an overlap of CEUS timings and patterns, dynamic CEUS parameters cannot effectively differentiate between benign and malignant peripheral pulmonary lesions. Chest CT remains the gold standard for lesion characterization and the eventual identification of other pneumonic non-subpleural localizations. Furthermore, in the case of malignancy, a chest CT is always needed for staging purposes.

Effectiveness and Safety of Real-Time Transthoracic Ultrasound-Guided Thoracentesis.

PURPOSE: The purpose of the present study was to specifically evaluate the effectiveness and safety of real-time ultrasound-guided thoracentesis in a case series of pleural effusion. PATIENTS AND METHODS: An observational prospective study was conducted. From February 2018 to December 2019, a total of 361 consecutive real-time transthoracic ultrasound (TUS)-guided thoracentesis were performed in the Unit of Diagnostic and Interventional Ultrasound of the Research Hospital "Fondazione Casa Sollievo della Sofferenza" of San Giovanni Rotondo, Foggia, Italy. The primary indication for thoracentesis was therapeutic in all the cases (i.e., evacuation of persistent small/moderate pleural effusions to avoid super-infection; drainage of symptomatic moderate/massive effusions). For completeness, further diagnostic investigations (including chemical, microbiological, and cytological analysis) were conducted. All the procedures were performed by two internists with more than 30 years of experience in interventional ultrasound using a multifrequency convex probe (3-8 MHz). For pleural effusions with a depth of 2-3 cm measured at the level of the costo-phrenic sinus was employed a dedicated holed convex-array probe (5 MHz). RESULTS: In all the cases, the attempts at thoracentesis were successful, allowing the achievement of the therapeutic purpose of the procedure (i.e., the complete drying of the pleural space or the withdrawal of fluid till a "safe" quantity [a mean of 1.5 L, max 2 L] producing relief from symptoms) regardless of the initial extent of the pleural effusion. There were only 3 cases of pneumothorax, for a prevalence rate of complications in this population of 0.83%. No statistical difference was recorded in the rate of pneumothorax according to the initial amount of pleural fluid in the effusion (p = 0.12). All the pleural effusions classified as transudates showed an anechoic TUS appearance. Only the exudative effusions showed a complex nonseptated or a hyperechoic TUS appearance. However, an anechoic TUS pattern was not unequivocally associated with transudates. Some chronic transudates have been classified as exudates by Light's criteria, showing also a complex nonseptated TUS appearance. The cytological examination of the drained fluid allowed the detection of neoplastic cells in 15.89% cases. On the other hand, the microbiological examination of effusions yielded negative results in all the cases. CONCLUSIONS: Real-time TUS-guided thoracentesis is a therapeutically effective and safe procedure, despite the diagnostic yield of the cytological or microbiological examinations on the collected liquid being very low. Future blinded randomized studies are required to definitely clarify the actual benefit of the real-time TUS-guided procedure over percussion-guided and other ultrasound-based procedures.

Transthoracic ultrasound shear wave elastography for the study of subpleural lung lesions.

PURPOSE: The aim of this study was to assess whether new-generation shear wave elastography (SWE) is suitable for the characterization of lung subpleural lesions. METHODS: In total, 190 consecutive patients with subpleural lung lesions received ultrasonography and SWE. Patients with suspected malignancy underwent ultrasound-guided transthoracic needle biopsy. Final diagnoses were made on the basis of patients' clinical course, microbiological studies, and histological results. SWE was also performed in 25 healthy volunteers. RESULTS: We found no statistically significant differences in stiffness between lung carcinomas, lung metastases, and pneumonia (P=0.296) or between different histological types of lung cancer (P=0.393). Necrosis was associated with reduced stiffness in pneumonia. Excluding necrotic lesions, pneumonia showed higher stiffness than lung carcinomas (2.95±0.68 m/s vs. 2.60±0.54 m/s, P=0.006). Chronic pneumonia showed increased stiffness (3.03±0.63 m/s), probably due to the presence of fibrotic tissue on histology. Pleural effusion was associated with a statistically significant reduction in stiffness, both in lung carcinomas (P=0.004) and lung metastases (P=0.002). The presence of air in healthy lung tissue may lead to incorrect speed estimates due to shear wave reflection (very high values, 14.64±2.19 m/s). CONCLUSION: Transthoracic SWE could not distinguish lung malignancy from pneumonia, or between different histological types of lung carcinomas. In particular, SWE seems unable to resolve the clinical dilemma of chronic subpleural consolidations.

