Management of patients with extensive small-cell lung cancer in the immunotherapy era: an Italian consensus through a Delphi approach.

BACKGROUND: Immunotherapy represented a turning point for treating extensive small-cell lung cancer (ES-SCLC). Although, many issues remain debated. METHODS: A group of Italian medical and radiation oncologists with expertise in managing patients with ES-SCLC developed a list of statements divided in six areas of interest. The Delphi method was used to assess the consensus on the defined list of statements. RESULTS: 32 statements were included in the final list to be voted by the Delphi panel, and 26 reached a consensus on the agreement. A prompt involvement of a multidisciplinary team is a priority to provide an integrated treatment strategy. First-line recommended treatment is immunotherapy in combination with platinum-based chemotherapy and etoposide for four cycles followed by maintenance immunotherapy. CONCLUSIONS: While awaiting new data from clinical trials and real-world studies, these recommendations can represent a useful tool to guide the management of ES-SCLC patients in daily practice.

Evaluation of RADIANCE Monte Carlo algorithm for treatment planning in electron based Intraoperative Radiotherapy (IOERT).

PURPOSE: To perform experimental as well as independent Monte Carlo (MC) evaluation of the MC algorithm implemented in RADIANCE version 4.0.8, a dedicated treatment planning system (TPS) for 3D electron dose calculations in intraoperative radiation therapy (IOERT). METHODS AND MATERIALS: The MOBETRON 2000 (IntraOp Medical Corporation, Sunnyvale, CA) IOERT accelerator was employed. PDD and profiles for five cylindrical plastic applicators with 50-90 mm diameter and 0°, 30° beveling were measured in a water phantom, at nominal energies of 6, 9 and 12 MeV. Additional PDD measurements were performed for all the energies without applicator. MC modeling of the MOBETRON was performed with the user code BEAMnrc and egs_chamber of the MC simulation toolkit EGSnrc. The generated phase space files of the two 0°-bevel applicators (50 mm, 80 mm) and three energies in both RADIANCE and BEAMnrc, were used to determine PDD and profiles in various set-ups of virtual water phantoms with air and bone inhomogeneities. 3D dose distributions were also calculated in image data sets of an anthropomorphic tissue-equivalent pelvis phantom. Image acquisitions were realized with a CT scanner (Philips Big Bore CT, Netherlands). Gamma analysis was applied to quantify the deviations of the RADIANCE calculations to the measurements and EGSnrc calculations. Gamma criteria normalized to the global maximum were investigated between 2%, 2 mm and 3%, 3 mm. RESULTS: RADIANCE MC calculations satisfied the gamma criteria of 3%, 3 mm with a tolerance limit of 85% passing rate compared to in- water phantom measurements, except for the dose profiles of the 30° beveled applicators. Mismatches lay in surface doses, in umbra regions and in the beveled end of the 30° applicators. A very good agreement to the EGSnrc calculations in heterogeneous media was observed. Deviations were more pronounced for the larger applicator diameter and higher electron energy. In 3D dose comparisons in the anthropomorphic phantom, gamma passing rates were higher than 96 % for both simulated applicators. CONCLUSIONS: RADIANCE MC algorithm agrees within 3%, 3 mm criteria with in-water phantom measurements and EGSnrc MC dose distributions in heterogeneous media for 0°-bevel applicators. The user should be aware of missing scattering components and the 30° beveled applicators should be used with attention.

Non-Small Cell Lung Cancer Testing on Reference Specimens: An Italian Multicenter Experience.

