Spatially resolved, high-dimensional transcriptomics sorts out the evolution of biphasic malignant pleural mesothelioma: new paradigms for immunotherapy.

BACKGROUND: Malignant Pleural Mesothelioma (MPM) is a dreadful disease escaping the classical genetic model of cancer evolution and characterized by wide heterogeneity and transcriptional plasticity. Clinical evolution of MPM is marked by a progressive transdifferentiation that converts well differentiated epithelioid (E) cells into undifferentiated and pleomorphic sarcomatoid (S) phenotypes. Catching the way this transition takes place is necessary to understand how MPM develops and progresses and it is mandatory to improve patients' management and life expectancy. Bulk transcriptomic approaches, while providing a significant overview, failed to resolve the timing of this evolution and to identify the hierarchy of molecular events through which this transition takes place. METHODS: We applied a spatially resolved, high-dimensional transcriptomic approach to study MPM morphological evolution. 139 regions across 8 biphasic MPMs (B-MPMs) were profiled using the GeoMx™Digital Spatial Profiler to reconstruct the positional context of transcriptional activities and the spatial topology of MPM cells interactions. Validation was conducted on an independent large cohort of 84 MPMs by targeted digital barcoding analysis. RESULTS: Our results demonstrated the existence of a complex circular ecosystem in which, within a strong asbestos-driven inflammatory environment, MPM and immune cells affect each other to support S-transdifferentiation. We also showed that TGFB1 polarized M2-Tumor Associated Macrophages foster immune evasion and that TGFB1 expression correlates with reduced survival probability. CONCLUSIONS: Besides providing crucial insights into the multidimensional interactions governing MPM clinical evolution, these results open new perspectives to improve the use of immunotherapy in this disease.

Trocar vs. Seldinger small bore pleural drains: does the technique influence the outcomes? A prospective single-centre study.

OBJECTIVE: The aim of this study is to compare two positioning techniques of 12-French (Fr) thoracic drains in terms of efficacy, safety, and patient comfort. PATIENTS AND METHODS: This is a prospective, non-randomized, competitive, non-inferiority study comparing the Seldinger vs. Trocar technique. The primary endpoint was an analysis of the factors that led to unsuccessful drainage positioning. Between the two groups, clinical variables, procedure times, pain, and complications were compared. RESULTS: Seventy-two patients were enrolled in group 1 (Seldinger) and 45 in group 2 (Trocar). The mean procedural time was 7.93±3.02 min vs. 7.09±3.67 min, respectively (p: 0.33). The mean VAS for procedural pain was 2.22±1.47 vs. 2.80±1.88, p: 0.07, and the mean at day 2 was 3.6±1.2 in the SBWGD group vs. 2.7±1.1 in the Unico Group (p: 0.04). There was no difference in terms of complications, residual effusion, and pneumothorax at the first post-procedural chest X-ray. Four days after the procedure, the drain removal rate was 11.6% in group 1 vs. 25% in group 2 p: 0.063). The chest tube was removed after a mean period of 8.87±7.20 days after resolution of pleural effusion or tube dislodgement (7 cases in group 1 vs. 11 in group 2, p: 0.053). CONCLUSIONS: The two techniques resulted in comparable pain and complication rates. Both drains are well-tolerated and efficient at draining pleural effusion, with very low rates of complications and failure. We recommend inserting a longer tube for patients who require chest drainage for an extended period of time.

Diagnostic role of internal mammary lymph node involvement in tuberculous pleurisy: a multicenter study.

BACKGROUND AND OBJECTIVES: Diagnosis of tuberculous pleurisy (TP) may be challenging and it often requires pleural biopsy. A tool able to increase pre-test probability of TP may be helpful to guide diagnostic work-up and enlargement of internal mammary lymph node (IMLN) has been suggested to play a potential role. The aim of the present investigation was to assess role of IMLN involvement in TP in a multi-centric case-control study, by comparing its prevalence and test performance to those observed in patients with infectious, non-tuberculous pleurisy (NTIP), and in controls free from respiratory diseases (CP). METHODS: A total of 419 patients, from 14 Pulmonology Units across Italy were enrolled (127 patients affected by TP, 163 affected by NTIP and 129 CP). Prevalence, accuracy and predictive values of ipsilateral IMLN involvement between cases and control groups were assessed, as well as concordance between chest computed tomography (CT scan) and thoracic ultrasound (TUS) measurements. RESULTS: The prevalence of ipsilateral IMLN involvement in TP was significantly higher than that observed in NTIP and CP groups (respectively 77.2%, 39.3% and 14.7%). Results on test performance, stratified by age, revealed a high positive predictive value in patients aged ≤50 years, while a high negative predictive value in patients aged >50 years. The comparison between CT scan and ultrasound showed moderate agreement (Kappa=0.502). CONCLUSIONS: Evaluation of IMLN involvement plays a relevant role in assessing the pre-test probability of TP. Considering the increasing global prevalence of mycobacterial infections, a tool able to guide diagnostic work-up of suspected TP is crucial, especially where local sources are limited.

