Adverse Prognostic Impact of Transitional and Pleomorphic Patterns in Pleural Nonepithelioid Mesothelioma: Insights From Comprehensive Analysis and Reticulin Stain.

CONTEXT.­: Mesothelioma subtyping into epithelioid and nonepithelioid categories plays a crucial role in prognosis and treatment selection, with emerging recognition of the impact of various histologic patterns. OBJECTIVE.­: To investigate the prognostic implications of transitional and pleomorphic patterns in sarcomatoid mesothelioma. DESIGN.­: A total of 132 mesothelioma cases (87 biphasic, 45 sarcomatoid) were analyzed. Histologic slides were assessed, treatment data collected, and cases categorized into predominant epithelioid or sarcomatoid patterns. The sarcomatoid mesotheliomas were classified into usual, pleomorphic, and transitional patterns, with reticulin staining for the latter. Statistical analysis included Cox regression and Kaplan-Meier methods. RESULTS.­: Younger age (P = .02) and receiving therapy (P < .001) correlated with improved survival for both histotypes. Advanced stage was associated with shorter survival in sarcomatoid cases (P = .02). Predominant epithelioid pattern in biphasic cases led to longer survival (P < .001). Transitional and pleomorphic patterns were indicative of worse prognosis, with significantly lower survival in cases with both patterns than with usual sarcomatoid (P = .046). Multivariate analysis identified independent survival factors, including predominant epithelioid component in biphasic mesothelioma (P = .001) and chemotherapy (P < .001). CONCLUSIONS.­: Histologic subtyping in mesothelioma plays a pivotal role in prognosis. Transitional and pleomorphic patterns, even in low percentages, indicate poorer outcomes. This study highlights the need for standardized diagnostic support and suggests the potential utility of histochemical staining in identifying more aggressive morphologic aspects. Recognizing the significance of these patterns can guide treatment decisions and patient care strategies.

Extensive-stage small-cell lung cancer in patients receiving atezolizumab plus carboplatin-etoposide: stratification of outcome based on a composite score that combines gene expression profiling and immune characterization of microenvironment.

PURPOSE: Small-cell lung cancer (SCLC) is an aggressive disease with a dismal prognosis. The addition of immune checkpoints inhibitors to standard platinum-based chemotherapy in first-line setting achieves a durable benefit only in a patient subgroup. Thus, the identification of predictive biomarkers is an urgent unmet medical need. EXPERIMENTAL DESIGN: Tumor samples from naive extensive-stage (ES) SCLC patients receiving atezolizumab plus carboplatin-etoposide were analyzed by gene expression profiling and two 9-color multiplex immunofluorescence panels, to characterize the immune infiltrate and SCLC subtypes. Associations of tissue biomarkers with time-to-treatment failure (TTF), progression-free survival (PFS) and overall survival (OS), were assessed. RESULTS: 42 patients were included. Higher expression of exhausted CD8-related genes was independently associated with a longer TTF and PFS while increased density of B lymphocytes correlated with longer TTF and OS. Higher percentage of M2-like macrophages close to tumor cells and of CD8+T cells close to CD4+T lymphocytes correlated with increased risk of TF and longer survival, respectively. A lower risk of TF, disease progression and death was associated with a higher density of ASCL1+tumor cells while the expression of POU2F3 correlated with a shorter survival. A composite score combining the expression of exhausted CD8-related genes, B lymphocyte density, ASCL1 tumor expression and quantification of CD163+macrophages close to tumor cells, was able to stratify patients into high-risk and low-risk groups. CONCLUSIONS: In conclusion, we identified tissue biomarkers and a combined score that can predict a higher benefit from chemoimmunotherapy in ES-SCLC patients.

The role of pathologists in the diagnosis of occupational lung diseases: an expert opinion of the European Society of Pathology Pulmonary Pathology Working Group.