INTRODUCTION: Biomarker testing is mandatory for the clinical management of patients with advanced non-small cell lung cancer (NSCLC). Myriads of technical platforms are now available for biomarker analysis with differences in terms of multiplexing capability, analytical sensitivity, and turnaround time (TAT). We evaluated the technical performance of the diagnostic workflows of 24 representative Italian institutions performing molecular tests on a series of artificial reference specimens built to mimic routine diagnostic samples. METHODS: Sample sets of eight slides from cell blocks of artificial reference specimens harboring exon 19 EGFR (epidermal growth factor receptor) p.E746_AT50del, exon 2 KRAS (Kirsten rat sarcoma viral oncogene homologue) p.G12C, ROS1 (c-ros oncogene 1)-unknown gene fusion, and MET (MET proto-oncogene, receptor tyrosine kinase) Δ exon 14 skipping were distributed to each participating institution. Two independent cell block specimens were validated by the University of Naples Federico II before shipment. Methodological and molecular data from reference specimens were annotated. RESULTS: Overall, a median DNA concentration of 3.3 ng/µL (range 0.1-10.0 ng/µL) and 13.4 ng/µL (range 2.0-45.8 ng/µL) were obtained with automated and manual technical procedures, respectively. RNA concentrations of 5.7 ng/µL (range 0.2-11.9 ng/µL) and 9.3 ng/µL (range 0.5-18.0 ng/µL) were also detected. KRAS exon 2 p.G12C, EGFR exon 19 p.E736_A750del hotspot mutations, and ROS1 aberrant transcripts were identified in all tested cases, whereas 15 out of 16 (93.7%) centers detected MET exon 14 skipping mutation. CONCLUSIONS: Optimized technical workflows are crucial in the decision-making strategy of patients with NSCLC. Artificial reference specimens enable optimization of diagnostic workflows for predictive molecular analysis in routine clinical practice.

Clinical impact of mixed pulmonary carcinoma and carcinoid: the driver from their mono-clonal origin.

The combination of neuroendocrine/non neuroendocrine lung tumors (CNNELT) mentioned in the last edition of the World Health Organization (WHO) of Thoracic Tumors refers to small cell carcinoma (SCLC) or large cell neuroendocrine carcinoma (LCNEC) mixed with any other non-small cell lung carcinoma (NSCLC). Typical Carcinoid (TC)/Atypical Carcinoid (AC) combined with NSCLC is not included among this category. However, case reports of TC/AC combined with NSCLC have been described. We previously reported 2 cases of lung adenocarcinoma (LUA) mixed with carcinoid sharing mutations in both components supporting the hypothesis of a clonal origin. We extended our analysis to other four cases of mixed NSCLC-carcinoid by performing targeted-DNA and RNA-based NGS analysis in both primary and their paired lymph nodes metastasis. In all cases, LUA and AC components shared at least 1 common mutation (KRAS driver mutation p.Gly12Val in cases 1 and 3, AKAP13-RET fusion in case 2, and missense KRAS driver mutation p.Gly12Ala in case 4, reinforcing the hypothesis of a clonal origin. Moreover, the same mutation was detected in the metastasis constituted only by AC (cases 2 and 4). Although it is a rare malignancy in the lung, mixed LUA and TC/AC could be included among the histotypes for which a deep molecular characterization of both components is needed to identify the presence of potential druggable genetic alterations.

COVID-19 and lung cancer.

COVID-19 pandemic had affected health services around the world, also reducing the diagnosis of lung cancer. On the other hand, examination of surgical specimens in patients with lung cancer and SARS-CoV-2 gave the opportunity to evidence early histologic features related to this emerging pandemic.Different prioritization of health organizations during COVID-19 pandemic resulted in a significant decline of lung cancer screening (up to 56%), delayed diagnosis (up to 30-40%) and higher advanced stage, with some exceptions (i.e., Canada). Increased use of stereotactic radiation treatments in stage I-IIA have been noticed in better-organized health systems. Surgical specimens performed for lung cancer in patients with incipient SARS-CoV-2 permitted to appreciate early histologic findings of COVID-19 with hyperplastic pneumocytes with/without fibrin exudate, alveolar macrophages/myeloid cells, perivascular T-lymphocytic infiltrate and lack of hyaline membrane.While the COVID-19 pandemic has declined the rate of lung cancer diagnosis worldwide, some institutions have significantly limited detrimental effects. Histology related to early SARS-CoV-2 infection in surgical samples for lung cancer revealed specific histologic changes.

Evaluation of a Novel Fixative Solution for Liquid-Based Cytology in Diagnostic Cytopathology.