Effectiveness and Safety of Transthoracic Ultrasound in Guiding Percutaneous Needle Biopsy in the Lung and Comparison vs. CT Scan in Assessing Morphology of Subpleural Consolidations.

(1) Background: The aim of this study was to conduct a prospective analysis on the diagnostic accuracy of transthoracic ultrasound-guided percutaneous needle biopsy (TUS-PNB) for the histological assessment of peripheral lung lesions and to assess the performance of transthoracic ultrasound (TUS) examination vs. chest CT (gold standard) in the differentiation between malignant and benign peripheral lung lesions. (2) Methods: A total of 961 consecutive patients with subpleural pulmonary lesions were enrolled. All the patients received a CT scan with contrast; 762 patients underwent TUS-PTNB for suspicion of malignancy, and the remaining 199 enrolled patients underwent only TUS examination as a part of routine follow-up for known non-malignant subpleural consolidations. (3) Results: Among the 762 TUS-guided biopsies, there were 627 (82.28%) malignant lesions, 82 (10.76%) benign lesions, and 53 (6.96%) indeterminate lesions. The overall diagnostic accuracy was 93.04%. The rates of pneumothorax not requiring chest-tube insertion and self-limited hemoptysis were 0.79 and 0.26%, respectively. Patients were divided into two groups based on the benign or malignant nature of the subpleural consolidations. On TUS, both malignant and benign lesions showed mostly irregular margins and a hypoechoic pattern, but no differences were assessed in terms of sonographic margins and pattern between the two groups. There was poor agreement between TUS and chest CT in assessing air bronchograms and necrotic areas. The only finding in the detection of which TUS showed superiority compared to chest-CT was pleural effusion. (4) Conclusions: TUS-PNB was confirmed to be an effective and safe diagnostic method for peripheral pulmonary consolidation, but their sonographic pattern did not allow to rule out a malignant nature. A pre-operative evaluation on CT images, combined with the possibility of performing additional immunohistochemical and cytological investigations and the experience of the medical staff, may improve the diagnostic yield of TUS-guided biopsies.

Intraoperative Lung Ultrasound (ILU) for the Assessment of Pulmonary Nodules.

BACKGROUND: The primary aim of this study was to confirm the validity of intraoperative lung ultrasound (ILU) as a safe and effective method of localization for difficult to visualize pulmonary nodules during Video-Assisted Thoracoscopic Surgery (VATS) and open thoracotomy. The secondary aim was to enhance knowledge on the morphological patterns of presentation of pulmonary nodules on direct ultrasound examination. MATERIALS AND METHODS: 131 patients with lung nodule and indication for surgery were enrolled. All patients underwent pre-operative imaging of the chest, including Chest Computed Tomography (CT) and Transthoracic Ultrasound (TUS), and surgical procedures for histological assessment of pulmonary nodules (VATS or open thoracotomy). RESULTS: The identification of 100.00% of lung nodules was allowed by ILU, while the detection rate of digital palpation was 94.66%. It was not possible to associate any specific ILU echostructural pattern to both benign or malignant lesions. However, the actual histological margins of the lesions in the operating samples were corresponding to those visualized at ILU in 125/131 (95.42%) cases. No complications have been reported with ILU employment. CONCLUSIONS: In our experience, ILU performed during both open surgery and VATS demonstrated to be a reliable and safe method for visualization and localization of pulmonary nodules non previously assessed on digital palpation. In addition, ILU showed to allow a clear nodule's margins' definition matching, in most cases, with the actual histological margins.

Transthoracic Ultrasound in Infectious Organizing Pneumonia: A Useful Guide for Percutaneous Needle Biopsy.