Occupational lung/thoracic diseases are a major global public health issue. They comprise a diverse spectrum of health conditions with complex pathology, most of which arise following chronic heavy workplace exposures to various mineral dusts, metal fumes, or following inhaled organic particulate reactions. Many occupational lung diseases could become irreversible; thus accurate diagnosis is mandatory to minimize dust exposure and consequently reduce damage to the respiratory system. Lung biopsy is usually required when exposure history is inconsistent with imaging, in case of unusual or new exposures, in case of unexpected malignancy, and in cases in which there are claims for personal injury and legal compensation. In this paper, we provide an overview of the most frequent occupational lung diseases with a focus on pathological diagnosis. This is a paper that summarizes the expert opinion from a group of European pathologists, together with contributions from other specialists who are crucial for the diagnosis and management of these diseases. Indeed, tight collaboration of all specialists involved in the workup is mandatory as many occupational lung diseases are misdiagnosed or go unrecognized. This document provides a guide for pathologists in practice to facilitate the accurate diagnosis of occupational lung disease. The review article reports relevant topics discussed during an educational course held by expert pathologists, active members of the Pulmonary Pathology Working Group of the European Society of Pathology. The course was endorsed by the University of Padova as a "winter school" (selected project in the call for "Shaping a World-class University" 2022).

Tumor inflammatory microenvironment contribution to survival in resected upstaged adenocarcinomas.

INTRODUCTION: Tumor Inflammatory microenvironment (TIME) encompasses several immune pathways modulating cancer development and escape that are not entirely uncoded. The results achieved with immunotherapy elicited the scientific debate on TIME also in non-small cell lung cancer (NSCLC). We aimed to investigate whether TIME (in terms of PD-L1 expression and/or Tumor Infiltrating Lymphocytes - TILs) played a separate role in terms of survival (OS) in resected upstaged lung adenocarcinomas (ADCs), excluding other perioperative variables as confounders. MATERIALS AND METHODS: This retrospective study included 50 patients with a clinically resectable lung ADC, undergoing surgery (lobectomy or segmentectomy) at the Thoracic Unit of Padova University Hospital between 2016 and 2022 and receiving an unexpected pathological upstaging (IIB or higher). RESULTS: Despite microscopical variables increasing from IIB to IIIB, survival was not significantly related to them. OS was better in TIME-active patients (defined as the presence of positive PD-L1 and/or TILs>10 %) than double negatives (PD-L1-/TILs-) (p = 0.01). In IIB or higher ADCs, TIME-active patients showed an improved survival compared to double negatives, merging the current TIME theories. CONCLUSION: TIME seems to be associated with survival independently from other microscopical parameter, even in case of resected upstaged adenocarcinomas.

Pathological complete response in a patient with pleural mesothelioma treated with immunotherapy: a case report.

The role of immunotherapy in the multimodal treatment for pleural mesothelioma (PM) is still under investigation, particularly in the preoperative setting. Pathological complete response (pCR) has been previously described after chemotherapy and immunotherapy; however, there is no prior experience reported with immunotherapy alone before surgery. We report the case of a 58-year-old male with biphasic PM treated with immunotherapy, resulting in a major clinical partial response. Following a multidisciplinary evaluation between thoracic surgeons, medical oncologists, pathologists, radiologists and radiation oncologists, the patient underwent surgery with radical intent through a right extended pleurectomy/decortication (eP/D). Histopathological examination of the specimen confirmed a pathological Complete Response (pCR). This case supports the feasibility and potential efficacy of combining preoperative immunotherapy with surgery in the management of advanced PM.

Significance of Spread Through Air Spaces and Vascular Invasion in Early-stage Adenocarcinoma Survival: A Comprehensive Clinicopathologic Study of 427 Patients for Precision Management.