Since its introduction in the early 2000s, liquid-based cytology (LBC) has been increasingly used for gynecologic and non-gynecologic cytology, and its multiple advantages have been widely recognized. The aim of this study was to investigate the use of a new fixative and pre-analytical method for morphological diagnosis in cytological samples. In particular, we evaluated the effect of a novel preservative solution on the preparation of diagnostic slides by comparing it with the standard reference used globally in cytology laboratories. This study included both gynecological (n = 139) and non-gynecological (n = 183) samples. Several morphologic variables were then identified and evaluated. Using this approach, we were then able to demonstrate the suitability of the new system, with improved safety, to be integrated within current pathology clinical practice. Overall, using a safer preservative solution, the study shows no statistical difference (and then non-inferiority) in the new fixation protocol compared with the standard reference used in routine practice in terms of diagnostic adequacy, evaluated both in clinically relevant gyn and non-gyn datasets.

Clinicopathological Features of Non-Small Cell Lung Carcinoma with BRAF Mutation.

(1) Background: BRAF mutations affect 4-5% of lung adenocarcinomas. This study aimed to analyze the clinicopathological features of lung carcinomas with BRAF mutations, focusing on V600E vs. non-V600E and the presence of co-mutations. (2) Methods: All BRAF-mutated lung carcinomas were retrieved from a molecular diagnostic unit (the reference unit for four different hospitals). The samples were analyzed using next-generation sequencing. Statistical analyses included log-rank tests for overall survival (OS) and progression-free survival (PFS). (3) Results: In total, 60 BRAF-mutated lung carcinomas were retrieved: 24 (40.0%) with V600E and 36 (60.0%) with non-V600E mutations, and 21 (35.0%) with other co-mutations and 39 (65.0%) with only BRAF mutations. Survival data were available for 54/60 (90.0%) cases. Targeted therapy was documented in 11 cases. Patients with V600E mutations exhibited a better prognosis than patients with non-V600E mutations (p = 0.008 for OS, p = 0.018 for PFS); this was confirmed in PFS (p = 0.036) when considering only patients who received no targeted therapy. Patients with co-mutations displayed no prognostic difference compared to patients carrying only BRAF mutations (p = 0.590 for OS, p = 0.938 for PFS). (4) Conclusions: BRAF-mutated lung carcinomas with V600E (40.0%) had a better prognosis than those without V600E. Concomitant co-mutations (35.0%) did not affect the prognosis.

Up-regulation by overexpression of c-MET in fibroblastic foci of usual interstitial pneumonia.

Background: Usual interstitial pneumonia (UIP) is the radiologic and histologic hallmark of idiopathic pulmonary fibrosis (IPF) and the commonest histologic pattern of other progressive fibrosing interstitial lung diseases (e.g., fibrotic hypersensitivity pneumonia). Analogous to lung cancer, activation of epithelial-to-mesenchymal transition (EMT) is one of the main molecular pathways recently identified by transcriptomic studies in IPF. Fibroblastic foci (FF) are considered the active/trigger component of UIP pattern. The proto-oncogene C-MET is a key gene among molecules promoting EMT against which several inhibitors are currently available or promising in ongoing studies on lung cancer. Methods: Twenty surgical cases of diffuse fibrosing interstitial lung diseases (fILD) with UIP pattern and FF-rich (17 IPF and 3 patients with fibrotic hypersensitivity pneumonia, fHP) were retrospectively selected. FF were manually microdissected and analysed for c-MET gene alterations (FISH amplification and gene hot-spot mutations Sanger sequencing) and tested with a c-MET companion diagnostic antibody (clone SP44 metmab) by immunohistochemistry. Results: FF are characterized by upregulation of c-MET as shown by overexpression of the protein in 80% of cases, while no gene amplification by FISH or mutations were detected. C-MET upregulation of FF was observed either in IPF and fHP, with a tropism for the epithelial cell component only. Conclusion: Upregulation of c-MET in FF of ILD with UIP pattern further confirms the key role of the proto-oncogene c-MET in its pathogenesis, possibly representing an interesting and easily-detectable molecular target for selective therapy using specific inhibitors in future clinical trials, similar to lung cancer. It is reasonable to speculate that molecular alterations in FF can also be detected in FF by transbronchial cryobiopsy.