Probiotic intake unmasking a gastro-pleural fistula.

OBJECTIVE: Gastropleural fistula represents a rare clinical event often resulting in an iatrogenic complication of gastrointestinal surgery. Clinical presentation is insidious, patients complain of chronic and non-specific respiratory symptoms and may be conservatively treated for lung infections for several months until detailed tests finally reveal the correct diagnosis. PATIENTS AND METHODS: We describe a case of a healthy patient with an unexpected diagnosis of empyema due to a gastropleural fistula. RESULTS: A 51-year-old man with a past history of splenectomy for cyst was admitted because of high fever and cough. A chest radiography and CT-scan revealed a left-side pneumonia complicated with pleural empyema. Broad spectrum empirical antibiotics and pleural drainage did not significantly improve the clinical picture. While the need for a surgical complex thoracic approach becomes a collective awareness, questions about causes of empyema and its unfavorable evolution in our patient did not initially find a common satisfactory answer. It was only by the identification of probiotics bacteria in the pleural fluid that a gastropleural fistula was suspected, and then, it was confirmed by CT-scan and by digestive endoscopy. A combined thoraco-abdominal surgical treatment was therefore scheduled, leading to progressive improvement till total healing. CONCLUSIONS: Although gastropleural fistula is rare, it is necessary to include this pathological condition in the differential diagnosis of a persistent complicated pneumonia, because early diagnosis and, consequently, surgical management, may significantly impact on the prognosis of these patients. In our case, the detection of probiotics bacteria in the pleural fluid helped us to suspect and to look for the fistula.

Hyperthermic intrathoracic chemotherapy combined to iterative cytoreductive surgery to treat a pleural carcinosis from psudomixoma peritonei. A case report.

Pseudomyxoma peritonei (PMP) is an uncommon disease with locally-invasive attitude. Intrathoracic spread is rarely reported and its management extremely challenging. A 51-year-old Caucasian female presented with left pleural carcinosis 9-months after two sequential abdominal surgical procedures combined with HIPEC for low-grade PMP. Cytoreductive surgery (pleurectomy/decortication) was followed by 60-minutes hyperthermic intrathoracic chemotherapy mitomycin-C (215 mg/m2) infusing at same temperature (42°C) and intrapleural pression (2-4 mmH2O). No intra-operative complication occurred, the post-op stay was uneventful and no sign of recurrence was observed 9-months after surgery. Cytoreductive thoracic surgery and hyperthermic chemotherapy (HITHOC) could be a feasible therapeutic option in very selected cases.

A huge esophageal Schwannoma occurring in a Caucasian young male: a case report.

OBJECTIVE: Gastrointestinal schwannomas are rare benign mesenchymal tumors originating from Schwann cells, the nerve sheath belonging to the Auerbach's plexus or, less frequently, to Meisser's plexus. The esophagus is the least common site accounting for less than 2% of all esophageal tumors, and the upper to mid portion is usually involved. Esophageal schwannomas affect more frequently middle-aged Asian women. The most common symptom is dysphagia. Diagnosis requires histological and immunohistochemical studies and the standard of care is surgical resection. CASE REPORT: We present the case of a 22-year-old Caucasian male who was admitted to our hospital for progressive dysphagia and acute chest pain. An EGDS showed an elongated bulging of the lower esophagus with signs of a subcentimetric mucosal erosion. A CT-scan showed a lower esophageal ectasia and a huge postero-lateral wall mass measuring 37x28x70 mm. An endoscopic ultrasonography showed a hypoechoic heterogeneous mass with multiple anechoic areas and a fine needle biopsy was performed. Histological examination showed tissue made up of spindle cells with mild eosinophilic cytoplasm and rare nuclear atypia, which were intensively and diffusely positive for the S100 protein on immunohistochemical studies thus allowing pre-operative diagnosis of "ancient" schwannoma. after a multidisciplinary discussion, the patient underwent a surgical resection. Since the tumor had a transmural extension, a subtotal esophagectomy was performed to achieve complete resection with negative margins. CONCLUSIONS: This is the first case of a young Caucasian male patient with an "ancient" schwannoma of the lower esophagus, a benign but locally advanced lesion treated by subtotal esophagectomy.