Spread through air spaces (STAS) is a novel invasive pattern of lung cancer associated with poor prognosis in non-small cell cancer (NSCLC). We aimed to investigate the incidence of STAS in a surgical series of adenocarcinomas (ADCs) resected in our thoracic surgery unit and to identify the association of STAS with other clinicopathological characteristics. We retrospectively enrolled patients with stage cT1a-cT2b who underwent resection between 2016 and 2022. For each case, a comprehensive pathologic report was accessible which included histotype, mitoses, pleural invasion, fibrosis, tumor infiltrating lymphocytes, necrosis, inflammation, vascular and perineural invasion, as well as STAS. PD-L1 expression was also investigated. A total of 427 patients with ADCs underwent surgery. Regarding overall survival (OS), no significant difference was observed between the STAS positive (STAS+) and STAS negative (STAS-) groups ( P =0.44). However, vascular invasion (VI) was associated with a poorer survival probability ( P =0.018). STAS+/VI+ patients had tendentially worse survival compared with STAS+/VI- ( P =0.089). ADCs with pathologic evidence of immune system (IS) activation (TILs>10% and PD-L1≥1) demonstrated significantly increased OS compared with ADCs with no IS and VI. In terms of recurrence rate, no statistical differences were found between the STAS+ and STAS- samples ( P =0.2). VI was also linked to a significantly elevated risk of recurrence ( P =0.0048). Our study suggests that in resected early-stage ADCs, STAS+ does not seem to influence recurrence or mortality. VI was instead an adverse pathologic prognostic factor for both survival and recurrence, whereas IS seemed to be protective.

Endobronchial solitary fibrous tumors: An enigma for diagnosis.

Solitary fibrous tumors (SFTs) are rare mesenchymal neoplasms constituting less than 2% of all soft tissue tumors. They typically originate in the thoracic cavity, mainly in the pleura, but can also occur in other various sites such as lung parenchyma, pericardium, and bronchus. In this study, a 49-year-old non-smoking female with a history of allergies presented to our pulmonary clinic with a chronic cough. An explorative bronchoscopy revealed an intrabronchial mass in the left superior bronchi, and a 68 Ga-DOTATOC positron emission computed tomography suggested a carcinoid tumor. Subsequent pulmonary segmentectomy unveiled a well-circumscribed polypoid lesion diagnosed as a low-grade bronchus SFT through histopathological and immunohistochemical assessments. The patient was asymptomatic after surgical excision and showed no other lesion during the 6-month follow-up. The endobronchial location of SFT is uncommon, with only a few reported cases in the literature, underscoring the necessity of considering various differential diagnoses, including carcinoid, mucoepidermoid carcinoma, endobronchial pleomorphic adenoma, hamartoma, leiomyoma, and metastasis, depending on location and imaging features. This report underscores the importance of careful histological and immunohistochemical evaluation in understanding and appropriately stratifying the risk associated with polypoid lesions.

The 2022 Banff Meeting Lung Report.

The Lung Session of the 2022 16th Banff Foundation for Allograft Pathology Conference-held in Banff, Alberta-focused on non-rejection lung allograft pathology and novel technologies for the detection of allograft injury. A multidisciplinary panel reviewed the state-of-the-art of current histopathologic entities, serologic studies, and molecular practices, as well as novel applications of digital pathology with artificial intelligence, gene expression analysis, and quantitative image analysis of chest computerized tomography. Current states of need as well as prospective integration of the aforementioned tools and technologies for complete assessment of allograft injury and its impact on lung transplant outcomes were discussed. Key conclusions from the discussion were: (1) recognition of limitations in current standard of care assessment of lung allograft dysfunction; (2) agreement on the need for a consensus regarding the standardized approach to the collection and assessment of pathologic data, inclusive of all lesions associated with graft outcome (eg, non-rejection pathology); and (3) optimism regarding promising novel diagnostic modalities, especially minimally invasive, which should be integrated into large, prospective multicenter studies to further evaluate their utility in clinical practice for directing personalized therapies to improve graft outcomes.

Assessing the role of phosphorylated S6 ribosomal protein in the pathological diagnosis of pulmonary antibody-mediated rejection.