Update in Lung Cancer Molecular Pathology: Technological Advances and Clinical Practice.

This Special Issue of eleven articles, including six original works and five reviews, demonstrates the modern heterogenous approach to lung cancer by means of various methodologies from international experts from various countries [...].

Passively CEP stable sub-2-cycle source in the mid-infrared by adiabatic difference frequency generation.

We report on the generation of a passive carrier-envelope phase (CEP) stable 1.7-cycle pulse in the mid-infrared by adiabatic difference frequency generation. With sole material-based compression, we achieve a sub-2-cycle 16-fs pulse at a center wavelength of 2.7 µm and measured a CEP stability of <190 mrad root mean square. The CEP stabilization performance of an adiabatic downconversion process is characterized for the first time, to the best of our knowledge.

Parametric waveform synthesis: a scalable approach to generate sub-cycle optical transients.

The availability of electromagnetic pulses with controllable field waveform and extremely short duration, even below a single optical cycle, is imperative to fully harness strong-field processes and to gain insight into ultrafast light-driven mechanisms occurring in the attosecond time-domain. The recently demonstrated parametric waveform synthesis (PWS) introduces an energy-, power- and spectrum-scalable method to generate non-sinusoidal sub-cycle optical waveforms by coherently combining different phase-stable pulses attained via optical parametric amplifiers. Significant technological developments have been made to overcome the stability issues related to PWS and to obtain an effective and reliable waveform control system. Here we present the main ingredients enabling PWS technology. The design choices concerning the optical, mechanical and electronic setups are justified by analytical/numerical modeling and benchmarked by experimental observations. In its present incarnation, PWS technology enables the generation of field-controllable mJ-level few-femtosecond pulses spanning the visible to infrared range.

Rapid on-site evaluation improves the sensitivity of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for solid pancreatic lesions irrespective of technique: A single-centre experience.

OBJECTIVE: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is the first-line technique for the sampling of pancreatic lesions. Many factors can influence the diagnostic performance of this procedure, including the use of rapid on-site evaluation (ROSE). The primary aim of this study was to compare the adequacy, diagnostic yield, accuracy, sensitivity and specificity of EUS-FNA for solid pancreatic lesions before and after the introduction of ROSE. METHODS: This retrospective single-centre study evaluated all consecutive patients who underwent EUS-FNA for suspicious, solid pancreatic masses from April 2012 to March 2015. We compared the findings of EUS-FNA procedures performed during the first and second years following the adoption of ROSE ("ROSE1" and "ROSE2", respectively) to those performed the year before ROSE introduction (the "pre-ROSE" group). RESULTS: Ninety-one consecutive patients with a total of 93 pancreatic lesions were enrolled. For the pre-ROSE, ROSE1 and ROSE2 groups, the adequacy rates were 96.2%, 96.6% and 100%, the diagnostic yield values were 76.9%, 89.7% and 92.1% and accuracy values were 69.2%, 86.2% and 89.5% (p = NS). Sensitivity for malignancy improved from 63.7% in the pre-ROSE group to 91.7% and 91.2% in the post-ROSE groups (p < 0.05). Specificity for malignancy was 100% in all groups. CONCLUSIONS: ROSE can improve the diagnostic performance of EUS-FNA for solid pancreatic lesions, although only sensitivity reached statistical significance.

Integrated Decision-Making in the Treatment of Colon-Rectal Cancer: The Case of KRAS-Mutated Tumors.

In recent years, precision medicine has taken an increasing place in various branches of medical oncology, including colorectal cancer. Among the potentially relevant mutations for this cancer is the KRAS mutation, initially defined as "untargetable"; today, we see the birth of new molecules that target one of the variants of the KRAS mutation, KRAS G12C, having a significant impact on the therapeutic options for other malignancies, such as metastatic lung cancer. This fundamental step forward has stimulated scientific research on other potential targets of KRAS, both indirect and direct, and combination treatments aiming to overcome the mechanisms of resistance to these drugs that decrease in efficacy in colorectal cancer. What was once a negative predictive marker of response to anti-EGFR drugs today has become a potential target for targeted treatments. In turn, the prognostic role of the mutation has become extremely interesting, making it a potentially useful element in therapeutic decision-making, not only regarding oncological treatments but also in a more complex and complete manner within a global vision of the patient, involving other figures on the multidisciplinary team, such as surgeons, radiotherapists, and interventional radiologists.