In patients presenting with classical features of CAP (i.e., new peripheral pulmonary consolidations and symptoms including fever, cough, and dyspnea), a clinical response to the appropriate therapy occurs in few days. When clinical improvement has not occurred and chest imaging findings are unchanged or worse, a more aggressive approach is needed in order to exclude other non-infective lesions (including neoplasms). International guidelines do not currently recommend the use of transthoracic ultrasound (TUS) as an alternative to chest X-ray (CXR) or chest computed tomography (CT) scan for the diagnosis of CAP. However, a fundamental role for TUS has been established as a guide for percutaneous needle biopsy (US-PNB) in pleural and subpleural lesions. In this retrospective study, we included 36 consecutive patients whose final diagnosis, made by a US-guided percutaneous needle biopsy (US-PTNB), was infectious organizing pneumonia (OP). Infective etiology was confirmed by additional information from microbiological and cultural studies or with a clinical follow-up of 6-12 months after a second-line antibiotic therapy plus corticosteroids. All patients have been subjected to a chest CT and a systematic TUS examination before biopsy. This gave us the opportunity to explore TUS performance in assessing CT findings of infective OP. TUS sensitivity and specificity in detecting air bronchogram and necrotic areas were far lower than those of CT scan. Conversely, TUS showed superiority in the detection of pleural effusion. Although ultrasound findings did not allow the characterization of chronic subpleural lesions, TUS confirmed to be a valid diagnostic aid for guiding percutaneous needle biopsy of subpleural consolidations.

BRAFV600E mutation impinges on gut microbial markers defining novel biomarkers for serrated colorectal cancer effective therapies.

BACKGROUND: Colorectal cancer (CRC) harboring BRAFV600E mutation exhibits low response to conventional therapy and poorest prognosis. Due to the emerging correlation between gut microbiota and CRC carcinogenesis, we investigated in serrated BRAFV600E cases the existence of a peculiar fecal microbial fingerprint and specific bacterial markers, which might represent a tool for the development of more effective clinical strategies. METHODS: By injecting human CRC stem-like cells isolated from BRAFV600E patients in immunocompromised mice, we described a new xenogeneic model of this subtype of CRC. By performing bacterial 16S rRNA sequencing, the fecal microbiota profile was then investigated either in CRC-carrying mice or in a cohort of human CRC subjects. The microbial communities' functional profile was also predicted. Data were compared with Mann-Whitney U, Welch's t-test for unequal variances and Kruskal-Wallis test with Benjamini-Hochberg false discovery rate (FDR) correction, extracted as potential BRAF class biomarkers and selected as model features. The obtained mean test prediction scores were subjected to Receiver Operating characteristic (ROC) analysis. To discriminate the BRAF status, a Random Forest classifier (RF) was employed. RESULTS: A specific microbial signature distinctive for BRAF status emerged, being the BRAF-mutated cases closer to healthy controls than BRAF wild-type counterpart. In agreement, a considerable score of correlation was also pointed out between bacteria abundance from BRAF-mutated cases and the level of markers distinctive of BRAFV600E pathway, including those involved in inflammation, innate immune response and epithelial-mesenchymal transition. We provide evidence that two candidate bacterial markers, Prevotella enoeca and Ruthenibacterium lactatiformans, more abundant in BRAFV600E and BRAF wild-type subjects respectively, emerged as single factors with the best performance in distinguishing BRAF status (AUROC = 0.72 and 0.74, respectively, 95% confidence interval). Furthermore, the combination of the 10 differentially represented microorganisms between the two groups improved performance in discriminating serrated CRC driven by BRAF mutation from BRAF wild-type CRC cases (AUROC = 0.85, 95% confidence interval, 0.69-1.01). CONCLUSION: Overall, our results suggest that BRAFV600E mutation itself drives a distinctive gut microbiota signature and provide predictive CRC-associated bacterial biomarkers able to discriminate BRAF status in CRC patients and, thus, useful to devise non-invasive patient-selective diagnostic strategies and patient-tailored optimized therapies.

Balò's concentric sclerosis in a case of cocaine-levamisole abuse.

Baló's concentric sclerosis is a rare variant of multiple sclerosis. It belongs to the group of primary inflammatory central nervous system demyelinating diseases having no clear etiology. Peculiar radiological findings on magnetic resonance imaging are alternating rings of demyelinated and myelinated axons resembling an "onion bulb." We report on a case of a patient with cocaine abuse who presented with Balò's-like acute multifocal leukoencephalopathy supported by histological and radiological findings. The abuse of cocaine and its most frequent adulterant, levamisole, may induce ischemic or hemorrhagic stroke and metabolic or multifocal inflammatory leukoencephalopathy. Only a few studies described levamisole-induced leukoencephalopathy mimicking Balò round lesions. Nevertheless, it has not yet been established the correlation between them; it might also be possible that the cocaine/levamisole addiction represents just a coincidence in some of those patients affected by Balò sclerosis disease.