BACKGROUND: Pulmonary antibody-mediated rejection is still a challenging diagnosis as C4d immunostaining has poor sensitivity. Previous studies have indicated that the phosphorylated S6 ribosomal protein, a component of the mammalian target of rapamycin (mTOR) pathway, is correlated with de novo donor-specific antibodies in lung transplantation. The objective of this study was to evaluate the phosphorylation of S6 ribosomal protein as a surrogate for antibody-mediated rejection diagnosis in lung transplant patients. METHODS: This multicentre retrospective study analyzed transbronchial biopsies from 216 lung transplanted patients, 114 with antibody-mediated rejection and 102 without (19 with acute cellular rejection, 17 with ischemia/reperfusion injury, 18 with infection, and 48 without post-transplant complications). Immunohistochemistry was used to quantify phosphorylated S6 ribosomal protein expression in macrophages, endothelium, epithelium, and inter-pathologist agreement was assessed. RESULTS: Median phosphorylated S6 ribosomal protein expression values were higher in antibody-mediated rejection cases than in controls for all cell components, with the highest sensitivity in macrophages (0.9) and the highest specificity in endothelial expression (0.8). The difference was mainly significant in macrophages compared to other post-lung transplantation complications. Inter-pathologist agreement was moderate for macrophages and endothelium, with higher agreement when phosphorylated S6 ribosomal protein expression was dichotomized into positive/negative. The inclusion of phosphorylated S6 ribosomal protein in the diagnostic algorithm could have increased antibody-mediated rejection certainty levels by 25%. CONCLUSIONS: The study supports the role of the mTOR pathway in antibody-mediated rejection-related graft injury and suggests that tissue phosphorylation of S6 ribosomal protein could be a useful surrogate for a more accurate pathological diagnosis of lung antibody-mediated rejection.

Diaphragm Dysfunction Predicts Weaning Outcome after Bilateral Lung Transplant.

BACKGROUND: Diaphragm dysfunction and its effects on outcomes of ventilator weaning have been evaluated in mixed critical care populations using diaphragm thickening fraction (the ratio of the difference between ultrasound diaphragm thickness at end-inspiration and end-expiration to diaphragm thickness at end-expiration) or neuroventilatory efficiency (the ratio of tidal volume and peak electrical activity of the diaphragm). Such data are not available in bilateral-lung transplant recipients. The authors hypothesized that (1) diaphragm dysfunction, as defined by a diaphragm thickening fraction less than 29%, is more likely to occur in difficult weaning; (2) diaphragm thickening fraction and neuroventilatory efficiency predict weaning outcome; and (3) duration of mechanical ventilation before the first spontaneous breathing trial is associated with diaphragm dysfunction. METHODS: Adult bilateral-lung transplant patients admitted to the intensive care unit were screened at the time of the first spontaneous breathing trial (pressure-support of 5 cm H2O and 0 positive end-expiratory pressure). At the fifth minute, diaphragm thickening fraction and neuroventilatory efficiency were measured during three respiratory cycles. Weaning was classified as simple, difficult, or prolonged (successful extubation at the first spontaneous breathing trial, within three or after three spontaneous breathing trials, respectively). RESULTS: Forty-four subjects were enrolled. Diaphragm dysfunction occurred in 14 subjects (32%), all of whom had difficult weaning (78% of the subgroup of 18 patients experiencing difficult weaning). Both diaphragm thickening fraction (24 [20 to 29] vs. 39 [35 to 45]%) and neuroventilatory efficiency (34 [26 to 45] vs. 55 [43 to 62] ml/µV) were lower in difficult weaning (both P < 0.001). The areas under the receiver operator curve predicting difficult weaning were 0.88 (95% CI, 0.73 to 0.99) for diaphragm thickening fraction and 0.85 (95% CI, 0.71 to 0.95) for neuroventilatory efficiency. The duration of ventilation demonstrated a linear inverse correlation with both diaphragm thickening fraction and neuroventilatory efficiency. CONCLUSIONS: Diaphragm dysfunction is common after bilateral-lung transplantation and associated with difficult weaning. In such patients, average values for diaphragm thickening fraction and neuroventilatory efficiency were reduced compared to patients with simple weaning. Both parameters showed similar accuracy for predicting success of ventilator weaning, demonstrating an inverse relationship with duration of ventilation.

Exploring the pathologist's role in understanding COVID-19: from pneumonia to long-COVID lung sequelae.