Diffuse Pulmonary Meningotheliomatosis: Clinic-Pathologic Entity or Indolent Metastasis from Meningioma (or Both)?

Pulmonary minute meningothelial-like nodules (MMNs) are common incidental findings in surgical specimens, consisting of tiny proliferation (usually no larger than 5-6 mm) of bland-looking meningothelial cells showing a perivenular and interstitial distribution, sharing morphologic, ultrastructural, and immunohistochemical profiles with meningiomas. The identification of multiple bilateral MMNs leading to an interstitial lung disease characterized by diffuse and micronodular/miliariform patterns radiologically allows the diagnosis of diffuse pulmonary meningotheliomatosis (DPM). Nevertheless, the lung is the most common site of metastatic primary intracranial meningioma, and differential diagnosis with DPM may be impossible without clinic-radiologic integration. Herein, we report four cases (three females; mean age, 57.5 years) fitting the criteria of DPM, all incidentally discovered and histologically evidenced on transbronchial biopsy (2) and surgical resection (2). All cases showed immunohistochemical expression of epithelial membrane antigen (EMA), progesterone receptor, and CD56. Notably, three of these patients had a proven or radiologically suspected intracranial meningioma; in two cases, it was discovered before, and in one case, after the diagnosis of DPM. An extensive literature review (44 patients with DPM) revealed similar cases with imaging studies excluding intracranial meningioma in only 9% (4 of 44 cases studied). The diagnosis of DPM requires close correlation with the clinic-radiologic data since a subset of cases coexist with or follow a previously diagnosed intracranial meningioma and, thus, may represent incidental and indolent metastatic deposits of meningioma.

Immunohistochemistry for Claudin-4 and BAP1 in the Differential Diagnosis between Sarcomatoid Carcinoma and Sarcomatoid Mesothelioma.

(1) Background. In the differential diagnosis between sarcomatoid carcinoma (SC) and sarcomatoid mesothelioma (SM), we aimed to investigate the role of Claudin-4 and BAP1, a panel recently used to distinguish conventional carcinoma from epithelioid mesothelioma. (2) Methods. We collected 41 surgical pleural biopsies of SM, 46 surgical resections of SC from different sites and 49 pleural biopsies of normal/hyperplastic mesothelium. All the cases were tested for Claudin-4 and BAP1 using immunohistochemistry. The statistical calculations of the sensitivity, specificity and positive and negative predictive values were performed. (3) Results: Claudin-4 was negative in 41/41 SMs, while it was positive in 18/36 (50.1%) SCs (eight diffusely, 10 focally) within their sarcomatous component. BAP1 was lost in 23/41 SMs, while it was regularly expressed in 46/46 SCs. All the cases of the normal/hyperplastic mesothelium were negative for Claudin-4 and retained the regular expression of BAP1. The Claudin-4 expression was useful for detecting SC (sensitivity, 39.1%; specificity, 100%) and the BAP1 loss was useful for diagnosing SM (sensitivity, 56.1%; specificity, 100%). (4) Conclusions. The staining for Claudin-4 and BAP1 exhibited a low/moderate sensitivity in diagnosing SC and SM (39.1% and 56.1%, respectively), but a very high specificity (100%). Claudin-4 was expressed only in SC and BAP1 loss was noted only in SM.

Post-traumatic glomus tumor of the left anterior supraclavicular nerve: a case report.