Video-assisted thoracic surgery ultrasound (VATS-US) in the evaluation of subpleural disease: preliminary report of a systematic study.

We provide a pictorial essay examining the preliminary data of an ongoing study whose primary aim is to assess the usefulness and safety of video-assisted thoracic surgery ultrasound (VATS-US) in the identification of different lung diseases. We studied 14 patients (five women and nine men with a mean age of 56.2 ± 8.4 SD years) with indication for VATS. All patients underwent pre-operative imaging of the chest using high-resolution computed-tomography, contrast-enhanced computed-tomography, and/or positron emission tomography and transthoracic ultrasound. VATS-US was performed under general anesthesia with single-lung ventilation through double-lumen endotracheal intubation in all patients, and the Esaote MyLab 25 laparoscope probe with flexible tip and a linear array transducer at frequencies 8.0-12.0 MHz was used. The final histological diagnoses in our cohort were cancer (three cases), usual interstitial pneumonia (five cases), nonspecific interstitial pneumonia (two cases), and hypersensitivity pneumonitis (one case). In patients with pulmonary fibrosis, the VATS-US showed a thick hyperechoic pleural line and no B-lines. Regarding cancer nodules, the VATS-US images showed a uniform hypoechogenic pattern with jagged margins. In patients with hamartochondroma and histocytosis X, VATS-US showed a mixed hyperechoic structure of the margins. In conclusion, we described the US semeiotics of various lung disorders assessed during VATS by reporting the preliminary data of the first study which applies the methodology systematically to all patients undergoing the surgery procedure. Final results from the study will further elucidate how the technique could be of use during the VATS procedure.

Safety maximization of percutaneous transthoracic needle biopsy with ultrasound guide in subpleural lesions in the evaluation of pulmonary consolidation.

The study by Kiranantawat et al. "Clinical role, safety and diagnostic accuracy of percutaneous transthoracic needle biopsy in the evaluation of pulmonary consolidation" highlights how "pulmonary consolidation can be safely evaluated with CT-guided percutaneous needle biopsy". Even if we agree about the role of CT guidance, we would like to point out how Thoracic Ultrasound could be better than CT for biopsy of subpleural lesions that could easily be detected and reached with this "real-time" and quicker technique.

Left Supraclavicular Swelling: Sclerosing Perineurioma.

A sclerosing perineurioma presents as a single asymptomatic papule or nodule located on the hands of adult patients; approximately 60 cases have been reported in medical literature since 1997. Histologically, it originates from the perineural cells of the peripheral nerves and presents epithelial membrane antigen (EMA) positivity and S100 protein negativity. Here, we present the case of a 58-year-old male admitted to our surgery unit complaining of left supraclavicular swelling of 1-cm in size, having no significant past medical history. A lymph node neck tumor was suspected, and the patient underwent surgery under local anesthesia in outpatient care. The intraoperative finding was a whitish mass, wooden-fibrous in consistency, strictly adhering to the skin and apparently fixed to the deep planes. Upon histological examination, a sclerosing perineurioma was diagnosed: neoplastic cells were immunoreactive for CD34, CD99, and EMA, and negative for S100 protein, smooth-muscle actin, pancytokeratin (AE1-AE3), CD31, neurofilaments, and beta-catenin. According to the benign biological tumor behavior, radical resection was considered an adequate treatment. Our case presents as peculiarity the unusual non-acral location (first reported as supraclavicular swelling) and the rare immunopositivity for CD34 and CD99.

Assessment of thoracic ultrasound in complementary diagnosis and in follow up of community-acquired pneumonia (cap).