The crucial role of pathologists in enhancing our understanding of SARS-CoV-2-related disease, from initial pneumonia manifestations to persistent long COVID lung symptoms, is the focus of this review. Pathological explorations have offered unprecedented insights into the early stages of severe COVID-19, shedding light on the interplay between the virus and subsequent complications, thereby shaping clinical approaches. Growing interest is directed to residual lung abnormalities of COVID-19 survivors. Although various radiological studies reported long-lasting pulmonary changes (e.g., ground glass opacities, reticulations, and bronchiectasis), the true incidence of pulmonary fibrosis and corresponding pathological findings in these patients remains largely unknown. There are a few high-impact and knowledgeable works on late complications in COVID-19 survivors, several coming from explant or autopsy cases, and rare cases from in vivo sampling. The study of biopsy samples has further deepened our knowledge of the aftermath of COVID-19 on lung tissue, uncovering alterations at the cellular level and shifts in vascular and epithelial dynamics. Despite the substantial progress made, future research is needed to devise a uniform strategy for interpreting lung biopsies, with a focus on leveraging advanced tools such as molecular and digital pathology techniques, along with artificial intelligence.

Microscopical Variables and Tumor Inflammatory Microenvironment Do Not Modify Survival or Recurrence in Stage I-IIA Lung Adenocarcinomas.

Microscopical predictors and Tumor Immune Microenvironment (TIME) have been studied less in early-stage NSCLC due to the curative intent of resection and the satisfactory survival rate achievable. Despite this, the emerging literature enforces the role of the immune system and microscopical predictors as prognostic variables in NSCLC and in adenocarcinomas (ADCs) as well. Here, we investigated whether cancer-related microscopical variables and TIME influence survival and recurrence in I-IIA ADCs. We retrospectively collected I-IIA ADCs treated (lobectomy or segmentectomy) at the University Hospital (Padova) between 2016 and 2022. We assigned to pathological variables a cumulative pathological score (PS) resulting as the sum of them. TIME was investigated as tumor-infiltrating lymphocytes (TILs < 11% or ≥11%) and PD-L1 considering its expression (<1% or ≥1%). Then, we compared survival and recurrence according to PS, histology, TILs and PD-L1. A total of 358 I-IIA ADCs met the inclusion criteria. The median PS grew from IA1 to IIA, indicating an increasing microscopical cancer activity. Except for the T-SUVmax, any pathological predictor seemed to be different between PD-L1 < 1% and ≥1%. Histology, PS, TILs and PD-L1 were unable to indicate a survival difference according to the Log-rank test (p = 0.37, p = 0.25, p = 0.41 and p = 0.23). Even the recurrence was non-significant (p = 0.90, p = 0.62, p = 0.97, p = 0.74). According to our findings, resection remains the best upfront treatment in I-IIA ADCs. Microscopical cancer activity grows from IA1 to IIA tumors, but it does not affect outcomes. These outcomes are also unmodified by TIME. Probably, microscopical cancer development and immune reaction against cancer are overwhelmed by an adequate R0-N0 resection.

A Complex Case of Pulmonary Silico-Tuberculosis and Review of Literature.

Silicosis caused by the inhalation/deposition of free silica particles is characterized by pulmonary inflammation/fibrosis. Among the clinical disorders associated with silicosis, tuberculosis is by far the most prominent. A 66-year-old male non-smoker, originally from North Africa, reported a dry cough and significant weight loss. He was a foundry worker. He had a medical history of bladder carcinoma associated with schistosomiasis. Computed tomography (CT) and positron emission tomography (PET)/CT showed bilateral multiple hypermetabolic lung nodules, some with cavitation. The patient underwent surgical resection of the largest nodule, which was highly suspicious of lung metastasis. The histological examination revealed multiple nodular formations. Several lesions showed the characteristic features of silicotic nodules. There were also adjacent well-formed granulomas, some with central caseous necrosis. A real-time polymerase chain reaction, performed for the identification and quantification of the DNA of the Mycobacterium tuberculosis complex, was positive. Pulmonary silico-tuberculosis is often encountered in patients with a history of silica exposure in tuberculosis-endemic areas. This case serves as a reminder to never underestimate patient occupational exposure and geographic origin. A careful histological diagnosis and molecular investigation are mandatory when approaching difficult cases, especially patients with a prior cancer history and clinical/radiological features suggestive of tumour recurrence/metastasis.