OBJECTIVES: Peripheral nerve glomus tumors are extremely rare and occur with typical symptoms of peripheral neuropathic pain. Clinicians hardly consider this entity when faced with the swelling of a peripheral nerve and the diagnosis is reached only with histological examination. Nerves of limbs are usually affected and the solid glomus tumor is the most frequent histological variant. CASE DESCRIPTION: A 55-year-old man presented with a glomus tumor of the anterior supraclavicular nerve of the left cervical plexus, misdiagnosed clinically and radiologically as neuroma. Despite the preoperative suspicion and the intraoperative appearance, the histological examination revealed a glomus tumor with a prevalent muscular component, a glomangiomyoma. Once the tumor was removed, pain regressed completely. CONCLUSIONS: Because of its rarity, pre-operative diagnosis of glomus tumors is still a challenge, especially when arising from peripheral nerves. In the presence of chronic localized neuroma-type pain and sensitivity, glomus tumors should be considered in the pool of differential diagnosis, even if the imaging is not conclusive.

Monophasic synovial sarcoma mimicking schwannoma: a case report of a rare peripheral nerve tumor and literature review.

INTRODUCTION: Synovial sarcomas occurring as primary nerve tumors (SSPN) are rare and only 69 cases of SSPNs are reported in literature. Despite the little data available, SSPNs differ from other SSs in some distinctive aspects such as epidemiology, location, and early onset of symptoms. SSPN are consequently underdiagnosed and easily mistaken for benign or malignant peripheral nerve sheath tumors (PNST). Therefore, cytogenetic or molecular testing becomes essential in order to make a correct diagnosis. This article deals with an extremely rare case of monophasic SSPN of the posterior cords of the right brachial plexus. To our knowledge, this is only the tenth case of intraneural synovial sarcoma involving the brachial plexus. CASE PRESENTATION: We report the case of a 64-year-old man, who came to our attention due to a slow-growing painful right axillary neoformation, approximately 25 mm in size. The patient did not show any neurological impairments. Ultrasonography and constrast MRI showed a heterogeneous mass arising from the posterior cord of the right brachial plexus, resembling a schwannoma. The patient underwent total resection of tumor and capsule. Histologically, a diagnosis of monophasic synovial sarcoma was made based on histologic features and the immunohistochemical profile. CONCLUSIONS: We report a rare primary synovial sarcoma of the brachial plexus. Given its rarity, the diagnosis may be challenging and requires a core biopsy or the surgical specimen to permit immune-molecular analysis. Margin-free surgery is the mainstay of curative treatment, while chemo- or radiotherapy may have a role in advanced or margin-positive neoplasms.

Determination of the dose rate around a HDR 192Ir brachytherapy source with the microDiamond and the microSilicon detector.

PURPOSE: To employ the microDiamond and the microSilicon detector (mDD and mSD, both PTW-Freiburg, Germany) to determine the dose rate around a HDR 192Ir brachytherapy source (model mHDR-v2r, Elekta AB, Sweden). METHODS: The detectors were calibrated with a 60Co beam at the PTW Calibration Laboratory. Measurements around the 192Ir source were performed inside a PTW MP3 water phantom. The detectors were placed at selected points of measurement at radial distances r, ranging from 0.5 to 10 cm, keeping the polar angle θ = 90°. Additional measurements were performed with the mSD at fixed distances r = 1, 3 and 5 cm, with θ varying from 0 to 150°, 0 to 166°, and 0 to 168°, respectively. The corresponding mDD readings were already available from a previous work (Rossi et al., 2020). The beam quality correction factor of both detectors, as well as a phantom effect correction factor to account for the difference between the experimental geometry and that assumed in the TG-43 formalism, were determined using the Monte Carlo (MC) toolkit EGSnrc. The beam quality correction factor was factorized into energy dependence and volume-averaging correction factors. Using the abovementioned MC-based factors, the dose rate to water at the different points of measurement in TG-43 conditions was obtained from the measured readings, and was compared to the dose rate calculated according to the TG-43 formalism. RESULTS: The beam quality correction factor was considerably closer to unity for the mDD than for the mSD. The energy dependence of the mDD showed a very weak radial dependence, similar to the previous findings showing a weak angular dependence as well (Rossi et al., 2020). Conversely, the energy dependence of the mSD decreased significantly with increasing distances, and also showed a considerably more pronounced angular dependence, especially for the smallest angles. The volume-averaging showed a similar radial dependence for both detectors: the correction had a maximal impact at 0.5 cm and then approached unity for larger distances, as expected. Concerning the angular dependence, the correction for the mSD was also similar to the one previously determined for the mDD (Rossi et al., 2020): a maximal impact was observed at θ = 0°, with values tending to unity for larger angles. In general, the volume-averaging was less pronounced for the mSD due to the smaller sensitive volume radius. After the application of the MC-based factors, differences between mDD dose rate measurements and TG-43 dose rate calculations ranged from -2.6% to +4.3%, with an absolute average difference of 1.0%. For the mSD, the differences ranged from -3.1% to +5.2%, with an absolute average difference of 1.0%. For both detectors, all differences but one were within the combined uncertainty (k = 2). The differences of the mSD from the mDD ranged from -3.9% to +2.6%, with the vast majority of them being within the combined uncertainty (k = 2). For θ ≠ 0°, the mDD was able to provide sufficiently accurate results even without the application of the MC-based beam quality correction factor, with differences to the TG-43 dose rate calculations from -1.9% to +3.4%, always within the combined uncertainty (k = 2). CONCLUSION: The mDD and the mSD showed consistent results and appear to be well suitable for measuring the dose rate around HDR 192Ir brachytherapy sources. MC characterization of the detectors response is needed to determine the beam quality correction factor and to account for energy dependence and/or volume-averaging, especially for the mSD. Our findings support the employment of the mDD and mSD for source QA, TPS verification and TG-43 parameters determination.