BACKGROUND: Chest X-ray (CXR) is the primary diagnostic tool for community-acquired pneumonia (CAP). Some authors recently proposed that thoracic ultrasound (TUS) could valuably flank or even reliably substitute CXR in the diagnosis and follow-up of CAP. We investigated the clinical utility of TUS in a large sample of patients with CAP, to challenge the hypothesis that it may be a substitute for CXR. METHODS: Out of 645 consecutive patients with a CXR-confirmed CAP diagnosed in the emergency room of our hospital over a three-years period, 510 were subsequently admitted to our department of Internal Medicine. These patients were evaluated by TUS by a well-trained operator who was blinded of the initial diagnosis. TUS scans were performed both at admission and repeated at day 4-6th and 9-14th during stay. RESULTS: TUS identified 375/510 (73.5%) of CXR-confirmed lesions, mostly located in posterior-basal or mid-thoracic areas of the lungs. Pleural effusion was detected in 26.9% of patients by CXR and in 30.4% by TUS. TUS documented the change in size of the consolidated areas as follows: 6.3 ± 3.4 cm at time 0, 2.5 ± 1.8 at 4-6 d, 0.9 ± 1.4 at 9-14 d. Out of the 12 patients with delayed CAP healing, 7 of them turned out to have lung cancer. CONCLUSIONS: TUS allowed to detect lung consolidations in over 70% of patients with CXR-confirmed CAP, but it gave false negative results in 26.5% of cases. Our longitudinal results confirm the role of TUS in the follow-up of detectable lesions. Thus, TUS should be regarded as a complementary and monitoring tool in pneumonia, instead of a primary imaging modality.

The role of ultrasound-guided fine needle aspiration biopsy in musculoskeletal diseases.

Ultrasonography (US) is a readily available non-invasive tool useful for the detection of musculoskeletal and soft tissue masses. Although X-Ray is often the first imaging study for evaluating both bone and soft tissue lesions, and magnetic resonance imaging and computed tomography are mandatory in lesions staging, US is increasingly used for the early assessment of musculoskeletal and soft-tissue masses and for guiding procedures and biopsies. Surgical biopsy or fine needle aspiration biopsy (FNAB) is needed to ascertain the nature of any lesion. FNAB is a low cost technique, safer and less traumatic than an open surgical biopsy. Significant complications are rare, mostly related to the site of biopsy. Knowledge of indications, limitations, anatomical and pathological access, adequate technical expertise in US imaging and in intervention skills are the critical factors of the appropriate and safe use of FNAB. By now, the role of FNAB in musculoskeletal diseases is controversial and there is still a heated debate in the scientific community.

Contrast-enhanced ultrasound does not discriminate between community acquired pneumonia and lung cancer.

We investigated if contrast-enhanced ultrasound (CEUS) may differentiate community acquired pneumonia (CAP) from lung cancer (LC). Among 1374 patients admitted in a 5-year period for lung opacities, 728 (329 CAP and 399 LC) were investigated by CEUS, comparing the time of appearance, disappearance, duration and pattern of distribution of contrast enhancement (CE). The patients with CAP and LC did not differ in terms of age, time of CE appearance, disappearance and duration or CE distribution. Our data show that the timing and pattern of CE detected by chest CEUS does not distinguish between CAP and LC and overly optimistic beliefs on this matter should be abandoned.

TRIM8 downregulation in glioma affects cell proliferation and it is associated with patients survival.

BACKGROUND: Human gliomas are a heterogeneous group of primary malignant brain tumors whose molecular pathogenesis is not yet solved. In this regard, a major research effort has been directed at identifying novel specific glioma-associated genes. Here, we investigated the effect of TRIM8 gene in glioma. METHODS: TRIM8 transcriptional level was profiled in our own glioma cases collection by qPCR and confirmed in the independent TCGA glioma cohort. The association between TRIM8 expression and Overall Survival and Progression-free Survival in TCGA cohort was determined by using uni-multivariable Cox regression analysis. The effect of TRIM8 on patient glioma cell proliferation was evaluated by performing MTT and clonogenic assays. The mechanisms causing the reduction of TRIM8 expression were explored by using qPCR and in vitro assays. RESULTS: We showed that TRIM8 expression correlates with unfavorable clinical outcome in glioma patients. We found that a restored TRIM8 expression induced a significant reduction of clonogenic potential in U87MG and patient's glioblastoma cells. Finally we provide experimental evidences showing that miR-17 directly targets the 3' UTR of TRIM8 and post-transcriptionally represses the expression of TRIM8. CONCLUSIONS: Our study provides evidences that TRIM8 may participate in the carcinogenesis and progression of glioma and that the transcriptional repression of TRIM8 might have potential value for predicting poor prognosis in glioma patients.