Radiomics of spinal muscles: toward a radiological biomarker for allograft rejection in lung transplant.

PURPOSE: To assess the role of muscle composition and radiomics in predicting allograft rejection in lung transplant. MATERIAL AND METHODS: The last available HRCT before surgery of lung transplant candidates referring to our tertiary center from January 2010 to February 2020 was retrospectively examined. Only scans with B30 kernel reconstructions and 1 mm slice thickness were included. One radiologist segmented the spinal muscles of each patient at the level of the 11th dorsal vertebra by an open-source software. The same software was used to extract Hu values and 72 radiomic features of first and second order. Factor analysis was applied to select highly correlating features and then their prognostic value for allograft rejection was investigated by logistic regression analysis (level of significance p < 0.05). In case of significant results, the diagnostic value of the model was computed by ROC curves. RESULTS: Overall 200 patients had a HRCT prior to the transplant but only 97 matched the inclusion criteria (29 women; mean age 50.4 ± 13 years old). Twenty-one patients showed allograft rejection. The following features were selected by the factor analysis: cluster prominence, Imc2, gray level non-uniformity normalized, median, kurtosis, gray level non-uniformity, and inverse variance. The radiomic-based model including also Hu demonstrated that only the feature Imc2 acts as a predictor of allograft rejection (p = 0.021). The model showed 76.6% accuracy and the Imc2 value of 0.19 demonstrated 81% sensitivity and 64.5% specificity in predicting lung transplant rejection. CONCLUSION: The radiomic feature Imc2 demonstrated to be a predictor of allograft rejection in lung transplant.

Benefit Over Risk Assessment of CT-guided Lung Core Needle Biopsy With the Coaxial Technique.

BACKGROUND/AIM: Lung percutaneous needle biopsy (PNB) under CT guidance can be performed with a single-needle or with a coaxial (CX) technique. This study evaluated the CX technique in a large cohort of patients who underwent to CT-guided lung PNB in our Institute over a period of 7 years. PATIENTS AND METHODS: We retrospectively collected and analyzed data relative to 700 CT-guided lung PNBs performed from August 2012 to August 2019 in 700 patients (M:F=436:264; mean age=69 years, range=6-93 years) with normal coagulation and pulmonary function. PNB was considered diagnostic if at least one of the collected tissue specimens allowed for histological diagnosis. Pulmonary hemorrhage (PH) and pneumothorax (PNX) were evaluated as present or absent. Statistical analysis was made by Chi-square test of Pearson, Fisher's exact test and Wilcoxon test. RESULTS: The CX technique showed a high diagnostic accuracy (93.0%) and allowed the collection of a great number of appropriate tissue specimens with a single pleural puncture (≥3 specimens in 77.4% of cases). PH was the complication more frequent (55.4%), without significant clinical impact. Global PNXs incidence was high (42.9%), but the introducer allowed to aspirate the PNX with a lower percentage of chest tube placement vs. PNXs not aspirated (6.3% and 13.3%, respectively). CONCLUSION: This large retrospective study confirmed the high diagnostic accuracy of lung PNB with the CX technique and allowed identification of significant factors to achieve a greater diagnostic power and decrease complication rates.

Intrathymic Localization of Melanoma: A Brief Report of Two Cases and a Review of the Literature.

Intrathymic localizations of melanoma represent a very rare entity, with fewer than ten cases of intrathymic melanoma described in the literature. Herein, we describe two cases of patients who underwent surgical removal of a thymic mass at our thoracic surgery department between 2015 and 2022. The final pathological examination revealed a malignant melanoma in both cases; we therefore carried out a literature review to identify such rare and similar cases. In the first case, the intrathymic localization of melanoma was the first manifestation of the disease, posing a dilemma regarding the metastatic and primitive nature of the neoplasm. The second case described a thymic metastasis from a known previous cutaneous melanoma, for which the patient had successfully been treated six years earlier. After carefully reviewing the literature, we identified only six cases of verified primary intrathymic melanomas and one case of intrathymic metastasis resulting from melanoma previously described. Pathologists should be aware of the occurrence of this rare entity and mindful of the differential diagnoses. Several tools, including immunostaining of melanocytic markers and molecular investigations, are mandatory for final pathological diagnosis.