Valor de la PET/TC con 68Ga-DOTATOC en la detección de recidiva de un tumor fibroso solitario de la pleura / The role of 68Ga-DOTATOC PET/CT in the detection of relapsed malignant solitary fibrous tumor of the pleura

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Metástasis infrecuente de mesotelioma pleural detectada mediante 18F-FDG PET/TC de cuerpo entero / Uncommon distant metastasis of pleural mesothelioma detected by whole-body 18F-FDG PET/CT

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Disseminated nocardiosis complicated by multiple brain abscesses and pleural empyema in a young diabetic man: a case report.

Nocardiosis is a life-threatening infection usually affecting immunocompromised patients. Very rarely it presented with intracranial abscesses and pleuro-parenchymal infections. We herein report a very challenging case of a 34-year-old obese and diabetic man affected by disseminated nocardiosis with multiple brain abscesses and pleural empyema. Despite rare, this entity should be taken into account by the pathologists and urgently communicated to clinicians in order to promptly start an effective treatment.

Does V600E BRAF mutation predict vinorelbine efficacy? A proof-of-concept from a lung micropapillary adenocarcinoma metastatic to the breast.

BRAF mutations occur in about 3% of all lung adenocarcinomas and V600E missense mutation characterizes about half of BRAF-mutated lung adenocarcinomas and is significantly associated with micropapillary pattern and shorter disease-free and overall survival rates. In this report, we report a challenging case of a patient with a metastatic micropapillary adenocarcinoma of the lung harbouring V600E BRAF mutation who experienced a surprising protracted clinical response to metronomic vinorelbine. The possible association between the V600E BRAF mutation pathway and the effective use of vinca alkaloid is discussed.

Dedifferentiated primary mediastinal liposarcoma mimicking a thymic tumor.

Mediastinal tumors are heterogeneous and the diagnosis depends on their location in the mediastinum. The most frequent tumors are germinal tumor, lymphoma and thymoma. The clinical and radiological aspects are often not sufficient to orient the diagnosis and biopsy is necessary to confirmed it. Here, we present a rare case of an anterior mediastinal mass incidentally detected in a 63 years old man during assessment for asthma. The lesion was presumptively diagnosed as a thymic epithelial tumor based on location and radiological characteristics. Surgical biopsy revealed a primary dedifferentiated mediastinal liposarcoma with multiple lung metastases.

Breast granulomatosis with polyangiitis mimicking breast cancer.

Inflammatory lesions of the breast encompass primary reactive processes and local manifestation of systemic diseases. They are very rare and they are generally treated without resort to biopsy. Nevertheless they could be clinically challenge mimicking malignant process and needing surgery to reach a correct diagnosis. Here we describe a rare case of breast granulomatosis with polyangiitis, which presented with radiological and clinical alarming features that immediately raised the suspicious of malignancy leading to breast-conserving surgery.

Pulmonary talcosis caused by methadone misuse and mimicking primary lung cancer. FDG-PET/CT findings / Talcosis pulmonar por uso inadecuado de metadona que imita cáncer de pulmón. Hallazgos en FDG-PET/TC

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Prognostic grading after complete resection for thymic malignancies.

OBJECTIVE: Despite the World Health Organization (WHO) and Masaoka classifications have been widely accepted as the main describers of prognosis determinants in thymic malignancies, so far, these have been considered independently from one another. We have reviewed our single-centre 40-year results after surgical treatment of thymic malignancies evaluating the inter-relationships between the clinical, surgical and pathological variables and investigating their prognostic impact in completely resected patients. PATIENTS AND METHODS: A surgical series of 347 patients was reviewed and, of these, 305 with complete resection enrolled. Long-term and disease-free survival (LTS, DFS) analyses were performed. Kaplan-Meir curves for WHO histotypes and Masaoka-stages were inspected and matched with the log-rank test; the Cox regression analysis was adopted in a multivariable approach. RESULTS: Considered independently, the WHO-histotypes did not differentiate clearly from one to another in terms of LTS and DFS; however, types A-AB-B1-B2 and B3-C clustered in 2, statistically different, malignancy groups (LTS, DFS: Cox-p < 0.001). Masaoka staging was confirmed to be a relevant prognostic determinant, even if no evident difference between stages I vs II and stages III vs IV emerged when the Masaoka-classification was factored in. Thus, when investigating 13 surgical and pathological factors of invasiveness, these showed a clustering in 2 groups according to the presence/absence of pathological proven infiltration in the peri-thymic structures (LTS, DFS: Cox-p < 0.001). By matching the WHO-malignancy clusters and infiltration clusters, 4 classes may be identified, which proved to have a distinct prognostic significance: (LTS-Cox: stage-I vs stage-II, p = 0.003; III: p < 0.001, IV: p < 0.001; DFS-Cox: stage-I vs stage-II, p < 0.001; III: p < 0.001; IV: p < 0.001). CONCLUSIONS: When analyzing the long-term outcome of patients underwent complete resection for thymic malignancies, the combination between pathological and surgical variables showed accurate prognosis predictability.