Validation of a Cytological Classification System for the Rapid On-Site Evaluation (Rose) of Pulmonary and Mediastinal Needle Aspirates.

Rapid on-site evaluation (ROSE) is a procedure that allows immediate assessment of adequacy of cytological specimens obtained by fine needle aspiration (FNA). The application of ROSE diagnostic categories has been applied in various organs, but not in thoracic pathology. We aimed to retrospectively assess the concordance with the final diagnosis of a categorization from C1 (inadequate) to C5 (neoplastic) during ROSE performed with bronchoscopic or percutaneous sampling procedures of thoracic lesions in a large series of consecutive cases. This retrospective single-center study evaluated 2282 consecutive ROSEs performed on 1827 patients from January 2016 to December 2020 in 994 cases of transbronchial needle aspiration (TBNA) in peripheral pulmonary lesions, in 898 transthoracic FNAs, in 318 ultrasound-guided TBNAs, in 50 conventional TBNAs and in 22 endobronchial TBNAs. False positive and false negative cases of ROSE were 43 (1.88%) and 73 (3.2%), respectively, when compared with the definitive diagnosis. The sensitivity, specificity and the positive and negative prognostic values of ROSE were 94.84%, 95.05%, 96.89% and 91.87%, respectively. Overall concordance between ROSE and the final diagnosis was 0.8960 (Cohen's kappa). No significant differences were observed in terms of sampling procedures and type and location of the lesions. A tiered classification scheme of ROSE from C1 to C5 during bronchoscopic and percutaneous sampling procedures is helpful in effectively guiding clinical management of patients with thoracic lesions.

An unexpected cause of recurrent pneumothorax.

The thoracic district is the most frequent visceral location of synovial sarcoma, generally involving lung and pleura as a large solid mass. We present herein a 57-year-old man with recurrent pneumothorax and a localized bulla at the lingula. The lesion was excised by a Video-Assisted-Thoracoscopic-Surgery (VATS) wedge resection and surprisingly consisted of a unilocular cyst with fibrous wall intermingled by a longitudinal proliferation of bland-looking, dense, monomorphic spindle cells diffusely expressing EMA, CD99, CD56 and focally staining with cytokeratins. Fluorescent in situ hybridization demonstrated the presence of SYT rearrangement and a diagnosis of pulmonary cystic monophasic synovial sarcoma was made. Only few similar cases have been reported in literature, mainly occurring in young male adults. A meticulous examination of all resected tissue from pneumothorax is the prerequisite to suspect this extremely challenging condition, while immuno-molecular studies are mandatory to achieve the correct diagnosis.