Lung Transplantation for Pleuroparenchymal Fibroelastosis: A Single-Center Experience with Revision of Literature.

Pleuroparenchymal fibroelastosis (PPFE) is a rare condition characterized by fibrosis involving the pleura and the upper lobes which can be idiopathic or secondary to chemotherapy, transplantations and occupational exposure. For the end-stage form, lung transplantation (LT) is the treatment of choice. The aim of this study was to report our single-center experience for patients subjected to LT for PPFE and comparing it with the already published evidence on this topic. At our center, we have performed 6 bilateral LTs for patients with PPFE (3 males and 3 females) with a median age of 52 years. Median ICU and in-hospital length of stay were 8 and 30 days, respectively. To date, two patients are alive and four are dead, with a median overall survival of 10 months. In addition, after a formal search using the terms "pleuroparenchymal fibroelastosis AND lung transplantation", we collected 14 studies focused on outcomes after LT. LT for PPFE is technically challenging and its post-operative course could also be complicated. Current available data on LT outcomes are extremely poor and mostly limited to case reports. Further studies need to be published to improve knowledge of this disease and to achieve best outcomes for LT.

Comprehensive bronchoalveolar lavage characterization in COVID-19 associated acute respiratory distress syndrome patients: a prospective cohort study.

COVID-19-related acute respiratory distress syndrome (CARDS) is associated with high mortality rates. We still have limited knowledge of the complex alterations developing in the lung microenvironment. The goal of the present study was to comprehensively analyze the cellular components, inflammatory signature, and respiratory pathogens in bronchoalveolar lavage (BAL) of CARDS patients (16) in comparison to those of other invasively mechanically ventilated patients (24). In CARDS patients, BAL analysis revealed: SARS-CoV-2 infection frequently associated with other respiratory pathogens, significantly higher neutrophil granulocyte percentage, remarkably low interferon-gamma expression, and high levels of interleukins (IL)-1ß and IL-9. The most important predictive variables for worse outcomes were age, IL-18 expression, and BAL neutrophilia. To the best of our knowledge, this is the first study that was able to identify, through a comprehensive analysis of BAL, several aspects relevant to the complex pathophysiology of CARDS.

An unexpected guest: Pulmonary echinococcosis diagnosed by intraoperative frozen section examination. A case report and literature review.

Echinococcosis is caused by tapeworms belonging to the Echinococcus genus. The most common site of infection is the liver although it may involve almost any organ. Symptoms of pulmonary echinococcosis vary depending on the location and structure of the cyst. While uncomplicated cysts usually appear at imaging as well-defined homogeneous lesions with fluid content and smooth walls of variable thickness, complicated lesions may have a more heterogeneous content with higher density making more difficult the distinction from malignancies or other infections. Hereby we describe the case of a 61-year-old Northern African male admitted to our tertiary center for left upper chest pain who then underwent a chest computed tomography (CT) scan which demonstrated a large hypodense lesion, with smooth and thick walls, in the upper left lobe. The following magnetic resonance confirmed the homogeneous fluid content, and the 18 F- fluorodeoxyglucose-positron emission tomography/CT demonstrated a mild uptake of the walls. According to these findings, the main differential diagnoses at imaging included bronchogenic cyst, synovial sarcoma, and pulmonary hematoma although the patient denied any recent trauma. Given the large size and clinical symptoms he underwent surgery. Intra-operative frozen section, supported by imprint cytology, excluded the presence of malignancy while suggested an echinococcal laminar exocyst. The final pathological examination confirmed the diagnosis of echinococcosis (i.e., Echinococcus Granulosus protoscolex). After surgery he was treated with albendazole and at the six-month follow-up he was in good clinical conditions. Our case highlights the importance of considering rare infections, particularly in individuals from endemic areas. Frozen tissue analyses can be a diagnostic challenge and often require ancillary tools such as imprint cytology and serial sections for more sensitive and accurate diagnosis.